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The ethanolic extract of Amaranthus tricolor L. (ATE) leaves was tested for its efficacy against CCl4-induced liver toxicity in rats. The hepatoprotective activity of ATE was evaluated via measuring various liver toxicity parameters, the lipid profile, and a histopathological evaluation. A sleeping time determination study and an acute toxicity test were performed in mice. The results clearly showed that oral administration of ATE for three weeks significantly reduced the elevated levels of serum GOT, GPT, GGT, ALP, bilirubin, cholesterol, LDL, VLDL, TG, and MDA induced by CCl4. Moreover, ATE treatment was also found to significantly increase the activities of NP-SH and TP in liver tissue. These biochemical findings have been supported by the evaluation of the liver histopathology in rats. The prolongation of narcolepsy induced by pentobarbital was shortened significantly by the extract. The acute toxicity test showed that no morbidity or mortality was caused by the extract. The observed hepatoprotective effect appears to be due to the antioxidant properties of A. tricolor, which may pave the way to finding a new drug to be used for fighting liver diseases. [ABSTRACT FROM AUTHOR]

Trace detection of bioactive small molecules (BSMs) in body fluids is of great importance for disease diagnosis, drug discovery, and health monitoring. Based on the chiral ligand of 4,4'-(1,2-dihydroxyethane-1,2-diyl)dibenzoic acid (H 2 L), an achiral 3D porous Ni(II)-MOF, with a trinuclear cluster based (3,9)-c {4 2 ·6} 3 {4 6 ·6 21 ·8 9 }-xmz net, was constructed under solvothermal conditions. Benefiting from its robust framework and excellent luminescent performance, NiMOF was endowed with remarkable capabilities in efficiently, rapidly, and sensitively detecting the 3-nitrotyrosine (3-NT) biomarker and 6-propyl-2-thiouracil (6-PTU) thyroid drug based on the spectral overlap and photo-induced electron transfer (PET) caused luminescence quenching response. Notably, NiMOF exhibited exceptional performance in quantifying 3-NT and 6-PTU in urine samples, yielding highly satisfactory results. Additionally, an intelligent detection system was crafted to enhance the reliability and practicability of 3-NT/6-PTU detection in urine, based on tandem combinational logic gates. This work not only heralds a promising trajectory in the development of MOF-based luminescent sensors, but also paves the way for the intelligent monitoring of BSMs in real bodily fluids.

VP30 and VP40 proteins of Ebola and Marburg viruses have been recognized as potential targets for antiviral drug development due to their essential roles in the viral lifecycle. Targeting these proteins could disrupt key stages of the viral replication process, inhibiting the viruses' ability to propagate and cause disease. The current study aims to perform molecular docking and virtual screening on deep-sea fungal metabolites targeting Marburg virus VP40 Dimer, matrix protein VP40 from Ebola virus Sudan, Ebola VP35 Interferon Inhibitory Domain, and VP35 from Marburg virus. The top ten compounds for each protein target were chosen using the glide score. All the compounds obtained indicate a positive binding interaction. Furthermore, AdmetSAR was utilized to investigate the pharmacokinetics of the inhibitors chosen. Gliotoxin was used as a ligand with Marburg virus VP40 Dimer, Austinol with matrix protein VP40 from Ebola virus Sudan, Ozazino-cyclo-(2,3-dihydroxyl-trp-tyr) with Ebola VP35 Interferon Inhibitory Domain, and Dehydroaustinol with VP35 from Marburg virus. MD modeling and MMPBSA studies were used to provide a better understanding of binding behaviors. Pre-clinical experiments can assist validate our in-silico studies and assess whether the molecule can be employed as an anti-viral drug., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Alanzi 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.)

Apolipoproteins and Scavenger Receptor Class B1 (SCARB1) proteins are involved in the etiology of HIV-associated lipodystrophy (HIVLD). APOC3 3238C/G , APOB 12669G/A and SCARB1 1050C/T polymorphisms were linked with increased level of APOB, TG, HDL-C and risk of cardiovascular diseases (CVDs). Hence, we evaluated the genetic variations of APOC3 3238C/G, APOB 12669G/A and SCARB1 1050C/T in 187 patients of HIV (64 with HIVLD, 123 without HIVLD) and 139 healthy controls using PCR-RFLP and expression by qPCR . The genotypes of SCARB1 1050 TT and APOB 12669AA showed a risk to severe HIVLD (P = 0.23, OR = 4.95; P = 0.16, OR = 2.02). The APOC3 3238 GG genotype was associated with a lesser risk of severe HIVLD (P = 0.07, OR = 0.22). The APOB 12669 GA genotype was associated with a greater risk of HIVLD severity in patients with impaired LDL, triglyceride (TG), and cholesterol levels (P = 0.34, OR = 4.13; P = 0.25, OR = 3.64; P = 0.26, OR = 5.47). Similarly, APOB 12669AA genotypes in the presence of impaired triglyceride levels displayed the susceptibility to severity of HIVLD (P = 0.77, OR = 2.91). APOB 12669 GA genotype along with impaired HDL and cholesterol levels indicated an increased risk for HIVLD acquisition among patients without HIVLD (P = 0.42, OR = 2.42; P = 0.26, OR = 2.27). In patients with and without HIVLD, APOC3 3238CG genotypes having impaired cholesterol and glucose levels had higher risk for severity and development of HIVLD (P = 0.13, OR = 2.84, P = 0.34, OR = 1.58; P = 0.71, OR = 1.86; P = 0.14, OR = 2.30). An increased expression of APOB and SCARB1 genes were observed in patients with HIVLD (+0.51 vs. -0.93; +4.78 vs. +3.29), and decreased expression of APOC3 gene was observed in patients with HIVLD (-0.35 vs. -1.65). In conclusion, the polymorphisms mentioned above were not associated with the modulation of HIVLD. However, in the presence of impaired triglyceride, HDL, cholesterol and glucose levels, APOB 12669AA and 12669 GA, APOC3 3238CG genotypes indicated a risk for the development and severity of HIVLD., Competing Interests: There are no conflict of interest among the Authors., (© 2024 The Authors. Published by Elsevier Ltd.)

Protease inhibitors (PIs) are associated with an incidence of lipodystrophy among people living with HIV(PLHIV). Lipodystrophiesare characterised by the loss of adipose tissue. Evidence suggests that a patient's lipodystrophy phenotype is influenced by genetic mutation, age, gender, and environmental and genetic factors, such as single-nucleotide variants (SNVs). Pathogenic variants are considered to cause a more significant loss of adipose tissue compared to non-pathogenic. Lipid metabolising enzymes and transporter genes have a role in regulating lipoprotein metabolism and have been associated with lipodystrophy in HIV-infected patients (LDHIV). The long-term effect of the lipodystrophy syndrome is related to cardiovascular diseases (CVDs). Hence, we determined the SNVs of lipid metabolising enzymes and transporter genes in a total of 48 patient samples, of which 24 were with and 24 were without HIV-associated lipodystrophy (HIVLD) using next-generation sequencing. A panel of lipid metabolism, transport and elimination genes were sequenced. Three novel heterozygous non-synonymous variants at exon 8 (c.C1400A:p.S467Y, c.G1385A:p.G462E, and c.T1339C:p.S447P) in the ABCB6 gene were identified in patients with lipodystrophy. One homozygous non-synonymous SNV (exon5:c.T358C:p.S120P) in the GRN gene was identified in patients with lipodystrophy. One novelstop-gain SNV (exon5:c.C373T:p.Q125X) was found in the GRN gene among patients without lipodystrophy. Patients without lipodystrophy had one homozygous non-synonymous SNV (exon9:c.G1462T:p.G488C) in the ABCB6 gene. Our findings suggest that novel heterozygous non-synonymous variants in the ABCB6 gene may contribute to defective protein production, potentially intensifying the severity of lipodystrophy. Additionally, identifying a stop-gain SNV in the GRN gene among patients without lipodystrophy implies a potential role in the development of HIVLD., 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 © 2024. Published by Elsevier B.V.)

Chronic diabetes mellites related hyperglycemia is a major cause of mortality and morbidity due to further complications like retinopathy, hypertension and cardiovascular diseases. Though several synthetic anti-diabetes drugs specifically targeting glucose-metabolism enzymes are available, they have their own limitations, including adverse side-effects. Unlike other natural or marine-derived pharmacologically important molecules, deep-sea fungi metabolites still remain under-explored for their anti-diabetes potential. We performed structure-based virtual screening of deep-sea fungal compounds selected by their physiochemical properties, targeting crucial enzymes viz., α -amylase, α -glucosidase, pancreatic-lipoprotein lipase, hexokinase-II and protein tyrosine phosphatase-1B involved in glucose-metabolism pathway. Following molecular docking scores and MD simulation analyses, the selected top ten compounds for each enzyme, were subjected to pharmacokinetics prediction based on their AdmetSAR- and pharmacophore-based features. Of these, cladosporol C, tenellone F, ozazino-cyclo-(2,3-dihydroxyl-trp-tyr), penicillactam and circumdatin G were identified as potential inhibitors of α -amylase, α -glucosidase, pancreatic-lipoprotein lipase, hexokinase-II and protein tyrosine phosphatase-1B, respectively. Our in silico data therefore, warrants further experimental and pharmacological studies to validate their anti-diabetes therapeutic potential., 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., (© 2023 The Author(s).)

Aim: Virtual screening of deep-sea fungal metabolites against SARS-CoV-2 Delta and Omicron spikes as potential antivirals. Materials & methods: Deep-sea fungal alkaloids (n ≥ 150) were evaluated against SARS-CoV-2, Delta and Omicron spikes, using various in silico approaches, including Admet scores, physiochemical properties, molecular docking (MD) and MD simulation (150 ns). Results: The test alkaloids complied with Admet scores and physiochemical properties within acceptable ranges, and followed Lipinski's rule of five. Of these, Cladosporium sphaerospermum -derived cladosin K (tetramate alkaloid) for SARS-CoV-2, Cystobasidium laryngis -derived saphenol (phenazine alkaloid) for Delta and Chaetomium globosum -derived chaetoglobosin E (quinoline alkaloid) for Omicron were identified as potential spike-inhibitors. Conclusion: Our data therefore, strongly warrants further experimental validations of cladosin K, saphenol and chaetoglobosin E, especially against the Omicron and Delta spikes., Competing Interests: The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed., (© 2023 Future Medicine Ltd.)

Milletia pinnata oil and Nardostachys jatamansi are rich sources of bioactive compounds and have been utilized to formulate various herbal formulations, however, due to certain environmental conditions, pure extract form is prone to degradation. Therefore, in this, study, a green hydrodistillation technology was used to extract M. pinnata oil and N. jatamansi root for the further application in development of pectin crosslinked carboxymethyl cellulose/guar-gum nano hydrogel. Both oil and extract revealed the presence of spirojatamol and hexadecanoic acid methyl ester. Varied concentrations (w/w) of cross-linker and gelling agent were used to formulate oil emulsion extract gel (OEEG1, OEG1, OEEG2, OEG2, OEEG3, OEG3, OEEG4, OEG4, OEEG5, OEG5), in which OEEG2 and OEG2 were found to be stable. The hydrogel displayed an average droplet size of 186.7 nm and a zeta potential of -20.5 mV. Endo and exothermic peaks and the key functional groups including hydroxyl, amide II, and amide III groups confirmed thermal stability and molecular structure. The smooth surface confirmed structural uniformity. Bactericidal activity against both Gram-positive (25.41 ± 0.09 mm) and Gram-negative (27.25 ± 0.01 mm) bacteria and anti-inflammatory activity (49.25%-83.47%) makes nanohydrogel a potential option for treating various infections caused by pathogenic microorganisms. In conclusion, the use of green hydrodistillation technology can be used to extract the bioactive compounds that can be used in formulation of biocompatible and hydrophobic nanohydrogels. Their ability to absorb target-specific drugs makes them a potential option for treating various infections caused by pathogenic microorganisms., 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 Bhagyashree Devidas, Patil, Sharma, Ali, Parvez, Al-Dosari, Liu, Inbaraj, Bains and Wen.)

Drug‑resistance in hepatitis B virus (HBV), especially due to prolonged treatment with nucleoside analogs, such as lamivudine (LAM), remains a clinical challenge. Alternatively, several plant products and isolated phytochemicals have been used as promising anti‑HBV therapeutics with no sign of resistance. Among all known Rhus species, R. coriaria , R. succedanea and R. tripartite have been widely studied for their anti‑HBV efficacy, however, the effects of R. retinorrhoea have not been previously investigated. The current study reported the isolation of two flavonoids, namely sakuranetin (SEK) and velutin (VEL), from the dichloromethane fraction of R. retinorrhoea aerial parts using chromatography and spectral analyses. The two flavonoids (6.25‑50 µg/ml) were pre‑tested for non‑hepatocytotoxicity using an MTT assay and their dose‑ and time‑dependent inhibitory activities against HBV [hepatitis B surface antigen (HBsAg) and hepatitis B 'e' antigen (HBeAg)] in cultured HepG2.2.15 cells were assessed by ELISA. SEK and VEL at the selected doses (12.5 µg/ml) significantly inhibited HBsAg by ~58.8 and ~56.4%, respectively, and HBeAg by ~55.5 and ~52.4%, respectively, on day 5. The reference drugs LAM and quercetin (anti‑HBV flavonoids), suppressed the production of HBsAg/HBeAg by ~86.4/~64 and ~84.5/~62%, respectively. Furthermore, molecular docking of the flavonoids with HBV polymerase and capsid proteins revealed the formation of stable complexes with good docking energies, thus supporting their structure‑based antiviral mechanism. In conclusion, the present study was the first to demonstrate the anti‑HBV therapeutic activities of SEK and VEL isolated from R. retinorrhoea .

Diabetes, characterized by high blood glucose level, is a progressive metabolic disease that leads to serious health complications. One of the major pathological consequences associated with diabetes is the accumulation of highly reactive carbonyl compounds called advanced glycation end products (AGEs). Most of the AGEs are dicarbonyls and have the potential to covalently modify proteins especially at the lysine residues in a non-enzymatic fashion (a process termed as glycation) resulting in the functional impairment and/or toxic gain in function. Therefore, non-toxic small molecules that can inhibit glycation are of interest for the therapeutic intervention of diabetes. In the present communication, we have investigated the effect of organosulfurs (S-allyl cysteine, SAC and N-acetyl cysteine, NAC) that are major principal components of Allium sativa against the glycation of different proteins. We discovered that both SAC and NAC are potent anti-glycating agents. We also found that both SAC and NAC reduce ROS level and inhibit apoptosis caused by protein glycation., (© 2023. Springer Nature Limited.)

Apolipoprotein not only have a role in cholesterol metabolism but also play a role in normal brain function. Apolipoprotein gene polymorphisms are known risk factors for a number of mental and neurological disorders. The expression of brain apolipoproteins is significantly altered in several brain disorders. Therefore, we assed ApoC33238 C/G polymorphism in a total of 248 patient infected with HIV (45 with HAND, 89 without HAND, 114 without ART) and 134 healthy controls using PCR-RFLP. ApoC3 3238CG, 3238 GG genotypes and 3238G allele showed a non-significant increased risk for severity of HAND (P = 0.16, OR = 1.83; P = 0.32, OR = 2.78; P = 0.10, OR = 1.65) while comparing individuals with and without HAND. ApoC3 3238 GG genotype and 3238G allele revealed an increased risk for disease progression when compared between HIV patients with and without ART (P = 0.55, OR = 1.76; P = 0.65, OR = 1.12) though risk could not reach statistical significance. ApoC3 3238 GG genotype and 3238G allele were associated with the reduced risk of acquiring HIV infection when comparing HIV patients who are not on ART with healthy controls (P = 0.05, OR = 0.29; P = 0.04, OR = 0.66). In HIV patients on ART,ApoC3 3238 GG genotype showed an increased susceptibility to development of HAND (P = 0.48, OR = 2.24) when comparing alcohol drinkers and non-drinkers however risk could not reach statistical significance. In conclusion, the genotype ApoC33238GG displayed an inclination of risk for the severity of HAND and HIV disease progression. The polymorphism of APOC3 3238C/G may have a role to reduce the risk for acquisition of HIV infection. ApoC33238GG genotype in presence of alcohol may increase susceptibility to development of HAND., Competing Interests: Declaration of competing interest There are no conflict among the Authors. The authors declare that they have no competing interest., (Copyright © 2023. Published by Elsevier Ltd.)

Hepatitis B virus (HBV) causes acute and chronic liver diseases, leading to cirrhosis and hepatocellular carcinoma. Although direct-acting nucleoside analogs, such as lamivudine (LAM), adefovir and famciclovir, are available, emergence of drug-resistance due to mutations in HBV polymerase (POL) restricts their further use. Alternatively, numerous plant products and compounds isolated from plants have been reported to confer anti-HBV efficacies without any sign of resistance in vitro or in vivo . As, flavonoids and alkaloids are the most widely reported antivirals, the anti-HBV activities of the flavonoid acacetin (ACT) and the alkaloid acetyl-β-carboline (ABC) from the aerial parts of Rhazya stricta were assessed in the present study. Both compounds were isolated from the ethyl acetate fraction of the total methanol extract using column and thin-layer chromatography, and their structures were determined by nuclear magnetic resonance spectroscopy (NMR). Both compounds (at 6.25-50 µg/ml) showed a lack of hepatocytotoxicity in cultured HepG2.2.15 cells. Anti-HBV ELISA [hepatitis B surface antigen (HBsAg) and hepatitis B pre-core-antigen (HBeAg)] on HepG.2.2.15 cells following treatment with selected concentrations (12.5, 25 and 50 µg/ml) of both compounds showed dose- and time-dependent anti-HBV activities. Compared with those in the untreated control at day 5, ACT and ABC (25 µg/ml, each) maximally inhibited HBsAg synthesis by 43.4 and 48.7%, respectively, whilst also maximally inhibiting HBeAg synthesis by 41.2 and 44.2%, respectively, in HepG2.2.15 cells. Comparatively, quercetin and LAM (standards; POL inhibitors) suppressed HBsAg (63.9 and 60.2%, respectively) and HBeAg synthesis (87.1 and 84.3%, respectively) by larger magnitudes. Molecular docking of ACT and ABC structures performed in AutoDock revealed their hydrogen bonding with the drug-sensitive [wild-type (wt)-POL] 'Tyr-Met-Asp-Asp' motif, in addition to the drug-resistant [mutant (mut)-POL] 'Tyr-Ile-Asp-Asp' motif residues of the polymerase binding-pocket, along with other electrostatic interactions. In the wt-POL complex, both compounds showed good interactions with Asp205. In the mut-POL complex, ACT and ABC interacted with Tyr203-Asp205 and Tyr203-Ile204, respectively. In conclusion, to the best of our knowledge, the present study demonstrates anti-HBV efficacies of ACT and ABC in vitro for the first time, endorsed by in silico data. However, further molecular and pharmacological studies are required to validate their pre-clinical therapeutic potential., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020, Spandidos Publications.)

Aim: Structure-based identification of natural compounds against SARS-CoV-2, Delta and Omicron target proteins., Materials & Methods: Several known antiviral natural compounds were subjected to molecular docking and MD simulation against SARS-CoV-2 Mpro, Helicase and Spike, including Delta and Omicron Spikes., Results: Of the docked ligands, 20 selected for each complex exhibited overall good binding affinities (-7.79 to -5.06 kcal/mol) with acceptable physiochemistry following Lipinski's rule. Finally, two best ligands from each complex upon simulation showed structural stability and compactness., Conclusion: Quercetin-3-acetyl-glucoside, Rutin, Kaempferol, Catechin, Orientin, Obetrioside and Neridienone A were identified as potential inhibitors of SARS-CoV-2 Mpro, Helicase and Spike, while Orientin and Obetrioside also showed good binding affinities with Omicron Spike. Catechin and Neridienone A formed stable complexes with Delta Spike., Competing Interests: The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed., (© 2023 Future Medicine Ltd.)

The present study assessed the in vitro anti-hepatitis B virus (HBV) effects of cold-adapted sea buckthorn ( Hippophae rhamnoides ). Sea buckthorn leaf ethanol extracts subjected to chloroform (SB-Chl), ethyl acetate (SB-Eac), n -butanol (SB-But) and aqueous (SB-Aqu) fractionation were first examined (MTT assay) for their toxic effects on HepG2 cells. While SB-Chl (IC 50 , 32.58 µg/ml) exhibited high cytotoxicity, SB-Eac, SB-But SB-Aqu were non-toxic at up to 150 µg/ml. High performance liquid chromatography analysis led to the identification of the anti-HBV active flavonols, quercetin (93.09 µg/g), kaempferol (44.19 µg/g) and isorhamnetin (138.75 µg/g) in the extract. The analysis of the anti-HBV effects of SB-Eac, SB-But and SB-Aqu (50 µg/ml, each) on HepG2.2.15 cells revealed the marked inhibition of HBsAg and HBeAg expression levels. At the concentration of 10 µg/ml, quercetin and kaempferol exerted potent inhibitory effects on HBsAg (60.5 and 62.3%, respectively) and HBeAg synthesis (64.4 and 60.2%, respectively), as compared to isorhamnetin (30.5 and 28.4%, respectively). The HBV-polymerase inhibitor drug, lamivudine (2 µM), inhibited HBsAg and HBeAg expression by 87.4 and 83.5%, respectively. The data were in good agreement with a previous in vitro and in silico molecular docking analysis performed by the authors where quercetin, kaempferol and lamivudine had formed stable complexes with HBV-polymerase binding-pocket amino acids. On the whole, to the best of our knowledge, the present study provides the first report of the anti-HBV therapeutic potential of sea buckthorn, attributed to quercetin, kaempferol and isorhamnetin., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020, Spandidos Publications.)

Interleukin-4 (IL-4), an anti-inflammatory cytokine plays significant in the development of various diseases especially asthmatic allergies. Previous structural and functional studies of IL-4 with its receptor bring forth different types of inhibitors to block their interaction but each of them failed in clinical trials. Since, no synthetic molecules have been identified against IL-4, so far. Therefore, 21 in-house tested IL-4 inhibitors were blindly docked over the entire surface of IL-4 to predict a suitable and druggable binding site as the crystal structure of IL-4 protein in complex with ligand has not been reported yet. After binding site prediction, both ligand-based and structure-based pharmacophore were generated to screen three ZINC libraries (24.5 M) i.e. purchasable, natural product and natural derivative. A total 5,800 top-scored compounds were further subjected towards score-based screening to find the potential leads. Following protein-ligand interaction fingerprints (PLIF) and molecular visualization of selected hits, six top-scored compounds (five from purchasable and one from natural product library) were further moved towards their stability dynamics, followed by their absolute binding free energy and residue-based energy decomposition calculation by MM-GBSA method. These efforts help us to reveal the key factors responsible for ligand binding that might help to improve the binding and stability of these newly discovered hits by structural modifications.Communicated by Freddie R. Salsbury.

Bioactive natural or phytoproducts have emerged as a potential source of antiviral agents. Of the Rhus spp., R. coriaria and R. succedanea have been reported for their antiviral activities against hepatitis B virus (HBV), while the anti-HBV efficacy of R. tripartita has remained elusive. In the present study, the anti-HBV activities of R. tripartita -derived novel catechin [3,5,13,14-flavantetrol-catechin or rhuspartin (RPT)] and epicatechin-3- O -rhamnoside (ECR), were assessed using the HBV-reporter cell line HepG2.2.15. RPT and ECR proved to efficiently inhibit HBV surface antigen (HBsAg) synthesis by 68.8 and 71.3%, respectively, and HBV pre-core antigen (HBeAg) production by 62.3 and 71.2%, respectively, after 5 days of treatment. Of note, RPT had a lower anti-HBV activity than ECR. In comparison, the reference drug lamivudine (LAM) inhibited HBsAg and HBeAg expression by 83.6 and 85.4%, respectively. Further molecular docking analysis revealed formations of strong complexes of RPT, ECR and LAM with HBV polymerase through interactions with binding pocket residues. Taken together, the present results demonstrated promising therapeutic potential of the novel R. tripartita -derived catechin and epicatechin for HBV, warranting their further molecular and pharmacological evaluation., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020, Spandidos Publications.)

HIV-integrase is an important drug target because it catalyzes chromosomal integration of proviral DNA towards establishing latent infection. Computer-aided drug design has immensely contributed to identifying and developing novel antiviral drugs. We have developed various machine learning-based predictive models for identifying high activity compounds against HIV-integrase. Multiclass models were built using support vector machine with reasonable accuracy on the test and evaluation sets. The developed models were evaluated by rigorous validation approaches and the best features were selected by Boruta method. As compared to the model developed from all descriptors set, a slight improvement was observed among the selected descriptors. Validated models were further used for virtual screening of potential compounds from ChemBridge library. Of the six high active compounds predicted from selected models, compounds 9103124, 6642917 and 9082952 showed the most reasonable binding-affinity and stable-interaction with HIV-integrase active-site residues Asp64, Glu152 and Asn155. This was in agreement with previous reports on the essentiality of these residues against a wide range of inhibitors. We therefore highlight the rigorosity of validated classification models for accurate prediction and ranking of high active lead drugs against HIV-integrase.

Chronic liver disease caused by hepatitis B virus (HBV) remains an important health issue. Though there are effective HBV-polymerase inhibitors (e.g., lamivudine), their prolonged use leads to emergence of drug-resistant (polymerase mutant) strains. Several herbal formulations and phytochemicals have been therefore, reported as potential anti-HBV agents with no sign of resistance in experimental and clinical settings. In this study, we assessed the anti-HBV as well as hepatoprotective salutations of solanopubamine, a rare alkaloid isolated from S. schimperianum. In cultured HepG2.2.15 cells, solanopubamine showed marked anti-HBV activity in a time and dose-dependent manner. Solanopubamine (30 μM) efficiently inhibited HBsAg and HBeAg expressions by 66.5%, 70.5%, respectively as compared to 82.5% and 86.5% respective inhibition by lamivudine (2 μM) at day 5. Molecular docking analyses of solanopubamine revealed formations of stable complexes with lamivudine-sensitive as well as lamivudine-resistant polymerase through interactions of catalytic 'YMDD/YIDD' motif residues. Moreover, solanopubamine attenuated DCFH-induced oxidative and apoptotic damage and restored HepG2 cell viability by 28.5%, and downregulated caspase-3/7 activations by 33%. Further docking analyses of solanopubamine showed formation of stable complexes with caspase-3/7. Taken together, our data demonstrates promising anti-HBV and anti-hepatotoxic therapeutic potential of solanopubamine, and warrants further molecular and pharmacological studies., 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).)

The genus Crepis constitutes cold-adapted plant spp., of these some are traditionally used in folk medicine against inflammation or fungal infections without scientific validations. Here, we report the biological activities of Crepis flexuosa total ethanol-extract (CF-EtOH) and its hexane (CF-Hex), ethyl acetate (CF-EtOA), butanol (CF-ButOH), and aqueous (CF-Aqua) fractions. Our in vitro DPPH and ABTS radical-scavenging assays showed CF-EtOH, CF-ButOH and CF-Aqua with maximal, CF-EtOA with moderate, and CF-Hex with mild anti-oxidant activities. When tested on human cancer cell lines, high cytotoxicity was demonstrated by CF-EtOH (IC 50 : 42.45 μg/ml) and CF-Aqua (IC 50 : 46.37 μg/ml) on HepG2, followed by CF-Hex (IC 50 : 63.24 μg/ml) and CF-ButOH (IC 50 : 65.32 μg/ml) on MCF7 cells. The human primary cell line (HUVEC) had comparatively lower cytotoxicity for the tested samples. Moreover, when assessed for anti-microbial efficacy, CF-ButOH and CF-Aqua exhibited the strongest activity (MIC: 156.25 μg/ml) against S. aureus , E. faecalis and C. albicans . Further, while the developed RP-HPTLC identified the bioactive flavonoid luteolin-7- O -glucoside (17.58 mg/g), GS/MS analysis revealed sixteen compounds in C. flexuosa extract. In conclusion, we for the first time show the promising anti-oxidative, anti-cell proliferative and anti-microbial efficacies of C. flexuosa . This warrants further phytochemical and bio-efficacy studies towards isolations and identifications of active principles., 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).)

Hepatitis B virus (HBV) infection is prevalent and continues to be a global health concern. In this study, we determined the anti-hepatitis B virus (HBV) potential of the Socotra-endemic medicinal plant Dracaena cinnabari and isolated and characterized the responsible constituents. A bioassay-guided fractionation using different chromatographic techniques of the methanolic extract of D. cinnabari led to the isolation of two chalcone derivatives. Using a variety of spectroscopic techniques, including 1 H-, 13 C-, and 2D-NMR, these derivatives were identified as 2,4'-dihydroxy-4-methoxydihydrochalcone (compound 1 ) and 2,4'-dihydroxy-4-methoxyhydrochalcone (compound 2 ). Both compounds were isolated for the first time from the red resin (dragon's blood) of D. cinnabari . The compounds were first evaluated for cytotoxicity on HepG2.2.15 cells and 50% cytotoxicity concentration (CC50) values were determined. They were then evaluated for anti-HBV activity against HepG2.2.15 cells by assessing the suppression of HBsAg and HBeAg production in the culture supernatants and their half maximum inhibitory concentration (IC 50 ) and therapeutic index (TI) values were determined. Compounds 1 and 2 indicated inhibition of HBsAg production in a dose- and time-dependent manner with IC 50 values of 20.56 and 6.36 μg/mL, respectively.

Hepatitis E virus (HEV) is a major causative agent of hepatitis E infections across the globe. Although the essentiality of HEV nonstructural polyprotein (pORF1) putative Y-domain (Yd) has been established in viral pathogenesis, its structural-functional role remains elusive. The current research discusses the novel exploration on Yd protein expression, purification, biophysical characterization and structure-based docking analysis. The codon optimized synthetic gene and optimized expression parameters i.e., 5 h induction with 0.25 mM IPTG at 37 °C, resulted in efficient production of Yd protein (~40 kDa) in E. coli BL21(DE3) cells. Majority of the recombinant Yd (rYd) protein expressed as inclusion bodies was solubilized in 0.5% N-lauroylsarcosine and purified using Ni-NTA chromatography. Circular dichroism (CD) and UV visible absorption spectroscopic studies on Yd revealed both secondary and tertiary structure stability in alkaline range (pH 8.0-10.0), suggesting correlation with its physiological activity. Thus, loss in structure at low pH perhaps play crucial role in cytoplasmic-membrane interaction. The biophysical data were in good agreement with insilico structural analyses, which suggested mixed α/β fold, non-random and basic nature of Yd protein. Furthermore, due to Yd protein essentiality in HEV replication and pathogenesis, it was considered as a template for docking and drug-likeness analyses. The 3D modeling of Yd protein and structure-based screening and drug-likeness of inhibitory compounds, including established antiviral drugs led to the identification of top nine promising candidates. Nonetheless, in vitro studies on the predicted interaction of Yd with intracellular-membrane towards establishing replication-complexes as well as validations of the proposed therapeutic agents are warranted., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Natural or plant products, because of their structural diversity, are a potential source for identifying new anti-hepatitis B virus (HBV) agents. Here, we report the anti-HBV activity of Euphorbia schimperi and its quercetin (QRC) and kaempferol derivatives. The anti-HBV-active methanol fraction of E. schimperi was subjected to chromatographic techniques, leading to isolation of three flavonols, following their structure determination by 1 H and 13 C NMR spectroscopies. Their cytotoxicity and anti-HBV potential were assessed using HBV reporter HepG2.2.15 cells, and their modes of action were delineated by molecular docking. The isolated compounds identified as quercetin-3- O -glucuronide (Q3G), quercetin-3- O -rhamnoside (Q3R), and kaempferol-3- O -glucuronide (K3G) were non-cytotoxic to HepG2.2.15 cells. The viral HBsAg/HBeAg production on day 5 was significantly inhibited by K3G (∼70.2/∼73.4%), Q3G (∼67.8/∼72.1%), and Q3R (∼63.2%/∼68.2%) as compared to QRC (∼70.3/∼74.8%) and lamivudine (∼76.5/∼84.5%) used as standards. The observed in vitro anti-HBV potential was strongly supported by in silico analysis, which suggested their structure-based activity via interfering with viral Pol/RT and core proteins. In conclusion, this is the first report on the anti-HBV activity of E. schimperi -derived quercitrin-3- O -glucuronide, quercitrin-3- O -rhamnoside, and kaempferol-3- O -glucuronide, most likely through interfering with HBV proteins., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Elevation in hyperglycemia-associated methylglyoxal level can trigger vascular endothelial cells oxidative stress and apoptosis. The present work assesses the cell proliferative, anti-oxidative and anti-apoptotic potential of Suaeda monoica derived four new terpenes: a norsesquaterpenol (normonisesquaterpenol), a monocyclic triterpenoid (suaedanortriterpene dione), an aromatic monoterpenic ester and a labdane-type norditerpenic xyloside as well as two new phenols: an alkylated β-naphthol and a β-methoxy naphthalene in cultured human umbilical vein endothelial cells (HUVEC). Of these, suaedanortriterpenedione (53.7%), normonisesquaterpenol (51.4%) and norditerpenic xyloside (48%) showed the most promising cell proliferative activities compared to others. Moreover, normonisesquaterpenol, norditerpenic xyloside and suaedanortriterpenedione efficiently reversed the oxidative and apoptotic cell damage via downregulation of capase-3/7 by 44.3%, 42.2% and 39.4%, respectively against dichlorofluorescin, whereas by 46.2%, 43.5% and 42.5%, respectively against methylglyoxal. Aminoguanidine, the reference drug inhibited caspase-3/7 activity by 56.2% and 54.7% through attenuation of dichlorofluorescin and methylglyoxal, respectively. Further in silico molecular docking analysis revealed formation of stable complexes between the tested compounds and caspase-3/7. Conclusively, we for the first time demonstrate the growth stimulatory, anti-oxidative and anti-apoptotic salutations of S. monoica derived novel compounds in human endothelial cells. This warrants their further assessment as vascular cell protective and rejuvenating therapeutics, especially in hyperglycemic conditions., 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., (© 2021 The Author(s).)

Two new polycyclic pyrroloquinazoline alkaloids with unprecedented skeleton, anisulcusines A ( 1 ) and B ( 2 ), along with four known compounds ( 3 - 6 ), were identified from the aerial parts of Anisotes trisulcus (Forssk.) Nees. To our knowledge, anisulcusines A and B are the first polycyclic pyrroloquinazoline alkaloids that possess a unique N -methyl-1,2-dihydro-1' H -spiro[benzo[ d ][1,3]oxazine moiety. The chemical structures of the new compounds were elucidated through extensive spectroscopic analyses and high-resolution mass spectroscopy. Anisulcusine B ( 2 ) exerted moderate cytotoxic effect on cultured human hepatoma (HuH7) cells, whereas compounds 1 and 3 - 5 exhibited mild cell proliferative or growth stimulatory activity. HIGHLIGHTS Two new polycyclic pyrroloquinazoline alkaloids from Anisotes trisulcus . Structures were elucidated on the basis of 1D- and 2D-NMR and HR-ESI-MS spectra. Compound ( 2 ) exerted moderate cytotoxic effect against human hepatoma (HuH7) cells. Compounds ( 1 , 3 - 5 ) exhibited mild cell proliferative or growth stimulatory activity.

Couple of ethnopharmacological surveys in the Indian Ladakh and Pakistani Shigar valleys has reported the medicinal use of Acantholimon lycopodioides against cardiac and gastric disorders that however, remains without scientific rationale or experimental validations. Here, we assess the in vitro bio/therapeutic activities of A. lycopodioides extracts as well as chloroform, ethyl acetate, n-butanol and aqueous fractions. The in vitro β-carotene-linoleic acid bleaching and DPPH radical scavenging methods demonstrated a very high anti-oxidative property of chloroform and ethyl acetate fractions compared to others. Cell viability assay (MTT) on human cervical (HeLa), breast (MDA-MB321) and liver (HepG2) cancer cells revealed their differential cytotoxicity, except the chloroform fraction. Of these, the precipitate exerted highest cytotoxicity on HepG2 cells followed by aqueous fraction on MDA-MB321 cells. Notably, the non-cytotoxicity of chloroform fraction coincided with its highest anti-oxidative activity. Further, the chloroform fraction showed marked hepatoprotection (up to 84%) against 3'7'dichlorofluorescin triggered free radicals induced oxidative damage. Also, the hepatoprotective chloroform fraction mildly activated CYP3A4 in HepG2 cells (dual-luciferase assay). Moreover, the A. lycopodioides extracts and fractions showed differential anti-bacterial and anti-fungal activities. Of these, while S. aureus was more sensitive to the water-insoluble extract, ethyl acetate fraction showed moderate activity against E. coli and C. albicans . On the other hand, the chloroform fraction showed promising activity against S. Aureus , C. albicans, P. vulgaris and E. faecalis. In conclusion, our data for the first time, demonstrated promising anti-oxidative, hepatoprotective, anti-cancer, anti-microbial and CYP3A4 activating salutations of A. lycopodioides . This warrants further studies towards isolation and identification of its therapeutically active principles., 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).)

Active herbal or natural compounds have high chemical diversity and specificity than synthetic drugs. Recently, we have validated the hypoglycemic salutation of Oncocalyx glabratus in rodent model, and demonstrated the activation of PPARα/γ by its newly ioslated flavan derivative Oncoglabrinol C (5,3'-Dihydroxyflavan 7-4'- O -digallate) in liver cells (HepG2). Here we evaluated the potential of Oncoglabrinol C against Dichlorofluorescin (DCFH) and Methylglyoxal (MGO) induced endothelial cells (HUVEC) oxidative and apoptotic damage, including activation of PXR-mediated hepatic CYP3A4. Our MTT assay showed protection of ~57% and ~63.5% HUVEC cells by 10 and 20 μg/ml doses of Oncoglabrinol C, respectively through attenuating DCFH triggered free-radicals. Also, the two doses effectively protected ~53% and ~65.5% cells, respectively by reversing MGO toxicity. In DCFH and MGO treated cells, Oncoglabrinol C (20 μg/ml) effectively downregulated caspase 3/7 activity by ~33% and ~43.5%, respectively. Moreover, in reporter gene (dual-luciferase) assay, Oncoglabrinol C (20 μg/ml) moderately activated hepatic CYP3A4. Molecular docking of Oncoglabrinol C indicated its strong interactions with cellular caspase 3/7, PPARα/γ and PXR proteins, which supported its anti-apoptotic (antagonistic) as well as pro-hypoglycemic and PXR/CYP activating (agonistic) activities. Taken together, our findings demonstrated the potential of Oncoglabrinol C in reversing the endothelial oxidative and apoptotic damage as well as in the activation of hepatic CYP3A4. This warrants further evaluations of Oncoglabrinol C and related compounds towards developing effective and safe drugs against diabetes associated cardiovascular disorders., (© 2020 The Author(s).)

Recently, we have shown in vitro anti-hepatitis B virus (HBV) activity of G. senegalensis J.F. Gmel leaves, and Identified quercetin and other flavonoids by HPTLC. Here we report bioassay-directed fractionation of G. senegalensis leaves using column chromatography and isolation of two flavonoinds from the n -butanol fraction, their structure determination ( 1 H NMR, 13 C NMR and 2D-NMR) and assessment of antiviral activities (HBsAg and HBeAg assay) in HBV-reporter HepG2.2.2.15 cells. Further molecular docking was performed against HBV polymerase (Pol/RT) and capsid (Core) proteins as well as host-receptor sodium taurocholate co-transporting polypeptide (NTCP). The two isolated bioactive compounds were identified as quercetin and myricetin-3- O -rhamnoside. Quercetin significantly inhibited synthesis of HBsAg and HBeAg by about 60% and 62%, respectively as compared to myricetin-3- O -rhamnoside by 44% and 35%, respectively. Molecular docking of the two anti-HBV flavonoids revealed their higher binding affinities towards Pol/RT than Core and NTCP. In conclusion, this is the first report on anti-HBV active myricetin-3- O -rhamnoside along with quercetin isolated from G. senegalensis leaves. Their possible mode of anti-HBV activities are suggested through binding with viral Pol/RT and Core as well as host NTCP proteins., 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).)

Using different chromatographic methods, four new compounds were isolated from the aerial parts of Suaeda monoica (Chenopodiaceae) along with 2-hydroxy-1-naphthoic acid (SCM-3). The structures of the new compounds were established as 6'-hydroxy-10'-geranilanyl naphtha-1-oate (SMC-1), 4,4,8β,10β-Tetramethyl-9β-isobutanyl decalin-13-ol-13-O-β-D-xylopyranoside (SCM-2), 6'-(2-hydroxynaphthalen-3-yl) hexanoic acid (SCM-4) and 1'-(2-Methoxy-3-naphthyl)-4'-(2''-methylbenzoyl)- n -butane (SMC-5) by IR, EIMS and NMR (1 & 2D) analyses. All compounds (50 μg/mL) were tested for cell proliferative potential on cultured human liver cell HepG2 cells by MTT assay. The results revealed a marked cell proliferative potential of all compounds (1.42-1.48 fold) as compared to untreated control. The results of molecular docking and binding with specific proteins such as PTEN (Phosphatase and Tensin homolog) and p53 also justify the cell proliferative potential of the isolated compounds. Glide program with Schrodinger suit 2018 was used to evaluate the binding between SMC compounds and proteins (PTEN and p53). The binding affinity of all compounds was in order of 10 4 -10 5 M -1 towards both PTEN and p53. All the SMC compounds have been found to bind at the active site of PTEN, thereby may prevent the binding of phosphatidylinositiol 3,4,5-triphosphate (PI3P). In the locked position, PTEN would not be able to hydrolyze PI3P and hence the PI3P regulated signaling pathway remains active. Similarly, SMC molecules were found to interact with the amino acid residues (Ser99, Thr170, Gly199, and Asp224) which are critically involved in the formation of tetrameric p53. The blockage of p53 to attain its active conformation thus may prevent the recruitment of p53 on DNA and hence may promote cell proliferation., (© 2019 The Author(s).)

Although the approved hepatitis B virus (HBV)-polymerase inhibitors (e.g., lamivudine) often lead to drug-resistance, several natural products have shown promising efficacies. Though Aloe vera (AV) gel and its constituents are shown inhibitors of many viruses, their anti-HBV activity still remains elusive. We therefore, tested the anti-HBV potential of AV extract and its anthraquinones in hepatoma cells, including molecular docking, high-performance thin layer chromatography (HPTLC), and cytochrome P450 (CYP3A4) activation analyses. Our anti-HBV assays (HBsAg/HBeAg Elisa) showed maximal inhibition of viral antigens production by aloe-emodin (~83%) > chrysophanol (~62%) > aloin B (~61%) > AV extract (~37%) in HepG2.2.15 cells. Interestingly, the effect of aloe-emodin was comparable with lamivudine (~86%). Moreover, sequential treatment with lamivudine (pulse) followed by aloe-emodin (chase) enhanced the efficacy of monotherapy by ~12%. Docking (AutoDock Vina) of the anthraquinones indicated strong interactions with HBV-polymerase residues that formed stable complexes with high Gibbs's free energy. Further, identification of aloe-emodin and aloin B by validated HPTLC in AV extract strongly endorsed its anti-HBV potential. In addition, our luciferase-reporter gene assay of transfected HepG2 cells showed moderate induction of CYP3A4 by aloe-emodin. In conclusion, this is the first report on anti-HBV potential of AV-derived anthraquinones, possibly via HBV-polymerase inhibition. Of these, although aloin B exhibits novel antiviral effect, aloe-emodin appears as the most promising anti-HBV natural drug with CYP3A4 activating property towards its enhanced therapeutic efficacy., (© 2019 John Wiley & Sons, Ltd.)

Background: Of over 35 Saudi plants traditionally used to treat liver disorders, majority still lack scientific validations. We therefore, evaluated the anti-oxidative, anti-apoptotic and hepatoprotective potential of Solanum surattense leaves total ethanol-extract (SSEE)., Methods: The cytoprotective (4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide/ MTT assay) and anti-apoptotic (caspase-3/7) potential of SSEE (25-200 μg/mL) were assessed in cultured HepG2 cells against dichlorofluorescein (DCFH)-induced toxicity. The hepatoprotective salutation of SSEE (100 and 200 mg/kg.bw/day) in carbon tetrachloride (CCl 4 )-intoxicated rats was evaluated by serum biochemistry and histopathology. The anti-oxidative activity of SSEE (31.25-500 μg/mL) was tested by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging and linoleic acid bleaching assays. Also, SSEE was subjected to qualitative phytochemical analysis, and standardized by validated high-performance liquid chromatography (HPTLC)., Results: SSEE at doses 50, 100 and 200 μg/mL showed HepG2 cell proliferative and protective potential by about 61.0, 67.2 and 95%, respectively through inhibition of caspase-3/7 against DCFH-toxicity. In CCl 4 -injured rats, SSEE (200 mg/kg) significantly (P < 0.001) normalized serum transaminases, alkaline phosphatase, bilirubin, cholesterol, triglycerides, and total protein, including tissue malondialdehyde and nonprotein sulfhydryls levels, supported by the liver histopathology. SSEE further showed strong in vitro anti-oxidative and anti-lipid peroxidative activities, evidenced by the presence of alkaloids, flavonoids, tannins, sterols and saponins. Identification of β-sitosterol (3.46 μg/mg) strongly supported the anti-oxidative and hepatoprotective salutation of SSEE., Conclusion: Our findings suggest the therapeutic potential of S. surattense against chemical-induced oxidative stress and liver damage. However, isolation of the active principles and elucidation of mechanism of action remain to be addressed.

In traditional Arabian medicine, the Rhus tripartita plant (family Anacardiaceae) has been used to treat inflammatory conditions. Although Rhus extracts have been reported for their cardioprotective effects, information regarding their active principle compounds remains insufficient. The present investigation was aimed at determining the antioxidant chemical constituents of the methanolic extract of R. tripartita stem bark and evaluating their ability to ameliorate methylglyoxal-induced endothelial cell apoptosis. Ten flavonoid compounds (1-10) were isolated and identified using DPPH radical scavenging bioassay-guided chromatographic separation. A new proanthocyanidin (rhuspartin) (1) was isolated and identified as 3,5,13,14-flavantetrol-(4β→8)-catechin, using extensive spectroscopic data and high resolution-mass spectrometry. Among the compounds (1, 5, 7-10) tested for toxicity toward cultured endothelial cells (HUVECs), the non-cytotoxic compounds 1 and 7 evinced cytoprotective potential that reversed the methylglyoxal-induced apoptosis (by 62% and 64%, respectively) through downregulation of caspase 3/7., (Copyright © 2019. Published by Elsevier Taiwan LLC.)

In the present study we investigated the hepatotoprotective, hepatitis B virus (HBV) inhibitory and hepatic CYP450 enzyme (CYP3A4) modulatory potential of Cyperus rotundus rhizome fractions. The crude ethanol-extract, including different organic and aqueous fractions were tested for in vitro cytoprotection on HepG2 cells (MTT assay), followed by in vivo evaluation in Wistar rats (serum biochemistry and lipid profile). The in vitro anti-HBV activity was tested on HepG2.2.15 cells (HBsAg and HBeAg Elisa). Of these, the n-butanol and aqueous fractions showed the most promising, dose-dependent hepatoprotection in DCFH-injured HepG2 cells. Further, in CCl 4 -injured rats, oral administration of C. rotundus (100 and 200 mg/kg·bw/day) significantly normalized serum markers of healthy liver function (SGOT, SGPT, GGT, ALP and bilirubin) and lipid profile (cholesterol, HDL, LDL, VLDL, TG and MDA), including tissue NP-SH and TP levels. Compared to other fractions, the ethyl acetate, n-butanol and aqueous fractions exhibited the best inhibitory effects on viral HBsAg and HBeAg secretions in dose- and time-dependent manner. In addition, reporter gene assay (Dual-luciferase) of transfected HepG2 cells showed mild activation of nuclear PXR-mediated CYP3A4 gene by the three active fractions. Taken together, C. rotundus showed very promising hepatoprotective and anti-HBV potential in experimental settings . In addition, this is the first report on modulation of CYP3A4 by C. rotundus that suggests its safe consumption in relation to drug metabolism and efficacy. Our data could therefore, provide the basis for the ethnobotanical medicinal use of C. rotundus in metabolic liver disorder and hepatitis B patients.

Despite high anti-HBV efficacies, while the nucleoside analogs (e.g., lamivudine) lead to the emergence of drug-resistance, interferons (e.g., IFN-α causes adverse side-effects. Comparatively, various natural or plant products have shown similar or even better efficacy. Hence, new antiviral strategies must focus not only on synthetic molecules but also on potential natural compounds. In this report, we have combined the in vitro cell culture and in silico molecular docking methods to assess the novel anti-HBV activity and delineate the inhibitory mechanism of selected plant-derived pure compounds of different classes. Of the tested (2.5-50 μg/ml) twelve non-cytotoxic compounds, ten (10 μg/ml) were found to maximally inhibit HBsAg production at day 5. Compared to quercetin (73%), baccatin III (71%), psoralen (67%), embelin (65%), menisdaurin (64%) and azadirachtin (62%) that showed high inhibition of HBeAg synthesis, lupeol (52%), rutin (47%), β-sitosterol (43%) and hesperidin (41%) had moderate efficacies against HBV replication. Further assessment of quercetin in combination with the highly active compounds, enhanced its anti-HBV activity up to 10%. Being the most important drug target, a 3-D structure of HBV polymerase (Pol/RT) was modeled and docked with the active compounds, including lamivudine as standard. Docking of lamivudine indicated strong interaction with the modeled HBV Pol active-site residues that formed stable complex (∆G = -5.2 kcal/mol). Similarly, all the docked antiviral compounds formed very stable complexes with HBV Pol (∆G = -6.1 to -9.3 kcal/mol). Taken together, our data suggest the anti-HBV potential of the tested natural compounds as novel viral Pol/RT inhibitors.

The cytochrome P450 3A4 (CYP3A4) is the most abundant CYP450 enzyme involved in the metabolism of endogenous products and xenobiotics, including prescription drugs and herbals. Modulation of hepatic CYP3A4 gene expression via nuclear receptors, like pregnane X receptor (PXR), is a major cause of adverse effects like drug-unresponsiveness and toxicity. In the present study, ethanol extracts of 58 medicinal plants, belonging to 27 families, were evaluated for potential activities in CYP3A4 induction in HepG2 cells by reporter gene assay. For PXR-mediated CYP3A4 induction, a 50 μg/ml concentration was used for all non-cytotoxic plants extracts. Rifampicin (10 μM) and DMSO (0.1%) were used as standard inducer and untreated (negative) control, respectively. The comparative fold-induction of CYP34A by the plant extracts in relation to the untreated control was determined. As a result, Dodonaea angustifolia (2.62 fold; P  < 0.0001) was found to be the most promising inducer of CYP3A4, followed by Euphorbia tirucalli (1.95 fold; P  = 0.0004), Alternanthera pungens (1.74 fold, P  = 0.0035), and Ficus palmata (1.65 fold; P  = 0.0097). Further phytochemical characterizations of the active plants are therefore, warranted.

Guiera senegalensis J.F. Gmel is a broad-spectrum African folk- medicinal plant, having activities against fowlpox and herpes viruses. Very recently, we have shown the anti-hepatitis B vius (HBV) potential of G. senegalensis leaves extract (GSLE). Here, we report the antioxidative and hepatoprotective efficacy of GSLE, including HPTLC quantification of four biomarkers of known antioxidative and antiviral activities. In cultured liver cells (HuH7) GSLE attenuated DCFH-induced oxidative stress and cytotoxicity. This was supported by in vitro DPPH radical-scavenging and β-carotene-linoleic acid bleaching assays that showed strong antioxidant activity of GSLE. Further, two simple and sensitive HPTLC methods (I and II) were developed and validated to quantify β-amyrin, β- sitosterol, lupeol, ursolic acid in GSLE. While HPTLC-I (hexane: ethylacetate; 75:25; v/v) enabled quantification of β-amyrin (Rf = 0.39; 20.64 μg/mg) and β-sitosterol (Rf = 0.25; 18.56 μg/mg), HPTLC-II (chloroform: methanol; 97:3; v/v) allowed estimation of lupeol (Rf = 0.47; 6.72 μg/mg) and ursolic acid (Rf = 0.23; 5.81 μg/mg) in GSLE. Taken together, the identified biomarkers strongly supported the antioxidant and anti-HBV potential of GSLE, suggesting its activity via abating the oxidative stress. To our knowledge, this is the first report on HPTLC analysis of these biomarkers in G. senegalensis that could be adopted for standardization and quality-control of herbal-formulations.

Atriplex suberecta I. Verd is a known phytomedicinal species of Atriplex ; however, studies into its bioactivity remain inconclusive. The in vitro and in vivo antioxidative and hepatoprotective potential of A. suberecta ethanol-extract (ASEE) was assessed in the present study. 1,1-diphenyl-2-picrylhydrazyl radical scavenging and β-carotene bleaching assays revealed that ASEE possesses free radical scavenging and anti-lipid peroxidative activities. These results were supported by the in vitro protection of HepG2 hepatoblastoma cells via abating 2,7-dichlorofluorescein-activated oxidative and apoptotic molecules (caspase-3/-7). In carbon tetrachloride-treated rats, the oral administration of ASEE significantly normalized serum biomarkers of liver function (serum glutamate oxaloacetate, serum pyruvate transaminase, alkaline phosphatase, γ-glutamyl transferase and bilirubin) and the lipid profile (total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides and malondialdehyde), including tissue non-protein sulfhydryl and total protein levels. These results were also supported by liver histopathology, which demonstrated that the therapeutic effect of ASEE was comparable to silymarin. Furthermore, phytochemical analysis of ASEE revealed the presence of flavonoids, alkaloids, tannins and saponins. Rutin, an antioxidant flavonoid, was identified using the validated high-performance thin-layer chromatography method. In conclusion, this is the first report on the therapeutic potential of A. suberecta against chemical-induced oxidative stress and liver damage.

We report isolation of a new sesquiterpene (compound 2: plectranol A) along with three known compounds (1: maaliol, 3: penduletin and 4: chrysosplenol D) from the aerial parts of Plectranthus cylindraceus Hoechst. Ex. Benth ethyl acetate extract (PCEAE). Their structures were established by UV, IR, NMR ( 1 H & 13 C), HRESIMS and HSQC methods. The MTT cell proliferation assay of the compounds and the extract performed on human breast, skin and cervical cancer cell lines showed high toxicity, and their IC 50 (μg/mL) values were determined. The validated HPTLC analyses of maaliol and PCEAE (method I) and, penduletin, chrysosplenol D and PCEAE (method II) furnished sharp and compact peaks. The estimated high contents (μg/mg) of maaliol (17.06), penduletin (39.36) and chrysosplenol D (31.66) in PCEAE approved the plant's cytotoxic property. Since, P. cylindraceus contains a variety of cytotoxic terpenoids and flavonoids; our data warrant its further phytochemical and biological characterisation towards developing promising anti-cancer drugs.

Context: Guiera senegalensis J.F. Gmel (Combretaceae) is a folk medicinal plant used in various metabolic and infectious diseases. In addition to its antiviral activities against herpes and fowlpox, the anti-HBV efficacy is very recently reported., Objective: To develop and validate simple, sensitive RP-/NP-HPTLC methods for quantitative determination of biomarkers rutin, quercetin, naringenin, and gallic acid in the anti-HBV active G. senegalensis leaves ethanol-extract., Materials and Methods: RP-HPTLC (rutin & quercetin; phase- acetonitrile:water, 4:6) and NP-HPTLC (naringenin & gallic acid; phase- toluene:ethyl acetate:formic acid, 6:4:0.8) were performed on glass-backed silica gel plates 60F 254 -RP18 and 60F 254 , respectively. The methods were validated according to the ICH guidelines., Results: Well-separated and compact spots (R f ) of rutin (0.52 ± 0.006), quercetin (0.23 ± 0.005), naringenin (0.56 ± 0.009) and gallic acid (0.28 ± 0.006) were detected. The regression equations (Y) were 12.434x + 443.49, 10.08x + 216.85, 11.253x + 973.52 and 11.082x + 446.41 whereas the coefficient correlations (r 2 ) were 0.997 ± 0.0004, 0.9982 ± 0.0001, 0.9974 ± 0.0004 and 0.9981 ± 0.0001, respectively. The linearity ranges (ng/spot) were 200-1400 (RP-HPTLC) and 100-1200 (NP-HPTLC). The LOD/LOQ (ng/band) were 33.03/100.1 (rutin), 9.67/29.31 (quercetin), 35.574/107.8 (naringenin), and 12.32/37.35 (gallic acid). Gallic acid (7.01 μg/mg) was the most abundant biomarker compared to rutin (2.42 μg/mg), quercetin (1.53 μg/mg) and naringenin (0.14 μg/mg) in the extract., Conclusion: The validated NP-/RP-HPTLC methods were simple, accurate, and sensitive for separating and quantifying antiviral biomarkers in G. senegalensis, and endorsed its anti-HBV activity. The developed methods could be further employed in the standardization and quality-control of herbal formulations.

Currently, >35 Saudi Arabian medicinal plants are traditionally used for various liver disorders without a scientific rationale. This is the first experimental evaluation of the anti-hepatitis B virus (HBV) potential of the total ethanolic and sequential organic extracts of 60 candidate medicinal plants. The extracts were tested for toxicity on HepG2.2.15 cells and cytotoxicity concentration (CC 50 ) values were determined. The extracts were further investigated on HepG2.2.15 cells for anti-HBV activities by analyzing the inhibition of HBsAg and HBeAg production in the culture supernatants, and their half maximal inhibitory concentration (IC 50 ) and therapeutic index (TI) values were determined. Of the screened plants, Guiera senegalensis (dichloromethane extract, IC 50 =10.65), Pulicaria crispa (ethyl acetate extract, IC 50 =14.45), Coccinea grandis (total ethanol extract, IC 50 =31.57), Fumaria parviflora (hexane extract, IC 50 =35.44), Capparis decidua (aqueous extract, IC 50 =66.82), Corallocarpus epigeus (total ethanol extract, IC 50 =71.9), Indigofera caerulea (methanol extract, IC 50 =73.21), Abutilon figarianum (dichloromethane extract, IC 50 =99.76) and Acacia oerfota (total ethanol extract, IC 50 =101.46) demonstrated novel anti-HBV activities in a time- and dose-dependent manner. Further qualitative phytochemical analysis of the active extracts revealed the presence of alkaloids, tannins, flavonoids and saponins, which are attributed to antiviral efficacies. In conclusion, P. crispa, G. senegalensis and F. parviflora had the most promising anti-HBV potentials, including those of C. decidua , C. epigeus, A. figarianum , A. oerfota and I. caerulea with marked activities. However, a detailed phytochemical study of these extracts is essential to isolate the active principle(s) responsible for their novel anti-HBV potential.

The present study assessed the comparative antioxidant potential of the ethanol extract (EE) of leaves of four Acacia species ( Acacia salicina , AS; Acacia laeta , AL; Acacia hamulosa AH; and Acacia tortilis , AT) grown in Saudi Arabia, including RP-HPTLC quantification of antioxidant biomarker rutin. In vitro DPPH radical scavenging and β-carotene-linoleic acid bleaching assays showed the promising antioxidant activities of Acacia extracts: ASEE (IC 50 : 60.39 and 324.65 μg/ml) >ALEE (IC 50 : 217.06 and 423.36 μg/ml) >ATEE (IC 50 : 250.13 and 747.50 μg/ml) >AHEE (IC 50 : 255.83 and 417.28 μg/ml). This was comparable to rutin tested at 500 μg/ml. Further, a RP- HPTLC densitometric method was developed (acetonitrile:water; 6:4; v/v) using glass-backed RP-18 silica gel F 254 plate, and scanned at UV max 254 nm. The method was validated as per the ICH guidelines. Analysis of the validated RP-HPTLC displayed an intense peak ( R f  = 0.65 ± 0.004) of rutin that was estimated (μg/mg dry weight) to be highest in ASEE (10.42), followed by ALEE (2.67), AHEE (1.36) and ATEE (0.31). Taken together, presence of rutin strongly supported the high antioxidant property of the tested Acacia species, especially Acacia salicina . The developed RP-HPTLC method therefore, affirms its application in the quality control of commercialized herbal drugs or formulation containing rutin.

Chromatographic purification of the n -hexane and dichloromethane extracts of Nuxia oppositifolia aerial parts, growing in Saudi Arabia, resulted in the isolation and characterization of three new labdane-type diterpene acids, 2β-acetoxy-labda-7-en-15-oic acid ( 1 ), 2β-acetoxy-7-oxolabda-8-en-15-oic acid ( 2 ), 2β-acetoxy-6-oxolabda-7-en-15-oic acid ( 3 ), and one new seco-triterpene, 3,4-seco olean-12-en-3,30 dioic acid ( 4 ), together with 10 known lupane, oleanane and ursane-type triterpenes, as well as the common phytosterols, β-sitosterol and stigmasterol ( 5 - 16 ). Their structures have been assigned on the basis of different spectroscopic techniques including 1D and 2D NMR. Moreover, 13 of the isolated compounds were tested on the human cancer cell lines HeLa (cervical), A549 (lung) and MDA (breast), and most of the compounds showed potent cytotoxic activities in vitro.

The present study describes a method developed for quantification and stability study of a rare steroidal alkaloid solanopubamine (SPN) in aerial parts of six different species of genus Solanum extracted with two different solvents. The Solanum species selected for investigation include S. schimperianum (SS), S. villosum (SV), S. coagulans (SC), S. glabratum (SG), S. incanum (SI) and S. nigrum (SN). The estimation of SPN was done by a validated high-performance thin layer chromatography method. The developed chromatographic system was found to give a sharp spot for solanopubamine at R f  = 0.39 ± 0.01. The steroidal alkaloid SPN was observed to be present only in extracts of aerial parts of S. schimperianum . The sensitivity of developed method produced 40 ng and 115 ng band -1 , respectively as LOD and LOQ values. The percentage yield of SPN in aerial parts of S. schimperianum extracted by ethanol (95%) only and a mixture of ethanol and ammonium hydroxide (6:4) was found to be 1.03 w/w and 2.09 w/w, respectively. Stability studies of SPN exhibited the maximum (100%) degradation in an alkaline environment and H 2 O 2 treated samples and 61.4% in acidic conditions. The SPN was found to be significantly stable against UV exposure, photo-oxidation and at room temperature while 13.83% and 57.88% destruction has been observed when exposed to dry heat at 40 °C and 60 °C, respectively.

Glucuronidation is an important phase II pathway responsible for many endogenous substances and drug metabolism. The present work evaluated allele frequencies of certain UDP-glucuronosyl-transferases (UGT 1A6∗2, A7∗12, A8∗3, A9∗3, 2B7∗2, and 2B15∗2) in Saudi Arabians that could provide essential ethnic information. Blood samples from 192 healthy unrelated Saudi males of various geographic regions were collected. Genomic DNA was isolated and genotyping of various UGTs was carried out using polymerase chain reaction (PCR) followed by direct sequencing. For UGT1A6∗2 A/G genotype, the most common variant was the homozygous repeat (AA) and the most common allele was (A) with a frequency of 46.5% and 67.3%, respectively. Similarly, the most common variant for UGT1A7∗12 T/C genotype was the heterozygous repeat (TC) with a frequency of 78.7% while the mutant allele (C) was present in 60.6% of the study population. Both UGT1A8∗3 (G/A) and UGT1A9∗3 (T/C) showed only a wild homozygous pattern in all screened subjects. For UGT2B7∗2, the heterozygous repeat (TC) was found with a frequency of 57.3% and the alleles (A) showed a frequency of 50.8%. In contrast, for UGT2B15∗2 (G253T), the heterozygous repeat (TG) presented 62.3% of the subjects where the most common allele (G) was with a frequency of 66.2%. In conclusion, our data indicate that Saudis harbor some important UGT mutations known to affect enzyme activity. Additional studies are therefore, warranted to assess the clinical implications of these gene polymorphisms in this ethnic group.

Background/purpose: Ajwa, a special variety of Saudi Arabian dates (Phoenix dactylifera L.) is a rich source of nutrients, fibers and bioactive molecules. While previous studies have shown the therapeutic value of dates phytoconstituents in liver and kidney diseases etc., its cardioprotective potential remains elusive. We therefore, investigated the cardioprotective effect of lyophilized Ajwa extract (AJLE) ex vivo as well as in vivo., Methods: Ex vivo cardioprotective effect of AJLE was evaluated on DCFH-toxicated cardiomyoblast cells (H9C2). In vivo hemodynamics, cardiac function, serum cardiac enzymes, myocardial antioxidant, inflammatory and apoptotic biomarkers as well as histopathological parameters were studied in IPS-injured Wistar rat heart tissues., Results: AJLE (250 µg/ml) attenuated the cytotoxicity and enhanced the H9C2 proliferation by up to 40%. Oral administration of AJLE (250 and 500 mg/kg.bw) prevented the depletion of endogenous antioxidants (CAT, SOD, NP-SH and NO) and myocyte injury marker enzymes, and inhibited lipid peroxidation (MDA, MPO). Moreover, AJLE downregulated the expressions of proinflammatory cytokines (IL-6, IL-10 and TNFα) and apoptotic markers (caspase-3 and Bax), and upregulated the anti-apototic protein Bcl2. Histological data showed that AJLE pretreatment reduced myonecrosis, edema, and infiltration of inflammatory cells and restored the cardiomyocytes architecture., Conclusion: Taken together, our data revealed that AJLE had strong antioxidant, hypolipidimic, cardioprotective, anti-inflammatory and anti-apoptotic potential against myocardial damage. This further endorses the use of Ajwa in Arabian traditional medicine against cardiovascular diseases., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

Background: Consumption of plant-derived nutraceuticals and crude drugs in traditional medicine is widely believed to confer beneficial effects in thwarting the progression of cardiovascular diseases. Rhus tripartita (family Anacardiaceae) has been traditionally used to treat a wide range of ailments., Methods: In the present study we investigated the protective effects of an alcoholic extract of the stem part of Rhus tripartita male genotype (RTSM) on experimentally induced myocardial injury in rats. To this end, cardiac injury was induced by administration of isoproterenol (ISO) and serum enzyme markers, lipid profiles and cardiac tissue redox status were determined following RTSM treatment (250 and 500 mg/kg)., Results: As a result, RTSM treatment significantly mitigated ISO-triggered upregulation of cardiac-specific markers of injury creatine kinase and lactate dehydrogenase. RTSM treatment significantly attenuated ISO-induced increase in serum cholesterol and triglycerides as well alterations in serum lipoproteins. Determination of oxidative balance showed that RTSM treatment significantly blunted ISO-induced increase in malondialdehyde and decrease in nonprotein sulfhydryl in cardiac tissue. Six compounds were isolated and identified as gallocatechin 1, taxifolin 2, myricetin-3-O-β-glucoside 3, catechin 4, epicatechin 5, and 3',8-binaringenin 6. Compound 6 was isolated for the first time from the stem part of Rhus tripartita. Furthermore, RTSM treatment enhanced the survival fraction of cardiac cells exposed to oxidative stress in vitro., Conclusion: We conclude that the antioxidant properties of RTSM treatment underpin its cardioprotective pharmacological effects, thus, providing biological evidence for the treatment of cardiovascular diseases using Rhus tripartita in indigenous medicine.

As a part of ongoing studies in developing new anticancer agents, novel 1,2-dihydropyridine 4, thienopyridine 5, isoquinolines 6-20, acrylamide 21, thiazolidine 22, thiazoles 23-29 and thiophenes 33-35 bearing a biologically active quinoline nucleus were synthesized. The structure of newly synthesized compounds was confirmed on the basis of elemental analyses and spectral data. All the newly synthesized compounds were evaluated for their cytotoxic activity against the breast cancer cell line MCF7. 2,3-Dihydrothiazole-5-carboxamides 27, 25, 4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (34), 1,2-dihydroisoquinoline-7-carbonitrile (7), 5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide (35), 1,2-dihydroisoquinoline-7-carbonitrile (6), 2-cyano-3-(dimethylamino)-N-(quinolin-3-yl)acrylamide (21), 1,2-dihydroisoquinoline-7-carbonitriles (11) and (8) exhibited higher activity (IC50 values of 27-45 μmol L-1) compared to doxorubicin (IC50 47.9 μmol L-1). LQ quinolin-3-yl)-1,2-dihydroisoquinoline-7-carbonitrile (12), 2-thioxo-2,3-dihydrothiazole-5-carboxamide (28) and quinolin-3-yl)-1,2-dihydroisoquinoline-7-carbonitrile (15) show activity comparable to doxorubicin, while (quinolin-3-yl)-1,2-dihydroisoquinoline-7-carbonitrile (9), 2,3-dihydrothiazole-5-carboxamide (24), thieno [3,4-c] pyridine-4(5H)-one (5), cyclopenta[b]thiophene-3-carboxamide (33) and (quinolin-3-yl)-6-stryl-1,2-dihydroisoquinoline-7-carbonitrile (10) exhibited moderate activity, lower than doxorubicin.

Ehlers-Danlos syndrome (EDS) describes a group of clinical entities in which the connective tissue, primarily that of the skin, joint and vessels, is abnormal, although the resulting clinical manifestations can vary widely between the different historical subtypes. Many cases of hereditary disorders of connective tissue that do not seem to fit these historical subtypes exist. The aim of this study is to describe a large series of patients with inherited connective tissue disorders evaluated by our clinical genetics service and for whom a likely causal variant was identified. In addition to clinical phenotyping, patients underwent various genetic tests including molecular karyotyping, candidate gene analysis, autozygome analysis, and whole-exome and whole-genome sequencing as appropriate. We describe a cohort of 69 individuals representing 40 families, all referred because of suspicion of an inherited connective tissue disorder by their primary physician. Molecular lesions included variants in the previously published disease genes B3GALT6, GORAB, ZNF469, B3GAT3, ALDH18A1, FKBP14, PYCR1, CHST14 and SPARC with interesting variations on the published clinical phenotypes. We also describe the first recessive EDS-like condition to be caused by a recessive COL1A1 variant. In addition, exome capture in a familial case identified a homozygous truncating variant in a novel and compelling candidate gene, AEBP1. Finally, we also describe a distinct novel clinical syndrome of cutis laxa and marked facial features and propose ATP6V1E1 and ATP6V0D2 (two subunits of vacuolar ATPase) as likely candidate genes based on whole-genome and whole-exome sequencing of the two families with this new clinical entity. Our study expands the clinical spectrum of hereditary disorders of connective tissue and adds three novel candidate genes including two that are associated with a highly distinct syndrome.

Background: Liver diseases, the fifth most common cause of global death, can be metabolic, toxin-induced, or infective. Though approximately 35 Saudi medicinal plants are traditionally used to treat liver disorders, the hepatoprotective potential of Aerva javanica has not been explored., Objective: To investigate the antioxidative and hepatoprotective effect of Aerva javanica., Design: Total ethanol extract of A. javanica aerial parts was prepared and tested on DCFH-toxicated HepG2 cells ex vivo, and in CCl4-injured Wistar rats in vivo. MTT assay was used to determine cell viability and the serum biochemical markers of liver injury as well as histopathology was performed. In vitro 1,1-diphenyl-2-picrylhydrazyl and β-carotene free-radical scavenging assay and phytochemical screening of the extract were done. Furthermore, A. javanica total extract was standardized and validated by high-performance thin layer chromatographic method., Results: MTT assay showed that, while DCFH-injured cells were recovered to ~56.7% by 100 µg/ml of the extract, a 200 µg/ml dose resulted in hepatocytes recovery by ~90.2%. Oral administration of the extract (100 and 200 mg/kg.bw/day) significantly normalized the serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, gamma-glutamyl transferase, alkaline phosphatase, bilirubin, cholesterol, high-density lipoprotein, low-density lipoprotein, very-low-density lipoprotein, triglyceride, and malondialdehyde levels, including tissue nonprotein sulfhydryl and total protein in CCl4-injured rats. In addition, the histopathology of dissected liver also revealed that A. javanica cured the tissue lesion compared to silymarin treatment. In vitro assays revealed strong free-radical scavenging ability of the extract and presence of alkaloids, flavonoids, tannins, sterols, and saponins where rutin, a well-known antioxidant flavonoid, was identified., Conclusions: Our findings demonstrate the potential of A. javanica in the attenuation of ex vivo and in vivo hepatotoxicity and oxidative damage. This further suggests its therapeutic value in various liver diseases. However, isolations of the active principles, their mechanisms of action, and other therapeutic contributions remain to be addressed.