Teng Yu-Ning
Department of Pharmacy, College of Pharmacy, China Medical University, 100, Sec. 1, Jingmao Rd., Beitun Dist., Taichung City 406040, Taiwan.
Department of Pharmacy, E-Da Cancer Hospital, 21 Yida Road, Kaohsiung 82445, Taiwan.
Antioxidants (Basel). 2025 Aug 16;14(8):1001. doi: 10.3390/antiox14081001.
This review explores the therapeutic promise of natural compounds in modulating 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), a key enzyme in cholesterol synthesis. HMGCR dysregulation is implicated in dyslipidemia, cardiovascular disease, and cancer, conditions linked to oxidative stress. While statins inhibit HMGCR, their side effects necessitate exploring alternatives. The review highlights various natural compounds-flavonoids, phenolic acids, stilbenes, and herbal formulations-with HMGCR-modulating and antioxidant capabilities. In vitro and in vivo studies suggest these compounds offer a promising avenue for treating HMGCR-related conditions. Synergistic effects are observed when combining natural products with statins, hinting at combination therapies that could lower statin dosages and reduce adverse effects. Natural HMGCR modulators hold therapeutic promise but face hurdles like limited in vivo data, regulatory issues, variability in composition, potential drug interactions, and safety concerns. Future research must prioritize comprehensive mechanistic studies, standardized preparations, and well-designed clinical trials. Overcoming these challenges through rigorous science is essential for integrating natural HMGCR modulators into clinical practice and improving patient outcomes in a safe and effective manner. Specifically, clinical trials should consider combination therapies and comparison with standard treatments like statins. More research is also needed on optimal dosages and treatment regimens.
本综述探讨了天然化合物在调节3-羟基-3-甲基戊二酰辅酶A还原酶（HMGCR）方面的治疗前景，HMGCR是胆固醇合成中的关键酶。HMGCR失调与血脂异常、心血管疾病和癌症有关，这些疾病都与氧化应激有关。虽然他汀类药物可抑制HMGCR，但其副作用促使人们探索替代药物。该综述重点介绍了具有HMGCR调节和抗氧化能力的各种天然化合物——黄酮类化合物、酚酸、芪类化合物和草药配方。体外和体内研究表明，这些化合物为治疗与HMGCR相关的疾病提供了一条有前景的途径。将天然产物与他汀类药物联合使用时可观察到协同效应，这暗示了联合疗法可降低他汀类药物剂量并减少不良反应。天然HMGCR调节剂具有治疗前景，但面临着诸如体内数据有限、监管问题、成分变异性、潜在药物相互作用和安全性问题等障碍。未来的研究必须优先进行全面的机制研究、标准化制剂和精心设计的临床试验。通过严谨的科学克服这些挑战对于将天然HMGCR调节剂安全有效地纳入临床实践并改善患者预后至关重要。具体而言，临床试验应考虑联合疗法并与他汀类药物等标准治疗方法进行比较。还需要对最佳剂量和治疗方案进行更多研究。
