General

Scientific Names: Mylabris phalerata Pallas

Common Names: Da Ban Mao, Nan Fang Da Ban Mao.

BOTANICAL:

来 源： 为芫青科(Meloidae)昆虫南方大斑蟊 Mylabris phalerata Pallas 的干燥成虫。

动物形状： 体长l5—30mm，黑色，被黑绒毛。头部具粗密刻点，复眼大，略呈肾形，触角线状，11节，触角末节基部明显窄于第l0节。鞘翅端部阔于基部，底色黑 色，每翅基部各有2个大黄斑；翅中央前后各有一黄色波纹状横带。足有黑色长绒毛，前足、中足财节均为5节，后足跗节为4节。腹面亦具黑色长绒毛。

生药材鉴定： 本品呈长椭圆形，头部下垂，眼大突起，背部鞘翅黑色，被三条黄色宽带纹。腹面黑色发亮，有特臭，刺激性强，易引起粘膜发疱。其中体形粗长者为大斑蟊，体形小者为小斑蟊。

Pharmacology

化学成分: 含斑蟊素(斑蟊酸酐cantharidin)1—2％，尚含脂肪12％、甲酸、色素及树脂。

Efficacy

Mylabris phalerata (MP) is an insect that has been used for the treatment of cancer in oriental medicine. In the present study, the butanol (BuOH) fraction of MP (BFMP) was examined to determine whether it can exert anti-cancer activity through an apoptotic pathway with little toxicity. BFMP was found to have a specific cytotoxic effect on human monocytic leukemic U937 cells (IC(50) = 140 microg/ml) rather than on peripheral blood mononuclear lymphocytes (PBML, IC(50) = over 500 microg/ml). BFMP also induced the morphological changes of apoptosis, such as chromatin condensation, cell shrinking and DNA fragmentation at a concentration of 31.25 microg/ml. In addition, BFMP significantly increased the portion of apoptotic annexin-V positive cells in a dose-dependent manner, and effectively activated caspases (cysteine aspartase) cascade involving caspases 8, 9 and 3. BFMP also effectively cleaved Bid, a death agonist member of the Bcl-2 family and (poly(ADP-ribose)polymerase) (PARP) and induced the subsequent release of cytochrome c from mitochondria into the cytosol. However, it did not affect Bcl-2 and Bax expression. Taken together, these data suggest that the BuOH extract of Mylabris phalerata can induce apoptosis in U937 cells by caspase cascade activation in conjunction with cytochrome c release, induced by a product of Bid. Therefore, we conclude that BFMP has anti-cancer activity, which is achieved through apoptosis and is associated with little toxicity. (source)

Cantharidin is isolated from Mylabris phalerata Pallas and is a potent inhibitor of hepatocellular carcinoma cells (Hep 3B cells). In the present study, the IC(50) values of cantharidin on Hep 3B cells and normal Chang liver cells were found to be 2.2 and 30.2 microM for 36 h, respectively. Furthermore, cantharidin-treated Hep 3B cells induced cell death within 1 h (IC(50)=52.8 microM), suggesting that cantharidin is an acute cytotoxic agent. We found that although cantharidin could induce cell death, it could not directly inhibit the activity of nucleic acid biosynthesis by the cellular incorporation of 3H-thymidine, 3H-uridine or 3H-leucine. Cantharidin-treated Hep 3B cells showed no evidence of major alterations in the cell cycle distribution within 1 h. However, examination of cells after treatment for 36 h showed that cantharidin regulated the cell cycle at the G(2)/M phase. Moreover, the treated Hep 3B cells had a rounded and shrunken appearance. The microvilli of treated Hep 3B cells were reduced in number and replaced by numerous blebs. Other ultrastructural changes following cantharidin treatment included the presence of lipid droplets, swelling of the mitochondria and accumulation of glycogen particles. The findings of damaged mitochondria in the cantharidin treated Hep 3B cells in this study suggest that cantharidin can induce acute and lethal toxic effects on Hep 3B cells by inhibiting the mitochondria energy system. (source)

Mylabris is the dried body of the Chinese blister beetle. The species used in medicine are Mylabris phalerata and M. cichorii. The use of mylabris as a traditional medicine in China can be traced back more than 2000 years, and it is still used as a folk medicine today. In recent studies, it has been found that mylabris possesses antitumor properties, increases the number of leucocytes, and has irritant effects on the urinary organs. The active constituent of mylabris is cantharidin. The synthesis of cantharidin is rather difficult. In order to find a less toxic analogue of cantharidin, its hydrolytic compound, disodium cantharidate, and its demethylated form, norcantharidin, were prepared. By biochemical and biological methods, it was found that these compounds may affect cancer cells in several ways. In clinical studies, antihepatoma effectiveness sequentially increased from cantharidin to disodium cantharidate to norcantharidin. Disodium cantharidate showed less urinary irritation than cantharidin while norcantharidin showed little to no such irritation. It appears that the two methyl groups of cantharidin are not the main functional groups for antitumor activity and for the stimulation of bone marrow but are associated with urinary irritation. Hydrocantharidimide, methylcantharidimide and dehydronorcantharidin have also been studied. All these compounds, except the last one, have been produced as antitumor agents in China. Since demethylated cantharidin may be prepared by total synthesis, it may be more suitable for medical investigation than cantharidin itself. (source)

本品对多种实验动物移植肿瘤有一定程度的抑制作用，尤其当 腹水型肿瘤接种的细胞数目较少时，可见小鼠生存期延长。实验证明斑蟊素对小鼠腹水肝癌有抑制作用，对网状细胞肉瘤L2也有效。其作用原理可能是抑制癌细胞 的蛋白质和核酸的合成，口服或腹腔注射都容易吸收，在血中维持的浓度也较持久，在肠、胃、胆、肝和瘤组织中的含量较高。中、小剂量对机体免疫功能不抑制， 但较大剂量可使免疫能力下降。

　　 临床用于原发肝癌有一定的疗效，主观症状改善，生存时间延长，部发病例可见肿块缩小。对乳腺癌、食道癌、肺癌等亦有一定效果。 (source)

IN VITRO:

1. Efferth T. Microarray-based prediction of cytotoxicity of tumor cells to cantharidin. Oncol Rep. 2005 Mar; 13(3):459-63.
2. Nakatani T, et al., Three novel cantharidin-related compounds from the Chinese blister beetle, Mylabris phalerata Pall. Chem Pharm Bull (Tokyo). 2004 Jul; 52(7):807-9.
3. Huh JE, et al., Mylabris phalerlata induces apoptosis by caspase activation following cytochrome c release and Bid cleavage. Life Sci. 2003 Sep 12; 73(17):2249-62.
4. Wang CC, et al., Cytotoxic effects of cantharidin on the growth of normal and carcinoma cells. Toxicology. 2000 Jun 8; 147(2):77-87.
5. Zhang Z, et al., [Pharmacological action of various processed Mylabris phalerata Pallas]. Zhongguo Zhong Yao Za Zhi. 1990 Apr;15(4):214-7, 254. Chinese.
6. Wang GS. Medical uses of mylabris in ancient China and recent studies. J Ethnopharmacol. 1989 Sep; 26(2):147-62. Review.
   
   
   
   
   

Safety

宜忌: 对泌尿系统和胃肠系统的刺激，如尿频、尿急、血尿和恶心。个别人面部麻木，心跳增快等神经、心血管系统反应。对骨髓无抑制作用。服药期间多饮水可减轻副作用。心肾功能不全、严重消化道溃疡、有出血倾向者及孕妇慎用。