Jiangtang Sanhao formula ameliorates skeletal muscle insulin resistance via regulating GLUT4 translocation in diabetic mice

Abstract

Jiangtang Sanhao formula (JTSHF), one of the prescriptions for treating the patients with diabetes mellitus (DM) in traditional Chinese medicine clinic, has been demonstrated to effectively ameliorate the clinical symptoms of diabetic patients with overweight or hyperlipidemia. The preliminary studies demonstrated that JTSHF may enhance insulin sensitivity and improve glycolipid metabolism in obese mice. However, the action mechanism of JTSHF on skeletal muscles in diabetic mice remains unclear. To this end, high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic mice were subjected to JTSHF intervention. The results revealed that JTSHF granules could reduce food and water intake, decrease body fat mass, and improve glucose tolerance, lipid metabolism, and insulin sensitivity in the skeletal muscles of diabetic mice. These effects may be linked to the stimulation of GLUT4 expression and translocation via regulating AMPKα/SIRT1/PGC-1α signaling pathway. The results may offer a novel explanation of JTSHF to prevent against diabetes and IR-related metabolic diseases.

Exploring the Therapeutic Mechanism of Jiangtang Sanhao Formula in Alleviating Insulin Resistance in Skeletal Muscle Cells: Involvement of AMPK/SIRT1/PGC-1α pathway？

“…Further, after incubated with 10% JTSHF-containing serum, IR-C2C12 cells exhibited a prominent enhancement of glucose consumption and uptake coupled with negligible cytotoxicity. This outcome was consistent with JTSHF's hypoglycemic effect in vivo(Ye et al 2022). Previous studies have illuminated that palmitate could induce cellular oxidative stress(Yang et al 2019), and elevated FFAs are linked to an over-production of free radicals, which causes mitochondrial dysfunction, further intensifying oxidative stress(Ly et al 2017).…”

“…Chinese herbal medicine, a major branch of alternative medicine, holds distinct advantages, such as notable effectiveness with lower side effects in the management of IR-related diseases ( Subsequently, our research team initially investigated the anti-diabetic properties and correlative mechanisms of JTSHF in mice with T2DM induced by high-fat diet and streptozotocin. The available results demonstrated that JTSHF had bene cial effects on relieving skeletal muscle IR and appeared to be an activator of AMPK, playing a pivotal role in regulating GLUT4 expression and translocation (Ye et al 2022). As yet, it remains uncertain whether JTSHF has similar effects in vitro, and further exploration is required to uncover the underlying mechanism.…”

“…T2DM. Building upon the encouraging ndings from animal studies(Ye et al 2022), this research was projected to further delve deeper into the effect and mechanisms of JTSHF on IR reversal through in vitro experiments. The C2C12 murine skeletal muscle cell line, offers a useful model, especially for researching into glycolipid metabolism, oxidative stress, and IR.…”

Histone deacetylase functions and therapeutic implications for adult skeletal muscle metabolism

“…Numerous natural phytochemicals with anti-diabetic activity (due to their effects on SIRT1 levels or activation) have been characterized, including quercetin ( Oboh et al, 2016 ), fisetin ( Liou et al, 2018 ), curcumin ( Mohammadi et al, 2021 ), berberine ( Yin et al, 2008 ), and sesamine ( Majdalawieh et al, 2020 ; Kou et al, 2022 ). In addition, recent studies have unveiled the effectiveness against insulin resistance of new active components from plants, due to their ability to increase SIRT1 levels or activation, including Kaempferol3-O-rutinoside (KOR) from the leaf of Antidesma acidum ( Kashyap et al, 2023 ), or the Jiangtang Sanhao formula, a mix of plants from traditional Chinese medicine ( Ye et al, 2022 ), or the plant hormone Abscisic acid (ABA) ( Spinelli et al, 2021 ). These discoveries have given rise to a novel category of food named Sirtfoods™, which have pleiotropic health functions by mitigating metabolic disorders ( Akan et al, 2022 ).…”