Zishen Huoxue decoction (ZSHX) enhances cardiomyocyte viability following hypoxic stress; however, its upstream therapeutic targets remain unclear. Network pharmacology and RNA sequencing analyses revealed that ZSHX target genes were closely associated with mitophagy and apoptosis in the mitochondrial pathway.
The research and development of new traditional Chinese medicine (TCM) drugs have progressively established a novel system founded on the integration of TCM theory, human experience, and clinical trials (termed the “Three Combinations”). However, considering TCM’s distinctive features of “syndrome differentiation and treatment” and “multicomponent formulations and complex mechanisms”, current TCM drug development faces challenges such as insufficient understanding of the material basis and the overall mechanism of action and an incomplete evidence chain system. Moreover, significant obstacles persist in gathering human experience data, evaluating clinical efficacy, and controlling the quality of active ingredients, which impede the innovation process in TCM drug development. Network pharmacology, centered on the “network targets” theory, transcends the limitations of the conventional “single target” reductionist research model. It emphasizes the comprehensive effects of disease or syndrome biological networks as targets to elucidate the overall regulatory mechanism of TCM prescriptions. This approach aligns with the holistic perspective of TCM, offering a novel method consistent with TCM’s holistic view for investigating the complex mechanisms of TCM and developing new TCM drugs. It is internationally recognized as a “next-generation drug research model”. To advance the research of new tools, methods, and standards for TCM evaluation and to overcome fundamental, critical, and cutting-edge technical challenges in TCM regulation, this consensus aims to explore the characteristics, progress, challenges, applicable pathways, and specific applications of network pharmacology as a new theory, method, and tool in TCM drug development. The goal is to enhance the quality of TCM drug research and development and accelerate the efficiency of developing new TCM products.
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The inhibition of cyclin-dependent kinases (CDKs) is considered a promising strategy for cancer treatment due to their role in cell cycle regulation. However, CDK inhibitors with no selectivity among CDK families have not been approved. A CDK inhibitor with high selectivity for CDK4/6 exhibited significant treatment effects on breast cancer and has become a heavy bomb on the market. Subsequently, resistance gradually decreased the efficacy of selective CDK4/6 inhibitors in breast cancer treatment. In this review, we first introduce the development of selective CDK4/6 inhibitors and then explain the role of CDK2 activation in inducing resistance to CDK4/6 inhibitors. Moreover, we focused on the development of CDK2/4/6 inhibitors and selective CDK2 inhibitors, which will aid in the discovery of novel CDK inhibitors targeting the cell cycle in the future.
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Researcher of Zhuhai UM University of Science and Technology Research Institute. She is also the duty director of Joint Laboratory of Chinese Herbal Glycoengineering and Testing Technology, National Glycoengineering Research Centre and University of Macau. In addition, she is an advisor of South West Collaborative Innovation Center of Authentic Herbal Materials, a guest professor of Guiyang University of Traditional Chinese Medicine and the Expert of National Natural Science Foundation of China. As a specialist in quality control of Chinese medicines, she proposed the strategies of chemical standards industrialization, virtual chemical standards development and quality control of herbal glycans. As a PI/co-PI, Dr. Zhao held 30 research grants with national, ministerial and provincial levels. 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He was selected in the Power List 2020 (Around the World in 60 Scientists) and 2021 (Around the World in 100 Scientists), as an expert in herbal glycoanalysis and the development of quality control methods for Chinese medicines, by Analytical Scientists, and he is the Secretary General of Permanent Secretariat of the West Pacific Reginal Forum for the Harmonization of Herbal Medicine (FHH), a member of USP’s Herbal Medicines Compendium−East Asia Expert Panel, ISO standard for honey, Advisor of American Herbal Pharmacopoeia and member of Chinese Pharmacopoeia Commission. He is also an Executive Editor-in-Chief of Science of Traditional Chinese Medicine, Editor of Journal of Pharmaceutical and Biomedical Analysis (2020-2023), International Journal of Analytical Chemistry, Associate Editor of Journal of Separation Science (2016-2019), Frontiers in Pharmacology, Chinese Medicine, etc","corresper":true,"correspinfoEn":"spli@um.edu.mo (S. 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However, the underlying mechanisms have not been completely clarified yet. This study aimed to assess the effects and mechanisms of (−)-epigallocatechin-3-gallate (EGCG) and (−)-epicatechin-3-gallate (ECG) on human melanoma skin A375 cells. Results showed that EGCG and ECG inhibited the proliferation of A375 cells and ECG showed better inhibitory effect. Flow cytometry analysis had shown that EGCG and ECG induced apoptosis and led to cell cycle arrest. EGCG and ECG decreased Bcl-2 expression and upregulated Caspase-3 protein level, indicating the development of apoptosis. Furthermore, EGCG and ECG could decreased mitochondrial membrane potential of A375 cells. In addition, the expression of Beclin-1, LC3 and Sirt3 were downregulated at protein levels, which known to be associated with autophagy. After autophagy was increased by rapamycin, the apoptotic trend was not change, indicating that apoptosis and autophagy are independent. Mechanistically, EGCG and ECG treatments decreased phosphorylated-AMPK (p-AMPK) and increased the ratios of p-PI3K, p-AKT and p-mTOR in melanoma cells. Conclusively, EGCG and ECG induced apoptosis