Synthesis of Competitive and Noncompetitive Inhibitors of Alpha-Glucosidase and Anticancer Agents.

Imidazoles and phenylthiazoles are an important class of heterocycles that demonstrate a wide range of biological activities against various types of cancers, diabetes mellitus and pathogenic microorganisms. The heterocyclic structure having oxothiazolidine moiety is an important scaffold present in various drugs, with potential for enzyme inhibition. In an effort to discover new heterocyclic compounds, we synthesized 26 new 4,5-diphenyl-1H-imidazole, phenylthiazole, and oxothiazolidine heterocyclic analogues that demonstrated potent α-glucosidase inhibition and anticancer activities. Majority of the compounds noncompetitively inhibited α-glucosidase except for two that exhibited competitive inhibition of the enzyme. Docking results suggested that the noncompetitive inhibitors bind to an apparent allosteric site on the enzyme located in the vicinity of the active site. Additionally, the analogues also exhibited significant activity against various types of cancers including non-small lung cancer. Since tubulin protein plays an important role in the pathogenesis of non-small lung cancer, molecular docking with one of the target compounds provided important clues to its binding mode. The current work on imidazoles and phenylthiazole derivatives bears importance for designing of new antidiabetic and anticancer drugs.

Marine Natural Compound (Neviotin A) Displays Anticancer Efficacy by Triggering Transcriptomic Alterations and Cell Death in MCF-7 Cells.

We investigated the anticancer mechanism of a chloroform extract of marine sponge (Haliclona fascigera) (sample C) in human breast adenocarcinoma (MCF-7) cells. Viability analysis using MTT and neutral red uptake (NRU) assays showed that sample C exposure decreased the proliferation of cells. Flow cytometric data exhibited reactive oxygen species (ROS), nitric oxide (NO), dysfunction of mitochondrial potential, and apoptosis in sample C-treated MCF-7 cells. A qPCR array of sample C-treated MCF-7 cells showed crosstalk between different pathways of apoptosis, especially BIRC5, BCL2L2, and TNFRSF1A genes. Immunofluorescence analysis affirmed the localization of p53, bax, bcl2, MAPKPK2, PARP-1, and caspase-3 proteins in exposed cells. Bioassay-guided fractionation of sample C revealed Neviotin A as the most active compound triggering maximum cell death in MCF-7, indicating its pharmacological potency for the development of a drug for the treatment of human breast cancer.

The anti-oxidative, anti-cell proliferative and anti-microbial efficacies of cold-adapted Crepis flexuosa: HPTLC and GC/MS analyses.

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 (IC50: 42.45 µg/ml) and CF-Aqua (IC50: 46.37 µg/ml) on HepG2, followed by CF-Hex (IC50: 63.24 µg/ml) and CF-ButOH (IC50: 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.

Sterols and Triterpenes from Dobera glabra Growing in Saudi Arabia and Their Cytotoxic Activity.

A new lupane caffeoyl ester, lup-20(29)-ene 3ß-caffeate-30-al (7), and a new oleanane-type triterpene, 3ß-hydroxyolean-13(18)-en-12-one (17), were isolated from the aerial parts of Dobera glabra (Forssk), along with ten known triterpenes, including seven lupane-type lupeol (1), 30-nor-lup-3ß-ol-20-one (2), ∆1-lupenone (3), lup-20(29)-en-3ß,30-diol (4), lupeol caffeate (5), 30-hydroxy lup-20(29)-ene 3ß-caffeate (6), and betunaldehyde (8); three oleanane-type compounds were also identified, comprising δ-amyrone (15), δ-amyrin (16), and 11-oxo-ß-amyrin (18); together with six sterols, comprising ß-sitosterol (9), stigmasterol (10), 7α-hydroxy-ß-sitosterol (11), 7α-hydroxy-stigmasterol (12), 7-keto-ß-sitosterol (13), and 7-keto-stigmasterol (14). Their structures were elucidated using a variety of spectroscopic techniques, including 1D (1H, 13C, and DEPT-135 13C) and 2D (1H-1H COSY, 1H-13C HSQC, and 1H-13C HMBC) nuclear magnetic resonance (NMR) and accurate mass spectroscopy. Subsequently, the different plant extracts and some of the isolated compounds (1-9, 11 and 13) were investigated for their possible cytotoxic activity in comparison to cisplatin against a wide array of aggressive cancer cell lines, such as colorectal cancer (HCT-116), hepatocellular carcinoma (HepG-2), and prostate cancer (PC-3) cell lines. Compound 11 displayed broad cytotoxicity against all of the tested cell lines (IC50 ≅ 8 µg/mL in all cases), and a high safety margin against normal Vero cells (IC50 = 70 µg/mL), suggesting that 11 may be a highly selective and effective anticancer agent candidate. Notably, the evidence indicated that the mode of action of compound 11 could possibly consist of the inhibition of phosphodiesterase I (80.2% enzyme inhibition observed at 2 µM compound concentration).

Identification of potential TNF-α inhibitors: from in silico to in vitro studies.

Tumor Necrosis Factor Alpha (TNF-α) is a pleiotropic pro-inflammatory cytokine. It act as central biological regulator in critical immune functions, but its dysregulation has been linked with a number of diseases. Inhibition of TNF-α has considerable therapeutic potential for diseases such as cancer, diabetes, and especially autoimmune diseases. Despite the fact that many small molecule inhibitors have been identified against TNF-α, no orally active drug has been reported yet which demand an urgent need of a small molecule drug against TNF-α. This study focuses on the development of ligand-based selective pharmacophore model to perform virtual screening of plant origin natural product database for the identification of potential inhibitors against TNF-α. The resultant hits, identified as actives were evaluated by molecular docking studies to get insight into their potential binding interaction with the target protein. Based on pharmacophore matching, interacting residues, docking score, more affinity towards TNF-α with diverse scaffolds five compounds were selected for in vitro activity study. Experimental validation led to the identification of three chemically diverse potential compounds with the IC50 32.5 ± 4.5 µM, 6.5 ± 0.8 µM and 27.4 ± 1.7 µM, respectively.

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

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.

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

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 (1H NMR, 13C 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.

Tambulin from Zanthoxylum armatum acutely potentiates the glucose-induced insulin secretion via KATP-independent Ca2+-dependent amplifying pathway.

Tambulin, a flavonol isolated from Zanthoxylum armatum, showed potent insulin secretory activity in our preliminary anti-diabetic screening. Here, we explored the insulin secretory mechanism(s) of tambulin focusing in glucose-dependent, KATP ‒ and Ca2+‒channels dependent, and cAMP-PKA pathways. Mice islets and MIN6 cells were incubated with tambulin in the presence of pharmacological agonists/antagonists and the secreted insulin was measured using mouse insulin ELISA kit. The intracellular cAMP was measured by an acetylation cAMP ELISA kit. Tambulin (200 µM) showed potent insulin secretory activity only at stimulatory glucose (11-25 mM) concentrations; however, no change in insulin release was observed at basal glucose both in mice islets and MIN6 cells. Notably, in the presence of diazoxide, a KATP channel opener; the incomplete inhibition of tambulin-induced insulin secretion was observed whereas, complete inhibition was found using verapamil, an L-type Ca2+ channel blocker. Furthermore, the insulinotropic potential of tambulin was amplified in tolbutamide treated, and depolarized islets suggest tambulin's target other than tolbutamide. Tambulin showed no additive effect in the IBMX-induced intracellular cAMP; whereas, exerted an additive effect in the IBMX-induced insulin secretion. Furthermore, tambulin-induced insulin secretion was dramatically inhibited by PKA inhibitor (H-89), while moderate inhibition was found by using PKC inhibitor (calphostin C). Molecular docking studies also showed the best binding affinities of tambulin with PKA suggest the PKA dependent signaling cascade is involved more in tambulin-induced insulin secretion. Based on these findings, it is concluded that tambulin stimulates insulin secretion in a Ca2+ channel-dependent but KATP channel-independent manner, most likely by activating the cAMP-PKA pathway.

Analysis of Chemical Composition and Assessment of Cytotoxic, Antimicrobial, and Antioxidant Activities of the Essential Oil of Meriandra dianthera Growing in Saudi Arabia.

The essential oil of Meriandra dianthera (Konig ex Roxb.) Benth. (Synonym: Meriandra bengalensis, Lamiaceae) collected from Saudi Arabia was studied utilizing GC and GC/MS. Forty four constituents were identified, representing 96.8% of the total oil. The M. dianthera essential oil (MDEO) was characterized by a high content of oxygenated monoterpenes (76.2%). Camphor (54.3%) was the major compound in MDEO followed by 1,8-cineole (12.2%) and camphene (10.4%). Moreover, MDEO was assessed for its cytotoxic, antimicrobial, and antioxidant activities. MDEO demonstrated an interesting cytotoxic activity against all cancer cell lines with IC50 values of 83.6 to 91.2 µg/mL, especially against MCF-7 cancer cells. Using labeling with annexin VFITC and/or propidium iodide (PI) dyes and flow cytometer analysis, the apoptosis induction was quantitatively confirmed for MCF-7 cells. The MDEO exhibited a considerable antimicrobial activity against all bacterial and fungal strains with minimum inhibitory concentration (MIC)-values of 0.07 to 1.25 mg/mL. The most sensitive microbial strain was Staphylococcus aureus (MIC: 0.07 mg/mL). Minimum bactericidal concentration (MBC) or minimum fungicidal concentration (MFC) values were determined one time higher than that of MIC's. Additionally, the MDEO revealed a strong activity for reducing ß-carotene bleaching with a total antioxidant value of 72.6% and significant DPPH free radical scavenging activity (78.4%) at the concentration 1000 µg/mL.

Phytochemical analysis and anti-diabetic, anti-inflammatory and antioxidant activities of Loranthus acaciae Zucc. Grown in Saudi Arabia.

The Loranthus genus has been demonstrated to be used in the treatment of wide range of diseases e.g. diabetes, inflammations and cancers. Many species of Loranthus represent a major source of biologically active constituents. Therefore, our study was carried out to investigate the anti-diabetic, anti-inflammatory and antioxidant effects of Loranthus acaciae Zucc. (Loranthaceae) grown in Saudi Arabia. Moreover, our research concerned the guided-fractionation and isolation of possible active compounds from this species. The crude ethanolic extract and its n-hexane, chloroform and n-butanol fractions were investigated for antidiabetic activity utilizing two methods namely, in alloxan-induced diabetic rats and glucose tolerance test in normal rats. Additionally, the anti-inflammatory activity was studied by the carrageenan-induced rat paw oedema method while DPPH free radical scavenging and ß-carotene bleaching assays were utilized to determine the antioxidant activity. Various chromatographic and spectroscopic techniques were utilized for the isolation and characterization of the active compounds. Our results exhibited that the crude extract and chloroform fraction has the greatest hypoglycemic and antidiabetic effects. The chloroform fraction and crude extract produced at a dose of 500 mg/kg a significant hypoglycemic effect in diabetic rats with 47.0 and 33.6% reduction in blood sugar levels and in normoglycemic rats 35.6 and 35.4% respectively. A potent anti-inflammatory effect (67.2% at 500 mg/kg) was detected for the chloroform fraction. In addition, the chloroform fraction exhibited a high antioxidative and DPPH-radical inhibitory activity (85.4 and 88.3% respectively). The phytochemical analysis of L. acaciae led to the isolation and characterization of four compounds namely, quercetin 3-O-ß-D-glucopyranoside (compound 1), quercetin 3-O-ß-(6-O-galloyl)-glucopyranoside (compound 2), (-) catechin (compound 3), and catechin 7-O-gallate (compound 4). Among these compounds quercetin 3-O-ß-D- glucopyranoside, quercetin 3-O-ß-(6-O-galloyl)-glucopyranoside and catechin 7-O-gallate, are isolated for the first time from this plant.

Comparative evaluation of cytotoxic, antimicrobial and antioxidant activities of the crude extracts of three Plectranthus species grown in Saudi Arabia.

Natural products from medicinal plants represent major resource of novel therapeutic substances for combating serious diseases including cancers and microbial infections. The genus Plectranthus (Family: Labiatae) represents a large and widespread group of species with a diversity of traditional uses in treatment of various ailments. Therefore, this research study aimed to evaluate the cytotoxic, antimicrobial and antioxidant activities of three Plectranthus species growing in Saudi Arabia namely P. cylindraceus Hocst. ex Benth., P. asirensis JRI Wood and P. barbatus Andrews. Moreover, this work focused on the isolation of the active constituents responsible for the activities from the most active Plectranthus species. The extracts were tested for their cytotoxic activity against three cancer cell lines (Hela, HepG2 and HT-29), using MTT-test, antimicrobial activity against Gram positive, Gram negative bacterial and fungal strains using broth micro-dilution assay for minimum inhibitory and bactericidal concentrations (MIC and MBC) and antioxidant activity using scavenging activity of DPPH radical and ß-carotene-linoleic acid methods. The ethanolic extracts of the Plectranthus species showed remarkable cytotoxic activity against all cancer cell lines with IC50 values ranging between 10.1 ±â€¯0.33 to 102.6 ±â€¯8.66 µg/mL and a great and antimicrobial activity with MIC values between 62.5 and 250 µg/mL. In addition, the three Plectranthus species showed almost moderate antioxidant activity. The most interesting cytotoxic and antimicrobial results were observed with the extract of P. barbatus. Consequently, this extract was partitioned between water and n-hexane, chloroform and n-butanol and tested. The cytotoxic activity resided predominantly in the n-hexane and chloroform fractions. The analysis of the chloroform fraction led to the isolation of four diterpenoid compounds, two of labdane- and two of abietane-type, which were identified as coleonol B, forskolin, sugiol and 5,6-dehydrosugiol. Purification of the n-hexane fraction led to isolation of a major abietane-type diterpene, which was identified as ferruginol. Sugiol, 5,6-dehydrosugiol and ferruginol were isolated for the first time from P. barbatus in this study. The isolated diterpenoids showed variable cytotoxic effects with IC50 values between 15.1 ±â€¯2.03 and 242 ±â€¯13.3 µg/mL, a great antimicrobial activity with MIC values between 15.6 and 129 µg/mL and a total antioxidant activity ranging from 23.1 ±â€¯2.9 to 69.2 ±â€¯3.8%.

Phytochemical analysis and evaluation of the cytotoxic, antimicrobial and antioxidant activities of essential oils from three Plectranthus species grown in Saudi Arabia.

BACKGROUND: Cancers and microbial infections are still a major health problem, therefore research on new anticancer and antimicrobial agents ought to be continued. Natural products including essential oils from medicinal plants continue to be an important resource to manage various diseases. Thus, the particular objectives of this study are to investigate the chemical composition, cytotoxic, antimicrobial and antioxidant activities of three Plectranthus species namely P. cylindraceus Hocst. ex Benth., P. asirensis JRI Wood and P. barbatus Andrews grown in Saudi Arabia. METHODS: The essential oils of the three Plectranthus species were obtained by hydrodistllation and analyzed using GC/FID and GC-MS. The essential oils were further assessed for their cytotoxic, antimicrobial and antioxidant activities. Determination of the cytotoxic activity was carried out against Hela, HepG2 and HT-29 cancer cell lines by utilizing MTT-assay. The antimicrobial activity was assessed against six bacterial and fungal strains by using broth micro-dilution assay. In addition, the antioxidant activity was evaluated utilizing the DPPH and ß-Carotene-linoleic acid assays. RESULTS: The GC/FID and GC-MS analysis led to the identification of 59, 60 and 42 compounds representing 89.0% 95.0 and 97.1% of the total essential oils of P. cylindraceus, P. asirensis and P. barbatus, respectively. The essential oils were characterized by a high content of oxygenated sesquiterpenes in P. cylindraceus, sesquiterpene hydrocarbons in P. asirensis and monoterpene hydrocarbons in P. barbatus where maaliol (42.8%), ß-caryophyllene (13.3%) and α-pinene, (46.2%) were the predominant compounds. Additionally, the oils particularly of P. cylindraceus and P. barbatus exhibited remarkable cytotoxic and antimicrobial activities with IC50-values between 3.8 and 7.5 µg/mL and MIC-values ranging from 0.137 to 4.40 mg/mL. Moreover, the oils showed moderate to high radical scavenging and antioxidative activities ranging from 52 to 75% at the highest concentration of 1 mg/mL. CONCLUSIONS: The observed results back the suggestion that these three Plectranthus species represent a promising source of cytotoxic and antimicrobial agents.

Protective effect of Atriplex suberecta extract against oxidative and apoptotic hepatotoxicity.

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 ß-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.

Two New Sesquiterpene Alcohols Isolated from Senecio hadiensis Forssk. Grown in Saudi Arabia.

Phytochemical investigation on the aerial parts of Senecio hadiensis Forssk. led to the isolation of two new sesquiterpenoids, presilphiperfolan-2α,5α,8α-triol (1) and presilphiperfolan-2α,5α,8α,10α-tetraol (2) featuring the rare presilphiperfolane-type frameworks. The structures of 1 and 2 were elucidated on the basis of extensive spectroscopic (1D- and 2D-NMR, HR-ESI-MS) methods and by comparison with the literature data. The isolates 1 and 2 were evaluated in-vitro for antiinflammatory, cytotoxic, and peroxisome proliferator activated receptor alpha and gamma (PPARα and PPARγ) agonistic activities.

Neoclerodane Diterpenoids from Reehal Fatima, Teucrium yemense.

Teucrium yemense (Defl), locally known as Reehal Fatima, is a medicinal plant commonly grown in Saudi Arabia and Yemen. Phytochemical investigation of the aerial parts of T. yemense yielded six new neoclerodane diterpenoids, namely fatimanol A-E (1, 2, 3, 5, and 6) and fatimanone (4), and the known teulepicephin (7). As both the Teucrium genus and the related Lamiaceae family have previously been widely reported to possess anthelmintic and antimicrobial activities, the structural and biological characterization of the seven diterpenoids was pursued. The structures of the new compounds were elucidated from their 2D NMR and MS profiles and by comparison to related compounds. The structure of fatimanol D (5) was confirmed by X-ray crystallographic analysis. The new structures contribute to the breadth of knowledge of secondary metabolites in this genus.

Antimicrobial, anticancer, and antioxidant compounds from Premna resinosa growing in Saudi Arabia.

CONTEXT: Premna resinosa (Hochst.) Schauer (Lamiaceae) is used in many places to treat bronchitis, respiratory illness and convulsions of the rib cage. OBJECTIVE: This study evaluates the anticancer, antimicrobial and antioxidant activities of P. resinosa, and isolates some responsible constituents. MATERIALS AND METHODS: The methanol extract of P. resinosa aerial parts and its fractions (n-hexane, dichloromethane, ethyl acetate and n-butanol) were tested. Antimicrobial activity was tested using microdilution method against three Gram-positive and four Gram-negative bacteria. The tested concentrations ranged from 4000 to 7.8 µg/mL and MIC values were determined after 24 h incubation. Anticancer activity was evaluated against three human cancer cell lines (Daoy, HepG2 and SK-MEL28) using MTT assay. Antioxidant activity was investigated by DPPH scavenging method and ß-carotene-linoleic acid assay. RESULTS: The greatest antimicrobial activity was exhibited by n-hexane fraction (MIC 10 µg/mL) against Staphylococcus aureus, Enterococcus faecalis, and Shigella flexneri. The n-hexane fraction induced the greatest cytotoxic activity against Daoy, HepG2, and SK-MEL28 cell lines with IC50 values of 9.0, 8.5 and 13.2, respectively. Moreover, the dichloromethane and ethyl acetate fractions showed the highest antioxidant potential. A bioassay-guided fractionation led to the isolation and characterization of seven compounds for the first time, namely, quercetin (1), 3-methoxy quercetin (2), kaempferol (3), 3-methoxy kaempferol (4), myricetin 3,7,3'-trimethyl ether (5), lupeol (6), and stigmasterol (7). CONCLUSION: Our results indicate that P. resinosa is a source for antimicrobial and cytotoxic compounds. However, further work is required to isolate other active principles and to determine the mechanism of action.

Chemical Composition, In Vitro Antimicrobial, Free-Radical-Scavenging and Antioxidant Activities of the Essential Oil of Leucas inflata Benth.

The essential oil of Leucas inflata Balf.f. (Lamiaceae), collected in Yemen, was analyzed using gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) techniques. Forty-three components were recognized, representing 89.2% of the total oil. The L. inflata volatile oil was found to contain a high percentage of aliphatic acids (51.1%). Hexadecanoic acid (32.8%) and n-dodecanoic acid (7.8%) were identified as the major compounds. Oxygenated monoterpenes were distinguished as the second significant group of constituents (16.0%). Camphor (6.1%) and linalool (3.2%) were found to be the main components among the oxygenated monoterpenes. In addition, the volatile oil was assessed for its antimicrobial activity against four bacterial strains and one yeast species using broth micro-dilution assay for minimum inhibitory concentrations (MIC). In addition, antioxidant activity was measured utilizing the anti-radical activity of the sable free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ß-Carotene-linoleic acid assays. The oil of L. inflata showed an excellent antibacterial activity against only the tested Gram-positive bacteria with a MIC-value of 0.81 mg/mL. Furthermore, the oil demonstrated, at a concentration of 1 mg/mL, a weak to moderate antiradical and antioxidant activity of 38% and 32%, respectively.

Antiviral Natural Products Against Chronic Hepatitis B: Recent Developments.

Hepatitis B virus (HBV) is inherently a hepatotropic virus that causes acute and chronic hepatitis in about one-third of world population. Of the estimated 360 million chronically infected individuals, more than one million die of liver cirrhosis, fulminant liver failure or hepatocellular carcinoma (HCC) every year. Though there is an effective vaccine available, failure to protection because of vaccine-escape viral mutants in some population is also reported. Moreover, all the currently approved antiviral drugs have their limitations, too. Interferon (IFN-α) has limited efficacy and a high incidence of adverse side-effects in a proportion of chronic patients. Nucleos(t)ide analogs like, lamivudine, adefovir, tenofovir and entecavir are very effective in treating chronic hepatitis B (CHB), but long-term therapy eventually leads to drug-resistance. As an alternative approach, natural or plant products have provided promising therapeutics in modern pharma industry. Owing to their characteristics of high chemical diversity and biochemical specificity, natural products offer great promises as potentially effective antiviral drugs. A broad spectrum of phytochemicals including flavonoids (e.g., Vogonin), terpenes (e.g., Artemisinin), alkaloids (e.g., Oxymatrine), polyphenolics (e.g., geraniin), saponins (e.g., Astragaloside IV) and lignans (e.g., Helioxanthin) has been isolated and investigated for anti-HBV activities in vitro as well as in vivo. Nevertheless, these promising compounds have different and overlapping mechanisms of action by either inhibiting viral antigens secretion or suppression of DNA replication. The present article reviews the recent developments in anti-HBV natural products.

Hepatoprotective and antiviral efficacy of Acacia mellifera leaves fractions against hepatitis B virus.

The present study investigated the hepatoprotective and anti-HBV efficacy of Acacia mellifera (AM) leaves extracts. The crude ethanolic-extract, including organic and aqueous fractions, were tested for cytotoxicity on HepG2 and HepG2.2.15 cells (IC50=684 µg/mL). Of these, the ethyl acetate and aqueous fractions showed the most promising, dose-dependent hepatoprotection in DCFH-toxicated cells at 48 h. In CCl4-injured rats, oral administration of AM ethanol extract (250 and 500 mg/kg·bw) for three weeks significantly normalized the sera aminotransferases, alkaline phosphatase, bilirubin, cholesterol, triglycerides, and lipoprotein levels and elevated tissue nonprotein sulphydryl and total protein. The histopathology of dissected livers also revealed that AM cured the tissue lesions. The phytochemical screening of the fractions showed presence of alkaloids, flavonoids, tannins, sterols, and saponins. Further, anti-HBV potential of the fractions was evaluated on HepG2.2.15 cells. Of these, the n-butanol and aqueous fractions exhibited the best inhibitory effects on HBsAg and HBeAg expressions in dose- and time-dependent manner. Taken together, while the ethyl acetate and aqueous fractions exhibited the most promising antioxidant/hepatoprotective and anti-HBV activity, respectively, the n-butanol partition showed both activities. Therefore, the therapeutic potential of AM extracts warrants further isolation of the active principle(s) and its phytochemical as well as biological studies.

GC and GC/MS analysis of essential oil composition of the endemic Soqotraen Leucas virgata Balf.f. and its antimicrobial and antioxidant activities.

Leucas virgata Balf.f. (Lamiaceae) was collected from the Island Soqotra (Yemen) and its essential oil was obtained by hydrodistillation. The chemical composition of the oil was investigated by GC and GC-MS. Moreover, the essential oil was evaluated for its antimicrobial activity against two Gram-positive bacteria, two Gram-negative bacteria, and one yeast species by using broth micro-dilution assay for minimum inhibitory concentrations (MIC) and antioxidant activity by measuring the scavenging activity of the DPPH radical. The investigation led to the identification of 43 constituents, representing 93.9% of the total oil. The essential oil of L. virgata was characterized by a high content of oxygenated monoterpenes (50.8%). Camphor (20.5%) exo-fenchol (3.4%), fenchon (5.4%), and borneol (3.1%) were identified as the main components. Oxygenated sesquiterpenes were found as the second major group of compounds (21.0%). ß-Eudesmol (6.1%) and caryophyllene oxide (5.1%) were the major compounds among oxygenated sesquiterpenes. The results of the antimicrobial assay showed that the oil exhibited a great antibacterial activity against the tested S. aureus, B. subtilis, and E. coli. No activity was found against P. aeruginosa and C. albicans. Moreover, the DPPH-radical scavenging assay exhibited only a moderate antioxidant activity (31%) for the oil at the highest concentration tested (1 mg/mL).