中华剑角蝗内生真菌Penicillium oxalicum次级代谢产物Secalonic acid A的分离及毒性实验研究

Experimental Study of Separation and Toxicity of Secalonic Acid A,a Kind of Secondary Metabolites fromPenicillium oxalicum,a Fungus Residing in Acrida Cinerea Gut

从中华剑角蝗肠道内生真菌分离鉴定Penicillium oxalicum,并进行其次级代谢产物的分离研究;在前期研究证实具有良好的抗肿瘤活性基础上,进行其毒性实验研究,为临床应用提供毒理学依据.采用活性追踪法,从中华剑角蝗肠道共生真菌Penicillium oxalicum的发酵产物中分离得到具有较高抗肿瘤活性的化合物;将40只昆明小鼠随机分为空白对照组和Secalonic acid A三个剂量给药组,每组10只,分别按照175、550、1 750mg/kg药物剂量(用橄榄油溶解),1次灌胃,灌胃体积为40mL/kg,逐日观察动物行为、外观及大小便,计算LD50,对主要脏器进行病理学检查.结果从内生真菌Penicillium oxalicum的发酵产物中分离得到一个具有较高抗肿瘤活性的苯并吡喃酮二聚体类化合物,经波谱数据及理化性质鉴定为Secalonic acid A,为首次从该属菌种中分离得到;Secalonic acid A给药后出现明显的活动异常,并随后相继死亡;肉眼观察可见肝脏表面呈红褐色,有少量出血点,胃肠臌胀,小肠充血扩张,其余器官肉眼观未见明显异常;病理学检查可见心、肝、肾、脾、胃、大小肠有不同程度病理学改变.结论表明,在动物水平上发现Secalonic acid A具有较强的毒性,其毒性机制正在进一步研究之中.

To separate secalonic acid A,a kind of secondary metabolites fromPenicillium oxalicum,a fungus residing in Acrida cinerea gut,based on previous investigation of anti-tumor activity,the study of the toxicity is carried out to provide toxicological basis for clinical application.The dimeric naphthopyrone,screened by MTT method,is isolated from the fermentation broth extract of Penicillium oxalicum,a fungus residing in Acrida cinerea.40 Kunming mice are randomly divided into the control groups and secalonic acid A（175,550,1750mg/kg,respectively）with 10 mice in every group and half male and half female by p.o.once a day;while mice＇s behavior and appearance are observed,and the amounts of night shit and urine in everyday are measured.Calculated LD50 and organ coefficient are also measured,and the main organs are examined by pathological method.On the basis of spectral data and physicochemical properties,the secalonic acid A is isolated for the first time from the endophytic fungus of Penicillium oxalicum.Mice show abnormal activity after administration of secalonic acid A,then died,and the liver surface show reddish brown,a small amount of bleeding point,gastrointestinal bloat,intestinal congestion expansion are observed,while other organs show no obvious abnormalities.Pathological examination shows that heart,liver,kidney,visible spleen,stomach,small intestine and so forth have different degrees of pathological changes.In the animal level,the secalonic acid A is confirmed to have strong toxicity,and the detailed mechanisms of toxicity is under studying.