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Background: Polygala fallax Hemsl. is a plant that is commonly used as a folk medicine by Guangxi ethnic minorities, and it is also widely used in the clinical treatment of chronic diseases in China. The extract of P. fallax (EPF) contains key biologically active components from the roots and stems. However, the role of P. fallax or EPF in diabetic nephropathy (DN) is unclear.Purpose: This study aimed to investigate the effects and mechanisms of EPF on high glucose (HG)-induced human glomerular mesangial cell (HMC) injury, inflammation, fibrosis, and apoptosis in vitro.Methods: For the in vitro study, MTT and ELISA assays were performed with HG-treated HMCs, as well as MMP, Hoechst, flow cytometry, qRT-PCR, and western blot analyses. The expression of the TLR4/NF-κB pathway, along with its downstream inflammatory, apoptosis, and fibrosis factors, was measured. The expression of the TLR4/NF-κB pathway and its downstream inflammatory factors were also measured after the addition of TLR4 inhibitors.Results: Our results suggest that EPF can reverse the hyperproliferation and apoptosis of HMCs induced by HG. In addition, the extract inhibited the increase in inflammatory factors IL-6, TNF-α, IL-1β, MCP-1, and IL-18 in cells treated with HG. The mRNA and protein expression of TLR4, MyD88, NF-κB, Col IV, FN, MMP-9, and MMP-2 were downregulated by EPF. In addition, EPF significantly reduced the loss of MMP and the upregulation of Bcl-2/Bax mRNA and protein levels after HG treatment.Conclusion: These results demonstrated that EPF protects against diabetes-induced renal injury in vitro. EPF protected against HG-induced HMCs proliferation, apoptosis, fibrosis, and inflammation likely via inhibition of TLR4-dependent NF-κB signaling. This herbal extract may also be a novel treatment for DN. [ABSTRACT FROM AUTHOR]

Spermidine have been reported a role in antioxidative, antiaging, and antiinflammatory. Oxidative stress causes granulosa cell (GC) apoptosis, follicular atresia, and impairs poultry reproductive functions. Studies have found that autophagy is the protective mechanism against antioxidant stress and apoptosis in cells. However, the relationship between spermidine-induced autophagy, oxidative stress, and apoptosis in goose GCs remains unclear. In this study, we investigated the autophagy mechanism to mediate spermidine effects on the alleviation of oxidative stress and apoptosis in goose GCs. Follicular GCs were treated with spermidine combination with 3-Nitropropanoic acid (3-NPA), rapamycin (RAPA), and chloroquine (CQ) or with hydrogen peroxide, RAPA, and CQ. Spermidine upregulated the ratio of LC3-II/I, inhibited the accumulation of p62 protein, and induced autophagy. 3-NPA treatment significantly increased ROS production, MDA content, SOD activity, cleaved CASPASE-3 protein expression, and decreased BCL-2 protein expression in follicular GCs. Spermidine inhibited oxidative stress and apoptosis induced by 3-NPA. In addition, hydrogen peroxide-induced oxidative stress was inhibited by spermidine. However, the inhibitory effect of spermidine was eliminated under chloroquine. Our results demonstrated that spermidine relieved oxidative stress and apoptosis of GCs by inducing autophagy, indicating that spermidine has a great potential to maintain proteostasis and sustain granulosa cell viability in geese. [ABSTRACT FROM AUTHOR]