Current Computer-Aided Drug Design
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2024
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IF 1.5
Na An,Dongxing Zhang,Jile Xin,Xinyi Zhang,Zhijuan Zhang,Ligang Ma,Le Zhao,Huimin Wu,Weisheng Feng,Xiaoke Zheng
Background: Si-Ni-San (SNS) is the formula prescription of Traditional Chinese Medicine (TCM) with anti-depression properties, but its underlying mechanisms remain unclear. Objective: This study provides novel approaches for the study of Traditional Chinese Medicine (TCM) and offers new opportunities for exploring the pharmacological properties of SNS. Methods: The ingredients in SNS implicated in the treatment of depression were identified and studied using network pharmacology. SwissTargetPrediction and molecular docking were used to study the interaction of SNS ingredients and their targets. The protective effect of these ingredients and their cocktail in rat pheochromocytoma cells (PC12) exposed to corticosterone (Cor) were evaluated using the CCK-8 assay, Hoechst 33342 staining, 2',7'-dichlorodihydro fluorescein diacetate (H2DCFDA) staining, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, and in-cell Western analysis. Results: The network pharmacology study showed that the HIF-1 signaling pathway was the most crucial pathway implicated in the anti-depressive property of SNS. MAPK1 (ERK2), MAPK3 (ERK1), AKT1, VEGFA, STAT3, and EGF were identified as hub target proteins in the HIF-1 signaling pathway. Quercetin, naringenin, licochalcone A, and kaempferol from SNS, which targeted the six proteins mentioned above, were used to create a cocktail. This cocktail exerted protective properties, decreased the oxidative stress in PC12 exposed to Cor, and successfully regulated the expressions of AKT1, p-AKT1, ERK1, ERK2, p-ERK1/2, STAT3, p- STAT3, and VEGFA induced by Cor exposure. The SwissTargetPrediction and molecular docking study showed that the cocktail may regulate the HIF-1 signaling pathway by directly binding with AKT1 and MAPK1. Conclusion: The cocktail from SNS comprised of quercetin, naringenin, licochalcone A, and kaempferol exerts anti-depression potentiality by modulating the HIF-1 signaling pathway via direct interactions with AKT1 and MAPK1.
研究领域:
神经药理学
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传统中药研究
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分子生物学
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药效学
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细胞信号传导
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2024
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IF 4.4
Wu Qiong,Zhu Fangsi,Yao Yu,Chen Luyun,Ding Yijie,Su Yong,Ge Chaoliang
Introduction: Si-Ni-San (SNS), a traditional Chinese medicine, is effective in treating liver fibrosis with an unclear mechanism. Although disturbance of intestinal flora and the subsequent secretion of short-chain fatty acids (SCFAs) is suggested to be involved in the progression of liver fibrosis, whether SNS produces the anti-fibrosis effect through the regulation of intestinal flora and SCFAs remains unclear.Methods: In the current study, carbon tetrachloride (CCl4)-treated mice were dosed with SNS to examine the anti-fibrotic effects and the involved mechanism. Biochemical parameters, histological staining, and analyses of fibrotic gene expression were used to evaluate the anti-fibrotic effect of SNS, while intestinal flora and SCFA content were determined by 16S rRNA and LC–MS to evaluate the mechanism.Results: In vivo results showed that SNS improved liver function, reduced hepatocyte apoptosis and FFAR2/3 expression, and restored intestinal dysbiosis and reduced PA, BA, and IsA levels. In vitro experiments showed that PA, BA, and IsA exacerbated TNF-α-induced HepG2 apoptosis. Notably, the protective effects of SNS were compromised in pseudo-sterile mice.Discussion: In conclusion, our experimental results suggest that the disturbance in intestinal flora results in elevated SCFA levels, which further exacerbates hepatocyte apoptosis in liver fibrosis, while SNS suppresses CCl4-induced liver fibrosis at least partially by reinstating intestinal flora homeostasis and reducing SCFA levels.
研究领域:
药理学
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肝病学
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微生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Current Research in Food Science
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2024
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IF 6.2
Weidong Xu,Shasha Tian,Guanqun Mao,Yu Li,Hua Qian,Wenhua Tao
Sini San (SNS) is used to treat liver depression and is applied in both food and herbal medicine. Hyperprolactinemia (HPRL) is a common endocrine disorder, and patients with HPRL are usually associated with depressive symptoms. However, whether SNS is effective in treating HPRL combined with liver depression and its underlying mechanisms are unknown. We applied network pharmacology and molecular docking to predict the mechanism of SNS for the treatment of liver-depressed HPRL. Therapeutic effects were validated in animal models and cells. Metabolomics was also used to evaluate the effect of SNS on liver-depressed HPRL. Network pharmacology and molecular docking analysis showed that AKT1, TNF and IL6 were the key targets, and SNS improved depressive behaviors, regulated sex hormone levels, and improved ovarian morphology. Combined network pharmacology and metabolomics analyses showed that SNS could act by regulating lipid metabolism. In addition, SNS significantly reduced the release of prolactin (PRL) in rat pituitary tumor MMQ cells. Overall, SNS can significantly treat HPRL liver depression at both animal and cellular levels, and effectively alleviate the related symptoms by regulating lipid metabolism. AKT1, TNF and IL6 may be key targets.
研究领域:
药理学
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内分泌学
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神经科学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
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2021
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IF 5.34
Yajie Cai,Bing Xu,Fei Zhou,Jianzhi Wu,Shuo Li,Qi Zheng,Yajing Li,Xiaojiaoyang Li,Feng Gao,Shifen Dong,Runping Liu
Background Ulcerative colitis (UC) is a chronic relapsing inflammatory disease that markedly elevates the risk of colon cancers and results in disability. The disrupted immune homeostasis has been recognized as a predominant player in the pathogenesis of UC. However, the overall remission rate of current therapies based on immunoregulation is still unsatisfactory. Si-Ni-San (SNS) has been found effective in relieving UC through thousands of years of clinical practice, yet the specific mechanisms of the protective effect of SNS were not fully elucidated. Purpose We aim to investigate the therapeutic effects of SNS against the development of chronic colitis and the underlying mechanisms. Methods We established a DSS-induced chronic experimental colitis mouse model to evaluate the effect of SNS. RNA-sequencing, bioinformatic analysis, and in vitro studies were performed to investigate the underlying mechanisms. Results Our data demonstrated that SNS significantly ameliorated chronic experimental colitis via inhibiting the expression of genes associated with inflammatory responses. Interestingly, SNS significantly suppressed DSS-induced type I interferon (IFN) responses instead of directly downregulating the production of pro-inflammatory cytokines, such as Il-6. In vitro study further found that SNS selectively inhibited STING and RIG-I pathway-induced type I IFN responses by modulating TBK1- and IRF3-dependent signaling transduction. SNS also suppressed the expression of IFN-stimulated genes by directly inhibiting STAT1 and STAT2 activation. Conclusion Our study not only provides novel insights into the pathogenic role of type I IFN responses in colitis but also suggested that SNS or bioactive compounds derived from SNS may serve as novel therapeutic strategies for the treatment of UC via interfering type I IFN-mediated inflammation.
研究领域:
药理学
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免疫学
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胃肠病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2022
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IF 5.195
Yajie Cai,Xiaojiaoyang Li,Qi Han,Jinzhao Bai,Qi Zheng,Rong Sun,Runping Liu
Ethnopharmacological relevance Ulcerative colitis (UC) is widely believed to be a leading risk factor of colorectal cancer . Gut microbiota is a known vital player in the progression of UC. Si–Ni-San (SNS) has been considered to effectively treat colitis in clinical practice during thousands of years, yet whether SNS ameliorated acute colitis mouse model by modulating intestinal flora has not been distinctly elucidated. Aim of the study Our study aimed to elucidate the effect of SNS against acute murine colitis and focused on the underlying mechanisms of SNS targeting gut microbiota . Materials and methods 16S RNA sequencing, molecular biological analysis, and fecal microbiota transplants (FMT) were conducted to reveal the mechanisms of SNS in regulating gut microbiota. Results In our study, SNS dramatically inhibited DSS-induced acute inflammatory responses by improving gut microbiota dysbiosis , as evidenced by decreased abundance proinflammatory species, upregulated abundance of anti-inflammatory species and potentially altered microbiota metabolite metabolism. Additionally, intestinal flora knockout and FMT experiments confirmed that the therapeutic effect of SNS on colitis was dependent on gut microbiota, and specifically on favoring the growth of potential probiotics , Akkermansia genus. Furthermore, we found that SNS alone and SNS combined with Akkermansia muciniphila ( A. muciniphila ) increased Mucin 2 (MUC2) production, thus enhancing the competitive edge of A. muciniphila among pathogenic gut microbiota. Conclusion Our study shed lights on the underlying mechanism of SNS in attenuating acute murine colitis from the perspective of intestinal flora and provides novel insights into the discovery of adjacent therapeutic strategy against colitis based on SNS and probiotics. Classification Gastro-intestinal system
研究领域:
消化系统
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药理学
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微生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
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2023
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IF 4.8
Ning Zhang,Tong Liu,Jianan Wang,Yingying Xiao,Ying Zhang,Jun Dai,Zhihong Ma,Donglai Ma
Background Metabolic associated fatty liver disease (MAFLD) is a chronic disease characterized by excessive lipid deposition in the liver without alcohol or other clear liver-damaging factors. AMP-activated protein kinase (AMPK)/silencing information regulator (SIRT)1 signaling pathway plays an important role in MAFLD development. Si-Ni-San (SNS), a traditional Chinese medicine, has shown reducing hepatic lipid deposition in MAFLD rats, however, the underlying mechanisms of SNS are barely understood.Purpose The aim of this research was to investigate the mechanisms of SNS in reducing hepatic lipid deposition in MAFLD rats by regulating AMPK/SIRT1 signaling pathways.Methods The components of SNS were determined by high performance liquid chromatography with mass spectrometry (HPLC-MS) analysis. MAFLD rats were induced by high-fat and high-cholesterol diet (HFHCD), and treated by SNS. SNS-containing serum and Compound C (AMPK inhibitor) were used to treat palmitic acid (PA)-induced HepG2 cells. To elucidate the potential mechanism, lipid synthesis-related proteins (SREBP-1c and FAS), fatty acid oxidation (PPARα and CPT-1), and AMPK/SIRT1 signaling pathway (p-AMPK and SIRT1) were assessed by Western blot.Results SNS improved serum lipid levels, liver function and reduced hepatic lipid deposition in MAFLD rats. SNS-containing serum reduced lipid deposition in PA-induced HepG2 cells. SNS could up-regulate protein expressions of PPARα, CPT-1, p-AMPK and SIRT1, and down-regulate protein expressions of SREBP-1c and FAS. Similar effects of SNS-containing serum were observed in PA-induced HepG2 cells. Meanwhile, Compound C weakened the therapeutic effects of SNS-containing serum on lipid deposition.Conclusion SNS could reduce hepatic lipid deposition by inhibiting lipid synthesis and promoting fatty acid oxidation, which might be related with activating the AMPK/SIRT1 signaling pathway. This study could provide a theoretical basis for the clinical use of SNS to treat MAFLD.
研究领域:
药理学
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肝病学
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中医药
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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