Young-Chang Cho, Lulu Yao, Da Young Lee, Xiangying Li, Guijae Yoo, Sang Yoon Choi, Namki Cho, Su-Jin Park, Somy Yoon, Jae Sung Lim
{"title":"8-甲氧基双酚C通过脂多糖诱导小鼠Kupffer细胞的Nrf2/HO-1和NF-κB/MAPK通路减轻炎症和氧化应激。","authors":"Young-Chang Cho, Lulu Yao, Da Young Lee, Xiangying Li, Guijae Yoo, Sang Yoon Choi, Namki Cho, Su-Jin Park, Somy Yoon, Jae Sung Lim","doi":"10.4014/jmb.2503.03013","DOIUrl":null,"url":null,"abstract":"<p><p><i>Lespedeza bicolor</i> (<i>L. bicolor</i>) is known for its anti-inflammatory, antioxidant, and anticancer properties, making it a common choice in traditional medicine practices. Researchers in several recent studies have focused on isolating individual phytochemicals from this plant through chromatography analysis to explore their therapeutic potential. In our previous work, we identified 8-methoxybicolosin C (8-MC) as a novel flavonoid derivative, isolated and purified from the roots of <i>L. bicolor</i>, which exhibited inhibitory effects on cell proliferation. In this study, we further investigated the biological activities of 8-MC by examining its antioxidant and anti-inflammatory effects in LPS-induced mouse Kupffer cells. The results showed that 8-MC suppresses the expression of inflammation-related mediators, including inducible nitric oxide synthase (iNOS), nitric oxide (NO), and pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β, in a dose-dependent manner. Additionally, 8-MC improves the GSH/GSSG balance by increasing glutathione (GSH) levels and decreasing oxidized glutathione (GSSG) levels. Interestingly, 8-MC was found to bind Keap1, preventing roteasomal degradation, and promoting the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), thereby increasing the expression of antioxidant-related proteins such as heme oxygenase-1 (HO-1). Moreover, 8-MC suppressed the activation of inflammatory signaling pathways, including c-Jun N-terminal kinases (JNKs) and p38 mitogen-activated protein kinases (MAPKs), while also inhibiting the nuclear translocation of nuclear factor kappa B (NF-κB), effectively reducing inflammatory responses. These findings collectively demonstrated that 8-MC possesses potent anti-inflammatory and antioxidant activities through the regulation of NF-κB, MAPK, and Nrf2/HO-1 signaling pathways. Consequently, 8-MC shows potential as a valuable therapeutic agent for managing various inflammatory disorders.</p>","PeriodicalId":16481,"journal":{"name":"Journal of microbiology and biotechnology","volume":"35 ","pages":"e2503013"},"PeriodicalIF":3.1000,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12375545/pdf/","citationCount":"0","resultStr":"{\"title\":\"8-Methoxybicolosin C from <i>Lespedeza bicolor</i> Attenuates Inflammation and Oxidative Stress via Nrf2/HO-1 and NF-κB/MAPK Pathways in Lipopolysaccharide-Induced Mouse Kupffer Cells.\",\"authors\":\"Young-Chang Cho, Lulu Yao, Da Young Lee, Xiangying Li, Guijae Yoo, Sang Yoon Choi, Namki Cho, Su-Jin Park, Somy Yoon, Jae Sung Lim\",\"doi\":\"10.4014/jmb.2503.03013\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><i>Lespedeza bicolor</i> (<i>L. bicolor</i>) is known for its anti-inflammatory, antioxidant, and anticancer properties, making it a common choice in traditional medicine practices. Researchers in several recent studies have focused on isolating individual phytochemicals from this plant through chromatography analysis to explore their therapeutic potential. In our previous work, we identified 8-methoxybicolosin C (8-MC) as a novel flavonoid derivative, isolated and purified from the roots of <i>L. bicolor</i>, which exhibited inhibitory effects on cell proliferation. In this study, we further investigated the biological activities of 8-MC by examining its antioxidant and anti-inflammatory effects in LPS-induced mouse Kupffer cells. The results showed that 8-MC suppresses the expression of inflammation-related mediators, including inducible nitric oxide synthase (iNOS), nitric oxide (NO), and pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β, in a dose-dependent manner. Additionally, 8-MC improves the GSH/GSSG balance by increasing glutathione (GSH) levels and decreasing oxidized glutathione (GSSG) levels. Interestingly, 8-MC was found to bind Keap1, preventing roteasomal degradation, and promoting the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), thereby increasing the expression of antioxidant-related proteins such as heme oxygenase-1 (HO-1). Moreover, 8-MC suppressed the activation of inflammatory signaling pathways, including c-Jun N-terminal kinases (JNKs) and p38 mitogen-activated protein kinases (MAPKs), while also inhibiting the nuclear translocation of nuclear factor kappa B (NF-κB), effectively reducing inflammatory responses. These findings collectively demonstrated that 8-MC possesses potent anti-inflammatory and antioxidant activities through the regulation of NF-κB, MAPK, and Nrf2/HO-1 signaling pathways. Consequently, 8-MC shows potential as a valuable therapeutic agent for managing various inflammatory disorders.</p>\",\"PeriodicalId\":16481,\"journal\":{\"name\":\"Journal of microbiology and biotechnology\",\"volume\":\"35 \",\"pages\":\"e2503013\"},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2025-08-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12375545/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of microbiology and biotechnology\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://doi.org/10.4014/jmb.2503.03013\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of microbiology and biotechnology","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.4014/jmb.2503.03013","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
胡枝子(L. bicolor)以其抗炎、抗氧化和抗癌特性而闻名,使其成为传统医学实践中的常见选择。近年来,研究人员致力于通过色谱分析从该植物中分离出单个植物化学物质,以探索其治疗潜力。在我们之前的工作中,我们鉴定了8-methoxybicolosin C (8-MC)是一种新的类黄酮衍生物,从L. bicolor的根中分离纯化,具有抑制细胞增殖的作用。在本研究中,我们通过检测8-MC对lps诱导的小鼠Kupffer细胞的抗氧化和抗炎作用,进一步研究了8-MC的生物活性。结果表明,8-MC抑制炎症相关介质的表达,包括诱导型一氧化氮合酶(iNOS)、一氧化氮(NO)和促炎细胞因子如肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6和IL-1β,并呈剂量依赖性。此外,8-MC通过增加谷胱甘肽(GSH)水平和降低氧化谷胱甘肽(GSSG)水平来改善GSH/GSSG平衡。有趣的是,8-MC被发现结合Keap1,阻止roteasomal降解,促进核因子红细胞2相关因子2 (Nrf2)的核易位,从而增加抗氧化相关蛋白如血红素加氧酶-1 (HO-1)的表达。此外,8-MC抑制炎症信号通路的激活,包括c-Jun n末端激酶(JNKs)和p38丝裂原活化蛋白激酶(MAPKs),同时还抑制核因子κB (NF-κB)的核易位,有效减轻炎症反应。这些发现共同表明,8-MC通过调节NF-κB、MAPK和Nrf2/HO-1信号通路具有强大的抗炎和抗氧化活性。因此,8-MC显示出作为治疗各种炎症性疾病的有价值的治疗剂的潜力。
8-Methoxybicolosin C from Lespedeza bicolor Attenuates Inflammation and Oxidative Stress via Nrf2/HO-1 and NF-κB/MAPK Pathways in Lipopolysaccharide-Induced Mouse Kupffer Cells.
Lespedeza bicolor (L. bicolor) is known for its anti-inflammatory, antioxidant, and anticancer properties, making it a common choice in traditional medicine practices. Researchers in several recent studies have focused on isolating individual phytochemicals from this plant through chromatography analysis to explore their therapeutic potential. In our previous work, we identified 8-methoxybicolosin C (8-MC) as a novel flavonoid derivative, isolated and purified from the roots of L. bicolor, which exhibited inhibitory effects on cell proliferation. In this study, we further investigated the biological activities of 8-MC by examining its antioxidant and anti-inflammatory effects in LPS-induced mouse Kupffer cells. The results showed that 8-MC suppresses the expression of inflammation-related mediators, including inducible nitric oxide synthase (iNOS), nitric oxide (NO), and pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β, in a dose-dependent manner. Additionally, 8-MC improves the GSH/GSSG balance by increasing glutathione (GSH) levels and decreasing oxidized glutathione (GSSG) levels. Interestingly, 8-MC was found to bind Keap1, preventing roteasomal degradation, and promoting the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), thereby increasing the expression of antioxidant-related proteins such as heme oxygenase-1 (HO-1). Moreover, 8-MC suppressed the activation of inflammatory signaling pathways, including c-Jun N-terminal kinases (JNKs) and p38 mitogen-activated protein kinases (MAPKs), while also inhibiting the nuclear translocation of nuclear factor kappa B (NF-κB), effectively reducing inflammatory responses. These findings collectively demonstrated that 8-MC possesses potent anti-inflammatory and antioxidant activities through the regulation of NF-κB, MAPK, and Nrf2/HO-1 signaling pathways. Consequently, 8-MC shows potential as a valuable therapeutic agent for managing various inflammatory disorders.
期刊介绍:
The Journal of Microbiology and Biotechnology (JMB) is a monthly international journal devoted to the advancement and dissemination of scientific knowledge pertaining to microbiology, biotechnology, and related academic disciplines. It covers various scientific and technological aspects of Molecular and Cellular Microbiology, Environmental Microbiology and Biotechnology, Food Biotechnology, and Biotechnology and Bioengineering (subcategories are listed below). Launched in March 1991, the JMB is published by the Korean Society for Microbiology and Biotechnology (KMB) and distributed worldwide.