Zhang Xiaoyi, Wang Kexin, Dai Hui, Cai Jieqi, Liu Yujie, Yin Chuanhui, Wu Jie, Li Xiaowei, Wu Guiyong, Lu Aiping, Liu Qinwen, Guan Daogang
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Southern Medical University, Guangzhou, China.
Front Pharmacol. 2022 Oct 20;13:1018273. doi: 10.3389/fphar.2022.1018273. eCollection 2022.
Traditional Chinese medicine (TCM) usually acts in the form of compound prescriptions in the treatment of complex diseases. The herbs contained in each prescription have the dual nature of efficiency and toxicity due to their complex chemical component, and the principle of prescription is usually to increase efficiency and reduce toxicity. At present, the studies on prescriptions have mainly focused on the consideration of the material basis and possible mechanism of the action mode, but the quantitative research on the compatibility rule of increasing efficiency and reducing toxicity is still the tip of the iceberg. With the extensive application of computational pharmacology technology in the research of TCM prescriptions, it is possible to quantify the mechanism of synergism and toxicity reduction of the TCM formula. Currently, there are some classic drug pairs commonly used to treat complex diseases, such as Hook. f. with Hance for lung cancer, Debeaux with Fisch. in the treatment of coronary heart disease, but there is a lack of systematic quantitative analysis model and strategy to quantitatively study the compatibility rule and potential mechanism of synergism and toxicity reduction. To address this issue, we designed an integrated model which integrates matrix decomposition and shortest path propagation, taking into account both the crosstalk of the effective network and the propagation characteristics. With the integrated model strategy, we can quantitatively detect the possible mechanisms of synergism and attenuation of Hook. f. nd Hance in the treatment of lung cancer. The results showed the compatibility of Hook. f. and Hance could increase the efficacy and decrease the toxicity of lung cancer treatment through MAPK pathway and PD-1 checkpoint pathway in lung cancer.
中医在治疗复杂疾病时通常采用复方制剂的形式。由于其化学成分复杂，每个方剂中的草药都具有功效和毒性的双重性质，方剂的原则通常是增效减毒。目前，对方剂的研究主要集中在作用方式的物质基础和可能机制的考虑上，但对增效减毒配伍规律的定量研究仍只是冰山一角。随着计算药理学技术在中医方剂研究中的广泛应用，量化中医方剂协同增效和减毒机制成为可能。目前，有一些常用于治疗复杂疾病的经典药对，如用于治疗肺癌的钩藤与汉防己，用于治疗冠心病的青木香与广木香，但缺乏系统的定量分析模型和策略来定量研究其配伍规律以及协同增效和减毒的潜在机制。为了解决这个问题，我们设计了一个综合模型，该模型整合了矩阵分解和最短路径传播，同时考虑了有效网络的相互作用和传播特性。通过综合模型策略，我们可以定量检测钩藤与汉防己在治疗肺癌中的协同增效和减毒的可能机制。结果表明，钩藤与汉防己的配伍可通过肺癌中的MAPK通路和PD-1检查点通路提高肺癌治疗的疗效并降低毒性。
