Chemical and Pharmacological Analysis of Caesalpinia Volkensii (H.), Senna Didymobotrya (F.) and Vitex Doniana (S.) from Kenya

Abstract

Despiteefforts to eradicate malaria, it remains a deadly disease with severe pathophysiological impacts, due to parasitic resistance to available drugs. The success of plant-based drugs motivated a study aimed at evaluating anti plasmodial and other pharmacologically active principles from the plants, Caesalpinia volkensii (Leguminocae) root- and stem-bark, Senna didymobotrya (Leguminocae) roots and Vitex doniana (Lamiaceae) stem-bark, which have been used to manage malaria and other ailments by different African communities. Antiplasmodial, analgesic, anti-inflammatory, antidyslipidaemic, and antioxidants bioassay guided isolation and spectroscopic characterization of compounds on the three plants were carried out by subjecting their crude extracts, fractions, and pure isolates to: in vitro anti plasmodial assay, in vivo antinociceptive and anti-inflammatory assay, in vivo hyperlipidaemic assays followed by in vitro adipocyte differentiation inhibition, and in vitro antioxidant assays. Two new furanoditerpenes [Ic.Su-dihydroxyvoucapane (400) and 1a,6~-dihydroxyvoucapane-19~-methyl ester (401)] together with voucapan-5a-ol (19), caesaldekarin C (38), deoxycaesaldekarin C (95), voucapane (398), 5-hydroxyvinhaticoic acid (399), triacontanyl-(E)-ferrulate (402), triacontanyl-(E)- cafIaete (403) and 30'-hydroxytriacontanyl-(E)-ferulate (404) were isolated from the root bark of C. volkensii. The furanoditerpenes 19, 38, 95, 401 at 100 mg/kg, showed significantly (P:S0.05) high antinociceptive activities in the two chemical models of nociception, however, the compounds showed low to moderate (25-50~ antiplasmodial activities. Triacontanyl-Ecinnamoates (402, 403 and 404) exhibited significant (p:S0.05) superoxide (02) scavenging, hydroxyl radical (OH·) and lipid peroxidation inhibitions. Three new cas sane diterpenes [voulkensin A, (408), voulkensin B, (407), and voulkensin A, (406)] and one new steroidal glycoside [3-0-[~-glucopyranosyl(l ~ 2)-O-~-xylopyranosyl]-stigmasterol (409)] together with oleanolic acid (185), 3-~-acetoxyolean-12-en-28-methyl ester (406), stigmasterol (176) and ~- sitosterol (177) were isolated from the stem bark of C. volkensii. The novel diterpenes [406-408] and 409 exhibited moderate (2-22J.tM) antiplasmodial activities. Seven anthraquinones, chrysophanol (269), physcion (273), natalo-emodin-8-methyl ether (279), obtusifolin (285), chrysophanol-I 0, 10'-biathrone (295), physcion-l 0,10' -bianthrone (299), 1,6-0-dimethylemodin (410), and 176 were isolated from the roots of S. didymobotrya. These anthraquinones showed significant (P:SO.Ol) lipid lowering and significant (p:S0.05) antioxidant effects, with 299 (50~M) exhibiting potent (P::;O.05) adipocytes growth inhibition. Four new phytoecdysteroids, 2,3- acetonide-24-hydroxyecdysone (411), I I -hydroxy-20-deoxyshidasterone (412), 21- hydroxyshidasterone (413) 2,3-acetonide-22-0-~-glucosyl-20-hydroxyecdysone (415) together with a known 24-hydroxyecdysone (414) were isolated from V doniana stem bark. These ecdysteroids (1Omglkg) displayed potent in vivo anti-inflammatory activities comparable (P:::;O.05)to diclofenac (50mg/kg). Compound 415 showed appreciably dose-dependent inhibition of adipocytes maturation by 29, 31 and 42% at 0.1, 10 and 50J.lM. These results supported the applications of the investigated plants in management of malaria and the cited pathophysiological conditions in ethnomedicine.