Flavokawains a and B in kava, not dihydromethysticin, potentiate acetaminophen-induced hepatotoxicity in C57BL/6 mice.
Flavokawains a and B in kava, not dihydromethysticin, potentiate acetaminophen-induced hepatotoxicity in C57BL/6 mice.
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DOI：
10.1021/tx5003194
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发表时间：
2014-10-20
影响因子：
4.1
通讯作者：
Xing C
中科院分区：
文献类型：
--
作者：
Narayanapillai SC;Leitzman P;O'Sullivan MG;Xing C
抗焦虑的卡瓦产品与人类罕见但严重的肝毒性有关。这种不利的潜力从未在动物模型中被捕捉到，责任化合物(S)仍有待确定。缺乏这种知识极大地阻碍了更安全的卡瓦产品的制备，并限制了其有益的应用。在这项研究中，我们评估了卡瓦作为单一实体或与对乙酰氨基酚(APAP)合用对C57BL/6小鼠的毒性。仅Kava一项显示，即使在500毫克/公斤体重的剂量下，长期使用也没有不良影响。相反，卡瓦预处理3天可加重APAP诱导的肝毒性，导致血清ALT和AST升高，肝脏损害加重。卡瓦中查尔酮基黄酮类A(FKA)和B(FKB)与APAP具有肝毒性协同作用，而二氢甲基粘菌素(DHM)则无此作用。这些结果首次证明了卡瓦及其基于查尔酮的FKA和FKB在体内的肝脏毒性风险，并表明药物与药物的相互作用可能解释了人类使用抗焦虑卡瓦造成的罕见肝毒性。
Anxiolytic kava products have been associated with rare but severe hepatotoxicity in humans. This adverse potential has never been captured in animal models, and the responsible compound(s) remains to be determined. The lack of such knowledge greatly hinders the preparation of a safer kava product and limits its beneficial applications. In this study we evaluated the toxicity of kava as a single entity or in combination with acetaminophen (APAP) in C57BL/6 mice. Kava alone revealed no adverse effects for long-term usage even at a dose of 500 mg/kg bodyweight. On the contrary a three-day kava pretreatment potentiated APAP-induced hepatotoxicity, resulted in an increase in serum ALT and AST, and increased severity of liver lesions. Chalcone-based flavokawains A (FKA) and B (FKB) in kava recapitulated its hepatotoxic synergism with APAP while dihydromethysticin (DHM, a representative kavalactone and a potential lung cancer chemopreventive agent) had no such effect. These results, for the first time, demonstrate the hepatotoxic risk of kava and its chalcone-based FKA and FKB in vivo and suggest that herb–drug interaction may account for the rare hepatotoxicity associated with anxiolytic kava usage in humans.
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影响因子：
11.2
作者：
Zi, XL;Simoneau, AR
通讯作者：
Simoneau, AR
DOI：
10.1080/01635581.2012.689917
发表时间：
2012-01-01
影响因子：
2.9
作者：
Triolet, Julie;Shaik, Ahmad Ali;Xing, Chengguo
通讯作者：
Xing, Chengguo
DOI：
10.1158/1940-6207.capr-13-0301
发表时间：
2014-01
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Leitzman P;Narayanapillai SC;Balbo S;Zhou B;Upadhyaya P;Shaik AA;O'Sullivan MG;Hecht SS;Lu J;Xing C
通讯作者：
Xing C
影响因子：
6.1
作者：
Jhoo, JW;Freeman, JP;Ang, CYW
通讯作者：
Ang, CYW
影响因子：
1.7
作者：
Sarris, Jerome;Kavanagh, David J.;Bone, Kerry M.
通讯作者：
Bone, Kerry M.