Ganoderic acid A from Ganoderma lucidum ameliorates lipid metabolism and alters gut microbiota composition in hyperlipidemic mice fed a high-fat diet.

Ganoderic acid A (GA) is one of the most abundant triterpenoids in Ganoderma lucidum, and has been proved to possess a wide range of beneficial health effects. The aim of the current study is to investigate the amelioration effects and mechanism of GA on improving hyperlipidemia in mice fed a high-fat diet (HFD). The results showed that GA intervention significantly inhibited the abnormal growth of body weight and epididymal white adipose tissue (eWAT), prevented the hypertrophy of epididymal adipocytes, and ameliorated the biochemical parameters of serum and liver related to lipid metabolism in HFD-fed mice. Histological analysis also showed that the excessive accumulation of lipid droplets in the liver induced by HFD-feeding was greatly alleviated by GA intervention. In addition, GA intervention also increased the level of short chain fatty acids (SCFAs) in the intestine and promoted the excretion of bile acids (BAs) through feces. High-throughput sequencing of bacterial full-length 16S rDNA revealed that daily supplementation with GA made significant structural changes in the gut microbial population of mice fed with HFD, in particular modulating the relative abundance of some function related microbial phylotypes. The relationships between lipid metabolic parameters and gut microbial phylotypes were also revealed by correlation analysis based on a heatmap and network. The result showed that 46 key gut microbial phylotypes (OTUs) were markedly correlated with at least one lipid metabolic parameter. Moreover, UPLC-QTOF/MS-based liver metabolomics showed that 111 biomarkers (47 up-regulated metabolites and 64 down-regulated metabolites) were significantly changed after high-dose GA intervention (75 mg kg-1 day-1), compared with the HFD-fed hyperlipidemic mice. Metabolic pathway enrichment analysis of the differential hepatic metabolites demonstrated that GA intervention had significant regulatory effects on primary bile acid biosynthesis, fatty acid biosynthesis, amino sugar and nucleotide sugar metabolism, inositol phosphate metabolism, and so on. In addition, GA intervention regulated the mRNA levels of hepatic genes involved in fatty acid metabolism and bile acid homeostasis. These findings present new evidence supporting that GA from G. lucidum has the potential to alleviate lipid metabolic disorders and ameliorate the imbalance of gut microflora in a positive way.

[The influence of zi-hua burn cream on the survival of random skin flaps in rats].

OBJECTIVE: To observe the effect of zi-hua burn cream on the survival of skin flaps in rats, and its mechanisms. METHODS: 72 Wistar rats, were randomly divided into four groups as zi-hua group(n = 18, external application of alfalfa burn cream), control group (n = 18, external application of heparin sodium cream), model group (n = 18, external application of vaseline) , negative control (n = 18, no operation). 8 cm x 2 cm random skin flaps with pedicle on the side of head were designed on the back of Wistar rats. The drug was applied on the flap surface, 2 times a day. The survival of skin flaps was observed. The change of serum superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), turner necrosis factor-alpha(TNF-alpha)and interleukin-6(IL-6)were compared at 1,2,3,7 d after operation, and histologic examination was performed. RESULTS: The survival rate of zi-hua group (73.58 - 10. 74)% was significantly higher than that of model group (33.40 - 16.05) %, showing a statistical difference (Q = 10.63, P <0.01). There was no significant difference between the zi-hua group and control group (71.65 +/- 11. 92) %. The level of serum SOD, NO in zi-hua group and control group was higher than that in model group, while the level of serum MDA, TNF-alpha and IL-6 was lower than that in model group(P <0.01). On 7 day after operation, skin flaps tissue edema,necrosis and inflammatory cell infiltration in zi-hua group and control group was less obvious than that in model group. There was significant proliferation of granuloma and fibroblast and formation of neonatal capillary in zi-hua group and control group. The vascular density in zi-hua group was obviously higher than that in the model group and control group(P <0. 01). CONCLUSIONS: Zi-hua burn cream could significantly improve the blood supply of skin flaps, increase the survival rate of skin flaps in rats. Its mechanism may be associated with the anti-free-radical-damage action, improve local microcirculation, improve the NO content, reduce the TNF-alpha and IL-6 level, reduce inflammation factor release, improve oxidative stress state, and reduce inflammation reaction.