Schisandra sphenanthera extract modulates sweet taste receptor pathway, IRS/PI3K, AMPK/mTOR pathway and endogenous metabolites against T2DM.

Background: Southern Schisandra is the dried and matured fruit of Schisandra sphenanthera Rehd. et Wils. in the family of Magnoliaceae; Traditional medicine reports that Schisandra sphenanthera has astringent and astringent properties, benefiting qi and promoting the production of body fluid, tranquilising the heart and calming the mind; it is clinically utilized for prolonged cough, thirst due to injury of the body fluid, internal heat and thirst, palpitation and insomnia, etc., and thirst belongs to the category of diabetes mellitus; the literature reports and the preliminary study of our team showed that Schisandra sphenanthera can be used to prevent and control diabetes mellitus.

Purpose: In the research, we investigated the mechanism of action of SDP against T2DM by integrating pharmacodynamics, endogenous metabolite assays and signalling pathways.

Materials And Methods: UPLC-MS/MS was used to identify the chemical constituents. HPLC was utilized to determine the content of eight lignan-like components in SDP. A T2DM rat model was established by the combined induction of high-fat and high-sugar feed and STZ, and the mechanism of action of SDP on T2DM was investigated by using biochemical indices, Western blot analysis of protein expression, mRNA expression, immunohistochemistry and endogenous metabolites.

Results: The chemical components in SDP were determined by UPLC-MS/MS and HPLC, and biochemical indicators determined that SDP has the effects of lowering blood glucose, anti-glycolipid metabolism, and anti-oxidative stress, and is able to restore pathological damage in the liver and pancreas, activate the PI3K/AKT, AMPK/mTOR, and sweetness receptor signalling pathways, restore the sweetness receptor mRNAs, and modulate the urinary compounds such as malic acid, γ-aminobutyric acid, leucine, N-acetylaspartic acid and other compounds thereby achieving the therapeutic effect of T2DM.

Conclusion: SDP can ameliorate diabetes-induced symptoms related to elevated blood glucose, dyslipidaemia, elevated fasting insulin levels and impaired glucose tolerance in rats; the anti-T2DM of SDP may be through the regulation of the sweet taste receptor pathway, the PI3K/AKT/mTOR and the AMPK/mTOR signalling pathway, which leads to the development of a normal level and exerts an antidiabetic effect.