Publications by authors named "Mohammad K Parvez"

36 Publications

Role of "dual-personality" fragments in HEV adaptation-analysis of Y-domain region.

J Genet Eng Biotechnol 2021 Oct 12;19(1):154. Epub 2021 Oct 12.

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India.

Background: Hepatitis E is a liver disease caused by the pathogen hepatitis E virus (HEV). The largest polyprotein open reading frame 1 (ORF1) contains a nonstructural Y-domain region (YDR) whose activity in HEV adaptation remains uncharted. The specific role of disordered regions in several nonstructural proteins has been demonstrated to participate in the multiplication and multiple regulatory functions of the viruses. Thus, intrinsic disorder of YDR including its structural and functional annotation was comprehensively studied by exploiting computational methodologies to delineate its role in viral adaptation.

Results: Based on our findings, it was evident that YDR contains significantly higher levels of ordered regions with less prevalence of disordered residues. Sequence-based analysis of YDR revealed it as a "dual personality" (DP) protein due to the presence of both structured and unstructured (intrinsically disordered) regions. The evolution of YDR was shaped by pressures that lead towards predominance of both disordered and regularly folded amino acids (Ala, Arg, Gly, Ile, Leu, Phe, Pro, Ser, Tyr, Val). Additionally, the predominance of characteristic DP residues (Thr, Arg, Gly, and Pro) further showed the order as well as disorder characteristic possessed by YDR. The intrinsic disorder propensity analysis of YDR revealed it as a moderately disordered protein. All the YDR sequences consisted of molecular recognition features (MoRFs), i.e., intrinsic disorder-based protein-protein interaction (PPI) sites, in addition to several nucleotide-binding sites. Thus, the presence of molecular recognition (PPI, RNA binding, and DNA binding) signifies the YDR's interaction with specific partners, host membranes leading to further viral infection. The presence of various disordered-based phosphorylation sites further signifies the role of YDR in various biological processes. Furthermore, functional annotation of YDR revealed it as a multifunctional-associated protein, due to its susceptibility in binding to a wide range of ligands and involvement in various catalytic activities.

Conclusions: As DP are targets for regulation, thus, YDR contributes to cellular signaling processes through PPIs. As YDR is incompletely understood, therefore, our data on disorder-based function could help in better understanding its associated functions. Collectively, our novel data from this comprehensive investigation is the first attempt to delineate YDR role in the regulation and pathogenesis of HEV.
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http://dx.doi.org/10.1186/s43141-021-00238-8DOI Listing
October 2021

Structural exploration of Y-domain reveals its essentiality in HEV pathogenesis.

Protein Expr Purif 2021 Nov 24;187:105947. Epub 2021 Jul 24.

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India. Electronic address:

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.
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http://dx.doi.org/10.1016/j.pep.2021.105947DOI Listing
November 2021

Structure and ligand-based drug discovery of IL-4 inhibitors via interaction-energy-based learning approaches.

J Biomol Struct Dyn 2021 Feb 23:1-19. Epub 2021 Feb 23.

Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.

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.
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http://dx.doi.org/10.1080/07391102.2021.1886172DOI Listing
February 2021

The first bioactivity studies of from high altitude Karakoram-Himalayan desert.

Saudi J Biol Sci 2020 Oct 14;27(10):2514-2520. Epub 2020 Apr 14.

Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

Couple of ethnopharmacological surveys in the Indian Ladakh and Pakistani Shigar valleys has reported the medicinal use of against cardiac and gastric disorders that however, remains without scientific rationale or experimental validations. Here, we assess the bio/therapeutic activities of extracts as well as chloroform, ethyl acetate, n-butanol and aqueous fractions. The 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 extracts and fractions showed differential anti-bacterial and anti-fungal activities. Of these, while was more sensitive to the water-insoluble extract, ethyl acetate fraction showed moderate activity against and . On the other hand, the chloroform fraction showed promising activity against , In conclusion, our data for the first time, demonstrated promising anti-oxidative, hepatoprotective, anti-cancer, anti-microbial and CYP3A4 activating salutations of . This warrants further studies towards isolation and identification of its therapeutically active principles.
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http://dx.doi.org/10.1016/j.sjbs.2020.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499106PMC
October 2020

Oncoglabrinol C, a new flavan from protects endothelial cells against oxidative stress and apoptosis, and modulates hepatic CYP3A4 activity.

Saudi Pharm J 2020 Jun 19;28(6):648-656. Epub 2020 Apr 19.

Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

Active herbal or natural compounds have high chemical diversity and specificity than synthetic drugs. Recently, we have validated the hypoglycemic salutation of in rodent model, and demonstrated the activation of PPARα/γ by its newly ioslated flavan derivative Oncoglabrinol C (5,3'-Dihydroxyflavan 7-4'--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.
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http://dx.doi.org/10.1016/j.jsps.2020.04.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292873PMC
June 2020

Bioassay-guided isolation of anti-hepatitis B virus flavonoid myricetin-3--rhamnoside along with quercetin from leaves.

Saudi Pharm J 2020 May 19;28(5):550-559. Epub 2020 Mar 19.

Department of Pharmaceutical Chemistry, Al-Neelain University, Khartoum, Sudan.

Recently, we have shown anti-hepatitis B virus (HBV) activity of J.F. Gmel leaves, and Identified quercetin and other flavonoids by HPTLC. Here we report bioassay-directed fractionation of leaves using column chromatography and isolation of two flavonoinds from the -butanol fraction, their structure determination (H NMR, 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--rhamnoside. Quercetin significantly inhibited synthesis of HBsAg and HBeAg by about 60% and 62%, respectively as compared to myricetin-3--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--rhamnoside along with quercetin isolated from leaves. Their possible mode of anti-HBV activities are suggested through binding with viral Pol/RT and Core as well as host NTCP proteins.
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http://dx.doi.org/10.1016/j.jsps.2020.03.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229332PMC
May 2020

Cell proliferation activity delineated by molecular docking of four new compounds isolated from the aerial parts of Forssk. ex. J.F. Gmel.

Saudi Pharm J 2020 Feb 7;28(2):172-186. Epub 2019 Dec 7.

Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia.

Using different chromatographic methods, four new compounds were isolated from the aerial parts of (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)--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 10-10 M 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.
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http://dx.doi.org/10.1016/j.jsps.2019.11.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000348PMC
February 2020

Novel polycyclic pyrroloquinazoline alkaloids from and their biological activity.

J Asian Nat Prod Res 2020 Dec 23;22(12):1159-1167. Epub 2019 Dec 23.

Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.

Two new polycyclic pyrroloquinazoline alkaloids with unprecedented skeleton, anisulcusines A () and B (), along with four known compounds (-), were identified from the aerial parts of (Forssk.) Nees. To our knowledge, anisulcusines A and B are the first polycyclic pyrroloquinazoline alkaloids that possess a unique -methyl-1,2-dihydro-1'-spiro[benzo[][1,3]oxazine moiety. The chemical structures of the new compounds were elucidated through extensive spectroscopic analyses and high-resolution mass spectroscopy. Anisulcusine B () exerted moderate cytotoxic effect on cultured human hepatoma (HuH7) cells, whereas compounds and - exhibited mild cell proliferative or growth stimulatory activity. HIGHLIGHTS Two new polycyclic pyrroloquinazoline alkaloids from . Structures were elucidated on the basis of 1D- and 2D-NMR and HR-ESI-MS spectra. Compound () exerted moderate cytotoxic effect against human hepatoma (HuH7) cells. Compounds (, -) exhibited mild cell proliferative or growth stimulatory activity.
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http://dx.doi.org/10.1080/10286020.2019.1694514DOI Listing
December 2020

The anti-hepatitis B virus therapeutic potential of anthraquinones derived from Aloe vera.

Phytother Res 2019 Nov 13;33(11):2960-2970. Epub 2019 Aug 13.

Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

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.
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http://dx.doi.org/10.1002/ptr.6471DOI Listing
November 2019

Proanthocyanidins from the stem bark of Rhus tripartita ameliorate methylgloxal-induced endothelial cell apoptosis.

J Food Drug Anal 2019 07 17;27(3):758-765. Epub 2019 Mar 17.

Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.

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.
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http://dx.doi.org/10.1016/j.jfda.2019.02.002DOI Listing
July 2019

Hepatoprotective effect of Solanum surattense leaf extract against chemical- induced oxidative and apoptotic injury in rats.

BMC Complement Altern Med 2019 Jul 3;19(1):154. Epub 2019 Jul 3.

Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

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)-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-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.
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http://dx.doi.org/10.1186/s12906-019-2553-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610804PMC
July 2019

The and anti-hepatotoxic, anti-hepatitis B virus and hepatic CYP450 modulating potential of .

Saudi Pharm J 2019 May 5;27(4):558-564. Epub 2019 Feb 5.

Department of Biosciences, Rani Durgavati University, Jabalpur 482001, India.

In the present study we investigated the hepatotoprotective, hepatitis B virus (HBV) inhibitory and hepatic CYP450 enzyme (CYP3A4) modulatory potential of rhizome fractions. The crude ethanol-extract, including different organic and aqueous fractions were tested for cytoprotection on HepG2 cells (MTT assay), followed by evaluation in Wistar rats (serum biochemistry and lipid profile). The 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-injured rats, oral administration of (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, showed very promising hepatoprotective and anti-HBV potential in experimental settings In addition, this is the first report on modulation of CYP3A4 by 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 in metabolic liver disorder and hepatitis B patients.
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http://dx.doi.org/10.1016/j.jsps.2019.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488921PMC
May 2019

Plant-derived antiviral drugs as novel hepatitis B virus inhibitors: Cell culture and molecular docking study.

Saudi Pharm J 2019 Mar 26;27(3):389-400. Epub 2018 Dec 26.

Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.

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.
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http://dx.doi.org/10.1016/j.jsps.2018.12.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439212PMC
March 2019

Herb-Drug Interactions and Hepatotoxicity.

Curr Drug Metab 2019 ;20(4):275-282

National Agri-Food Biotechnology Institute, Mohali, Punjab 140306, India.

Background: In recent times, herbals or phytomedicines have become very popular due to their global acceptance as a complementary and alternative remedy. While modern drugs are commercially available only after laboratory validations, clinical trials, as well as approval from drug regulatory authorities, majority of the marketed herbal products lack such scientific evidence of efficacy and safety. This results in herb or herb-drug interaction induced unfavorable clinical outcomes without crucial documentation on their temporal relations and concomitant use.

Methods: An online literature search for peer-reviewed articles was conducted on the PubMed, Europe PMC, Medline and Google Scholar portals, using the phrases: complementary & alternative medicine, traditional Chinese medicine, herb-drug interaction, mechanisms of herb-drug interaction, herb-induced toxicity, herbal hepatotoxicity and causality, traditional medicine, viral hepatitis, etc.

Results: The retrieved data showed that globally, patients are attracted to herbal remedies with the misconception that these are completely safe and therefore, use them simultaneously with prescription drugs. Notably, there exists a potential risk of herb-drug interactions leading to some adverse side effects, including hepatotoxicity. The toxicological effect of a drug or herb is due to the inhibition of drug metabolizing enzymes (e.g., cytochrome P450), including interactions with certain prescription drugs through various mechanisms. Several cases of hepatotoxicity due to use of herbals in viral hepatitis-related liver diseases have been recently reported. However, limited experimental data and clinical evidence on herbal pharmacokinetics hamper the evaluation and reporting of adverse reactions and the underlying mechanisms.

Conclusion: Herb-drug interaction related morbidity is thus an emerging serious public health issue with broad implications for clinicians, pharmaceutical industries and health authorities. Nonetheless, despite increasing recognition of herb-drug interaction, a standard system for interaction prediction and evaluation is still nonexistent. This review article discusses the herb-drug interactions related hepatotoxicity and underlying mechanisms, including drug metabolizing enzymes and their regulation.
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http://dx.doi.org/10.2174/1389200220666190325141422DOI Listing
November 2019

Novel plant inducers of PXR-dependent cytochrome P450 3A4 expression in HepG2 cells.

Saudi Pharm J 2018 Dec 1;26(8):1069-1072. Epub 2018 Jun 1.

Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.

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, (2.62 fold;  < 0.0001) was found to be the most promising inducer of CYP3A4, followed by (1.95 fold;  = 0.0004), (1.74 fold,  = 0.0035), and (1.65 fold;  = 0.0097). Further phytochemical characterizations of the active plants are therefore, warranted.
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http://dx.doi.org/10.1016/j.jsps.2018.05.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260467PMC
December 2018

Molecular Analysis and Modeling of Hepatitis E Virus Helicase and Identification of Novel Inhibitors by Virtual Screening.

Biomed Res Int 2018 30;2018:5753804. Epub 2018 Aug 30.

School of Computational and Integrative Sciences, Jawaharlal Nehru University, New Delhi, India.

The hepatitis E virus- (HEV-) helicase as a novel drug-target was evaluated. While cell culture model was used for mutational characterization of helicase, protein modeling and virtual screening were employed to identify helicase inhibitors. None of the saturation mutant replicons significantly affected RNA replication. Notably, mutants encompassing the Walker motifs replicated as wild-type, showing indispensability of nucleotides conservation in viability compared to known criticality of amino acids. A 3D modeling of HEV-helicase and screening of a compound dataset identified ten most promising inhibitors with drug likeness, notably, JFD02650, RDR03130, and HTS11136 that interacted with Walker A residues Gly975, Gly978, Ser979, and Gly980. Our model building and virtual identification of novel helicase inhibitors warrant further studies towards developing anti-HEV drugs.
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http://dx.doi.org/10.1155/2018/5753804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6136533PMC
December 2018

Analysis of antioxidative and antiviral biomarkers β-amyrin, β-sitosterol, lupeol, ursolic acid in leaves extract by validated HPTLC methods.

Saudi Pharm J 2018 Jul 9;26(5):685-693. Epub 2018 Feb 9.

Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.

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 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 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 that could be adopted for standardization and quality-control of herbal-formulations.
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http://dx.doi.org/10.1016/j.jsps.2018.02.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6035322PMC
July 2018

Protective effect of extract against oxidative and apoptotic hepatotoxicity.

Exp Ther Med 2018 Apr 2;15(4):3883-3891. Epub 2018 Mar 2.

Medicinal, Aromatic and Poisonous Plants Research Center, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.

I. Verd is a known phytomedicinal species of ; however, studies into its bioactivity remain inconclusive. The and antioxidative and hepatoprotective potential of 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 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 against chemical-induced oxidative stress and liver damage.
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http://dx.doi.org/10.3892/etm.2018.5919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5863606PMC
April 2018

A novel monocyclic triterpenoid and a norsesquaterpenol from the aerial parts of Forssk. ex J.F. Gmel with cell proliferative potential.

Saudi Pharm J 2017 Nov 31;25(7):1005-1010. Epub 2017 Mar 31.

Department of Pharmacognosy & Phytochemistry, College of Pharmacy, Prince Sattam Binabdulaziz University, Al-Kharj, Riyadh, Saudi Arabia.

Forssk. ex J.F. Gmel (Chenopodiaceae), a mangrove herb, is distributed in tropical Africa, Arabian Peninsula, India, Pakistan, Palestine and Jordan. The plant parts are used to treat sore throat, hepatitis, wounds, rheumatism, paralysis, asthma, snakebites, skin disease and ulcer. Two new phytoconstituents characterized as 13,17-octahydropentalene-4,4,10,23-tetramethyl-17,21-diisopropyl-tetradecahydrocyclo-[a]-phenanthrene-(14), 20(23), 21(30)-trien-5α-ol (SMC-3) and [1,4,4-trimethyl-cyclopent-1(5)-enyl]-9,10,17,21-tetramethyl-9α-ol-16α (17α)-epoxy heptadecan-6,10-dione (SMC-4) belong to the class norsesquaterpenol and monocyclic triterpenoid, respectively, along with two known compounds 3-epi-lupeol (SMC-1) and 4-cyclopentylpyrocatechol (SMC-2) have been isolated from the ethanol extract of aerial parts of using normal and reverse phase column as well as planar chromatography. The spectroscopic studies including 1D, 2D NMR (DEPT, COSY, HMBC and HSQC) aided by EIMS mass and IR spectra were used to establish their structures. All the four compounds were tested for cytotoxicity on cultured HepG2 cells and for cell proliferation activities. The results revealed no cytotoxicity even at highest (6.25-50 μg/ml) dose of all the four compounds. The compound SMC-1 showed prominent cell proliferative activity as compared to other SMC compounds.
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http://dx.doi.org/10.1016/j.jsps.2017.03.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5681308PMC
November 2017

Isolation and validated HPTLC analysis of four cytotoxic compounds, including a new sesquiterpene from aerial parts of Plectranthus cylindraceus.

Nat Prod Res 2018 Apr 8;32(7):804-809. Epub 2017 Aug 8.

a Department of Pharmacognosy, College of Pharmacy , King Saud University , Riyadh , Saudi Arabia.

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 (H & 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 (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.
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http://dx.doi.org/10.1080/14786419.2017.1363750DOI Listing
April 2018

Evolution and Emergence of Pathogenic Viruses: Past, Present, and Future.

Intervirology 2017 4;60(1-2):1-7. Epub 2017 Aug 4.

Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

Incidences of emerging/re-emerging deadly viral infections have significantly affected human health despite extraordinary progress in the area of biomedical knowledge. The best examples are the recurring outbreaks of dengue and chikungunya fever in tropical and sub-tropical regions, the recent epidemic of Zika in the Americas and the Caribbean, and the SARS, MERS, and influenza A outbreaks across the globe. The established natural reservoirs of human viruses are mainly farm animals, and, to a lesser extent, wild animals and arthropods. The intricate "host-pathogen-environment" relationship remains the key to understanding the emergence/re-emergence of pathogenic viruses. High population density, rampant constructions, poor sanitation, changing climate, and the introduction of anthropophilic vectors create selective pressure on host-pathogen reservoirs. Nevertheless, the knowledge and understanding of such zoonoses and pathogen diversity in their known non-human reservoirs are very limited. Prevention of arboviral infections using vector control methods has not been very successful. Currently, new approaches to protect against food-borne infections, such as consuming only properly cooked meats and animal products, are the most effective control measures. Though significant progress in controlling human immunodeficiency virus and hepatitis viruses has been achieved, the unpredictable nature of evolving viruses and the rare occasions of outbreaks severely hamper control and preventive modalities.
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http://dx.doi.org/10.1159/000478729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179518PMC
May 2018

Comparative study of antioxidant activity and validated RP-HPTLC analysis of rutin in the leaves of different species grown in Saudi Arabia.

Saudi Pharm J 2017 Jul 5;25(5):715-723. Epub 2016 Nov 5.

Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia.

The present study assessed the comparative antioxidant potential of the ethanol extract (EE) of leaves of four species (, AS; , AL; AH; and , AT) grown in Saudi Arabia, including RP-HPTLC quantification of antioxidant biomarker rutin. DPPH radical scavenging and β-carotene-linoleic acid bleaching assays showed the promising antioxidant activities of extracts: ASEE (IC: 60.39 and 324.65 μg/ml) >ALEE (IC: 217.06 and 423.36 μg/ml) >ATEE (IC: 250.13 and 747.50 μg/ml) >AHEE (IC: 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 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 ( = 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 species, especially . The developed RP-HPTLC method therefore, affirms its application in the quality control of commercialized herbal drugs or formulation containing rutin.
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http://dx.doi.org/10.1016/j.jsps.2016.10.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5506739PMC
July 2017

Prevalence of UDP-glucuronosyltransferase polymorphisms (UGT1A6∗2, 1A7∗12, 1A8∗3, 1A9∗3, 2B7∗2, and 2B15∗2) in a Saudi population.

Saudi Pharm J 2017 Feb 2;25(2):224-230. Epub 2016 Jun 2.

Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

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.
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http://dx.doi.org/10.1016/j.jsps.2016.05.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355556PMC
February 2017

High-performance thin layer chromatography based assay and stress study of a rare steroidal alkaloid solanopubamine in six species of grown in Saudi Arabia.

Saudi Pharm J 2017 Feb 26;25(2):184-195. Epub 2016 May 26.

Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

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 extracted with two different solvents. The species selected for investigation include (SS), (SV), (SC), (SG), (SI) and (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  = 0.39 ± 0.01. The steroidal alkaloid SPN was observed to be present only in extracts of aerial parts of . The sensitivity of developed method produced 40 ng and 115 ng band, respectively as LOD and LOQ values. The percentage yield of SPN in aerial parts of 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 HO 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.
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http://dx.doi.org/10.1016/j.jsps.2016.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355553PMC
February 2017

Quantitative analysis of rutin, quercetin, naringenin, and gallic acid by validated RP- and NP-HPTLC methods for quality control of anti-HBV active extract of Guiera senegalensis.

Pharm Biol 2017 Dec;55(1):1317-1323

a Department of Pharmacognosy, College of Pharmacy , King Saud University , Riyadh , Saudi Arabia.

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-RP18 and 60F, respectively. The methods were validated according to the ICH guidelines.

Results: Well-separated and compact spots (R) 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) 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.
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http://dx.doi.org/10.1080/13880209.2017.1300175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6130481PMC
December 2017

New Cytotoxic Seco-Type Triterpene and Labdane-Type Diterpenes from Nuxia oppositifolia.

Molecules 2017 Mar 2;22(3). Epub 2017 Mar 2.

Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.

Chromatographic purification of the -hexane and dichloromethane extracts of 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 (), 2β-acetoxy-7-oxolabda-8-en-15-oic acid (), 2β-acetoxy-6-oxolabda-7-en-15-oic acid (), and one new seco-triterpene, 3,4-seco olean-12-en-3,30 dioic acid (), together with 10 known lupane, oleanane and ursane-type triterpenes, as well as the common phytosterols, β-sitosterol and stigmasterol (-). 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.
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http://dx.doi.org/10.3390/molecules22030389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6155346PMC
March 2017

Treatment with Rhus tripartita extract curtails isoproterenol-elicited cardiotoxicity and oxidative stress in rats.

BMC Complement Altern Med 2016 Sep 8;16:351. Epub 2016 Sep 8.

Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium.

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.
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http://dx.doi.org/10.1186/s12906-016-1318-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5017009PMC
September 2016

Therapeutic efficacy of ethanolic extract of Aerva javanica aerial parts in the amelioration of CCl4-induced hepatotoxicity and oxidative damage in rats.

Food Nutr Res 2016 7;60:30864. Epub 2016 Apr 7.

Medicinal, Aromatic and Poisonous Plants Research Center, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

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.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826463PMC
http://dx.doi.org/10.3402/fnr.v60.30864DOI Listing
April 2016

Design, Synthesis and Anticancer Evaluation of Novel Quinazoline-Sulfonamide Hybrids.

Molecules 2016 Feb 4;21(2). Epub 2016 Feb 4.

Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.

By combining the structural features of quinazoline and sulfonamides, novel hybrid compounds 2-21 were synthesized using a simple and convenient method. Evaluation of these compounds against different cell lines identified compounds 7 and 17 as most active anticancer agents as they showed effectiveness on the four tested cell lines. The anticancer screening results of the tested compounds provides an encouraging framework that could lead to the development of potent new anticancer agents.
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http://dx.doi.org/10.3390/molecules21020189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274562PMC
February 2016

'Ajwa' dates (Phoenix dactylifera L.) extract ameliorates isoproterenol-induced cardiomyopathy through downregulation of oxidative, inflammatory and apoptotic molecules in rodent model.

Phytomedicine 2016 Oct 14;23(11):1240-8. Epub 2015 Dec 14.

Center for Medicinal, Aromatic and Poisonous Plants Research, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.

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.
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http://dx.doi.org/10.1016/j.phymed.2015.10.019DOI Listing
October 2016
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