Bioassay-guided isolation of antiplasmodial and antimicrobial constituents from the roots of Terminalia albida.

ETHNOPHARMACOLOGICAL RELEVANCE: Terminalia albida (Combretaceae), widely used in Guinean traditional medicine, showed promising activity against Plasmodium falciparum and Candida albicans in previous studies. Bioassay-guided fractionation was carried out in order to isolate the compounds responsible for these activities. MATERIALS AND METHODS: Fractionation and isolation were performed by flash chromatography, followed by semi-preparative HPLC-DAD-MS. The structural elucidation of the isolated compounds was carried out by 1D and 2D NMR as well as HR-ESI-MS. Isolated compounds were evaluated against Plasmodium falciparum, Candida albicans, Staphylococcus aureus and Escherichia coli, and their cytotoxicity against MRC-5 cells was determined. RESULTS: Bioassay-guided fractionation of Terminalia albida root resulted in the isolation of 14 compounds (1-14), and their antimicrobial properties were evaluated. Pantolactone (1) (IC50 0.60 ± 0.03 µM) demonstrated significant activity against P. falciparum. Other compounds, including 3,4,3'-tri-O-methyl-ellagic acid (3), the triterpenes arjunolic acid (5), arjungenin (6), arjunic acid (7) and arjunglucoside II (10), and the phenol glycoside calophymembranside-B (14), were less active and showed IC50 values in the range 5-15 µM. None of the tested compound showed antibacterial or antifungal activity. CONCLUSION: These results may explain at least in part the activity of the root extract of T. albida against P. falciparum.

Mutagenicity and oral toxicity studies of Terminalia chebula.

The fruit of Terminalia chebula Retz. (T. chebula), which is a member of the Combfreetaceae family, is used widely in Asian countries as a traditional folk medicine, and its extract has been reported to be an anticancer, antidiabetic and anticaries agent. In our previous study, chebulic acid isolated from T. chebula extract was confirmed to show antioxidant activity and protective action against endothelial cell dysfunction. In order to support the safety-in-use of the ethyl acetate (EtOAc)-soluble portion of a T. chebula ethanol extract containing 29.4% chebulic acid content, the prepared portion was tested in an in vitro mutagenicity assay, and a single- and 14-day repeated dose oral toxicity study. In the bacterial mutation assay, up to 5000 µg/mL concentration of the EtOAc-soluble portion, the numbers of colonies did not increase whether with or without metabolic activation. In the oral toxicity study, the single oral dose of the extract at 2000 mg/kg did not produce mortality or abnormal lesions in the internal organs of rats. The results of a 14-day orally repeated dose showed that the EtOAc-soluble portion of T. chebula ethanol extracts gave no adverse effects at dosages of 2000 mg/kg in rats in the study.

Molluscicidal activity of Sapindus mukorossi and Terminalia chebula against the freshwater snail Lymnaea acuminata.

The molluscicidal activity of Sapindus mukorossi and Terminalia chebula fruit powder against the vector snail Lymnaea acuminata was time and concentration dependent. The molluscicidal activity of T. chebula fruit powder (96 h LC(50):93.59 mg L(-1)) was more pronounced than that of S. mukorossi fruit powder (96 h LC(50):119.57 mg L(-1)). Ethanolic extracts of S. mukorossi and T. chebula fruit powder were more toxic than their other organic solvent extracts. The molluscicidal activity of ethanolic extract of S. mukorossi fruit powder (24h LC(50):2.75 mg L(-1)) was more effective than the ethanolic extract of T. chebula fruit powder (24h LC(50):124.06 mg L(-1)). The 96 h LC(50) of column-purified fraction of S. mukorossi fruit powder was 5.43 mg L(-1) whereas those of T. chebula fruit powder was 7.49 mg L(-1). Column, thin layer and high performance liquid chromatography analysis demonstrates that the active molluscicidal component in S. mukorossi and T. chebula is saponin (96 h LC(50):1.31 mg L(-1)) and tannic acid (96 h LC(50):1.64 mg L(-1)), respectively. These plants may be used as potent source of molluscicides against the snail L. acuminata.

Terminalia arjuna Wight & Arn.--a useful drug for cardiovascular disorders.

Ancient Indian physicians used the powdered tree bark of Terminalia arjuna Wight & Arn. for alleviating "hritshool" (angina) and other cardiovascular conditions. Its stem bark possesses glycosides, large quantities of flavonoids, tannins and minerals. Flavonoids have been detected to exert antioxidant, anti-inflammatory and lipid lowering effects while glycosides are cardiotonic, thus making Terminalia arjuna unique amongst currently used medicinal plants. In this review an attempt has been made to discuss various aspects of its ethnomedical, pharmacognostical, phytochemical, pharmacological and clinical relevance to cardiovascular conditions. Experimental studies have revealed its bark exerting significant inotropic and hypotensive effect, increasing coronary artery flow and protecting myocardium against ischemic damage. It has also been detected to have mild diuretic, antithrombotic, prostaglandin E(2) enhancing and hypolipidaemic activity. There is ample clinical evidence of its beneficial effect in coronary artery disease alone and along with statin. However, toxicological studies in experimental animals are lacking. Considering its anti-ischemic activity and its potential to correct dyslipidemia, reduce left ventricular mass and increase left ventricular ejection fraction, it is essential to examine the molecular mechanism of its action and its core constituents. Proposition to administer Terminalia arjuna along with statins deserves to be explored in depth for defining its place in the over all management and prevention of coronary artery disease.

Evaluation of genotoxicity of medicinal plant extracts by the comet and VITOTOX tests.

We report the results of our genotoxic evaluation of extracts from three medicinal plants Acacia nilotica, Juglans regia, and Terminalia chebula and the herbal drug Triphala employing the VITOTOX and comet tests.These tests detect DNA damage in prokaryotic and eukaryotic test systems, respectively. In the VITOTOX test, none of the extracts were identified as genotoxic. In the comet assay, extracts of Acacia nilotica showed statistically significant DNA damage only in a concentration of 2500 ppm (highest tested dose), whereas extracts from Juglans regia showed significant damage in concentrations above 250 ppm and more. Extracts from Terminalia chebula and Tripahala significantly increased DNA damage in a concentration above 500 ppm. This is not considered contradictory, because DNA damage in the alkaline comet assay may not be permanent and hence may not necessarily result in mutations. All the extracts were previously found in the Ames assay to have potent antimutagenic effects against the direct acting mutagens NPD, sodium azide, and the S9-dependent mutagen 2-AF. The results of the previous study using the Ames assay are in conformity with those of the VITOTOX test. It was found that the extracts were safe in concentrations of up to 1000 microg/0.1 mL and 2500 microg/0.1 mL. A literature survey also showed that plant extracts can be mutagenic as well as antimutagenic depending on the test system used. This indicates that a battery of assays is needed before any conclusion can be reached.