Pub Date : 2024-04-18DOI: 10.4103/wjtcm.wjtcm_60_24
Meng-Hua Li, Wan-Qi Wang, Li-Ting Zheng, Meng-Bing Chen, Yang Chu, Miao Qiao, Zuo-Li Zhang, Konduru Naveena, Yong Pan, Yun-Shi Zhang, He Sun, Xiao-Hui Ma, Xi Shi
This study aimed to explore andrographolide’s mechanism of action and its protective effect on noise-induced hearing loss (NIHL). A mice animal model for NIHL was established through exposure to broadband noise at 120 dB sound pressure level for 4 h. Transcriptomics analysis and pharmacodynamic experiments were carried out. Andrographolide enters the inner ear and effectively prevents hearing damage following noise exposure in the mice model for permanent hearing loss. Moreover, treatment with andrographolide inhibited the excessive activation of inflammatory factors in the cochleae of noise-exposed mice. Andrographolide might be a promising candidate for auditory protective drug investigation.
{"title":"Andrographolide Attenuates Noise-induced Hearing Loss by Ameliorating Cochlear Inflammation","authors":"Meng-Hua Li, Wan-Qi Wang, Li-Ting Zheng, Meng-Bing Chen, Yang Chu, Miao Qiao, Zuo-Li Zhang, Konduru Naveena, Yong Pan, Yun-Shi Zhang, He Sun, Xiao-Hui Ma, Xi Shi","doi":"10.4103/wjtcm.wjtcm_60_24","DOIUrl":"https://doi.org/10.4103/wjtcm.wjtcm_60_24","url":null,"abstract":"\u0000 \u0000 \u0000 This study aimed to explore andrographolide’s mechanism of action and its protective effect on noise-induced hearing loss (NIHL).\u0000 \u0000 \u0000 \u0000 A mice animal model for NIHL was established through exposure to broadband noise at 120 dB sound pressure level for 4 h. Transcriptomics analysis and pharmacodynamic experiments were carried out.\u0000 \u0000 \u0000 \u0000 Andrographolide enters the inner ear and effectively prevents hearing damage following noise exposure in the mice model for permanent hearing loss. Moreover, treatment with andrographolide inhibited the excessive activation of inflammatory factors in the cochleae of noise-exposed mice.\u0000 \u0000 \u0000 \u0000 Andrographolide might be a promising candidate for auditory protective drug investigation.\u0000","PeriodicalId":23692,"journal":{"name":"World Journal of Traditional Chinese Medicine","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140690107","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}
Idiosyncratic drug-induced liver injury (IDILI) is a serious side effect of drugs, Epimedii Folium (EF) is unequivocally implicated in idiosyncratic liver injury onset, potentially due to its ability to perturb the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome. Fructus Ligustri Lucidi (FLL), a frequently used medicinal combination with EF, has not yet been investigated for its ability to ameliorate EF-associated hepatotoxicity. Study on the mechanism of compatibility of FLL to alleviate liver injury caused by EF. Materials and Methods: Western blot was used to determine the expression of related proteins, ELISA was used to detect the secretion of related inflammatory factors IL-1β, IL-18, IL-6 and TNF-α, liver injury indexes were detected and liver pathological tissue staining was used to evaluate the liver injury. Our results demonstrated that EF exerted a particular augmenting effect on the stimulation of the NLRP3 inflammasome mediated by nigericin or ATP, whereas FLL suppressed the NLRP3 inflammasome stimulation. Furthermore, an equal EF to FLL ratio significantly reduced the stimulatory effects of EF. Moreover, EF has the potential to induce hepatic injury and augment pro-inflammatory cytokine synthesis in rats subjected to LPS. However, when combined with FLL, the detrimental effects of EF were mitigated. FLL possesses the capacity to attenuate EF-associated hepatotoxicity by suppressing EF-triggered NLRP3 inflammasome activation. Thus, FLL holds promise for improving the clinical safety profile of EF, shedding light on the potential of compatibility and detoxification theories in traditional Chinese medicine.
特发性药物性肝损伤（IDILI）是一种严重的药物副作用，Epimedii Folium（EF）明确与特发性肝损伤的发生有关，这可能是由于它能够扰乱NOD样受体家族含吡咯啉结构域3（NLRP3）炎性体。Fructus Ligustri Lucidi（FLL）是一种经常与 EF 合用的药物，但尚未对其改善 EF 相关肝毒性的能力进行研究。 研究 FLL 缓解 EF 引起的肝损伤的相容性机制。材料和方法：用 Western blot 检测相关蛋白的表达，用 ELISA 检测相关炎症因子 IL-1β、IL-18、IL-6 和 TNF-α的分泌，检测肝损伤指标，用肝病理组织染色评估肝损伤。 我们的研究结果表明，EF对尼革酶或ATP介导的NLRP3炎性体的刺激有特殊的增强作用，而FLL则抑制NLRP3炎性体的刺激。此外，EF 与 FLL 的比例相等时，EF 的刺激作用会明显减弱。此外，EF 有可能诱发大鼠肝损伤并增加促炎细胞因子的合成。然而，当与 FLL 结合使用时，EF 的有害作用得到了缓解。 FLL 有能力通过抑制 EF 触发的 NLRP3 炎性体活化来减轻 EF 相关的肝毒性。因此，FLL有望改善EF的临床安全性，并揭示了中药中相容解毒理论的潜力。
{"title":"Compatibility with Fructus Ligustri Lucidi Effectively Mitigates Idiosyncratic Liver Injury of Epimedii Folium by Modulating NOD-like Receptor Family Pyrin Domain Containing 3 Inflammasome Activation","authors":"Xiaomei Zhao, Zhi-Xin Wu, Yan Wang, Ying-Jie Xu, Ye Xiu, Xu Dong, Junjie Li, Guiji Lv, Si-Hao Wang, Yu-Rong Li, Zhao-fang Bai, Xiao-He Xiao","doi":"10.4103/wjtcm.wjtcm_61_24","DOIUrl":"https://doi.org/10.4103/wjtcm.wjtcm_61_24","url":null,"abstract":"\u0000 \u0000 \u0000 Idiosyncratic drug-induced liver injury (IDILI) is a serious side effect of drugs, Epimedii Folium (EF) is unequivocally implicated in idiosyncratic liver injury onset, potentially due to its ability to perturb the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome. Fructus Ligustri Lucidi (FLL), a frequently used medicinal combination with EF, has not yet been investigated for its ability to ameliorate EF-associated hepatotoxicity.\u0000 \u0000 \u0000 \u0000 Study on the mechanism of compatibility of FLL to alleviate liver injury caused by EF. Materials and Methods: Western blot was used to determine the expression of related proteins, ELISA was used to detect the secretion of related inflammatory factors IL-1β, IL-18, IL-6 and TNF-α, liver injury indexes were detected and liver pathological tissue staining was used to evaluate the liver injury.\u0000 \u0000 \u0000 \u0000 Our results demonstrated that EF exerted a particular augmenting effect on the stimulation of the NLRP3 inflammasome mediated by nigericin or ATP, whereas FLL suppressed the NLRP3 inflammasome stimulation. Furthermore, an equal EF to FLL ratio significantly reduced the stimulatory effects of EF. Moreover, EF has the potential to induce hepatic injury and augment pro-inflammatory cytokine synthesis in rats subjected to LPS. However, when combined with FLL, the detrimental effects of EF were mitigated.\u0000 \u0000 \u0000 \u0000 FLL possesses the capacity to attenuate EF-associated hepatotoxicity by suppressing EF-triggered NLRP3 inflammasome activation. Thus, FLL holds promise for improving the clinical safety profile of EF, shedding light on the potential of compatibility and detoxification theories in traditional Chinese medicine.\u0000","PeriodicalId":23692,"journal":{"name":"World Journal of Traditional Chinese Medicine","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140710895","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}
Huazhi Rougan granules (HRGs) are a promising drug to improve alcoholic liver disease (ALD), but its mechanism remains unclear. Network pharmacology, molecular docking, and animal experiments were used to reveal the potential mechanism of HRG against ALD. A total of 245 potential targets of HRG against ALD were obtained. Functional enrichment analysis suggests that HRG could synergistically regulate various biological pathways to exert therapeutic effects on ALD. Molecular docking showed that the key targets exhibited the good binding ability with the key compounds. The in vivo experiments showed that HRG can effectively alleviate pathological changes in liver tissue, improve blood lipid levels, antioxidant stress ability, and liver function, and reduce the release of inflammatory cytokines in the liver. This study reflects that HRG is an effective strategy for treating ALD, providing a basis for revealing the prevention and treatment mechanisms of ALD.
{"title":"Investigating the Potential Mechanism of Huazhi Rougan Granules against Alcoholic Liver Disease by Network Pharmacology and Experiment","authors":"Yingying Tan, Yingying Liu, Yi-Yan Zhai, Yi-Xuan Wang, Zhishan Wu, Antony Stalin, Guo-Liang Cheng, Bing Li, Chao-yong Wu, Zhihong Huang, Shan Lu, Xiaotian Fan, Zheng Zhao, Jia-Rui Wu","doi":"10.4103/wjtcm.wjtcm_34_23","DOIUrl":"https://doi.org/10.4103/wjtcm.wjtcm_34_23","url":null,"abstract":"\u0000 \u0000 \u0000 Huazhi Rougan granules (HRGs) are a promising drug to improve alcoholic liver disease (ALD), but its mechanism remains unclear.\u0000 \u0000 \u0000 \u0000 Network pharmacology, molecular docking, and animal experiments were used to reveal the potential mechanism of HRG against ALD.\u0000 \u0000 \u0000 \u0000 A total of 245 potential targets of HRG against ALD were obtained. Functional enrichment analysis suggests that HRG could synergistically regulate various biological pathways to exert therapeutic effects on ALD. Molecular docking showed that the key targets exhibited the good binding ability with the key compounds. The in vivo experiments showed that HRG can effectively alleviate pathological changes in liver tissue, improve blood lipid levels, antioxidant stress ability, and liver function, and reduce the release of inflammatory cytokines in the liver.\u0000 \u0000 \u0000 \u0000 This study reflects that HRG is an effective strategy for treating ALD, providing a basis for revealing the prevention and treatment mechanisms of ALD.\u0000","PeriodicalId":23692,"journal":{"name":"World Journal of Traditional Chinese Medicine","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140710863","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}
Pub Date : 2024-04-10DOI: 10.4103/wjtcm.wjtcm_48_23
Guo-Hong Wang, Long-Fei Yang, Shi-Wei Wang, Yue-Tao Liu
This study aimed to investigate the orientated effective components of Astragali Radix Huangqi (HQ) in HQ Jianzhong Tang (HQJZ), a classical formula of traditional Chinese medicine (TCM) used for treating chronic atrophic gastritis (CAG), using HQ as a monarch medicine. The spectra of HQJZ containing different polar parts of HQ were obtained using ultra-high-performance liquid chromatography-Q-Exactive mass spectrometry. Furthermore, the efficacy of HQJZ, which contains different polar parts of HQ, in treating rats with CAG was evaluated using traditional pharmacodynamic and nuclear magnetic resonance-based metabonomics. Grey relation analysis and partial least squares analysis were applied to analyze the spectrum–effect relationship and to screen out the orientated effective components related to HQ in the treatment of CAG. Spectrum–effect relationship analysis showed that 24 compounds identified from the fingerprint spectrum were strongly correlated with efficacy. Compounds 8 (calycosin-7-O-glc-6”- O-acetate), 9 (3-hydroxy-9, 10-dimethoxyptercarpan), and 22 (astragaloside II) were ranked among the top three. This study showed that integrating metabolomics and spectrum–effect relationship analysis is a powerful tool for obtaining orientated effective components of Chinese medicine in a given TCM formula.
{"title":"Research on the Orientated Effective Components of Huangqi in Huangqi Jianzhong Tang Against Chronic Atrophic Gastritis Based on Multi-Spectrum–Effect Correlation","authors":"Guo-Hong Wang, Long-Fei Yang, Shi-Wei Wang, Yue-Tao Liu","doi":"10.4103/wjtcm.wjtcm_48_23","DOIUrl":"https://doi.org/10.4103/wjtcm.wjtcm_48_23","url":null,"abstract":"\u0000 \u0000 \u0000 This study aimed to investigate the orientated effective components of Astragali Radix Huangqi (HQ) in HQ Jianzhong Tang (HQJZ), a classical formula of traditional Chinese medicine (TCM) used for treating chronic atrophic gastritis (CAG), using HQ as a monarch medicine.\u0000 \u0000 \u0000 \u0000 The spectra of HQJZ containing different polar parts of HQ were obtained using ultra-high-performance liquid chromatography-Q-Exactive mass spectrometry. Furthermore, the efficacy of HQJZ, which contains different polar parts of HQ, in treating rats with CAG was evaluated using traditional pharmacodynamic and nuclear magnetic resonance-based metabonomics. Grey relation analysis and partial least squares analysis were applied to analyze the spectrum–effect relationship and to screen out the orientated effective components related to HQ in the treatment of CAG.\u0000 \u0000 \u0000 \u0000 Spectrum–effect relationship analysis showed that 24 compounds identified from the fingerprint spectrum were strongly correlated with efficacy. Compounds 8 (calycosin-7-O-glc-6”- O-acetate), 9 (3-hydroxy-9, 10-dimethoxyptercarpan), and 22 (astragaloside II) were ranked among the top three.\u0000 \u0000 \u0000 \u0000 This study showed that integrating metabolomics and spectrum–effect relationship analysis is a powerful tool for obtaining orientated effective components of Chinese medicine in a given TCM formula.\u0000","PeriodicalId":23692,"journal":{"name":"World Journal of Traditional Chinese Medicine","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140718626","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}
Pub Date : 2024-04-05DOI: 10.4103/wjtcm.wjtcm_64_24
Yu-Zhi Mao, Chen-Zi Li, Weiquan Bu, Bing Yang, Ya-ping Chen, Jun Liu, Jing Zhao, E. Sun, X. Jia, Liang Feng
Allergic asthma (AA) is a chronic airway inflammatory disease characterized by airway hyper-responsiveness (AHR). Pudilan anti-inflammatory oral liquid (PDL) along with its main medicinal material, Taraxaci Herba (Taraxacum mongolicum Hand.-Mazz, TH) has been widely used to treat upper respiratory tract infections. Research has shown that the major ingredient of TH, the organic acid component (OAC), possesses favorable AA activity. However, the attenuated effects of PDL and OAC from TH (TH-OAC) on AA and their possible mechanisms remain poorly understood. This study analyzed the attenuating effects of PDL and TH-OAC on AA and the underlying mechanisms. Young BALB/c mice were sensitized and stimulated to develop asthma using ovalbumin. Histological examinations were performed by hematoxylin and eosin staining. Western blotting, immunohistochemistry, and protein expression detection of toll-like receptor 2 (TLR2), TLR4, and orosomucoid 1-like protein 3 (ORMDL3) were performed to detect the presence of inflammatory components in the lung tissue. The messenger RNA (mRNA) expression levels were determined using quantitative real-time polymerase chain reaction. Results showed that PDL and TH-OAC alleviated augmented AHR and typical asthmatic pathological changes, including inflammatory infiltration and thickening of the alveolar wall. They also significantly reduced the levels of the immunoglobulin E, IL-4, IL-5, IL-6, tumor necrosis factor-α, and Nitric oxide (NO) in lung tissues of mice. Protein and mRNA expression levels of TLR2, TLR4, and ORMDL3 were downregulated following treatment with PDL and TH-OAC. PDL and TH-OAC can reduce asthma-induced inflammatory damage to the bronchi. These results provide a theoretical basis for the treatment of asthma in clinical settings.
{"title":"Pudilan Anti-inflammatory Oral Liquid and Organic Acid Component from Taraxaci Herba Attenuate Allergic Asthma in Young Mice through Toll-like Receptor 2/Toll-like Receptor 4 Signaling Pathway","authors":"Yu-Zhi Mao, Chen-Zi Li, Weiquan Bu, Bing Yang, Ya-ping Chen, Jun Liu, Jing Zhao, E. Sun, X. Jia, Liang Feng","doi":"10.4103/wjtcm.wjtcm_64_24","DOIUrl":"https://doi.org/10.4103/wjtcm.wjtcm_64_24","url":null,"abstract":"\u0000 \u0000 \u0000 Allergic asthma (AA) is a chronic airway inflammatory disease characterized by airway hyper-responsiveness (AHR). Pudilan anti-inflammatory oral liquid (PDL) along with its main medicinal material, Taraxaci Herba (Taraxacum mongolicum Hand.-Mazz, TH) has been widely used to treat upper respiratory tract infections. Research has shown that the major ingredient of TH, the organic acid component (OAC), possesses favorable AA activity. However, the attenuated effects of PDL and OAC from TH (TH-OAC) on AA and their possible mechanisms remain poorly understood. This study analyzed the attenuating effects of PDL and TH-OAC on AA and the underlying mechanisms.\u0000 \u0000 \u0000 \u0000 Young BALB/c mice were sensitized and stimulated to develop asthma using ovalbumin. Histological examinations were performed by hematoxylin and eosin staining. Western blotting, immunohistochemistry, and protein expression detection of toll-like receptor 2 (TLR2), TLR4, and orosomucoid 1-like protein 3 (ORMDL3) were performed to detect the presence of inflammatory components in the lung tissue. The messenger RNA (mRNA) expression levels were determined using quantitative real-time polymerase chain reaction.\u0000 \u0000 \u0000 \u0000 Results showed that PDL and TH-OAC alleviated augmented AHR and typical asthmatic pathological changes, including inflammatory infiltration and thickening of the alveolar wall. They also significantly reduced the levels of the immunoglobulin E, IL-4, IL-5, IL-6, tumor necrosis factor-α, and Nitric oxide (NO) in lung tissues of mice. Protein and mRNA expression levels of TLR2, TLR4, and ORMDL3 were downregulated following treatment with PDL and TH-OAC.\u0000 \u0000 \u0000 \u0000 PDL and TH-OAC can reduce asthma-induced inflammatory damage to the bronchi. These results provide a theoretical basis for the treatment of asthma in clinical settings.\u0000","PeriodicalId":23692,"journal":{"name":"World Journal of Traditional Chinese Medicine","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140738054","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}
Chronic atrophic gastritis (CAG) is a complex and burdensome disease. However, side effects and compliance issues cannot be ignored due to the long treatment cycle. Numerous studies have confirmed the effectiveness of rutaecarpine (RUT) for treating digestive dysfunction. However, the potential mechanism of action of RUT in the context of CAG treatment remains unclear. This study aimed to explore the therapeutic effects and mechanisms of RUT in 1-methyl-3-nitro-1-nitrosoguanidine-induced CAG using network pharmacology, metabolomics, and traditional pharmacological approaches. Pathological tests and ELISA assays were used to observe the therapeutic effects of RUT treatment on CAG. Differential metabolites were identified using ultra-high-performance liquid chromatography-tandem mass spectrometry, and metabolism-related target genes were enriched. The same target genes were identified between RUT and CAG diseases. The intersectional target genes were uploaded to Cytoscape for enrichment, and the nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway was selected to validate the mechanisms of the study. Finally, cell pyroptosis status was evaluated using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, and the expressions of associated proteins of the NOD-like receptor signaling pathway were assessed by Western blotting and immunohistochemistry. RUT alleviated gastric mucosal damage and significantly downregulated indicators associated with inflammation and gastric atrophy. A total of 29 intersection target genes were identified, and core pathways were obtained. The NOD-like receptor signaling pathway and pyroptosis status were selected to validate the mechanisms of RUT treatment in CAG rats. The expression of NOD-related proteins and downstream factors was downregulated in the RUT group. RUT exerts a pharmacological effect on relieving gastric damage in CAG rats by inhibiting NOD-like receptors and inflammasomes.
{"title":"Effects of Rutaecarpine on Chronic Atrophic Gastritis Through Nucleotide-binding Oligomerization Domain-like Receptors and Inflammasomes","authors":"Yong He, Xin Wang, Li-Sheng Chen, Lei Chang, Tingting He, Aozhe Zhang, Hao-Ttian Li, Shi-Zhang Wei, Manyi Jing, Yan-Ling Zhao","doi":"10.4103/wjtcm.wjtcm_55_24","DOIUrl":"https://doi.org/10.4103/wjtcm.wjtcm_55_24","url":null,"abstract":"\u0000 \u0000 \u0000 Chronic atrophic gastritis (CAG) is a complex and burdensome disease. However, side effects and compliance issues cannot be ignored due to the long treatment cycle. Numerous studies have confirmed the effectiveness of rutaecarpine (RUT) for treating digestive dysfunction. However, the potential mechanism of action of RUT in the context of CAG treatment remains unclear. This study aimed to explore the therapeutic effects and mechanisms of RUT in 1-methyl-3-nitro-1-nitrosoguanidine-induced CAG using network pharmacology, metabolomics, and traditional pharmacological approaches.\u0000 \u0000 \u0000 \u0000 Pathological tests and ELISA assays were used to observe the therapeutic effects of RUT treatment on CAG. Differential metabolites were identified using ultra-high-performance liquid chromatography-tandem mass spectrometry, and metabolism-related target genes were enriched. The same target genes were identified between RUT and CAG diseases. The intersectional target genes were uploaded to Cytoscape for enrichment, and the nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway was selected to validate the mechanisms of the study. Finally, cell pyroptosis status was evaluated using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, and the expressions of associated proteins of the NOD-like receptor signaling pathway were assessed by Western blotting and immunohistochemistry.\u0000 \u0000 \u0000 \u0000 RUT alleviated gastric mucosal damage and significantly downregulated indicators associated with inflammation and gastric atrophy. A total of 29 intersection target genes were identified, and core pathways were obtained. The NOD-like receptor signaling pathway and pyroptosis status were selected to validate the mechanisms of RUT treatment in CAG rats. The expression of NOD-related proteins and downstream factors was downregulated in the RUT group.\u0000 \u0000 \u0000 \u0000 RUT exerts a pharmacological effect on relieving gastric damage in CAG rats by inhibiting NOD-like receptors and inflammasomes.\u0000","PeriodicalId":23692,"journal":{"name":"World Journal of Traditional Chinese Medicine","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140377272","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}
Illumination of the integrative effects of herbs in a formula is a bottleneck that limits the development of traditional Chinese medicine (TCM). In the present study, we developed a transcriptome-based multi-scale network pharmacology model to explore the combined effects of different herbs. First, we curated gene signatures at different biological scales, from the molecular to higher tissue levels, including tissues, cells, pathological processes, biological processes, pathways, and targets. Second, using the Xiexin Tang (XXT) formula as an example, we collected transcriptomic data in response to the treatment of XXT or its three compositive herbs on Michigan cancer foundation7 cells. Third, we linked each herbal drug to different biological scales by calculating the correlation scores between herb-induced gene expression profiles and gene signatures. Finally, the combined mechanisms of the three constituent herbs in XXT were deciphered by comparing their multi-scale effects with those of the formula. The results showed that although XXT or single herbs regulated a large number of signatures on each biological scale, the phenotypic effects of these herbal drugs are concentrated onto the “Blood” tissue, types of hemocytes, and hemorrhagic injury-related pathological processes. At the molecular level, these herbs consistently regulate processes such as the cell cycle and blood coagulation-related pathways, as well as protein targets related to the immunoinflammatory response and blood coagulation, such as proteinase-activated receptor 2, integrin beta-3, inhibitor of nuclear factor kappa-B kinase subunit beta, and coagulation factor XII. The analysis of the combinational modes demonstrated that different herbs can cooperate by acting on the same objects and/or regulating different objects in related functions, and cooperative behaviors change at different biological scales. Our model can dissect the combined effects of herbal formulae from a multi-scale perspective and should be beneficial for the development and exploitation of TCM.
{"title":"Dissecting Combinational Mechanisms of Herbal Formula from a Transcriptome-based Multi-scale Network Pharmacology Model","authors":"Peng Li, Tong Jin, Qing-Qiong Deng, Ning Chen, Hao-Ran Zhang, Wu-Xia Zhang, Yi-Jie Li, Zi-Yu Meng, Lin Xing, Yuan-Yuan Zhang, Ling-Min Zhan, Cai-Ping Cheng, Jin-Zhong Zhao, Bang-Ze Fu, Tian-Gang Li, Peng Lu","doi":"10.4103/wjtcm.wjtcm_54_23","DOIUrl":"https://doi.org/10.4103/wjtcm.wjtcm_54_23","url":null,"abstract":"\u0000 \u0000 \u0000 Illumination of the integrative effects of herbs in a formula is a bottleneck that limits the development of traditional Chinese medicine (TCM). In the present study, we developed a transcriptome-based multi-scale network pharmacology model to explore the combined effects of different herbs.\u0000 \u0000 \u0000 \u0000 First, we curated gene signatures at different biological scales, from the molecular to higher tissue levels, including tissues, cells, pathological processes, biological processes, pathways, and targets. Second, using the Xiexin Tang (XXT) formula as an example, we collected transcriptomic data in response to the treatment of XXT or its three compositive herbs on Michigan cancer foundation7 cells. Third, we linked each herbal drug to different biological scales by calculating the correlation scores between herb-induced gene expression profiles and gene signatures. Finally, the combined mechanisms of the three constituent herbs in XXT were deciphered by comparing their multi-scale effects with those of the formula.\u0000 \u0000 \u0000 \u0000 The results showed that although XXT or single herbs regulated a large number of signatures on each biological scale, the phenotypic effects of these herbal drugs are concentrated onto the “Blood” tissue, types of hemocytes, and hemorrhagic injury-related pathological processes. At the molecular level, these herbs consistently regulate processes such as the cell cycle and blood coagulation-related pathways, as well as protein targets related to the immunoinflammatory response and blood coagulation, such as proteinase-activated receptor 2, integrin beta-3, inhibitor of nuclear factor kappa-B kinase subunit beta, and coagulation factor XII. The analysis of the combinational modes demonstrated that different herbs can cooperate by acting on the same objects and/or regulating different objects in related functions, and cooperative behaviors change at different biological scales.\u0000 \u0000 \u0000 \u0000 Our model can dissect the combined effects of herbal formulae from a multi-scale perspective and should be beneficial for the development and exploitation of TCM.\u0000","PeriodicalId":23692,"journal":{"name":"World Journal of Traditional Chinese Medicine","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140387690","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}
Shuangshen granules (SSGs) are extensively utilized for the treatment of lung cancer in China and have been reported to possess tumor-protective and anti-metastatic effects. Therefore, it is crucial to understand the precise mechanism. Building upon the findings of our previous study, the objective of the present study was to explore the impact of SSGs on the sphingosine-1-phosphate receptor-1 (S1PR1)/signal transducer and activator of transcription 3 (STAT3) axis, as well as the recruitment of myeloid-derived suppressor cells (MDSCs) during the formation of the premetastatic niches (PMNs). In a mouse xenograft model utilizing Lewis lung carcinoma (LLC) cells that express green fluorescent protein (GFP), the initiation of lung metastasis was monitored every three days until day 35 following transplantation. Lung metastasis, MDSC recruitment, the expression of PMN and S1PR1/STAT3 axis biomarkers, as well as the blood levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor-β (TGF-β) were assessed in the SSG treatment and control groups. The LLC cells did not reach the lung until 14–17 days following subcutaneous implantation, which was concurrent with the formation of lung PMNs. SSG significantly postponed the initiation of lung metastasis and reduced the recruitment of MDSCs to the lung PMNs. SSG also suppressed the S1PR1/STAT3 axis in tumor tissues, bone marrow, and lung PMNs. Additionally, SSG suppressed the blood levels of GM-CSF and TGF-β, as well as the PMN markers, matrix metalloproteinase-9 and versican. Our findings suggested that SSG suppressed the development of MDSC-mediated PMNs by inhibiting the S1PR1/STAT3 axis, consequently postponing the initiation of lung metastasis.
{"title":"Shuangshen Granules Suppress Myeloid-derived Suppressor Cell-mediated Lung Premetastatic Niche Development by Targeting Sphingosine-1-Phosphate Receptor-1/Signal Transducer, Activator of Transcription 3 Signaling","authors":"Rui Liu, Jia-Qi Hu, Xing Zhang, Xiao-Yi Wu, Hua-Min Wei, Yuan-Chen Zhao, Shu-Lin He, Jing Yu, Xin Qi, Y. Pei, Hong Chen, Wei-Dong Li, Bao-Jin Hua","doi":"10.4103/wjtcm.wjtcm_51_23","DOIUrl":"https://doi.org/10.4103/wjtcm.wjtcm_51_23","url":null,"abstract":"\u0000 \u0000 \u0000 Shuangshen granules (SSGs) are extensively utilized for the treatment of lung cancer in China and have been reported to possess tumor-protective and anti-metastatic effects. Therefore, it is crucial to understand the precise mechanism. Building upon the findings of our previous study, the objective of the present study was to explore the impact of SSGs on the sphingosine-1-phosphate receptor-1 (S1PR1)/signal transducer and activator of transcription 3 (STAT3) axis, as well as the recruitment of myeloid-derived suppressor cells (MDSCs) during the formation of the premetastatic niches (PMNs).\u0000 \u0000 \u0000 \u0000 In a mouse xenograft model utilizing Lewis lung carcinoma (LLC) cells that express green fluorescent protein (GFP), the initiation of lung metastasis was monitored every three days until day 35 following transplantation. Lung metastasis, MDSC recruitment, the expression of PMN and S1PR1/STAT3 axis biomarkers, as well as the blood levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor-β (TGF-β) were assessed in the SSG treatment and control groups.\u0000 \u0000 \u0000 \u0000 The LLC cells did not reach the lung until 14–17 days following subcutaneous implantation, which was concurrent with the formation of lung PMNs. SSG significantly postponed the initiation of lung metastasis and reduced the recruitment of MDSCs to the lung PMNs. SSG also suppressed the S1PR1/STAT3 axis in tumor tissues, bone marrow, and lung PMNs. Additionally, SSG suppressed the blood levels of GM-CSF and TGF-β, as well as the PMN markers, matrix metalloproteinase-9 and versican.\u0000 \u0000 \u0000 \u0000 Our findings suggested that SSG suppressed the development of MDSC-mediated PMNs by inhibiting the S1PR1/STAT3 axis, consequently postponing the initiation of lung metastasis.\u0000","PeriodicalId":23692,"journal":{"name":"World Journal of Traditional Chinese Medicine","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140229831","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}
Pub Date : 2024-03-15DOI: 10.4103/wjtcm.wjtcm_62_24
Yu-Qi Zhou, Jun-Fei Yuan, Hong-Shi Shen, Ya-Ping Wang, Han-Fei Shi, De-Jian Pan, Min Ye
The purpose of this research was to examine the potential anticancer properties of Xiao Tan San Jie Fang (XTSJF) and its potential mechanism of action against colorectal cancer. HCT116 cells were induced into HCT116 spheres in DMEM/F12 medium by treatment with epidermal growth factor + fibroblast growth factor + leukemia inhibitory factor + B27. The proliferation ability and stemness of HCT116 spheres was examined. Various concentrations of XTSJF were used to treat HCT116 spheres to observe the impact on proliferation, apoptosis, and expression of stem cell markers. Next, Wnt/β-catenin pathway-related factor proteins were detected. The findings revealed that XTSJF suppressed cell growth and induced cell death in HCT116 cells in a dosage-dependent manner. Similarly, XTSJF promotes apoptosis, inhibits cell proliferation, prolongs survival, and maintains the expression of stem cells through the Wnt/-catenin/TCF4 axis. XTSJF also inhibits AKT activity and subsequently activates glycogen synthesis kinase-3β expression, inhibiting Wnt/beta-catenin pathway activity and downstream target gene transcript expression. The Wnt/β-catenin signaling pathway is inhibited by the XTSJF, leading to the suppression of colon cancer stem cell proliferation. Xiaotan Sanjie Prescription inhibited colon cancer stem cell growth through Wnt/β-catenin signaling pathway.
{"title":"Xiao Tan San Jie Fang Hampers the Growth of Colon Cancer Stem Cells through the Wnt/β-catenin Signaling Pathway","authors":"Yu-Qi Zhou, Jun-Fei Yuan, Hong-Shi Shen, Ya-Ping Wang, Han-Fei Shi, De-Jian Pan, Min Ye","doi":"10.4103/wjtcm.wjtcm_62_24","DOIUrl":"https://doi.org/10.4103/wjtcm.wjtcm_62_24","url":null,"abstract":"\u0000 \u0000 \u0000 The purpose of this research was to examine the potential anticancer properties of Xiao Tan San Jie Fang (XTSJF) and its potential mechanism of action against colorectal cancer.\u0000 \u0000 \u0000 \u0000 HCT116 cells were induced into HCT116 spheres in DMEM/F12 medium by treatment with epidermal growth factor + fibroblast growth factor + leukemia inhibitory factor + B27. The proliferation ability and stemness of HCT116 spheres was examined. Various concentrations of XTSJF were used to treat HCT116 spheres to observe the impact on proliferation, apoptosis, and expression of stem cell markers. Next, Wnt/β-catenin pathway-related factor proteins were detected.\u0000 \u0000 \u0000 \u0000 The findings revealed that XTSJF suppressed cell growth and induced cell death in HCT116 cells in a dosage-dependent manner. Similarly, XTSJF promotes apoptosis, inhibits cell proliferation, prolongs survival, and maintains the expression of stem cells through the Wnt/-catenin/TCF4 axis. XTSJF also inhibits AKT activity and subsequently activates glycogen synthesis kinase-3β expression, inhibiting Wnt/beta-catenin pathway activity and downstream target gene transcript expression. The Wnt/β-catenin signaling pathway is inhibited by the XTSJF, leading to the suppression of colon cancer stem cell proliferation.\u0000 \u0000 \u0000 \u0000 Xiaotan Sanjie Prescription inhibited colon cancer stem cell growth through Wnt/β-catenin signaling pathway.\u0000","PeriodicalId":23692,"journal":{"name":"World Journal of Traditional Chinese Medicine","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140240403","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}
Pub Date : 2024-03-05DOI: 10.4103/wjtcm.wjtcm_53_23
Pan Chen, Bo-Yang Wang, Peng Zhang, Shaokun Li
The core principle of diagnosis and treatment in traditional Chinese medicine (TCM) is the identification of different syndromes. Cold and hot syndromes are important elements in TCM theory. Identifying the biological basis of cold and hot syndromes in TCM will help elucidate TCM theories scientifically, thus promoting precise treatment in TCM. Although the biological basis of cold/hot syndromes in TCM remains poorly understood, growing evidence suggests that immunometabolic interactions play an important role in balancing cold and hot syndromes. Immunometabolism involves complex interactions between the immune and metabolic systems. Multilevel mechanisms of interaction between the immune and metabolic systems may underlie many inflammatory diseases and offer substantial therapeutic promise. Therefore, dissecting the relationship between immunometabolism and the biological network of cold/hot syndromes has become a priority. This article reviews the progress of cold/hot syndrome research from the perspective of immunometabolic homeostasis, thus further clarifying cold/hot syndromes in TCM.
{"title":"Cold and Hot Syndromes in Traditional Chinese Medicine: Insights from the Perspective of Immunometabolic Homeostasis","authors":"Pan Chen, Bo-Yang Wang, Peng Zhang, Shaokun Li","doi":"10.4103/wjtcm.wjtcm_53_23","DOIUrl":"https://doi.org/10.4103/wjtcm.wjtcm_53_23","url":null,"abstract":"\u0000 The core principle of diagnosis and treatment in traditional Chinese medicine (TCM) is the identification of different syndromes. Cold and hot syndromes are important elements in TCM theory. Identifying the biological basis of cold and hot syndromes in TCM will help elucidate TCM theories scientifically, thus promoting precise treatment in TCM. Although the biological basis of cold/hot syndromes in TCM remains poorly understood, growing evidence suggests that immunometabolic interactions play an important role in balancing cold and hot syndromes. Immunometabolism involves complex interactions between the immune and metabolic systems. Multilevel mechanisms of interaction between the immune and metabolic systems may underlie many inflammatory diseases and offer substantial therapeutic promise. Therefore, dissecting the relationship between immunometabolism and the biological network of cold/hot syndromes has become a priority. This article reviews the progress of cold/hot syndrome research from the perspective of immunometabolic homeostasis, thus further clarifying cold/hot syndromes in TCM.","PeriodicalId":23692,"journal":{"name":"World Journal of Traditional Chinese Medicine","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140264654","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}
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