{"title":"Proteomic analysis and experimental validation reveal the blood-brain barrier protective of Huanshaodan in the treatment of SAMP8 mouse model of Alzheimer's disease.","authors":"Yunfang Su, Ningning Liu, Pan Wang, Congcong Shang, Ruiqin Sun, Jinlian Ma, Zhonghua Li, Huifen Ma, Yiran Sun, Zijuan Zhang, Junying Song, Zhishen Xie, Jiangyan Xu, Zhenqiang Zhang","doi":"10.1186/s13020-024-01016-7","DOIUrl":"10.1186/s13020-024-01016-7","url":null,"abstract":"<p><strong>Background: </strong>Huanshaodan (HSD) is a Chinese Herbal Compound which has a definite clinical effect on Alzheimer's disease (AD), however, the underlying mechanism remains unclear. The aim of this study is to preliminarily reveal the mechanism of HSD in the treatment of AD model of SAMP8 mice.</p><p><strong>Methods: </strong>Chemical composition of HSD and its drug-containing serum were identified by Q-Orbitrap high resolution liquid mass spectrometry. Six-month-old SAMP8 mice were treated with HSD and Donepezil hydrochloride by gavage for 2 months, and Wogonin for 28 days. Behavioral test was performed to test the learning and memory ability of mice. Immunofluorescence (IF) or Western-blot methods were used to detect the levels of p<sup>Ser404</sup>-tau and β-amyloid (Aβ) in the brain of mice. Hematoxylin-eosin (H&E) staining and Transmission electron microscopy (TEM) assay was applied to observe the pathological changes of neurons. Proteomic technology was carried out to analyze and identify the protein network of HSD interventions in AD. Then the pathological process of the revealed AD-related differential proteins was investigated by IF, Q-PCR, Western-blot, Fluorescence in situ hybridization (FISH) and 16S rRNA sequencing methods.</p><p><strong>Results: </strong>The results showed that HSD and Wogonin, one of the components in its drug-containing serum, can effectively improve the cognitive impairments of SAMP8 mice, protect hippocampal neurons and synapses, and reduce the expression of p<sup>Ser404</sup>-tau and Aβ. HSD and Wogonin reduced the levels of fibrinogen β chain (FGB) and γ chain (FGG), the potential therapeutic targets revealed by proteomics analysis, reduced the colocalization of FGB and FGG with Aβ, ionized calcium binding adaptor molecule 1 (Iba-1), glial fibrillary acidic protein (GFAP), increased level of and myelin basic protein (MBP). Meanwhile, HSD and Wogonin increased ZO-1 and Occludin levels, improved brain microvascular injury, and reduced levels of bacteria/bacterial DNA and lipopolysaccharide (LPS) in the brain of mice. In addition, 16S rRNA sequencing indicated that HSD regulated the structure of intestinal microbiota of mice.</p><p><strong>Conclusion: </strong>The effects of HSD on AD may be achieved by inhibiting the levels of fibrinogen and the interactions on glia cells in the brain, and by modulating the structure of intestinal microbiota and improving the blood-brain barrier function.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"19 1","pages":"137"},"PeriodicalIF":5.3,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11456246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese MedicinePub Date : 2024-10-04DOI: 10.1186/s13020-024-00998-8
Boyang Wang, Lihao Xiao, Pan Chen, Tingyu Zhang, Peng Zhang, Liang Cao, Ziyi Zhou, Haibo Cheng, Tong Zhang, Shao Li
{"title":"Uncovering the role of traditional Chinese medicine in immune-metabolic balance of gastritis from the perspective of Cold and Hot: Jin Hong Tablets as a case study.","authors":"Boyang Wang, Lihao Xiao, Pan Chen, Tingyu Zhang, Peng Zhang, Liang Cao, Ziyi Zhou, Haibo Cheng, Tong Zhang, Shao Li","doi":"10.1186/s13020-024-00998-8","DOIUrl":"10.1186/s13020-024-00998-8","url":null,"abstract":"<p><p>Chronic gastritis (CG) is a common inflammatory disease of chronic inflammatory lesion of gastric mucosa and in the diagnosis of gastritis in traditional Chinese medicine (TCM), CG can be classified into Cold ZHENG (syndrome in TCM) and Hot ZHENG. However, the molecular features of Cold/Hot ZHENG in CG and the mechanism of Cold/Hot herbs in formulae for CG remained unclear. In this study, we collected a transcriptomics data including 35 patients of Cold/Hot ZHENG CG and 3 scRNA-seq CG samples. And 25 formulae for CG and 89 herbs recorded in these formulae were also collected. We conduct a comprehensive analysis based on the combination of transcriptomics datasets and machine learning algorithms, to discover biomarkers for Cold/Hot ZHENG CG. Then the target profiles of the collected formulae and Cold/Hot herbs were predicted to uncover the features and biomarkers of them against Cold/Hot ZHENG CG. These biomarkers suggest that Hot ZHENG CG might be characterized by over-inflammation and exuberant metabolism, and Cold ZHENG CG showed a trend of suppression in immune regulation and energy metabolism. Biomarkers and specific pathways of Hot herbs tend to regulate immune responses and energy metabolism, while those of Cold herbs are more likely to participate in anti-inflammatory effects. Finally, the findings were verified based on public transcriptomics datasets, as well as transcriptomics and ELISA detection, taking Jin Hong tablets as a case study. Biomarkers like leptin and IL-6 together with proportions of immune cells showed significant changes after the intervention. These findings might reflect the mechanism and build a bridge between macro and micro views of Cold/Hot ZHENG as well as Cold/Hot herbs.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"19 1","pages":"134"},"PeriodicalIF":5.3,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11451182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese MedicinePub Date : 2024-10-04DOI: 10.1186/s13020-024-00990-2
Peng Li, Jiangna Zhao, Xiuxiang Wei, Longfei Luo, Yuzhou Chu, Tao Zhang, Anning Zhu, Juntao Yan
{"title":"Acupuncture may play a key role in anti-depression through various mechanisms in depression.","authors":"Peng Li, Jiangna Zhao, Xiuxiang Wei, Longfei Luo, Yuzhou Chu, Tao Zhang, Anning Zhu, Juntao Yan","doi":"10.1186/s13020-024-00990-2","DOIUrl":"10.1186/s13020-024-00990-2","url":null,"abstract":"<p><p>Depression has emerged as a significant global health concern, exerting a profound impact on individuals, as evidenced by its high prevalence and associated suicide rates. Considering its pervasive nature, the absence of optimal treatment modalities remains a challenge. Acupuncture has garnered substantial clinical and experimental validation for its efficacy in addressing diverse forms of depression, including postpartum, post-stroke, and adolescent depression. This article endeavors to elucidate the distinctive attributes and underlying mechanisms of acupuncture in the contemporary treatment of depression. Research has demonstrated that acupuncture exerts diverse physiological effects in animal models of depression, encompassing modulation of the brain, serum, and brain-gut axis. These effects are attributed to various mechanisms, including anti-inflammatory and anti-oxidative actions, promotion of neuronal plasticity, neuroprotection, neurotrophic effects, modulation of neurotransmitters, regulation of endocrine and immune functions, and modulation of cell signal pathways. Currently, the therapeutic mechanism of acupuncture involves the engagement of multiple targets, pathways, and bidirectional regulation. Hence, acupuncture emerges as a promising alternative medical modality, exhibiting substantial research prospects and meriting comprehensive worth further study and dissemination.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"19 1","pages":"135"},"PeriodicalIF":5.3,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11451062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese MedicinePub Date : 2024-09-28DOI: 10.1186/s13020-024-01003-y
Chengxian Li, Xinyu Li, Ming Niu, Dake Xiao, Ye Luo, Yinkang Wang, Zhi-E Fang, Xiaoyan Zhan, Xu Zhao, Mingxia Fang, Jiabo Wang, Xiaohe Xiao, Zhaofang Bai
{"title":"Unveiling correlations between aristolochic acids and liver cancer: spatiotemporal heterogeneity phenomenon.","authors":"Chengxian Li, Xinyu Li, Ming Niu, Dake Xiao, Ye Luo, Yinkang Wang, Zhi-E Fang, Xiaoyan Zhan, Xu Zhao, Mingxia Fang, Jiabo Wang, Xiaohe Xiao, Zhaofang Bai","doi":"10.1186/s13020-024-01003-y","DOIUrl":"https://doi.org/10.1186/s13020-024-01003-y","url":null,"abstract":"<p><p>Aristolochic acids are a class of naturally occurring compounds in Aristolochiaceae that have similar structural skeletons and chemical properties. Exposure to aristolochic acids is a risk factor for severe kidney disease and urinary system cancer. However, the carcinogenicity of aristolochic acids to the liver, which is the main site of aristolochic acid metabolism, is unclear. Although the characteristic fingerprint of aristolochic acid-induced mutations has been detected in the liver and aristolochic acids are known to be hepatotoxic, whether aristolochic acids can directly cause liver cancer is yet to be verified. This review summarizes the findings of long-term carcinogenicity studies of aristolochic acids in experimental animals. We propose that spatiotemporal heterogeneity in the carcinogenicity of these phytochemicals could explain why direct evidence of aristolochic acids causing liver cancer has never been found in adult individuals. We also summarized the reported approaches to mitigate aristolochic acid-induced hepatotoxicity to better address the associated global safety issue and provide directions and recommendations for future investigation.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"19 1","pages":"132"},"PeriodicalIF":5.3,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11439320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese MedicinePub Date : 2024-09-26DOI: 10.1186/s13020-024-01001-0
Teng Li, Lianglin Zhang, Menghan Cheng, En Hu, Qiuju Yan, Yao Wu, Weikang Luo, Hong Su, Zhe Yu, Xin Guo, Quan Chen, Fei Zheng, Haigang Li, Wei Zhang, Tao Tang, Jiekun Luo, Yang Wang
{"title":"Metabolomics integrated with network pharmacology of blood-entry constituents reveals the bioactive component of Xuefu Zhuyu decoction and its angiogenic effects in treating traumatic brain injury.","authors":"Teng Li, Lianglin Zhang, Menghan Cheng, En Hu, Qiuju Yan, Yao Wu, Weikang Luo, Hong Su, Zhe Yu, Xin Guo, Quan Chen, Fei Zheng, Haigang Li, Wei Zhang, Tao Tang, Jiekun Luo, Yang Wang","doi":"10.1186/s13020-024-01001-0","DOIUrl":"https://doi.org/10.1186/s13020-024-01001-0","url":null,"abstract":"<p><strong>Background: </strong>Xuefu Zhuyu decoction (XFZYD) has been extensively utilized to treat traumatic brain injury (TBI). However, the bioactive compounds and the underlying mechanisms have not yet been elucidated.</p><p><strong>Objectives: </strong>This study aimed to investigate the bioactive constituents of XFYZD that are absorbed in the blood and the mechanisms in treating TBI.</p><p><strong>Methods: </strong>The study presents an integrated strategy in three steps to investigate the material basis and pharmacological mechanisms of XFZYD. The first step involves: (1) performing metabolomics analysis of XFZYD to obtain the main functions and targets; (2) screening the blood-entry ingredients and targets of XFZYD from databases; (3) obtaining the potential components targeting the key functions by integrated analysis of metabolomics and network pharmacology. The second step involves screening pharmacological effects with active ingredients in vitro. In the third step, the effects of the top active compound were validated in vivo, and the mechanisms were explored by protein antagonist experiments.</p><p><strong>Results: </strong>Metabolomics analysis revealed that XFZYD treated TBI mice mainly through affecting the functions of blood vessels. We screened 62 blood-entry ingredients of XFZYD by network pharmacology. Then, we focused on 39 blood-entry ingredients related to vascular genes enriched by XFZYD-responsive metabolites. Performing the natural products library, we verified that hydroxysafflor yellow A (HSYA), vanillin, ligustilide, paeoniflorin, and other substances promoted endothelial cell proliferation significantly compared to the control group. Among them, the efficacy of HSYA was superior. Further animal studies demonstrated that HSYA treatment alleviated neurological dysfunction in TBI mice by mNSS and foot fault test, and decreased neuronal damage by HE, nissl, and TUNEL staining. HSYA increased the density of cerebral microvessels, raised the expression of angiogenesis marker proteins VEGFA and CD34, and activated the PI3K/Akt/mTOR signaling pathway significantly. The angiogenic effects disappeared after the intervention of PI3K antagonist LY294002.</p><p><strong>Conclusion: </strong>By applying a novel strategy of integrating network pharmacology of constituents absorbed in blood with metabolomics, the research screened HSYA as one of the top bioactive constituents of XFZYD, which stimulates angiogenesis by activating the PI3K/Akt/mTOR signaling pathway after TBI.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"19 1","pages":"131"},"PeriodicalIF":5.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11425933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese MedicinePub Date : 2024-09-26DOI: 10.1186/s13020-024-01006-9
Feng Xu, Jingyi Hu, Yanan Li, Cheng Cheng, Ryan Au, Yiheng Tong, Yuguang Wu, Yuan Cui, Yulai Fang, Hongxin Chen, Lei Zhu, Hong Shen
{"title":"Qin-Yu-Qing-Chang decoction reshapes colonic metabolism by activating PPAR-γ signaling to inhibit facultative anaerobes against DSS-induced colitis.","authors":"Feng Xu, Jingyi Hu, Yanan Li, Cheng Cheng, Ryan Au, Yiheng Tong, Yuguang Wu, Yuan Cui, Yulai Fang, Hongxin Chen, Lei Zhu, Hong Shen","doi":"10.1186/s13020-024-01006-9","DOIUrl":"https://doi.org/10.1186/s13020-024-01006-9","url":null,"abstract":"<p><strong>Background: </strong>Qin-Yu-Qing-Chang decoction (QYQC), an herbal formula from China, is extensively employed to manage ulcerative colitis (UC) and exhibits potential benefits for colonic function. Nevertheless, the fundamental molecular mechanisms of QYQC remain largely uncharted.</p><p><strong>Methods: </strong>The primary constituents of QYQC were determined utilizing UHPLC-MS/MS analysis and the effectiveness of QYQC was assessed in a mouse model of colitis induced by dextran sulfate sodium. Evaluations of colon inflammatory responses and mucosal barrier function were thoroughly assessed. RNA sequencing, molecular docking, colonic energy metabolism, and 16S rRNA sequencing analysis were applied to uncover the complex mechanisms of QYQC in treating UC. Detect the signal transduction of the peroxisome proliferator-activated receptor-γ (PPAR-γ) both in the nucleus and cytoplasm. Furthermore, a PPAR-γ antagonist was strategically utilized to confirm the functional targets that QYQC exerts.</p><p><strong>Results: </strong>Utilizing UHPLC-MS/MS, the principal constituents of the nine traditional Chinese medicinal herbs comprising QYQC were systematically identified. QYQC treatment substantially ameliorated colitis in mice, as evidenced by the improvement in symptoms and the reduction in colonic pathological injuries. Besides, QYQC treatment mitigated the inflammatory response and improved mucosal barrier function. Furthermore, QYQC enhanced the mitochondria citrate cycle (TCA cycle) by triggering PPAR-γ signaling and increasing the proportion of PPAR-γ entering the nucleus. This prevented the unconstrained expansion of facultative anaerobes, particularly pathogenic Escherichia coli (E. coli, family Enterobacteriaceae) and thus improved colitis. Results of molecular docking indicated that the representative chemical components of QYQC including Baicalin, Paeoniflorin, Mollugin, and Imperatorin bound well with PPAR-γ. The impact of QYQC on colitis was diminished in the presence of a PPAR-γ antagonist.</p><p><strong>Conclusions: </strong>In summary, QYQC ameliorates UC by activating PPAR-γ signaling and increasing the proportion of PPAR-γ entering the nucleus, which enhances the energy metabolism of intestinal epithelial cells and thereby preventing the uncontrolled proliferation of facultative anaerobes.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"19 1","pages":"130"},"PeriodicalIF":5.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11425999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mechanism of norcantharidin intervention in gastric cancer: analysis based on antitumor proprietary Chinese medicine database, network pharmacology, and transcriptomics","authors":"Yiyan Zhai, Fanqin Zhang, Jiying Zhou, Chuanqi Qiao, Zhengsen Jin, Jingyuan Zhang, Chao Wu, Rui Shi, Jiaqi Huang, Yifei Gao, Siyu Guo, Haojia Wang, Keyan Chai, Xiaomeng Zhang, Tieshan Wang, Xiaoguang Sheng, Xinkui Liu, Jiarui Wu","doi":"10.1186/s13020-024-01000-1","DOIUrl":"https://doi.org/10.1186/s13020-024-01000-1","url":null,"abstract":"Combining antitumor proprietary Chinese medicine (pCm) with radiotherapy and chemotherapy can effectively improve tumor cure rates and enhance patients’ quality of life. Gastric cancer (GC) severely endangers public health. Despite satisfactory therapeutic effects achieved by using antitumor pCm to treat GC, its underlying mechanism remains unclear. To integrate existing research data, construct a database of antitumor pCm, and study the intervention mechanisms in GC by focusing on their monomer components. We constructed an antitumor pCm database based on China’s medical insurance catalog, and employed network pharmacology, molecular docking methods, cell experiments, transcriptomics, and bioinformatics to investigate the intervention mechanisms of effective pCm components for GC. The study built an antitumor pCm database including 55 pCms, 171 Chinese herbal medicines, 1955 chemical components, 2104 targets, and 32 disease information. Network pharmacology and molecular docking technology identified norcantharidin as an effective component of antitumor pCm. In vitro experiments showed that norcantharidin effectively inhibited GC cell proliferation, migration, and invasion; blocked the G2/M cell cycle phase; and induced GC cell apoptosis. Transcriptomic results revealed that norcantharidin affected biological processes, such as cell adhesion, migration, and inflammatory responses by influencing PI3K-AKT, NF-κB, JAK-STAT, TNF-α signaling pathways, and EMT-related pathways. Core molecules of norcantharidin involved in GC intervention include SERPINE1, SHOX2, SOX4, PRDM1, TGFR3, TOX, PAX9, IL2RB, LAG3, and IL15RA. Additionally, the key target SERPINE1 was identified using bioinformatics methods. Norcantharidin, as an effective component of anti-tumor pCm, exerts its therapeutic effects on GC by influencing biological processes such as cell adhesion, migration, and inflammation. This study provides a foundation and research strategy for the post-marketing re-evaluation of antitumor pCms.","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"188 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142259076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese MedicinePub Date : 2024-09-16DOI: 10.1186/s13020-024-00997-9
Zebiao Cao, Xianzhe Wang, Zhili Zeng, Zhaojun Yang, Yuping Lin, Lu Sun, Qiyun Lu, Guanjie Fan
{"title":"The improvement of modified Si-Miao granule on hepatic insulin resistance and glycogen synthesis in type 2 diabetes mellitus involves the inhibition of TNF-α/JNK1/IRS-2 pathway: network pharmacology, molecular docking, and experimental validation","authors":"Zebiao Cao, Xianzhe Wang, Zhili Zeng, Zhaojun Yang, Yuping Lin, Lu Sun, Qiyun Lu, Guanjie Fan","doi":"10.1186/s13020-024-00997-9","DOIUrl":"https://doi.org/10.1186/s13020-024-00997-9","url":null,"abstract":"Modified Si-Miao granule (mSMG), a traditional Chinese medicine, is beneficial for T2DM and insulin resistance (IR), but the underlying mechanism remains unknown. Using network pharmacology, we screened the compounds of mSMG and identified its targets and pathway on hepatic IR in T2DM. Using molecular docking, we identified the affinity between the compounds and hub target TNF-α. Then these were verified in KK-Ay mice and HepG2 cells. 50 compounds and 170 targets of mSMG against IR in T2DM were screened, and 9 hub targets such as TNF and MAPK8 were identified. 170 targets were mainly enriched in insulin resistance and TNF pathway, so we speculated that mSMG might act on TNF-α, JNK1 and then regulate insulin signaling to mitigate IR. Experimental validation proved that mSMG ameliorated hyperglycemia, IR, and TNF-α, enhanced glucose consumption and glycogen synthesis, relieved the phosphorylation of JNK1 and IRS-2 (Ser388), and elevated the phosphorylation of Akt (Ser473) and GSK-3β (Ser9) and GLUT2 expression in KK-Ay mice. Molecular docking further showed berberine from mSMG had excellent binding capacity with TNF-α. Then, in vitro validation experiments, we found that 20% mSMG-MS or 50 μM berberine had little effect in IR-HepG2 cell viability, but significantly increased glucose consumption and glycogen synthesis and regulated TNF-α/JNK1/IRS-2 pathway. Network pharmacology and molecular docking help us predict potential mechanism of mSMG and further guide experimental validation. mSMG and its representative compound berberine improve hepatic IR and glycogen synthesis, and its mechanism may be related to the inhibition of TNF-α/JNK1/IRS-2 pathway.","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142259074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese MedicinePub Date : 2024-09-15DOI: 10.1186/s13020-024-00992-0
Wen Sun, Minghua Bai, Ji Wang, Bei Wang, Yixing Liu, Qi Wang, Dongran Han
{"title":"Machine learning-assisted rapid determination for traditional Chinese Medicine Constitution","authors":"Wen Sun, Minghua Bai, Ji Wang, Bei Wang, Yixing Liu, Qi Wang, Dongran Han","doi":"10.1186/s13020-024-00992-0","DOIUrl":"https://doi.org/10.1186/s13020-024-00992-0","url":null,"abstract":"The aim of this study was to develop a machine learning-assisted rapid determination methodology for traditional Chinese Medicine Constitution. Based on the Constitution in Chinese Medicine Questionnaire (CCMQ), the most applied diagnostic instrument for assessing individuals’ constitutions, we employed automated supervised machine learning algorithms (i.e., Tree-based Pipeline Optimization Tool; TPOT) on all the possible item combinations for each subscale and an unsupervised machine learning algorithm (i.e., variable clustering; varclus) on the whole scale to select items that can best predict body constitution (BC) classifications or BC scores. By utilizing subsets of items selected based on TPOT and corresponding machine learning algorithms, the accuracies of BC classifications prediction ranged from 0.819 to 0.936, with the root mean square errors of BC scores prediction stabilizing between 6.241 and 9.877. Overall, the results suggested that the automated machine learning algorithms performed better than the varclus algorithm for item selection. Additionally, based on an automated machine learning item selection procedure, we provided the top three ranked item combinations with each possible subscale length, along with their corresponding algorithms for predicting BC classification and severity. This approach could accommodate the needs of different practitioners in traditional Chinese medicine for rapid constitution determination.","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"33 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142259075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}