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Background: The current study was designed to evaluate the effect of Platycodin D (PD), triterpenoid saponins extracted from the roots of Platycodon grandiflorum (PG) on alcohol-induced fatty liver (AFL) and investigate the possible mechanism. Methods and Materials: A rat model was set up by feeding ethanol and fish oil to experimental rats, which then were treated with PD of 10, 20, 30 mg/kg body weight/day for 4 weeks, respectively, whereafter, liver function enzymes, endotoxin of serum and liver lipid were assayed by biochemical methods, cytokines, histochemistry of hepatic tissue, the protein expression of CD14 and TLR4, the mRNA expression of MD-2, MyD 88 and TRAF-6 were assayed. Results: Treatment with PD on AFL rats significantly decreased the levels of serum ALT, AST and TBIL, coefficient of liver index and the hepatic tissue contents of TG, additionally and dramatically decreased serum endotoxin levels, down-regulated MD-2 and CD14 levels, as well as the mRNA expression of TLR4, MyD88 and TRAF-6, accordingly suppressed NF-B p65 as well as endotoxin-mediated inflammatory factors such as TNF-α and IL-6. Conclusions: Treatment with PD effectively protects against AFL through anti-inflammatory and anti-endotoxic process, and the confirmed mechanism is that PD treatment ameliorate alcoholic-induced liver injury mainly via TLR4-MyD88-NF-B signal path in AFL rat.

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Maresin1 (MaR1) is an endogenous pro-resolving lipid mediator produced from polyunsaturated fatty acids and is believed to have antioxidant and anti-inflammatory properties. The objective of this study was to estimate MaR1′s impact on type 2 diabetic osteoporosis (T2DOP) and its pharmacological mode of action. An in vitro high-glucose model of the osteoblast cell line MC3T3-E1 was constructed and stimulated with MaR1. Type 2 diabetic rats were used to establish in vivo models of calvarial defects and were treated in situ with MaR1. The results revealed that, aside from preventing mortality and promoting the osteogenic capacity of MC3T3-E1 cells, MaR1 increased nuclear factor erythroid-2 related factor 2 (NRF2) signaling as well as the activity of glutathione peroxidase 4 (GPX4) and cystine-glutamate antiporter (SLC7A11) and caused the restraint of ferroptosis under hyperglycemic stimulation. However, the therapeutic impact of MaR1 was significantly diminished due to NRF2-siRNA interference and the ferroptosis activator Erastin. Meanwhile, these results were validated through in vivo experiments. These findings imply that MaR1 activated the NRF2 pathway in vivo and in vitro to alleviate high-glucose-induced ferroptosis greatly. More crucially, MaR1 might effectively reduce the risk of T2DOP.