| Earlier research on Piper methysticum (kava kava) roots was focused on phytochemistry and its application as anesthetic, muscle relaxation, anti-anxiety and analgesic agents. Little work has been done on antiinflammatory, antioxidant and anticancer activities of crude extracts and purified compounds of P. methysticum roots. My research on solvent extracts of P. methysticum roots and bioassay-directed isolation and characterization resulted in several antioxidant, cyclooxygenase (COX) and topoisomerase enzyme inhibitory compounds. The isolation and characterization of these compounds were accomplished by chromatographic (MPLC, TLC and HPLC) and spectral methods (1D- and 2D-NMR, FTIR and MS). P. methysticum roots were sequentially extracted with hexane, ethyl acetate and MeOH. In another extraction, P. methysticum roots were extracted sequentially with hot water and MeOH. Bioassay-directed isolation and purification of the ethyl acetate extract yielded dihydrokawain ( 1), desmethoxyyangonin (2), flavokawain A (3), kawain (4), dihydromethysticin (5), yangonin (6) and methysticin (7). The COX enzyme inhibitory assay directed purification of the MeOH extract yielded a novel bornyl ester of 3,4-methylene dioxy cinnamic acid (8), bornyl ester of cinnamic acid (9), pinostrobin (10), flavokawain B ( 11) and 5,7-dimethoxyflavonone (12). Compound 8 is novel and 9, 10 and 12 were isolated for the first time from P. methysticum roots.; At pH 7 and 100 μg mL−1, compounds 1–12 demonstrated cyclooxygenase-I (COX-I) and cyclooxygenase-II (COX-II) enzyme inhibitory activities. This is the first report of COX enzyme inhibitory activities of compounds 1–12. Compounds 6 and 7 showed moderate antioxidant activities in free radical scavenging assay at 2.5 mg mL−1. Topoisomerase (top-I and -II) enzyme inhibitory and gap junctional intercellular communication (GJIC) assays were used to test anticancer properties of compounds 1, 3, 7 and 11. Compound 1 is a moderate top-II inhibitor when tested at 250 μg concentration in plate agar assays. In ras-transduced rat liver epithelial cell line, compounds 1, 3 and 4 showed growth inhibition at 287, 46.8 and 217 μM, respectively. In ras- and myc/ras-transduced rat liver epithelial cell lines, compounds 5 and 7 showed growth inhibition at 181 and 182 μM, respectively, while 5 distinctly changed cell morphology and acted as a reversible cytostatic compound. It also slightly upregulated GJIC at 181 μM in ras-transduced rat liver epithelial cells. This is the first report of potential anticancer activities of compounds 1 and 5 using topoisomerase enzyme inhibitory and GJIC assays.; COX-I and -II enzyme inhibitory activities of compounds 1–12 provided scientific support for the anecdotal claims on the traditional use of kava kava roots for controlling inflammatory pain. Antiinflammatory, antioxidant and GJIC activities of isolated compounds might also help to explain the low cancer incidence in Fiji where the kava drink is consumed regularly. The isolation and characterization of antioxidant, cyclooxygenase and topoisomerase enzyme inhibitory compounds from P. methysticum roots might support the consumption of P. methysticum roots use as a healthy beverage and alternative medicine and also help to develop clinically useful products for preventing inflammation and cancers in human. |
