Ying Zhang, Yongqi Xue, Jing Zeng, Hezhen Wu, Yanfang Yang
{"title":"Oxyepiberberine from the Active Site of Coptidis Rhizoma Inhibits Lung Adenocarcinoma by Regulating SRC-related Pathways in vivo","authors":"Ying Zhang, Yongqi Xue, Jing Zeng, Hezhen Wu, Yanfang Yang","doi":"10.1177/09731296231213147","DOIUrl":"https://doi.org/10.1177/09731296231213147","url":null,"abstract":"Background: Huanglian (HL), also known as Coptis chinensis Franch., was initially documented in “Sheng Nong’s Herbal Classic” as a high-quality product used to cure ailments such as fever, indigestion, bloating, nausea, dysentery, diarrhea, abdominal pain, and tuberculosis. Nowadays, it is extensively employed in clinical settings to alleviate pulmonary diseases, like tuberculosis, lobular lung disease, and pulmonary abscess, and is worth exploring further. Nevertheless, there is limited research on the precise advancements of anti-lung adenocarcinoma (LUAD). Objectives: Using biological experiments and network pharmacology, the objective of this research was to investigate the most effective parts and chemical constituents of C. chinensis against LUAD and ascertain the probable targets and pathways. Materials and Methods: First, an MTT experiment verified the impact of each part on A549 and BEAS-2B cells. High performance liquid chromatography (HPLC) was then used to identify the chemical components of the effective substance in C. chinensis against LUAD. Then, network pharmacology was used to screen potential pathways and binding target proteins. Finally, a subcutaneous tumor model was established in mice using LLC cells to observe the effects of the effective components of C. chinensis against LUAD in tumor-bearing mice. Results: The MTT assay demonstrated the efficacy of oxyepiberberine (OPB) as an anti-LUAD compound with minimal toxicity and side effects. According to the results of network pharmacology and molecular docking, SRC appears to be the primary target of C. chinensis active substance against LUAD. In vivo experiments revealed that the OPB group exhibited lowered toxicity and side effects. Additionally, the density of tumor cells decreased and the nuclei were destroyed in OPB groups of tumor tissues. Finally, OPB could regulate apoptosis, migration, and protein expression significantly related to the SRC pathway in tumor cells. Conclusion: Our research reveals the anti-LUAD properties of C. chinensis through a combination of experimentation and network analysis. These findings establish a theoretical foundation for C. chinensis as a clinical antitumor agent. Furthermore, our work provided an essential groundwork for further investigations into the medicinal properties of C. chinensis.","PeriodicalId":508089,"journal":{"name":"Pharmacognosy Magazine","volume":"49 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139801131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ying Zhang, Yongqi Xue, Jing Zeng, Hezhen Wu, Yanfang Yang
{"title":"Oxyepiberberine from the Active Site of Coptidis Rhizoma Inhibits Lung Adenocarcinoma by Regulating SRC-related Pathways in vivo","authors":"Ying Zhang, Yongqi Xue, Jing Zeng, Hezhen Wu, Yanfang Yang","doi":"10.1177/09731296231213147","DOIUrl":"https://doi.org/10.1177/09731296231213147","url":null,"abstract":"Background: Huanglian (HL), also known as Coptis chinensis Franch., was initially documented in “Sheng Nong’s Herbal Classic” as a high-quality product used to cure ailments such as fever, indigestion, bloating, nausea, dysentery, diarrhea, abdominal pain, and tuberculosis. Nowadays, it is extensively employed in clinical settings to alleviate pulmonary diseases, like tuberculosis, lobular lung disease, and pulmonary abscess, and is worth exploring further. Nevertheless, there is limited research on the precise advancements of anti-lung adenocarcinoma (LUAD). Objectives: Using biological experiments and network pharmacology, the objective of this research was to investigate the most effective parts and chemical constituents of C. chinensis against LUAD and ascertain the probable targets and pathways. Materials and Methods: First, an MTT experiment verified the impact of each part on A549 and BEAS-2B cells. High performance liquid chromatography (HPLC) was then used to identify the chemical components of the effective substance in C. chinensis against LUAD. Then, network pharmacology was used to screen potential pathways and binding target proteins. Finally, a subcutaneous tumor model was established in mice using LLC cells to observe the effects of the effective components of C. chinensis against LUAD in tumor-bearing mice. Results: The MTT assay demonstrated the efficacy of oxyepiberberine (OPB) as an anti-LUAD compound with minimal toxicity and side effects. According to the results of network pharmacology and molecular docking, SRC appears to be the primary target of C. chinensis active substance against LUAD. In vivo experiments revealed that the OPB group exhibited lowered toxicity and side effects. Additionally, the density of tumor cells decreased and the nuclei were destroyed in OPB groups of tumor tissues. Finally, OPB could regulate apoptosis, migration, and protein expression significantly related to the SRC pathway in tumor cells. Conclusion: Our research reveals the anti-LUAD properties of C. chinensis through a combination of experimentation and network analysis. These findings establish a theoretical foundation for C. chinensis as a clinical antitumor agent. Furthermore, our work provided an essential groundwork for further investigations into the medicinal properties of C. chinensis.","PeriodicalId":508089,"journal":{"name":"Pharmacognosy Magazine","volume":"18 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139860941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Investigating the Antioxidant Effect of Deoxyschizandin in Doxorubicin-induced Hepatotoxicity: Role of PTEN Signaling Modulation","authors":"Naijing Zhou, Qilian Zhu","doi":"10.1177/09731296231222671","DOIUrl":"https://doi.org/10.1177/09731296231222671","url":null,"abstract":"Background: The hepatotoxicity of doxorubicin (DOX) is one of its main toxic side effects that cannot be ignored. As an important initiating factor for hepatocyte apoptosis and necrosis, oxidative stress is crucial in DOX-induced hepatotoxicity. Deoxyschizandin (Deo) is a highly effective antioxidant flavonoid that has potential therapeutic potential in liver diseases. Objectives: It is of great clinical significance to demonstrate that Deo can effectively treat DOX-related hepatotoxicity. Materials and methods: The hepatotoxicity animal model was established by DOX, and Deo was used for intervention to observe the therapeutic effect. At the cellular level, phosphatase and tensin homolog deleted on chromosome ten (PTEN) is used as a therapeutic target for Deo to explore its impact on oxidative stress in hepatocytes. Results: Liver function damage and oxidative stress successfully appear in animal bodies. Specific manifestations include biomarkers of liver function damage, abnormal biomarkers of oxidative stress, and excessive production of reactive oxygen species (ROS) in hepatocytes. PTEN signaling plays an important role in Deo’s inhibition of oxidative stress. Conclusion: Our studies indicate that Deo improved DOX-induced liver oxidative stress, whose mechanisms may be related to PTEN signaling.","PeriodicalId":508089,"journal":{"name":"Pharmacognosy Magazine","volume":"52 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139611800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Liying Zhang, Ting Zhou, Yi-ming Zhang, Lei Wang, Yangyang Li, Gucheng Zhou, Heng Zhou, Fan Niu, Zhiwei Liu, Zhiming Miao, Yongqi Liu
{"title":"RIBE from Multiple Irradiation and the Protective Effects of Astragalus Polysaccharides on Methylation and Cancer-associated Proteins in BMSCs","authors":"Liying Zhang, Ting Zhou, Yi-ming Zhang, Lei Wang, Yangyang Li, Gucheng Zhou, Heng Zhou, Fan Niu, Zhiwei Liu, Zhiming Miao, Yongqi Liu","doi":"10.1177/09731296231204762","DOIUrl":"https://doi.org/10.1177/09731296231204762","url":null,"abstract":"Ionizing radiation can induce bystander effects (RIBE), and astragalus polysaccharides (APS) have a protective effect against RIBE. It has been proved that RIBE occurred and APS played the inhibitory effects on the RIBE when radiation was carried out only one time. However, whether RIBE happened by multiple irradiations and the effects of APS on the RIBE are unclear. This study aimed to investigate whether APS suppress RIBE damage induced by multiple irradiations. A549 cells were irradiated with 2 Gy X-rays to obtain a conditioned medium. Bone mesenchymal stem cells (BMSCs) was incubated with the conditioned medium 5 times every 3 days or APS. Cell proliferation was detected by CCK-8 and colony formation assay, and genomic instability and DNA damages were detected by the micronucleus and immunofluorescence assay. The protein associated with methylation and cancer-associated proteins in BMSCs were detected by western blot. After five stimulations with a conditioned medium, the proliferative capacity of BMSCs decreased; APS pre-intervention promoted the proliferation of BMSCs. And conditional medium intervention increased the micronucleus rate and a number of 53BP1 foci; APS pre-intervention reduced the micronucleus rate and number of 53BP1 foci. In addition, the conditional medium intervention reduced the expression of methylation-related proteins and increased the expression of cancer-related proteins, while APS pre-intervention reversed this trend. Irradiated A549 conditioned medium can induce RIBE of BMSCs, which might be related to methylation and cancer-associated proteins and APS may block RIBE by multiple irradiations in BMSCs.","PeriodicalId":508089,"journal":{"name":"Pharmacognosy Magazine","volume":"115 25","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139614078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hareendran Nair J, Kasthuri Nair A, Sithara Ms, Shan Sasidharan
{"title":"Subacute Oral Toxicity Studies of Pankajakasthuri Orthoherb Tablets Formulated for Managing Pain and Inflammation of Joints","authors":"Hareendran Nair J, Kasthuri Nair A, Sithara Ms, Shan Sasidharan","doi":"10.1177/09731296231215578","DOIUrl":"https://doi.org/10.1177/09731296231215578","url":null,"abstract":"Objectives: The objective of this investigation was to assess the subacute oral toxicity of the Pankajakasthuri Orthoherb Tablets, a polyherbal formulation used to manage pain and inflammation due to various pathological reasons, including osteoarthrosis, polyarthritis, rheumatoid arthritis, and other chronic degenerative disorders. Materials and Methods: The subacute toxicity studies of Pankajakasthuri Orthoherb Tablets were conducted using Wistar albino rats of both sexes, according to Organization for Economic Cooperation and Development-approved procedures. In this study, rats were orally administered Pankajakasthuri Orthoherb Tablets daily at doses of 250, 500, and 1000 mg/kg body weight for 28 days. Throughout the study period, general behavior, mortality, and adverse effects were recorded. Body weight, selected hematological and clinical chemistry parameters were determined at the end of the investigation period. Finally, histopathological analysis was performed to determine whether the study drug was inducing any alternations in the vital organs. Results: Daily administration of Pankajakasthuri Orthoherb Tablets for a continuous 28 days did not record any major toxicity indications. Additionally, no significant variation in food and water consumption, body weight, relative organs and hematology and clinical chemistry parameters was recorded in both sexes compared to the control. Histopathological investigation of the vital organs also revealed normal architecture, which suggests no morphological alterations after the administration of Pankajakasthuri Orthoherb Tablets. Conclusion: The outcomes of this investigation confirmed that Pankajakasthuri Orthoherb Tablets did not have the potential to induce toxicity signs in the experimental rats. The No observed Adverse Effect Level (NOAEL) for female and male rats of Pankajakasthuri Orthoherb Tablets under these experimental conditions was 500 mg/kg body weight. Based on the NOAEL, the human equivalent dose of the Pankajakasthuri Orthoherb Tablet was calculated at 5.195 g/day.","PeriodicalId":508089,"journal":{"name":"Pharmacognosy Magazine","volume":" 32","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139621704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ying Liu, Leilei Ma, Wenxuan Xu, Xiao-jin La, Biwei Zhang, Jianmei Cui, Chunyu Tian, Hong Chang, Ji-an Li
{"title":"Ramulus Mori (Sangzhi) Alkaloids (SZ-A) Ameliorate Myocardial Injury in Type 2 Diabetic Rats by Regulating Autophagy","authors":"Ying Liu, Leilei Ma, Wenxuan Xu, Xiao-jin La, Biwei Zhang, Jianmei Cui, Chunyu Tian, Hong Chang, Ji-an Li","doi":"10.1177/09731296231220433","DOIUrl":"https://doi.org/10.1177/09731296231220433","url":null,"abstract":"Background: Diabetes mellitus (DM) is a persistent metabolic condition resulting from insufficient insulin or insulin resistance, which gives rise to diverse complications endangering human well-being. Ramulus Mori (Sangzhi) alkaloids (SZ-A) have various pharmacological effects, potentially benefiting clinical comprehensive kidney and cardiovascular protection. Nevertheless, the potential protective effect of SZ-A on myocardial injury in individuals with type 2 diabetes mellitus (T2DM) remains unexplored. Materials and Methods: Sprague-Dawley (SD) rats were divided into four groups, including control, model, metformin, and SZ-A. The establishment of the type 2 diabetes model was initiated by injecting streptozotocin (STZ) along with a diet of high glucose and fat. Following a 12-week period of treatment, measurements were taken for heart mass index (HMI), fasting blood glucose (FBG), and 2-h postprandial blood glucose (2hPG). Additionally, serum glycated hemoglobin (HbA1c), indicators of myocardial injury, and oxidative stress were assessed. The expressions of mammalian target of rapamycin (mTOR), p-mTOR, beclin-1, and LC3 in myocardial tissue were detected by Western blot. Results: The administration of SZ-A effectively reduced the levels of HMI, FBG, 2hPG, HbA1c, malondialdehyde (MDA), lactate dehydrogenase (LDH), and creatine kinase isoenzymes (CK-MB) in rats with type 2 diabetes while enhancing the activity of superoxide dismutase (SOD). Additionally, SZ-A could improve myocardial tissue arrangement structure and fibrosis degree. Additional analysis revealed that SZ-A suppressed the activation of p-mTOR while enhancing the levels of Beclin-1 and LC3, suggesting that the potential therapeutic impact of SZ-A on myocardial damage could be attributed to its ability to regulate autophagy, thereby mitigating oxidative stress. Conclusion: In summary, the results indicate that SZ-A might possess inhibitory properties against myocardial damage in rats with type 2 diabetes, presenting a potential therapeutic approach in the clinic.","PeriodicalId":508089,"journal":{"name":"Pharmacognosy Magazine","volume":" 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139621532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N. S. S. Chalichem, Prathiksha Nabhan, Bharathi Bethapudi, Nikita Agarwal, Sasikumar Murugan, Mundkinajeddu Deepak
{"title":"Assessment of Immunomodulatory Activity of AP-Bio® (KalmCold®), a Standardized Extract of Andrographis paniculata Using in vivo and ex vivo Models","authors":"N. S. S. Chalichem, Prathiksha Nabhan, Bharathi Bethapudi, Nikita Agarwal, Sasikumar Murugan, Mundkinajeddu Deepak","doi":"10.1177/09731296231222378","DOIUrl":"https://doi.org/10.1177/09731296231222378","url":null,"abstract":"Background: Andrographis paniculata (Burm. f.) Nees is a well-recognized medicinal plant known for its benefits against a multitude of ailments. The intent of the present study was to evaluate the effect of a standardized extract of A. paniculata on innate immunity. Materials and Methods: Phagocytic activity was measured in terms of phagocytic index using carbon clearance methodology in mice. In another experiment, NK cells (effector cells) were isolated from the mouse spleen after the dosing period, and NK cells-mediated lysis of target cells (YAC-1 cells) were determined using an MTT assay. Results: The phagocytic index and NK cell activity were found to be significantly ( p < 0.05) different in the treated group compared to the control group in the tested animal models at a dose of 41 mg/kg. Conclusion: The results suggest the potential of A. paniculata to enhance innate immunity.","PeriodicalId":508089,"journal":{"name":"Pharmacognosy Magazine","volume":" 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139620789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N. Choi, Woogyun Choi, M. Kwon, Joon Park, Yun Tai Kim, Min Jae Lee, Jae-Woo Park, Joo Han Woo, Byung Joo Kim
{"title":"Methanol Extract of Petasites japonicas Promotes Apoptosis via the MAPK and ROS-dependent Signaling Pathways","authors":"N. Choi, Woogyun Choi, M. Kwon, Joon Park, Yun Tai Kim, Min Jae Lee, Jae-Woo Park, Joo Han Woo, Byung Joo Kim","doi":"10.1177/09731296231216167","DOIUrl":"https://doi.org/10.1177/09731296231216167","url":null,"abstract":"Petasites japonicus (PJ), also known as Butterbur, has a rich history as a traditional healing remedy across numerous countries. This study was designed to evaluate the potential anti-cancer properties of the methanol extract derived from PJ (PJE). Cell viability was measured with 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide. Cell cycle analysis, caspase activity assays, western blotting, and reactive oxygen species (ROS) assays were also used to investigate the anticancer effects of PJE on cancer cells. It was shown that PJE inhibited the cell viability of the colon carcinoma cell line Caco-2 (half-maximal inhibitory concentration [IC50]: 268.4 µg/mL), of the hepatocellular carcinoma cell line Hep3B (IC50: 420.2 µg/mL), and of the bladder carcinoma cell line 5637 (IC50: 99.43 µg/mL). Analysis of DNA content indicated an increase in the sub-G1 population of 5637 cells as a result of PJE treatment. Furthermore, PJE caused a reduction in mitochondrial membrane potential and the ratio of Bcl-2 to Bax. Moreover, PJE enhanced the levels of various components involved in the proapoptotic cascade, such as caspase-3, caspase-9, and poly-adenosine diphosphate-ribose polymerase. Moreover, it was observed that PJE modulated mitogen-activated protein kinases (MAPKs) activation and induced an elevation in intracellular production of ROS. These combined results strongly suggest that PJE possesses significant proapoptotic properties as an herbal medicine, acting through ROS-dependent MAPK signaling pathways in bladder cancer cells.","PeriodicalId":508089,"journal":{"name":"Pharmacognosy Magazine","volume":" 41","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139627186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Anti-tumor Function of Shikonin by Targeting EGFR/AKT/mTOR Signaling in Human Osteosarcoma Cells","authors":"Rui-Dan Zhu, Jia-Jia Zhang, Xiao-Bin Yao, Zhang-Jiao Wang, Zhi-Ling Du, Qingxia Xu","doi":"10.1177/09731296231215938","DOIUrl":"https://doi.org/10.1177/09731296231215938","url":null,"abstract":"Shikonin, a purified naphthoquinone separated from a Traditional Chinese medicinal herb Lithospermum erythrorhixon, which exhibits anticancer properties. To clarify the molecular mechanisms of therapeutic effects of shikonin against osteosarcoma. Cell Counting Kit-8 (CCK-8) assay was employed to evaluate cell viability. Annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) double-staining was conducted to evaluate the apoptotic ratio of the MG-63 cells. The effects of shikonin on the invasiveness of osteosarcoma cells were implemented by a transwell cell migration assay. In the meantime, a western blot assay was employed to detect alterations in the relevant mechanism proteins within osteosarcoma cells. Molecular docking analysis was conducted to anticipate the binding interaction between shikonin and EGFR/protein kinase B (AKT)/mTOR. We observed that shikonin suppressed proliferation and induced apoptosis in the MG-63 cells in a dose-dependent manner. Pursuing these findings, the potential molecular mechanisms were detected. Shikonin intervention blocked epidermal growth factor receptor (EGFR) phosphorylation and decreased epidermal growth factor (EGF)-induced activation of downstream signaling molecules, such as AKT and mammalian target of rapamycin (mTOR) in the MG-63 cells. However, the additional recombinant human epidermal growth factor (rHuEGF) could stimulate the activation of EGFR/AKT/mTOR signaling and reverse cell apoptosis caused by shikonin. Molecular docking analysis showed that shikonin presented the highest bonding ability with EGFR, AKT, and mTOR. Our results show that shikonin inhibits human osteosarcoma development via inactivating EGFR/AKT/mTOR signaling. It demonstrates that shikonin may act as a potential therapeutic agent in osteosarcoma treatment.","PeriodicalId":508089,"journal":{"name":"Pharmacognosy Magazine","volume":"15 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139451463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genistein Alleviates Dextran Sulfate Sodium-induced Ulcerative Colitis in Mice by Regulating Th17/Treg Cell Balance: Implication for the G Protein-coupled Estrogen Receptor","authors":"Baolian Shu, Youxing Wu, Xiaoyang Wang, Jianlan Hu, Danxia Zhang, Xianghao Gong, Saiqi He, Yan-na Xie, Xuan Chen, Ruohu Gui","doi":"10.1177/09731296231217599","DOIUrl":"https://doi.org/10.1177/09731296231217599","url":null,"abstract":"Objectives: This study aimed to evaluate the therapeutic effects and mechanism of genistein on dextran sulfate sodium-induced mouse model of ulcerative colitis (UC). Materials and Methods: A DSS-induced mouse model for UC was used in this study. Mice were then treated with genistein or a combination of genistein and the G protein-coupled estrogen receptor (GPER) antagonist G15. Colon length, disease activity index (DAI), spleen index (SI), histopathological alterations, and integrity of the colonic barrier were evaluated. The expression of inflammatory cytokines and antioxidant capacity were detected. Populations of T helper 17 cells (Th17) and Regulatory T cells (Treg) in the mesenteric lymph nodes (MLN) were analyzed. The expression of a transcription factor for Th17 and Treg in the colonic tissues was detected. Results: Genistein treatment significantly alleviated DSS-induced colitis, summarized as increased colonic length, decreased DAI, SI, improved histopathological alterations, and colonic barrier integrity. Genistein treatment restrained pro-inflammatory cytokines and oxidative enzyme release while promoting anti-inflammatory and anti-oxidative enzyme release. Flow cytometry indicated that genistein significantly reduced the Th17 population while boosting Treg populations. Furthermore, genistein inhibited the expression of transcription factors associated with Th17 and promoted the expression of transcription factors associated with Treg in the colonic tissue. Intriguingly, these observed effects of genistein were abolished when UC mice were treated with a combination of genistein and GPER antagonist G15. Conclusion: This study suggests that genistein is potent in protecting against DSS-induced colonic injuries by rebalancing Th17/Treg and that GPER may be a vital target for genistein-mediated immunomodulatory effects in UC.","PeriodicalId":508089,"journal":{"name":"Pharmacognosy Magazine","volume":"63 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139451592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}