He Rupu, Ma Ruyun, Jin Zheng, Zhu Yanning, Yang Fude, Hu Fangdi, Dai Jianye
School of Pharmacy, Lanzhou University, Lanzhou, China.
School of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, China.
Front Pharmacol. 2022 Jul 19;13:933096. doi: 10.3389/fphar.2022.933096. eCollection 2022.
This study aimed to systematically evaluate the efficacy of (Franch.) Nannf. (, CR) and reveal the mechanism of its effects on suppressing Gastric Precancerous Lesions. First, we established the GPL rat model which was induced by N-methyl-N'-nitro-N-nitrosoguanidine, a disordered diet, and 40% ethanol. The CR's anti-Gastric Precancerous Lesions effect was comprehensively evaluated by body weight, pathological section, and serum biochemical indexes. Then, quantitative proteomics and metabolomics were conducted to unveil the disturbed protein-network and pharmacodynamic mechanism. Furthermore, serum pharmacology was employed to confirm that CR's anti-gastritis and anti-cancer phenotype in cell models. In animal models, CR had been shown to control inflammation and ameliorate Gastric Precancerous Lesions. Considering the combination of proteomics and metabolomics, we found that CR could significantly reverse the biological pathways related to energy metabolism which were disturbed by the Gastric Precancerous Lesions model. Furthermore, the results of serum pharmacology indicated that the containing serum could ameliorate gastritis injury and selectively inhibit the proliferation of gastric cancer cells rather than normal cells, which was closely related to ATP production in the above mentioned cells. In summary, CR exerted anti-Gastric Precancerous Lesions effects by ameliorating gastritis injury and selectively inhibiting the proliferation of gastric cancer cells rather than normal cells. Proteomics and metabolomics unveiled that its efficacy was closely related to its regulation of the energy-metabolism pathway. This research not only provided new ideas for exploring the mechanism of complex systems such as Chinese herbals but also benefited the treatment strategy of Gastric Precancerous Lesions via regulating energy metabolism.
本研究旨在系统评价山豆根（Franch.）Nannf.（苦参碱，CR）的疗效，并揭示其抑制胃癌前病变的作用机制。首先，我们建立了由N-甲基-N'-硝基-N-亚硝基胍、紊乱饮食和40%乙醇诱导的胃癌前病变大鼠模型。通过体重、病理切片和血清生化指标综合评价CR对胃癌前病变的防治作用。然后，进行定量蛋白质组学和代谢组学研究，以揭示受干扰的蛋白质网络和药效学机制。此外，采用血清药理学方法在细胞模型中证实CR的抗胃炎和抗癌表型。在动物模型中，CR已被证明可控制炎症并改善胃癌前病变。综合蛋白质组学和代谢组学的结果，我们发现CR可显著逆转胃癌前病变模型所干扰的与能量代谢相关的生物途径。此外，血清药理学结果表明，含CR血清可改善胃炎损伤，并选择性抑制胃癌细胞而非正常细胞的增殖，这与上述细胞中的ATP产生密切相关。总之，CR通过改善胃炎损伤和选择性抑制胃癌细胞而非正常细胞的增殖发挥抗胃癌前病变作用。蛋白质组学和代谢组学揭示其疗效与其对能量代谢途径的调节密切相关。本研究不仅为探索中药等复杂系统的作用机制提供了新思路，也通过调节能量代谢为胃癌前病变的治疗策略提供了帮助。
