The effect of phenolic active fraction on ficus deltoidea var. kunstleri (KING) corner on fatty acid-induced insulin resistance cell models

Abstract

Type 2 diabetes mellitus (T2DM) is the commonest type of diabetes mellitus and characterized by the insulin resistance. Many literatures showed that insulin resistance in T2DM and obesity is due to oxidative stress. Most of the traditional medicinal plants that are claimed useful in treating diabetes having antioxidant activity and believe to be beneficial in preventing the oxidative stress. The study tried to relate the relationship between antioxidant and insulin resistance. The study was conducted by determining the effect of Ficus deltoidea phenolics fraction that having the strongest antioxidant activity on glucose uptake of the myotubes and adipocytes in insulin resistance condition. The study consists of sequential extraction of the F. deltoidea and followed by fractionation using DPPH guided activity. The identified fraction by UPLC-QTOF-MS/MS that had the strongest antioxidant activity was used on insulin resistance models in order to see whether the fraction is able to enhance glucose uptake. Eleven fractions were collected. The DPPH assay result showed methanol extracts and F1 fraction (ethyl acetate fraction) was the strongest antioxidant active fraction. The identified components from the negative mode of UPLC-QTOF-MS/MS were euparin, dihydroresveratrol, feralolide, Moracin M-3’-O-?-D- glucopyranoside, cinchonain Ia, piceatannol, 3,5,4’- trihydroxystillbene, protosappanin A, cearoin, procyanidin C-1, protosappanin C, smilaxin, ceasalpins J, ceasalpins P, moracin F, protosappanin A, neosappanone A, 1-(4-hydroxybenzyl)-4-methoxy-2,7-dihydroxyphenanthrene, 1,5- Bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadien-3-one, albaspidin AA, moracin O and moracin C. The identified components from the positive mode of UPLC-QTOF-MS/MS were epicatechin gallate, populnin, catechin, kaempferol, chlorogenic acid, 4-O-?-D Glucopyranosyl-trans-cinnamic acid and kaempferol-7-O-?-L-rhamnoside. For the cell culture, palmitate was able to induce insulin resistance in C2C12 myotubes but not in 3T3-L1 adipocytes. None of the strength of the fraction able to improve the insulin resistance. 10 ?g/mL and 100 ?g/mL of ethyl acetate fraction significantly reduced glucose uptake in C2C12 myotubes at concentration of 17.92 ?M ± 2.53 and 7.40 ?M ± 3.92 whereas in 3T3-L1 adipocytes, all concentration of ethyl acetate fraction reduced glucose uptake but significant at 100 ?g/mL (18.6286 ?M ± 1.18). Further investigation is needed to be done on the other possible mode of action by F. deltoidea in reconciling its anti-diabetic claims. The finding implies that not all antioxidants rich medicinal plants can reverse the insulin resistance and their beneficial effects on T2DM need detail elaboration. It is suggested that palmitate induced insulin resistance in skeletal muscle is a useful screening tool in searching a potential remedy for T2DM particularly in considering the disease pathophysiological aspect.