Apigenin enhances viability of random skin flaps by activating autophagy.

Random skin flap is widely used in plastic surgery. However, flap necrosis caused by ischemia-reperfusion injury limits its clinical applications. Apigenin, a naturally occurring flavonoid mainly derived from plants, facilitates flap survival. In this study, we explored the effects of apigenin on flap survival and the underlying mechanisms. A total of 54 mice having a dorsal random flap model were randomly divided into control, apigenin, and apigenin +3-methyladenine groups. These groups were treated with dimethyl sulfoxide solution, apigenin, and apigenin +3-methyladenine, respectively. The animals were then euthanized to assess angiogenesis, apoptosis, oxidative stress, and autophagy levels through histological and protein analyses. Apigenin promotes survival of the skin flap area and reduces tissue edema. In addition, apigenin enhanced angiogenesis, attenuated apoptosis, alleviated oxidative stress, and activated autophagy. Interestingly, 3-methyladenine reversed the effects of apigenin on flap survival, angiogenesis, apoptosis, and oxidative stress through inhibition of autophagy. The findings of this study show that apigenin promotes angiogenesis, inhibits cell apoptosis, and lowers oxidative stress by mediating autophagy, thus the improving survival rate of random skin flaps.

Scutellarein Aggravated Carbon Tetrachloride-Induced Chronic Liver Injury in Gut Microbiota-Dysbiosis Mice.

Scutellarein (SCU) is an herbal flavonoid, showing hepatoprotective potentials. The study was aimed to investigate whether the hepatoprotective effect of SCU is dependent on the integrity of gut microbiota. Mice received repeated intraperitoneal injections of CCl4, followed with or without SCU treatment (15, 30, and 60 mg/kg). Gut microbial community of mice was disrupted by administrating a cocktail of antibiotics (ampicillin, neomycin sulfate, metronidazole, and vancomycin) in drinking water. The results showed SCU plus antibiotics aggravated CCl4-induced chronic liver injury, as demonstrated by liver function analysis, histological analysis, and TUNEL assay. SCU activated CYP2E1 expression and worsened CYP2E1-mediated lipid peroxidation and oxidative stress as coadministered with antibiotics. Moreover, when gut microbiota was disrupted by antibiotics, SCU activated IκBα/NF-κB pathway and promoted the release of subsequent proinflammatory cytokines including interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α). Remarkably, the 16 S rRNA sequencing demonstrated that SCU greatly decreased the relative abundance of Bifidobacterium and Lactobacillus and increased the relative abundance of Enterococcus in gut microbiota-dysbiosis mice. Spearman correlation analysis showed that Lactobacillus was positively correlated with SOD and negatively correlated with AST. Collectively, the hepatoprotective effect of SCU is reversed under antibiotics intervention, which may partly involve the activation of CYP2E1 and IκBα/NF-κB pathway and diminishment of Lactobacillus.