Polygonatum sibiricum polysaccharides (PSP) improve the palmitic acid (PA)-induced inhibition of survival, inflammation, and glucose uptake in skeletal muscle cells

Abstract

Polygonatum sibiricum polysaccharides (PSP) can decrease the levels of fasting blood glucose, total cholesterol, and triglyceride (TG) in hyperlipidemic and diabetic animals. It can also reduce inflammatory cytokines and promote glucose uptake in adipocytes. However, the underlying molecular mechanisms of PSP in improving insulin resistance (IR) in skeletal muscle remain unclear. In this study, palmitic acid (PA) induced an IR model in L6 myotubes. After treatment, cell proliferation was measured using the CCK8. miR-340-3p, glucose transporter 4 (GLUT-4), and interleukin-1 receptor-associated kinase 3 (IRAK3) expression was measured by qRT-PCR. IRAK3 protein levels were measured by Western blotting. Glucose in the cell supernatant, TG concentration in L6 myotubes, and the levels of IL-1β, IL-6, and TNF-α were measured by an ELISA. We found that cell survival, glucose uptake, and GLUT-4 expression in L6 myotubes were significantly suppressed, while lipid accumulation and inflammatory factor levels were enhanced by PA stimulation. Furthermore, PSP treatment markedly alleviated these effects. Interestingly, PSP also significantly reduced the upregulated expression of miR-340-3p in the L6 myotube model of IR. Furthermore, overexpression of miR-340-3p reversed the beneficial effects of PSP in the same IR model. miR-340-3p can bind to the 3′-untranslated regions of IRAK3 . Additionally, PA treatment inhibited IRAK3 expression, whereas PSP treatment enhanced IRAK3 expression in L6 myotubes. Additionally, miR-340-3p also inhibited IRAK3 expression in L6 myotubes. Taken together, PSP improved inflammation and glucose uptake in PA-treated L6 myotubes by regulating miR-340-3p/IRAK3, suggesting that PSP may be suitable as a novel therapeutic agent for IR.

Terpenoid-Rich Extract of Dillenia indica L. Bark Displays Antidiabetic Action in Insulin-Resistant C2C12 Cells and STZ-Induced Diabetic Mice by Attenuation of Oxidative Stress

“…To develop a PA-IR model, C2C12 myotubes were treated with 250 µM PA (Sigma-Aldrich, St. Louis, MO, USA) for 24 h, as described by Cai et al [ 26 ]. Briefly, PA was dissolved in ethanol and diluted to 1:10 in fatty acid-free (>98%) bovine serum albumin (BSA; Sigma; final concentration = 2% w / v ).…”

Pharmacological properties of Polygonatum and its active ingredients for the prevention and treatment of cardiovascular diseases

“…Polygonatum has also been shown to attenuate myocardial fibrosis and inflammation and restore the morphology and function of myocardial tissue by regulating AMPK-Nrf2, NF-κB, TGF-β1/Smads, and NLRP3 inflammasome signaling pathway [ 152 – 157 ]. In addition, Polygonatum also has significant efficacy in lipid regulation and anti-atherosclerosis, which can prevent and control the occurrence of atherosclerosis by regulating metabolic abnormality, reducing lipid accumulation, inhibiting hyperglycemia, and reducing vascular damage, so as to intervene in the risk factors of CVDs [ 129 – 139 ]. Atherosclerosis is closely related to hyperlipidemia, inflammation, and oxidative stress, so it is clear that the pharmacological effects exerted by Polygonatum are intertwined.…”

“…PSPs was reported to reduce lipid accumulation and diminish the expression level of inflammatory factors in insulin-resistant cell models by regulating microRNA-140-5p/interleukin-1 receptor-associated kinase 3 (miR-340-3p/IRAK3), which plays a crucial role in inhibiting atherogenesis [ 129 ]. Different from the lipid-lowering effect of PSPs, other studies have revealed that steroid saponins and homoisoflavones extracted from Polygonatum have potential hypoglycemic effects [ 130 – 132 ], and the latter has been found to be able to inhibit the formation of advanced glycosylation end products [ 131 ].…”

Polygonatum Polysaccharide Regulates Macrophage Polarization and Improves LPS-Induced Acute Lung Injury through TLR4-MAPK/NF-κB Pathway

“…M2-polarized macrophages are anti-inflammatory and protective, while M1-polarized macrophages are believed to have adverse effects on cells [ 21 ]. Previous research identified that compounds isolated from polygonatum had anti-inflammatory effects [ 22 , 23 ]. In the past, Liu et al found that PSPs could downregulate the LPS-mediated increase in neutrophil ratio and reduce the level of LPS-induced inflammatory factors in BALF of the rat ALI model [ 22 ].…”