The American journal of Chinese medicine最新文献

{"title":"Astragaloside IV Improves Pulmonary Vascular Endothelial Dysfunction in Pulmonary Arterial Hypertension by Inhibiting Ferroptosis through Modulation of the Calpain-1/TGF-β/TFRC Pathway.","authors":"Lin-Chao Niu, Ru Zhang, Qi Qi, Bai-Lin Tang, Sheng-Xue Yu, Guan Wang, Jingliang Zhang, Hong-Xin Wang","doi":"10.1142/S0192415X25500454","DOIUrl":"https://doi.org/10.1142/S0192415X25500454","url":null,"abstract":"<p><p>Pulmonary vascular endothelial dysfunction (PVED) is a significant contributor to pulmonary arterial hypertension (PAH). Research indicates that astragaloside IV (AS-IV) has a therapeutic effect on PAH, but the potential mechanism by which it improves the PVED in PAH remains unclear. This study primarily investigated the protective effect of AS-IV on PVED in PAH. Network pharmacological analysis revealed that AS-IV potentially exerts therapeutic effects on PVED in PAH patients mainly by affecting endothelial cell migration and ferroptosis-related biological processes. Elevated pulmonary arterial pressure, PVED, ferroptosis, and increased protein expression of calpain-1, TGF-β, TAZ, and TFRC have been found in hypoxia-induced PAH mice. However, AS-IV therapy reversed hypoxia-induced pulmonary arterial pressure elevation, endothelium-dependent diastolic impairment, elevated NO levels, iron accumulation, lipid peroxidation, and mitochondrial dysfunction. Moreover, AS-IV inhibited the calpain-1/TGF-β/TFRC signaling pathway. After calpain-1 gene knockout, Fer-1, MDL-28170, and SB-431542 induced effects similar to those of AS-IV. Furthermore, the overexpression of calpain-1 in HPAECs through viral transfection further decreased NO levels and aggravated ferroptosis induced by hypoxia. This also led to hypoxia-induced upregulation of the protein expression of calpain-1, TGF-β, TAZ, and TFRC. Moreover, the overexpression of calpain-1 reversed the ameliorative effect of AS-IV on hypoxia-induced dysfunction and ferroptosis in HPAECs. In conclusion, AS-IV can reduce ferroptosis-related iron accumulation, lipid peroxidation, and mitochondrial dysfunction by blocking the calpain-1/TGF-β/TFRC signaling pathway, ultimately improving PVED in hypoxia-induced PAH.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":"53 4","pages":"1181-1206"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532185","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":"Evodiamine Suppresses Lung Cancer Progression Through Modulating FAK/STAT3/AKT Signaling Pathway.","authors":"Wen-Xin Yuan, Wen Chen, Ping Hu, Qian-Wen Huang, Le-Hui Li, Hong Yang, Wei Zhang, Jian-Jun Tang, Long-Hua Sun","doi":"10.1142/S0192415X25500478","DOIUrl":"https://doi.org/10.1142/S0192415X25500478","url":null,"abstract":"<p><p>Lung cancer is a serious threat to human health and has become a major challenge to global public health. Evodiamine, a naturally indole alkaloid extracted from <i>Tetradium ruticarpum</i> (A. Juss.) T.G. Hartley, has been found to have toxic effects on various tumor cells. Nevertheless, the mechanism by which evodiamine on lung cancer remains unknown. In this study, the effects and possible mechanisms of evodiamine on lung cancer were investigated. Our data demonstrated that evodiamine suppressed the proliferation and migration of A549 and H1299 cells. Mechanistically, evodiamine operated by downregulating the phosphorylated expression of focal adhesion kinase (FAK), signal transducer and activator of transcription 3 (STAT3), and protein kinase B (AKT), while concurrently reducing the expression of CyclinA2 and CyclinB1. Notably, evodiamine inhibited the proliferation of A549 and H1299 cells by blocking the phosphorylation of FAK/STAT3/AKT induced by epidermal growth factor (EGF). Furthermore, the subcutaneous tumor models found that evodiamine slowed the growth of lung cancer <i>in vivo</i>. Collectively, our results showed that evodiamine inhibited the cell proliferation and migration of NSCLC and slowed subcutaneous tumor growth probably by the EGF-mediated FAK/STAT3/AKT pathway. These findings suggested that evodiamine is a promising therapeutic candidate worthy of further exploration for NSCLC treatment.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":"53 4","pages":"1225-1240"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532187","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":"Pharmacokinetics and Biological Activities of Notoginsenoside R1: A Systematical Review.","authors":"Chao Wen, Xiaofei Liao, Xinyun Ye, Wentao Lai","doi":"10.1142/S0192415X25500090","DOIUrl":"10.1142/S0192415X25500090","url":null,"abstract":"<p><p><i>Panax notoginseng</i> (PN) root is a renowned nutritional supplement, health food additive, and traditional medicine that maintains homeostasis within the human microcirculatory system. Notoginsenoside R1 (NG-R1), an active compound derived from PN root, has been reported to possess various pharmacological activities, including anti-inflammatory, antioxidant, anticancer, antimicrobial, and angiogenic effects. However, NG-R1's pharmacokinetic properties and pharmacological activities have not been systematically elucidated. In this paper, the pharmacokinetic properties of NG-R1, its pharmacological effects, mechanisms of actions, and structure-activity relationship have been reviewed. Notably, NG-R1 inhibits tumor necrosis factor α (TNF-α) expression, enhances the expression of nuclear factor erythroid 2-related factor 2 (NRF2), and enhances the expression of vascular endothelial growth factor receptor (VEGFR). The pharmacological effects of NG-R1 are associated with the modulation of several signaling pathways, such as mitogen-activated protein kinase (MAPK)/nuclear factor κ-B (NF-κB), NRF2/antioxidant response element (ARE), Wnt/β-catenin, and phosphoinositide-3 kinase (PI3K)/protein kinase B (AKT). NG-R1 offers potentially protective effects against numerous diseases, including cardiovascular, neurological, renal, pulmonary, bone, and diabetes-related conditions. Although the pharmacological activities and diverse effects of NG-R1 have been demonstrated in various diseases, its clinical applications are limited by poor bioavailability. Several strategies have been explored to improve the pharmacokinetic profile of NG-R1, making it a promising candidate for drug development.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"205-249"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070556","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":"Quercetin Ameliorates Learning and Memory in OVX/D-gal-Induced Alzheimer's Disease in Rats by Inhibiting Neuroinflammation via cGAS-STING Signal Pathway.","authors":"Xin Zhang, Meng-Fan Ma, Rui Zong, Hong-Bin Liu, Tian-Xu Wang, Ci Liu, Yong-Yuan Cui, Liang-Jing Liu, Miao-Miao Wu, Li-Xia Shen","doi":"10.1142/S0192415X25500569","DOIUrl":"10.1142/S0192415X25500569","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is an age-related degenerative disorder of the central nervous system. Neuroinflammation is considered a key factor in its etiology and progression. AD is more prevalent in women than men and may be related to postmenopausal hormone deficiency. This study constructed an AD rat model by bilateral ovariectomy (OVX) and intraperitoneal injection of D-galactose (D-gal) and an <i>in vitro</i> AD cell model was induced in PC12 cells using lipopolysaccharide (LPS). The Morris water maze test was employed to assess the impact of quercetin (Que) on learning and memory in OVX/D-gal rats. Immunohistochemistry was utilized to assess the impact of Que on the expression of Aβ protein, p-tau protein, GFAP, and Iba1 in the hippocampus of OVX/D-gal rats. Nissl staining was performed to examine hippocampal pathological damage. ELISA was conducted to measure serum estrogen levels and the release of inflammatory cytokines, specifically TNF-α and IL-1β, in the hippocampus of OVX/D-gal rats. HE staining was utilized to evaluate uterine pathological alterations in OVX/D-gal rats. Cell viability was assessed using the CCK-8 assay to determine the protective effect of quercetin on LPS-induced PC12 cells. Western Blot analysis was conducted to evaluate the expression levels of estrogen receptors and the proteins associated with the cGAS-STING pathway in both <i>in vitro</i> and <i>in vivo</i> models. Protein-protein docking studies were performed to investigate the binding affinity between the estrogen receptor and proteins involved in the cGAS-STING signaling pathway. Results demonstrated that Que enhanced learning and memory capabilities in OVX/D-gal rats, alleviated hippocampal pathological damage, reduced the expression of Aβ, p-tau, GFAP, and Iba1, and inhibited the release of inflammatory factors. Additionally, Que activated estrogen receptor expression and increased serum estrogen levels without exacerbating uterine lesions. Furthermore, Que activated the estrogen receptor in LPS-induced PC12 cells, which inhibited the release of IL-6 and exerted neuroprotective effects. Que also suppressed the expression of proteins associated with the cGAS-STING pathway both <i>in vitro</i> and <i>in vivo</i>. Estrogen receptors exhibited strong binding affinity with cGAS-STING pathway proteins. In conclusion, Que can inhibit neuroinflammation <i>in vitro</i> and <i>in vivo</i>, enhance learning and memory in OVX/D-gal rats, and exert neuroprotective effects. The underlying mechanism may involve the inhibition of the cGAS-STING signaling pathway, and the estrogen receptor potentially influences this pathway directly or indirectly.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"1477-1499"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144644470","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":"Therapeutic Prospects of Ursolic Acid in Colorectal Cancer: Modulation of the Wnt/β-Catenin Signaling Pathway and Gut Microbiota Composition.","authors":"Hui Zhao, Miaoxin Jin, Jingyi Qiao, Shuo Tian, Lihua Cao, Shun Tang, Mingsan Miao","doi":"10.1142/S0192415X25500831","DOIUrl":"10.1142/S0192415X25500831","url":null,"abstract":"<p><p>This investigation is designed to delineate the antineoplastic properties of ursolic acid against colorectal cancer and to elucidate underlying molecular mechanisms, including its influence on gut microbiota homeostasis as assessed by alpha/beta diversity and functional profiling. The study initially treated HCT116 and SW480 colorectal cancer cell lines with ursolic acid at concentrations ranging from 0 to 90 μM to evaluate its impact on cell proliferation. Building on this, the researchers re-exposed the colorectal cancer cells to ursolic acid at 5 μM, 10 μM, and 20 μM for 24[Formula: see text]h to comprehensively assess its effects on key cellular processes such as migration, colony formation, apoptosis, and cell cycle regulation. Additionally, the same concentrations (5 μM, 10 μM, and 20 μM) were used to re-expose the cells for 24[Formula: see text]h to evaluate the modulation of the Wnt/β-catenin signaling pathway by ursolic acid. In the <i>in vivo</i> experiments, based on previously published literature, researchers administered ursolic acid at doses of 15 mg/kg, 30 mg/kg, and 60 mg/kg to a CRC mouse model induced by azoxymethane/dextran sulfate sodium (AOM/DSS). Subsequently, the effects of ursolic acid were evaluated through multiple parameters, which included body weight, survival rate, colorectal length, inflammatory markers, pathological changes, apoptosis, cell cycle phase distribution, Wnt/β-catenin signaling pathway activity, and gut microbiota composition analyzed via 16S rRNA sequencing targeting the V3-V4 hypervariable regions. The results demonstrated that ursolic acid potently represses the proliferative, migratory, and clonogenic capabilities of HCT116 and SW480 while concomitantly inducing apoptosis and cell cycle arrest. The antineoplastic actions of ursolic acid are attributed to its inhibitory effect on Wnt/β-catenin signaling. In the azoxymethane/dextran sodium sulfate-induced colorectal cancer model, the administration of ursolic acid yields marked enhancements in terms of body weight maintenance, survival metrics, attenuation of inflammatory responses, reduction of histopathological lesions, potentiation of apoptosis, disruption of the cell cycle, suppression of the Wnt/β-catenin pathway, and remodeling of both the gut microbiota composition and its associated metabolic activities. Ursolic acid, a phytochemical prevalent in traditional medicinal plants, demonstrates potent anti-CRC activity by inducing apoptosis, inducing cell cycle arrest, inhibiting Wnt/β-catenin signaling, and exercising additional effects on gut microbiota modulation.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"2245-2275"},"PeriodicalIF":5.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144984590","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":"Identification of Flavonoid Compounds in Treating Alzheimer's Disease Based on Network Medicine Framework Strategy.","authors":"Min-Rui Ding, Cai-Yun Xia, Yan-Jie Qu, Li-Min Zhang, Meng-Xue Zhang, Rong-Rong Zhen, Tong Zhang, Jin-Fang Chen, Bing Hu, Hong-Mei An","doi":"10.1142/S0192415X25500806","DOIUrl":"10.1142/S0192415X25500806","url":null,"abstract":"<p><p>Alzheimer's disease (AD) currently lacks effective therapeutics, but blood-brain-barrier-penetrating flavonoids show promising therapeutic potential. To address this critical need, we employed a novel network medicine framework to systematically identify flavonoid compounds for AD therapy by quantifying their network proximity to AD targets. Our systematic screening identified 48 potential anti-AD flavonoids, of which luteolin, quercetin, apigenin (API), and baicalein demonstrated significant neuroprotective effects in A[Formula: see text]25-35-induced rat pheochromocytoma (PC12) cell models. Of these, API emerged as the most promising candidate. A network pharmacological analysis revealed that API likely exerts its anti-AD effects through modulating apoptosis and inflammatory response, and AKT1 and NFKBIA were identified as key therapeutic targets. Experimental validation demonstrated that API treatment impeded the H₂O₂-induced decline in the mitochondrial membrane potential of PC12 cells, suppressed apoptosis, and mitigated neuronal damage. Furthermore, API downregulated the AKT/NF-[Formula: see text]B signal pathway, promoted microglial M2 polarization, and attenuated LPS-induced neuroinflammation in BV2 cells. API also alleviated the toxic effects of M1 microglia on neurons. This network-based screening strategy provides an innovative approach for developing new AD therapeutics.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"2167-2198"},"PeriodicalIF":5.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144984586","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":"Panax notoginseng Saponins Activate Nuclear Factor Erythroid 2-Related Factor 2 to Inhibit Ferroptosis and Attenuate Inflammatory Injury in Cerebral Ischemia–Reperfusion","authors":"Lin-Lin Wang, Man-Lin Kang, Can-Wen Liu, Liang Liu, Biao Tang","doi":"10.1142/s0192415x24500332","DOIUrl":"https://doi.org/10.1142/s0192415x24500332","url":null,"abstract":"<p><i>Panax notoginseng</i> saponins (PNS), the primary medicinal ingredient of <i>Panax notoginseng</i>, mitigates cerebral ischemia–reperfusion injury (CIRI) by inhibiting inflammation, regulating oxidative stress, promoting angiogenesis, and improving microcirculation. Moreover, PNS activates nuclear factor erythroid 2-related factor 2 (Nrf2), which is known to inhibit ferroptosis and reduce inflammation in the rat brain. However, the molecular regulatory roles of PNS in CIRI-induced ferroptosis remain unclear. In this study, we aimed to investigate the effects of PNS on ferroptosis and inflammation in CIRI. We induced ferroptosis in SH-SY5Y cells via erastin stimulation and oxygen glucose deprivation/re-oxygenation (OGD/R) <i>in vitro</i>. Furthermore, we determined the effect of PNS treatment in a rat model of middle cerebral artery occlusion/reperfusion and assessed the underlying mechanism. We also analyzed the changes in the expression of ferroptosis-related proteins and inflammatory factors in the established rat model. OGD/R led to an increase in the levels of ferroptosis markers in SH-SY5Y cells, which were reduced by PNS treatment. In the rat model, combined treatment with an Nrf2 agonist, Nrf2 inhibitor, and PNS-Nrf2 inhibitor confirmed that PNS promotes Nrf2 nuclear localization and reduces ferroptosis and inflammatory responses, thereby mitigating brain injury. Mechanistically, PNS treatment facilitated Nrf2 activation, thereby regulating the expression of iron overload and lipid peroxidation-related proteins and the activities of anti-oxidant enzymes. This cascade inhibited ferroptosis and mitigated CIRI. Altogether, these results suggest that the ferroptosis-mediated activation of Nrf2 by PNS reduces inflammation and is a promising therapeutic approach for CIRI.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140829092","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":"Ginkgo biloba and Its Chemical Components in the Management of Alzheimer's Disease.","authors":"Yong Peng, Quan Chen, Ya-Hui Xue, Hong Jin, Shu Liu, Miao-qiao Du, Shun-yu Yao","doi":"10.1142/S0192415X24500277","DOIUrl":"https://doi.org/10.1142/S0192415X24500277","url":null,"abstract":"The pathogenesis of Alzheimer's disease (AD), a degenerative disease of the central nervous system, remains unclear. The main manifestations of AD include cognitive and behavioral disorders, neuropsychiatric symptoms, neuroinflammation, amyloid plaques, and neurofibrillary tangles. However, current drugs for AD once the dementia stage has been reached only treat symptoms and do not delay progression, and the research and development of targeted drugs for AD have reached a bottleneck. Thus, other treatment options are needed. Bioactive ingredients derived from plants are promising therapeutic agents. Specifically, Ginkgo biloba (Gb) extracts exert anti-oxidant, anticancer, neuroplastic, neurotransmitter-modulating, blood fluidity, and anti-inflammatory effects, offering alternative options in the treatment of cardiovascular, metabolic, and neurodegenerative diseases. The main chemical components of Gb include flavonoids, terpene lactones, proanthocyanidins, organic acids, polysaccharides, and amino acids. Gb and its extracts have shown remarkable therapeutic effects on various neurodegenerative diseases, including AD, with few adverse reactions. Thus, high-quality Gb extracts are a well-established treatment option for AD. In this review, we summarize the insights derived from traditional Chinese medicine, experimental models, and emerging clinical trials on the role of Gb and its chemical components in the treatment of the main clinical manifestations of AD.","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":"16 16","pages":"1-42"},"PeriodicalIF":0.0,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140660120","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":"Ginsenoside Rd Attenuates Myocardial Ischemia/Reperfusion Injury by Inhibiting Inflammation and Apoptosis through PI3K/Akt Signaling Pathway","authors":"Yuanping Wang, Jiading Zheng, Xieyang Xiao, Cailing Feng, Yinghong Li, Hui Su, Ding Yuan, Qinghai Wang, Peihong Huang, Lili Jin","doi":"10.1142/s0192415x24500186","DOIUrl":"https://doi.org/10.1142/s0192415x24500186","url":null,"abstract":"<p>Myocardial ischemia/reperfusion (I/R) injury is the leading cause of death worldwide. Ginsenoside Rd (GRd) has cardioprotective properties but its efficacy and mechanism of action in myocardial I/R injury have not been clarified. This study investigated GRd as a potent therapeutic agent for myocardial I/R injury. Oxygen-glucose deprivation and reperfusion (OGD/R) and left anterior descending (LAD) coronary artery ligation were used to establish a myocardial I/R injury model <i>in vitro</i> and <i>in vivo</i>. <i>In vivo</i>, GRd significantly reduced the myocardial infarct size and markers of myocardial injury and improved the cardiac function in myocardial I/R injury mice. <i>In vitro</i>, GRd enhanced cell viability and protected the H9c2 rat cardiomyoblast cell line from OGD-induced injury GRd. The network pharmacology analysis predicted 48 potential targets of GRd for the treatment of myocardial I/R injury. GO and KEGG enrichment analysis indicated that the cardioprotective effects of GRd were closely related to inflammation and apoptosis mediated by the PI3K/Akt signaling pathway. Furthermore, GRd alleviated inflammation and cardiomyocyte apoptosis <i>in vivo</i> and inhibited OGD/R-induced apoptosis and inflammation in cardiomyocytes. GRd also increased PI3K and Akt phosphorylation, suggesting activation of the PI3K/Akt pathway, whereas LY294002, a PI3K inhibitor, blocked the GRd-induced inhibition of OGD/R-induced apoptosis and inflammation in H9c2 cells. The therapeutic effect of GRd <i>in vivo</i> and <i>in vitro</i> against myocardial I/R injury was primarily dependent on PI3K/Akt pathway activation to inhibit inflammation and cardiomyocyte apoptosis. This study provides new evidence for the use of GRd as a cardiovascular drug.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":"53 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140601776","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":"Formononetin Alleviates Ischemic Acute Kidney Injury by Regulating Macrophage Polarization through KLF6/STAT3 Pathway.","authors":"Ning-Xin Zhang, Chen Guan, Chen-Yu Li, Ling-Yu Xu, Yan-Lu Xin, Zhuo Song, Tian-Yang Li, Cheng-Yu Yang, Long Zhao, Lin Che, Yan-Fei Wang, Xiao-Fei Man, Yan Xu","doi":"10.1142/S0192415X24500587","DOIUrl":"10.1142/S0192415X24500587","url":null,"abstract":"<p><p>Recent research has indicated that formononetin demonstrates a potent anti-inflammatory effect in various diseases. However, its impact on sterile inflammation kidney injury, specifically acute kidney injury (AKI), remains unclear. In this study, we utilized an ischemia/reperfusion-induced AKI (IRI-AKI) mouse model and bone marrow-derived macrophages (BMDMs) to investigate the effects of formononetin on sterile inflammation of AKI and to explore the underlying mechanism. The administration of formononetin significantly preserved kidney function from injury, as evidenced by lower serum creatinine and blood urea nitrogen levels compared to IRI-AKI mice without treatment. This was further confirmed by less pathological changes in renal tubules and low expression of tubular injury markers such as KIM-1 and NGAL in the formononetin-treated IRI-AKI group. Furthermore, formononetin effectively suppressed the expression of pro-inflammatory cytokines (MCP-1, TNF-α, and IL-1β) and macrophage infiltration into the kidneys of AKI mice. <i>In vitro</i> studies showed that formononetin led to less macrophage polarization towards a pro-inflammatory phenotype in BMDMs stimulated by LPS and IFN-[Formula: see text]. The mechanism involved the KLF6 and p-STAT3 pathway, as overexpression of KLF6 restored pro-inflammatory cytokine levels and pro-inflammatory polarization. Our findings demonstrate that formononetin can significantly improve renal function and reduce inflammation in IRI-AKI, which may be attributed to the inhibition of KLF6/STAT3-mediated macrophage pro-inflammatory polarization. This discovery presents a new promising therapeutic option for the treatment of IRI-AKI.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"1487-1505"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142020031","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}