Zhang Wei-Yun, Liu Fa-Gui, Zheng Yi-Nan
Department of Pharmacy,Xiamen Medical College Xiamen 361023,China.
College of Chinese Medicinal Material,Jilin Agricultural University Changchun 130118,China.
Zhongguo Zhong Yao Za Zhi. 2019 Sep;44(17):3758-3762. doi: 10.19540/j.cnki.cjcmm.20190508.201.
Ginsenoside Rh_2,firstly isolated from red ginseng,is protopanaxadiol type of steroidal saponin. Rh_2 possessed variety of activities,but bioavailability of oral administration Rh_2 was extremely low due to poor absorption. Moreover,ginsenoside Rh_2 exhibited toxicity on human normal cells. Therefore,to improve stronger anti-tumor activity and attenuate toxicity,it was essential to design and optimize chemical structure of ginsenoside Rh_2. Through n-octanoylchloride modifications,a novel ester derivative of ginsenoside Rh_2 named caprylic acid monoester of Rh_2( C-Rh_2) was designed and synthesized. Structure of novel ginsenoside derivative was identified by1 D and 2 D NMR,as well as ESI-MS analyses. Anti-tumor effect of C-Rh_2 was tested on H22 tumor bearing mice. C-Rh_2 displayed certain anti-tumor activities and exhibited less toxicity than Rh_2. In the present study,C-Rh_2 as ester form of ginsenoside Rh_2 showed better anti-tumor activity and less toxicity,but the specific mechanism needs further investigation.
人参皂苷Rh_2最早从红参中分离得到，是原人参二醇型甾体皂苷。Rh_2具有多种活性，但由于吸收不良，口服给药时Rh_2的生物利用度极低。此外，人参皂苷Rh_2对人正常细胞具有毒性。因此，为了提高更强的抗肿瘤活性并降低毒性，设计和优化人参皂苷Rh_2的化学结构至关重要。通过正辛酰氯修饰，设计并合成了一种新型人参皂苷Rh_2酯衍生物，命名为Rh_2辛酸单酯（C-Rh_2）。通过一维和二维核磁共振以及电喷雾电离质谱分析鉴定了新型人参皂苷衍生物的结构。在荷H22肿瘤小鼠身上测试了C-Rh_2的抗肿瘤作用。C-Rh_2显示出一定的抗肿瘤活性，且毒性比Rh_2小。在本研究中，C-Rh_2作为人参皂苷Rh_2的酯形式显示出更好的抗肿瘤活性和更低的毒性，但具体机制需要进一步研究。
