Effect of Yinchenhao Decoction on"Intestinal TPH1-Hepatic HTR2A Axis"in Mice with Metabolic Associated Fatty Liver Disease / 世界科学技术-中医药现代化

Objective To explore the mechanism of Yinchenhao Decoction in preventing and treating MAFLD based on"Intestinal TPH1-hepatic HTR2A axis".Methods Twenty-four C57BL/6J mice were arbitrarily splited up into control group,model group and Yinchenhao decoction group,eight in each group.Mice in the Yinchenhao decoction group and model group were fed with high-fat diet.After 12 weeks,the Yinchenhao decoction group was given Yinchenhao decoction by gavage,once a day for 4 consecutive weeks.Histopathological changes were observed by HE staining and oil red O staining.Serum HDL-C,LDL-C,TC,TG,AST,ALT and 5-HT contents,liver TC,TG,DAG,PLC contents were detected.Intestinal TPH1,SERT and liver HTR2A,SREBP-1c,GPAT1,FASN mRNA levels;Intestinal TPH1,SERT and liver HTR2A,SREBP-1c,GPAT1,FASN,P-PI3K,PKC-ε,P-AKT,P-mTOR protein expression level were detected.Results In the control group,the hepatocytes were arranged neatly without significant steatosis;In the model group,the hepatocytes were swollen in volume with significant steatosis;Compared with the control group,hepatocyte steatosis was significantly reduced in the Yinchenhao decoction group.Compared with the control group,liver lipid deposition was significantly higher in the model group,and the Yinchenhao decoction group significantly improved liver lipid deposition.Compared with the control group,the liver TG,TC levels in the model group were significantly increased(P<0.05);the serum AST,ALT,HDL-C,LDL-C,TG,TC levels were significantly increased(P<0.05);the serum 5-HT and liver DAG,PLC was significantly increased(P<0.05);the mRNA expression levels of HTR2A,SREBP-1c,GPAT1,FASN in the liver and TPH1 in the Intestinal were significantly increased,SERT in the Intestinal were significantly decreased(P<0.05);the protein expression levels of HTR2A,SREBP-1c,GPAT1,FASN,P-PI3K,P-AKT,P-mTOR,PKC-ε in the liver were significantly increased,and TPH1 in the Intestinal were significantly increased,SERT in the Intestinal were significantly decreased(P<0.05).Compared with the model group,the liver TG,TC levels in Yinchenhao decoction group were significantly decreased(P<0.05);the serum AST,ALT,LDL-C and TG levels were significantly decreased(P<0.05);the serum 5-HT and liver DAG,PLC level was significantly decreased;The mRNA expression levels of HTR2A,SREBP-1c,GPAT1,FASN in the liver and TPH1 in the Intestinal were significantly decreased,SERT in the Intestinal were significantly increased(P<0.05);the protein expression levels of HTR2A,SREBP-1c,GPAT1,FASN,P-PI3K,P-AKT,P-mTOR,PKC-ε in the liver were significantly decreased and TPH1 in the Intestinal were significantly increased,SERT in the Intestinal were significantly increased(P<0.05).Conclusion Yinchenhao decoction may regulate liver TG synthesis through Intestinal TPH1-hepatic HTR2A axis,thereby inhibiting the occurrence and development of MAFLD.

Gray Matter Volume Reductions Were Associated with TPH1 Polymorphisms in Depressive Disorder Patients with Suicidal Attempts

OBJECTIVE: Structural changes of brain areas have been reported in depressive disorder and suicidal behavior (SB), in which TPH1 also has been known as a promising candidate gene. We investigated gray matter volume (GMV) differences, TPH1 rs1800532 and rs1799913 polymorphisms previously found to be associated with depressive disorder and SB, and the relationship between the two markers. METHODS: Thirteen depressive disorder patients with suicidal attempts (SA) and twenty healthy controls were included. We examined GMV differences using a voxel-based morphometry and regions of interest analysis. Direct sequencing was used for genotyping. RESULTS: The patients showed significant GMV reduction in left cerebral region including middle frontal gyrus, inferior frontal gyrus, and anterior cingulate cortex; in right middle temporal gyrus; in left cerebellar tonsil; and in right cerebral region including precentral gyrus and postcentral gyrus (corrected p < 0.005). The right precentral and postcentral gyri GMV values of AA and CA genotypes patients were significantly decreased compared to those of CC genotype subjects (corrected p=0.040). CONCLUSION: These findings show the possibility that both GMV reductions and TPH1 rs1800532/rs1799913 A allele may be involved in the pathogenesis of depressive disorder patients with SA.

Effects of baldrinal of Valeriana jatamansi on expression of CRF, TPH1 mRNA and 5-HT in rats with irritable bowel syndrome / 中国中药杂志

This study aimed to investigate the effects of baldrinal of Valeriana jatamansi on the expression of corticotropin releasing factor (CRF) and tryptophan hydroxylase 1 (TPH1) mRNA and levels of 5-hydroxytryptamine (5-HT) in colon of rats with irritable bowel syndrome (IBS), and to explain its therapeutic mechanism on IBS through 5-HT pathway. Fifty-four male SD rats were randomly divided into 6 groups: blank group, model group, baldrinal high, medium and low dose groups, and pinaverium bromide group, n=9 in each group. The IBS rat models were established by using unpredictable chronic stress for 3 weeks followed by 1-hour acute restraint stress (CAS) after 7 days of rest and independent feeding. CRF expression was detected by IHC-P; TPH1 mRNA expression was detected by using RT-PCR and the 5-HT level was measured by high performance liquid chromatography(HPLC). The results indicated that the method of chronic stress with acute restrain stress method and independent feeding could lead to the increase in expressions of CRF and TPH1 mRNA and levels of 5-HT in IBS rats(P<0.05). The expressions of CRF, TPH1 mRNA and 5-HT in baldrinal groups were significantly lower than those in model group(P<0.05). The experimental results showed that IBS could result in increase in the expressions of CRF, TPH1 mRNA and levels of 5-HT, and the baldrinal of V. jatamansi could improve the symptoms of IBS by reducing the expressions of CRF, TPH1 mRNA and levels of 5-HT in colon of rats.