LEISHMANICIDAL, ANTI-INFLAMMATORY AND ANTI-OBESITY PROPERTIES OF NATURAL PRODUCTS FROM COMMON MEDICINAL AND EDIBLE PLANTS

Abstract

The dissertation aim was to present natural products derived from four common edible medicinal plants that could be applied for solving leishmaniasis, obesity and type 2 diabetes. This research showed leishmanicidal natural compounds isolated from Cichorium intybus L. (Asteraceae), Cornus florida L. (Cornaceae), Eryngium foetidum L. (Apiaceae), which have been used traditionally as antiparasitic remedies. The roots of C. intybus (chicory) yielded four sesquiterpene lactones: (1) 11(S),13-dihydrolactucopicrin, (2) lactucopicrin, (3) 11(S),13-dihydrolactucin and (4) lactucin. Only compound 2 presented leishmanicidal activity (IC 50 24.8 μM). The bark of C. florida (flowering dogwood) afforded eight compounds: (1) betulinic acid, (2) ursolic acid, (3) β-sitosterol, (4) ergosta-4,6,8,22-tetraene-3-one, (5) 3β-O-acetyl betulinic acid, (6) 3- epideoxyflindissol, (7) 3β-O-cis-coumaroyl betulinic acid, (8) 3β-O-trans-coumaroyl betulinic acid. The most active leishmanicidal compounds were (4) 11.5 µM, (6) 1.8 µM, (7) 8.3 µM and (8) 2.2 µM. The aerial parts of E. foetidum (culantro) generated two natural products: (1) lasidiol p-methoxybenzoate and (2) a terpene aldehyde ester derivative. Only compound 1 inhibited L. tarentolae and L. donovani with IC 14.33 and 7.84 μM, respectively. Obesity and type 2 diabetes are reaching alarming levels worldwide. This work presented the anti-inflammatory, anti-obesity and anti-diabetic effect in vitro and in vivo of Moringa oleifera Lam. (Moringaceae), which contains four bioactive isothiocyanates (MICs). Fresh leaves of M. oleifera were extracted with water to obtain a moringa concentrate (MC) containing 1.66% of total MICs. Also, MIC-1 and 4 were isolated from leaves. MC, MIC-1, and MIC-4 significantly decreased gene expression and production of inflammatory markers (NO, TNFα, IL-1β and IL-8) in LPS-stimulated RAW macrophages and Caco2 cells. The MC-treated animals, fed high-fat diet did not gain weight and did not develop fat liver disease compared to control animals. Also, when compared to control animals, the blood metabolic and inflammatory biomarkers from MC-treated mice were in the normal range. In addition MC-treated animals had normal levels of insulin signaling and inflammatory markers in liver, skeletal muscle, white adipose tissue and ileum. MC and MIC inhibited liver gluconeogenesis in vivo as well as in vitro. Finally, an indirect calorimetry acute study indicated that MC-treated mice had a higher fat oxidation rate compared to control mice.