Potential hepatic and renal toxicity induced by the biflavonoids from Ginkgo biloba  

作　　者：LI Yun-Ying LU Xiao-Yan SUN Jia-Li WANG Qing-Qing ZHANG Yao-Dan ZHANG Jian-Bing FAN Xiao-Hui 

机构地区：[1]Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China [2]Pharmaceutical Informatics Institute,College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310058,China [3]Zhejiang University-Wanbangde Pharmaceutical Group Joint Research Center for Chinese Medicine Modernization,Hangzhou 310058,China

出　　处：《Chinese Journal of Natural Medicines》2019年第9期672-681,共10页中国天然药物（英文版）

基　　金：supported by the National S&T Major Project(2018ZX09201011);the Key Program from Sci-Tech Plan of Zhejiang Province(2018C03075)

摘　　要：Evidence continues to grow on potential health risks associated with Ginkgo biloba and its constituents.While biflavonoid is a subclass of the flavonoid family in Ginkgo biloba with a plenty of pharmacological properties,the potential toxicological effects of biflavonoids remains largely unknown.Thus,the aim of this study was to investigate the in vitro and in vivo toxicological effects of the biflavonoids from Ginkgo biloba(i.e.,amentoflavone,sciadopitysin,ginkgetin,isoginkgetin,and bilobetin).In the in vitro cytotoxicity test,the five biflavonoids all reduced cell viability in a dose-dependent manner in human renal tubular epithelial cells(HK-2)and human normal hepatocytes(L-02),indicating they might have potential liver and kidney toxicity.In the in vivo experiments,after intragastrical administration of these biflavonoids at 20 mg·kg^–1·d^–1 for 7 days,serum biochemical analysis and histopathological examinations were performed.The activity of alkaline phosphatase was significantly increased after all the bifl avonoid administrations and widespread hydropic degeneration of hepatocytes was observed in ginkgetin or b ilobetin-treated mice.Moreover,the five biflavonoids all induced acute kidney injury in treated mice and the main pathological lesions were confirmed to the tubule,glomeruli,and interstitium injuries.As the in vitro and in vivo results suggested that these biflavonoids may be more toxic to the kidney than the liver,we further detected the mechanism of biflavonoids-induced nephrotoxicity.The increased TUNEL-positive cells were detected in kidney tissues of biflavonoids-treated mice,accompanied by elevated expression of proapoptotic protein BAX and unchanged levels of antiapoptotic protein BCL-2,indicating apoptosis was involved in biflavonoids-induced nephrotoxicity.Taken together,our results suggested that the five biflavonoids from Ginkgo biloba may have potential hepatic and renal toxicity and more attentions should be paid to ensure Ginkgo biloba preparations safety.Evidence continues to grow on potential health risks associated with Ginkgo biloba and its constituents. While biflavonoid is a subclass of the flavonoid family in Ginkgo biloba with a plenty of pharmacological properties, the potential toxicological effects of biflavonoids remains largely unknown. Thus, the aim of this study was to investigate the in vitro and in vivo toxicological effects of the biflavonoids from Ginkgo biloba（i.e., amentoflavone, sciadopitysin, ginkgetin, isoginkgetin, and bilobetin）. In the in vitro cytotoxicity test, the five biflavonoids all reduced cell viability in a dose-dependent manner in human renal tubular epithelial cells（HK-2） and human normal hepatocytes（L-02）, indicating they might have potential liver and kidney toxicity. In the in vivo experiments, after intragastrical administration of these biflavonoids at 20 mg·kg–1·d–1 for 7 days, serum biochemical analysis and histopathological examinations were performed. The activity of alkaline phosphatase was significantly increased after all the bifl avonoid administrations and widespread hydropic degeneration of hepatocytes was observed in ginkgetin or b ilobetin-treated mice. Moreover, the five biflavonoids all induced acute kidney injury in treated mice and the main pathological lesions were confirmed to the tubule, glomeruli, and interstitium injuries. As the in vitro and in vivo results suggested that these biflavonoids may be more toxic to the kidney than the liver, we further detected the mechanism of biflavonoids-induced nephrotoxicity. The increased TUNEL-positive cells were detected in kidney tissues of biflavonoids-treated mice, accompanied by elevated expression of proapoptotic protein BAX and unchanged levels of antiapoptotic protein BCL-2, indicating apoptosis was involved in biflavonoids-induced nephrotoxicity. Taken together, our results suggested that the five biflavonoids from Ginkgo biloba may have potential hepatic and renal toxicity and more attentions should be paid to ensure Ginkgo biloba prepa

关 键 词：BIFLAVONOIDS GINKGO biloba POTENTIAL TOXICITY Liver KIDNEY Apoptosis 

分 类 号：R965[医药卫生—药理学]