Effect of processing with vinegar on efficacy of Curcuma longa in treatment of dysmenorrhea in rats with syndrome of liver depression and Qi stagnation / 中国中药杂志

This study compared the effects of Curcuma longa before and after processing with vinegar on the rat model of dysmenorrhea with the syndrome of liver depression and Qi stagnation to reveal the mechanism of vinegar processing in improving the role of C. longa in soothing liver and relieving pain. The rat model of dysmenorrhea with the syndrome of liver depression and Qi stagnation was established according to the Preparation of the Animal Model of Dysmenorrhea(Draft) and the chronic unpredictable stress me-thod. The changes in the body weight, organ indexes, writhing latency, writhing score, and serum levels of six liver function indicators, sex hormones, pain factors, and blood rheological indicators were measured to evaluate the efficacy of C. longa processed with vinegar or not in treating dysmenorrhea in the rats with syndrome of liver depression and qi stagnation. Compared with the model group, the C. longa group(processed with vinegar or not) showed slow weight loss, increase in writhing latency, and decrease in writhing response(P<0.05). The inhibition rates on writhing in raw C. longa, vinegar-processed C. longa, and positive groups were 33.780%, 64.611%, and 62.466%, respectively. The significantly higher inhibition rate of the vinegar processing group indicated that vinegar-processed C. longa demonstrated more significant therapeutic effect. The vinegar-processed C. longa group showed lower levels of alanine aminotransferase(ALT), alkaline phosphatase(ALP), aspartate aminotransferase(AST), direct bilirubin(DBIL), and total bilirubin(TBIL) and higher level of albumin(ALB)(P<0.05), which indicated that vinegar processing enhanced the therapeutic effect of C. longa on liver injury. The serum levels of estradiol(E_2) and oxytocin(OT) were lower in the vinegar-processed C. longa group(P<0.05), indicating that the vinegar-processed C. longa could regulate the sex hormone levels, reduce the activity of uterine smooth muscle and contraction of uterus, and alleviate the symptoms of dysmenorrhea in rats. Moreover, the vinegar-processed C. longa group showed lower interleukin-6(IL-6) and arginine vasopressin(AVP) levels and higher beta-endorphin(β-EP) level(P<0.05), which indicated that vinegar-processed C. longa regulated the levels of pain factors to exert the pain-relieving effect. Drug intervention decreased the whole blood viscosity low-cut, medium-cut and high-cut values, plasma viscosity, whole blood reduction viscosity low-cut and high-cut values, erythrocyte cumulative pressure, and equation K value of erythrocyte sedimentation rate(P<0.05), and the vinegar-processed C. longa group outperformed other groups. This result indicated that vinegar processing enhanced the function of C. longa in improving the local blood rheology. C. longa processed with vinegar can enter the liver to relieve the da-mage to the heart, liver, kidney, and uterus, repair the liver function, and recover the sex hormone levels and immune function by regulating the levels of sex hormones and pain factors and improving the blood rheology. It activates the pain-relieving mechanism to relieve the pain, protect the liver, and fight inflammation, which is consistent with the theory that vinegar processing facilitates C. longa entering the liver to sooth liver and relieve pain.

Clinical Study of Jiawei Xiaochaihutang Combined with Microwave Ablation in Treatment of Primary Hepatocellular Carcinoma / 中国实验方剂学杂志

ObjectiveTo observe the clinical efficacy of Jiawei Xiaochaihutang combined with microwave ablation （MWA） in the treatment of primary hepatocellular carcinoma （HCC） and its influence on tumor microenvironment. MethodA total of 128 patients were randomly divided into control group （64 cases： 2 cases of dropout，2 cases of elimination，and 60 cases of completion） and observation group （64 cases： 3 cases of dropout，2 cases of elimination，and 59 cases of completion）. Both groups were given comprehensive treatment after MWA surgery. Patients in control group took Biejiajian Wan orally （3 g/time，3 times/d）， and those in observation group took Jiawei Xiaochaihutang （1 dose/d）. The treatment lasted for 3 consecutive months. The size of solid tumor before and after treatment was evaluated to record the progression-free survival （PFS）. The alpha-fetoprotein-L13 （AFP-L3），des-γ-carboxy prothrombin （DCP），Golgi protein 73 （GP73），tumor necrosis factor-α （TNF-α），transforming growth factor-β （TGF-β），vascular endothelial growth factor （VEGF） and matrix metalloproteinase-2 （MMP-2） levels，as well as performance status （PS），liver function and syndrome of liver depression and Qi stagnation scores were also detected before and after treatment. In addition， the incidence of side effects of grade Ⅲ and above was compared. ResultThe total effective rate of solid tumor in observation group was 91.53% （54/59），higher than that （76.67%， 46/60） in control group（χ2=4.895，P<0.05）. The PFS in observation group was （7.16±0.95） months， longer than that （6.24±0.89 months） in control group （P<0.01）. The effective rate of traditional Chinese medicine （TCM） syndrome in observation and control groups were 88.14% （52/59）and 70.00% （42/60）， respectively （χ2=5.897，P<0.05）. The observation group （57.63%，34/59） had higher marked effective rate of TCM syndrome than control group （31.67%，19/60） （χ2=8.116，P<0.01）. The AFP-13，DCP，GP73，TNF-α，TGF-β，VEGF and MMP-2 levels and the PS，liver function and syndrome of liver depression and Qi stagnation scores in observation group were lower than those in control group （both P<0.01）. The cumulative incidence of side effects of grade Ⅲ and above in observation and control groups was 16.95% and 33.33%， respectively（χ2=4.261，P<0.05）. ConclusionConsolidation treatment of HCC after MWA surgery with Jiawei Xiaochaihutang relieved symptoms and side effects，improved PS and liver function，regulated tumor microenvironment，inhibited tumor markers and prolonged survival time. The clinical effect was better than that of Biejia decoction pill， and thus it was worthy of clinical use.

Study on construction of rat model of acute pancreatitis with syndrome of liver depression and Qi stagnation / 中国中药杂志

The aim of this paper was to construct a rat model of acute pancreatitis(AP) with syndrome of liver depression and Qi stagnation, and provide evaluation tools for pharmacodynamic research and efficacy network verification of related traditional Chinese medicine in view of the etiology, pathogenesis and clinical manifestations of AP. According to the Chinese and Western medicine diagnosis and treatment guidelines for AP with syndrome of liver depression and Qi stagnation, etiology, pathogenesis and clinical syndromes in TCM, Meta-analysis results, and evaluation strategy of establishing an animal model combining disease and syndrome in our laboratory, the biological surrogate outcomes suitable for the evaluation of animal models of AP with syndrome of liver depression and Qi stagnation were extracted then. The chronic unpredictable stress(CUS) method and chronic unpredictable stress +L-arginine(CUS +L-Arg) method were used to construct the rat model, and the above biological surrogate outcomes were used to evaluate whether an AP rat model was established. During the experiment, the weight and syndrome scores of the rats were observed and recorded. At the end of the experiment, the rats' serum, organs and tissues were collected from the operation to detect the various indicators. As compared with the normal group, the syndrome scores of the CUS group and CUS +L-Arg group were significantly increased(P<0.01); the anti-syndrome medicine Chaihu Shugan Pills could significantly reduce the syndrome scores of the two groups of rats(P<0.01), indicating that both modeling methods can replicate the syndrome of liver depression and Qi stagnation in the rat model. As compared with the normal group, the serum amylase(AMY) activity level was increased by 3 times in the CUS +L-Arg group(P<0.01), and the AMY activity level was also increased in CUS group, but not up to 3 times of the normal value. As compared with the normal group, the le-vels of TNF-α and IL-6 mRNA in the pancreatic tissues of the CUS +L-Arg group were significantly increased(P<0.01); the levels of TNF-α mRNA in the pancreatic tissues of the CUS group were significantly increased(P<0.05), but IL-6 mRNA level only showed a rising trend, indicating that only the CUS + L-Arg method can be used to replicate the AP damage in the disease-syndrome combination model. The CUS + L-Arg method can be used for continuous modeling for 4 weeks to establish a disease-syndrome combination model of AP rats with syndrome of liver depression and Qi stagnation. The model has the characteristics of repeatability, stability after mode-ling, low animal mortality, and similar clinical pathogenesis. It can be used for the evaluation of traditional Chinese medicine efficacy and the verification of efficacy network.

Study on effective components and mechanism of Dachaihu Decoction in treatment of pancreatitis (syndrome of liver depression and qi stagnation) / 中草药

Objective: To study the effective components and mechanism of action of Dachaihu Decoction (DCHD) in the treatment of pancreatitis (syndrome of liver depression and qi stagnation). Methods: The PPI network and the multi-dimensional relationship network of “Chinese material medica prescription active ingredient key target” of DCHD in the treatment of pancreatitis with stagnation of liver qi. Based on network pharmacology, the software such as Cytoscape 3.6.0 was firstly used to construct the PPI interaction network of key targets in the Chinese material medica with the effect of soothing liver and regulating qi (“Shugan Liqi” in Chinese) and DCHD “Chinese material medica prescription-effective components-key target” multi-dimensional network for the treatment of pancreatitis, and then treat the two networks as an intersection to obtain the network of DCHD for the treatment of pancreatitis (syndrome of liver depression and qi stagnation) “Chinese material medica prescription-effective components-key target”, and finally analyzed with relevant software. Results: A total of 59 key targets for Shugan Liqi were obtained such as AKT1, VEGFA, and PRSS1; A total of 83 main active ingredients such as quercetin, kaempferol and baicalein were collected from DCHD. The treatment of pancreatitis (syndrome of liver depression and qi stagnation) involved 18 targets of Ganyu Qizhi such as PTGS2, DPP4, PRSS1, and 30 related biological processes and signaling pathways such as extracellular matrix degeadation, IL-17 signaling pathway, and AGE-RAGE signaling pathway in diabetic complications. Conclusion: The multi-component and multi-target in DCHD are the basis for its efficacy. It is worthwhile to deeply think about the use of network pharmacology in the context of syndrome research.