CENAR and Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
J Ethnopharmacol. 2013 May 2;147(1):157-63. doi: 10.1016/j.jep.2013.02.027. Epub 2013 Feb 28.
Lignosus rhinocerus (Tiger Milk mushroom) is distributed in South China, Thailand, Malaysia, Indonesia, Philippines and Papua New Guinea. In Malaysia, it is the most popular medicinal mushroom used by the indigenous communities to relieve fever, cough, asthma, cancer, food poisoning and as a general tonic. In China, this mushroom is an expensive traditional medicine used to treat liver cancer, chronic hepatitis and gastric ulcers. The sclerotium of the mushroom is the part with medicinal value. This rare mushroom has recently been successfully cultivated making it possible to be fully exploited for its medicinal and functional benefits. The present study was carried out to evaluate the chronic toxicity of the sclerotial powder of Lignosus rhinocerus cultivar (termed TM02), its anti-fertility and teratogenic effects as well as genotoxicity.
Sprague Dawley rats (10 rats/group/sex) were fed orally with 250, 500 and 1000 mg/kg of sclerotial powder of TM02. The sclerotial powder was orally administered once daily and consecutively for 180 days. At the completion of the oral feeding period, analysis of hematological and clinical biochemical parameters, urine profiles, organ weight as well as histopathological analysis were carried out. The effect of the sclerotial powder on fertility and its possible teratogenicity were examined by feeding rats orally with 100 mg/kg sclerotial powder consecutively for 7-8 weeks. Genotoxicity was evaluated by Ames test using Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and Escherichia coli WP2 uvrA.
The results showed that oral administration of the sclerotial powder of the Lignosus rhinocerus cultivar at daily dose of up to 1000 mg/kg for 180 days had no adverse effect on the general clinical observations, body weight, hematology, clinical biochemistry, urinalysis, absolute organ weight as well as relative organ weight, nor induced histological changes in the organs. Oral administration of 100 mg/kg sclerotial powder of the Lignosus rhinocerus for 7-8 weeks did not affect the fertility of the rats nor induce teratogenic effect on their offspring. Lignosus rhinocerus sclerotial powder up to 5000 μg/plate in the presence and absence of metabolic activation did not cause gene mutations by base pair changes or frameshifts in the genome of the tester strains used.
Our results showed that the no-observed-adverse-effect level (NOAEL) dose of the sclerotial powder of Lignosus rhinocerus in 180-day chronic toxicity study is more than 1000 mg/kg. Oral feeding of the sclerotial powder at 100mg/kg did not induce adverse effect on rats' fertility nor causing teratogenic effect on their offspring. In the reverse mutation Ames test, the sclerotial powder at all tested concentration did not show any genotoxicity.
ETHNOPHARMACOLOGICAL 相关性：Lignosus rhinocerus（虎奶菇）分布于中国南方、泰国、马来西亚、印度尼西亚、菲律宾和巴布亚新几内亚。在马来西亚，它是土著社区最受欢迎的药用蘑菇，用于缓解发热、咳嗽、哮喘、癌症、食物中毒和作为一般补品。在中国，这种蘑菇是一种昂贵的传统药物，用于治疗肝癌、慢性肝炎和胃溃疡。蘑菇的菌核是具有药用价值的部分。这种稀有的蘑菇最近已成功种植，使其有可能充分利用其药用和功能效益。本研究旨在评估 Lignosus rhinocerus 栽培种菌核粉（称为 TM02）的慢性毒性、抗生育和致畸作用以及遗传毒性。
10 只 SD 大鼠（每组/性别 10 只）经口给予 250、500 和 1000mg/kg 的 TM02 菌核粉。菌核粉每天口服一次，连续 180 天。在口服喂养期结束时，进行血液学和临床生化参数、尿液分析、器官重量以及组织病理学分析。通过连续 7-8 周给大鼠口服 100mg/kg 菌核粉，研究菌核粉对生育力的影响及其可能的致畸作用。采用鼠伤寒沙门氏菌 TA98、TA100、TA1535、TA1537 和大肠杆菌 WP2 uvrA 进行 Ames 试验评估遗传毒性。
结果表明，180 天内每日口服剂量高达 1000mg/kg 的 Lignosus rhinocerus 栽培种菌核粉对一般临床观察、体重、血液学、临床生化、尿液分析、绝对器官重量和相对器官重量均无不良影响，也未引起器官组织学变化。连续 7-8 周口服 100mg/kg 的 Lignosus rhinocerus 菌核粉对大鼠的生育力没有影响，也没有对其后代产生致畸作用。在有或没有代谢激活的情况下，虎奶菇菌核粉高达 5000μg/平板，不会引起试验菌株基因组中碱基对变化或移码的基因突变。
我们的研究结果表明，Lignosus rhinocerus 菌核粉在 180 天慢性毒性研究中的无明显不良效应水平（NOAEL）剂量大于 1000mg/kg。100mg/kg 口服菌核粉对大鼠生育力无不良影响，对其后代也无致畸作用。在回复突变 Ames 试验中，所有测试浓度的菌核粉均未显示任何遗传毒性。
