Quantity: 1 LB (453.60 G) | UCC: 1 82447 00015 4


Articles:

Traditionally-used antimalarials from the Meliaceae.

Omar S, Zhang J, MacKinnon S, Leaman D, Durst T, Philogene BJ, Arnason JT, Sanchez-Vindas PE, Poveda L, Tamez PA, Pezzuto JM.

Ottawa-Carleton Institute of Biology, University of Ottawa, Ottawa, ON K1N 6N5, Canada.

A quantitative ethnobotanical approach to antimalarial drug discovery led to the identification of Lansium domesticum Corr. Ser. (Meliaceae) as an important antimalarial used by Kenyah Dyak healers in Indonesian Borneo. Triterpenoid lansiolides with antimalarial activity were isolated from the bark and shown to have activity in both in vitro bioassays with Plasmodium falciparum, and in mice infected with P. berghei. A survey of African and tropical American Meliaceae led to further development of the limonoid gedunin from the traditionally used medicinal plants, tropical cedar, Cedrela odorata L., and neem, Azadirachta indica A. Juss. Gedunin has significant in vitro activity but initially showed poor in vivo activity. In vivo activity was improved by (1) incorporation into an easy to absorb suspension, (2) preparation of a more stable compound, 7-methoxygedunin; and (3) synergism with dillapiol, a cytochrome P450 3A4 inhibitor. The results show the potential for both antimalarial drug and phytomedicine development from traditionally used plants.

Antineoplastic agents. 489. Isolation and structures of meliastatins 1-5 and related euphane triterpenes from the tree Melia dubia.

Pettit GR, Numata A, Iwamoto C, Morito H, Yamada T, Goswami A, Clewlow PJ, Cragg GM, Schmidt JM.

Osaka University of Pharmaceutical Sciences, 4-20-1, Nasahara, Takatsuki, Osaka 569-1094, Japan.

The bark of the giant neem tree Melia dubia was found to contain 11 euphane-type triterpenes. Five new compounds, meliastatins 1-5 (1-5), proved to inhibit growth of the P388 lymphocytic leukemia cell line (ED(50) 1.7-5.6 microg/mL). Four of the others, the previously known methyl kulonate (8), kulinone (9), 16-hydroxybutyrospermol (10), and kulactone (11), were also found to inhibit (ED(50) 2.5-6.2 microg/mL) the P388 cancer cell line. In addition, two new euphane triterpenes were isolated and named dubione A (6) and dubione B (7). Structures for each of the 11 euphane triterpenes were established by spectral techniques that included HRMS and 2D NMR.

Gastroprotective effect of Neem (Azadirachta indica) bark extract: possible involvement of H(+)-K(+)-ATPase inhibition and scavenging of hydroxyl radical.

Bandyopadhyay U, Biswas K, Chatterjee R, Bandyopadhyay D, Chattopadhyay I, Ganguly CK, Chakraborty T, Bhattacharya K, Banerjee RK.

Department of Physiology, Indian Institute of Chemical Biology, 4, Raja S. C. Mullick road, Kolkata 700032, India.

The antisecretory and antiulcer effects of aqueous extract of Neem (Azadirachta indica) bark have been studied along with its mechanism of action, standardisation and safety evaluation. The extract can dose dependently inhibit pylorus-ligation and drug (mercaptomethylimidazole)-induced acid secretion with ED(50) value of 2.7 and 2 mg Kg(-1) b.w. respectively. It is highly potent in dose-dependently blocking gastric ulcer induced by restraint-cold stress and indomethacin with ED(50) value of 1.5 and 1.25 mg Kg(-1) b.w. respectively. When compared, bark extract is equipotent to ranitidine but more potent than omeprazole in inhibiting pylorus-ligation induced acid secretion. In a stress ulcer model, it is more effective than ranitidine but almost equipotent to omeprazole. Bark extract inhibits H(+)-K(+)-ATPase activity in vitro in a concentration dependent manner similar to omeprazole. It offers gastroprotection against stress ulcer by significantly preventing adhered mucus and endogenous glutathione depletion. It prevents oxidative damage of the gastric mucosa by significantly blocking lipid peroxidation and by scavenging the endogenous hydroxyl radical ((z.rad;)OH)-the major causative factor for ulcer. The (z.rad;)OH-mediated oxidative damage of human gastric mucosal DNA is also protected by the extract in vitro. Bark extract is more effective than melatonin, vitamin E, desferrioxamine and alpha-phenyl N-tert butylnitrone, the known antioxidants having antiulcer effect. Standardisation of the bioactive extract by high pressure liquid chromatography indicates that peak 1 of the chromatogram coincides with the major bioactive compound, a phenolic glycoside, isolated from the extract. The pharmacological effects of the bark extract are attributed to a phenolic glycoside which is apparently homogeneous by HPLC and which represents 10% of the raw bark extract. A single dose of 1g of raw extract per kg b.w. (mice) given in one day and application of 0.6g raw extract per kg b.w. per day by oral route over 15 days to a cumulative dose of 9g per kg was well tolerated and was below the LD(50). It is also well tolerated by rats with no significant adverse effect. It is concluded that Neem bark extract has therapeutic potential for the control of gastric hyperacidity and ulcer.

The inhibiting effect of aqueous Azadirachta indica (Neem) extract upon bacterial properties influencing in vitro plaque formation.

Wolinsky LE, Mania S, Nachnani S, Ling S.

Section of Oral Biology, University of California, School of Dentistry, Los Angeles 90095-1668, USA.

The purpose of this investigation was to examine the inhibitory effects of aqueous extracts derived from the bark-containing sticks (Neem stick) of Azadirachta indica upon bacterial aggregation, growth, adhesion to hydroxyapatite, and production of insoluble glucan, which may affect in vitro plaque formation. Neem stick extracts were screened for minimal bacterial growth inhibition (MIC) against a panel of streptococci by means of a broth dilution assay. Initial bacterial attachment was quantified by the measurement of the adhesion of 3H-labeled Streptococcus sanguis to saliva-conditioned synthetic hydroxyapatite. The effect of the Neem stick extract upon insoluble glucan synthesis was measured by the uptake of radiolabeled glucose from 14C-sucrose. Aggregating activity of the Neem stick extracts upon a panel of streptococci was also examined. No inhibition of bacterial growth was observed among the streptococcal strains tested in the presence of < or = 320 micrograms/mL of the Neem stick extract. The pre-treatment of S. sanguis with the Neem stick extract or the gallotannin-enriched extract from Melaphis chinensis at 250 micrograms/mL resulted in a significant inhibition of the bacterial adhesion to saliva-conditioned hydroxyapatite. Pre-treatment of saliva-conditioned hydroxyapatite with the Neem stick or gallotannin-rich extract prior to exposure to bacteria yielded significant reductions in bacterial adhesion. The Neem stick extract and the gallotannin-enriched extract from Melaphis chinensis inhibited insoluble glucan synthesis. Incubation of oral streptococci with the Neem stick extract resulted in a microscopically observable bacteria aggregation. These data suggest that Neem stick extract can reduce the ability of some streptococci to colonize tooth surfaces.