Anti‐inflammatory effects of chemical components from Ginkgo biloba L. male flowers on lipopolysaccharide‐stimulated RAW264.7 macrophages

Ginkgo biloba L., well known as living fossil, have various pharmacological activities. Eighteen compounds were isolated from Ginkgo male flowers including a novel matsutake alcohol glycoside, Ginkgoside A ( 1 ), and 17 known compounds—calaliukiuenoside ( 2 ), benzylalcohol O‐α‐l ‐arabinopyranosyl‐(1 → 6)‐β‐d ‐glucopyranoside ( 3 ), amentoflavone ( 4 ), sciadopitysin ( 5 ), bilobetin ( 6 ), isoginkgetin ( 7 ), olivil 4‐O‐β‐d ‐glucopyranoside ( 8 ), dihydrodehydrodiconiferyl alcohol‐4‐O‐β‐d ‐glucoside ( 9 ), (+)‐cyclo‐olivil‐6‐O‐β‐d ‐glucopyranoside ( 10 ), (?)‐isolariciresinol 4‐O‐β‐d ‐glucopyranoside ( 11 ), coniferin ( 12 ), trans‐cinnamic acid‐4‐O‐β‐d ‐glucopyranoside ( 13 ), p‐coumaryl alchol glucoside ( 14 ), stroside B ( 15 ), methylconiferin ( 16 ), cis‐p‐coumaric acid 4‐O‐β‐d ‐glucopyranoside ( 17 ), and cis‐coniferin ( 18 ). Thirteen of these compounds had not previously found in Ginkgo. All extractive fractions and isolated compounds were evaluated for their anti‐inflammatory ability in the lipopolysaccharide‐induced RAW264.7 macrophages. The ethanol extract of Ginkgo flowers and the chloroform and ethyl acetate fractions can significantly decrease nitric oxide (NO), interleukin‐6 (IL‐6), and prostaglandin E₂ (PGE₂) production at 100 μg/ml. The most effective compounds, bilobetin ( 6 ) and isoginkgetin ( 7 ), elevated the NO inhibition ratios to 80.19% and 82.37% at 50 μM, respectively. They also exhibited significant dose‐dependent inhibitory effects on tumor necrosis factor‐α, IL‐6, PGE₂, inducible NO synthase mRNA, and cyclooxygenase‐2 mRNA levels. So they can be promising candidates for the development of new anti‐inflammatory agents.     

Antifungal Saponins from the Maya Medicinal Plant Cestrum schlechtendahlii G. Don (Solanaceae)

Bioassay‐guided fractionation of the crude extract (80% EtOH) of the leaves of Cestrum schlechtendahlii, a plant used by Q'eqchi' Maya healers for treatment of athlete's foot, resulted in the isolation and identification of two spirostanol saponins (1 and 2). Structure elucidation by MS, 1D‐NMR, and 2D‐NMR spectroscopic methods identified them to be the known saponin (25R)‐1β,2α‐dihydroxy‐5α‐spirostan‐3‐β‐yl‐O‐α‐l ‐rhamnopyranosyl‐(1 → 2)‐β‐d ‐galactopyranoside (1) and new saponin (25R)‐1β,2α‐dihydroxy‐5α‐spirostan‐3‐β‐yl‐O‐β‐d ‐galactopyranoside (2). While 2 showed little or no antifungal activity at the highest concentration tested, 1 inhibited growth of Saccharomyces cerevisiae (minimum inhibitory concentration (MIC) of 15–25 μM), Candida albicans, Cryptococcus neoformans, and Fusarium graminearum (MIC of 132–198 μM). Copyright © 2015 John Wiley & Sons, Ltd.     

Biological Activities of Oleanolic Acid Derivatives from Calendula officinalis Seeds

Phytochemical examination of butanol fraction of Calendula officinalis seeds led to the isolation of two compounds identified as 28‐O‐β‐D‐glucopyranosyl‐oleanolic acid 3‐O‐β‐D–glucopyranosyl (1→3)‐β‐D‐glucopyranosiduronic acid (CS1) and oleanolic acid 3‐O‐β‐D–glucopyranosyl (1→3)‐β‐D‐glucopyranosiduronic acid (CS2). Biological evaluation was carried out for these two compounds such as melanin biosynthesis inhibitory, hyaluronic acid production activities, anti obesity using lipase inhibition and adipocyte differentiation as well as evaluation of the protective effect against hydrogen peroxide induced neurotoxicity in neuro‐2A cells. The results showed that, compound CS2 has a melanin biosynthesis stimulatory activity; however, compound CS1 has a potent stimulatory effect for the production of hyaluronic acid on normal human dermal fibroblast from adult (NHDF‐Ad). Both compounds did not show any inhibitory effect on both lipase and adipocyte differentiation. Compound CS2 could protect neuro‐2A cells and increased cell viability against H₂O₂. These activities (melanin biosynthesis stimulatory and protective effect against H₂O₂ of CS2 and hyaluronic acid productive activities of these triterpene derivatives) have been reported for the first time. Copyright © 2016 John Wiley & Sons, Ltd.     

Bioactive acylphloroglucinols from Hypericum densiflorum

Three acylphloroglucinol derivatives have been isolated from the hexane and acetone extracts of the aerial parts of Hypericum densiflorum Pursch. The compounds were characterized by NMR spectroscopy and mass spectrometry and identified as 4‐geranyloxy‐2,6‐dihydroxybenzophenone (1), 4‐geranyloxy‐1‐(2‐methylpropanoyl)‐ phloroglucinol (2) and 4‐geranyloxy‐1‐(2‐methylbutanoyl)‐phloroglucinol (3). Compounds 1–3 were evaluated for in vitro cell proliferation inhibitory activity against human breast (MCF‐7), lung (NCI H460), CNS (SF‐268), stomach (AGS) and colon (HCT‐116) tumor cell lines; antibacterial activity against methicillin‐resistant Staphylococcus aureus (MRSA); inhibition of cyclooxygenase (COX‐1 and ‐2) enzymes; and antioxidant activity in the lipid peroxidation (LPO) assay. All three compounds showed moderate to strong antitumor, antibacterial, antioxidant and inhibition of COX‐2 activities. Also, this is the first reported occurrence of compound 3 in the Hypericum genus. Copyright © 2009 John Wiley & Sons, Ltd.     

Phytochemical and Pharmacological Investigations on Nymphoides indica Leaf Extracts

Nymphoides indica (L.) Kuntze (Menyanthaceae) is traditionally used in the Indian subcontinent. However, scientific data reporting its constituents are poor. This study aimed at evaluating its phytochemical constituents and various biological activities. Phytochemical investigations of the extracts and fractions resulted in the isolation of 5 lipophilic compounds, i.e. azelaic (nonanedioic) acid (1) and 4‐methyl‐heptanedioic acid (3), hexadecanoic (2) and stearic acid (5) and the fatty alcohol hexadecanol (4); 3 seco‐iridoids, i.e. 7‐epiexaltoside (6), 6″,7″‐dihydro‐7‐epiexaltoside (7) and menthiafolin (8); 3 flavonoids, i.e. 3,7‐di‐O‐methylquercetin‐4′‐O‐β‐glucoside (9), 3‐O‐methylquercetin‐7‐O‐β‐glucoside (10) and 3,7‐di‐O‐methylquercetin (11); scopoletin (12) and ferulic acid (13); and the monoterpenoids foliamenthoic acid (14) and 6,7‐dihydrofoliamenthoic acid methyl ester (15). Compounds 1–5 showed moderate antimicrobial activities, whereas compound 9 presented mild antiprotozoal activities against Trypanosoma brucei (IC₅₀ 8 μM), Leishmania infantum (IC₅₀ 32 μM) and Trypanosoma cruzi (IC₅₀ 30 μM). Antiglycation activity was shown by compounds 7 (IC₅₀ 0.36 mM), 10 (IC₅₀ 0.42 mM) and 15 (IC₅₀ 0.61 mM). Finally α‐glucosidase inhibition was shown by compounds 7, 9, 11 and 13–15. It could be concluded that N. indica leaf extracts possess mild to moderate antimicrobial, antiprotozoal, antioxidant and antidiabetic activities. Copyright © 2016 John Wiley & Sons, Ltd.     

Antielastase and free radical scavenging activities of compounds from the stems of Cornus kousa

Bioassay‐guided investigation of the stems of Cornus kousa led to the isolation of 12 compounds such as four triterpenoids: betulinic acid (1), maslinic acid (2), arjunolic acid (3), 3‐isoarjunolic acid (4), four flavanoids; catechin (5), epi‐catechin (6), 2‐hydroxynaringenin (7), 2‐hydroxynaringenin‐7‐O‐β‐d ‐glucopyranoside (8), two ellagic acid derivatives; 3,4,3′‐tri‐O‐methylellagic acid (9), 3,4‐di‐O‐methylellagic acid (10), a daucosterol (11) and a sucrose derivative; (3′‐O‐p‐coumaroyl)‐β‐d ‐fructofuranosy‐(2?1)‐(6‐O‐p‐coumaroyl)‐α‐d ‐glucopyranoside (12). Their structures were elucidated on the basis of spectroscopic studies as well as by comparison with available data in the literature. The free radical scavenging activity and elastase inhibition activity were investigated for the development of antiaging ingredients as a raw material for use in cosmetics. Among these compounds, compounds 1, 2 and 8 showed significant elastase inhibition activity and IC₅₀ was 10.81 µg/mL, 21.21 µg/mL and 44.63 µg/mL, respectively, on porcine pancreatic elastase, whereas compounds 5, 6, 7 and 8 showed significant free radical scavenging activity and SC₅₀ was 8.37 µg/mL, 9.31 µg/mL, 9.23 µg/mL and 17.45 µg/mL, respectively. Copyright © 2007 John Wiley & Sons, Ltd.     

Inhibition of Inducible Nitric Oxide Synthase and Cyclooxygenase‐2 Expression by Phenolic Compounds from Roots of Rhododendron mucronulatum

The roots of Rhododendron mucronulatum Turzaninov have been used in Oriental traditional medicine for the treatment of dysuria, fever, increase of digestive activity and tonics in China and Korea. Activity guided isolation of the roots of Rhododendron mucronulatum Turzaninov has led to the isolation of three flavonoids, one flavan 3‐ol and one proanthocyanidin. Chemical investigation of the 80% Me₂CO extract from the roots of Rhododendron mucronulatum led to the isolation and identification of five compounds: taxifolin (1), taxifolin 3‐O‐β‐d ‐glucopyranoside (2), quercetin 3‐O‐α‐l ‐arabinofuranoside (3), (‐)‐epicatechin (4), procyanidin B‐3 (5). To investigate the antioxidative and antiinflammatory effects of these compounds, their 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) radical scavenging activities and the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2) in LPS‐stimulated HaCaT cells were also quantified by western blotting and their end products, nitric oxide (NO) and prostaglandin E₂ (PGE₂), respectively. Compounds (1–5) showed potent DPPH radical scavenging compared with positive controls (l ‐ascorbic acid). Also, compounds 1 and 2 dose‐dependently inhibited the expressions of inflammatory mediators, NO and PGE₂, suggesting they are promising candidates as antiinflammatory agents. Copyright © 2011 John Wiley & Sons, Ltd.     

Steroidal Glycosides with Antiproliferative Activities from Digitalis trojana

The phytochemical investigation of Digitalis trojana led to the isolation of two cardiac glycosides (1, 2), one pregnane glycoside (3), three furostanol type saponins (4–6), along with three cleroindicins (7–9), four phenylethanoid glycosides (10–13), two flavonoids (14, 15) and two phenolic acid derivatives (16, 17). The structure elucidation of the isolates was carried out by NMR experiments as well as ESI‐MS. The cytotoxic activity of compounds 1–13 against a small panel of cancer cell lines, namely MCF‐7, T98G, HT‐29, PC‐3, A375 and SH‐SY5Y, was investigated. Compounds 1–6 showed antiproliferative activity against human breast MCF‐7 and colon HT‐29 cancer cell lines with IC₅₀ values ranging from 8.3 to 50 μM. In order to understand the mechanism involved in the cell death, the active compounds were tested as pro‐apoptotic agents using propidium iodide staining by flow cytometry method. No significant increase was observed in the apoptosis of the MCF‐7 and HT‐29 cancer cells. Moreover, the effects of the active compounds on cell proliferation were assessed on the same cancer cell lines by cell cycle analysis of DNA content using flow cytometry. No significative changes were observed in the cell cycle of MCF‐7, while significant changes in G₂/M cell cycle phase of HT‐29 cells were observed after treatment with digitalin (1), cariensoside (3) and 22‐O‐methylparvispinoside B (6) at 10 μM. Copyright © 2013 John Wiley & Sons, Ltd.     

Antiprotozoal activity of Melampyrum arvense and its metabolites

An activity guided isolation of the H₂O subextract of the crude extract of Melampyrum arvense L. afforded iridoid glucosides: aucubin (1), melampyroside (2), mussaenoside (3), mussaenosidic acid (4), 8‐epi‐loganin (5); flavonoids: apigenin (6), luteolin (7), luteolin 7‐O‐β‐glucopyranoside (8); a lignan glycoside dehydrodiconiferyl alcohol 9‐O‐β‐glucopyranoside (9); and benzoic acid (10). β‐Sitosterol (11) and a fatty acid mixture (12) were identified as the active principles of the CHCl₃ subextract. The structures of the isolates were elucidated by spectroscopic methods, while the composition of 12 was identified by GC‐MS after methylation. Luteolin (7) appeared as the most active compound against Trypanosoma brucei rhodesiense and Leishmania donovani (IC₅₀ values 3.8 and 3.0 μg/mL). Luteolin 7‐O‐β‐glucopyranoside (8) displayed the best antiplasmodial activity against Plasmodium falciparum (IC₅₀ value 2.9 μg/mL). This is the first detailed phytochemical study on Turkish M. arvense and the first report of the antiprotozoal effect of Melampyrum species and its constituents. Copyright © 2010 John Wiley & Sons, Ltd.     

Rutin,a Quercetin Glycoside,Restores Chemosensitivity in Human Breast Cancer Cells

Several studies have documented the ability of flavonoids to sensitize cancer cells to chemotherapeutics and reverse multidrug resistance by inhibition of efflux pumps (adenosine triphosphate‐binding cassette transporters), apoptosis activation, and cell cycle arrest. In this study, the flavonoid rutin (quercetin 3‐O‐β‐d ‐rutinoside) was investigated as chemosensitizer towards two different human epithelial breast cancer cell lines: (i) MB‐MDA‐231, selected as representative for triple‐negative breast cancer and (ii) MCF‐7 used as a well‐characterized model of HER2‐negative breast cancer. To assess the cytocompatibility of rutin against non‐cancer cells, primary human mammary fibroblasts were used as control and non‐target cells. In MDA‐MB‐231 cells, 20 μM rutin enhanced cytotoxicity related to cyclophosphamide and methotrexate. Rutin significantly (p < 0.05) increased the anticancer activity of both chemotherapeutics, at 24–48–72 h, and decreased the activity of the adenosine triphosphate‐binding cassette transporters, namely, P‐glycoprotein (P‐gp) and breast cancer resistance protein (BCRP). Flow cytometry analysis showed 20 μM and 50 μM rutin arrested cell cycle at G2/M and G0/G1 phases, respectively, significantly promoting cell apoptosis. Rutin, via non‐selective inhibition of P‐gp and BCRP pumps, efficiently reverses multidrug resistance and restores chemosensitivity to cyclophosphamide and cyclophosphamide of human chemoresistant, triple‐negative breast cancer cells, successfully arresting cell cycle progression. Copyright © 2017 John Wiley & Sons, Ltd.     

Phenol Glycosides with In Vitro anti‐Helicobacter pylori Activity from Hypericum erectum Thunb

To evaluate the anti‐Helicobacter pylori activity of Hypericum erectum methanol extracts in order to provide the primary evidence for their use in clinical practice. An ethyl acetate fraction of H. erectum suspension‐cell cultures inhibited the growth of H. pylori in vitro, with a MIC₅₀ range of 38.7–63.2 μg/mL, comparable to metronidazole (MIC₅₀ = 43.2 μg/mL). To further investigate the involved active compounds of the H. erectum extracts, four phenol glycosides were isolated for the current study: quercetin‐3′‐O‐β‐d ‐galactopyranoside, quercetin‐3′‐O‐(2′′‐acetyl)‐β‐d ‐glucopyranoside, 4,6‐dihydroxy‐2‐methoxyphenyl‐1‐O‐β‐d ‐glucopyranoside and 4‐hydroxy‐2,6‐dimethoxyphenyl‐1‐O‐α‐l ‐rhamnopyranosyl(1–6)‐β‐d ‐glucopyranoside. The MIC₅₀ values of 4,6‐dihydroxy‐2‐methoxyphenyl‐1‐O‐β‐d ‐glucopyranoside and 4‐hydroxy‐2,6‐dimethoxyphenyl‐1‐O‐α‐l ‐rhamnopyranosyl(1–6)‐β‐d ‐glucopyranoside from ATCC43504 strains were 7.3 and 27.3 μg/mL, respectively. The other two phenol glycosides did not show anti‐H. pylori activity. The results of this work suggest that H. erectum has some therapeutic potential against H. pylori infection, which could be explored for patients with gastroduodenal disorders. Copyright © 2011 John Wiley & Sons, Ltd.     

Inhibitory Effect of Verbascoside Isolated from Buddleja brasiliensis Jacq. ex Spreng on Prolyl Oligopeptidase Activity

The phenylpropanoid glycoside verbascoside [2‐(3,4‐dihydroxyphenylethyl)‐1‐O‐α‐l ‐rhamnopyranosyl‐(1→3)‐β‐d ‐(4‐O‐caffeyl)‐glucopyranoside] (1) has been isolated as the main constituent of the crude extract of Buddleja brasiliensis Jacq. ex Spreng from Southern Brazil. The crude extract, main fractions and the compound 1 were evaluated for inhibition of the enzymes acetylcholinesterase (AChE), dipeptidyl peptidase‐IV (DPP‐IV) and prolyl oligopeptidase (POP). Compound 1 showed weak activity against DPP‐IV with an IC₅₀ >> 150 µm and was inactive against AChE, with a pMIQ determined by bioautography of 9.6. In contrast, 1 displayed significant inhibition of POP in a dose‐dependent manner with an IC₅₀ value of 1.3 ± 0.2 µm , similar to the positive control, baicalin, with a POP IC₅₀ of 12 ± 3 µm . Copyright © 2012 John Wiley & Sons, Ltd.     

Cytotoxic Properties of the Stem Bark of Citrus reticulata Blanco (Rutaceae)

The bioassay‐guided fractionation of the n‐hexane extract of Citrus reticulata Blanco (Rutaceae) stem bark yielded scoparone (1), xanthyletin (2), lupeol (3), β‐amyrin (4), stigmasterol (5), β‐sitosterol (6) and palmitic acid. The structures of these compounds were determined by comprehensive spectroscopic analyses, i.e., 1D and 2D NMR and EI‐MS, and by comparison with the reported data. Extracts, fractions and isolated compounds 1–6 were assessed for cytotoxicity by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐dphenyltetrazolium bromide (MTT) assay against three human cancer cell lines, i.e., human lung adenocarcinoma cell line A549, human breast adenocarcinoma cell line MCF7 and human Caucasian prostate adenocarcinoma cell line PC3. Significant activity of the n‐hexane and the dichloromethane extracts was observed against the breast cancer cell line MCF7 with IC₅₀s of 45.6 and 54.7 μg/mL, respectively. Moreover, the 70% ethyl acetate in n‐hexane chromatographic fraction showed significant activity displaying IC₅₀ values of 53.0, 52.4 and 49.1 μg/mL against the cancer cell lines A549, MCF7 and PC3, respectively. Encouragingly, an IC₅₀ of 510.0 μg/mL against the human normal prostate cell line PNT2 indicated very low toxicity and hence favourable selectivity indices for the 70% ethyl acetate in n‐hexane fraction in the range of 9.6–10.4 towards cell lines A549, MCF7 and PC3. Because compounds isolated from the above fraction only delivered IC₅₀ values in the range of 18.2–96.3, 9.2–34.1 and 7.5–97.2 μg/mL against A549, MCF7 and PC3 cell lines, respectively, synergistic action between compounds is suggested. Bioassay results valorize the anticancer effectivity of the stem bark of this plant in Cameroonian pharmacopoeia. Copyright © 2017 John Wiley & Sons, Ltd.     

Anticancer activity and molecular mechanisms of α‐conidendrin,a polyphenolic compound present in Taxus yunnanensis,on human breast cancer cell lines

α‐Conidendrin is a polyphenolic compound found mainly in Taxus yunnanensis, as the source of chemotherapy drug paclitaxel, which has been used in traditional medicine for treatment of cancer. This study aimed to investigate the anticancer activity and molecular mechanisms of α‐conidendrin on breast cancer cell lines. The results of the present study show that α‐conidendrin possesses potent antiproliferative effects on breast cancer cell lines MCF‐7 and MDA‐MB‐231. α‐Conidendrin significantly induced apoptosis in breast cancer cells via reactive oxygen species generation, upregulation of p53 and Bax, downregulation of Bcl‐2, depolarization of mitochondrial membrane potential (MMP), release of cytochrome c from mitochondria, and activation of caspases‐3 and ‐9. α‐Conidendrin remarkably inhibited the proliferation of breast cancer cells through induction of cell cycle arrest by upregulating p53 and p21 and downregulating cyclin D1 and CDK4. Unlike breast cancer cells, the antiproliferative effect of α‐conidendrin on human foreskin fibroblast cells (normal cells) was very small. In normal cells, reactive oxygen species levels, loss of MMP, release of cytochrome c, mRNA expression of p53, p21, cyclin D1, CDK4, Bax, and Bcl‐2 as well as mRNA expression and activity of caspases‐3 and ‐9 were significantly less affected by α‐conidendrin compared with cancer cells. These results suggest that α‐conidendrin can be a promising agent for treatment of breast cancer with little or no toxicity against normal cells.     

Anti‐complement activity of isolated compounds from the roots of Clerodendrum bungei Steud.

To determine the anti‐complement activity of natural diterpenes, chromatographic separation of the acetone‐soluble fraction from the roots of Clerodendrum bungei (Verbenaceae) led to the isolation of five diterpenoids. An acetone‐soluble extract of the roots of C. bungei exhibited significant anti‐complement activity on the classical pathway complement system, which was expressed as total hemolytic activity. Five compounds isolated from the roots of C. bungei, namely 12‐O‐β‐d ‐glucopyranosyl‐3,11,16‐trihydroxyabieta‐8,11,13‐triene (1), 3,12‐O‐β‐d ‐diglucopyranosyl‐11,16‐dihydroxyabieta‐8,11,13‐triene (2), ajugaside A (3), uncinatone (4) and 19‐hydroxyteuvincenone F (5). Compounds 1, 2, 3, 4 and 5 showed inhibitory activity against complement system with 50% inhibitory concentrations (IC₅₀) values of 24 µm , 138 µm , 116 µm , 87 µm and 232 µm . Among the compounds tested, 1 showed the most potent anti‐complement activity (IC₅₀, 24 µm ). Copyright © 2010 John Wiley & Sons, Ltd.     

Resveratrol derivatives from Commiphora africana (A. Rich.) Endl. display cytotoxicity and selectivity against several human cancer cell lines

Commiphora africana (A. Rich.) Endl. (Burseraceae) is a medicinal plant widely used in Nigerian ethnomedicine. The in vitro cytotoxicity of the stem bark extract of C. africana and isolated cytotoxic compounds was investigated. Three resveratrol derivatives: (E)‐resveratrol 3‐O‐rutinoside ( 1 ), 5‐methoxy‐(E)‐resveratrol 3‐O‐rutinoside ( 2 ), and pinostilbene ( 3 ), together with 3‐hydroxy‐5‐methoxybenzoic acid ( 4 ) were isolated from the methanol fraction of C. africana. Their structures were determined by extensive analysis of their HREIMS and NMR spectra. The cytotoxicity of the isolated compounds against four human carcinoma cells was determined using the MTT assay. Compound 1 displayed the highest antiproliferative effect on the cell lines, with IC₅₀ values of 16.80, 21.74, 17.89, and 17.44 μM, against MCF7, A549, PC3, and HepG2 human cancer cell lines, respectively. In addition, compounds 1 – 3 showed low toxicity against normal human prostate cell line, with selectivity indices greater than five across the carcinoma cells, indicating that the compounds possess potential in the development of low‐toxicity chemotherapeutic agents. These results support the traditional use of this plant in the treatment of cancer.     

In vitro anti-herpes simplex virus activity of 1,2,4,6-tetra-O-galloyl-β-D-glucose from Phyllanthus emblica L. (Euphorbiaceae)

In this study, 1,2,4,6‐tetra‐O‐galloyl‐β‐d ‐glucose (1246TGG), a polyphenolic compound isolated from traditional Chinese medicine Phyllanthus emblica L. (Euphorbiaceae), was found to inhibit herpes simplex virus type 1 (HSV‐1) and type 2 (HSV‐2) infection at different magnitudes of activity in vitro. Further studies revealed that 1246TGG directly inactivated HSV‐1 particles, leading to the failure of early infection, including viral attachment and penetration. 1246TGG also suppressed the intracellular growth of HSV‐1 within a long period post‐infection (from 0 h p.i. to 12 h p.i.), while it might exert an antiviral effect mainly before 3 h p.i. It inhibited HSV‐1 E and L gene expressions as well as viral DNA replication but did not affect the RNA synthesis of IE gene in our study. Also, in the presence of 1246TGG, the synthesis of viral protein was reduced. Taken together, it was suggested that 1246TGG might exert anti‐HSV activity both by inactivating extracellular viral particles and by inhibiting viral biosynthesis in host cells. These results warrant further studies on the antiviral mechanisms of 1246TGG and suggest that it might be a candidate for HSV therapy. Copyright © 2011 John Wiley & Sons, Ltd.