Swertia mussotii Franch. Improves skeletal muscle glucose uptake and mitochondrial function via Ampk/Pgc-1α signaling in type 2 diabetes mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Swertia mussotii Franch, which Tibetan name is "Di-da" or "Zang Yin Chen," represents a significant Tibetan medicinal herb with an extensive background of use in clearing heat, detoxification, liver calming, promotion of bile secretion based on the Tibetan medicine theory. In Tibetan medicine, diabetes ("gcin snyi sa khu") is believed to result from imbalances among the three fundamental factors-Lung, Tripa, and Pekén-and is classified into subtypes with distinct clinical manifestations. S. mussotii is traditionally used to treat Tripa-type disorders and is incorporated into Tibetan formulations such as Tibetan Hypolipidemic Capsules and Shibawei Hezi Liniao Wan, as well as classical prescriptions including Shiwei Hezi Tangsan, for managing symptoms such as polyuria and hyperlipidemia. Despite its broad clinical use, there is limited understanding of the molecular mechanisms that contribute to its ability to hypoglycemic effects.

AIM OF THE STUDY: This investigation pay attention to the hypoglycemic effects of Swertia mussotii Franch (SMF) and elucidate the regulatory mechanisms governing glucose metabolism and mitochondrial function in skeletal muscle.

MATERIALS AND

METHODS

The biological activities of SMF were tested using two experimental models following chemical profiling with UPLC-Q-TOF-MS: (i) in vitro experiments were performed in L6 myotubes at SMF concentrations of 20 and 40 μg/ml (n = 3). (ii) T2DM mice induced by STZ-HFD were used for in vivo studies, which received 100 or 200 mg/kg SMF (n = 3). Therapeutic efficacy was assessed using an integrated approach combining biochemical measurements, histological analyses, and molecular assays.

RESULTS

Fifteen compounds were identified in SMF. In L6 myotubes, SMF significantly enhanced glucose uptake, improved mitochondrial function, and showed no cytotoxicity at the tested concentrations. In diabetic mice, SMF treatment conferred to decrease of body weight and fast blood glucose, alongside enhance insulin sensitivity and glucose tolerance. Additionally, this treatment restored mitochondrial functionality, maintained skeletal muscle fiber architecture, and promoted Glut4 expression. Mechanistic investigations indicated that these effects were associated with the activation of the Ampk/Pgc-1α signaling pathway.

CONCLUSIONS

This study demonstrates that SMF exerts significant hypoglycemic effects by improving skeletal muscle glucose metabolism and mitochondrial function. By targeting skeletal muscle mitochondria and elucidating the involvement of Ampk/Pgc-1α signaling, this work supports the ethnopharmacological use of S. mussotii, which highlights the potential of its management for T2DM.