Institute of Chinese Medicine and State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Shatin, Hong Kong.
Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming, China.
J Pharm Pharmacol. 2020 Nov;72(11):1657-1665. doi: 10.1111/jphp.13348. Epub 2020 Aug 5.
Two labdane diterpenoids, leojapone B and heteronone B, were isolated from Leonurus japonicus Houtt., and their biological activity were evaluated in this study.
Human and mouse cancer cells, human peripheral blood mononuclear cells (PBMCs) and mouse macrophages (RAW264.7 cells) were used to evaluate the activity of leojapone B and heteronone B, while the in vivo effects of leojapone B were further examined in Lewis Lung Cancer tumour-bearing mice.
In vitro studies showed that leojapone B selectively inhibited the proliferation of lung cancer cells, and both leojapone B and heteronone B inhibited the production of pro-inflammatory cytokines in activated PBMCs. In tumour-bearing mice model, lung tumours were reduced in size in mice treated with intraperitoneal injections of leojapone B at 20 and 30 mg/kg for 14 days. The population ratio of CD4 /CD8 T cells in mouse spleens was found to be increased, while regulatory T cells were decreased after leojapone B treatment.
The inhibitory effects of leojapone B in mouse lung tumours were demonstrated for the first time in this study. The immunomodulatory activity of heteronone B were also demonstrated. Our findings indicated that both leojapone B and heteronone B may act as active components in L. japonicus.
从益母草中分离得到两种贝壳杉烷二萜，即莱奥杰酮 B 和异诺酮 B，并对其生物活性进行了评价。
选用人及鼠癌细胞、人外周血单个核细胞（PBMCs）和鼠巨噬细胞（RAW264.7 细胞）来评价莱奥杰酮 B 和异诺酮 B 的活性，同时进一步在 Lewis 肺癌荷瘤小鼠模型中考察莱奥杰酮 B 的体内药效。
体外研究表明莱奥杰酮 B 选择性抑制肺癌细胞的增殖，莱奥杰酮 B 和异诺酮 B 均能抑制活化的 PBMCs 中促炎细胞因子的产生。在荷瘤小鼠模型中，腹腔注射莱奥杰酮 B（20 和 30mg/kg）14 天可使小鼠肺部肿瘤体积缩小。莱奥杰酮 B 处理后，小鼠脾脏中 CD4+/CD8+T 细胞的比例增加，而调节性 T 细胞减少。
本研究首次证明了莱奥杰酮 B 对鼠肺肿瘤的抑制作用，同时也证明了异诺酮 B 的免疫调节活性。研究结果表明，莱奥杰酮 B 和异诺酮 B 可能是益母草中的活性成分。
