Huganbuzure Granule Attenuates Concanavalin-A-Induced Immune Liver Injury in Mice via Regulating the Balance of Th1/Th2/Th17/Treg Cells and Inhibiting Apoptosis.
Wang Mengheng,Yin Hailong,Xia Yu,Tu Yijun,Zou Xinshuang,Song Wanci,Luo Laichun,Wu Hezhen,Yang Yanfang,Zan Junfeng,Liu Yanwen,Dan Hanxiong,Yin Qiang,You Pengtao
Evidence-based complementary and alternative medicine : eCAM
In Uygur medicine, Huganbuzure granule (HBG) is one of the classical prescriptions for liver protection. However, its role in immune liver injury remains unknown. This study evaluates the effect of HBG on concanavalin-A- (ConA-) induced immune liver injury and investigates its protective underlying mechanism. BALB/c mice were randomly divided into five groups ( = 24 mice per group): control, ConA, 1.6 g/kg HBG + ConA, 3.2 g/kg HBG + ConA, and 6 mg/kg prednisolone + ConA. HBG was intragastrically administrated once daily for ten consecutive days, prior to ConA (20 mg/kg) injection. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), superoxide dismutase (SOD), and malondialdehyde (MDA) in mouse serum were measured after ConA injection. Moreover, liver-related mRNA levels were evaluated by qPCR. The detection of liver-related proteins was assessed by immunohistochemistry and western blot analysis. Compared with the ConA group, HBG reduced the mRNA expression of IL-17A and IFN- and the protein expression of T-bet and ROR-t. In addition, HBG increased the mRNA expression of IL-4 and TGF- and protein expression of GATA3 and Foxp3, indicating that HBG regulated the balance of Th1/Th2 and Th17/Treg. Furthermore, HBG alleviated immune liver injury by reducing oxidative stress, inhibiting apoptosis, and decreasing the expression of p-JNK, p-ERK, p-p38, p-JAK1, p-STAT1, p-STAT3, and IRF1. Our data suggested that HBG attenuated ConA-induced immune liver injury by regulating the immune balance and inhibiting JAK1/STATs/IRF1 signaling, thereby reducing apoptosis induced by JNK activation. The findings indicate that HBG may be a promising drug for immune liver injury.
Transcriptomic Analysis Exploring the Molecular Mechanisms of Hanchuan Zupa Granules in Alleviating Asthma in Rat.
Yin Hailong,Fan Yanbo,Mu Dandan,Song Fei,Tian Fang,Yin Qiang
Evidence-based complementary and alternative medicine : eCAM
Objective:To investigate the molecular mechanisms of HCZP treatment of asthma. Materials and Methods:Thirty Sprague Dawley (SD) rats were divided into normal, asthma, and HCZP groups ( = 10). The asthma model was sensitized by 1 mg ovalbumin (OVA)/aluminum hydroxide Al(OH)mixture and then challenged with 1% aerosolized OVA for four weeks. Rats in the HCZP group received 10.08 g/kg/d HCZP for four weeks during OVA challenge. Then, lung tissues of rats in each group were collected for RNA sequencing. Moreover, the expression level of some core genes was detected by using western blotting and immunohistochemistry. Results:Inflammatory cell infiltration and pathological damage of the lungs improved in the HCZP group. Compared with the asthma group (0.049 ± 0.002 mm/mm; 0.036 ± 0.006 mm/mm; and 0.014 ± 0.001 mm/mm), total wall thickness (0.042 ± 0.001 mm/mm), inner wall thickness (0.013 ± 0.001 mm/mm), and smooth muscle layer thickness (0.012 ± 0.001 mm/mm) significantly decreased in the HCZP group. Bioinformatics analysis showed that hub genes such as bradykinin receptor B2 (Bdkrb2) and CD4 molecule (Cd4) had different expression patterns between model and HCZP groups. Two transcription factors, forkhead box Q1 (Foxq1) and nuclear factor of activated T cells 2 (Nfatc2), served important regulatory roles in asthma. Compared with the model group, Bdkrb2 protein expression increased and Nfatc2 protein expression decreased in the HCZP group. . HCZP could alleviate asthma via regulating the expression of several hub genes, which might serve as therapeutic targets for asthma. However, the mechanism of these genes will be studied in the future.
Network pharmacology analysis and experimental validation to explore the mechanism of Hanchuan Zupa Granule in asthma.
Zhang Ya-Li,Yin Qiang,Peng Hui-Ming,Huang Rong,Zhou Jie-Wen,Liu Lin-Hui,Gao Han-Qi,Zhao Chuan-Peng,Peng Xin-Hang,Xiao Ling,Nie Jing,Yang Quan-Cheng,He Chun-Ye,Hu Gao-Sheng,Chen Jia-Chun,Jia Jing-Ming,Fang Jin-Bo
Journal of ethnopharmacology
ETHNOPHARMACOLOGICAL RELEVANCE:Hanchuan Zupa Granule (HCZP) is a classic prescription of Uyghur medicine, that is used for cough and abnormal mucinous asthma caused by a cold and "Nai-Zi-Lai". AIM OF THE STUDY:This study aimed to explore the possible molecular mechanism of HCZP in the treatment of asthma, using a network pharmacology method and in vivo experiments. MATERIALS AND METHODS:First, we conducted qualitative analysis of the chemical composition of HCZP as a basis for network pharmacology analysis. Using network pharmacology tools, the possible signaling pathways of HCZP in the treatment of asthma were obtained. An OVA-sensitized asthma model was established, and HCZP was continuously administered for one week. BALF was collected for cell counting, and serum and lung tissues were collected to analyze the expression of IgE, IL-4, IL-5, IL-13 and IFN-γ. Hematoxylin & eosin (H&E) staining was performed to assess the pathological changes in the lung tissues. Related protein expression in the lung tissues was analyzed by Western blotting for molecular mechanism exploration. RESULTS:Fifty-six chemical compounds were identified by UPLC Q-TOF MS. According to the network pharmacology results, 18 active compounds were identified among the 56 compounds, and 68 target genes of HCZP in the treatment of asthma were obtained. A total of 19 pathways were responsible for asthma (P < 0.05) according to KEGG pathway analysis. In vivo results showed that OVA sensitivity induced increased respiratory system resistance and inflammatory responses, which included inflammatory cell infiltration and high levels of IgE, IL-4, IL-5 and IL-13 in serum and lung tissues. Furthermore, OVA upregulated p-PI3K, p-JNK and p-p38 expression in lung tissues. Moreover, HCZP treatment significantly downregulated respiratory system resistance, and the expression of IL-4, IL-5, IL-13 and IgE, as well as significantly improved inflammatory cell infiltration in lung tissues. Moreover, the protein expression of p-PI3K, p-JNK and p-p38 in lung tissues decreased after HCZP treatment. CONCLUSION:HCZP significantly inhibited the OVA-induced inflammatory response via the PI3K-Akt and Fc epsilon RI signaling pathways.