Hepatoprotective effects of Xiaoyao San formula on hepatic steatosis and inflammation via regulating the sex hormones metabolism

BACKGROUND The modified Xiaoyao San(MXS)formula is an adjuvant drug recommended by the National Health Commission of China for the treatment of liver cancer,which has the effect of preventing postoperative recurrence and metastasis of hepatocellular carcinoma and prolonging patient survival.However,the molecular mechanisms underlying that remain unclear.AIM To investigate the role and mechanisms of MXS in ameliorating hepatic injury,steatosis and inflammation.METHODS A choline-deficient/high-fat diet-induced rat nonalcoholic steatohepatitis(NASH)model was used to examine the effects of MXS on lipid accumulation in primary hepatocytes.Liver tissues were collected for western blotting and immunohisto chemistry(IHC)assays.Lipid accumulation and hepatic fibrosis were detected using oil red staining and Sirius red staining.The serum samples were collected for biochemical assays and NMR-based metabonomics analysis.The inflammation/lipid metabolism-related signaling and regulators in liver tissues were also detected to reveal the molecular mechanisms of MXS against NASH.RESULTS MXS showed a significant decrease in lipid accumulation and inflammatory response in hepatocytes under metabolic stress.The western blotting and IHC results indicated that MXS activated AMPK pathway but inhibited the expression of key regulators related to lipid accumulation,inflammation and hepatic fibrosis in the pathogenesis of NASH.The metabonomics analysis systemically indicated that the arachidonic acid metabolism and steroid hormone synthesis are the two main target metabolic pathways for MXS to ameliorate liver inflammation and hepatic steatosis.Mechanistically,we found that MXS protected against NASH by attenuating the sex hormone-related metabolism,especially the metabolism of male hormones.CONCLUSION MXS ameliorates inflammation and hepatic steatosis of NASH by inhibiting the metabolism of male hormones.Targeting male hormone related metabolic pathways may be the potential therapeutic approach for NASH.

Inverse relationship between bioavailable testosterone and subclinical coronary artery calcification in non-obese Korean men

Although low testosterone levels in men have been associated with high risk for cardiovascular disease, little is known about the association between male sex hormones and subclinical coronary disease in men with apparently low cardiometabolic risk. This study was performed to investigate the association between male sex hormones and subclinical coronary artery calcification measured as coronary calcium score in non-obese Korean men. We examined the relationship of total testosterone, sex hormone-binding globulin, bioavai lable testosterone and free testosterone with coronary calcium score in 291 non-obese Korean men （mean age： 52.8--- 9.3 years） not having a history of cardiovascular disease. Using multiple linear regression, we evaluated associations between log （sex hormone） levels and log （coronary calcium score） after adjusting for confounding variables in 105 men with some degree of coronary calcification defined as coronary calcium score ~〉 1. In multiple linear regression analysis, bioavailable testosterone was inversely associated with coronary calcium score （P=0.046） after adjusting for age, body mass index, smoking status, alcohol consumption, regular exercise, mean blood pressure, resting heart rate, C-reactive protein, fasting plasma glucose, total cholesterol, triglyceride, high-density lipoprotein （HDL） cholesterol, hypertension medication and hyperlipidernia medication, whereas total testosterone, sex hormone-binding globulin and free testosterone were not （P=0.674, P=O. 121 and P=O. 102, respectively）. Our findings indicate that bioavailable testosterone is inversely associated with the degree of subclinical coronary artery calcification in non-obese men.

Aphrodisiac potential of Polyalthia bullata (Tongkat Ali) in fowl

Objective:To study the aphrodisiac potential of Polyalthia(P.)bullata in fowl.Methods:In this study,testosterone,as an indicator of the aphrodisiac potential of P.bullata,was investigated for its release from TM3 Leydig cells grown in vitro and in 4 fowls given capsules containing P.bullata at a dose of 10 mg in each capsule twice a day,for 50 days.In the latter in vivo evaluation,mating behaviours were additionally determined after the treated fowls were released to the individual hens,and their testes and liver were dissected for histological examinations.Blood drawn from the fowls was assessed for any changes in diagnostic parameters.Results:In the in vitro test(TM3 Leydig cells),P.bullata was able to increase testosterone to 0.48 nmol/L within 72 h of incubation,compared to the untreated control with only 0.18 nmol/L,i.e.,an increase of 170%.In the in vivo test,outcomes in the fowls dosed with P.bullata showed similar positive elevations of testosterone to(9.72±1.10)nmol/L in comparison to the controls that showed a level of only(4.05±0.84)nmol/L.Total frequencies of mating behaviours were observed(wing flapping,body shakes,crowing and beak pecking)to be 23 counts for the test compared to only 15 for the control fowls.Histological examination of the male reproductive organs provided evidence of testosterone boosting based on an observable increase in the activity at the seminiferous tubules of testis tissues without any damaging effects,compared to the controls.In the nine diagnostic blood parameters assessed,including alanine aminotransferase,aspartate aminotransferase,and gamma glutamyltransferase,none was remarkably elevated compared to the controls.The histological changes in the liver were not severe and mainly consisted of only localized moderate but recoverable obstructions and swellings of the vessels and tubules.Conclusions:P.bullata is able to boost testosterone both in vitro and in vivo,with no acute toxicities.