{"title":"巴西林通过调节炎症、氧化应激和线粒体功能障碍减轻肾缺血再灌注损伤。","authors":"Jinyi Zhao, Lulu Zhang, Fei Mu, Ying Yu, Chen Cui, Meng Tang, Kexin Sun, Yanping Yin, Jingwen Wang, Rui Gong","doi":"10.14670/HH-18-982","DOIUrl":null,"url":null,"abstract":"<p><p>Brazilin, a natural homoisoflavonoid, is the primary bioactive ingredient derived from the bark and heartwood of <i>Caesalpinia sappan</i> L. It has been proven to exhibit multiple biological activities and therapeutic potential in chronic degenerative diseases, fibrotic disorders, inflammatory diseases, and cancers. However, whether it is involved in regulating the pathological process of acute kidney injury (AKI) is not fully understood. This study aimed to elucidate the role and key pharmacological molecular mechanisms of brazilin in AKI. Our data demonstrated that pretreatment with brazilin can significantly reduce the high expression of serum creatinine (Scr), blood urea nitrogen (BUN), and lipocalin-2 (LCN2) in mice exposed to ischemia/reperfusion (I/R) and alleviate kidney histopathological damage. Meanwhile, pretreatment with brazilin can alleviate apoptosis, inflammation, and oxidative stress injury in the kidney tissue cells by partially inhibiting the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB)/NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammatory pathway or activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) antioxidant pathway. <i>In vitro</i>, pretreatment with brazilin significantly downregulated pro-apoptotic Bax and upregulated anti-apoptotic Bcl-2 expression in human renal proximal tubular cells (HK-2) subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). Besides, it ameliorated mitochondrial dysfunction by enhancing mitochondrial biogenesis and restoring mitochondrial membrane potential. These effects collectively suppressed oxidative stress injury and NLRP3 inflammasome signaling pathway activation. In summary, brazilin exhibits significant protective effects against I/R-induced AKI by attenuating inflammation, oxidative stress and cell apoptosis, and mitochondrial damage. These findings suggest that brazilin holds promise as a potential therapeutic agent for AKI.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"18982"},"PeriodicalIF":2.0000,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Brazilin attenuates kidney ischemia-reperfusion injury by regulating inflammation, oxidative stress, and mitochondrial dysfunction.\",\"authors\":\"Jinyi Zhao, Lulu Zhang, Fei Mu, Ying Yu, Chen Cui, Meng Tang, Kexin Sun, Yanping Yin, Jingwen Wang, Rui Gong\",\"doi\":\"10.14670/HH-18-982\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Brazilin, a natural homoisoflavonoid, is the primary bioactive ingredient derived from the bark and heartwood of <i>Caesalpinia sappan</i> L. It has been proven to exhibit multiple biological activities and therapeutic potential in chronic degenerative diseases, fibrotic disorders, inflammatory diseases, and cancers. However, whether it is involved in regulating the pathological process of acute kidney injury (AKI) is not fully understood. This study aimed to elucidate the role and key pharmacological molecular mechanisms of brazilin in AKI. Our data demonstrated that pretreatment with brazilin can significantly reduce the high expression of serum creatinine (Scr), blood urea nitrogen (BUN), and lipocalin-2 (LCN2) in mice exposed to ischemia/reperfusion (I/R) and alleviate kidney histopathological damage. Meanwhile, pretreatment with brazilin can alleviate apoptosis, inflammation, and oxidative stress injury in the kidney tissue cells by partially inhibiting the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB)/NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammatory pathway or activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) antioxidant pathway. <i>In vitro</i>, pretreatment with brazilin significantly downregulated pro-apoptotic Bax and upregulated anti-apoptotic Bcl-2 expression in human renal proximal tubular cells (HK-2) subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). Besides, it ameliorated mitochondrial dysfunction by enhancing mitochondrial biogenesis and restoring mitochondrial membrane potential. These effects collectively suppressed oxidative stress injury and NLRP3 inflammasome signaling pathway activation. In summary, brazilin exhibits significant protective effects against I/R-induced AKI by attenuating inflammation, oxidative stress and cell apoptosis, and mitochondrial damage. These findings suggest that brazilin holds promise as a potential therapeutic agent for AKI.</p>\",\"PeriodicalId\":13164,\"journal\":{\"name\":\"Histology and histopathology\",\"volume\":\" \",\"pages\":\"18982\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2025-09-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Histology and histopathology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.14670/HH-18-982\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Histology and histopathology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.14670/HH-18-982","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Brazilin attenuates kidney ischemia-reperfusion injury by regulating inflammation, oxidative stress, and mitochondrial dysfunction.
Brazilin, a natural homoisoflavonoid, is the primary bioactive ingredient derived from the bark and heartwood of Caesalpinia sappan L. It has been proven to exhibit multiple biological activities and therapeutic potential in chronic degenerative diseases, fibrotic disorders, inflammatory diseases, and cancers. However, whether it is involved in regulating the pathological process of acute kidney injury (AKI) is not fully understood. This study aimed to elucidate the role and key pharmacological molecular mechanisms of brazilin in AKI. Our data demonstrated that pretreatment with brazilin can significantly reduce the high expression of serum creatinine (Scr), blood urea nitrogen (BUN), and lipocalin-2 (LCN2) in mice exposed to ischemia/reperfusion (I/R) and alleviate kidney histopathological damage. Meanwhile, pretreatment with brazilin can alleviate apoptosis, inflammation, and oxidative stress injury in the kidney tissue cells by partially inhibiting the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB)/NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammatory pathway or activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) antioxidant pathway. In vitro, pretreatment with brazilin significantly downregulated pro-apoptotic Bax and upregulated anti-apoptotic Bcl-2 expression in human renal proximal tubular cells (HK-2) subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). Besides, it ameliorated mitochondrial dysfunction by enhancing mitochondrial biogenesis and restoring mitochondrial membrane potential. These effects collectively suppressed oxidative stress injury and NLRP3 inflammasome signaling pathway activation. In summary, brazilin exhibits significant protective effects against I/R-induced AKI by attenuating inflammation, oxidative stress and cell apoptosis, and mitochondrial damage. These findings suggest that brazilin holds promise as a potential therapeutic agent for AKI.
期刊介绍:
HISTOLOGY AND HISTOPATHOLOGY is a peer-reviewed international journal, the purpose of which is to publish original and review articles in all fields of the microscopical morphology, cell biology and tissue engineering; high quality is the overall consideration. Its format is the standard international size of 21 x 27.7 cm. One volume is published every year (more than 1,300 pages, approximately 90 original works and 40 reviews). Each volume consists of 12 numbers published monthly online. The printed version of the journal includes 4 books every year; each of them compiles 3 numbers previously published online.