Search

The current study aimed to determine the safety and efficacy of Coag-A through in vivo analysis in CFA induced mice model. Treatment of CFA induced arthritis in mice with Coagulansin-A (10 mg/kg i.p. daily for 28 days), a withanolide obtained from Withania coagulans, as well as standard drug treatment with Dexamethasone (5 mg/kg i.p) was provided. The effect of Coag-A on body weight, relative organ weight, hematology, serum biochemistry, survival rate, oxidative stress markers, and antioxidant enzymes was evaluated. The liver and kidney histopathology were also assessed to ascertain its safety profile. Treatment of arthritic mice with Coag-A considerably improved body weight, relative organ weight of liver, kidney, and spleen, ameliorated hematology and serum biochemistry, and increased survival and antioxidant potential. Coag-A was found to be safer with fewer adverse effects showing hepato-protective, nephroprotective, and anti-inflammatory effect. It also significantly (p < 0.001) improved histopathology of CFA-induced mice when compared with Dexa. In conclusion, compared to dexamethasone, Coag-A has demonstrated a greater therapeutic benefit and fewer side effects in the treatment of arthritis against the CFA-induced model., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The aphid, Schizaphis graminum Rondani (Hemiptera: Aphididae), is one of the most destructive pests of wheat. It is responsible for significant economic losses in the agricultural sector, with an estimated 45% of wheat fields affected. Plant-based insecticides have seen a rapid increase in popularity in recent years due to their efficacy, cost-effectiveness, biodegradability, and lower toxicity compared to synthetic pesticides. The study aimed to evaluate the toxic potential of S. longipedunculata extracts against S. graminum and investigate the insect's feeding behavior on wheat. Initially macerated in methanol, the different extracts of S. longipedunculata organs were fractionated using n -hexane, chloroform, ethyl acetate, and butanol. The feeding behavior was analyzed by comparing the waveforms generated by the EPG with the control. After 72 h of treatment, the ethyl acetate fraction extracted from root had the highest toxicity against aphids, with mean 26 mortality of S. graminum at LC50 of 330 ppm; 25 mortality S. graminum at LC50 of 400 ppm for leaves; and mean 24.5 mortality S. graminum at LC50 of 540 ppm in stem bark. EPG analysis indicated that the extract fractions enhanced plant tissue resistance by significantly preventing aphid access to the phloem. The toxic effect of the botanical extracts significantly enhanced the chemical composition of the leaf medium, resulting in a drastic reduction in the number of tissue attacks by S. graminum . In summary, besides their toxicity to S. graminum , extracts of S. longipedunculata reinforce the plant's defense mechanisms, significantly reducing the S. graminum population. They also reinforce wheat's defense mechanisms. S. longipedunculata can, therefore, be used as a promising agent in the biological control of S. graminum ., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

For many years, the synthesis of graphene oxide (GO) had involved exfoliating graphite flakes, and the methods applied were expensive and time-consuming. Thus, an attempt had been made to create an inventive, less expensive method for the synthesis of GO using unrefined, raw carbon-containing material. Modified Hummer's method was used to prepare GO from banana peel. In addition, the metallic silver nanocomposite was also synthesized along with laoding of drug Rocephin where they interact with each other through electrostatic hydrogen bond interaction. The degree of crystallinity and the crystallite size were through x-ray diffraction (XRD) analysis and the crystallite size of AgNPs was found to be 40.40 nm. The scanning electron microscopy (SEM) analysis shows that the morphology of the GO gradually changes with the addition of AgNPs and Rocephin. A blue shift was seen in the absorbance maxima of the raw carbon upon the conjugation of Rocephin in UV analysis. The Fourier-transform infrared spectroscopy, and energy dispersive X-ray (EDX) spectroscopy were used to determine the chemical composition of the samples. Furthermore, a broad biological screening of the synthesized samples had been carried out following the total reducing power (TRP), total antioxidant capacity (TAC), antibacterial, antifungal, MTT (Cytotoxicity of biologically synthesized silver nanoparticles in MDA-MB-231 human breast cancer cells) cell viability, brine shrimp lethality, and hemolytic protocols. Significant results were obtained, and the Rocephin-GO-AgNPs had depicted promising activity as compared with their counterparts. RESEARCH HIGHLIGHTS: The GO was prepared from the raw carbon extracted from banana peels and was used as a substrate for the synthesis Graphene oxide silver nanoparticles (GO-AgNPs) and Rocephin-loaded graphene oxide silver nanoparticles (Rocephin-GO-AgNPs) The structural and compositional analysis of the nanomaterial was carried out, and they were screened for several biomedical applications. The Rocephin-GO-AgNPs exhibit the highest activity as compared with their counterparts., (© 2024 Wiley Periodicals LLC.)

Artemisinin, artemether, artesunate, and dihydroartemisinin are renowned for their antimalarial potential. The current study aims to repurpose the above-mentioned artemisinic compounds (ACs) by conducting an intercomparison to evaluate their antiinflammatory potential (AIP). In order to develop potential candidates for the evaluation of AIP of ACs (50 and 100 mg/kg BW), carbon tetrachloride (1ml/kg body weight (BW)) was administered intraperitoneally to BALB/c mice. Alterations in animal behavior were assessed weekly through tail suspension test, force swim test, open field test, Y-maze test, inverted screen analysis, and weight lifting test. Aberrations in hematological, serological, endogenous antioxidants, and oxidative stress marker profiles were assessed in all twelve groups. Histological alterations were read using hematoxylin and eosin staining. Levels of inflammatory markers including nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α), and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), were determined using immunohistochemical analysis (IHCA). Antioxidant markers i.e., nuclear factor erythroid-2-related factor (Nrf-2) and thioredoxin (TRX) were also quantified through IHCA. Comet assay was performed to quantify DNA damage. Oral administration of ACs to mice significantly alleviated the carbon tetrachloride induced inflammation in comparison with silymarin. Reduced levels of several inflammatory markers including nitric oxide, thiobarbituric acid reactive substances, interleukin-1 beta, NF-κB, TNF-α, and NLRP3, underscore the substantial AIP of ACs. IHCA depicted the revitalized percent relative expression of Nrf-2 and TRX in groups treated with ACs. Behavioral analysis revealed that ACs-treated groups significantly (p<0.05) attenuated the memory deficit, anxiety, and depressive-like behavior. Moreover, histopathological, hematological, serological, and endogenous antioxidant profiles indicated substantial AIP of ACs. Findings of comet assay further bolstered the compelling evidence as DNA damage was significantly (p<0.05) curbed down after ACs (100 mg/kg) treatment. All these outcomes implied that ACs exhibited AIP in a dose-dependent manner with maximal AIP imparted by artemisinin (100 mg/kg). This pre-clinical investigation avers the tremendous AIP of ACs targeting key molecular pathways. The current study divulges artemisinin as the most potent antiinflammatory agent among the tested compounds., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kazmi, Fatima, Naz, Kanwal and Haq.)

Mycotoxins are toxic mycological products that when consumed, absorbed or inhaled cause sickness or even the death of humans. Therefore, the present study aimed to evaluate the contamination levels of mycotoxins (aflatoxins, AFB 1 , AFB 2 , AFG 1 , AFG 2 , and ochratoxin A, OTA) in selected medicinal herbs and shrubs using thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC). A total of 15 samples of medicinal herbs and shrubs were selected. Among them, four samples were aflatoxin contaminated while two samples were ochratoxin A contaminated. The highest level of aflatoxin was detected in Justicia adhathoda (4,704.94 ppb) through HPLC (153.4 ppb) and through TLC, while the lowest level of aflatoxin was detected in Pegnum harmala (205.1 ppb) through HPLC. Similarly, the highest level of OTA was detected in Dodonia viscosa (0.53 ppb) through HPLC (0.5 ppb) and through TLC, while the lowest level was detected in J. adhathoda (O.11 ppb) through HPLC (0.4 ppb) and through TLC. The OTA concentration was very low, being negligible and below permissible limits. The present study concludes that there is a potential risk for the consumption of herbal decoctions. Therefore, regular monitoring and proper management of mycotoxins, including aflatoxins and OTA, in herbal medicines are needed to ensure the safety of herbal drugs to protect consumers., (© 2024 John Wiley & Sons Ltd.)

In agroecosystems, insects contend with chemical insecticides often encountered at sublethal concentrations. Insects' exposure to these mild stresses may induce hormetic effects, which has consequences for managing insect pests. In this study, we used an electrical penetration graph (EPG) technique to investigate the feeding behavior and an age-stage, two-sex life table approach to estimate the sublethal effects of thiamethoxam on greenbug, Schizaphis graminum. The LC 5 and LC 10 of thiamethoxam significantly decreased longevity and fecundity of directly exposed adult aphids (F 0 ). However, the adult longevity, fecundity, and reproductive days (RP d )-indicating the number of days in which the females produce offspring - in the progeny generation (F 1 ) exhibited significant increase when parental aphids (F 0 ) were treated with LC 5 of the active ingredient. Subsequently, key demographic parameters such as intrinsic rate of increase (r) and net reproductive rate (R 0 ) significantly increased at LC 5 treatment. EPG recordings showed that total durations of non-probing (Np), intercellular stylet pathway (C), and salivary secretion into the sieve element (E1) were significantly increased, while mean duration of probing (Pr) and total duration of phloem sap ingestion and concurrent salivation (E2) were decreased in F 0 adults exposed to LC 5 and LC 10 . Interestingly, in the F 1 generation, total duration of Np was significantly decreased while total duration of E2 was increased in LC 5 treatment. Taken together, our results showed that an LC5 of thiamethoxam induces intergenerational hormetic effects on the demographic parameters and feeding behavior of F 1 individuals of S. graminum. These findings have important implications on chemical control against S. graminum and highlight the need for a deeper understanding of the ecological consequences of such exposures within pest management strategies across the agricultural landscapes., (© 2024. The Author(s).)

Thiamethoxam, a second-generation neonicotinoid insecticide is widely used for controlling sap-sucking insect pests including Rhopalosiphum padi . The current study aimed to investigate the life-history parameters and feeding behavior of R. padi following treatments with sublethal concentrations of thiamethoxam. The lethal concentration 50 (LC 50 ) value of thiamethoxam against adult R. padi was 11.458 mg L -1 after 48 h exposure. The sublethal concentrations of thiamethoxam (LC 5 and LC 10 ) significantly decreased the adult longevity, fecundity, and reproductive days in the directly exposed aphids (F 0 generation). In the progeny R. padi (F 1 ), the developmental durations and total prereproductive period (TPRP) were decreased while the adult longevity, fecundity, and reproductive days (RP d ) were increased at both thiamethoxam concentrations. The demographic parameters including the net reproductive rate ( R 0 ), intrinsic rate of increase ( r ), and finite rate of increase ( λ ) were prolonged only at the LC 5 of thiamethoxam. The EPG results indicated that the sublethal concentrations of thiamethoxam increases the total duration of non-probing (Np) while reducing the total duration of E2 in directly exposed aphids (F 0 ). Interestingly, the E2 were significantly increased in the progeny generation (F 1 ) descending from previously exposed parental aphids (F 0 ). Overall, this study showed that thiamethoxam exhibited high toxicity against directly exposed individuals (F 0 ), while inducing intergenerational hormetic effects on the progeny generation (F 1 ) of R. padi . These findings provided crucial details about thiamethoxam-induced hormetic effects that might be useful in managing resurgences of this key pest.

Background: The peach fruit fly, Bactrocera zonata (Saunders) (Diptera: Tephritidae) is an economically important polyphagous, quarantine pest endemic to South and South-East Asia. The male annihilation technique (MAT) and the sterile insect technique (SIT) are environmentally benign techniques used to suppress fruit fly populations on an area-wide basis. The MAT and SIT are typically used sequentially to avoid killing released sterile males; however, MAT and SIT potentially could be used simultaneously and thereby increase the overall efficiency of control programmes. Mating competitiveness of sterile males against wild counterparts is critical for the success of the SIT. Feeding on a semiochemical, methyl eugenol (ME) has been reported to enhance the male mating performance of many Bactrocera spp., including B. zonata, but its use in SIT operational programmes is limited owing to the absence of a viable delivery system., Results: In the present study, we demonstrated that ME aromatherapy, a practical method for large-scale delivery of ME olfactorily, enhances the mating success of treated B. zonata males. ME aromatherapy application to 5-day-old immature males for a duration of 5 h resulted in increased mating success of males tested when sexually mature, compared to untreated males. The ME-aromatized males also exhibited reduced attraction to ME-lure., Conclusion: A practical delivery system for applying ME by aromatherapy to mass-reared males was developed. ME-aromatherapy enhanced male mating success and suppressed their subsequent attraction to ME, thus enabling the application of MAT and SIT at the same time. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Psoriasis is a common immune-mediated skin condition characterized by aberrant keratinocytes and cell proliferation. The purpose of this study was to explore the FDA-approved drugs by 3D-QSAR pharmacophore model and evaluate their efficiency by in-silico, in vitro, and in vivo psoriasis animal model. A 3D-QSAR pharmacophore model was developed by utilizing HypoGen algorithm using the structural features of 48 diaryl derivatives with diverse molecular patterns. The model was validated by a test set of 27 compounds, by cost analysis method, and Fischer's randomization test. The correlation coefficient of the best model (Hypo2) was 0.9601 for the training set while it was 0.805 for the test set. The selected model was taken as a 3D query for the virtual screening of over 3000 FDA-approved drugs. Compounds mapped with the pharmacophore model were further screened through molecular docking. The hits that showed the best docking results were screened through in silico skin toxicity approach. Top five hits were selected for the MD simulation studies. Based on MD simulations results, the best two hit molecules, that is, ebastine (Ebs) and mebeverine (Mbv) were selected for in vitro and in vivo antioxidant studies performed in mice. TNF-α and COX pro-inflammatory mediators, biochemical assays, histopathological analyses, and immunohistochemistry observations confirmed the anti-inflammatory response of the selected drugs. Based on these findings, it appeared that Ebs can effectively treat psoriasis-like skin lesions and down-regulate inflammatory responses which was consistent with docking predictions and could potentially be employed for further research on inflammation-related skin illnesses such as psoriasis., (© 2024 Wiley-VCH GmbH.)

Background: CoFe 2 O 4 are important magnetic NPs with high coercivity and moderate magnetization. These properties of CoFe 2 O 4 NPs show variation when doped with various metals. Recent studies explained that Cobalt ferrites doped with metal ion like Mn +2 , have attracted increasing attention in many applications, particularly in biomedical applications. A relatively simple way is employing plants and their extracts as precursors instead of toxic chemicals to produce NPs with desirable characteristic. In current study we report green synthesis and characterization of magnetic (CoFe 2 O 4 , MnCoFe 2 O 4 , CoFe 2 O 4 @S.C, MnCoFe 2 O 4 @S.C) nanoparticles using ethanolic extract of Swertia Chirata. To enhance application as biocompatible magnetic nano drug delivery vector and cell targeting efficacy of drugs, Glimepiride (GLM), Dexamethasone (DXM), Fexofenadine (FEX) and Levofloxacin (LVX) 1were loaded on synthesized NPs. Synthesized CFNPs has been broadly characterized and applied for in vitro anticancer, antidiabetic and antibacterial potential., Methods: For synthesis of CoFe 2 O 4 (CF), CoMnFe 2 O 4 (CFM), CoFe 2 O 4 @S.C (SCF) & CoMnFe 2 O 4 @S.C (SCFM), stochiometric amounts 5 mmol of CoCl 2 ·6 H 2 O (0.284 g) and 10 mmol FeCl 3 ·6 H 2 O (0.378 g) were dissolved in 13 mL of deionized water. To this sodium acetate (3.05 g) and urea (0.6 g) were added until complete dissolution. Afterward n-heptane was added, and contents were then transferred to Teflon lining autoclave at 180 °C for 4 h. Black powder CoFe 2 O 4 NPs after washing, were dried and calcined at 450 oC for 2 h., Results: XRD diffractogram of CF have proved the single-phase cubic spinel structure formation for all samples. Swertia Chirata formulations were shown to have effective in vitro antidiabetic activity. CF, CFM & SCFM showed good inhibition of α-glucosidase with very low concentration 6 µg/mL, 5 µg/mL and 4 µg/mL as compare to 12.41 µg/mL of acarbose. SCF showed that the value slightly higher than 16 µg/mL compared to standard. Drug loaded CFNPs (L-CFNPs, F-CFNPs, D-CFNPs & G-CFNPs) also effectively inhibited α-glucosidase. IC50 value for CFNPs inhibition of α-glucosidase was 12.4 µg/mL. All synthesized CF NPs showed cytotoxic potential against breast cancer cells MCF-7. About 50-60% cell viability and cytotoxicity 40% were observed for bare CFNPs as compare to Doxorubicin with related toxicity 80% and 20% cell viability. Among synthesized samples almost all samples without conjugation of any drug showed activities against at least one bacterial strain. CFM, SCF, SCFM were active against S. aureus at concentration 100 µg/mL, 100 µg/mL, and 50 µg/mL respectively., Conclusion: The synthesized CF NPs showed significant cytotoxic potential against MCF-7 breast cancer cell line. Further, drug loaded samples displayed lesser cell viability and slightly increased cytotoxicity in range of 40-50% in comparison with bare CFNPs. However, higher toxicity was observed for CFMGS towards MCF-7 cells with results nearly equal to Doxorubicin with significant decrease in viability. CF, CFM & SCFM showed good inhibition of α-glucosidase with very low concentration 6 µg/mL, 5 µg/mL and 4 µg/mL as compare to 12.41 µg/mL of acarbose. Among synthesized samples almost all samples without conjugation of any drug showed activities against at least one bacterial strain., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Introduction: Natural antioxidants are vital to promote health and treat critical disease conditions in the modern healthcare system. This work adds to the index of natural medicines by exploring the antioxidant potential of Dodonaea viscosa Jacq. (Plant-DV). Material and Methods: The aqueous extract of leaves and flower-containing seeds from plant-DV in freshly prepared phosphate buffer is evaluated for antioxidant potential. In vitro antioxidant potential of the nascent and oxidatively stressed extracts was analyzed through glutathione (GSH) assay, hydrogen peroxide (H 2 O 2 ) scavenging effect, glutathione-S-transferase (GST) assay, and catalase (CAT) activity. In vivo therapeutic assessment is performed in Wistar Albino rats using vitamin C as a positive control. The livers and kidneys of individual animals are probed for glutathione, glutathione-S-transferase, and catalase activities. Results: flower-containing seeds have GSH contents (59.61 µM) and leaves (32.87 µM) in the fresh aqueous extracts. The hydrogen peroxide scavenging effect of leaves is superior to flower-containing seeds with 17.25% and 14.18% respectively after 30 min incubation. However, oxidatively stressed extracts with Ag(I) and Hg(II) show declining GSH and GST levels. The plant extracts are non-toxic in rats at 5000 mg/Kg body weight. Liver and kidneys homogenate reveal an increase in GSH, GST, and CAT levels after treatment with 150 ± 2 mg/kg and 300 ± 2 mg/kg body weight plant extract compared with normal saline-treated negative and vitamin C treated positive control. Discussion: The crude aqueous extracts of leaves and flower-containing seeds of plant-DV show promising antioxidant potential both in in vitro and in vivo evaluation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Khan, Rehman, Khan, Kousar, Muhammad, Haq, Ijaz Khan, Almasoud, Alomar and Rauf.)

Objective: Berberis lycium is an indigenous plant of Pakistan that is known for its medicinal properties. In the current study, we investigated the anti-Alzheimer's effect of berberine isolated from Berberis lycium., Methods: Root extract of B. lycium was subjected to acetylcholinesterase inhibition assay and column chromatography for bioassays guided isolation of a compound. The neuroprotective and memory improving effects of isolated compound were evaluated by aluminium chloride induced Alzheimer's disease rat model, elevated plus maze (EPM) and Morris water maze (MWM) tests., Levels of dopamine and serotonin in rats brains were determined using HPLC. Moreover, western blot and docking were performed to determine interaction between berberine and β-secretase., Results: During fractionation, ethyl acetate and methanol (3:7) fraction was collected from solvent mixture of ethyl acetate and methanol. This fraction showed the highest anti-acetylcholinesterase activity and was alkaloid positive. The results of TLC and HPLC analysis indicated the presence of the isolated compound as berberine. Additionally, the confirmation of isolated compound as berberine was carried out using FTIR and NMR analysis. In vivo EPM and MWM tests showed improved memory patterns after berberine treatment in Alzheimer's disease model. The levels of dopamine, serotonin and activity of antioxidant enzymes were significantly (p<0.05) enhanced in brain tissue homogenates of berberine treated group. This was supported by decreased expression of β-secretase in berberine treated rat brain homogenates and good binding affinity of berberine with β-secretase in docking studies. Binding energies for interaction of β-secretase with berberine and drug Rivastigmine is -7.0 kcal/mol and -5.8 kcal/mol respectively representing the strong interactions. The results of docked complex of secretase with berberine and Rivastigmine was carried out using Gromacs which showed significant stability of complex in terms of RMSD and radius of gyration. Overall, the study presents berberine as a potential drug against Alzheimer's disease by providing evidence of its effects in improving memory, neurotransmitter levels and reducing β-secretase expression in the Alzheimer's disease model., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ismail 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.)

(1) Background: A possible solution to antimicrobial resistance (AMR) is synergism with plants like Artemisia brevifolia Wall. ex DC. (2) Methods: Phytochemical quantification of extracts (n-hexane (NH), ethyl acetate (EA), methanol (M), and aqueous (Aq)) was performed using RP-HPLC and chromogenic assays. Extracts were screened against resistant clinical isolates via disc diffusion, broth dilution, the checkerboard method, time-kill, and protein quantification assays. (3) Results: M extract had the maximum phenolic (15.98 ± 0.1 μg GAE/mgE) and flavonoid contents (9.93 ± 0.5 μg QE/mgE). RP-HPLC displayed the maximum polyphenols in the M extract. Secondary metabolite determination showed M extract to have the highest glycosides, alkaloids, and tannins. Preliminary resistance profiling indicated that selected isolates were resistant to cefixime (MIC 20-40 µg/mL). Extracts showed moderate antibacterial activity (MIC 60-100 µg/mL). The checkerboard method revealed a total synergy between EA extract and cefixime with 10-fold reductions in cefixime dose against resistant P. aeruginosa and MRSA. Moreover, A. brevifolia extracts potentiated the antibacterial effect of cefixime after 6 and 9 h. The synergistic combination was non- to slightly hemolytic and could inhibit bacterial protein in addition to cefixime disrupting the cell wall, thus making it difficult for bacteria to survive. (4) Conclusion: A. brevifolia in combination with cefixime has the potential to inhibit AMR.

The bird cherry-oat aphid, Rhopalosiphum padi (L.) (Hemiptera: Aphididae) is one of the most economically important pests of wheat crops worldwide. Thiamethoxam, bifenthrin, and flonicamid are extensively used insecticides for controlling this key pest. However, the indiscriminate use of chemical insecticides has led to the development of resistance in insects. In this study, we assessed the development of selection-induced resistance to bifenthrin, flonicamid, and thiamethoxam under controlled laboratory conditions. Additionally, we employed the age-stage, two-sex life table method to examine the fitness of R. padi . After ten generations of selection, bifenthrin-, flonicamid-, and thiamethoxam-resistant strains of R. padi were developed with resistance levels of 34.46, 31.97, and 26.46-fold, respectively. The life table analysis revealed a significant decrease in adult longevity and fecundity in these resistant strains compared to susceptible strain. Furthermore, the key demographic parameters such as net reproductive rate ( R 0 ) and reproductive days exhibited a significant reduction in all resistant strains, while the intrinsic rate of increase ( r ) and finite rate of increase ( λ ) were decreased only in resistant strains to bifenthrin and thiamethoxam. Taken together, these findings provide a comprehensive understanding of laboratory-induced insecticide resistance evolution and the associated fitness costs in R. padi . This knowledge could help to design resistance management strategies against this particular pest of wheat.

Objective: The main objective of this study was to develop a highly sensitive, accurate, and reproducible analytical method for the simultaneous detection of LEF and FA in polymeric nanocarriers., Significance: Leflunomide (LEF), is widely employed in the treatment of rheumatoid arthritis (RA). However, long-term delivery of the drug is associated with systemic side effects. Therefore, folate (FA) conjugated LEF nanocarriers were fabricated for targeting the nanocarriers toward activated macrophages. HPLC is considered one of the most sensitive and precise analytical techniques for the simultaneous detection and estimation of different components in a particular sample., Methods: Analysis was performed on HPLC (Shimadzu 10 A), having a reversed-phase C-18 column (Beckmen, 250 X 4.6 mm, 5 µm) equipped with a photodiode detector set at a wavelength of 260 nm (LEF) and 285 nm (Folic acid). The isocratic mobile phase was composed of acetonitrile, water, and trimethylamine in a ratio of 65:35:0.5 at pH 4. Rapid analysis of both agents was performed, with a total run time of 10 min (FA = 2.1 ± 0.1 min, LEF = 5.9 ± 1 min) at a 1 mL/min flow rate., Results: The assay demonstrated good linearity of 0.9989 of 0.9997 for LEF and FA respectively with a recovery in the range of 95-100%. The method also depicted good specificity, and intra and inter-day precision based on relative standard deviation (RSD) values., Conclusions: The study concludes, that the developed method was helpful in the detection and quantitation of lower values of both agents from polymeric nanocarriers.

Multiple sclerosis (MS) is a debilitating neurodegenerative autoimmune disease of the central nervous system (CNS). The current study aimed to investigate the neuroprotective properties of Ajugarin-I (Aju-I) against the experimental autoimmune encephalomyelitis (EAE) model of MS and explored the underlying mechanism involved. The protective potential of Aju-I was first confirmed against glutamate-induced HT22 cells and hydrogen peroxide (H 2 O 2 )-induced BV2 cells. Next, an EAE model has been established to investigate the mechanisms of MS and identify potential candidates for MS treatment. The behavioral results demonstrated that Aju-I post-immunization treatment markedly reduced the EAE-associated clinical score, motor impairment, and neuropathic pain. Evans blue and fluorescein isothiocyanate extravasation in the brain were markedly reduced by Aju-I. It effectively restored the EAE-associated histopathological changes in the brain and spinal cord. It markedly attenuated EAE-induced inflammation in the CNS by reducing the expression levels of p-38/JNK/NF-κB but increased the expression of IkB-α. It suppressed oxidative stress by increasing the expression of Nrf2 but decreasing the expression of keap-1. It suppressed EAE-induced apoptosis in the CNS by regulating Bax/Bcl-2 and Caspase-3 expression. Taken together, this study suggests that Aju-I treatment exhibits neuroprotective properties in the EAE model of MS via regulation of MAPK/NF-κB, Nrf2/Keap-1, and Bcl2/Bax signaling., (© 2023 John Wiley & Sons, Ltd.)

Diabetic neuropathic pain is one of the microvascular complications of diabetes mellitus characterized by symmetrical pain and sensory abnormalities. A steroidal lactone isolated from the datura innoxa plant, withametelin (WMT), exhibited significant neuroprotective, anti-inflammatory, antioxidant, and anticancer properties. The current study aimed to investigate anti-neuropathic pain activity and the molecular mechanism of WMT against streptozotocin (STZ)-induced diabetic neuropathy. Rats were given a single injection of STZ (60 mg/kg, intraperitoneally (i.p.)) for induction of diabetes on the first day of the study. After the onset of diabetic neuropathy, pregabalin (10 mg/kg, i.p.) and WMT (0.1 and 1 mg/kg, i.p.) treatments were started from day 14 up to day 42. It was found that STZ-induced neuropathic pain behaviors were markedly reduced by WMT. It inhibited the STZ-associated histopathological changes and genotoxicity in the sciatic nerve and spinal cord. Additionally, Fourier transforms infrared (FTIR) spectroscopy results revealed that STZ-induced alterations in the biochemical components of the sciatic nerve's myelin sheath were inhibited by WMT. In the spinal cord, it markedly reduced the immunoreactivity of mitogen-activated protein kinases (MAPKs) signaling components such as p38-MAPK, c-Jun N-terminal kinase (JNK), extracellular-signal-regulated-kinase (ERK), and activator-protein 1 (AP-1). It also reduced the expression levels of nuclear factor-kappa-B (NF-κB), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). The production of inflammatory cytokines was considerably reduced by WMT. This study provides convincing evidence that WMT treatment attenuated STZ-induced diabetic neuropathic pain by inhibition of MAPK/NF-κB signaling., 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.)

Materials and Methods: The extract library (n-hexane (NH), ethyl acetate (EA), methanol (M), distilled water (DW), and combined extract (CE)) was standardized using in vitro phytochemical, antioxidant, and α -amylase inhibition assays, after which the protective effect of selected "hit," i.e., CE against metabolic syndrome, was determined in vivo , using rats fed a high-fat diet supplemented with additional cholesterol administration. CE was administered to Sprague Dawley rats in high dose as 100 mg/kg in carboxymethyl cellulose (CMC) (1 ml; 0.75% in DW) and low-dose group as 50 mg/kg in CMC (0.5 ml; 0.75% in DW). After 10 weeks, the effects of CE on insulin resistance, lipid metabolism, nonalcoholic fatty liver disease (NAFLD), oxidative stress, and genotoxicity were assessed through histological, biochemical, and hematological investigations., Results: Phytochemical analysis including RP-HPLC analysis of the extracts showed that flavonoids and phenolics (myricetin, kaempferol, and apigenin), previously known to be effective against obesity and diabetes, are present in the extracts. Antioxidant studies revealed that the plant possesses a highly significant ( p < 0.05) concentration of antioxidants. Satisfactory α -amylase inhibitory activity was also observed in in vitro experiments. In vivo studies showed that CE-administered animals had significantly ( p < 0.05) lower weight gain and smaller adipocytes than the control group. Moreover, CE resisted any significant ( p < 0.05) change in the organ weights. Analogous to findings from its traditional use, the plant extract had a positive modulatory effect on insulin resistance and hyperglycemia. The study also indicated that CE resisted high-fat diet-induced disturbance in lipid profile and countered any pathological changes in liver enzymes caused by fat-infused diet. Furthermore, a study on endogenous antioxidant levels indicated that CE was effective in maintaining catalase and peroxidase levels within the normal range and resisted the effects of lipid peroxidation of thiobarbituric acid reactive substances., Conclusion: In principle, the current study's findings scientifically validate the implication of T. linearis in metabolic syndrome and recommend further studies on molecular insights of the observed therapeutic activity., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2023 Yamema Younatan et al.)

Ethnopharmacological Relevance: People of all ages experience injuries, whether mild or severe. The most available option to treat wounds as an alternative to allopathic care in both urban and rural populations is traditional medicine, which is mostly target inflammation. Bergenia ciliata (Haw.) Sternb rhizome and leaf powder are used in Ayurveda and local communities for various ailments including healing of wounds and burns. Owing to this property it is traditionally known as "Zakham-e-hayat" (wound healer)., Aim of the Study: In the present study, we compared biological activity and wound healing potential of B. ciliata rhizome (R) extract and bergenin, a glycoside isolated from B. ciliata., Materials and Methods: Reverse-phase high performance liquid chromatography (RP-HPLC) was performed to analyze polyphenols and bergenin in B. ciliata R extract. Samples were subjected to in vitro antioxidant assays including free radical scavenging, ferric chloride reducing power and total antioxidant capacity. Micro-broth dilution method, brine shrimp lethality assay and isolated RBC hemolysis assay were conducted to assess in vitro antibacterial and cytotoxic activities. Moreover, in vivo wound healing potential was determined by an excision wound model in mice., Results: RP-HPLC showed significant content of polyphenols and bergenin (6.05 ± 0.12 μg/mg) in B. ciliata R extract. Crude extract possesses higher overall antioxidant and antibacterial capacities than bergenin due to presence of multiple phytoconstituents in extract. Both samples showed low hemolytic activity indicating their safe profile. Furthermore, mice treated with B. ciliata R extract depicted substantial decrease in wound area (99.3%; p < 0.05) as compared to bergenin, which showed 88.8% of wound closure after 12 days of treatment. Additionally, both treatments reduced epithelization duration by 1.6- and 1.4-fold in B. ciliata R extract (12.0 ± 0.6 days) and bergenin (14.2 ± 0.8 days) treated mice, respectively. This was supported by histopathological examination that showed greater epithelization, fibroblast proliferation, collagen synthesis, and revascularization in mice treated with B. ciliata R., Conclusion: Concisely, it is evident that B. ciliata R contains phytoconstituents in addition to bergenin, which potentiated wound healing activity of the extract. Hence, B. ciliata R is good source of compounds for treating wounds., Competing Interests: Declaration of competing interest The authors declare that there are to conflict of interest in this manuscript., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Living donor liver transplant in addition to its lifesaving therapy is a cost-effective alternate to long-term disease management in patients with chronic liver disease. Financial constraint is the biggest hurdle faced by patients in developing countries in availing the liver transplantation. So, we conducted this study to report a government-funded financial support system for liver transplant services. A total of 198 patients who underwent living donor liver transplant with at least 90 days follow-up were included in the study. According to proxy means test score, 52.2% patients were from low and middle socioeconomic groups and 64.6% of patients underwent liver transplantation through government support. Out of 198 patients who underwent liver transplantation 29.6% had monthly income below 25,000 Pakistani rupees ($114). In recipients, 90-day mortality was 7.1% and morbidity was 67.1%. Donor morbidity was 23.2% without any mortality. This financial model can serve as a valuable source for middle and low income group countries to overcome the financial challenge and make liver transplant an accessible, affordable, and economically viable option., Competing Interests: DISCLOSURE All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Multidrug resistance and infectious disease have enormous spread despite drug discovery and development advancements. 1, 2, 4 -triazoles have been extensively studied, playing an imperative role in many pathologic conditions. A series of Schiff base triazoles; derived from Indole -3- acetic acid with substituted Benzaldehydes (5a-5g) were designed, synthesized, and evaluated through various Spectroanalytical techniques. SwissADME was used to assess physicochemical properties and pharmacokinetic drug-likeliness behavior. (5a-5g) were evaluated for their varied biological potential through antioxidant, antimicrobial, enzyme inhibition, and cytotoxic evaluation. Schiff bases express drug-like nature as they follow Lipinski's rule of five. 5b showed good antioxidant potential in total antioxidant capacity (TAC) and total reducing power (TRP) assays and was most active in the library in % free radical scavenging assay (%FRSA), showing 32% inhibition at 50 μg/mL concentration. Compounds showed antibacterial activity against various tested strains. 5e and 5f showed a minimum inhibitory concentration (MIC) value of 3.12 μg/mL for P.aeruginosa and K . pneumoniae , respectively. In the antifungal assay, only 5e inhibited one strain with a zone of inhibition >6 mm. These synthetic molecules possess good cytotoxic potential in the Brine Shrimp Lethality screening; 5c, 5d, and 5f exhibited LC 50 = 5.7 μg/mL. In the protein kinase inhibition assay, 5a, 5b, and 5g demonstrated inhibitory potential, showcasing the zone of inhibition as 7.5-10.5 mm for the bald one and 6-7.5 for the clear zone. These findings suggest that the compounds have antibacterial and cytotoxic potential, and there is a chance for further research and development in this area., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Javaid, Haq, Nadeem, Fatima, Khan and Irshad.)

Green nanoparticle synthesis is considered the most efficient and safe nanoparticle synthesis method, both economically and environmentally. The current research was focused on synthesizing zinc oxide nanoparticles (ZnONPs) from fruit and leaf extracts of Citrullus colocynthis . Four solvents (n-hexane, methanol, ethyl acetate, and aqueous) were used to prepare the extracts from both plant parts by maceration and extraction. Zinc acetate was used to synthesize the nanoparticles (NPs), and color change indicated the synthesis of ZnONPs. X-ray diffraction, UV spectroscopy, and scanning electron microscopy were used to study the ZnONPs. UV-visible spectroscopy revealed an absorbance peak in the 350-400 nm range. XRD patterns revealed the face-centered cubic structure of the ZnONPs. SEM confirmed a spherical morphology and a size range between 64 and 82 nm. Phytochemical assays confirmed that the complete flavonoid, phenolic, and alkaloid concentrations were higher in unrefined solvent extracts than in nanoparticles. Nanoparticles of C. colocynthis fruit aqueous extracts showed stronger antioxidant activity compared with the crude extracts. Strong antifungal activity was exhibited by the leaves, crude extracts, and nanoparticles of the n-hexane solvent. In a protein kinase inhibition assay, the maximum bald zone was revealed by nanoparticles of ethyl acetate extracts from leaves. The crude extracts and nanoparticles of leaves showed high cytotoxic activities of the n-hexane solvent, with LC 50 values of 42.08 and 46.35, respectively. Potential antidiabetic activity was shown by the n-hexane (93.42%) and aqueous (82.54%) nanoparticles of the fruit. The bioactivity of the plant showed that it is a good candidate for therapeutic use. The biosynthesized ZnONPs showed promising antimicrobial, cytotoxic, antidiabetic, and antioxidant properties. Additionally, the in vivo assessment of a nano-directed drug delivery system for future therapeutic use can be conducted based on this study.

The pentacyclic triterpenoids (PTs) of plant origin are reputed to restrain prostate cancer (PCa) cell proliferation. This study aims to assess 3-epifriedelinol (EFD) isolated from aerial part of Ipomoea batatas against PCa and its potential mechanism, in vitro and in vivo. Molecular docking affirms good binding affinity of the compound with target proteins exhibiting binding energy of −7.9 Kcal/mol with BAX, −8.1 Kcal/mol (BCL-2), −1.9 Kcal/mol (NF-κB) and −8.5 Kcal/mol with P53. In the MTT assay, EFD treatment (3−50 µM) showed a significant (p < 0.05 and p < 0.01) dose and time dependent drop in the proliferative graph of DU145 and PC3, and an upsurge in apoptotic cell population. EFD displayed substantial IC50 against DU145 (32.32 ± 3.72 µM) and PC3 (35.22 ± 3.47 µM). According to Western blots, EFD administration significantly enhanced the cleavage of caspases and PARP, elevated BAX and P53 and decreased BCL-2 and NF-κB expression, thereby triggering apoptosis in PCa cells. When male Sprague Dawley rats were intoxicated with Bisphenol A (BPA), an apparent increase in prostate mass (0.478 ± 0.08 g) in comparison to control (0.385 ± 0.03 g) indicates prostatitis. Multidose treatment of EFD (10 mg/kg) significantly reduced prostate size (0.404 ± 0.05 g). EFD exhibited substantial curative potential in vivo, as hematological, hormonal and histopathological parameters have been significantly improved. Reduced peroxidation (TBARS), and suppression of inflammatory markers i.e., NO, IL-6 and TNF-α, signposts substantial antiinflammatory potential of the compound. Overall, EFD has shown better binding affinity with target molecules, acceptable ADMET profile, potent antiproliferative and apoptotic nature and significant reduction in inflamed prostate mass of rats. The present study demonstrates acceptable physicochemical and pharmacokinetic properties of the compound with excellent drugable nature, hence EFD in the form of standardized formulation can be developed as primary or adjuvant therapy against PCa and toxins-induced gonadotoxicity.

Safe preclinical dose determination is predictive of human toxicity and can have a profound impact on the overall progress of the compound in early drug discovery process. In this respect, current study sought to investigate for the first time the acute and subacute oral toxicity of two pharmacologically active natural compounds i.e., withametelin and daturaolone in Sprague Dawley rats following OECD guideline 420 and 407, respectively. As per acute toxicity studies, withametelin and daturaolone were characterized as Globally Harmonized System (GHS) category 4 and 5 compounds, respectively. Sub-acute daily dose of withametelin was 5, 2.5, and 1.25 mg/kg but, for daturaolone, it was 10, 5, and 2.5 mg/kg. High dose (5 and 2.5 mg/kg) withametelin groups showed dose dependent changes in the general, hematological, biochemical and histopathological parameters in both sexes, the most prominent being hyperthyroidism while no toxicity was observed at lower doses (1.25 and 0.75 mg/kg), No Observable Adverse Effect Level (NOAEL) being 1.25 mg/kg. Daturaolone was comparatively safer and showed dose dependent significant changes in hepatic enzyme (Alanine Transaminase), bilirubin, creatinine, and glucose levels while histological changes in testes were also observed. Lower doses (5, 2.5, and 1.25 mg/kg) of daturaolone showed no significant toxic effects and 5 mg/kg was declared as its NOAEL. Depending upon our findings, starting effective oral dose levels of 1.25 mg/kg/day for withametelin and 5 mg/kg/day for daturaolone are proposed for repeated dose (up to 28 days) preclinical pharmacological evaluation models. Long term studies with more behavioral, biochemical, histopathological and hormonal parameters are proposed to strengthen the findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Baig, Majid, Nasir, Hassan, Bungau and Haq.)

This study aimed to investigate the anti-neuropathic pain activity and its underlying molecular mechanism of Ajugarin-I (Aju-I) in a rat model of diabetic neuropathic pain. The rats were given a single injection of 60 mg/kg of streptozotocin (STZ) intraperitoneally (i.p.) to induce diabetic neuropathic pain. After two weeks, rats were given Aju-I (1 and 5 mg/kg/day) i.p. for four consecutive weeks. The results demonstrated that in diabetic rats, treatment with Aju-I decreased STZ-induced hyperglycemia. It reduced the pain hypersensitivity (mechanical, thermal, and cold nociception) caused by STZ. It effectively restored STZ-associated pathological changes in the pancreas. In the sciatic nerve and spinal cord, it attenuated STZ-associated histopathological alterations and DNA damage. It suppressed oxidative stress by increasing the expression of nuclear factor-erythroid factor 2-related factor 2 (Nrf2), thioredoxin (Trx), and heme oxygenase (HO-1), but decreasing the immunoreactivity of Kelch-like ECH-associated protein 1 (Keap1). Additionally, TRPV1 (transient receptor potential vanilloid 1) and TRPM8 (transient receptor potential melastatin 8) expression levels were considerably reduced by Aju-I treatment. It enhanced antioxidant levels and suppressed inflammatory cytokines production. Taken together, this research suggests that Aju-I treatment reduces pain behaviors in the STZ model of diabetic neuropathy via modulating Nrf2/Keap-1/HO-1 signaling and TRPV1/TRPM8 nociceptors., 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 © 2022 Elsevier Ltd. All rights reserved.)

This study adopts a very effective high-performance liquid chromatography (HPLC) technique for the quantitative determination of rosmarinic acid (RA) and PCR-based amplification of biosynthetic key regulators in Isodon rugosus, Daphne mucronata, and Viburnum grandiflorum from the lower Himalayan regions. Rosmarinic acid is engaged in a variety of biological processes and has significant industrial significance. In this study, it was identified from crude methanolic extract using thin-layer chromatography with a standard, and its content was quantified using HPLC without interrupting spikes using a mixture of methanol and deionized water containing acetonitrile (70:30 v/v) and acetic acid (0.1% v/v) at UV 310 nm absorption. We used RT-PCR to identify cDNAs encoding PAL, C4H, and RAS, and Image J's semi-quantitative analysis to quantify the expression levels of genes involved in RA production from chosen plant material. The highest levels of PAL, C4H, and RAS were detected, by band intensity, in the leaves and flowers of I. rugosus, which also exhibited a substantial quantity of RA. However, in V. grandiflorum and D. mucronata the transcript of the given genes was low. The concentration of RA ranged from 187.7 to 21.2 mg g -1 for I. rugosus, 17.42 to 5.42 mg g -1 for V. grandiflorum, and 15.19 mg g -1 for D. mucronata. This study demonstrated that the method for quantifying RA from a crude methanolic extract was effective, indicating that I. rugosus might be used as an indigenous alternative source of RA., (© 2022 Scandinavian Plant Physiology Society.)

Organotin (IV) compounds are a focus of research for potential use in cancer chemotherapy. Here, we established anticancer profile of dibutyltin (IV) carboxylate derivatives in prostate cancer (PCa) model. We determined cytotoxicity of a library of dibutyltin (IV) carboxylate derivatives and observed that dibutylstannanediyl (2Z,2'Z)-bis(4-(benzylamino)-4-oxobut-2-enoate (Ch-620; 10 μM) was minimally toxic to normal fibroblasts. Ch-620 (1-1.25 μM) inhibited proliferation of PCa and melanoma cells on short- and long-term exposures with induction of cell cycle arrest. Ch-620 treatment increased population of apoptotic cells, as assessed by flow cytometry, and activated caspase 3. Proteomics showed activation of PPARα, with repression of SMAD4 and integrin β5 (ITGB5) in Ch-620-treated PCa cells. Further analysis demonstrated that Ch-620 resulted in phosphorylation of p38 MAPK, upregulation of PPARα and decreased expression of SMAD4 and ITGB5 with reduced migration of PCa cells. In vivo studies in PC3M grafted athymic nude mice showed that Ch-620 (5 μg/week; 7 weeks) treatment reduced tumor growth as opposed to untreated controls. Immunoblot analysis of tumors demonstrated upregulated p-p38 MAPK and PPARα, followed by a decline in SMAD4 and ITGB5. Immunohistochemistry reinforced these results with increased caspase 3 and p-p38 MAPK and diminished Ki67 staining in Ch-620 treated animals. Taken together, our data indicate that Ch-620 inhibited proliferation of PCa through modulation of MAPK/PPARα/SMAD4 signaling. Organotin (IV) carboxylate compounds; specifically Ch-620 can be a potential anticancer agent for the treatment of PCa subject to detailed pre-clinical and clinical investigations. This unlocks prospects for the development of new tin-based drugs in cancer therapeutics., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The use of the green approach for nanoparticle synthesis yielded noticeable concern due to its eco-friendliness, cost-effectiveness, and reduced production of toxic chemicals. The current study was designed to formulate Zinc oxide nanoparticles (ZnO NPs) by using Fagonia cretica extracts, evaluating its phytochemical content, and different biological activities. Four different solvents; methanol (MeOH), n-Hexane (n-H), aqueous (Aq), and ethyl acetate (EA), had been utilized in the extracting method. ZnO NPs were successfully synthesized and characterized by UV-vis spectroscopy and scanning electron microscopy (SEM). The UV-vis spectra showed absorbance peaks between 350-400 nm range and SEM analysis revealed spherical morphology with particle sizes ranging from 65-80 nm. In phytochemical analysis, crude extracts exhibited the highest phytochemical content as they contain enriched secondary metabolites. n-hexane extract showed the highest phenolic contents while aqueous extracts showed the highest flavonoid content. Maximum free radicle scavenging activity was observed in NPs synthesized from ethyl-acetate extract with an IC 50 value of 35.10 µg/ml. Significant antibacterial activity was exhibited by NPs polar solvents against K. pneumonae, E. coli, and B. subtilis. Polar solvents showed considerable antifungal potential against A. flavus and F. solani. NPs synthesized from nH extract showed potential cytotoxic activity with an LC 50 value of 42.41 µg/ml against brine shrimps. A noteworthy antidiabetic activity was exhibited by nanoparticles synthesized from methanol extract i.e., 52.61 ± 0.36%. Significant bald zones were observed in nanoparticles synthesized from methanol extract rendering protein kinase inhibition. The present study highlights the significance of F. indica as a natural source for synthesizing functional nanoparticles with substantial antioxidant, antimicrobial, cytotoxic, protein kinase inhibitory, and antidiabetic properties., (© 2022. The Author(s).)

Green synthesis of metal nanoparticles is of great importance in the modern health care system. In this study, zinc nanoparticles (ZnONPs) were synthesized using leaf and root extracts of Withania somnifera using four different solvents. ZnONPs were characterized by UV-vis spectrophotometer with a range between 350-400 nm. Scanning electron microscope revealed spherical morphology with an overall size of 70-90 nm and XRD pattern confirmed the crystalline structure. The total flavonoids, phenolic, and alkaloid contents were significantly greater in the crude extracts as compared to ZnONPs. The highest scavenging activity was observed in ZnONPs from n-hexane and ethyl-acetate extracts of roots with IC 50 values of 27.36 µg/mL and 39.44 µg/mL, respectively. ZnONPs from methanol and aqueous extracts showed significant antibacterial activity against Escherichia coli, Staphylococcus aureus, and Bacillus subtilis while none of the extracts were found to have significant antifungal activity. Maximum cytotoxic activity was observed in ZnONPs synthesized from aqueous and n-hexane root extracts with LC 50 values of 9.36 µg/mL and 18.84 µg/mL, respectively. The highest antidiabetic potential was exhibited by ZnONPs from n-hexane leaf extracts, i.e., 47.67 ± 0.25%. Maximum protein kinase inhibitory potential was observed in ZnONPs of ethyl-acetate extract of roots with a bald zone of 12 mm. These results indicated that Withania somnifera -based ZnONPs showed significant biological activities compared to crude extracts. These findings can further be utilized for in-vivo analysis of nano-directed drug delivery systems.

Multitude of diseases and side effects from conventional drugs have surged the use of herbal remedies. Thus, the current study aimed to appraise various pharmacological attributes of Artemisia brevifolia Wall. ex DC. Extracts prepared by successive solvent extraction were subjected to phytochemical and multimode antioxidant assays. Various polyphenolics and artemisinin derivatives were detected and quantified using RP-HPLC analysis. Compounds present in methanol (M) and distilled water (DW) extracts were identified using high resolution mass spectrometry (HRMS). Extracts were pharmacologically evaluated for their antibacterial, antifungal, antimalarial, antileishmanial and antidiabetic potentials. Moreover, cytotoxicity against Artemiasalina, human cancer cell lines and isolated lymphocytes was assessed. Genotoxicity was evaluated using comet, micronucleus and chromosomal aberration assays. Lastly, anti-inflammatory potential was determined through a series of in vitro and in vivo assays using BALB/c mice. Maximum extract recovery (5.95% w/w) was obtained by DW extract. Highest phenolics and flavonoids content, total antioxidant capacity, total reduction potential, percentfree radical scavenging, β-carotene scavenging and iron chelating activities were exhibited by M extract. RP-HPLC analysis revealed significant amounts of various polyphenolic compounds (vanillic acid, syringic acid, emodin and luteolin), artemisinin, dihydro artemisinin, artesunate and artemether in ethyl acetate (EA) extract. Total 40 compounds were detected through HRMS. A noteworthy antimicrobial activity (MIC 22.22 µg/ml) was exhibited by EA extract against A. fumigatus and several bacterial strains. Maximum antimalarial, antileishmanial, brine shrimp lethality and cytotoxic potential against cancer cells was manifested by EA extract. None of the extracts exhibited genotoxicity and toxicity against isolated lymphocytes. Highest α-amylase and α-glucosidase inhibition capacities were demonstrated by DW extract. Various in-vivo anti-inflammatory models revealed significant ( p  < 0.05) anti-inflammatory potential of M and DW extracts. In conclusion, present findings divulged theremarkable pharmacological potential of A. brevifolia and endorse its richness in artemisinin., Competing Interests: 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., (© 2022 The Author(s).)

Rapid progress in developing multifunctional nanocarriers for drug delivery has been observed in recent years. Inorganic mesoporous silica nanocarriers (MSNs), emerged as an ideal candidate for gene/drug delivery with distinctive morphological features. These ordered carriers of porous nature have gained unique attention due to their distinctive features. Moreover, transformation can be made to these nanocarriers in terms of pores size, pores volume, and particle size by altering specific parameters during synthesis. These ordered porous materials have earned special attention as a drug carrier for treating multiple diseases. Herein, we highlight the strategies employed in synthesizing and functionalizing these versatile nanocarriers. In addition, the various factors that influence their sizes and morphological features were also discussed. The article also summarizes the recent advancements and strategies for drug and gene delivery by rendering smarter MSNs by incorporating functional groups on their surfaces. Averting off-target effects through various capping strategies is a massive milestone for the induction of stimuli-responsive nanocarriers that brings out a great revolution in the biomedical field., Competing Interests: Authors declare no conflict of Interest., (© 2022 The Authors.)

Prostate cancer (PCa) is the most common cancer in men, accounting for approximately 10% of all new cases in the United States. Plant-derived bioactive compounds, such as pentacyclic triterpenoids (PTs), have the ability to inhibit PCa cell proliferation. We isolated and characterized nummularic acid (NA), a potent PT, as a major chemical constituent of Ipomoea batatas, a medicinal food plant used in ethnomedicine for centuries. In the current study, in vitro antiproliferative potential against PCa cells (DU145 and PC3) via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay; Western blot protein expression analysis; absorption, distribution, metabolism, excretion (ADME); pharmacokinetic prediction studies; and bisphenol A (BPA)-induced prostate inhibition in Sprague Dawley rats were conducted to gauge the anti-cancer ability of NA. Significant (p < 0.05 and p < 0.01) time- and dose-dependent reductions in proliferation of PCa cells, reduced migration, invasion, and increased apoptotic cell population were recorded after NA treatment (3−50 µM). After 72 h of treatment, NA displayed significant IC50 of 21.18 ± 3.43 µM against DU145 and 24.21 ± 3.38 µM against PC3 cells in comparison to the controls cabazitaxel (9.56 ± 1.45 µM and 12.78 ± 2.67 µM) and doxorubicin (10.98 ± 2.71 µM and 15.97 ± 2.77 µM). Further deep mechanistic studies reveal that NA treatment considerably increased the cleavage of caspases and downstream PARP, upregulated BAX and P53, and downregulated BCL-2 and NF-κB, inducing apoptosis in PCa cells. Pharmacokinetic and ADME characterization indicate that NA has a favorable physicochemical nature, with high gastrointestinal absorption, low blood−brain barrier permeability, no hepatotoxicity, and cytochrome inhibition. BPA-induced perturbations of prostate glands in Sprague Dawley rats show a potential increase (0.478 ± 0.28 g) in prostate weight compared to the control (0.385 ± 0.13 g). Multi-dose treatment with NA (10 mg/kg) significantly reduced the prostate size (0.409 ± 0.21 g) in comparison to the control. NA-treated groups exhibited substantial restoration of hematological and histological parameters, reinstatement of serum hormones, and suppression of inflammatory markers. This multifaceted analysis suggests that NA, as a novel small molecule with a strong pharmacokinetic and pharmacological profile, has the potential to induce apoptosis and death in PCa cells.

The ethyl 2-[2-(2-nitrobenzylidene)hydrazinyl]thiazole-4-carboxylate (1), a thiazole ester, was synthesized by refluxing 1-(2-nitrobenzylidene)thiosemicarbazide and ethyl bromopyruvate. The compound is characterized by spectrometric, spectroscopic and single crystal (SC-XRD) techniques. Non-covalent interactions that are responsible for crystal packing are explored by Hirshfeld surface analysis. All theoretical calculations were performed by DFT quantum chemical methods using 6-311G(d,p) and cc-pVTZ basis sets and compared. Theoretical harmonic frequencies of ethyl 2-[2-(2-nitrobenzylidene)hydrazinyl]thiazole-4-carboxylate (1) were optimized. Confirmation of hydrogen bonding sites was analyzed by molecular electrostatic potential (MEP) and Mulliken population analysis. The vibrational frequencies of characteristic functional groups and chemical shifts were found in good agreement with experimental assignments. Frontier molecular orbital (FMO) revealed relatively small HOMO-LUMO (highest occupied molecular orbital-lowest unoccupied molecular orbital) gape, which speaks off the nearly planar geometry and extended conjugation, as compared to the substituents with no conjugation possible. It has also been observed that -NO 2 substituent plays a vital role for this relatively small HOMO-LUMO gape and overall electronic properties when compared with similar thiazole carboxylates (2-6, Table 6). Ethyl 2-[2-(2-nitrobenzylidene)hydrazinyl]thiazole-4-carboxylate (1) was also evaluated for its anti-oxidant and anti-microbial activities., (© 2022. The Author(s).)

Background: Inflammation is a frequent phenomenon in the pathogenesis of hepatic disorders leading to fibrosis and cirrhosis. Phytopharmaceuticals developed from traditional medicine can provide effective therapeutic alternatives to conventional medications. Datura stramonium (DS) has reported traditional uses in inflammatory diseases. In this study, we have tried to validate its potential as a source of anti-inflammatory agents., Methods: Powdered leaf part of DS was extracted using ethyl acetate (EA) to provide the extract (DSL-EA). Lymphocyte and macrophage viability and acute toxicity assays established the safety profile, while nitric oxide (NO) scavenging assay estimated the in vitro anti-inflammatory potential. Noninvasive anti-inflammatory, antidepressant, and antinociceptive activities were monitored using BALB/c mice using low and high doses (150 and 250 mg/kg). Major inflammatory studies were performed on Sprague-Dawley male rats using CCl 4 -induced liver injury model. Disease induction was initiated by intraperitoneal injections of CCl 4 (1 mL/kg of 30% CCl 4 in olive oil). The rats were divided into six groups. The anti-inflammatory potential of DSL-EA in low and high doses (150 and 300 mg/kg, respectively) was assessed through hematological, biochemical, liver antioxidant defense, oxidative stress markers, and histological studies as well as the expression of Nrf2 and iNOS., Results: DSL-EA exhibited prominent in vitro NO scavenging (IC 50 : 7.625 ± 0.51  μ g/mL) and in vivo anti-inflammatory activity in paw and anal edema models. In CCl 4 model, hematological investigations revealed vasotonic effects. Liver functionality was significantly ( P < 0.001 - 0.05) improved in DSL-EA-treated rats. The activity level of endogenous antioxidant enzymes in liver tissues was improved in a manner identical to silymarin. The extract reduced the percent concentration of oxidative stress markers in liver tissues. Furthermore, DSL-EA displayed restorative effects on histological parameters (H and E and Masson's trichrome staining). Immunohistochemistry studies showed marked decline in Nrf2 expression, while overexpression of iNOS was also observed in disease control rats. The damage was distinctly reversed by the extract., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Bakht Nasir et al.)

Background: Pharmaceuticals and personal care products (PPCPs) are emerging contaminants that have been extensively used in present time to improve the living standards. Their persistence in water resources due to various anthropogenic sources such as wastewater treatment plants, pharmaceutical industries, and runoff from agricultural and livestock farms has not only threaten aquatic life but their occurrence in groundwater has also raised concerns related to humans' wellbeing., Methods: Considering this as a neglected area of research in Pakistan, a systematic monitoring study was designed to investigate their occurrence, sources, and potential environmental and human health risks in groundwater from urban-rural areas of six cities. Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS/MS) was used to analyze the collected samples preceded by solid-phase extraction., Results: Overall, 8 out of 11 selected PPCPs were detected in groundwater samples with detection frequency ranging from 5.5-65%. Their concentrations ranged from below limit of detection (

In a quest to discover new formulations for the treatment of various parasitic diseases, a series of heteroleptic triorganobismuth(V) biscarboxylates of type [BiR 3 (O 2 CR') 2 ], where R=C 6 H 5 for 1-4 and p-CH 3 C 6 H 4 for 5-8, were synthesized, characterized and evaluated for their biological potential against L. tropica. All the synthesized complexes were fully characterized by elemental analysis, FT-IR, multinuclear ( 1 H and 13 C) NMR spectroscopy and X-ray crystallography. The crystal structures for [BiPh 3 (O 2 CC 6 H 4 (o-Br)) 2 ] (1), [BiPh 3 (O 2 CC 2 H 2 C 6 H 4 ) 2 ] (2), [BiPh 3 (O 2 CC 6 H 4 (m-NO 2 )) 2 ] (3) and [BiPh 3 (O 2 CC 6 H 4 (2-OH,3-CH 3 )) 2 ] (4) were determined and found to have a distorted pentagonal bipyramidal molecular geometry with seven coordinated bismuth center for 1-3 and for 4 distorted octahedral geometry, respectively. All the synthesized complexes demonstrated a moderate to significant activity against leishmania parasites. A broad analytical approach was followed to testify the stability for (1-8) in solid state as well as in solution and in leishmanial culture M199, ensuring them to be stable enough to exert a significant antileishmanial effect with promising results. Cytotoxicity profile suggests that tris(tolyl) derivatives show lower toxicity against isolated lymphocytes with higher antileishmanial potential. Molecular docking studies were carried out to reveal the binding modes for (1-8) targeting the active site of trypanothione reductase (TR) (PDB ID: 4APN) and Trypanothione Synthetase-Amidase structure (PDB ID 2vob)., (© 2021. The Author(s), under exclusive licence to Society for Biological Inorganic Chemistry (SBIC).)

Wheat is a staple crop of Pakistan that covers almost 40% of the cultivated land and contributes almost 3% in the overall Gross Domestic Product (GDP) of Pakistan. However, due to increasing seasonal variation, it was observed that wheat is majorly affected by rust disease, particularly in rain-fed areas. Rust is considered the most harmful fungal disease for wheat, which can cause reductions of 20-30% in wheat yield. Its capability to spread rapidly over time has made its management most challenging, becoming a major threat to food security. In order to counter this threat, precise detection of wheat rust and its infection types is important for minimizing yield losses. For this purpose, we have proposed a framework for classifying wheat yellow rust infection types using machine learning techniques. First, an image dataset of different yellow rust infections was collected using mobile cameras. Six Gray Level Co-occurrence Matrix (GLCM) texture features and four Local Binary Patterns (LBP) texture features were extracted from grayscale images of the collected dataset. In order to classify wheat yellow rust disease into its three classes (healthy, resistant, and susceptible), Decision Tree, Random Forest, Light Gradient Boosting Machine (LightGBM), Extreme Gradient Boosting (XGBoost), and CatBoost were used with (i) GLCM, (ii) LBP, and (iii) combined GLCM-LBP texture features. The results indicate that CatBoost outperformed on GLCM texture features with an accuracy of 92.30%. This accuracy can be further improved by scaling up the dataset and applying deep learning models. The development of the proposed study could be useful for the agricultural community for the early detection of wheat yellow rust infection and assist in taking remedial measures to contain crop yield.

The current study was intended to explore the phytochemical profiling and therapeutic activities of Putranjiva roxburghii Wall. Crude extracts of different plant parts were subjected to the determination of antioxidant, antimicrobial, antidiabetic, cytotoxic, and protein kinase inhibitory potential by using solvents of varying polarity ranges. Maximum phenolic content was notified in distilled water extracts of the stem (DW-S) and leaf (DW-L) while the highest flavonoid content was obtained in ethyl acetate leaf (EA-L) extract. HPLC-DAD analysis confirmed the presence of various polyphenols, quantified in the range of 0.02 ± 0.36 to 2.05 ± 0.18 μg/mg extract. Maximum DPPH scavenging activity was expressed by methanolic extract of the stem (MeOH-S). The highest antioxidant capacity and reducing power was shown by MeOH-S and leaf methanolic extract (MeOH-L), respectively. Proficient antibacterial activity was shown by EA-L extract against Bacillus subtilis and Escherichia coli . Remarkable α-amylase and α-glucosidase inhibition potential was expressed by ethyl acetate fruit (EA-F) and n-Hexane leaf (nH-L) extracts, respectively. In case of brine shrimp lethality assay, 41.67% of the extracts (LC 50 < 50 µg/mL) were considered as extremely cytotoxic. The test extracts also showed mild antifungal and protein kinase inhibition activities. The present study explores the therapeutic potential of P . roxburghii and calls for subsequent studies to isolate new bioactive leads through bioactivity-guided isolation.

Withaferin A (WA) is a pivotal withanolide that has conquered a conspicuous place in research, owning to its multidimensional biological properties. It is an abundant constituent in Withania somnifera Dunal. (Ashwagandha, WS) that is one of the prehistoric pivotal remedies in Ayurveda. This article reviews the literature about the pharmacological profile of WA with special emphasis on its anticancer aspect. We reviewed research publications concerning WA through four databases and provided a descriptive analysis of literature without statistical or qualitative analysis. WA has been found as an effective remedy with multifaceted mechanisms and a broad spectrum of pharmacological profiles. It has anticancer, anti-inflammatory, antiherpetic, antifibrotic, antiplatelet, profibrinolytic, immunosuppressive, antipigmentation, antileishmanial, and healing potentials. Evidence for wide pharmacological actions of WA has been established by both in vivo and in vitro studies. Further, the scientific literature accentuates the role of WA harboring a variable therapeutic spectrum for integrative cancer chemoprevention and cure. WA is a modern drug from traditional medicine that is necessary to be advanced to clinical trials for advocating its utility as a commercial drug.

Solubility of phytoconstituents depends on the polarity of the extraction medium used, which might result in the different pharmacological responses of extracts. In line with this, ethnomedicinally important food plant (i.e., Caralluma tuberculata extracts) have been made in fourteen distinct solvent systems that were then analyzed phytochemically via total phenolic amount estimation, total flavonoid amount estimation, and HPLC detection and quantification of the selected polyphenols. Test extracts were then subjected to a battery of in vitro assays i.e., antioxidants (DDPH scavenging, antioxidant capacity, and reducing power estimation), antimicrobial (antibacterial, antifungal, and antileishmanial), cytotoxic (brine shrimps, THP-1 human leukemia cell lines and normal lymphocytes), and protein kinase inhibition assays. Maximum phenolic and flavonoid contents were computed in distilled water-acetone and acetone extracts (i.e., 16 ± 1 μg/mg extract and 8 ± 0.4/mg extract, respectively). HPLC-DAD quantified rutin (0.58 µg/mg extract) and gallic acid (0.4 µg/mg extract) in methanol-ethyl acetate and methanol extracts, respectively. Water-acetone extract exhibited the highest DPPH scavenging of 36 ± 1%. Total reducing potential of 76.0 ± 1 μg/mg extract was shown by ethanol chloroform while maximum total antioxidant capacity was depicted by the acetone extract (92.21 ± 0.70 μg/mg extract). Maximal antifungal effect against Mucor sp. , antileishmanial, brine shrimp cytotoxicity, THP-1 cell line cytotoxicity, and protein kinase inhibitory activities were shown by ethyl acetate-methanol (MIC: 50 µg/disc), n-hexane (IC 50 : 120.8 ± 3.7 µg/mL), ethyl acetate (LD 50 : 29.94 ± 1.6 µg/mL), distilled water-acetone (IC 50 : 118 ± 3.4 µg/mL) and methanol-chloroform (ZOI: 19 ± 1 mm) extracts, respectively. Our findings show the dependency of phytochemicals and bioactivities on the polarity of the extraction solvent and our preliminary screening suggests the C. tuberculata extract formulations to be tested and used in different ailments, however, detailed studies remain necessary for corroboration with our results.

Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system (CNS) that remains incurable. Withametelin (WMT), a phytosterol, showed diverse biological activities isolated from the leaves of Datura innoxa. In the present study, we used an in vitro model of HT22 and BV-2 cell lines and an in vivo murine model of MS, experimental autoimmune encephalomyelitis (EAE), to explore the antioxidant and anti neuroinflammatory potential of WMT. The results showed that pretreatment with WMT markedly inhibited H 2 O 2 -induced cytotoxicity and oxidative stress in a dose-dependent manner. Correspondingly, WMT post-immunization treatment significantly attenuated EAE-induced clinical score, weight loss, neuropathic pain behaviors, and motor dysfunction. It markedly lowers EAE-induced elevated circulating leucocytes, spinal deformity, and splenomegaly. It strikingly inhibited the Evans blue and FITC extravasation in the brain. It remarkably reversed the EAE-induced histopathological alteration of the brain, spinal cord, eye, and optic nerve. It significantly intensified the antioxidant defense mechanism by improving the expression level of nuclear factor-erythroid-related factor-2 (Nrf2), heme-oxygenase-1 (HO-1) but reducing the expression level of the Kelch-like-ECH-associated-protein-1 (keap-1), inducible-nitric-oxide-synthase (iNOS) in the CNS. Likewise, it markedly suppressed neuroinflammation by reducing the expression level of toll-like-receptor 4 (TLR4), nuclear-factor-kappa-B (NF-κB), activator-protein-1 (AP-1) but increased the expression level IkB-α in the CNS. Furthermore, molecular dynamics simulations and MMPBSA binding free energies were determined to validate the dynamic stability of complexes and shed light on the atomic level intermolecular interaction energies. Taken together, this study showed that WMT has significant neuroprotective potential in EAE via modulation of Nrf2 mediated-oxidative stress and NF-κB mediated inflammation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Exploration of leads with therapeutic potential in inflammatory disorders is worth pursuing. In line with this, the isolated natural compound daturaolone from Datura innoxia Mill. was evaluated for its anti-inflammatory potential using in silico, in vitro and in vivo models. Daturaolone follows Lipinski's drug-likeliness rule with a score of 0.33. Absorption, distribution, metabolism, excretion and toxicity prediction show strong plasma protein binding; gastrointestinal absorption (Caco-2 cells permeability = 34.6 nm/s); no blood-brain barrier penetration; CYP1A2, CYP2C19 and CYP3A4 metabolism; a major metabolic reaction, being aliphatic hydroxylation; no hERG inhibition; and non-carcinogenicity. Predicted molecular targets were mainly inflammatory mediators. Molecular docking depicted H-bonding interaction with nuclear factor kappa beta subunit (NF-κB), cyclooxygenase-2, 5-lipoxygenase, phospholipase A2, serotonin transporter, dopamine receptor D1 and 5-hydroxy tryptamine. Its cytotoxicity (IC 50 ) value in normal lymphocytes was >20 µg/mL as compared to cancer cells (Huh7.5; 17.32 ± 1.43 µg/mL). Daturaolone significantly inhibited NF-κB and nitric oxide production with IC 50 values of 1.2 ± 0.8 and 4.51 ± 0.92 µg/mL, respectively. It significantly reduced inflammatory paw edema (81.73 ± 3.16%), heat-induced pain (89.47 ± 9.01% antinociception) and stress-induced depression (68 ± 9.22 s immobility time in tail suspension test). This work suggests a possible anti-inflammatory role of daturaolone; however, detailed mechanistic studies are still necessary to corroborate and extrapolate the findings.

Wheat yellow rust is a common agricultural disease that affects the crop every year across the world. The disease not only negatively impacts the quality of the yield but the quantity as well, which results in adverse impact on economy and food supply. It is highly desired to develop methods for fast and accurate detection of yellow rust in wheat crop; however, high-resolution images are not always available which hinders the ability of trained models in detection tasks. The approach presented in this study harnesses the power of super-resolution generative adversarial networks (SRGAN) for upsampling the images before using them to train deep learning models for the detection of wheat yellow rust. After preprocessing the data for noise removal, SRGANs are used for upsampling the images to increase their resolution which helps convolutional neural network (CNN) in learning high-quality features during training. This study empirically shows that SRGANs can be used effectively to improve the quality of images and produce significantly better results when compared with models trained using low-resolution images. This is evident from the results obtained on upsampled images, i.e., 83% of overall test accuracy, which are substantially better than the overall test accuracy achieved for low-resolution images, i.e., 75%. The proposed approach can be used in other real-world scenarios where images are of low resolution due to the unavailability of high-resolution camera in edge devices.

A worldwide increase in the incidence of fungal infections, emergence of new fungal strains, and antifungal resistance to commercially available antibiotics indicate the need to investigate new treatment options for fungal diseases. Therefore, the interest in exploring the antifungal activity of medicinal plants has now been increased to discover phyto-therapeutics in replacement to conventional antifungal drugs. The study was conducted to explore and identify the mechanism of action of antifungal agents of edible plants, including Cinnamomum zeylanicum, Cinnamomum tamala, Amomum subulatum, Trigonella foenumgraecum, Mentha piperita, Coriandrum sativum, Lactuca sativa, and Brassica oleraceae var. italica . The antifungal potential was assessed via the disc diffusion method and, subsequently, the extracts were assessed for phytochemicals and total antioxidant activity. Potent polyphenols were detected using high-performance liquid chromatography (HPLC) and antifungal mechanism of action was evaluated in silico. Cinnamomum zeylanicum exhibited antifungal activity against all the tested strains while all plant extracts showed antifungal activity against Fusarium solani . Rutin, kaempferol, and quercetin were identified as common polyphenols. In silico studies showed that rutin displayed the greatest affinity with binding pocket of fungal 14-alpha demethylase and nucleoside diphosphokinase with the binding affinity (K d , -9.4 and -8.9, respectively), as compared to terbinafine. Results indicated that Cinnamomum zeylanicum and Cinnamomum tamala exert their antifungal effect possibly due to kaempferol and rutin, respectively, or possibly by inhibition of nucleoside diphosphokinase (NDK) and 14-alpha demethylase (CYP51), while Amomum subulatum and Trigonella foenum graecum might exhibit antifungal potential due to quercetin. Overall, the study demonstrates that plant-derived products have a high potential to control fungal infections.

Quercus floribunda Lindl. ex A. Camus nuts have important folklore uses, assessed for underexplored biological potential. Nuts galls or cores and coats were utilized for the preparation of extracts using 14 solvent systems. Antioxidant, antimicrobial, cytotoxic and enzyme inhibition assays along with phytochemical profiling was carried out. Distilled water cores extract demonstrated maximum percent yield, phenolics content and total antioxidant capacity. Methanol: ethyl acetate cores extract showed maximum flavonoids content, total reducing power and protein kinase inhibition. Highest percentage radical scavenging and brine shrimp lethality was revealed by acetone: distilled water cores extract. Ethyl acetate cores extract indicated maximum α-amylase inhibition. Methanol: water coats extract showed substantial leishmanial growth inhibition. n -Hexane and chloroform coats extracts showed maximum cytotoxicity against HepG2 and THP-1 cell lines, respectively. Polyphenols quantified through RP-HPLC analysis were quercetin, pyrocatechol, gallic acid, catechin and chlorogenic acid ranging from 0.003 ± 0.001 to 1.785 ± 0.5 μg/mg extract.

The present study aims to determine the neuroprotective effect of Bergenin against spatial memory deficit associated with neurodegeneration. Preliminarily, the protective effect of Bergenin was observed against H 2 O 2 -induced oxidative stress in HT-22 and PC-12 cells. Further studies were performed in 5xFAD Tg mouse model by administering Bergenin (1, 30 and 60 mg/kg; orally), whereas Bergenin (60 mg/kg) significantly attenuated the memory deficit observed in the Y-maze and Morris water maze (MWM) test. Fourier transform-infrared (FT-IR) spectroscopy displayed restoration of lipids, proteins and their derivatives compared to the 5xFAD Tg mice group. The differential scanning calorimeter (DSC) suggested an absence of amyloid beta (Aβ) aggregation in Bergenin-treated mice. The immunohistochemistry (IHC) analysis suggested the neuroprotective effect of Bergenin by increasing Reelin signaling (Reelin/Dab-1) and attenuated Aβ (1-42) aggregation in hippocampal regions of mouse brains. Furthermore, IHC and western blot results suggested antioxidant (Keap-1/Nrf-2/HO-1), anti-inflammatory (TLR-4/NF-kB) and anti-apoptotic (Bcl-2/Bax/Caspase-3) effect of Bergenin. Moreover, a decrease in Annexin V/PI-stained hippocampal cells suggested its effect against neurodegeneration. The histopathological changes were reversed significantly by Bergenin. In addition, a remarkable increase in antioxidant level with suppression of pro-inflammatory cytokines, oxidative stress and nitric oxide production were observed in specific regions of the mouse brains.

Aim: This study aimed to utilise the proficient function of diacerein (DCR) and anti-inflammatory polymers to develop sustained release nanoencapsulated emulgel for potential use in osteoarthritis (OA)., Methods: Chitosan (CHS) and chondroitin sulphate (CS) were employed as natural anti-inflammatory polymers to encapsulate nanoformulation of DCR. Optimised nanoformulation was prepared and characterised by investigating impact of polymers and surfactant on particle size, PDI, and encapsulation efficiency (EE). Afterwards, nanoemulgel of optimised DCR-NPs was formulated and evaluated for transdermal application., Results: Optimised nanoformulation depicted spherical shape with particle size of 320 nm having PDI and EE of 0.3 ± 0.07 and 82 ± 4% (w/w), respectively. DCR-nanoemulgel depicts sustained action of drug up to 96 h with enhanced permeation activity and non-irritancy index., Conclusions: The elaborated nanoemulgel sustained release of drug having superior penetration properties with provision of enhanced therapeutic effect owing to the presence of CHS, CS, and Argan oil possessing indelible anti-inflammatory attributes.

Withanolides are natural medicinal agents whose safety and therapeutic profiles make them valuable to mankind. Among multiple withanolides, withametelin is underexplored. The present study was aimed to create a general biological profile of isolated withametelin from Datura innoxia Mill. targeting different biological models. In-silico studies include drug-likeliness, pharmacokinetics, toxicity, molecular targets and cytotoxicity to cancer cell lines predictions. In silico directed preliminary in-vitro evaluation comprised of cancer/normal cell cytotoxicity, DPPH and protein kinase inhibition assays while in-vivo bioactivities include antiinflammatory, analgesic, antidepressant and anticoagulant assays. Pharmacological findings were strengthened by molecular docking studies to check interactions with various proteins and to propose the future path of studies. Results indicated compliance with Lipinski drug-likeliness rule (score -0.55). ADMET prediction showed strong plasma protein binding, GI absorption (Caco-2 cells permeability = 46.74 nm/s), blood brain barrier penetration (Cbrain/Cblood = 0.31), efflux by P-glycoprotein, metabolism by CYP1A2, CYP2C19 and CYP3A4, medium hERG inhibition and non-carcinogenicity in rodents. Predicted molecular targets included mainly receptors (glucocorticoid, kappa opioid, delta opioid, adrenergic and dopamine), oxidoreductase (arachidonate 5-lipoxygenase and cyclooxygenase-2), enzymes (HMG-CoA reductase) and kinase (NFκb). Withametelin was more cytotoxic to cancer cells (DU145 IC 50 7.67 ± 0.54 µM) than normal lymphocytes (IC 50 33.55 ± 1.31 µM). It also showed good antioxidant and protein kinase inhibition potentials. Furthermore, withametelin (20 mg/kg) significantly reduced inflammatory paw edema (68.94 ± 5.55%), heat-induced pain (78.94 ± 6.87%) and immobility time (50%) in animals. Molecular docking showed hydrogen bonding interactions (binding energies: -11.3 to -7.8 kcal/mol) with arachidonate 5 lipoxygenase, NFκb and glucocorticoid receptor. Withametelin has potential for advance investigations for its cytotoxic, anti-inflammatory, analgesic and antidepressant activities., Competing Interests: 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., (© 2020 The Author(s).)

In this paper, a modified form of the Proportional Integral Derivative (PID) controller known as the Integral- Proportional Derivative (I-PD) controller is developed for Automatic Generation Control (AGC) of the two-area multi-source Interconnected Power System (IPS). Fitness Dependent Optimizer (FDO) algorithm is employed for the optimization of proposed controller with various performance criteria including Integral of Absolute Error (IAE), Integral of Time multiplied Absolute Error (ITAE), Integral of Time multiplied Square Error (ITSE), and Integral Square Error (ISE). The effectiveness of the proposed approach has been assessed on a two-area network with individual source including gas, hydro and reheat thermal unit and then collectively with all three sources. Further, to validate the efficacy of the proposed FDO based PID and I-PD controllers, comprehensive comparative performance is carried and compared with other controllers including Differential Evolution based PID (DE-PID) controller and Teaching Learning Based Optimization (TLBO) hybridized with Local Unimodal Sampling (LUS-PID) controller. The comparison of outcomes reveal that the proposed FDO based I-PD (FDO-I-PD) controller provides a significant improvement in respect of Overshoot (Osh), Settling time (Ts), and Undershoot (Ush). The robustness of an I-PD controller is also verified by varying parameter of the system and load variation., Competing Interests: The authors have declared that no competing interests exist.

Current report is paramount contribution via nanotechnology to the existing remedies of health diseases. The lag in application of capped metallic oxide nanoparticles in restorative dentistry exist which is covered by this promising study. The uncapped and chitosan encapsulated ZnO nanoparticles were fabricated by facile co-precipitation method, and characterized using various biophysical strategies including X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM), Transmission electron microscopy (TEM) and Energy dispersive x-ray (EDX). ZnO nanoparticles and ZnO-Citosan nanoparticles were estimated to be <30 nm and <25 nm in size on respective basis. Significant in vitro antibacterial, antioxidant, cytotoxic and antidiabetic activity of ZnO nanoparticles has been elucidated that is enhanced by capping with chitosan polymer. 90% cytotoxicity against brine shrimps, 69.6% antidiabetic activity against α-amylase, and noteworthy antioxidation power by chitosan decorated ZnO nanoparticles has been effectively illustrated. Furthermore, the effective secondary caries remediation approach has been established by an amalgamation of ZnO nanoparticles and ZnO-Chitosan nanoparticles into dentine bonding agents. A remarkable reduction in Streptococcus mutans and Lactobacillus acidophillus strains has been observed, in-specific boosted by chitosan capped ZnO nanoparticles reinforced dental adhesive discs. Additionally, augmented mechanical properties, greater resistance to water sorption and solubility, notably high release profile, and slight variation of shear bond strength values have been obtained. In short, the prepared nanoparticles reported are detected to be auspicious theranostic agents for combating wide array of human pathogens in healthcare system., 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 © 2020 Elsevier B.V. All rights reserved.)