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Calcium Hydroxide-based endodontic sealer loaded with antimicrobial agents have been commonly employed in conventional root canal treatment. These sealers are not effective against E. faecalis due to the persistent nature of this bacterium and its ability to evade the antibacterial action of calcium hydroxide. Therefore, endodontic sealer containing Carbon nanodots stabilized silver nanoparticles (CD-AgNPs) was proposed to combat E. faecalis. The therapeutic effect of CD-AgNPs was investigated and a new cytocompatible Calcium Hydroxide-based endodontic sealer enriched with CD-AgNPs was synthesized that exhibited a steady release of Ag+ ions and lower water solubility at 24 hours, and enhanced antibacterial potential against E. faecalis. CD-AgNPs was synthesized and characterized morphologically and compositionally by Scanning Electron Microscopy, Fourier Transform Infrared Spectroscopy (FTIR), and UV-Vis Spectroscopy, followed by optimization via minimum inhibitory concentration (MIC) determination against E. faecalis by broth microdilution technique and Cytotoxicity analysis against NIH3T3 cell lines via Alamar Blue assay. Calcium hydroxide in distilled water was taken as control (C), Calcium hydroxide with to CD-AgNPs (5mg/ml and 10mg/ml) yielded novel endodontic sealers (E1 and E2). Morphological and chemical analysis of the novel sealers were done by SEM and FTIR; followed by in vitro assessment for antibacterial potential against E. faecalis via agar disc diffusion method, release of Ag+ ions for 21 days by Atomic Absorption Spectrophotometry and water solubility by weight change for 21 days. CD-AgNPs were 15-20 nm spherical-shaped particles in uniformly distributed clusters and revealed presence of constituent elements in nano-assembly. FTIR spectra revealed absorption peaks that correspond to various functional groups. UV-Vis absorption spectra showed prominent peaks that correspond to Carbon nanodots and Silver nanoparticles. CD-AgNPs exhibited MIC value of 5mg/ml and cytocompatibility of 84.47% with NIH3T3 cell lines. Novel endodontic sealer cut-discs revealed irregular, hexagonal particles (100-120 nm) with aggregation and rough structure with the presence of constituent elements. FTIR spectra of novel endodontic sealers revealed absorption peaks that correspond to various functional groups. Novel endodontic sealers exhibited enhanced antibacterial potential where E-2 showed greatest inhibition zone against E. faecalis (6.3±2 mm), a steady but highest release of Ag+ ions was exhibited by E-1 (0.043±0.0001 mg/mL) and showed water solubility of <3% at 24 hours where E-2 showed minimal weight loss at all time intervals. Novel endodontic sealers were cytocompatible and showed enhanced antibacterial potential against E. faecalis, however, E2 outperformed in this study in all aspects., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ali et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Risedronate sodium (RIS) exhibits limited bioavailability and undesirable gastrointestinal effects when administered orally, necessitating the development of an alternative formulation. In this study, mPEG-coated nanoparticles loaded with RIS-HA-TCS were created for osteoporosis treatment. Thiolated chitosan (TCS) was synthesized using chitosan and characterized using DSC and FTIR, with thiol immobilization assessed using Ellman's reagent. RIS-HA nanoparticles were fabricated and conjugated with synthesized TCS. Fifteen batches of RIS-HA-TCS nanoparticles were designed using the Box-Behnken design process. The nanoparticles were formulated through the ionic gelation procedure, employing tripolyphosphate (TPP) as a crosslinking agent. In silico activity comparison of RIS and RIS-HA-TCS for farnesyl pyrophosphate synthetase enzyme demonstrated a higher binding affinity for RIS. The RIS-HA-TCS nanoparticles exhibited 85.4 ± 2.21% drug entrapment efficiency, a particle size of 252.1 ± 2.44 nm, and a polydispersity index of 0.2 ± 0.01. Further conjugation with mPEG resulted in a particle size of 264.9 ± 1.91 nm, a PDI of 0.120 ± 0.01, and an encapsulation efficiency of 91.1 ± 1.17%. TEM confirmed the spherical particle size of RIS-HA-TCS and RIS-HA-TCS-mPEG. In vitro release studies demonstrated significantly higher release for RIS-HS-TCS-mPEG (95.13 ± 4.64%) compared to RIS-HA-TCS (91.74 ± 5.13%), RIS suspension (56.12 ± 5.19%), and a marketed formulation (74.69 ± 3.98%). Ex vivo gut permeation studies revealed an apparent permeability of 0.5858 × 10 -1 cm/min for RIS-HA-TCS-mPEG, surpassing RIS-HA-TCS (0.4011 × 10 -4 cm/min), RIS suspension (0.2005 × 10 -4 cm/min), and a marketed preparation (0.3401 × 10 -4 cm/min).

Risedronate-loaded mPEG-coated hydroxyapatite, thiolated chitosan-based (coated) and non-coated nanoparticles were tested for their potential effects in the treatment of osteoporosis. The prepared nanoparticles were evaluated for their bone-targeting potential by inducing osteoporosis in female Wistar rats via oral administration of Dexona (dexamethasone sodium phosphate). In vivo pharmacokinetic and pharmacodynamic studies were performed on osteoporotic rat models treated with different formulations. The osteoporotic model treated with the prepared nanoparticles indicated a significant effect on bone. The relative bioavailability was enhanced for RIS-HA-TCS-mPEG nanoparticles given orally compared to RIS-HA-TCS, marketed, and API suspension. Biochemical investigations also showed a significant change in biomarker levels, ultimately leading to bone formation/resorption. Micro-CT analysis of bone samples also demonstrated that the RIS-HA-TCS-mPEG-treated group showed the best results compared to other treatment groups. Moreover, the histology of bone treated with RIS-HA-TCS-mPEG showed a marked restoration of the architecture of trabecular bone along with a well-connected bone matrix and narrow inter-trabecular spaces compared to the toxic group. A stability analysis was also carried out according to ICH guidelines (Q1AR2), and it was found that RIS-HA-TCS-mPEG was more stable than RIS-HA-TCS at 25 °C. Thus, the results of present study indicated that mPEG-RIS-HA-TCS has excellent potential for sustained delivery of RIS for the treatment and prevention of osteoporosis, and for minimizing the adverse effects of RIS typically induced via oral administration.

Exemestane (EXE), an irreversible aromatase inhibitor, is primarily used as a first-line therapy for estrogen receptor-positive breast cancer patients. However, complex physicochemical characteristics of EXE limit its oral bioavailability (<10%) and anti-breast cancer efficacy. The present study aimed to develop a novel nanocarrier system to improve the oral bioavailability and anti-breast cancer efficacy of EXE. In this perspective, EXE-loaded TPGS-based polymer lipid hybrid nanoparticles (EXE-TPGS-PLHNPs) were prepared by the nanoprecipitation method and evaluated for their potential in improving oral bioavailability, safety, and therapeutic efficacy in the animal model. EXE-TPGS-PLHNPs showed significantly higher intestinal permeation in comparison to EXE-PLHNPs (without TPGS) and free EXE. After oral administration, EXE-TPGS-PLHNPs and EXE-PLHNPs revealed 3.58 and 4.69 times higher oral bioavailability in Wistar rats compared to the conventional EXE suspension. The results of the acute toxicity experiment suggested that the developed nanocarrier was safe for oral administration. Furthermore, EXE-TPGS-PLHNPs and EXE-PLHNPs represented much better anti-breast cancer activity in Balb/c mice bearing MCF-7 tumor xenograft with tumor inhibition rate of 72.72% and 61.94% respectively in comparison with the conventional EXE suspension (30.79%) after 21 days of oral chemotherapy. In addition, insignificant changes in the histopathological examination of vital organs and hematological analysis further confirm the safety of the developed PLHNPs. Therefore, the findings of the present investigation advocated that the encapsulation of EXE in PLHNPs can be a promising approach for oral chemotherapy of breast cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The aim of this investigation was to develop and analyze a tacrolimus and thymoquinone co-loaded nanostructured lipid carriers (TAC-THQ-NLCs)-based nanogel as a new combinatorial approach for the treatment of psoriasis. The NLCs were formulated by an emulsification-solvent-evaporation technique using glyceryl monostearate, Capryol 90 (oil), and a mixture of Tween 80 and Span 20 as a solid lipid, liquid lipid, and surfactant, respectively. Their combination was optimized using a three-factor and three-level Box-Behnken design (3 3 -BBD). The optimized TAC-THQ-NLCs were observed to be smooth and spherical with a particle size of 144.95 ± 2.80 nm, a polydispersity index of 0.160 ± 0.021, a zeta potential of -29.47 ± 1.9 mV, and an entrapment efficiency of >70% for both drugs. DSC and PXRD studies demonstrated the amorphous state of TAC and THQ in the lipid matrix of the NLCs. An FTIR analysis demonstrated the excellent compatibility of the drugs with the excipients without interactions. The TAC-THQ-NLC-based nanogel (abbreviated as TAC-THQ-NG) exhibited a good texture profile and good spreadability. The in vitro release study demonstrated a sustained drug release for 24 h from the TAC-THQ-NG that followed the Korsmeyer-Peppas kinetic model with a Fickian diffusion mechanism. Moreover, the TAC-THQ-NG revealed significantly higher dose-dependent toxicity against an HaCaT cell line compared to a TAC-THQ suspension gel (abbreviated as TAC-THQ-SG). Furthermore, the developed formulations demonstrated antioxidant activity comparable to free THQ. Confocal microscopy revealed improved permeation depth of the dye-loaded nanogel in the skin compared to the suspension gel. Based on these findings, it was concluded that TAC-THQ-NG is a promising combinatorial treatment approach for psoriasis.

Taxol and 10-Deacetyl baccatin III are major taxanes in the bark, needles, and endophytes of Taxus baccata. The current study aimed to develop a process for their separation from different matrices. Crude taxoid was prepared by extraction of samples with methanol, followed by partitioning with dichloromethane and precipitation with hexane. Analytical high-performance liquid chromatography involved isocratic elution on C18 column (4.6 × 250 mm, 5 μm) with methanol-water (70:30 v/v) at a flow rate of 1 ml/min. Injection volume was 20 μl and detection was carried out at 227 nm. The content of Taxol and 10-Deacetyl baccatin III in bark, needles and endophytic culture broth was 11.19 and 1.75 μg/mg; 11.19 and 1.75 μg/mg; and 2.80 and 0.22 μg/L, respectively. Preparative high-performance liquid chromatography was done on C18 column (10 × 250 mm, 5 μm) at a flow rate of 10 ml/min. About 20 g crude taxoid was processed in < 3 h with a recovery of about 90% for both the analytes. The purity of recovered Taxol and 10-Deacetyl baccatin III determined by ultra-high-performance liquid chromatography-mass spectrometry was found to be 95.78 ± 3.63% and 99.72 ± 0.18%, respectively. The structure of recovered Taxol was confirmed by nuclear magnetic resonance. The method can find use in biotransformation studies., (© 2023 Wiley-VCH GmbH.)

Phytochemical investigation of the seeds of Cichorium intybus L (C. intybus) led to isolate n-hexacosane (CI-1), an aliphatic higher ketone, n-nonacosan-3-one (CI-2), two aliphatic acid esters characterized as n-octacosanyl decanoate (CI-3) and n-tricosanyl hexadecanoate (CI-4), two mixed glycerides identified as as glyceryl-1-(hexadec-7- enoyl)-2- tetradecanoyl-3-hexadecanoate (Cl-5) and glyceryl-1- (eicos-9-enoyl)-2,3, bis-eicosanoate (Cl-6), and three e steroidal constituents and their structures were elucidated as as stigmast-5, 22-dien-3β -ol-21-oic acids (Cl-7), stigmasterol-3β-d-glucopyranoside (Cl-8) and stigmast-5, 22-dien-3-β-ol-3-β-d-glucuronopyranoside (Cl-9). The dry seeds powder was defatted and finally extracted with ethanol by using a maceration method. The ethanol was evaporated near to dryness and silica gel was added to the extract and a slurry with the help of methanol solvent was prepared. The slurry was loaded to the column by using petroleum ether and was eluted with a mixture of chloroform and methanol. A series of test tubes were collected and each test tube with 2 mL eluents was collected. Based on the thin layer chromatography (TLC) the content of nine test tubes were considered as pure compounds. The solvent was evaporated from the test tube at room temperature. All the nine compounds from the column were characterized by using Infrared (IR), Nuclear Magnetic Resonance (NMR) and Mass spectrometry (MS). Eight compounds were previously isolated from the plant and they showed various biological activities. A new compound was isolated for the first time from the plant kingdoms. Based on the chromatographic and spectroscopic analysis the new compound was characterized as stigmasterol carboxylic acid (CI-9). The isolated new compound could be used to treat liver and cardiac diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Sepsis is a serious health concern globally, which necessitates understanding the root cause of infection for the prevention of proliferation inside the host's body. Phytochemicals present in plants exhibit antibacterial and anti-proliferative properties stipulated for sepsis treatment. The aim of the study was to determine the potential role of Carica papaya leaf extract for sepsis treatment in silico and in vitro. We selected two phytochemical compounds, carpaine and quercetin, and docked them with bacterial proteins, heat shock protein (PDB ID: 4PO2), surfactant protein D (PDB ID: 1PW9), and lactobacillus bacterial protein (PDB ID: 4MKS) against imipenem and cyclophosphamide. Quercetin showed the strongest interaction with 1PW9 and 4MKS proteins. The leaves were extracted using ethanol, methanol, and water through Soxhlet extraction. Total flavonoid content, DPPH assay, HPTLC, and FTIR were performed. In vitro cytotoxicity of ethanol extract was screened via MTT assay on the J774 cell line. Ethanol extract (EE) possessed the maximum number of phytocomponents, the highest amount of flavonoid content, and the maximum antioxidant activity compared to other extracts. FTIR analysis confirmed the presence of N-H, O-H, C-H, C=O, C=C, and C-Cl functional groups in ethanol extract. Cell viability was highest (100%) at 25 µg/mL of EE. The present study demonstrated that the papaya leaves possessed antibacterial and cytotoxic activity against sepsis infection.

Purpose: The current research investigated the development and evaluation of dual drug-loaded nanostructure lipidic carriers (NLCs) of green tea extract and Ribociclib., Method: In silico study were performed to determine the effectiveness of combinational approach. The prepared NLCs were subjected to in vitro drug release, lipolysis, haemolysis and cell line studies to assess their in vivo prospect., Results: In silico study was done to get docking score of EGCG (-8.98) close to Ribociclib (-10.78) in CDK-4 receptors. The prepared NLCs exhibited particle size (175.80 ± 3.51 nm); PDI (0.571 ± 0.012); and %EE [RBO (80.91 ± 1.66%) and GTE 75.98 ± 2.35%)] respectively. MCF-7 cell lines were used to evaluate the MTT assay, cellular uptake and antioxidant (ROS and SOD) of prepared NLCs. In vitro drug release showed the controlled release up to 72 h. In vitro lipolysis and in vitro haemolysis studies showed the availability of drugs at absorption sites and the greater in vivo prospects of NLCs respectively. Pharmacokinetic study revealed a 3.63-fold and 1.53-fold increment in RBO and GTE bioavailability in female Wistar rats respectively., Conclusion: The prominent potential of green tea extract and RBO-loaded NLCs in enhancing their therapeutic efficacy for better treatment of breast cancer.

Vincristine is an anti-cancer compound and one of the most crucial vinca alkaloids produced by the medicinal plant Catharanthus roseus (L.) G. Don. (Apocynaceae). This plant is home to hundreds of endophytic microbes, which produce a variety of bioactive secondary metabolites that are known for their medicinal properties. In this study, we focused on isolating an endophytic fungus that could increase the yield of vincristine under laboratory conditions as an alternative to plant-mediated extraction of vincristine. The endophytic fungus Nigrospora zimmermanii (Apiosporaceae) was isolated from Catharanthus roseus and it was found to be producing the anticancer compound vincristine. It was identified using high-performance thin-layer chromatography by matching the Rf value and spectral data with the vincristine standard and mass spectrometry data and the reference molecule from the PubChem database. The generation study of this microbe showed that the production of vincristine in the parent fungus was at its maximum, i.e., 5.344 µg/mL, while it was slightly reduced in subsequent generations. A colonization study was also performed and it showed that the fungus N. zimmermanii was able to re-infect the plant Catharanthus roseus after 20 days of inoculation. The colonization study showed that N. zimmernanii could infect the plant after isolation. This method is an efficient and easy way to obtain a high yield of vincristine, as compared to plant-mediated production., Competing Interests: The authors declare no conflict of interest.

Oryza sativa L. (Family Poaceae) is cultivated in tropical regions as a staple food all over the world. The rice grain husk is considered as a tonic and administered orally to relieve dysentery. The air-dried seeds husks of O. sativa were exhaustively extracted with methanol in a Soxhlet apparatus. The concentrated methanol extract was adsorbed on silica gel and chromatographed on a silica gel column. The column was eluted with petroleum ether, chloroform and methanol successively to isolate four phytoconstituents characterised as 7-ketostigmasterol ( 1 ), 3β-benzyloxy-stigmast-7-one-22-en-19-oic acid 29-ethyleneglycol ether ( 2 ), sesquaurs-11-en- 2β, 3β,5α-triol ( 3 ) and 2'-(1''β-hydroxypropyl)-7,4'-dimethoxyapigenin ( 4 ). These phytoconstituents were identified on the basis of spectral data analysis.

Cannabidiol (CBD) is a prescribed drug for epilepsy but has low oral bioavailability and gastric instability. Because of the direct link between the nasal cavity and the central nervous system, intranasal administration of CBD as nanoemulsions which are the small sized lipid carriers seem to improve the bioavailability. CBD-nanoemulsions (NEs) were made using Capryol 90, Tween 80, and Transcutol P as oil, surfactant, and co-surfactant, respectively, following aqueous titration approach. Then, using the Box-Behnken design, CBD-NE was statistically optimised for the selection of desirable excipient concentrations in order to create the optimal CBD-NE formulation. As independent variables in the statistical design, Capryol 90 (oil; coded as A ), Tween 80 (surfactant; coded as B ), and Transcutol P (co-surfactant; coded as C ) were used. The dependent variables were droplet size (DS; coded as R 1 ) and polydispersity index (PDI; coded as R 2 ). The average DS, PDI, and the zeta potential of the optimized CBD-NEs were observed to be 88.73 ± 2.67 nm, 0.311 ± 0.015, and -2.71 ± 0.52 mV respectively. Pure CBD and lyophilized CBD-NE Fourier-transform infrared spectra demonstrated no physicochemical interaction between excipients and the drug. Furthermore, differential scanning calorimetry and x-ray diffraction measurements revealed the amorphous CBD in the NE. As compared to pure CBD, the optimised CBD-NE showed considerably better in vitro drug release as well as ex vivo nasal permeability. The drug targeting efficiency and direct transport percentage of the optimised CBD-NEs were found to be 419.64% and 76.17%, respectively, in this research. Additionally, pharmacokinetic investigations after intranasal administration of CBD-NE revealed considerably higher drug concentrations in the brain with better brain targeting efficiency. As a result, the development of CBD-NE may be an excellent alternative for better intranasal delivery., (© 2022 IOP Publishing Ltd.)

Vincristine, one of the major vinca alkaloid of Catharanthus roseus (L.) G. Don. (Apocynaceae), was enhanced under in vitro callus culture of C. roseus using fungal extract of an endophyte Alternaria sesami isolated from the surface-sterilized root cuttings of C. roseus. Vindoline, a precursor molecule for vincristine production, was detected for the first time in the fungal endophyte A. sesami which was used as a biotic elicitor in this study to enhance vincristine content in the C. roseus callus. It was identified using high-performance liquid chromatography and mass spectroscopy techniques by matching retention time and mass data with reference molecule. Supplementing the heat sterilized A. sesami endophytic fungal culture extract into the callus culture medium of C. roseus resulted in the enhancement of vincristine content in C. roseus callus by 21.717% after 105-day culture., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Toll-like receptors (TLRs) are one of the major sensors to regulate innate immunity. It is present in inactive form within immune cells. However, after recognizing the conserved region of the foreign body, it gets activated by the foreign body, such as bacteria, viruses, fungus, etc. Recently, it is reported that apart from participating in innate immunity, these TLRs also play an important role in apoptosis and cancer. Moreover, very few reported that it is cross-talk with p53 protein within the cell. P53 protein is a transcription factor for many cellular proteins involved in cellular transduction. It directly as well as indirectly regulates a wide variety of cellular processes such as apoptosis, senescence, cell cycle arrest, differentiation, and DNA repair and replication and cancer dynamics. Various studies reported genetic level interaction between p53 and TLRs. However, molecular interaction studies are still few reported. In the present work, we computationally characterized molecular interaction between p53 and toll-like receptors. We used open web resources for docking and analyzing the data. Our molecular docking and molecular dynamics simulation results suggest that there is a significant interaction between p53 and toll-like receptors. The study could important for the possible therapeutic intervention.

Black pepper (Piper nigrum L.) is a climbing perennial plant in the Piperaceae family. Pepper has been known since antiquity for its use both as a medicine and a spice. It is particularly valued for its pungency attributed to its principal constituent - piperine. This review summarizes the information on the biological source of piperine, its extraction and isolation strategies, physicochemical properties, and pharmacological activity - analgesic, immunomodulatory, anti-depressive, anti-diarrheal, hepatoprotective, etc. The effect of piperine on biotransformation of co-administered drugs is also presented in this review, along with the mechanisms involved in its bioavailability-enhancing effect. Its important medicinal uses, including anti-hepatotoxic, anti-diarrheal, anti-depressive, analgesic, and immunomodulatory effects, besides many other traditional uses, are compiled. Based on an exhaustive review of literature, it may be concluded that piperine is a very promising alkaloid found in members of the Piperaceae family.

Ficus bengalensis (F. bengalensis) is a popular medicinal plant species used extensively in the Ayurveda treatment as hypoglycemic, diuretic, tonic, rheumatism, astringent, and inflammation. The goal of this study is to separate and characterize - compounds from fruits of the selected F. bengalensis. The dried fruits coarse power was defatted with non-polar solvent petroleum ether and then systematically extracted with ethanol by using maceration method for 3 days. The ethanol was evaporated and the prepared extract was separated by several chromatographic methods. After separation, the ethanol extract of F. bengalensis afforded nine compounds including two new triterpenoid glycoside derivatives Compound 1: Bengalensursenyl diglycoside and Compound 2: Ficusbengursenyl diglycoside and other minor known phytochemicals. The chemical structures of these separated phytochemicals were elucidated based on spectroscopic analysis and minor chemical transformations. This paper reports isolation and structure elucidation of compounds 1 and 2. In conclusion, the isolated Compound 1 and Compound 2 could be further investigated for any pharmacological activities. This is the first report in our laboratory on isolation of Compound 1 and Compound 2 from the fruits of F. bengalensis., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Context: Traditionally, Inula racemosa Hook. f. (Asteraceae) has been reported to be effective in cancer treatment which motivated the authors to explore the plant for novel anticancer compounds., Objective: To isolate and characterize new cytotoxic phytoconstituents from I. racemosa roots., Materials and Methods: The column chromatography of I. racemosa ethyl acetate extract furnished a novel sesquiterpene lactone whose structure was established by NMR (1D/2D), ES-MS and its cytotoxic properties were assessed on HeLa, MDAMB-231, and A549 cell lines using MTT and LDH (lactate dehydrogenase) assays. Further, morphological changes were analyzed by flow cytometry, mitochondrial membrane potential, AO-EtBr dual staining, and comet assay. Molecular docking and simulation were performed using Glide and Desmond softwares, respectively, to validate the mechanism of action., Results: The isolated compound was identified as racemolactone I (compound 1 ). Amongst the cell lines tested, considerable changes were observed in HeLa cells. Compound 1 (IC 50 = 0.9 µg/mL) significantly decreased cell viability (82%) concomitantly with high LDH release (76%) at 15 µg/mL. Diverse morphological alterations along with significant increase (9.23%) in apoptotic cells and decrease in viable cells were observed. AO-EtBr dual staining also confirmed the presence of 20% apoptotic cells. A gradual decrease in mitochondrial membrane potential was observed. HeLa cells showed significantly increased comet tail length (48.4 µm), indicating broken DNA strands. In silico studies exhibited that compound 1 binds to the active site of Polo-like kinase-1 and forms a stable complex., Conclusions: Racemolactone I was identified as potential anticancer agent, which can further be confirmed by in vivo investigations.

The aim of the present study was to develop and characterize karanjin-loaded ethosomes-based gel formulation for enhanced topical delivery and effective therapy of skin acne. Karanjin-loaded ethosomes (K-ETH) presented a nanometric size of 140.87 ± 2.35 nm, entrapment of 71.41 ± 2.74% and enhanced permeation with 1.9 times increase in the flux and 2.4 times higher skin deposition compared to the hydro-ethanolic solution of karanjin. The DSC analysis confirmed successful entrapment of the karanjin within the ethosomes. The developed ethosomes were incorporated in the carbopol gel for adequate application on the skin surface. The ethosomal gel (K-EGF) also exhibited greater penetration in the rat skin as revealed by CLSM. The optimized K-EGF formulation was non-irritant to the skin as evident by Draize score test and histopathological examination. The highest zone of inhibition, 30.0 ± 1.52 mm and 36.22 ± 0.57 mm was produced by the K-EGF against Propionibacterium acnes and Staphylococcus epidermidis , respectively, indicating substantial antibacterial properties of the K-EGF. DPPH assay indicated its potent antioxidant effects. Substantial anti-inflammatory effects in the carrageenan-induced edema in the rat paw were evident with inhibition of rat paw edema by 66.66% and 70.37% upon application of K-EGF and standard anti-inflammatory agent, respectively. Anti-acne effects were also evident with K-EGF treatment with significant decrease in number and size of sebaceous gland units in dermis. Overall, the above findings vouch for a therapeutic opportunity to improve topical delivery of karanjin in acne treatment employing ethosomal gels as the promising carrier system., Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-021-02978-3., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest. This article does not contain any studies with human participants performed by any of the authors., (© King Abdulaziz City for Science and Technology 2021.)

The hydro-alcoholic extract of Withania coagulans fruits was investigated for preliminary phytochemical screening and characterized by high-performance thin-layer chromatography. Column chromatography of the hydro-alcoholic extract of W. coagulans eluted with four different combinations of ethyl acetate and methanol yielded four fractions (WCF 01 , WCF 02 , WCF 03, and WCF 04 ). One of these fractions, WCF 02 , significantly ( P < 0.05) inhibited in vitro α-amylase and α-glucosidase activity with IC 50 values of 104.71 μg/mL and 70.79 μg/mL, respectively. WCF 02 further reduced blood glucose levels in comparison to control in the starch tolerance test. The extract showed a relative dose-dependent effect. It was observed that none of the extracts could delay the peak blood glucose that was achieved after 60 min of carbohydrate challenge, but these blunted the glycemic peak., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Pharmacy And Bioallied Sciences.)

P53 is one of the most important proteins for its role in cellular signal transduction pathways. It regulates a wide variety of cellular processes, which includes apoptosis, senescence, cell cycle arrest, differentiation, and DNA repair and replication and cancer dynamics. It is a transcription factor for various cellular proteins. Recent report suggests that P53 is linked with transduction proteins involved in cellular immunity. Toll like receptors are needed for communication in cellular immunity. The interaction between p53 and toll like receptors is reported in various studies. Therefore, it is of interest to document the molecular docking analysis of p53 with Toll-like receptors for further consideration in therapeutic development. In the present paper we studied molecular interaction between p53 and toll like receptors using molecular docking approach. We used open-source tools for molecular docking and analyzing the data. Our molecular docking results suggest there is a promising interaction between p53 and toll like receptors. Our study will be a very useful for molecular therapeutics and drug design strategies. Further, molecular dynamics studies can be useful to determine of the stability of complex form by p53 and toll like receptors., (© 2021 Biomedical Informatics.)

Polymer-lipid hybrid nanoparticles (PLHNPs) are novel nanoplatforms for the effective delivery of a lipophilic drug in the management of a variety of solid tumors. The present work was designed to develop exemestane (EXE) encapsulated D-alpha-tocopheryl polyethylene glycol succinate (TPGS) based PLHNPs (EXE-TPGS-PLHNPs) for controlled delivery of EXE for breast cancer management. EXE-TPGS-PLHNPs were formulated by single-step nano-precipitation technique and statistically optimized by a 3 3 Box-Behnken design using Design expert ® software. The polycaprolactone (PCL; X 1 ), phospholipon 90 G (PL-90G; X 2 ), and surfactant ( X 3 ) were selected as independent factors while particles size (PS; Y 1 ), polydispersity index (PDI; Y 2 ), and %entrapment efficiency (%EE; Y 3 ) were chosen as dependent factors. The average PS, PDI, and %EE of the optimized EXE-TPGS-PLHNPs was observed to be 136.37 ± 3.27 nm, 0.110 ± 0.013, and 88.56 ± 2.15% respectively. The physical state of entrapped EXE was further validated by Fourier-transform infrared spectroscopy, differential scanning calorimetry, and powder x-ray diffraction that revealed complete encapsulation of EXE in the hybrid matrix of PLHNPs with no sign of significant interaction between drug and excipients. In vitro release study in simulated gastrointestinal fluids revealed initial fast release for 2 h after that controlled release profile up to 24 h of study. Moreover, optimized EXE-TPGS-PLHNPs exhibited excellent stability in gastrointestinal fluids as well as colloidal stability in different storage concentrations. Furthermore, EXE-TPGS-PLHNPs exhibited distinctively higher cellular uptake and time and dose-dependent cytotoxicity against MCF-7 breast tumor cells compared to EXE-PLHNPs without TPGS and free EXE. The obtained results suggested that EXE-TPGS-PLHNPs can be a promising platform for the controlled delivery of EXE for the effective treatment of breast cancer., (© 2021 IOP Publishing Ltd.)

Parthenolide, a strong cytotoxic compound found in different parts of Tarchonanthus camphoratus which motivated the authors to develop an optimized microwave-assisted extraction (MEA) method using Box-Behnken design (BBD) for efficient extraction of parthenolide from the stem of T. camphoratus and its validation by high-performance thin-layer chromatography (HPTLC) and cytotoxic analysis. The optimized parameters for microwave extraction were determined as: 51.5 °C extraction temperature, 50.8 min extraction time, and 211 W microwave power. A quadratic polynomial model was found the most suitable model with R 2 of 0.9989 and coefficient of variation (CV) of 0.2898%. The high values of adjusted R 2 (0.9974), predicted R 2 (0.9945), and signal-to-noise ratio (74.23) indicated a good correlation and adequate signal, respectively. HPTLC analyzed the parthenolide (R f = 0.16) content in T. camphoratus methanol extract (TCME) at λ max = 575 nm and found it as 0.9273% ± 0.0487% w / w , which was a higher than expected yield (0.9157% w / w ). The TCME exhibited good cytotoxicity against HepG2 and MCF-7 cell lines (IC 50 = 30.87 and 35.41 µg/mL, respectively), which further supported our findings of high parthenolide content in TCME. This optimized MAE method can be further applied to efficiently extract parthenolide from marketed herbal supplements containing different Tarconanthus species.

Context: Nephrotoxicity is a renal dysfunction that arises from direct exposure to environmental chemicals or as a side effect of therapeutic drugs. Boerhaavia diffusa Linn. (Nyctaginaceae), Rheum emodi Wall. Ex. Meissn. (Polygonaceae), Nelumbo nucifera Gaertn. (Nelumbonaceae) and Crataeva nurvala Buch-Ham. (Capparidaceae) are well-recognized medicinal plants of Indian traditional system of medicine used for kidney disorders. Objectives: The present investigation was undertaken to develop a chromatographically characterized polyherbal combination and to evaluate its nephroprotective activity. Materials and methods: Roots of B. diffusa and R. emodi , flowers of N. nucifera and stem bark of C. nurvala were extracted by decoction using 70% ethanol. Response surface methodology (RSM) was used for the optimization of extraction parameters. Polyherbal combinations with different doses (150-300 mg/kg) were tested against methotrexate-induced nephrotoxicity in Wistar rats. Results: The optimized extract contained 27% phenols and 15% flavonoids, which showed 75% 1, 1-diphenyl-2-picryl-hydrazyl (DPPH) scavenging potential. Based on the retention time of high-performance liquid chromatography (HPLC) analysis, 17 out of 122 constituents were found common in all extracts and combinations. Two combinations showed significantly higher ( p  ≤ 0.05) DPPH scavenging potential and xanthine oxidase inhibition. The half maximal inhibitory concentration (IC 50 ) of the best combination for DPPH scavenging and xanthine oxidase inhibition were 80 and 74 µg/mL, respectively. Treatment of methotrexate-induced nephrotoxic rats with polyherbal combination significantly ( p  ≤ 0.05) improved the kidney function markers, oxidative stress markers and histological parameters. Discussion and conclusion: The developed combination was found to be effective in nephrotoxicity; it can be explored further for the management of drug-induced nephrotoxicity and other chronic kidney diseases.

At present, cancer is the most deadly disease and one of the most common causes of death worldwide providing different obstacles to chemotherapy including non-specific biodistribution of chemotherapeutic drugs, dose-related adverse effects, development of metastasis and chemoresistance. Nanoparticle-based targeted delivery of chemotherapeutics gained enormous attention in the treatment of solid tumors as they provide many significant advantages including prolonged drug release, enhanced systemic half-life, decreased toxicity and targeted drug delivery. Polymer-lipid hybrid nanoparticles (PLHNPs) are the most effective nanoplatform that develop from building blocks of polymers and lipids. PLHNPs combine the unique advantages of both lipid-based nanoparticles as well as polymeric nanoparticles. PLHNPs integrate biocompatible polymers and biomimetic lipids in their architecture, which imparts PLHNPs with wide versatility for delivering chemotherapeutic drugs of different physicochemical characteristics to their target site of action. The hybrid architecture of PLHNPs provides many exceptional advantages such as small particle size, encapsulation of more than one anticancer drugs, high drug loading capacity and modified drug release profile. Furthermore, the surface decoration of PLHNPs improves the therapeutic potential of the chemotherapeutic drug by selective targeting of tumor tissue and reduces the side effects by decreasing non-specific biodistribution. This review highlights the challenges in the treatment of solid tumors by using nanoparticles system, rationale and targeting strategies of PLHNPs in the targeted treatment of solid tumors, and current progress of PLHNPs in the management of different types of solid tumors., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Olive (Olea europaea Linn., Fam. Oleaceae) is commonly known as Zaytoon in Mediterranean region. Its fruits and oil are essential components of Mediterranean diets. Olive tree is a prevalent plant species and one of the important cultivated crops of Mediterranean region. Oleuropein is a phenolic constituents of olive, which, along with its related compounds, has been indicated to be majorly responsible for its beneficial effects. Oleuropein is a secoiridoid type of phenolic compound and consists of three structural subunits: hydroxytyrosol, elenolic acid, and a glucose molecule. It is also reported to be the chemotaxonomic marker of olive. The oleuropein is reported to possess a number of biological activities including action against dyslipidemia, antiobesity, antidiabetic, antioxidant, antiatherogenic, antihypertensive, antiinflammatory, and hepatoprotective actions. The scientific evidence supports the role of oleuropein as a potential agent against metabolic syndrome. The present review discusses chemistry of oleuropein along with potential role of oleuropein with reference to pathophysiology of metabolic syndrome., (© 2019 John Wiley & Sons, Ltd.)

Cancer continues to be one in all the leading reasons for death worldwide. The mean cancer survival through standard therapeutic strategies has not been significantly improved over the past few decades. Hence, alternate remedies are needed to treat this terrible disease. Recently, natural compounds present in the plants, i.e. phytochemicals have been widely exploited for their anticancer potential. Phytochemicals may exhibit their anticancer activity through targeting different cancer cell signalling pathways, promoting cell cycle arrest and apoptosis, regulating antioxidant status and detoxification. Despite their excellent anticancer activity, the phytochemicals are limited by their low aqueous solubility, poor bioavailability, and poor penetration into cells, hepatic disposition, narrow therapeutic index and rapid uptake by normal tissues. Therefore, to address these challenges, the scientific community has shifted its significant interests towards nanocarriers-based delivery of phytochemicals due to their ability to enhance aqueous solubility, and bioavailability, specific tumour cell/tissue targeting, improved cellular uptake, reducing doses of phytochemicals and achieving steady-state therapeutic levels of the phytochemicals over an extended period of time. Additional advantages include excellent blood stability, multifunctional design of nanocarriers and improvement in anticancer activities. This review aims to summarise recent progress in phytochemical based nanomedicines for effective treatment of cancer.

The seeds of Nigella sativa Linn. (Ranunculaceae), commonly known as Black cumin, are predominantly used as carminative, antispasmodic, and stimulant. The main objective of the present study was to evaluate the effect of N. sativa seed extract on the permeation of co-infused amoxicillin across the gut wall. The methanolic extract of N. sativa improved intestinal permeability of amoxicillin in in-vitro experiments in a dose-dependent manner. Two new glycosides, decanyl nigelloic acid diglucoside [n-decanyl-3-aldehydic-4-methoxy-5-hydroxy benzoate-5-β-D-glucofuranosyl (2→1)-β-D-glucopyranosyl-(2→1)-β-D-glucopyranoside]] and nigelabdienoyl triglucoside [homo-labd-5, 9(11)-dien-16-onyl-β-D-glucopyranosyl (2→1)-β-D-glucopyranosyl (2→1)-β-D-glucopyranoside], along with seven known fatty acid glycerides/esters, were isolated from the gut permeation enhancing extract. The structures of these new glycosides were elucidated by detailed spectroscopic analyses., (Copyright © 2018 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Embelin is a natural compound possessing a plethora of pharmacological activities, including antidiabetic activity. When formulated as niosomes, embelin offers additional advantages of nanoformulations and can be further exploited for clinical use. An oral niosome formulation of embelin was developed using a thin-film hydration technique, and its antidiabetic activity was studied. The formulation was characterized in terms of entrapment efficiency, vesicle size and morphology, in vitro release profile, and stability. Antidiabetic evaluation was performed in streptozotocin (STZ)-induced diabetic Wistar rats. An antioxidant assay was carried out by evaluating superoxide dismutase (SOD), catalase (CAT), thiobarbituric acid reactive substances (TBARS), and glutathione (GSH). The optimized formulation showed a significant hypoglycemic effect, which was comparable with that of repaglinide. Moreover, significant increases in SOD, CAT, and GSH, along with a decrease in the lipid peroxidation level, were observed, which confirmed the antioxidant efficacy of the formulation. Thus, it is evident that the embelin-loaded niosome formulation was efficacious in diabetes management in Wistar rats., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Ethnopharmacological Relevance: Careya arborea Roxb. (Lecythidaceae) is a large tree found throughout India in deciduous forests and grasslands. C. arborea is traditionally used in tumors, inflammation, anthelmintic, bronchitis, epileptic fits, astringents, antidote to snake-venom, skin disease, diarrhea, dysentery with bloody stools, dyspepsia, ulcer, tooth ache, and ear pain., Aim of the Study: In our previous work, the methanolic extract of Careya arborea stem bark showed significant anti-inflammatory activity. As a continuity of that work, this study aimed at the isolation and evaluation of the anti-inflammatory effect of coumaroyl lupendioic acid, a new lupane-type triterpene from Careya arborea stem bark. Further, to give an insight into the underlying mechanism of action of the compound on the modulation of proinflammatory mediators., Materials and Methods: Methanolic extract of Careya arborea stem bark was suspended in water, and sequentially fractionated with n-hexane and ethyl acetate. Further ethyl acetate fraction was subjected to medium pressure liquid chromatography (MPLC) to isolate the active molecules. The isolated compounds were characterized by the various spectral techniques namely UV, IR, 1 H NMR, 13 C NMR, DEPT, 1 H- 1 H COSY, HMBC and Mass spectral techniques. In vitro COX-1 and COX-2 enzyme inhibition assays using human whole blood was performed to investigate the inhibitory effect of the isolated compounds. The resulted potent COX-2 inhibitor of the isolated constituents compound 5, designated as coumaroyl lupendioic acid (CLA), was investigated in carrageenan induced inflammation and its effect was also compared with betulinic acid (BA) at the doses of 10 and 20mgkg -1 , p.o. using indomethacin and celecoxib (10 and 20mgkg -1 , p.o., respectively) as reference drugs. The effect of CLA on the production of NO, MPO, PGE2, TNF-α, IL-1β and IL-6 were assessed. In addition, the histopathology and immunohistochemistry (NF-ҡB, COX-2 and TNF-α protein expression) in paw tissues were also carried out., Results: The chromatographic fractionation of the methanolic extract resulted in isolation of six new derivatives of lupane type triterpenes for the first time from the stem bark of C. arborea; 3β-hydroxy-lup-5,20 (29),21-trien-28-oic acid (Compound 1), 1, 3, 13, 16-tetrahydroxy-lup-9(11), 20(29)-diene-28-oic acid (Compound 2), 1, 7-di hydroxy betulinic acid (Compound 3), 3β-O-dihydrocinnamyl betulinic acid (Compound 4), 3β-O-trans-coumaryl-lup-6, 9(11), 20(29)-triene-27, 28-dioic acid (Compound 5), 16β-hydroxy-2, 3-seco-lup-5, 20(29)-dien-2, 3, 28-trioic acid (Compound 6). Among the all isolated compounds 3β-O-trans-coumaryl-lup-6, 9(11), 20(29)-triene-27, 28-olioic acid designated as coumaroyl lupendioic acid (CLA) showed higher COX-2 selectivity which is comparable to reference drug (celecoxib). CLA significantly reduced carrageenan induced inflammation whereas CLA revealed greater effect as compared to BA at the similar corresponding doses. Moreover, CLA significantly inhibited pro-inflammatory mediators elevated by carrageenan. CLA also preserved the tissue architecture as evidenced by the histopathology. Furthermore, immunohistochemical studies revealed that CLA significantly down regulated NF-ҡB, COX-2 and TNF-α protein expression., Conclusion: The study gives an insight into the molecular mechanisms of coumaroyl lupendioic acid and suggests that the down-regulations of proinflammatory mediators provide credence to the ethno botanical use of the plant in the management of inflammation., (Copyright © 2017. Published by Elsevier B.V.)

Background: The seeds of Zizyphus jujuba Mill. (Rhamnaceae) are astringent, aphrodisiac, tonic; used to cure cough, asthma, vomiting, burning sensation, biliousness, leucorrhoea, and eye infections in traditional systems of medicine., Materials and Methods: The methanol extract of seeds of Z. jujuba was partitioned into petroleum ether and water soluble fractions. Isolation of compounds was performed by silica gel column chromatography. The structures of isolated compounds were established on the basis of spectral studies and chemical reactions., Results: Chromatographic separation of methanolic extract of seeds yielded three new phyto-constituents characterized as 3, 5, 7-trimethoxy-8, 3 ' , 4 ' , 5 ' -tetrahydroxy flavone-6-oxy hexahydrobisabolene ether (4), 1, 9-dihydroxy tetrahydrogeranyl-8-oxy- O -β- D -glucuronopyranoside (5) and terahydrogeranyl-8-oxy- O -β-D-glucuronopyranosyl (2a→1b)- O -β-D-glucofuranosyl (2b→1c)- O -β-D-glucofuranosyl (2c→1d)- O -β-D-glucopyranosyl (2d→1e)- O -β-D-glucopyranosyl (2c→f)- O -β-D-glucopyranosyl-2f-benzoate (6) along with five known compounds, palmitoyl palmitoleoyl arachidoyl glyceride (1), tetratriacontenoic acid (2), palmitoyl oleoyl linolenoyl glyceride (3), hexanyl tetraglucoside (7) and pentasaccharide (8)., Conclusion: This is the first report of saturated monoterpene and sesquiterpene derivatives from jujuba seeds., Competing Interests: There are no conflicts of interest.

Ethnopharmacological Relevance: Euphorbia hirta L. (Euphorbiaceae) is a pantropical medicinal rhizomatous herb, traditionally used in the treatment of diabetes, respiratory and gastro-intestinal disorders., Aim of the Study: To isolate and characterize the constituents of Euphorbia hirta and evaluate their in-vitro α-glucosidase inhibitory activity. The study is also aimed at describing structural activity relationship, type of α-glucosidase inhibition and in-vivo potential to regulate post prandial hyperglycemia in Wistar rats., Materials and Methods: Methanolic extract of whole plant was suspended in water, and sequentially fractionated with n-hexane and ethyl acetate. Further ethyl acetate fraction was subjected to medium pressure liquid chromatography (MPLC) to isolate the active molecules under the following experimental conditions, pressure (up to 5 kg/cm(2)) and flow rate (2 in./min). The structural elucidation of isolated compounds was done on the basis of detailed spectral analysis. The α-glucosidase inhibitory potential of isolated compounds was evaluated and compared with standard drug acarbose. In addition, type of inhibition was dwelled by Lineweaver-Burk plot analysis. Further, sucrose tolerance test was performed in Wistar rats pre-treated with the isolated compounds and acarbose (0.015 mM) followed by a sucrose load (2g/kg, p.o.) and blood glucose level was measured up to 120 min by the glucose oxidase method., Results: The ethyl acetate fraction afforded quercetrin (1), dimethoxy quercetrin (2), along with two new prenylated flavonosides designated as hirtacoumaroflavonoside (3) and hirtaflavonoside-B (4) characterized as 7-O-(p-coumaroyl)-5,7,4'-trihydroxy-6-(3,3-dimethyl allyl)-flavonol-3-O-β-D-glucopyranosyl-(2" → 1"')-O-α-L-rhamnopyranoside and 5, 7, 3', 4'-trihydroxy-6-(3, 3-dimethyl allyl)-8-(iso-butenyl)-flavonol-3-C-β-d-glucopyranoside, respectively. All the isolated compounds showed dose dependent inhibition of α-glucosidase which was found to be comparable to acarbose. Maximum α-glucosidase inhibition was achieved with compound 3 (IC50 0.022 mM) followed by 4 (IC50 0.071 mM) in comparison to acarbose (IC50 0.092 mM). The results revealed that 5,7,4'- trihydroxyflavone structure is imperative for the inhibitory activity. The prenylation in the flavonoids increase the potency and p-coumaroyl substitution at C-7 further enriched the α-glucosidase inhibition. Compound 3 exhibited non-competitive inhibition while compounds 1, 2 and 4 showed mixed non-competitive inhibitory pattern. The results of sucrose tolerance test corresponded well with the in vitro studies., Conclusion: α-Glucosidase inhibitory activity and sucrose tolerance test demonstrated by the prenylated flavonoids present in E. hirta provide credence to the ethnomedicinal use of the plant in the management of diabetes in folk medicine., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The aim of the present study was to optimize niosomes by experimental design for enhanced transdermal delivery of ursolic acid for the effective treatment of arthritis. The experimental design (3 factor 3 levels, Box-Behnken design) was used to study individual and combined effects of different formulation variables. The variables cholesterol (X1), span 60 (X2) and phospholipid (X3) were taken as independent factors and their effect was observed on size (Y1) entrapment efficiency (Y2), and transflux (Y3). The formulation composition with span 60 (85mg), cholesterol (12.3mg), and phospholipid (65mg) was found to fulfil requisites of optimized ursolic acid niosome formulation (URNF). URNF had shown vesicle size of 665.45nm, entrapment efficiency of 92.74% with transflux of 17.25μg/cm(2)/h. The in vivo bioactivity showed that the prepared URNF-gel was able to provide good anti-arthritic activity due to enhanced permeation of UA through the skin and results were found to be comparable to standard gel (Omni gel). The radiographical image confirmed that, the developed URNF-gel was found to be effective to treat arthritis. Thus niosomal gel of ursolic acid would be a promising alternative to conventional therapy for safe and efficient treatment of arthritis and musculoskeletal disorders., (Copyright © 2015 Elsevier B.V. All rights reserved.)

In the present research, effect of sequential addition of Bifidobacterium bifidum, Bacillus subtilis and Rhizopus oligosporus on content and composition of vitamin K2 and isoflavones in fermented soy foods have been investigated. Initially, soybeans were fermented with B. bifidum; then this fermented mass was re-fermented with co-culture of B. subtilis and R. oligosporus. The evolved sequence of microbes inoculation tended towards significantly (p < 0.5) higher enzymes levels (126.16 ± 2.23 IU/mg lipase, 36.52 ± 1.25 IU/mg phytase and 8.52 ± 1.12 IU/mg β-glucosidase); maximum menaquinone-7 production (9.3 ± 1.27 μg/g); and isoflavone content (84.64 ± 1.97 % daidzein, 99.29 ± 0.86 % genistein, 96.42 ± 1.32 % glycitein) after 72 h of solid-state fermentation. The study showed that co-fermentation of soybean with different microbes in a particular sequence can enhance nutritional value batter than the mono-culture fermentation due to the positive correlation between enzymes (lipase, phytase, β-glucosidase) levels, menaquinone-7 and soy isoflavones content.

Background: Momordica charantia Linn. (Cucurbitaceae) fruits are well known for their beneficial effects in diabetes that are often attributed to its bioactive component charantin., Objective: The aim of the present study is to develop and optimize an efficient protocol for the extraction of charantin from M. charantia fruits., Materials and Methods: Response surface methodology (RSM) was used for the optimization of ultrasound-assisted extraction (UAE) conditions. RSM was based on a three-level, three-variable Box-Behnken design (BBD), and the studied variables included solid to solvent ratio, extraction temperature, and extraction time., Results: The optimal conditions predicted by the BBD were: UAE with methanol: Water (80:20, v/v) at 46°C for 120 min with solid to solvent ratio of 1:26 w/v, under which the yield of charantin was 3.18 mg/g. Confirmation trials under slightly adjusted conditions yielded 3.12 ± 0.14 mg/g of charantin on dry weight basis of fruits. The result of UAE was also compared with Soxhlet extraction method and UAE was found 2.74-fold more efficient than the Soxhlet extraction for extracting charantin., Conclusions: A facile UAE protocol for a high extraction yield of charantin was developed and validated.

Background: Black cumin oil is obtained from the seeds of Nigella sativa L. which belongs to family Ranunculaceae. The seed oil has been reported to possess antitumor, antioxidant, antibacterial, anti-inflammatory, hypoglycemic, central nervous system depressant, antioxidant, and immunostimulatory activities. These bioactivities have been attributed to the fixed oil, volatile oil, or their components. Seed oil consisted of 15 saturated fatty acids (17%) and 17 unsaturated fatty acids (82.9%). Long chain fatty acids and medium chain fatty acids have been reported to increase oral bioavailability of peptides, antibiotics, and other important therapeutic agents. In earlier studies, permeation enhancement and bioenhancement of drugs has been done with black cumin oil., Objective: In order to recognize the mechanism of binding of fatty acids to P-glycoprotein (P-gp), linoleic acid, oleic acid, margaric acid, cis-11, 14-eicosadienoic acid, and stearic acid were selected for in silico studies, which were carried out using AutoDock 4.2, based on the Lamarckian genetic algorithm principle., Materials and Methods: Template search with BLAST and HHblits has been performed against the SWISS-MODEL template library. The target sequence was searched with BLAST against the primary amino acid sequence of P-gp from Rattus norvegicus., Results: The amount of energy needed by linoleic acid, oleic acid, eicosadienoic acid, margaric acid, and stearic acid to bind with P-gp were found to be - 10.60, -10.48, -9.95, -11.92, and - 10.37 kcal/mol, respectively. The obtained data support that all the selected fatty acids have contributed to inhibit P-gp activity thereby enhances the bioavailability of drugs., Conclusion: This study plays a significant role in finding hot spots in P-gp and may offer the further scope of designing potent and specific inhibitors of P-gp., Summary: Generation of 3D structure of fatty acid compounds from Black cumin oil and 3D homology modeling of Rat P glycoprotein as a receptor.Rat P-gp structure quality shows 88.5% residues in favored region obtained by Ramchandran plot analysis.Docking analysis revealed that Some amino acids common for all compounds like Ser221, Pro222, Ile224, Gly225, Ser228, Ala229, Lys233, Tyr302, Tyr309, Ile337, Leu338 and Thr341 in the P-gp and ligands binding patterns.Eicosadeinoic acid has highest binding affinity with P-gp as the amount of energy needed to bind with P-gp was lowest (-11.92 kcal/mol). Abbreviations used: P-gp: P-glycoprotein.

Gymnemic acid and charantin are well-established antidiabetic phytosterols found in Gymnema sylvestre and Momordica charantia, respectively. The fact that these plants are often used together in antidiabetic poly-herbal formulations lured us to develop an HPTLC densitometric method for the simultaneous quantification of their bioactive compounds. Indirect estimation of gymnemic acid as gymnemagenin and charantin as β-sitosterol after hydrolysis has been proposed. Aluminum-backed silica gel 60 F254 plates (20 × 10 cm) were used as stationary phase and toluene-ethyl acetate-methanol-formic acid (60 : 20 : 15 : 5, v/v) as mobile phase. Developed chromatogram was scanned at 550 nm after derivatization with modified vanillin-sulfuric acid reagent. Regression analysis of the calibration data showed an excellent linear relationship between peak area versus concentration of the analytes. Linearity was found to be in the range of 500-2,500 and 100-500 ng/band for gymnemagenin and β-sitosterol, respectively. The suitability of the developed HPTLC method for simultaneous estimation of analytes was established by validating it as per the ICH guidelines. The limits of detection and quantification for gymnemagenin were found to be ≈60 and ≈190 ng/band, and those for β-sitosterol ≈30 and ≈90 ng/band, respectively. The developed method was found to be linear (r(2) = 0.9987 and 0.9943), precise (relative standard deviation <1.5 and <2% for intra- and interday precision) and accurate (mean recovery ranged between 98.43-101.44 and 98.68-100.20%) for gymnemagenin and β-sitosterol, respectively. The proposed method was also found specific and robust for quantification of both the analytes and was successfully applied to herbal drugs and in-house herbal formulation without any interference., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Erythrocentaurin is a relatively simple natural product present among the members of Gentianaceae. A preparative method for the isolation of erythrocentaurin from the ethyl acetate fraction of Enicostemma littorale using medium-pressure liquid chromatography has been reported. The method consisted of a simple step gradient from 10 to 20% ethyl acetate in n-hexane. Using a 70 × 460 mm Si60 column, this method is capable of processing 20 g of material in <3 h (purity ≈ 97%). The recovery of erythrocentaurin was 87.77%. Estimation of erythrocentaurin in extracts and fractions based on high-pressure thin-layer chromatography was carried out on silica gel 60 F(254) plates with toluene/ethyl acetate/formic acid (80:18:2 v/v/v) as the mobile phase. The densitometric analysis was performed at 230 nm. A well-separated compact band of erythrocentaurin appeared at R(f )0.54 ± 0.04. The analytical method showed good linearity in the concentration range of 200-1500 ng/band with a correlation coefficient of 0.99417. The limits of detection and quantification were found to be ≈60 and ≈180 ng/band, respectively. Erythrocentaurin exhibited a concentration-dependent α-amylase inhibition (IC(50) 1.67 ± 0.28 mg/mL). The outcome of the study should be considered for pharmacokinetic and biotransformation studies involving E. littorale., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Cucurbitacins which are structurally diverse triterpenes found in the members of Cucurbitaceae and several other plant families possess immense pharmacological potential. This diverse group of compounds may prove to be important lead molecules for future research. Research focused on these unattended medicinal leads from the nature can prove to be of immense significance in generating scientifically validated data with regard to their efficacy and possible role in various diseases. This review is aimed to provide an insight into the chemical nature and medicinal potential of these compounds exploring their proposed mode of action, probable molecular targets and to have an outlook on future directions of their use as medicinal agents.

Objective: To find out the ideal organic solvent and extraction technique for the isolation of luteolin from the leaves of Vitex negundo Linn. (V. negundo) by quantitative estimation of luteolin through high performance liquid chromatography (HPLC) method., Methods: The leaves of V. negundo were identified by a botanist, cleaned, dried under shade and powdered. Maceration, reflux, Soxhlet and ultrasound assisted extraction techniques were used for the extraction of luteolin from the leaves by using four different solvents of varying polarity such as methanol, ethanol, chloroform, and dichloromethane. A simple HPLC method was used to determine the quantity of luteolin in each sample extract., Results: The calibration plot of standard luteolin showed a linear relationship in the concentration range of 100-500 μg/mL with a correlation coefficient, r(2) of 0.998. The methanolic extract was found to contain highest amount of luteolin and among various techniques employed for extraction and isolation of luteolin, reflux technique was observed to be the most efficient., Conclusion: Based on the HPLC results, it can be concluded that reflux technique using methanol is better than the other extraction techniques and should be preferred for the extraction and isolation of luteolin from V. negundo leaves extract in research labs or industries., (Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.)

Background: Phytochemical investigation of hydroalcoholic extract of the root of Inula racemosa Hook., Materials and Methods: Open silica gel column chromatographic techniques with different solvent systems was used for isolation of aliphatic and eudesmalolide esters from hydroalcoholic extract of the root of Inula racemosa. The structure elucidation of the compounds was done on the basis of spectral data analysis, chemical reactions and comparision with literature data., Results: Phytochemical investigation of the hydroalcoholic extract of the root of Inula racemosa Hook. f. led to the isolation of (5z, 13z)-n-decanyl-n-docos-5, 13-dienoate, a new fatty acid ester, two new sesquiterpenic ester identified as 15-[(13z, 18'z, 20'z)-n-tricos-13, 18, 20-trienyl]-eudesmal-4 (11), 6, 12 (13)-trien-8,14-olide-15-oate and 15- [(16'z), (21'z)-n- tetracos-16', 21'- dienyl]-eudesmal-4 (11) 6, 12 (13)-trien-8, 14-olide-15-oate, two new eudesmanolide ester i.e. 15-[(16z)-n-monadec-16'- enyl]-eudesmal-4 (11) 6, 12 (13)-trien-8,14-olide-15-oate and 15-[(16'z)-n-tetracos-16'- enyl]-endesmal-4 (11), 6, 12 (13)-trien-8,14-olide-15-oate along with the known compound n-Hexadecanyl n-docosanoate., Conclusion: Five new phytoconstituents were identified along with one known compound as aliphatic and eudesmalolide esters from the hydroalcoholic extract of the root of Inula racemosa, as mentioned above.

Objective: To evaluate hypoglycemic and hypolipidemic effects of Salvadora persica aqueous extracts on streptozotocin-induced diabetic rats by measuring fasting blood glucose levels, lipid profiles and histopathological analysis of pancreas., Materials and Methods: Experimental Diabetes was induced by single intraperitoneal injection of streptozotocin (60 mg/kg) to albino Wistar rats. Salvadora persica extracts were administered orally at 250 and 500 mg/kg dose levels for 21 days. Glucose tolerance test (GTT) was performed on 16 h fasted rats and changes in blood glucose levels, total cholesterol, triglycerides, low-density lipoprotein (LDL), very low density lipoprotein (VLDL), high density lipoprotein (HDL) and histopathology of pancreas were performed., Results: At a dose level of 500 mg/kg, blood glucose 85.25 ± 13.20 mg/dl, total cholesterol (TC) 114.57 ± 15.81(mg/dl), triglycerides (TG) 75.40 ± 16.47(mg/dl), LDL 42.63 ± 13.17(mg/dl), VLDL 22.78 ± 1.88(mg/dl), and elevation of HDL 44.88 ± 11.61(mg/dl) were found in comparison with diabetic control on 28(th) day by Arabic origin Salvadora persica. It also accelerated the regeneration of β-cells in experimental animal's pancreas to 32.6 ± 2.4 compared to diabetic control animal's pancreas of 8.1 ± 0.5 at the end of 28(th) day., Conclusion: This study confirmed that Arabic Salvadora persica aqueous extracts at 500 mg/kg dose level, in comparison to other extracts (Indian Salvadora persica, 250 and 500 mg/kg, Arabic Salvadora persica 250 mg/kg) possessed significant hypoglycemic and hypolipidemic activities and regenerated pancreatic β-cells in streptozotocin treated diabetic rats.

Aim of present study was to develop a solid nanoemulsion preconcentrate of paclitaxel (PAC) using oil [propylene glycol monocaprylate/glycerol monooleate, 4:1 w/w], surfactant [polyoxyethylene 20 sorbitan monooleate/polyoxyl 15 hydroxystearate, 1:1 w/w], and cosurfactant [diethylene glycol monoethyl ether/polyethylene glycol 300, 1:1 w/w] to form stable nanocarrier. The prepared formulation was characterized for droplet size, polydispersity index, and zeta potential. Transmission electron microscopy (TEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) were used to assess surface morphology and drug encapsulation and its integrity. Cumulative drug release of prepared formulation through dialysis bag and permeability coefficient through everted gut sac were found to be remarkably higher than the pure drug suspension and commercial intravenous product (Intaxel), respectively. Solid nanoemulsion preconcentrate of PAC exhibited strong inhibitory effect on proliferation of MCF-7 cells in MTT assay. In vivo systemic exposure of prepared formulation through oral administration was comparable to that of Intaxel in γ scintigraphy imaging. Our findings suggest that the prepared solid nanoemulsion preconcentrate can be used as an effective oral solid dosage form to improve dissolution and bioavailability of PAC.