strangury and as a styptic. Kashiwada and others during their search for plant-derived anti-HIV agents from natural products, found that 95% EtOH extract of the leaves of N. nucifera display significant anti-HIV activity (EC
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چکیده
BLACK Natural Product Radiance 218 Nelumbo nucifera Gaertn. (Hindi ⎯ Kamal) is a perennial aquatic crop, grown and consumed throughout Asia. Its parts have been used for various medicinal purposes in oriental medicine. In particular, the leaves are known for diuretic and astringent properties, and are used to treat fever, sweating, and strangury and as a styptic. Kashiwada and others during their search for plant-derived anti-HIV agents from natural products, found that 95% EtOH extract of the leaves of N. nucifera display significant anti-HIV activity (EC 50 <2μg/mL, TI>5). The chemical compounds (+)-1(R)-Coclaurine (1) and (−)-1(S)-norcoclaurine (3), together with quercetin 3-O-β-D-glucuronide (4), were isolated from leaves and identified as anti-HIV principles. Compounds 1 and 3 demonstrated potent anti-HIV activity with EC 50 values of 0.8 and <0.8μg/mL, respectively and therapeutic index (TI) values of >125 and >25, respectively. Compound 4 was less potent (EC 50 2μg/mL). In a structure–activity relationship study, other benzylisoquinoline, aporphine, and bisbenzylisoquinoline alkaloids, including liensinine (14), negferine (15) and isoliensinine (16), which were previously isolated from the leaves and embryo of N. nucifera, were also evaluated for anti-HIV activity. Compounds 14–16 showed potent anti-HIV activities with EC 50 values of <0.8μg/mL and TI values of >9.9, >8.6 and >6.5, respectively. Nuciferine (12), an aporphine alkaloid, had an EC 50 value of 0.8μg/mL and TI of 36. In addition, synthetic Coclaurine analogs were also evaluated. Compounds 1, 3, 12 and 14–16 can serve as new leads for further development of anti-AIDS agents [Kashiwada Yoshiki, Aoshima Akihiro, Ikeshiro Yasumasa, Chen Yuh-Pan, Furukawa Hiroshi, Itoigawa Masataka, Fujioka Toshihiro, Mihashi Kunihide, Cosentino L Mark, Morris-Natschke Susan L and Lee Kuo-Hsiung, Anti-HIV benzylisoquinoline alkaloids and flavonoids from the leaves of Nelumbo nucifera and structure–activity correlations with related alkaloids, Bioorg Med Chem, 2005, 13 (2), 443-448]. There is a globally acknowledged demand for a broader, safer and also cheaper repertoire for the treatment of human immunodeficiency virus (HIV) infection. The medicinal plant Phyllanthus amarus Schum. & Th. has not only a recorded use in folk medicine for centuries, but has been shown to have multiple beneficial biological effects on a scientific level. P. amarus derived preparations were previously shown to inhibit RT inhibitor-resistant HIV variants as efficiently as wild-type strains. The drugs target different steps of the HIV life cycle, thereby presenting multiple antiviral activities. Researchers working at Institute of Medical Microbiology and Hygiene, University of Regensburg, Regensburg, Germany observed that a water/alcohol extract of P. amarus blocks HIV-1 attachment and the HIV-1 enzymes integrase, reverse transcriptase and protease to different degrees. A gallotannin containing fraction and the isolated ellagitannins, geraniin and corilagin were shown to be the most potent mediators of these antiviral activities. The P. amarus derived preparations blocked the interaction of HIV-1 gp120 with its primary cellular receptor CD4 at 50% inhibitory concentrations of 2.65 (water/alcohol extract) to 0.48μg/ ml geraniin. Inhibition was also evident for the HIV-1 enzymes integrase (0.48–0.16μg/ml), reverse transcriptase (8.17–2.53μg/ml) and protease (21.80– 6.28μg/ml). In order to prove the in vivo relevance of these biological activities, plant material was administered orally to volunteers and a potent anti-HIV activity in blood could be demonstrated. Sera at a final concentration of 5% reduced HIV replication by more than 30%. These results support the conclusion that P. amarus has inhibitory effects on HIV not only in vitro but also in vivo [Notka Frank, Meier Georg and Wagner Ralf, Concerted inhibitory activities of Phyllanthus amarus on HIV replication in vitro and ex vivo, Antiviral Res, 2004, 64 (2), 93-102]. Therapeutics
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