Antiviral triterpenoids from the medicinal plant Schefflera heptaphylla.

Schefflera heptaphylla (L.) Frodin is a principal ingredient of an herbal tea formulation widely used for the treatment of common cold in southern China. An extract of the long leafstalk of the compound leaf of S. heptaphylla exhibited the most potent antiviral activity against respiratory syncytial virus (RSV). Further antiviral-guided fractionation and isolation of the leafstalk extract of S. heptaphylla led to obtain two highly active pure triterpenoids, namely 3alpha-hydroxylup-20(29)-ene-23,28-dioic acid and 3-epi-betulinic acid 3-O-sulfate, together with an inactive saponin, 3alpha-hydroxylup-20(29)-ene-23,28-dioic acid 28-O-alpha-l-rhamnopyranosyl-(1-->4)-O-beta-d-glucopyranosyl-(1-->6)-beta-d-glucopyranoside. An antiviral assay using a cytopathic effect (CPE) reduction method showed that the two triterpenoids possessed broader antiviral activity against respiratory syncytial virus (RSV) with a similar 50% inhibition concentration (IC(50)) value of 6.25 microg/mL, influenza A (H1N1) virus with IC(50) values of 25 and 31.3 microg/mL, Coxsackie B3 (Cox B3) virus with IC(50) values of 12.5 and 20 microg/mL and herpes simplex virus type 1 (HSV-1) with IC(50) values of 18.8 and 25 microg/mL, respectively, whereas the saponin did not have antiviral activity against these four viruses at a concentration of 100 microg/mL.

Role of nitric oxide in the vasorelaxant and hypotensive effects of extracts and purified tannins from Geum japonicum.

Crude extracts and three purified tannins from Geum japonicum Thunberg (Rosaceae) were examined for relaxant effects in isolated rat thoracic aorta and for hypotensive effects in anesthetized normotensive and hypertensive rats. The acetone extract and the butyl alcohol extract of Geum japonicum at a cumulative concentration of 30mug/ml potently relaxed phenylephrine-precontracted aortic rings by 73+/-5% and 80+/-7%, respectively, without affecting the resting tension of these vessels. Removal of the vascular endothelium, inhibition of nitric oxide (NO) synthase with N(omega)-nitro-l-arginine (l-NA) or inhibition of cGMP biosynthesis with methylene blue all abolished the vasorelaxant effects of the Geum japonicum extracts. Addition of l-arginine, the substrate for NO biosynthesis, reversed the inhibitory effects of l-NA. Similar vasorelaxant effects of 82+/-10%, 61+/-8% and 82+/-14%, were observed with the purified tannins, penta-O-galloyl-beta-glucoside, casuariin and 5-desgalloylstachyurin, respectively, at a cumulative concentration of 10muM. Intravenous injection of the butyl alcohol extract of Geum japonicum at a cumulative dose of 2.5mg/kg into both hypertensive and normotensive rats resulted in a marked reduction in the mean arterial blood pressure by 46+/-6% and 34+/-7%, respectively, which was abolished by prior injection of l-NA. Therefore, these results suggest that tannins may be responsible for the vasorelaxant and hypotensive effects of Geum japonicum, mediated via endogenous NO and subsequent cGMP formation. The data suggest that extracts of Geum japonicum may have potential use as new anti-hypertensive agents for lowering arterial blood pressure in hypertensive patients.

Antiviral activity and mode of action of caffeoylquinic acids from Schefflera heptaphylla (L.) Frodin.

Schefflera heptaphylla is a popular medicinal plant in southern China. Three caffeoylquinic acid derivatives, namely 3,4-di-O-caffeoylquinic acid, 3,5-di-O-caffeoylquinic acid, and 3-O-caffeoylquinic acid, were isolated from this plant and investigated for their antiviral activity against respiratory syncytial virus (RSV). 3,4-Di-O-caffeoylquinic acid and 3,5-di-O-caffeoylquinic acid possessed potent anti-RSV activity. The median inhibitory concentrations (IC50) of 3,4-di-O-caffeoylquinic acid and 3,5-di-O-caffeoylquinic acid against RSV were 2.33 microM (1.2 microg/ml) and 1.16 microM (0.6 microg/ml), respectively, in a plaque reduction assay. The dicaffeoylquinic acids exhibited minimal cytotoxicity against HEp-2 cells with median cytotoxic concentration (CC50) higher than 1000 microM. The maximal non-cytotoxic concentration (MNCC) of the two dicaffeoylquinic acids were about 96.7 microM, which suggested their anti-RSV effect was not due to cytotoxicity. The antiviral action of 3,4-di-O-caffeoylquinic acid and 3,5-di-O-caffeoylquinic acid was specific against RSV, as they had no obvious antiviral activity against influenza A (Flu A), Coxsackie B3 (Cox B3), and Herpes simplex type one (HSV-1) viruses. Studies were performed that indicated that the dicaffeoylquinic acids could inhibit RSV directly, extracellularly, but only at much higher concentrations than seen in standard assays. Moreover, they could not inhibit RSV attachment to host cells, and could not protect HEp-2 cells from RSV infection at lower concentrations. The data suggest that the compounds exerted their anti-RSV effects via the inhibition of virus-cell fusion in the early stage, and the inhibition of cell-cell fusion at the end of the RSV replication cycle.

Antiviral activities of medicinal herbs traditionally used in southern mainland China.

The aqueous extracts from 21 medicinal herbs traditionally used in southern mainland China were screened for antiviral activities against human herpes simplex virus type 1 (HSV-1) and human respiratory syncytial virus (RSV) using a cytopathic effect (CPE) reduction assay. Three extracts from Agrimonia pilosa, Pithecellobium clypearia and Punica granatum, respectively, showed anti-HSV-1 activity, which was possibly contributed by the polyphenolic compounds in the herbal extracts. Six of the extracts, from Blumea laciniata, Elephantopus scaber, Laggera pterodonta, Mussaenda pubescens, Schefflera octophylla and Scutellaria indica, respectively, exhibited anti-RSV activity with 50% inhibition (IC50) concentrations ranging from 12.5 to 32 microg/mL, and selective indices (SI) ranging from 11.2 to 40. In addition to polyphenolic compounds, other constituents present in these extracts may also contribute to their anti-RSV activity.