Suzuki Ryuichiro, Sakagami Hiroshi, Amano Shigeru, Fukuchi Kunihiko, Sunaga Katsuyoshi, Kanamoto Taisei, Terakubo Shigemi, Nakashima Hideki, Shirataki Yoshiaki, Tomomura Mineko, Masuda Yoshiko, Yokose Satoshi, Tomomura Akito, Watanabe Hirofumi, Okawara Masaki, Matahira Yoshiharu
Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, Sakado, Japan
Meikai University School of Dentistry, Sakado, Japan
In Vivo. 2017 Jul-Aug;31(4):591-598. doi: 10.21873/invivo.11099.
Most previous mastic investigators have not considered its potent cytotoxicity that may significantly affect the interpretation of obtained data. In the present study, we re-evaluated several biological activities of mastic extracts, based on chemotherapeutic indexes.
Pulverized mastic gum was extracted with n-hexane and then with ethyl acetate or independently with methanol or n-butanol. Tumor specificity (TS) of the extracts was determined by their cytotoxicity against human malignant and non-malignant cells. Antibacterial activity was determined by their cytotoxicity against bacteria and normal oral cells. Antiviral activity was determined by their protection of viral infection and cytotoxic activity. Cytochrome P-450 (CYP) 3A4 activity was measured by β-hydroxylation of testosterone.
Ethyl acetate extract showed slightly higher tumor specificity (TS=2.6) and one order higher antibacterial activity (selectivity index (SI)=0.813) than other extracts (TS=1.4-2.5; SI=0.030-0.063). All extracts showed no anti-human immunodeficiency virus (HIV) activity, but some anti-herpes simplex virus (HSV) activity, which was masked by potent cytotoxicity. They showed strong inhibitory activity against CYP3A4.
Ethyl acetate extraction following the removal of cytotoxic and CYP3A4 inhibitory substances by n-hexane can enhance antitumor and antibacterial activity of mastic.
以往大多数乳香研究人员并未考虑其强大的细胞毒性,而这种毒性可能会显著影响所获数据的解读。在本研究中,我们基于化疗指数重新评估了乳香提取物的几种生物活性。
将乳香胶粉碎后先用正己烷提取,然后用乙酸乙酯提取,或者分别用甲醇或正丁醇提取。通过提取物对人恶性和非恶性细胞的细胞毒性来确定其肿瘤特异性(TS)。通过提取物对细菌和正常口腔细胞的细胞毒性来确定其抗菌活性。通过提取物对病毒感染的保护作用和细胞毒性活性来确定其抗病毒活性。通过睾酮的β-羟基化作用来测量细胞色素P-450(CYP)3A4活性。
乙酸乙酯提取物显示出略高的肿瘤特异性(TS = 2.6),且抗菌活性比其他提取物高一个数量级(选择性指数(SI)= 0.813)(TS = 1.4 - 2.5;SI = 0.030 - 0.063)。所有提取物均未显示出抗人类免疫缺陷病毒(HIV)活性,但有一些抗单纯疱疹病毒(HSV)活性,不过这种活性被强大的细胞毒性所掩盖。它们对CYP3A4显示出强烈的抑制活性。
先用正己烷去除细胞毒性和CYP3A4抑制物质后再用乙酸乙酯提取,可以增强乳香的抗肿瘤和抗菌活性。