Evaluation of the hepatotoxic potential of Tinospora crispa and its isolated borapetosides B, C and F in a murine model.

The hepatotoxic potential of the methanolic extract of the stems of Tinospora crispa and of its furano-diterpenoid-borapetosides B, C, and F-was investigated in normal and health-compromised mice. Health-compromised condition was established by a single intraperitoneal injection of LPS (6 mg/kg). Two different sets of experiments were conducted to evaluate the hepatotoxic potential. A 21-day study where the mice were dosed with the extract of T. crispa (1 gm/kg b. wt./day) or standardized combination of borapetosides B, C and F (500 mg/kg b. wt.) with or without a single dose of LPS (1 gm/kg b. wt./day). In the acute toxicity study, mice were dosed with borapetosides B, C, and F (500 mg/kg b. wt.). Results showed that the ALT levels were normal and liver histopathology unaltered. No conclusive hepatotoxicity was observed in the methanolic extract or pure compounds tested under the given experimental conditions.

Methicillin-resistant Staphylococcus aureus (MRSA)-active metabolites from Platanus occidentalis (American Sycamore).

One known and three new potent, selective, and nontoxic anti-MRSA metabolites, kaempferol 3-O-alpha-l-(2'',3''-di-E-p-coumaroyl)rhamnoside (1) (IC(50) 2.0 microg/mL), kaempferol 3-O-alpha-l-(2''-E-p-coumaroyl-3''-Z-p-coumaroyl)rhamnoside (2) (IC(50) 0.8 microg/mL), kaempferol 3-O-alpha-l-(2''-Z-p-coumaroyl-3''-E-p-coumaroyl)rhamnoside (3) (IC(50) 0.7 microg/mL), and kaempferol 3-O-alpha-l-(2'',3''-di-Z-p-coumaroyl)rhamnoside (4) (IC(50) 0.4 microg/mL), were isolated from the leaves of the common American sycamore, Platanus occidentalis. Compounds 2-4 are new. Due to the unusual selectivity, potency, and safety of the pure compounds and the semipure glycoside mixture against MRSA, it is clear that this represents a viable class of inhibitors to prevent growth of MRSA on surfaces and systemically.

Potent in vitro antifungal activities of naturally occurring acetylenic acids.

Our continuing effort in antifungal natural product discovery has led to the identification of five 6-acetylenic acids with chain lengths from C(16) to C(20): 6-hexadecynoic acid (compound 1), 6-heptadecynoic acid (compound 2), 6-octadecynoic acid (compound 3), 6-nonadecynoic acid (compound 4), and 6-icosynoic acid (compound 5) from the plant Sommera sabiceoides. Compounds 2 and 5 represent newly isolated fatty acids. The five acetylenic acids were evaluated for their in vitro antifungal activities against Candida albicans, Candida glabrata, Candida krusei, Candida tropicalis, Candida parapsilosis, Cryptococcus neoformans, Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Trichophyton mentagrophytes, and Trichophyton rubrum by comparison with the positive control drugs amphotericin B, fluconazole, ketoconazole, caspofungin, terbinafine, and undecylenic acid. The compounds showed various degrees of antifungal activity against the 21 tested strains. Compound 4 was the most active, in particular against the dermatophytes T. mentagrophytes and T. rubrum and the opportunistic pathogens C. albicans and A. fumigatus, with MICs comparable to several control drugs. Inclusion of two commercially available acetylenic acids, 9-octadecynoic acid (compound 6) and 5,8,11,14-eicosatetraynoic acid (compound 7), in the in vitro antifungal testing further demonstrated that the antifungal activities of the acetylenic acids were associated with their chain lengths and positional triple bonds. In vitro toxicity testing against mammalian cell lines indicated that compounds 1 to 5 were not toxic at concentrations up to 32 muM. Furthermore, compounds 3 and 4 did not produce obvious toxic effects in mice at a dose of 34 mumol/kg of body weight when administered intraperitoneally. Taking into account the low in vitro and in vivo toxicities and significant antifungal potencies, these 6-acetylenic acids may be excellent leads for further preclinical studies.