Effects of Huangqin Tang on NLRP3/Caspase-1 pathway in mice model of ulcerative colitis / 中国中药杂志

The aim of this study was to explore the effects of Huangqin Tang(HQT) on the NLRP3/Caspase-1 signaling pathway in mice with DSS-induced ulcerative colitis(UC). C57BL/6J mice were randomly divided into a blank group, a model group(DSS group), and low-, medium-and high-dose HQT groups(HQT-L, HQT-M, and HQT-H), and western medicine mesalazine group(western medicine group). The UC model was induced in mice. Subsequently, the mice in the HQT-L, HQT-M, HQT-H groups, and the western medicine group were given low-, medium-, high-dose HQT, and mesalazine suspension by gavage, respectively, while those in the blank and DSS groups were given an equal volume of distilled water by gavage. After 10 days of administration, the body weight, DAI scores, and colonic histopathological score of mice in each group were determined. The levels of IL-6, IL-10, IL-1β, and TNF-α in serum were determined by ELISA. The mRNA expression of NLRP3 and Caspase-1 in colon tissues was determined by RT-qPCR. The protein expression of NLRP3 and Caspase-1 in colon tissues was detected by immunohistochemistry. The results showed that compared with the blank group, the DSS group showed decreased body weight of mice and increased DAI scores and intestinal histopathological score. Compared with the DSS group, the HQT groups and the western medicine group showed improved DAI scores, especially in the HQT-M, HQT-H, and the western medicine groups(P<0.05). The intestinal histopathological scores of the HQT groups and the western medicine group significantly decreased, especially in the HQT-M, HQT-H, and the western medicine groups(P<0.05). In addition, compared with the blank group, the DSS group showed elevated expression of NLRP3 and Caspase-1 in colon tissues, increased serum levels of IL-6, IL-1β, and TNF-α, and decreased IL-10 level. Compared with the DSS group, the HQT groups and the western medicine group displayed decreased expression of NLRP3 and Caspase-1 in colon tissues, reduced serum levels of IL-6, IL-1β, and TNF-α, and increased IL-10 level. The improvement was the most significant in the HQT-H group and the western medicine group(P<0.01). In conclusion, HQT may reduce the expression of NLRP3 and Caspase-1 in colon tissues, reduce the se-rum levels of IL-6, IL-1β, and TNF-α, and increase the expression of IL-10 by regulating the classic pyroptosis pathway of NLRP3/Caspase-1, thereby improving the symptoms of intestinal injury and inflammatory infiltration of intestinal mucosa in DSS mice to achieve its therapeutic effect.

The effects of Huangqin Tang on oxidative stress and ulcerative colitis in rats through the Nrf2 signal pathway / 药学学报

This study aimed to investigate the effect of Huangqin Tang (HQT) on oxidative stress associated with ulcerative colitis in rats, and to explore its antioxidant mechanism. After approved by Institute of Chinese Materia Medica Ethics Committees in China Academy of Chinese Medical Sciences, the rats were given 2,4,6-trinitrobenzenesulfonic (TNBS)/ethanol mixture to induce the ulcerative colitis (UC), and were randomly divided into normal group, model group, the salazosulfapyridine (SASP) group, and high, middle or low dose (20, 10, 5 g·kg-1) of HQT groups. After 5 days of treatment, the activity of catalase (CAT) from micrococcus lysodeikticus, glutathione peroxidase (GSH-px), myeloperoxidase (MPO), superoxide dismutase (SOD) were detected by biochemical assays. The levels of lipid peroxide (LPO) were detected by ELISA. The positive protein expression of nuclear factor erythroid-2-related factor 2 (Nrf2) were detected by immunohistochemistry method and the downstream antioxidant enzymes of Nrf2 were determined by Western blot analyses. The levels of SOD, CAT and GSH-px activities in the normal group were significantly higher than the model group, while the serum MPO activity in the model group was obviously increased (P<0.05 or P<0.01). Compared with the model group, there was a significant difference in the activity of CAT in the high and middle dose groups of HQT (P<0.05 or P<0.01), the activity of GSH-px in the high, middle and low dose groups of HQT were apparently higher than the model group (P<0.05); The serum levels of LPO in the model group were significantly higher than those in the normal group (P<0.05), while the up-regulating effects on LPO were reversed by the high and middle dose groups of HQT (P<0.05). The expression of Nrf2 in the high-dose group of HQT and SASP group was statistically significant (P<0.05). The results of Western blot showed that compared with the model group, each of the HQT and SASP group could increase the heme oxygenase (HO-1) and NAD[P]H: quinone oxidoreductase 1 (NQO-1) expression in a dose-dependence manner. HQT has significant anti-oxidative stress and obviously improves the signs, mental status and defecation of UC rats. The mechanism of action for HQT maybe related to activate the Nrf2 pathway and increase the expression of Ⅱ phase metabolic enzymes such as HO-1 and NQO-1, reduce the content of LPO and MPO in serum and enhance the activity of SOD, CAT and GSH-px.

Effect of Huangqin Tang on serum metabolic profile in rats with ulcerative colitis based on UHPLC-MS / 药学学报

The study is aimed to test the effect of Huangqin Tang (HQT) on serum metabolic profile in rats with ulcerative colitis, and explore its possible action mechanism for ulcerative colitis (UC) rats. The model of UC rats with cell immunoreactivity was made using a compound method (trinitrobenzene sulfonic acid plus ethanol). Rats were randomly divided into the control group, the model group, and HQT group. Ultra performance liquid chromatography tandem mass spectrometry (UHPLC-MS), principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were employed to analyze the metabolic profile among normal group, the model group, HQT group. Potential biomarkers were screened in the serum based on the variable importance projection (VIP) value > 1, P< 0.05. As compared with the normal group, 16 potential biomarkers such as valine, tryptophan, lactic acid and urea were found and identified in the serum of model group rats. As compared with the model group, a part of the biomarkers were restored nearly to a normal state after HQT administration for 10 days. Metabolomic analysis revealed that the HQT has a certain therapeutic effect in UC rats, and the mechanism may be related to regulation of lipid metabolism, amino acid metabolism and energy metabolism.

Effect of Huangqin Tang on the function of regulatory TLR4/MyD88 signal pathway in rats with ulcerative colitis / 药学学报

This study was designed to investigate the effect of Huangqin Tang (HQT) on TLR4/Myd88 pathway and the downstream cytokines in rats with ulcerative colitis (UC) to explore its underlying mechanisms of action. The model of UC rats with cell immunoreactivity was made using a compound method (trinitrobenzene sulfonic acid plus ethanol). Rats were randomly divided into the control group, the model group, the salazosulfapyridine (SASP) group, high, medium and low dose (20, 10, 5 g·kg-1) of HQT groups. After a three-day treatment, production of NO in serum was detected by Griess assay, the levels of interleukin (IL)-4, IL-10, IL-17 and prostaglandin E2 (PGE2) in serum were detected by ELISA. After a five-day treatment, the positive protein expressions of COX-2 and iNOS in the colon tissue were determined by ICH method, the protein expressions of TLR4 and MyD88 in colon tissue were determined by Western blot. Compared with the control group, the levels of NO, IL-17, PGE2, the protein expressions of TLR4, MyD88 and the protein positive expressions of COX-2, iNOS were apparently higher in the model group. Compared with model group, the above indexes were significantly improved in the SASP and high-dose HQT groups (PκB signal pathway and down-regulation of NO, IL-17 and PGE 2 production.

The Pathoenesis of HuangQin Tang / 浙江中医药大学学报

Objective] The pathogenesis of HuangQin Tang is discussed little in six meridians syndrome differentiation, and which meridian syndrome does it belong to isn’t clear. So this article tries to discuss the belonging and pathogenesis of it. And the key point of using it in clinic will also be involved.[Method] Combining the observation of efficacy of XiaoChaiHu Tang and HuangQin Tang and the elaboration articles are related to that two prescriptions to analyze the difference of that two prescriptions in pathogenesis.[Result]It’s found that HuangQin Tang and XiaoChaiHu Tang all belong to ShaoYin in six meridian syndrome.But their pathogenesis is different. HuangQin Tang should be used in heat syndrome of ShaoYang disease which caused by heat pathogen of ShaoYang meridian and diarrhea will appear because belly is shocked. However, XiaoChaiHu Tang is used to drive cold pathogen of ShaoYang meridian. [Conclusion]Both of HuangQin Tang and XiaoChaiHu Tang belong to ShaoYang Meridian, but it’s known that HuangQin Tang is used less. And less discussion of HuangQin Tang should be blamed. The more we know on pathogenesis of HuangQin Tang, the better we use it.