80 results on '"Vegi Ganga Modi Naidu"'
Search Results
2. Immunonano-Lipocarrier-Mediated Liver Sinusoidal Endothelial Cell-Specific RUNX1 Inhibition Impedes Immune Cell Infiltration and Hepatic Inflammation in Murine Model of NASH
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Dinesh Mani Tripathi, Sumati Rohilla, Impreet Kaur, Hamda Siddiqui, Preety Rawal, Pinky Juneja, Vikash Kumar, Anupama Kumari, Vegi Ganga Modi Naidu, Seeram Ramakrishna, Subham Banerjee, Rekha Puria, Shiv K. Sarin, and Savneet Kaur
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inflammation ,liver sinusoidal endothelial cells ,immunonano-lipocarriers ,non-alcoholic steatohepatitis ,targeted delivery ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Background: Runt-related transcription factor (RUNX1) regulates inflammation in non-alcoholic steatohepatitis (NASH). Methods: We performed in vivo targeted silencing of the RUNX1 gene in liver sinusoidal endothelial cells (LSECs) by using vegfr3 antibody tagged immunonano-lipocarriers encapsulated RUNX1 siRNA (RUNX1 siRNA) in murine models of methionine choline deficient (MCD) diet-induced NASH. MCD mice given nanolipocarriers-encapsulated negative siRNA were vehicle, and mice with standard diet were controls. Results: Liver RUNX1 expression was increased in the LSECs of MCD mice in comparison to controls. RUNX1 protein expression was decreased by 40% in CD31-positive LSECs of RUNX1 siRNA mice in comparison to vehicle, resulting in the downregulation of adhesion molecules, ICAM1 expression, and VCAM1 expression in LSECs. There was a marked decrease in infiltrated T cells and myeloid cells along with reduced inflammatory cytokines in the liver of RUNX1 siRNA mice as compared to that observed in the vehicle. Conclusions: In vivo LSEC-specific silencing of RUNX1 using immunonano-lipocarriers encapsulated siRNA effectively reduces its expression of adhesion molecules, infiltrate on of immune cells in liver, and inflammation in NASH.
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- 2021
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3. Targeting TLR4/3 using chlorogenic acid ameliorates LPS+POLY I:C-induced acute respiratory distress syndrome via alleviating oxidative stress-mediated NLRP3/NF-κB axis
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Siddhi Jain, Pritam Saha, Nayadi Parambil Syamprasad, Samir Rajan Panda, Bishal Rajdev, Arun Kumar Jannu, Pawan Sharma, and Vegi Ganga Modi Naidu
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General Medicine - Abstract
Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a life-threatening condition caused due to significant pulmonary and systemic inflammation. Chlorogenic acid (CGA) has been shown to possess potent antioxidant, anti-inflammatory, and immunoprotective properties. However, the protective effect of CGA on viral and bacterial-induced ALI/ARDS is not yet explored. Hence, the current study is aimed to evaluate the preclinical efficacy of CGA in lipopolysaccharide (LPS) and polyinosinic:polycytidylic acid (POLY I:C)-induced ALI/ARDS models in vitro and in vivo. Human airway epithelial (BEAS-2B) cells exposed to LPS+POLY I:C significantly elevated oxidative stress and inflammatory signaling. Co-treatment with CGA (10 and 50 µM) prevented inflammation and oxidative stress mediated by TLR4/TLR3 and NLRP3 inflammasome axis. BALB/c mice, when chronically challenged with LPS+POLY I:C showed a significant influx of immune cells, up-regulation of pro-inflammatory cytokines, namely: IL-6, IL-1β, and TNF-α, and treatment with intranasal CGA (1 and 5 mg/kg) normalized the elevated levels of immune cell infiltration as well as pro-inflammatory cytokines. D-Dimer, the serum marker for intravascular coagulation, was significantly increased in LPS+ POLY I:C challenged animals which was reduced with CGA treatment. Further, CGA treatment also has a beneficial effect on the lung and heart, as shown by improving lung physiological and cardiac functional parameters accompanied by the elevated antioxidant response and simultaneous reduction in tissue damage caused by LPS+POLY I:C co-infection. In summary, these comprehensive, in vitro and in vivo studies suggest that CGA may be a viable therapeutic option for bacterial and viral-induced ALI-ARDS-like pathology.
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- 2023
4. An Evaluation of Antioxidant Potential of Memecylon sisparense Gamble Leaf in Doxorubicin-Induced Cardiotoxicity in Mice.
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Uppu, Jaya lakshmi, Challa, Veerabhadra Swamy, Vegi, Ganga Modi Naidu, and Asha, S
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- 2019
5. Synthesis of C5-tethered indolyl-3-glyoxylamide derivatives as tubulin polymerization inhibitors
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Guggilapu, Sravanthi Devi, Lalita, Guntuku, Reddy, T. Srinivasa, Prajapti, Santosh Kumar, Nagarsenkar, Atulya, Ramu, Shymala, Brahma, Uma Rani, Lakshmi, Uppa Jaya, Vegi, Ganga Modi Naidu, Bhargava, Suresh K., and Babu, Bathini Nagendra
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- 2017
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6. 11 Triazine based chemical entities for anticancer activity
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Jagadees Kumar Gangasani, Siwaswarup Yarasi, Vegi Ganga Modi Naidu, and Jayathirtha Rao Vaidya
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- 2022
7. Triazine based chemical entities for anticancer activity
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Jagadees Kumar Gangasani, Siwaswarup Yarasi, Vegi Ganga Modi Naidu, and Jayathirtha Rao Vaidya
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General Physics and Astronomy ,General Materials Science ,General Chemistry - Abstract
Triazine is a six-membered aromatic nitrogen heterocyclic moiety that was extensively investigated because of its biological properties and, in particular anticancer potentials. Kinases play a crucial role in cancer cell proliferation and metabolism. Triazine derivatives show anticancer activity by inhibiting the lipid kinases like phosphoinositide 3-kinases, mammalian target of rapamycin, receptor tyrosine kinases, like focal adhesion kinase, cyclin-dependent kinases, Rho-associated protein kinases, p21-activated kinases, carbonic anhydrases, enolase inhibitors, microtubules inhibitors, and histone deacetylases. The present chapter highlights the synthesis of triazine-based derivatives, their characterization, evaluation of anticancer properties, and their journey towards possible medicine for cancer.
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- 2022
8. Ameliorative effect of Dillenia indica fruits against doxorubicin-induced cardiomyocyte toxicity
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Jagadeesh Kumar, Kalyani Tene, Ranadeep Gogoi, Kalyan Kumar, Deepak Bharadwaj Pemmaraju, Vegi Ganga Modi Naidu, and P. A. Shantanu
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chemistry.chemical_classification ,Reactive oxygen species ,Cardiotoxicity ,Antioxidant ,biology ,medicine.medical_treatment ,Pharmacology ,Dillenia ,biology.organism_classification ,medicine.disease_cause ,chemistry.chemical_compound ,Complementary and alternative medicine ,chemistry ,Lactate dehydrogenase ,Toxicity ,medicine ,Doxorubicin ,Oxidative stress ,medicine.drug - Abstract
Drug-induced cardiotoxicity is a significant concern in cancer patients, and therefore cardio-oncology is gaining more attention. Doxorubicin (Dox) is a potent anticancer drug used against various malignancies, with cardiotoxicity as a dose-limiting factor. Although the mechanism of Dox-mediated cardiotoxicity is not fully understood, it is thought to encompass oxidative stress during the therapy leading to cardiotoxicity in cancer patients. Several oxidative stress-induced diseases and drug-induced toxicities can be effectively ameliorated using bioactive plant constituents. Dillenia indica (DI) is one such plant belonging to the family Dilleniaceae and is used as an ethno-medicinal agent for the treatment of various oxidative stress-mediated diseases like diabetes and cancer. In this study, we have evaluated the protective effect of the hydroalcoholic extract of Dillenia indica fruits (HADI) against the Dox-induced cardiomyocyte toxicity. The HADI was further evaluated for its efficacy in a Dox-induced cardiotoxicity models. Antioxidant assays (ABTS and DPPH) revealed a strong antioxidant potential of HADI. In vitro assay results indicated that pre-treatment with HADI had shown protective activity and reduced the ROS generation in H9c2 cell line. Non-invasive methods like high-frequency ultrasonography and electrocardiography were applied to evaluate the real time cardiac parameters. It was also found that pre-treatment with HADI restored functional parameters like ejection fraction, stroke volume as well as elevation of the T wave induced by Dox. Whereas the Dox treated mice had elevated levels of cardiac functional enzymes like creatinine kinase (CK-MB) and lactate dehydrogenase indicating the severity of cardiomyocyte toxicity. The results indicated that HADI pre-treatment has significantly reduced the upregulated enzyme levels. Taken together, our findings indicated that HADI ameliorated the Dox-induced cardiomyocyte toxicity by modulating the upregulated reactive oxygen species.
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- 2020
9. Characteristics of Molecularly Engineered Anticancer Drug Conjugated Organic Nanomicelles for Site-Selective Cancer Cell Rupture and Growth Inhibition of Tumor Spheroids
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Shalini Dimri, Vegi Ganga Modi Naidu, Rohit Srivastava, Gayathri Ravichandran, Abhijit De, Rajendra Prasad, and Nishant Kumar Jain
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chemistry.chemical_classification ,Biodistribution ,biology ,Biochemistry (medical) ,Biomedical Engineering ,Peptide ,General Chemistry ,Conjugated system ,Biomaterials ,chemistry.chemical_compound ,chemistry ,Cancer stem cell ,Cancer cell ,Cancer research ,biology.protein ,medicine ,Antibody ,Growth inhibition ,Niclosamide ,medicine.drug - Abstract
Site-selective uptake and specific biodistribution of chemotherapeutic drugs are essential prerequisites for targeted cancer therapy. Especially, antibody and peptide conjugated drugs have been attempted as localized therapeutic agents. However, the characteristics of drug conjugated nanosystems are less explored, which are limited with their toxicity, low therapeutic efficacy, complicated synthesis, and high costs. Herein, we report a biocompatible (about 95%) molecularly engineered anticancer drug conjugated nanomicelles (∼200 nm in size) for site-selective CD44 overexpressed cancer cell rupture and tumor growth inhibition. Microscopic analysis demonstrates the distinct visualization of organic-organic interfaces (∼5 nm), which are corroborated with spectroscopic measurements confirmed the conjugation of niclosamide drug with hyaluronic acid (NIC-HA). Uniformly distributed hemocompatible (about 99%) organic nanomicelles exhibit the cellular membrane and cytoplasmic targeting with significant cellular rupture (IC
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- 2020
10. Multifunctional Synthetic Amphiphile for Niche Therapeutic Applications: Mitigation of MRSA Biofilms and Potential in Wound Healing
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Poulomi Dey, Aiyagari Ramesh, Vegi Ganga Modi Naidu, Gopal Das, and Eswara Rao Puppala
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integumentary system ,Chemistry ,Biochemistry (medical) ,Biomedical Engineering ,Biofilm ,General Chemistry ,biochemical phenomena, metabolism, and nutrition ,bacterial infections and mycoses ,medicine.disease_cause ,Microbiology ,Biomaterials ,Staphylococcus aureus ,Amphiphile ,medicine ,Wound healing - Abstract
The relentless menace of implant- and skin wound-associated infections caused by methicillin-resistant Staphylococcus aureus (MRSA) biofilms demands the design of therapeutics that have an edge ove...
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- 2022
11. Chemistry of herbal biomolecules
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Deepak Bharadwaj Pemmaraju, Vegi Ganga Modi Naidu, Jagadeesh Kumar Gangasani, U.S.N. Murthy, and Aravind Kumar Rengan
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chemistry.chemical_classification ,Chemistry ,Biomolecule ,Nanotechnology - Published
- 2022
12. Herbal biomolecules as nutraceuticals
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Vegi Ganga Modi Naidu, Aparajita Ghosh, Jagadeesh Kumar Gangasani, Deepak Bharadwaj Pemmaraju, U.S.N. Murthy, and Aravind Kumar Rengan
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- 2022
13. Polymeric Core–Shell Combinatorial Nanomedicine for Synergistic Anticancer Therapy
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Vegi Ganga Modi Naidu, Navneet Kaur, Nishant Kumar Jain, Asifkhan Shanavas, Rajendra Prasad, Maruthi Prasanna, Dhirendra Bahadur, Rohit Srivastava, and Dinesh Thummuri
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Drug ,Biocompatibility ,General Chemical Engineering ,media_common.quotation_subject ,General Chemistry ,Article ,chemistry.chemical_compound ,Chemistry ,chemistry ,Docetaxel ,Cancer cell ,medicine ,Biophysics ,Nanomedicine ,Doxorubicin ,Growth inhibition ,QD1-999 ,medicine.drug ,Combination drug ,media_common - Abstract
Core–shell nanostructures are promising platforms for combination drug delivery. However, their complicated synthesis process, poor stability, surface engineering, and low biocompatibility are major hurdles. Herein, a carboxymethyl chitosan-coated poly(lactide-co-glycolide) (cmcPLGA) core–shell nanostructure is prepared via a simple one-step nanoprecipitation self-assembly process. Engineered core–shell nanostructures are tested for combination delivery of loaded docetaxel and doxorubicin in a cancer-mimicked environment. The drugs are compartmentalized in a shell (doxorubicin, Dox) and a core (docetaxel, Dtxl) with loading contents of ∼1.2 and ∼2.06%, respectively. Carboxymethyl chitosan with both amine and carboxyl groups act as a polyampholyte in diminishing ζ-potential of nanoparticles from fairly negative (−13 mV) to near neutral (−2 mV) while moving from a physiological pH (7.4) to an acidic tumor pH (6) that can help the nanoparticles to accumulate and release the drug on-site. The dual-drug formulation was found to carry a clinically comparable 1.7:1 weight ratio of Dtxl/Dox, nanoengineered for the sequential release of Dox followed by Dtxl. Single and engineered combinatorial nanoformulations show better growth inhibition toward three different cancer cells compared to free drug treatment. Importantly, Dox–Dtxl cmcPLGA nanoparticles scored synergism with combination index values between 0.2 and 0.3 in BT549 (breast ductal carcinoma), PC3 (prostate cancer), and A549 (lung adenocarcinoma) cell lines, demonstrating significant cell growth inhibition at lower drug concentrations as compared to single-drug control groups. The observed promising performance of dual-drug formulation is due to the G2/M phase arrest and apoptosis.
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- 2019
14. A novel bioavailable curcumin-galactomannan complex modulates the genes responsible for the development of chronic diseases in mice: A RNA sequence analysis
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Elina Khatoon, Vegi Ganga Modi Naidu, Ajaikumar B. Kunnumakkara, Eswara Rao Puppala, Kishore Banik, Krishan Kumar Thakur, and Mangala Hegde
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Curcumin ,Drug Compounding ,Biological Availability ,Inflammation ,Disease ,Pharmacology ,General Biochemistry, Genetics and Molecular Biology ,Transcriptome ,Mannans ,Galactomannan ,chemistry.chemical_compound ,Mice ,Downregulation and upregulation ,In vivo ,Medicine ,Animals ,General Pharmacology, Toxicology and Pharmaceutics ,Gene ,Mice, Inbred BALB C ,business.industry ,Sequence Analysis, RNA ,Computational Biology ,Galactose ,General Medicine ,Drug Combinations ,Trigonella ,chemistry ,Chronic Disease ,Female ,medicine.symptom ,business - Abstract
Background Chronic diseases or non-communicable diseases are a major burden worldwide due to the lack of highly efficacious treatment modalities and the serious side effects associated with the available therapies. Purpose/study design A novel self-emulsifying formulation of curcumin with fenugreek galactomannan hydrogel scaffold as a water-dispersible non-covalent curcumin-galactomannan molecular complex (curcumagalactomannosides, CGM) has shown better bioavailability than curcumin and can be used for the prevention and treatment of chronic diseases. However, the exact potential of this formulation has not been studied, which would pave the way for its use for the prevention and treatment of multiple chronic diseases. Methods The whole transcriptome analysis (RNAseq) was used to identify differentially expressed genes (DEGs) in the liver tissues of mice treated with LPS to investigate the potential of CGM on the prevention and treatment of chronic diseases. Expression analysis using DESeq2 package, GO, and pathway analysis of the differentially expressed transcripts was performed using UniProtKB and KEGG-KAAS server. Results The results showed that 559 genes differentially expressed between the liver tissue of control mice and CGM treated mice (100 mg/kg b.wt. for 14 days), with adjusted p-value below 0.05, of which 318 genes were significantly upregulated and 241 were downregulated. Further analysis showed that 33 genes which were upregulated (log2FC > 8) in the disease conditions were significantly downregulated, and 32 genes which were downregulated (log2FC Conclusion Overall, our study showed CGM has high potential in the prevention and treatment of multiple chronic diseases.
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- 2021
15. Immunonano-Lipocarrier-Mediated Liver Sinusoidal Endothelial Cell-Specific RUNX1 Inhibition Impedes Immune Cell Infiltration and Hepatic Inflammation in Murine Model of NASH
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Seeram Ramakrishna, Savneet Kaur, Subham Banerjee, Impreet Kaur, Hamda Siddiqui, Vegi Ganga Modi Naidu, Rekha Puria, Dinesh M. Tripathi, Anupama Kumari, Pinky Juneja, Preety Rawal, Shiv Kumar Sarin, Vikash Kumar, and Sumati Rohilla
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Male ,liver sinusoidal endothelial cells ,QH301-705.5 ,Inflammation ,immunonano-lipocarriers ,Article ,Catalysis ,Proinflammatory cytokine ,Inorganic Chemistry ,Mice ,Immune system ,Downregulation and upregulation ,Non-alcoholic Fatty Liver Disease ,hemic and lymphatic diseases ,medicine ,Animals ,Gene silencing ,RNA, Small Interfering ,Biology (General) ,Physical and Theoretical Chemistry ,QD1-999 ,Molecular Biology ,Spectroscopy ,Chemistry ,Cell adhesion molecule ,Organic Chemistry ,targeted delivery ,Endothelial Cells ,General Medicine ,medicine.disease ,Computer Science Applications ,Mice, Inbred C57BL ,Endothelial stem cell ,Disease Models, Animal ,RNAi Therapeutics ,Liver ,inflammation ,Core Binding Factor Alpha 2 Subunit ,embryonic structures ,Cancer research ,RNA Interference ,non-alcoholic steatohepatitis ,medicine.symptom ,Steatohepatitis - Abstract
Background: Runt-related transcription factor (RUNX1) regulates inflammation in non-alcoholic steatohepatitis (NASH). Methods: We performed in vivo targeted silencing of the RUNX1 gene in liver sinusoidal endothelial cells (LSECs) by using vegfr3 antibody tagged immunonano-lipocarriers encapsulated RUNX1 siRNA (RUNX1 siRNA) in murine models of methionine choline deficient (MCD) diet-induced NASH. MCD mice given nanolipocarriers-encapsulated negative siRNA were vehicle, and mice with standard diet were controls. Results: Liver RUNX1 expression was increased in the LSECs of MCD mice in comparison to controls. RUNX1 protein expression was decreased by 40% in CD31-positive LSECs of RUNX1 siRNA mice in comparison to vehicle, resulting in the downregulation of adhesion molecules, ICAM1 expression, and VCAM1 expression in LSECs. There was a marked decrease in infiltrated T cells and myeloid cells along with reduced inflammatory cytokines in the liver of RUNX1 siRNA mice as compared to that observed in the vehicle. Conclusions: In vivo LSEC-specific silencing of RUNX1 using immunonano-lipocarriers encapsulated siRNA effectively reduces its expression of adhesion molecules, infiltrate on of immune cells in liver, and inflammation in NASH.
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- 2021
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16. Polyphenolic-Rich Compounds From Dillenia pentagyna (Roxb.) Attenuates the Doxorubicin-Induced Cardiotoxicity: A High-Frequency Ultrasonography Assisted Approach
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G. Jagadeesh Kumar, Upadhyayula Suryanarayana Murty, Kalyani Tene, P. Eswara Rao, Vegi Ganga Modi Naidu, M. Kalyan Kumar, Ranadeep Gogoi, G. Basveshwar, Deepak Bharadwaj Pemmaraju, and Pramod Kumar
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Pharmacology ,Cardiotoxicity ,ABTS ,DPPH ,ultrasonography ,RM1-950 ,Syringic acid ,doxorubicin ,chemistry.chemical_compound ,chemistry ,Polyphenol ,dillenia pentagyna roxb ,cardioprotection ,Toxicity ,medicine ,oxidative stress ,Pharmacology (medical) ,Doxorubicin ,Gallic acid ,Therapeutics. Pharmacology ,medicine.drug - Abstract
Cardiovascular complications are the foremost concern in patients undergoing anticancer therapy. There is an unmet need to address the problems arising from the drug-induced toxicity for the long-term benefit of the patients undergoing chemotherapy. Alternative medicines are gaining their prosperity in addressing the various drug-induced organ toxicity. Dillenia pentagyna Roxb (DP) is an ethnomedicinal plant rich in flavonoids and phenolic contents. In India & Nepal, DP is a common ingredient of traditional medicines used to treat multiple ailments like inflammation, cancer, and diabetes. However, its protective role against doxorubicin (Dox) induced cardiotoxicity remains unexplored. Herein, we investigated the potential effects of various extracts/fractions obtained from the DP’s bark against Dox-induced cardiotoxicity, both in-vitro and in-vivo. The anti-oxidant content of the extracts/fractions was evaluated by using DPPH, ABTS and FRAP chemical assays. The results indicated that the hydroalcoholic (HA) extract of DP has intense anti-oxidant potential. Further fractionation of DP revealed that the phenolic-rich fraction (F1) has a high anti-oxidant potential. The protective effect of extract/fraction was also investigated in the H9c2 cell line following the Dox-induced cardiotoxicity model. We observed that the pre-treatment of extract/fraction in cardiomyocytes had exhibited increased cell viability. Fluorescence-based chemical assays indicated a decreased ROS levels in the treated groups in comparison to the Dox control group. The effect of DP was evaluated further in balb/c mice by the Dox-induced cardiotoxicity model. Non-invasive techniques like high-frequency ultrasonography and electrocardiogram revealed that the mice pre-treated with DP had improved cardiac functionality (left ventricular ejection fraction and stroke volume) and normalized the electrocardiograms compared to the Dox control group. Further, biochemical analysis with the cardiac tissues revealed that the cytoprotective proteins like HO-1, SOD-2, and Nrf-2 were elevated in the DP treated groups compared to the Dox control group. Overall, our results suggested that the bioactive extract/fractions of DP helped alleviate the Dox-induced cardiotoxicity. LC-QTOF-ESI-MS analysis of DP and F1 indicated that polyphenolic anti-oxidant compounds like gallic acid, syringic acid, and sinapic acid could be responsible for the potent -cardioprotective effect. Future understanding of the pharmacokinetics and pharmacodynamic parameters can help translate from the bench to the bedside.
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- 2021
17. Silkworm Silk Scaffolds Functionalized with Recombinant Spider Silk Containing a Fibronectin Motif Promotes Healing of Full-Thickness Burn Wounds
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Naresh Thatikonda, Tshewuzo-u Lohe, Vegi Ganga Modi Naidu, Dimple Chouhan, Biman B. Mandal, and My Hedhammar
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Scaffold ,biology ,Chemistry ,fungi ,0206 medical engineering ,Biomedical Engineering ,Fibroin ,02 engineering and technology ,021001 nanoscience & nanotechnology ,020601 biomedical engineering ,law.invention ,Biomaterials ,Fibronectin ,Full thickness burn ,SILK ,law ,biology.protein ,Recombinant DNA ,Spider silk ,0210 nano-technology ,Wound healing ,Biomedical engineering - Abstract
Full-thickness cutaneous wounds, such as deep burns, are complex wounds that often require surgical interventions. Herein, we show the efficacy of acellular grafts that can be made available off-the-shelf at an affordable cost using silk biomaterials. Silkworm silk fibroin (SF), being a cost-effective and natural biopolymer, provides essential features required for the fabrication of three-dimensional constructs for wound-healing applications. We report the treatment of third-degree burn wounds using a freeze-dried microporous scaffold of Antheraea assama SF (AaSF) functionalized with a recombinant spider silk fusion protein FN-4RepCT (FN-4RC) that holds the fibronectin cell binding motif. In order to examine the healing efficiency of functionalized silk scaffolds, an in vivo burn rat model was used, and the scaffolds were implanted by a one-step grafting procedure. The aim of our work is to investigate the efficacy of the developed acellular silk grafts for treating full-thickness wounds as well as to examine the effect of recombinant spider silk coatings on the healing outcomes. Following 14-day treatment, AaSF scaffolds coated with FN-4RC demonstrated accelerated wound healing when compared to the uncoated counterpart, commercially used DuoDERM dressing patch, and untreated wounds. Histological assessments of wounds over time further confirmed that functionalized silk scaffolds promoted wound healing, showing vascularization and re-epithelialization in the initial phase. In addition, higher extent of tissue remodeling was affirmed by the gene expression study of collagen type I and type III, indicating advanced stage of healing by the silk treatments. Thus, the present study validates the potential of scaffolds of combined silkworm silk and FN-4RC for skin regeneration.
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- 2019
18. Zanthoxylum alatum Roxb. seed extract ameliorates stress aggravated DSS-induced ulcerative colitis in mice: Plausible role on NF-κB signaling axis
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Kalyani Tene, Syamprasad N P, Vegi Ganga Modi Naidu, Gangasani Jagadeesh Kumar, Bidya Dhar Sahu, Eswara Rao Puppala, Chandana Choudhury Barua, Malayamarutham Kalyankumarraju, and Sahabuddin Ahmed
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Male ,Zanthoxylum ,Cell Survival ,Chromosomal translocation ,Stimulation ,Spleen ,Pharmacology ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Stress, Physiological ,Drug Discovery ,Toxicity Tests ,medicine ,Potency ,Animals ,Humans ,Colitis ,030304 developmental biology ,0303 health sciences ,biology ,Behavior, Animal ,business.industry ,Plant Extracts ,Dextran Sulfate ,NF-kappa B ,medicine.disease ,biology.organism_classification ,Ulcerative colitis ,Mice, Inbred C57BL ,medicine.anatomical_structure ,HEK293 Cells ,Gene Expression Regulation ,030220 oncology & carcinogenesis ,Seeds ,Tumor necrosis factor alpha ,Colitis, Ulcerative ,business ,Signal Transduction - Abstract
Ethnopharmacological relevance Zanthoxylum alatum (ZA) Roxb (family: Rutaceae) plant has been traditionally used for multiple indications by local healers among different communities of South Asian countries mainly in India and Bangladesh. The extracts of ZA have reported strong anti-inflammatory and anti-oxidant activities, but no scientific report is available on its efficacy in intestinal inflammatory disorders like ulcerative colitis. Aim of the study The overall objective of our study was to evaluate the anti-inflammatory potency of hydro-ethanolic extract of Zanthoxylum alatum seed (ZAHA) using both in-vitro NF-κB-luciferase translocation assay and in-vivo stress aggravated dextran sodium sulfate (DSS)-induced ulcerative colitis model. Materials and methods The in-vitro anti-inflammatory effect of ZAHA extract was evaluated by luciferase assay in HEK293 cells. Parameters such as body weights, behavioural, colonoscopy, colon lengths and spleen weights were measured and recorded in stress aggravated DSS-induced colitis model in C57BL/6 mice. Biochemical, histological and immunoblot analysis in the colon tissues were determined to prove its anti-inflammatory and anti-oxidant activities. Characterization of the extract was done by LC-MS/MS study. Results Initial in vitro NF-κB-luciferase translocation assay showed that the hydroalcoholic extract of ZA (ZAHA) showed potent inhibitory activity for NF-κB translocation by TNF-α stimulation and hence this particular extract was further evaluated in stress aggravated DSS-induced ulcerative colitis model in C57BL/6 mice. Treatment of ZAHA for two weeks at a dose of 200 mg/kg significantly ameliorated the stress aggravated DSS-induced colitis in mice. Histological alterations, infiltration of inflammatory cells, and the levels of IL-1β, IL-6, TNF-α in colon tissue and serum samples were significantly decreased in ZAHA treatment groups compared to the stress aggravated DSS induced colitis animals. Moreover, the protein expressions of p-NF-κB, p-IκBα, p-STAT3, COX-2, and TNF-α were significantly reduced in colon tissues of ZAHA treated groups and also increased anti-oxidant markers like SOD-1, Nrf2 significantly when compared with disease control group. Characterization of the extract further by LC-MS/MS revealed the presence of several active compounds which could be responsible for its anti-inflammatory activity. Conclusions Thus from the above findings it can be concluded that ZAHA ameliorates stress aggravated DSS-induced ulcerative colitis due to its anti-inflammatory and anti-oxidant activity.
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- 2021
19. Phytochemistry and polypharmacology of cleome species: A comprehensive Ethnopharmacological review of the medicinal plants
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Samir Ranjan Panda, Gangasani Jagadeesh Kumar, Upadhyayula Suryanarayana Murty, Siddhi Jain, Vegi Ganga Modi Naidu, Jagdish Chand, and Archana Moni Das
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Pharmacology ,Phytochemistry ,Future studies ,Plants, Medicinal ,biology ,Traditional medicine ,food and beverages ,biology.organism_classification ,Cleome ,Tanzania ,Functional Food ,Drug Discovery ,Ethnopharmacology ,Asian country ,Humans ,Cleomaceae ,Polypharmacology ,Medicine, Traditional ,Medicinal plants ,Phytotherapy - Abstract
Ethnopharmacological relevance Cleome species in particular (C. gynandra Linn, C. viscosa Linn, C. rutidosperma DC, C. felina Linn.), commonly known as spider flowers, belong to the genus of flowering plants in Cleomaceae family. Found primarily in the African countries (Kenya, Tanzania, Egypt, South Africa, and Nigeria), Asian countries (India and Afghanistan), European countries (Italy), and also in other countries like Brazil and Austria. These plants are commonly cultivated as a vegetable crop for their nutritional benefits, and the leaves are widely consumed for their health-promoting effects. The different parts of the plants, such as leaves, seeds, flowers, and roots, are used to treat acute and chronic inflammatory disorders, hepatotoxicity, malaria, fungal diseases, and cancer. Aim of the study Detailed investigations in underlining the molecular mechanisms and their wide variety of effects in treating various diseases remain ambiguous. The review focuses on an in-depth discussion of studies targeting phytochemistry and polypharmacology. Thus, the review aims to recapitulate the therapeutic potential of the components of Cleome involved in the treatment of a wide variety of ailments from ancient times were collected and presented along with strategies aiming for future studies. Materials and methods The information provided is collected from several scientific databases (PubMed, Elsevier, ScienceDirect) and traditional medicine books, and other professional websites. Results and conclusion Investigations and current evidence revealed that the different chemical constituents present in cleome species possess various health-promoting effects along with the aerial parts showing promising traditional uses in traditional healing and culinary. An explorative survey in the current review highlights the traditional healing effects along with a broad scope of studies that can be performed in the future.
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- 2021
20. Molecular Mechanisms, Therapeutic Targets and Pharmacological Interventions: An Update
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Vegi Ganga Modi Naidu, Nitika Gupta, Mohit Kwatra, Sahabuddin Ahmed, and Samir Ranjan Panda
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0301 basic medicine ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Pharmacological interventions ,business.industry ,InformationSystems_INFORMATIONSTORAGEANDRETRIEVAL ,Data_FILES ,Medicine ,Bioinformatics ,business ,GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries) ,030217 neurology & neurosurgery - Abstract
Muscles are the enriched reservoir of proteins in the body. During any workout or exercise, the demand in the form of energy is essentially required by the muscle. Energy expenditure of skeletal muscle is more dependent on the type of demand. There is particular homeostasis within the body that avoid surplus energy expenditure and this prevents any muscle loss. Muscle atrophy is termed as the loss of skeletal muscle mass due to immobility, malnutrition, medications, aging, cancer cachexia, variety of injuries or diseases that impact the musculoskeletal or nervous system. Hence, atrophy within the skeletal muscle initiates further cause fatigue, pain, muscle weakness, and disability in human subjects. Therefore, starvation and reduced muscle mass further initiate numerous signaling pathways including inflammatory, antioxidant signaling, mitochondria bio-energetic failure, AMP-activated protein kinase (AMPK), Sirtuin 1(SIRT1), BDNF/TrkB/PKC, Autophagy, ubiquitin-proteasome systems, etc. Here, in this chapter, we will mention molecular mechanisms involved in therapeutic targets and available Pharmacological Interventions with the latest updates.
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- 2021
21. Lipopolysaccharide exacerbates chronic restraint stress-induced neurobehavioral deficits: Mechanisms by redox imbalance, ASK1-related apoptosis, autophagic dysregulation
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P. A. Shantanu, Vegi Ganga Modi Naidu, Vijaya Kumar Gangipangi, Basveshwar Gawali, Nitika Gupta, Sahabuddin Ahmed, Mohit Kwatra, and Samir Ranjan Panda
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Lipopolysaccharides ,Male ,medicine.medical_specialty ,Lipopolysaccharide ,Inflammation ,Apoptosis ,Pathogenesis ,chemistry.chemical_compound ,Mice ,Neurochemical ,Internal medicine ,medicine ,Autophagy ,Animals ,ASK1 ,Biological Psychiatry ,Depressive Disorder, Major ,business.industry ,Psychiatry and Mental health ,Endocrinology ,Monoamine neurotransmitter ,chemistry ,medicine.symptom ,business ,Oxidation-Reduction - Abstract
Major depressive disorder (MDD) is the foremost leading psychiatric illness prevailing around the globe. It usually exists along with anxiety and other clinical conditions (cardiovascular, cancer, neurodegenerative diseases, and infectious diseases). Chronic restraint stress (RS) and LPS-induce neurobehavioral alterations in rodent models however their interaction studies in association with the pathogenesis of MDD are still unclear. Therefore, the current study was aimed to investigate the LPS influence on chronic RS mediated redox imbalance, apoptosis, and autophagic dysregulation in the hippocampus (HIP) and frontal cortex (FC) of mice brain. Male Balb/c mice were exposed to 28 days consecutive stress (6h/day) with a single-dose LPS challenge (0.83 mg/kg, i.p.) on the last day (Day 28). In addition, we also carried out separate study to understand physiological relevance, where we used the DSS (dextran sulfate sodium), a water soluble polysaccharide (negatively charged) and studied its influence on RS induced neurobehavioral and certain neurochemical anomalies. The obtained results in RS and RS + LPS animal groups showed significant immune dysfunction, depleted monoamines, lowered ATP & NAD level, elevated serum CORT level, serum and brain tissues IL-1β/TNF-α/IL-6, SOD activity but reduced CAT activity. Furthermore, the redox perturbation was found where significantly upregulated P-NFκB p65, Keap-1, Prx-SO3 and downregulated Nrf2, Srx1, Prx2 protein expression was seen in RS + LPS mice. The apoptosis signaling (P-ASK1, P-p38 MAPK, P-SAPK/JNK, cleaved PARP, cleaved Caspase-3, Cyto-C), autophagic impairment (p62, LC3II/I) were noticed in HIP and FC of RS and RS + LPS grouped animals. Our new findings provide a complex interplay of chemical (LPS) and physical (RS) stressors where both single dose LPS challenge and 3% DSS in drinking water (for 7 days) exaggerated chronic RS-induced inflammation, lowered redox status, increased apoptosis and dysregulated autophagy leading drastic neurobehavioral alterations in the mice.
- Published
- 2021
22. Biomaterials in treatment of Alzheimer's disease
- Author
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Gautam Singhvi, Amit Alexander, Hafiz Ahmed, Vegi Ganga Modi Naidu, Sunil Kumar Dubey, Eluri Prathyusha, Prashant Kesharwani, and Mukta Agrawal
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0301 basic medicine ,Drug ,Side effect ,media_common.quotation_subject ,Population ,Nanotechnology ,Biocompatible Materials ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Drug Delivery Systems ,Alzheimer Disease ,Animals ,Humans ,education ,media_common ,Liposome ,education.field_of_study ,Drug Carriers ,Chemistry ,Extracellular Polymeric Substance Matrix ,Brain ,Cell Biology ,Controlled release ,030104 developmental biology ,Colloidal gold ,Nanoparticles ,Nanocarriers ,Drug carrier ,030217 neurology & neurosurgery - Abstract
Alzheimer's disease (AD) is a non-recoverable progressive neurodegenerative disorder most prevalent but not limited to the old age population. After all the scientific efforts, there are still many unmet criteria and loopholes in available treatment and diagnostic strategies, limiting their efficacy. The poor drug efficacy is attributed to various biological hurdles, including blood-brain barrier (BBB) and peripheral side effects as most prominent ones and the lack of promising carriers to precisely deliver the drug to the brain by conserving its therapeutic potency. The increasing disease prevalence and unavailability of effective therapy calls for developing a more innovative, convenient and affordable way to treat AD. To fulfill such need, researchers explored various biomaterials to develop potential vectors or other forms to target the bioactives in the brain by preserving their inherent properties, improving the existing lacuna like poor solubility, permeability and bioavailability etc. and minimize the side effect. The unique characteristic properties of biomaterials are used to develop different drug carriers, surface modifying target active ligands, functional carriers, drug conjugate, biosensing probe, diagnostic tool and many more. The nanoparticulate system and other colloidal carriers like hydrogel and biodegradable scaffold can effectively target the drug moieties to the brain. Also, the use of different target-acting ligands and stimuli-responsive carriers assures the site-specificity and controlled release at the desired site by interaction with receptors and various exo- and endogenous stimuli. This review article has highlighted the application of biomaterials for targeting the drug to the brain and as promising diagnostic tools to detect the markers for better AD management. The work particularly focuses on the use of biomaterials as smart drug carriers including pH, thermo, photo, electro and magnetically triggered system; novel drug carriers for brain targeting including polymeric carriers (polymeric nanoparticle, dendrimer and polymeric micelle); lipid carrier (liposome, nanoemulsion, NLC and SLN); inorganic nanoparticles (quantum dots, gold nanoparticles etc.); and other drug vectors (hydrogel, biodegradable scaffold, and carbon nanotube) in treatment of AD. It also highlighted the application of some novel carrier systems and biomaterials as biosensor and other diagnostic tools for early and precise AD diagnosis.
- Published
- 2020
23. Potential role of TrkB agonist in neuronal survival by promoting CREB/BDNF and PI3K/Akt signaling in vitro and in vivo model of 3-nitropropionic acid (3-NP)-induced neuronal death
- Author
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Vegi Ganga Modi Naidu, Samir Ranjan Panda, Basveshwar Gawali, Sahabuddin Ahmed, and Mohit Kwatra
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0301 basic medicine ,Male ,Cancer Research ,Cell Survival ,Clinical Biochemistry ,Pharmaceutical Science ,Apoptosis ,Tropomyosin receptor kinase B ,CREB ,7,8-Dihydroxyflavone ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Animals ,Humans ,Cyclic AMP Response Element-Binding Protein ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Pharmacology ,Membrane Potential, Mitochondrial ,Neurons ,Membrane Glycoproteins ,biology ,Cell Death ,Chemistry ,Brain-Derived Neurotrophic Factor ,Biochemistry (medical) ,Cell Biology ,Protein-Tyrosine Kinases ,Flavones ,Nitro Compounds ,Cell biology ,Mitochondria ,Mice, Inbred C57BL ,030104 developmental biology ,Huntington Disease ,Neuroprotective Agents ,nervous system ,Mitochondrial biogenesis ,030220 oncology & carcinogenesis ,biology.protein ,Phosphorylation ,Phosphatidylinositol 3-Kinase ,Propionates ,Proto-Oncogene Proteins c-akt ,Neurotrophin ,Signal Transduction - Abstract
Striatal neurons depends on an afferent supply of brain-derived neurotrophic factor-(BDNF) that explicitly interacts with tropomyosin receptor kinase B (TrkB) receptor and performs sundry functions including synaptic plasticity, neuronal differentiation and growth. Therefore, we aimed to scrutinize an active molecule that functions identical to BDNF in activating TrkB receptor and it’s downstream targets for restoring neuronal survival in Huntington disease (HD). Data from in vitro Neuro-2a cell line showed that treatment with 7,8-dihydroxyflavone (7,8-DHF), improved 3-nitropropionic acid (3-NP) induced neuronal death by stabilizing the loss of mitochondrial membrane potential and transiently increased the activity of cAMP-response element-binding protein (CREB) and BDNF via TrkB receptor activation. Consistent with in vitro findings, our in vivo results stated that treatment with 7,8-DHF at a dose of 10 mg/kg body weight ameliorated various behavior alterations caused by 3-NP intoxication. Further histopathological and electron microscopy evidences from striatal region of 3-NP mice brain treated with 7,8-DHF showed more improved neurons with intact mitochondria and less autophagic vacuoles. Protein expression analysis of both in vitro and in vivo study showed that 7,8-DHF promotes neuronal survival through upregulation and phosphorylation of phosphatidylinositol 3-kinase (PI3K) and Akt at serine-473/threonine-308). Akt phosphorylation additionally phosphorylates Bad at serine-136 and inhibits its translocation to mitochondria thereby promoting mitochondrial biogenesis, enhanced ATP production and inhibit apoptosis mediated neuronal death. These aforementioned findings help in strengthening our hypothesis and has come up with a novel neuroprotective mechanism of 7,8-DHF against 3-NP induced neuronal death.
- Published
- 2020
24. Geometry encoded functional programming of tumor homing peptides for targeted drug delivery
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Ruchika Goyal, Vegi Ganga Modi Naidu, T.R. Santhoshkumar, Gaurav Jerath, Vibin Ramakrishnan, Eswara Rao Puppala, Srikanth Ponneganti, R. Akhil, Aneesh Chandrasekharan, and Anupam Sarma
- Subjects
Fluorescence-lifetime imaging microscopy ,Pharmaceutical Science ,Peptide ,Antineoplastic Agents ,Apoptosis ,Breast Neoplasms ,02 engineering and technology ,law.invention ,03 medical and health sciences ,Drug Delivery Systems ,In vivo ,Confocal microscopy ,law ,Cell Line, Tumor ,Humans ,Peptide library ,030304 developmental biology ,chemistry.chemical_classification ,0303 health sciences ,Chemistry ,021001 nanoscience & nanotechnology ,Cell biology ,Targeted drug delivery ,Pharmaceutical Preparations ,Drug delivery ,Female ,0210 nano-technology ,Peptides ,Homing (hematopoietic) - Abstract
Poly-peptide molecules have shown promising applications in drug delivery and tumor targeting. A series of tumor homing peptides were designed by exhaustively sampling low energy geometrical basins of amino acids at specific sites of a peptide molecule to induce a conformational lock. This peptide library was pruned to a limited set of eight molecules, employing electrostatic interactions, docking, and molecular dynamics simulations. These designed and optimized peptides were synthesized and tested on various cell lines, including breast cancer (MDA-MB-231), cervical cancer (HeLa), osteosarcoma (U2-OS), and non-cancerous mammary epithelial cells (MCF-10A) using confocal microscopy and flow cytometry. Peptides show differential uptake in cancerous MDA-MB-231, HeLa, U2-OS, and non-cancerous MCF-10A cells. Confocal imaging verified their ability to penetrate even in 3D tumorospheres of MDA-MB-231 cells. Further, experiments of mitochondrial membrane potential depolarization and Caspase-3 activation confirmed that their cytotoxic effects are by apoptosis. Homing ability of the designed peptides in in vivo system and fluorescence imaging with clinical samples of human origin have further confirmed that the in vitro studies are qualitatively identical and quantitatively comparable in their ability to selectively recognize tumor cells. Overall, we present a roadmap for the functional programming of peptide-based homing and penetrating molecules that can perform selective tumor targeting.
- Published
- 2020
25. Andrographolide suppresses NLRP3 inflammasome activation in microglia through induction of parkin-mediated mitophagy in in-vitro and in-vivo models of Parkinson disease
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Upadhyayula Suryanarayana Murty, Vegi Ganga Modi Naidu, Samir Ranjan Panda, Sahabuddin Ahmed, and Mohit Kwatra
- Subjects
0301 basic medicine ,Inflammasomes ,Andrographolide ,Ubiquitin-Protein Ligases ,Immunology ,Neuroprotection ,Parkin ,03 medical and health sciences ,Behavioral Neuroscience ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Mitophagy ,NLR Family, Pyrin Domain-Containing 3 Protein ,medicine ,Animals ,Endocrine and Autonomic Systems ,Chemistry ,Neurodegeneration ,Autophagy ,Inflammasome ,Parkinson Disease ,medicine.disease ,Cell biology ,Mice, Inbred C57BL ,030104 developmental biology ,Microglia ,Diterpenes ,NLRP3 inflammasome complex ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Cellular communication linking microglia activation and dopaminergic neuronal loss play an imperative role in the progression of Parkinson’s disease (PD); however, underlying molecular mechanisms are not precise and require further elucidation. NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome activation is extensively studied in context to microglial activation and progressive dopaminergic neuronal loss in PD. Several pathophysiological factors such as oxidative stress, mitochondrial dysfunction impaired mitophagy plays a crucial role in activating NLRP3 inflammasome complex. Hence, regulation of microglial activation through mitophagy could be a valuable strategy in controlling microglia mediated neurodegeneration. In this study we have developed a model of inflammasome activation by combining LPS with a mitochondrial complex-I inhibitor MPP+. The idea of using MPP+ after priming mouse microglia with LPS was to disrupt mitochondria and release reactive oxygen species, which act as Signal 2 in augmenting NLRP3 assembly, thereby releasing potent inflammatory mediators such as active interleukin-1 beta (IL-1β) and IL-18. LPS-MPP+ combination was seen to impaired the mitophagy by inhibiting the initial step of autophagosome formation as evidenced by protein expression and confocal imaging data. Treatment with Andrographolide promoted the parkin-dependent autophagic flux formation in microglia; resulting in the removal of defective mitochondria which in turn inhibit NLRP3 inflammasome activation. Additionally, the neuroprotective role of Andrographolide in inhibiting NLRP3 activation together with salvage ATP level via promoting parkin-dependent mitophagy was seen in the substantial nigra par compacta (SNpc) region of mice brain. Furthermore, Andrographolide rescued the dopaminergic neuron loss and improved the behavioural parameters in animal model. Collectively, our results reveal the role of mitophagy in the regulation of NLRP3 inflammasome by removing defective mitochondria. In addition, andrographolide was seen to abate NLRP3 inflammasome activation in microglia and rescue dopaminergic neuron loss.
- Published
- 2020
26. Stimuli-responsive In situ gelling system for nose-to-brain drug delivery
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Mukta Agrawal, Ajazuddin, Umesh Gupta, Vegi Ganga Modi Naidu, Upadhyayula Suryanarayana Murty, Swarnlata Saraf, Amit Alexander, V. Ravichandiran, Shailendra Saraf, Pramod Kumar, Anu Puri, Prashant Kesharwani, and Sunil Kumar Dubey
- Subjects
Drug ,0303 health sciences ,Mucociliary clearance ,Chemistry ,media_common.quotation_subject ,Pharmaceutical Science ,Brain ,02 engineering and technology ,Absorption (skin) ,Pharmacology ,021001 nanoscience & nanotechnology ,Smart polymer ,Dosage form ,03 medical and health sciences ,Nasal Absorption ,Nasal Mucosa ,Drug Delivery Systems ,Drug delivery ,Nasal administration ,0210 nano-technology ,Gels ,Administration, Intranasal ,030304 developmental biology ,media_common - Abstract
The diagnosis and treatment of neurological ailments always remain an utmost challenge for research fraternity due to the presence of BBB. The intranasal route appeared as an attractive and alternative route for brain targeting of therapeutics without the intrusion of BBB and GI exposure. This route directly and effectively delivers the therapeutics to different regions of the brain via olfactory and trigeminal nerve pathways. However, shorter drug retention time and mucociliary clearance curtail the efficiency of the intranasal route. The in situ mucoadhesive gel overthrow the limitations of direct nose-to-brain delivery by not only enhancing nasal residence time but also minimizing the mucociliary clearance and enzymatic degradation. This delivery system further improves the nasal absorption as well as bioavailability of drugs in the brain. The in situ mucoadhesive gel is a controlled and sustained release system that facilitates the absorption of various proteins, peptides and other larger lipophilic and hydrophilic moieties. Owing to multiple benefits, in situ gelling system has been widely explored to target the brain via nasal route. However, very few review works are reported which explains the application of in situ nasal gel for brain delivery of CNS acting moieties. Hence, in this piece of work, we have initially discussed the global statistics of neurological disorders reported by WHO and other reputed organizations, nasal anatomy, mechanism and challenges of nose-to-brain drug delivery. The work mainly focused on the use of different stimuli-responsive polymers, specifically thermoresponsive, pH-responsive, and ion triggered systems for the development of an effective and controlled dosage form, i.e., in situ nasal gel for brain targeting of bioactives. We have also highlighted the origin, structure, nature and phase transition behavior of the smart polymers found suitable for nasal administration, including poloxamer, chitosan, EHEC, xyloglucan, Carbopol, gellan gum and DGG along with their application in the treatment of neurological disorders. The article is aimed to gather all the information of the past 10 years related to the development and application of stimuli-responsive in situ nasal gel for brain drug delivery.
- Published
- 2020
27. Photo-Electro Active Nanocomposite Silk Hydrogel for Spatiotemporal Controlled Release of Chemotherapeutics: An In Vivo Approach toward Suppressing Solid Tumor Growth
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Praveen Kumar Jadi, Basveshwar Gawali, Ankit Gangrade, Biman B. Mandal, and Vegi Ganga Modi Naidu
- Subjects
Materials science ,Photochemistry ,Nanogels ,Biocompatible Materials ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Drug Delivery Systems ,In vivo ,Neoplasms ,medicine ,Animals ,Humans ,General Materials Science ,Doxorubicin ,Cardiotoxicity ,Nanocomposite ,technology, industry, and agriculture ,Hydrogels ,021001 nanoscience & nanotechnology ,Controlled release ,0104 chemical sciences ,SILK ,Apoptosis ,Drug delivery ,Biophysics ,0210 nano-technology ,medicine.drug - Abstract
Conventional systemic chemotherapeutic regimens suffer from challenges such as nonspecificity, shorter half-life, clearance of drugs, and dose-limiting toxicity. Localized delivery of chemotherapeutic drugs through noninvasive spatiotemporally controllable stimuli-responsive drug delivery systems could overcome these drawbacks while utilizing drugs approved for cancer treatment. In this regard, we developed photoelectro active nanocomposite silk-based drug delivery systems (DDS) exhibiting on-demand drug release in vivo. A functionally modified single-walled carbon nanotube loaded with doxorubicin (DOX) was embedded within a cross-linker free silk hydrogel. The resultant nanocomposite silk hydrogel showed electrical field responsiveness and near-infrared (NIR) laser-induced hyperthermal effect. The remote application of these stimuli in tandem or independent manner led to the increased thermal and electrical conductivity of nanocomposite hydrogel, which effectively triggered the intermittent on-demand drug release. In a proof-of-concept in vivo tumor regression study, the nanocomposite hydrogel was administered in a minimally invasive way at the periphery of the tumor by covering most of it. During the 21-day study, drastic tumor regression was recorded upon regular stimulation of nanocomposite hydrogel with simultaneous or individual external application of an electric field and NIR laser. Tumor cell death marker expression analysis uncovered the induction of apoptosis in tumor cells leading to its shrinkage. Heart ultrasound and histology revealed no cardiotoxicity associated with localized DOX treatment. To our knowledge, this is also the first report to show the simultaneous application of electric field and NIR laser in vivo for localized tumor therapy, and our results suggested that such strategy might have high clinical translational potential.
- Published
- 2020
28. Azithromycin Alleviates Cigarette Smoke Induced Epithelial Mesenchymal Transition (EMT), Airway Inflammation and Enhances Antioxidant Mechanisms in COPD
- Author
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Pritam Saha, S. Durugkar, Sukhwinder Singh Sohal, Siddhi Jain, Vegi Ganga Modi Naidu, Mathew Suji Eapen, and Pawan K. Sharma
- Subjects
COPD ,Antioxidant ,business.industry ,medicine.medical_treatment ,Cancer research ,Airway inflammation ,Medicine ,Cigarette smoke ,Epithelial–mesenchymal transition ,business ,medicine.disease ,Azithromycin ,medicine.drug - Published
- 2020
29. Effect of Long-Term Particulate Matter (PM10) Exposure on Lung Pathophysiology in Mice
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Pawan K. Sharma, Sukhwinder Singh Sohal, I. Mukherjee, Vegi Ganga Modi Naidu, Siddhi Jain, M. Das, Pritam Saha, S. Durugkar, and Sharad Gokhale
- Subjects
Lung ,medicine.anatomical_structure ,business.industry ,medicine ,Physiology ,Particulates ,business ,Pathophysiology ,Term (time) - Published
- 2020
30. Hesperidin alleviates chronic restraint stress and lipopolysaccharide-induced Hippocampus and Frontal cortex damage in mice: Role of TLR4/NF-κB, p38 MAPK/JNK, Nrf2/ARE signaling
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Basveshwar Gawali, Vegi Ganga Modi Naidu, Mohit Kwatra, Samir Ranjan Panda, and Sahabuddin Ahmed
- Subjects
0301 basic medicine ,Lipopolysaccharides ,Male ,Restraint, Physical ,medicine.medical_specialty ,Elevated plus maze ,MAP Kinase Signaling System ,NF-E2-Related Factor 2 ,Neuroprotection ,Hippocampus ,p38 Mitogen-Activated Protein Kinases ,Open field ,Proinflammatory cytokine ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Mice ,0302 clinical medicine ,Neurochemical ,Internal medicine ,medicine ,Animals ,Mice, Inbred BALB C ,Dose-Response Relationship, Drug ,business.industry ,Hesperidin ,NF-kappa B ,Cell Biology ,Tail suspension test ,Frontal Lobe ,Toll-Like Receptor 4 ,030104 developmental biology ,Endocrinology ,Chronic Disease ,TLR4 ,business ,030217 neurology & neurosurgery ,Stress, Psychological ,Behavioural despair test - Abstract
Stress and lipopolysaccharide (LPS) animal models are used for screening antidepressants and anxiolytic drugs. However, the lacunae for their combination (Restraint stress; RS and LPS) impacting inflammation, apoptosis and antioxidant signaling have not been explored. The present study investigated RS + LPS-induced neurobehavioral and neurochemical anomalies in hippocampus (HIP) and frontal cortex (FC) of mice. Furthermore, citrus-derived flavanone glycoside (Hesperidin; HSP) neuroprotective ability was also confirmed in this model. Male Balb/c mice were given RS (for 28 days) and LPS (single dose, 0.83 mg/kg, i.p.) on 28th day. RS + LPS challenge caused neurobehavioral deficits in mice as evaluated over elevated plus maze (EPM), open field test (OFT), light-dark box test, tail suspension test (TST), forced swim test (FST), sucrose preference test (SPT). Moreover, RS + LPS caused alteration via enhanced oxido-nitrosative stress, proinflammatory cytokines level (serum, HIP, FC), lower antioxidants (GSH, SOD, CAT), increased IBA-1, GFAP, TLR4/NF-κB, p38MAPK/JNK while decreased Nrf2/BDNF/HO-1 expression in HIP and FC of mice. The 21 days (8–28th day), HSP (50 and 100 mg/kg, p.o.) treatment significantly alleviated the anxiety and depressive-like behavior and reversed neurochemical, histopathological changes. HSP exerted the neuroprotective effect via its anti-inflammatory, anti-apoptotic, antioxidant and neurogenesis potential in treating psychiatric illness alone or associated with other diseases.
- Published
- 2020
31. Local administration of 4-Thiouridine, a novel molecule with potent anti-inflammatory properties, protects against experimental colitis and arthritis
- Author
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Dinesh Thummuri, Manish Kumar Jeengar, Vegi Ganga Modi Naidu, Srinivas Uppugunduri, Sudeep Chenna Narendra, and Mattias Magnusson
- Subjects
0301 basic medicine ,Male ,Knee Joint ,medicine.drug_class ,Colon ,medicine.medical_treatment ,Immunology ,Thiouridine ,Anti-Inflammatory Agents ,Arthritis ,Inflammation ,Pharmacology ,Anti-inflammatory ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Immunology and Allergy ,Animals ,Colitis ,Antigens ,biology ,business.industry ,Dextran Sulfate ,NF-kappa B ,Serum Albumin, Bovine ,medicine.disease ,Ulcerative colitis ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,Cytokine ,Cyclooxygenase 2 ,030220 oncology & carcinogenesis ,Myeloperoxidase ,biology.protein ,Cytokines ,Tumor necrosis factor alpha ,Colitis, Ulcerative ,Female ,medicine.symptom ,business - Abstract
Previous studies in a rat model of Sephadex induced lung inflammation showed that 4-Thiouridine (4SU), a thiol substituted nucleoside, was very effective in reducing edema, leukocyte influx and TNF levels in bronchoalvelolar lavage fluid. However, little is known about the factors and mechanisms underlying these effects. In the present study, we have used two separate mouse models of chronic inflammation, a model of dextran sulphate sodium (DSS) induced colitis and a model of antigen induced arthritis, to evaluate the anti-inflammatory effect of 4-thiouridine. We have analyzed a broad spectrum of inflammatory mediators in order to delineate the mechanisms behind a potential anti-inflammatory effect of 4SU. Colitis was induced in C57BL/6 mice by administration of 3.5% DSS in drinking water for 5 days and the potential anti-colitic effect of 4SU was assessed by monitoring the disease activity index (DAI), measurement of colon length and histopathological analysis of colon tissue. We analyzed tissue myeloperoxidase (MPO) activity, serum pro-inflammatory cytokines (IL-1β, IL-6 and TNF), mRNA and protein expression of pro-inflammatory cytokines, COX-2, and NF-κB activity in colitis tissue. Intracolonic administration of 4SU (5 mg/kg & 10 mg/kg.) significantly inhibited MPO activity and reduced the levels of pro-inflammatory cytokines (IL-1β, IL-6 and TNF) as well as COX-2. Further, NF-κB activation was also blocked by attenuating the phosphorylation of IkB kinase (IKK α/β) in DSS-induced colitis tissues. Arthritis was induced by intra-articular injection of mBSA in the knee of NMRI mice pre-immunized with mBSA and 4SU was administered locally by direct injection into the knee joint. The antiarthritic potential of 4SU was calculated by histopathological scores and histochemical analysis of joint tissue. Further, immunohistochemistry was used to study inflammatory cell infiltration and expression of cytokines and adhesion molecules in the synovium. Local administration of 50–100 mg/kg 4SU at the time of arthritis onset clearly prevented development of joint inflammation and efficiently inhibited synovial expression of CD18, local cytokine production and recruitment of leukocytes to the synovium. Taken together, our data clearly demonstrates a potent anti-inflammatory effect of 4SU in two experimental models. In conclusion 4SU could be a new promising candidate for therapeutic modulation of chronic inflammatory diseases like ulcerative colitis and arthritis.
- Published
- 2020
32. Effects of intranasal azithromycin on features of cigarette smoke-induced lung inflammation
- Author
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Vegi Ganga Modi Naidu, Sharad Gokhale, Pawan K. Sharma, Sneha Durugkar, Siddhi Jain, and Pritam Saha
- Subjects
Pharmacology ,COPD ,Combination therapy ,business.industry ,Inflammation ,Azithromycin ,medicine.disease ,Proinflammatory cytokine ,In vivo ,Fibrosis ,Medicine ,Tumor necrosis factor alpha ,medicine.symptom ,business ,Dexamethasone ,medicine.drug - Abstract
Airflow limitation in chronic obstructive pulmonary disease (COPD) is the result of exaggerated airway fibrosis and obliteration of the small airways due to persistent inflammation, and an impaired anti-oxidant response. EMT has been implicated as an active signalling process in cigarette smoke (CS)-induced lung pathology, and macrolide Azithromycin (AZT) use has gained interest in treating COPD. Here, we tested effectiveness of intra-nasal AZT alone and in combination with dexamethasone (DEX) on CS-induced acute lung inflammation. Human alveolar epithelial cells (A549) were treated with CS extract (CSE) for 48 h, and male Balb/c mice were exposed to CS (3 cigarettes-3 times/day) for 4 days. The effects of AZT alone (0.25 and 1.25 μM, in vitro; 0.5 and 5 mg/kg, in vivo) or in combination with DEX (1 μM, in vitro; 1 mg/kg, in vivo) on CS-induced cellular cytotoxicity, oxidative stress, inflammation, and lung function were assessed. AZT alone and in combination with DEX significantly inhibited the CS (E)-induced expression of mesenchymal protein markers and the regulatory protein β-catenin. Furthermore, AZT by itself or in combination with DEX significantly suppressed CS-induced expression of the proinflammtory cytokines TNFα, IL1β and IL6 and prevented pNFkB. Mechanistically, AZT restored the CS-induced reduction in anti-oxidant transcription factor NRF2 and upregulated HDAC2 levels, thereby repressing inflammatory gene expression. Beneficial effects of AZT functionally translated in improved lung mechanics in vivo. Further preclinical and clinical studies are warranted to fully establish and validate the therapeutic efficacy of AZT as a mono- or combination therapy for the treatment of COPD.
- Published
- 2022
33. Synthesis and Biological Evaluation of Thieno[2, 3-d ]pyrimidine-amides as Potential Anticancer Agents
- Author
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Ahmed Kamal, Sowjanya Thatikonda, Vegi Ganga Modi Naidu, Srinivas Angapelly, Bathini Nagendra Babu, and Posa Venkata Sri Ramya
- Subjects
Pyrimidine ,010405 organic chemistry ,General Chemistry ,Cell cycle ,01 natural sciences ,0104 chemical sciences ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Biochemistry ,chemistry ,Apoptosis ,030220 oncology & carcinogenesis ,Biological evaluation - Published
- 2018
34. Hepatoprotective Cocrystals and Salts of Riluzole: Prediction, Synthesis, Solid State Characterization, and Evaluation
- Author
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Rahul B. Chavan, Nalini R. Shastri, Vegi Ganga Modi Naidu, Sridhar Balasubramanian, Rajesh Thipparaboina, and Balvant Yadav
- Subjects
Fumaric acid ,Synthon ,02 engineering and technology ,General Chemistry ,Syringic acid ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,01 natural sciences ,Combinatorial chemistry ,Cinnamic acid ,0104 chemical sciences ,Riluzole ,Ferulic acid ,chemistry.chemical_compound ,chemistry ,medicine ,Vanillic acid ,General Materials Science ,Solubility ,0210 nano-technology ,medicine.drug - Abstract
Riluzole is a drug, used to slow the course of amyotrophic lateral sclerosis. Due to its unique structure and functionalities, it is able to form both salts and cocrystals. This is a BCS class II drug with poor solubility and causes hepatotoxicity which limits its application. The present study aims toward development of novel solid forms of riluzole to address the said limitations. Apart from this, an attempt has been made to develop a prediction model using software tools to identify the appropriate synthons for formation of cocrystals. It was observed that out of 33 coformers selected, prediction results were in agreement with the experimental outcome for 25 coformers, which demonstrated the potential of the model developed. Seven new solid forms of riluzole, five cocrystals with ferulic acid, syringic acid, vanillic acid, cinnamic acid, and proline, and two salts with 2,4 dihydroxybenzoic acid and fumaric acid were successfully developed. All the solid forms were characterized by DSC, powder XRD, FTIR...
- Published
- 2018
35. Quercetin and piperine enriched nanostructured lipid carriers (NLCs) to improve apoptosis in oral squamous cellular carcinoma (FaDu cells) with improved biodistribution profile
- Author
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Vishal Sharad Chaudhari, Upadhyayula Suryanarayana Murty, Basveshwar Gawali, Subham Banerjee, Pritam Saha, and Vegi Ganga Modi Naidu
- Subjects
Biodistribution ,Polyunsaturated Alkamides ,Apoptosis ,Pharmacology ,chemistry.chemical_compound ,Alkaloids ,Piperidines ,Oral administration ,Animals ,Humans ,Distribution (pharmacology) ,Tissue Distribution ,Benzodioxoles ,Particle Size ,Cytotoxicity ,IC50 ,Membrane Potential, Mitochondrial ,Squamous Cell Carcinoma of Head and Neck ,Fatty Acids ,In vitro ,Nanostructures ,Rats ,Drug Liberation ,chemistry ,Piperine ,Cancer cell ,Mouth Neoplasms ,Quercetin ,Drug Screening Assays, Antitumor ,Nanoparticle Drug Delivery System - Abstract
Oral squamous cellular carcinoma (OSCC) is considered a life-threatening disease with detection in late stages, which forces us to opt for dangerous treatment with a combination of chemotherapy and radiotherapy. Herbal components such as piperine and quercetin are derived from edible sources, proving their anticancer potential against oral cancer cells in vitro. Encapsulation into lipid matrix-mediated nanostructured lipid carriers (NLCs) can make both drugs bio-accessible. NLCs were synthesised using the high shear homogenisation method and characterised for their physicochemical properties, followed by in vitro cellular evaluation in FaDu oral cancer cells. NLCs showed negatively charged particles smaller than 180 nm with a polydispersity index (PDI) of 85% entrapment efficiency and an improved drug release profile compared to their pristine counterparts. Differential scanning calorimetry (DSC) thermograms showed conversion into an amorphous matrix in lyophilized NLCs, which was supported by X-ray diffraction (XRD) analysis. The cytotoxicity assay showed the IC50 concentration for dual drug-loaded NLCs, which was more effective than the pure drug solution. NLCs were found to be internalised in cells in a short time with an almost 95% co-localization rate. Dual drug-loaded NLCs showed maximum depolarisation of the mitochondrial membrane along with more apoptotic changes. Improved apoptosis was confirmed in NLCs using flow cytometry. The in vivo biodistribution of Coumarin-6 labelled NLCs in rats confirmed their efficient distribution in various parts of the oral cavity through oral administration. Optimised dual drug-loaded NLCs provide a better option for delivering both drugs through a single lipid matrix against oral cancer.
- Published
- 2021
36. Lithocholic acid-tryptophan conjugate (UniPR126) based mixed micelle as a nano carrier for specific delivery of niclosamide to prostate cancer via EphA2 receptor
- Author
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Eswara Rao Puppala, N P Syamprasad, Vegi Ganga Modi Naidu, Amit Alexander, Arun Kumar Jannu, Basveshwar Gawali, Naveen Chella, Jagadeesh Kumar Gangasani, and Srujan Marepally
- Subjects
Male ,Lithocholic acid ,Bile acid ,medicine.drug_class ,Receptor, EphA2 ,Tryptophan ,Prostatic Neoplasms ,Pharmaceutical Science ,Pharmacology ,chemistry.chemical_compound ,chemistry ,In vivo ,Cell Line, Tumor ,Cancer cell ,medicine ,Humans ,Niclosamide ,Lithocholic Acid ,Receptor ,Wnt Signaling Pathway ,Micelles ,medicine.drug ,Conjugate - Abstract
Targeted delivery of chemotherapeutic agents is considered a prominent strategy for the treatment of cancer due to its site-specific delivery, augmented penetration, bioavailability, and improved therapeutic efficiency. In the present study, we employed UniPR126 as a carrier in a mixed nanomicellar delivery system to target and deliver anticancer drug NIC specifically to cancer cells via EphA2 receptors as these receptors are overexpressed in cancer cells but not in normal cells. The specificity of the carrier was confirmed from the significant enhancement in the uptake of coumarin-6 loaded mixed nanomicelle by EphA2 highly expressed PC-3 cells compared to EphA2 low expressed H4 cells. Further, niclosamide-loaded lithocholic acid tryptophan conjugate-based mixed nanomicelle has shown significant synergistic cytotoxicity in PC-3 but not in H4 cells. In vivo anticancer efficacy data in PC-3 xenograft revealed a significant reduction in the tumor volume (66.87%) with niclosamide-loaded lithocholic acid tryptophan conjugate nanomicelle, where pure niclosamide showed just half of the activity. Molecular signaling data by western blotting also indicated that niclosamide-loaded lithocholic acid tryptophan conjugate nanomicelle interfered with the EphA2 receptor signaling and inhibition of the Wnt/beta-catenin pathway and resulted in the synergistic anticancer activity compared to niclosamide pure drug.
- Published
- 2021
37. Synthesis of 2,5-Disubstituted-1,3,4-oxadiazole Derivatives and Their Evaluation as Anticancer and Antimycobacterial Agents
- Author
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Bhaskar Kummari, Umarani Brahma, Sridhar Balasubramanian, Parsharamulu Rayam, Naveen Polkam, Jaya Shree Anireddy, and Vegi Ganga Modi Naidu
- Subjects
Veratric acid ,Antimycobacterial Agents ,010405 organic chemistry ,Stereochemistry ,medicine.drug_class ,Oxadiazole ,General Chemistry ,010402 general chemistry ,Antimycobacterial ,01 natural sciences ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Bromide ,medicine ,1 3 4 oxadiazole derivatives ,Bioisostere - Abstract
A series of regioisomeric (2,5-dimethoxybenzoic acid, veratric acid) analogues were prepared by swapping the carboxylic motif to its oxadiazole bioisostere and have been screened for in vitro anticancer studies by using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) colorimetric assay. All of them were well characterized by spectroscopic techniques. Among the screened compounds, 9 i (2-(2,5-dimethoxyphenyl)-5-(5-phenylthiophen-2-yl)-1,3,4-oxadiazole) demonstrated superior activity against MDA231 cells. Products 9 i displayed excellent activity against DU145, HCT15 and 10 i (2-(3,4-dimethoxyphenyl)-5-(5-phenylthiophen-2-yl)-1,3,4-oxadiazole) against MDA231 cells. Structure of 10 c (2-(3,4-dimethoxyphenyl)-5-(2,4,6-trimethoxyphenyl)-1,3,4-oxadiazole) was further authenticated through single crystal X-ray diffraction. Analogue 9 i have come out to be the best anticancer and antimycobacterial agent.
- Published
- 2017
38. Niclosamide encapsulated polymeric nanocarriers for targeted cancer therapy
- Author
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Rohit Srivastava, Nishant Kumar Jain, Rajdip Bandyopadhyaya, Rajendra Prasad, Vegi Ganga Modi Naidu, M. C. Bavya, and R S Prabhuraj
- Subjects
Drug ,chemistry.chemical_classification ,Reactive oxygen species ,General Chemical Engineering ,media_common.quotation_subject ,Cell ,02 engineering and technology ,General Chemistry ,Pharmacology ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,0104 chemical sciences ,chemistry.chemical_compound ,medicine.anatomical_structure ,chemistry ,Hyaluronic acid ,Cancer cell ,Zeta potential ,medicine ,Nanocarriers ,0210 nano-technology ,Niclosamide ,media_common ,medicine.drug - Abstract
Localized cancer rates are on an upsurge, severely affecting mankind across the globe. Timely diagnosis and adopting appropriate treatment strategies could improve the quality of life significantly reducing the mortality and morbidity rates. Recently, nanotherapeutics has precipitously shown increased efficacy for controlling abnormal tissue growth in certain sites in the body, among which ligand functionalized nanoparticles (NP) have caught much attention for improved survival statistics via active targeting. Our focus was to repurpose the antihelminthic drug, niclosamide (NIC), which could aid in inhibiting the abnormal growth of cells restricted to a specific region. The work here presents a one-pot synthesis of niclosamide encapsulated, hyaluronic acid functionalized core–shell nanocarriers [(NIC-PLGA NP)HA] for active targeting of localized cancer. The synthesized nanocarriers were found to possess spherical morphology with mean size of 150.8 ± 9 nm and zeta potential of −24.9 ± 7.21 mV. The encapsulation efficiency was found to be 79.19 ± 0.16% with a loading efficiency of 7.19 ± 0.01%. The nanohybrids exhibited extreme cytocompatibility upon testing with MDA-MB-231 and L929 cell lines. The rate of cancer cell elimination was approximately 85% with targeted cell imaging results being highly convincing. [(NIC-PLGA NP)HA] demonstrates increased cellular uptake leading to a hike in reactive oxygen species (ROS) generation, combating tumour cells aiding in the localized treatment of cancer and associated therapy.
- Published
- 2019
39. Toll-like receptor 4: An attractive therapeutic target for acute kidney injury
- Author
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Sourav Kundu, Pakpi Doye, Vegi Ganga Modi Naidu, Chetan Ram, Ankush Kumar Jha, Upadhyayula Suryanarayana Murty, Bidya Dhar Sahu, Shobhit Gairola, and Abu Mohammad Syed
- Subjects
0301 basic medicine ,Chemokine ,Inflammation ,urologic and male genital diseases ,Bioinformatics ,030226 pharmacology & pharmacy ,General Biochemistry, Genetics and Molecular Biology ,Pathogenesis ,03 medical and health sciences ,Drug Delivery Systems ,0302 clinical medicine ,medicine ,Animals ,Humans ,General Pharmacology, Toxicology and Pharmaceutics ,Glucocorticoids ,Kidney ,Toll-like receptor ,biology ,urogenital system ,business.industry ,Pattern recognition receptor ,Acute kidney injury ,Endothelial Cells ,Proton Pump Inhibitors ,General Medicine ,Acute Kidney Injury ,medicine.disease ,Toll-Like Receptor 4 ,030104 developmental biology ,medicine.anatomical_structure ,TLR4 ,biology.protein ,medicine.symptom ,business ,Drugs, Chinese Herbal - Abstract
Acute kidney injury (AKI) is a progressive renal complication which significantly affects the patient's life with huge economic burden. Untreated acute kidney injury eventually progresses to a chronic form and end-stage renal disease. Although significant breakthroughs have been made in recent years, there are still no effective pharmacological therapies for the treatment of acute kidney injury. Toll-like receptor 4 (TLR4) is a well-characterized pattern recognition receptor, and increasing evidence has shown that TLR4 mediated inflammatory response plays a pivotal role in the pathogenesis of acute kidney injury. The expression of TLR4 has been seen in resident renal cells, including podocytes, mesangial cells, tubular epithelial cells and endothelial cells. Activation of TLR4 signaling regulates the transcription of numerous pro-inflammatory cytokines and chemokines, resulting in renal inflammation. Therefore, targeting TLR4 and its downstream effectors could serve as an effective therapeutic intervention to prevent renal inflammation and subsequent kidney damage. For the first time, this review summarizes the literature on acute kidney injury from the perspective of TLR4 from year 2010 to 2020. In the current review, the role of TLR4 signaling pathway in AKI with preclinical evidence is discussed. Furthermore, we have highlighted several compounds of natural and synthetic origin, which have the potential to avert the renal TLR4 signaling in preclinical AKI models and have shown protection against AKI. This scientific review provides new ideas for targeting TLR4 in the treatment of AKI and provides strategies for the drug development against AKI.
- Published
- 2021
40. Emu oil based nano-emulgel for topical delivery of curcumin
- Author
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Shweta Shrivastava, Sri Vishnu Kiran Rompicharla, Manish Kumar Jeengar, Ramakrishna Sistla, Vegi Ganga Modi Naidu, Naveen Chella, and Nalini R. Shastri
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Curcumin ,Administration, Topical ,Chemistry, Pharmaceutical ,Anti-Inflammatory Agents ,Pharmaceutical Science ,02 engineering and technology ,Pharmacology ,Carrageenan ,Excipients ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,Drug Delivery Systems ,Pulmonary surfactant ,immune system diseases ,In vivo ,hemic and lymphatic diseases ,medicine ,Animals ,Edema ,Topical route ,Inflammation ,business.industry ,021001 nanoscience & nanotechnology ,Arthritis, Experimental ,Rats ,Surgery ,Disease Models, Animal ,030104 developmental biology ,Solubility ,chemistry ,Emu oil ,Drug delivery ,Nanoparticles ,Emulsions ,Swelling ,medicine.symptom ,0210 nano-technology ,business ,Oils - Abstract
Curcumin and emu oil derived from emu bird (Dromaius novaehollandiae) has shown promising results against inflammation. However, the delivery of curcumin is hindered due to low solubility and poor permeation. In addition, till date the role of emu oil in drug delivery has not been explored systemically. Hence, the current investigation was designed to evaluate the anti-inflammatory potential of curcumin in combination with emu oil from a nanoemulgel formulation in experimental inflammation and arthritic in vivo models. Nanoemulsion was prepared using emu oil, Cremophor RH 40 and Labrafil M2125CS as oil phase, surfactant and co-surfactant. The optimized curcumin loaded nanoemulsion with emu oil was incorporated into carbopol gel for convenient application by topical route. The anti-inflammatory efficacy was evaluated in carrageenan induced paw edema and FCA induced arthritic rat model in terms of paw swelling, weight indices of the liver and spleen, pathological changes in nuclear factor kappa B, iNOS, COX-2 expression and inflammatory cytokines. Arthritic scoring, paw volume, biochemical, molecular, radiological and histological examinations indicated significant improvement in anti-inflammatory activity with formulations containing curcumin in combination with emu oil compared to pure curcumin. These encouraging results demonstrate the potential of formulations containing curcumin and emu oil combination in rheumatoid arthritis.
- Published
- 2016
41. Targeting NLRP3 inflammasome as a promising approach for treatment of diabetic nephropathy: Preclinical evidences with therapeutic approaches
- Author
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Ankush Kumar Jha, Upadhyayula Suryanarayana Murty, Bidya Dhar Sahu, Vegi Ganga Modi Naidu, Abu Mohammad Syed, Aparajita Ghosh, Chetan Ram, and Shobhit Gairola
- Subjects
0301 basic medicine ,Inflammasomes ,Anti-Inflammatory Agents ,Inflammation ,Disease ,Bioinformatics ,Proinflammatory cytokine ,Diabetic nephropathy ,03 medical and health sciences ,0302 clinical medicine ,Mediator ,Diabetes mellitus ,NLR Family, Pyrin Domain-Containing 3 Protein ,medicine ,Animals ,Humans ,Diabetic Nephropathies ,Pharmacology ,business.industry ,Interleukin ,Inflammasome ,medicine.disease ,030104 developmental biology ,medicine.symptom ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Diabetes mellitus is an increasingly prevalent disease around the globe. The epidemic of diabetes mellitus and its complications pretenses the foremost health threat globally. Diabetic nephropathy is the notable complication in diabetes, leading to end-stage renal disease (ESRD) and premature death. Abundant experimental evidence indicates that oxidative stress and inflammation are the important mediators in diabetic kidney diseases and interlinked with various signal transduction molecular mechanisms. Inflammasomes are the critical components of innate immunity and are recognized as a critical mediator of inflammation and autoimmune disorders. NOD-like receptor protein 3 (NLRP3) inflammasome is the well-characterized protein and it exhibits the sterile inflammation through the regulation of pro-inflammatory cytokines interleukin (IL)-1β and IL-18 production in tissues. In recent years, the role of NLRP3 inflammasome in the pathophysiology of diabetic kidney diseases in both clinical and experimental studies has generated great interest. In the current review, we focused on and discussed the role of NLRP3 inflammasome in diabetic nephropathy. A literature review was performed using online databases namely, PubMed, Scopus, Google Scholar and Web of science to explore the possible pharmacological interventions that blunt the NLRP3 inflammasome-caspase-1-IL-1β/IL-18 axis and shown to have a beneficial effect in diabetic kidney diseases. This review describes the inhibition of NLRP3 inflammasome activation as a promising therapeutic target for drug discovery in future.
- Published
- 2020
42. IQOS exposure impairs human airway cell homeostasis: direct comparison with traditional cigarette and e-cigarette
- Author
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Mathew Suji Eapen, Pawan K. Sharma, Vegi Ganga Modi Naidu, and Sukhwinder Singh Sohal
- Subjects
Pulmonary and Respiratory Medicine ,Smoking device ,business.industry ,Original Research Letters ,lcsh:R ,lcsh:Medicine ,Cigarette use ,Human airway ,Nicotine Addiction ,Tobacco smoke ,Nicotine ,03 medical and health sciences ,0302 clinical medicine ,030228 respiratory system ,Smooth muscle ,Cigarette smoking ,Environmental health ,medicine ,030212 general & internal medicine ,business ,medicine.drug - Abstract
While cigarette smoking still remains one of the most pressing global health issues of our time, newer forms of smoking device have been introduced across the globe in the last decade [1]. Electronic nicotine/non-nicotine delivery systems commonly known as electronic cigarettes (eCig) heat a solution (e-liquid) to create vapour [2]; the latest addition to this list is the introduction of heat-not-burn (HNBs) tobacco products branded as IQOS [3]. HNBs are hybrids between eCigs and traditional cigarettes i.e. they are equipped with a device that heats the product, without burning to generate aerosol and the product being heated is not a liquid but real tobacco [4, 5]. eCig vaping is comparatively new but its use is increasing at an alarming rate; it is believed it will surpass the use of traditional cigarettes in next 5 years, with global sales reaching US$10 billion [6]. Since its launch in Italy and Japan in 2014, IQOS has become the leader in the HNB market [4, 7]. To date, IQOS is available in 41 countries, including 22 from the WHO-European region, and its market share has now reached the level of cigars in Italy [4]. Emerging data shows that eCig use, particularly in the young, is associated with future cigarette use [8]. Similarly, over half of the people interested in IQOS are never-smokers [4]. Therefore, both eCigs and IQOS may represent a gateway for nicotine addiction among never-smokers rather than a substitute used for harm-reduction purposes in current smokers [4]. It is now clear that eCig vapour contains high levels of toxic compounds [9], which adversely affect respiratory, gastrointestinal and cardiovascular systems both in vitro and in vivo [10–12]. It is also important to recognise that IQOS products are comparatively new but emerging research suggests that IQOS emits substantially high levels of carbonyls [13]. There is as yet no published comparison between the effect of eCigs, IQOS and tobacco smoke on human lungs. Here, we examine whether exposure to IQOS has the same damaging effect on human airway epithelial and smooth muscle cells as traditional tobacco cigarette and eCigs in vitro., Heat-not-burn (HNB) devices can alter vital physiological functions in the lung. HNB devices may not be a safer option than cigarette smoking or eCig vaping; this does not support the recommendation of their use over other nicotine delivery products. http://ow.ly/wZ5P30ng8bU
- Published
- 2018
43. Corrigendum to 'Preparation, characterization, and cytotoxicity studies of niclosamide loaded mesoporous drug delivery systems' [Int. J. Pharm. 528 (2017) 202-214]
- Author
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Vegi Ganga Modi Naidu, Rajesh Thipparaboina, Sowjanya Thatikonda, Vishwas Pardhi, Rahul B. Chavan, and Nalini R. Shastri
- Subjects
Chemistry ,INT ,Drug delivery ,medicine ,Pharmaceutical Science ,Cytotoxicity ,Mesoporous material ,Combinatorial chemistry ,Niclosamide ,medicine.drug - Published
- 2018
44. Spirooxindole-derived morpholine-fused-1,2,3-triazoles: Design, synthesis, cytotoxicity and apoptosis inducing studies
- Author
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V. Lakshma Nayak, T. Srinivasa Reddy, Nagula Shankaraiah, Manish Kumar Jeengar, Kishna Ram Senwar, Pankaj Sharma, Ahmed Kamal, and Vegi Ganga Modi Naidu
- Subjects
Indoles ,Morpholines ,Antineoplastic Agents ,Apoptosis ,HeLa ,Structure-Activity Relationship ,chemistry.chemical_compound ,Cell Line, Tumor ,Drug Discovery ,Humans ,Spiro Compounds ,Fragmentation (cell biology) ,Cell Proliferation ,Pharmacology ,A549 cell ,Dose-Response Relationship, Drug ,Molecular Structure ,biology ,Cytotoxins ,Cell growth ,Chemistry ,Cell Cycle ,Organic Chemistry ,Acridine orange ,General Medicine ,Triazoles ,Cell cycle ,biology.organism_classification ,Biochemistry ,Cell culture ,Drug Design ,Drug Screening Assays, Antitumor - Abstract
A series of new spirooxindole-derived morpholine-fused-1,2,3-triazole derivatives has been synthesized from isatin spiro-epoxides. The protocol involves regiospecific isatin-epoxide ring opening with azide nucleophile followed by sequential O-propargylation, and intramolecular 1,3-dipolar cycloaddition reaction. These compounds have been evaluated for their antiproliferative activity against selected human tumor cell lines of lung (A549), breast (MCF-7), cervical (HeLa), and prostate (DU-145). Among the tested compounds, 6i, 6n and 6p showed potent growth inhibition against A549 cell line with IC50 values in the range of 1.87-4.36 μM, which are comparable to reference standards doxorubicin and 5-flourouracil. The compounds 6i and 6p treated A549 cells displayed typical apoptotic morphological features such as cell shrinkage, nuclear condensation, fragmentation, and decreased migration potential. Flow-cytometry analysis revealed that the compounds arrested the cells in G2/M phase of cell cycle. Hoechst and acridine orange/ethidium bromide staining studies also showed that the cell proliferation was inhibited through induction of apoptosis. Moreover, the compounds treatment led to collapse of the mitochondrial membrane potential (DΨm) and increased levels of reactive oxygen species (ROS) were noted in A549 cells.
- Published
- 2015
45. Anticancer effect of celastrol on human triple negative breast cancer: Possible involvement of oxidative stress, mitochondrial dysfunction, apoptosis and PI3K/Akt pathways
- Author
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V. Sudhakar Reddy, Shweta Shrivastava, Vegi Ganga Modi Naidu, G. Bhanuprakash Reddy, and Manish Kumar Jeengar
- Subjects
Cell Survival ,Clinical Biochemistry ,Apoptosis ,Breast Neoplasms ,Pathology and Forensic Medicine ,Phosphatidylinositol 3-Kinases ,chemistry.chemical_compound ,Annexin ,Molecular Biology ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Chemistry ,Akt/PKB signaling pathway ,Triterpenes ,Mitochondria ,Cell biology ,Oxidative Stress ,Celastrol ,MCF-7 Cells ,Cancer research ,Phosphorylation ,Signal transduction ,Pentacyclic Triterpenes ,Proto-Oncogene Proteins c-akt ,Signal Transduction - Abstract
Signaling via the phosphatidylinositol-3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) is crucial for divergent physiological processes including transcription, translation, cell-cycle progression and apoptosis. The aim of work was to elucidate the anti-cancer effect of celastrol and the signal transduction pathways involved. Cytotoxic effect of celastrol was assessed by MTT assay on human triple negative breast cancer cells (TNBCs) and compared with that of MCF-7. Apoptosis induction was determined by AO/EtBr staining, mitochondrial membrane potential by JC-1, Annexin binding assays and modulation of apoptotic proteins and its effect on PI3K/Akt/mTOR pathway by western blotting. Celastrol induced apoptosis in TNBC cells, were supported by DNA fragmentation, caspase-3 activation and PARP cleavage. Meanwhile, celastrol triggered reactive oxygen species production with collapse of mitochondrial membrane potential, down-regulation of Bcl-2 and up-regulation of Bax expression. Celastrol effectively decreased PI3K 110α/85α enzyme activity, phosphorylation of Aktser473 and p70S6K1 and 4E-BP1. Although insulin treatment increased the phosphorylation of Aktser473, p70S6K1, 4E-BP1, celastrol abolished the insulin mediated phosphorylation. It clearly indicates that celastrol acts through PI3k/Akt/mTOR axis. We also found that celastrol inhibited the Akt/GSK3β and Akt/NFkB survival pathway. PI3K/Akt/mTOR inhibitor, PF-04691502 and mTOR inhibitor rapamycin enhanced the apoptosis-inducing effect of celastrol. These data demonstrated that celastrol induces apoptosis in TNBC cells and indicated that apoptosis might be mediated through mitochondrial dysfunction and PI3K/Akt signaling pathway.
- Published
- 2015
46. Abietic acid attenuates RANKL induced osteoclastogenesis and inflammation associated osteolysis by inhibiting the NF-KB and MAPK signaling
- Author
-
Vegi Ganga Modi Naidu, Veerabhadra Swamy Challa, Lalita Guntuku, Ravinder Naik Ramavat, and Dinesh Thummuri
- Subjects
0301 basic medicine ,Osteolysis ,Physiology ,Clinical Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,In vivo ,Osteoclast ,Osteogenesis ,medicine ,Animals ,Humans ,Polylysine ,Phosphorylation ,Receptor ,Inflammation ,Mitogen-Activated Protein Kinase Kinases ,Osteoblasts ,biology ,NFATC Transcription Factors ,Activator (genetics) ,Phosphatidylethanolamines ,RANK Ligand ,NF-kappa B ,NF-κB ,Cell Differentiation ,Cell Biology ,medicine.disease ,Actins ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,RANKL ,030220 oncology & carcinogenesis ,Abietanes ,Cancer research ,biology.protein ,Osteoporosis ,Signal Transduction - Abstract
Osteoporosis is a major debilitating cause of fractures and decreases the quality of life in elderly patients. Bone homeostasis is maintained by bone forming osteoblasts and bone resorpting osteoclasts. Substantial evidences have shown that targeting osteoclasts using natural products is a promising strategy for the treatment of osteoporosis. In the current study, we investigated the osteoprotective effect of Abietic acid (AA) in in vitro and in vivo models of osteolysis. In vitro experiments demonstrated that, AA suppressed receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis and F-actin ring formation in a concentration dependent manner. Mechanistically, AA abrogated RANKL-induced phosphorylation of IKKα/β (ser 176/180), IkBα (ser 32), and inhibited the nuclear translocation of NF-κB. We also found that, AA attenuated the RANKL-induced phosphorylation of MAPKs and decreased the expression of osteoclast specific genes such as TRAP, DC-STAMP, c-Fos, and NFATc1. Consistent with in vitro results, in vivo Lipoploysaccharide (LPS)-induced osteolysis model showed that AA inhibited the LPS-induced serum surge in cytokines TNF-α and IL-6. μ-CT analysis showed that AA prevented the LPS-induced osteolysis. Furthermore, histopathology and TRAP staining results suggested that AA decreased the number of osteoclasts in LPS-injected mice. Taken together, we demonstrated that the osteoprotective action of AA is coupled with the inhibition of NF-κB and MAPK signaling and subsequent inhibition of NFATc1 and c-Fos activities. Hence, AA may be considered as a promising drug candidate for the treatment of osteoporosis.
- Published
- 2017
47. Curcumin potentiates the anti-arthritic effect of prednisolone in Freund's complete adjuvant-induced arthritic rats†
- Author
-
Shankar Ganesh Gadepalli, Ramakrishna Sistla, Madhusudana Kuncha, Bidya Dhar Sahu, and Vegi Ganga Modi Naidu
- Subjects
Male ,Curcumin ,Necrosis ,Prednisolone ,Freund's Adjuvant ,Interleukin-1beta ,Pharmaceutical Science ,Arthritis ,Pharmacology ,medicine.disease_cause ,Antioxidants ,chemistry.chemical_compound ,medicine ,Animals ,Rats, Wistar ,Plant Extracts ,Tumor Necrosis Factor-alpha ,business.industry ,Body Weight ,medicine.disease ,Arthritis, Experimental ,Rats ,Drug Combinations ,chemistry ,Freund's adjuvant ,Toxicity ,Steroids ,Tumor necrosis factor alpha ,medicine.symptom ,business ,Spleen ,Oxidative stress ,medicine.drug - Abstract
Objectives The present study was aimed at investigating the effect of curcumin in combination with prednisolone for the effective treatment of arthritis with reduced side effects when glucocorticoids therapy is indicated. Methods Arthritis was induced in wistar rats by subplantar injection of Freund's complete adjuvant, and animals were observed for the symptoms of arthritis during the period of 21 days. Combined treatment of curcumin with various doses of prednisolone (1.25, 2.5 and 5 mg/kg) was evaluated in order to ascertain the efficacy and toxicity induced by steroid. Key findings Arthritic animals showed significant increase in tumour necrosis factor-α and IL-1β levels in paw tissue and IL-1β in serum. Combined therapy of curcumin with low doses of prednisolone showed pronounced beneficial effect on joint swelling, leucocyte count and biochemical parameters compared with prednisolone groups. Among the different doses used in the study, prednisolone at 1.25 mg/kg in combination with curcumin showed beneficial anti-arthritic activity and also reduced the steroid toxicity. This is evidenced by increase in body weight, low toxicity to immune organs, reduction in leucocyte count, increase in spleen anti-oxidant enzymes and potent inhibition of cytokines in combination group. Conclusion Therefore, combined treatment of curcumin with low doses of prednisolone may find therapeutic use in arthritis.
- Published
- 2013
48. Synthesis and anticancer activity of some new s-triazine derivatives
- Author
-
Shweta Shrivastava, Vegi Ganga Modi Naidu, G. Jagadeesh Kumar, Kolupula Srinivas, H. V. S. Sriramkumar Bomma, E. Srihari, and V. Jayathirtha Rao
- Subjects
Colorectal cancer ,Stereochemistry ,Organic Chemistry ,medicine.disease ,In vitro ,chemistry.chemical_compound ,Breast cancer ,chemistry ,Cancer cell ,medicine ,Potency ,General Pharmacology, Toxicology and Pharmaceutics ,Lung cancer ,Ovarian cancer ,Triazine - Abstract
New s-triazine derivatives 13a–h were synthesized for the structure–activity relationship studies as potent anticancer agents. The prepared analogues were evaluated for their in vitro inhibitory activity against the growth of PA-1 (Ovarian cancer), A549 (Lung cancer), MCF-7 (Breast cancer), and HT-29 (Colon cancer). Tri-substituted s-triazine derivatives (13e–h) with morpholino group on s-triazine scaffold exhibited potent anticancer activities compared to di-substituted s-triazine derivatives. Compounds 13e–h also showed relatively selective PA-1 and HT-29 cancer cell inhibition over other cancer cell lines. Structure–activity relationships provided useful insights in these classes of compounds and paved the way to design novel analogues with more potency.
- Published
- 2013
49. Fast dissolving drug-drug eutectics with improved compressibility and synergistic effects
- Author
-
Vegi Ganga Modi Naidu, Rahul B. Chavan, Dinesh Thumuri, Nalini R. Shastri, and Rajesh Thipparaboina
- Subjects
Drug ,Cancer chemotherapy ,Stereochemistry ,media_common.quotation_subject ,Pharmaceutical Science ,02 engineering and technology ,Synergistic combination ,010402 general chemistry ,01 natural sciences ,Cell Line ,Mice ,Propranolol Hydrochloride ,Cell Line, Tumor ,Spectroscopy, Fourier Transform Infrared ,medicine ,Animals ,Humans ,Etodolac ,Dissolution ,Chromatography, High Pressure Liquid ,Eutectic system ,media_common ,Acetaminophen ,Chemistry ,Drug Synergism ,021001 nanoscience & nanotechnology ,Propranolol ,0104 chemical sciences ,Solubility ,Dose reduction ,Inflammation Mediators ,0210 nano-technology ,Powder Diffraction ,medicine.drug ,Nuclear chemistry - Abstract
Combinational therapy has become increasingly popular in recent times due to various advantages like greater therapeutic effect, reduced number of prescriptions, lower administrative costs, and an increase in patient compliance. Drug-drug multicomponent adducts could help in combination of drugs at supramolecular level. Two drug-drug eutectics of etodolac with paracetamol (EP) and etodolac with propranolol hydrochloride (EPHC) were successfully designed and synthesized for the first time. These eutectics significantly improved dissolution and material properties. A 6 to 9 fold enhancement in % dissolution efficiency was found at 1min suggesting the fast dissolving capabilities of the eutectic mixtures when compared to plain drug. In addition, eutectic mixtures have shown improved hardness compared to plain drugs. EP and EPHC have shown around 5 fold and 3 fold improvements in hardness respectively at 10MPa when compared to plain etodolac. Cell culture studies have shown improved effects of EP. Western blotting analysis revealed that the said combination successfully reduced various inflammatory mediators like TNF-α, COX-2 and IL-6. Whereas, the eutectic combination EPHC has shown enhanced cytotoxic effects with synergistic combination index and favorable dose reduction index. The generated multi-component systems EP and EPHC with fast dissolving capabilities, improved hardness at lower pressures and synergistic effects represent prospective combinations for effective treatment of osteoarthritis and cancer chemotherapy respectively.
- Published
- 2016
50. Synthesis and biological evaluation of new benzimidazole-thiazolidinedione hybrids as potential cytotoxic and apoptosis inducing agents
- Author
-
Suresh K. Bhargava, Vegi Ganga Modi Naidu, Niggula Praveen Kumar, Dinesh Thummuri, T. Srinivasa Reddy, Kishna Ram Senwar, Pankaj Sharma, and Nagula Shankaraiah
- Subjects
Cell Survival ,Cell ,Antineoplastic Agents ,Apoptosis ,010402 general chemistry ,01 natural sciences ,chemistry.chemical_compound ,Inhibitory Concentration 50 ,Cell Line, Tumor ,Neoplasms ,Drug Discovery ,medicine ,Cytotoxic T cell ,Humans ,Propidium iodide ,DAPI ,Pharmacology ,A549 cell ,Molecular Structure ,010405 organic chemistry ,Chemistry ,Cell growth ,Organic Chemistry ,Cell Cycle ,General Medicine ,Flow Cytometry ,Molecular biology ,0104 chemical sciences ,Cell biology ,medicine.anatomical_structure ,Cell culture ,A549 Cells ,Benzimidazoles ,Thiazolidinediones - Abstract
A series of new benzimidazole-thiazolidinedione hybrids has been synthesized and evaluated for their cytotoxic potential against a selected human cancer cell lines of prostate (PC-3 and DU-145), breast (MDA-MB-231), lung (A549) and a normal breast epithelial cells (MCF10A). Among the tested compounds, 11p exhibited promising cytotoxicity with IC50 value of 11.46 ± 1.46 μM on A549 lung cancer cell line and did not show significant toxicity on normal MCF10A cells. Lung cancer cells (A549) have been used to know the mechanism of cell growth inhibition and apoptosis inducing effect with compound 11p. The treatment of A549 cells with 11p showed typical apoptotic morphology like cell shrinkage, chromatin condensation and horseshoe shaped nuclei formation. Flow-cytometry analysis revealed the G2/M phase of cell cycle arrest in a dose dependent manner. Preliminary mechanistic studies suggested that the cell migration was inhibited through the disruption of F-actin protein. Acridine orange-ethidium bromide (AO-EB), DAPI, annexin V-FITC/propidium iodide, rhodamine-123 and MitoSOX assays suggested the induction of apoptosis in A549 cells by compound 11p.
- Published
- 2016
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