PMID- 38171388 OWN - NLM STAT- MEDLINE DCOM- 20240214 LR - 20240214 IS - 1873-6971 (Electronic) IS - 0367-326X (Linking) VI - 173 DP - 2024 Mar TI - Free radical scavenging polyphenols isolated from Phyllanthus niruri L. ameliorates hyperglycemia via SIRT1 induction and GLUT4 translocation in in vitro and in vivo models. PG - 105803 LID - S0367-326X(23)00378-7 [pii] LID - 10.1016/j.fitote.2023.105803 [doi] AB - Type 2 diabetes milletus (T2DM) is a complex multifaceted disorder characterized by insulin resistance in skeletal muscle. Phyllanthus niruri L. is well reported sub-tropical therapeutically beneficial ayurvedic medicinal plant from Euphorbiaceae family used in various body ailments such as metabolic disorder including diabetes. The present study emphasizes on the therapeutic potential of Phyllanthus niruri L. and its phytochemical(s) against insulin resistance conditions and impaired antioxidant activity thereby aiding as an anti-hyperglycemic agent in targeting T2DM. Three compounds were isolated from the most active ethyl acetate fraction namely compound 1 as 1-O-galloyl-6-O-luteoyl-beta-D-glucoside, compound 2 as brevifolincarboxylic acid and compound 3 as ricinoleic acid. Compounds 1 and 2, the two polyphenols enhanced the uptake of glucose and inhibited ROS levels in palmitate induced C2C12 myotubes. PNEAF showed the potent enhancement of glucose uptake in palmitate-induced insulin resistance condition in C2C12 myotubes and significant ROS inhibition was observed in skeletal muscle cell line. PNEAF treated IR C2C12 myotubes and STZ induced Wistar rats elevated SIRT1, PGC1-alpha signaling cascade through phosphorylation of AMPK and GLUT4 translocation resulting in insulin sensitization. Our study revealed an insight into the efficacy of marker compounds isolated from P. niruri and its enriched ethyl acetate fraction as ROS scavenging agent and helps in attenuating insulin resistance condition in C2C12 myotubes as well as in STZ induced Wistar rat by restoring glucose metabolism. Overall, this study can provide prospects for the marker-assisted development of P. niruri as a phytopharmaceutical drug for the insulin resistance related diabetic complications. CI - Copyright (c) 2023. Published by Elsevier B.V. FAU - Swargiary, Deepsikha AU - Swargiary D AD - Chemical Biology Lab-I, Institute of Advanced Study in Science and Technology (IASST), Guwahati, Assam, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, U.P, India. FAU - Kashyap, Bhaswati AU - Kashyap B AD - Chemical Biology Lab-I, Institute of Advanced Study in Science and Technology (IASST), Guwahati, Assam, India. FAU - Sarma, Pranamika AU - Sarma P AD - Chemical Biology Lab-I, Institute of Advanced Study in Science and Technology (IASST), Guwahati, Assam, India. FAU - Ahmed, Semim Akhtar AU - Ahmed SA AD - Chemical Biology Lab-I, Institute of Advanced Study in Science and Technology (IASST), Guwahati, Assam, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, U.P, India. FAU - Gurumayum, Shalini AU - Gurumayum S AD - Chemical Biology Lab-I, Institute of Advanced Study in Science and Technology (IASST), Guwahati, Assam, India. FAU - Barge, Sagar Ramrao AU - Barge SR AD - Chemical Biology Lab-I, Institute of Advanced Study in Science and Technology (IASST), Guwahati, Assam, India. FAU - Basumatary, Devi AU - Basumatary D AD - Chemical Biology Lab-I, Institute of Advanced Study in Science and Technology (IASST), Guwahati, Assam, India. FAU - Borah, Jagat C AU - Borah JC AD - Chemical Biology Lab-I, Institute of Advanced Study in Science and Technology (IASST), Guwahati, Assam, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, U.P, India. Electronic address: borahjc@gmail.com. LA - eng PT - Journal Article DEP - 20240101 PL - Netherlands TA - Fitoterapia JT - Fitoterapia JID - 16930290R RN - 76845O8NMZ (ethyl acetate) RN - 0 (Polyphenols) RN - 0 (Reactive Oxygen Species) RN - EC 3.5.1.- (Sirtuin 1) RN - 0 (Insulin) RN - 0 (Palmitates) RN - 0 (Acetates) SB - IM MH - Rats MH - Animals MH - *Insulin Resistance MH - *Diabetes Mellitus, Type 2/drug therapy MH - Polyphenols/pharmacology/metabolism MH - *Phyllanthus MH - Reactive Oxygen Species/metabolism MH - Sirtuin 1 MH - Rats, Wistar MH - Molecular Structure MH - Muscle Fibers, Skeletal MH - Insulin/metabolism MH - *Hyperglycemia MH - Palmitates/metabolism MH - Muscle, Skeletal/metabolism MH - *Acetates OTO - NOTNLM OT - Free fatty acid OT - Oxidative stress OT - Phyllanthus niruri OT - Phytopharmaceuticals OT - Reactive oxygen species OT - T2DM COIS- Declaration of competing interest The authors have declared that there is no conflict of interest exists. EDAT- 2024/01/04 11:43 MHDA- 2024/02/11 16:42 CRDT- 2024/01/03 19:10 PHST- 2023/09/29 00:00 [received] PHST- 2023/12/12 00:00 [revised] PHST- 2023/12/28 00:00 [accepted] PHST- 2024/02/11 16:42 [medline] PHST- 2024/01/04 11:43 [pubmed] PHST- 2024/01/03 19:10 [entrez] AID - S0367-326X(23)00378-7 [pii] AID - 10.1016/j.fitote.2023.105803 [doi] PST - ppublish SO - Fitoterapia. 2024 Mar;173:105803. doi: 10.1016/j.fitote.2023.105803. Epub 2024 Jan 1.