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山奈酚:为衰老相关疾病的先进治疗铺平道路。

Kaempferol: Paving the path for advanced treatments in aging-related diseases.

机构信息

School of Pharmaceutical Sciences, Jaipur National University, Jagatpura, 302017 Jaipur, Rajasthan, India.

Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj 11942, Saudi Arabia.

出版信息

Exp Gerontol. 2024 Apr;188:112389. doi: 10.1016/j.exger.2024.112389. Epub 2024 Mar 8.

Abstract

Aging-related diseases (ARDs) are a major global health concern, and the development of effective therapies is urgently needed. Kaempferol, a flavonoid found in several plants, has emerged as a promising candidate for ameliorating ARDs. This comprehensive review examines Kaempferol's chemical properties, safety profile, and pharmacokinetics, and highlights its potential therapeutic utility against ARDs. Kaempferol's therapeutic potential is underpinned by its distinctive chemical structure, which confers antioxidative and anti-inflammatory properties. Kaempferol counteracts reactive oxygen species (ROS) and modulates crucial cellular pathways, thereby combating oxidative stress and inflammation, hallmarks of ARDs. Kaempferol's low toxicity and wide safety margins, as demonstrated by preclinical and clinical studies, further substantiate its therapeutic potential. Compelling evidence supports Kaempferol's substantial potential in addressing ARDs through several mechanisms, notably anti-inflammatory, antioxidant, and anti-apoptotic actions. Kaempferol exhibits a versatile neuroprotective effect by modulating various proinflammatory signaling pathways, including NF-kB, p38MAPK, AKT, and the β-catenin cascade. Additionally, it hinders the formation and aggregation of beta-amyloid protein and regulates brain-derived neurotrophic factors. In terms of its anticancer potential, kaempferol acts through diverse pathways, inducing apoptosis, arresting the cell cycle at the G2/M phase, suppressing epithelial-mesenchymal transition (EMT)-related markers, and affecting the phosphoinositide 3-kinase/protein kinase B signaling pathways. Subsequent studies should focus on refining dosage regimens, exploring innovative delivery systems, and conducting comprehensive clinical trials to translate these findings into effective therapeutic applications.

摘要

衰老相关疾病(ARDs)是一个全球性的健康关注点,急需开发有效的治疗方法。山奈酚是几种植物中发现的一种类黄酮,已成为改善 ARD 的有前途的候选药物。这篇综述全面检查了山奈酚的化学性质、安全性概况和药代动力学,并强调了其针对 ARD 的潜在治疗用途。山奈酚的治疗潜力源于其独特的化学结构,赋予其抗氧化和抗炎特性。山奈酚抵抗活性氧(ROS)并调节关键细胞途径,从而对抗氧化应激和炎症,这是 ARD 的标志。临床前和临床研究表明,山奈酚的低毒性和广泛的安全范围进一步证实了其治疗潜力。有充分的证据表明,山奈酚通过几种机制在治疗 ARD 方面具有很大的潜力,特别是抗炎、抗氧化和抗细胞凋亡作用。山奈酚通过调节多种促炎信号通路,包括 NF-kB、p38MAPK、AKT 和 β-连环蛋白级联,表现出多功能的神经保护作用。此外,它还阻止β-淀粉样蛋白的形成和聚集,并调节脑源性神经营养因子。就其抗癌潜力而言,山奈酚通过多种途径发挥作用,诱导细胞凋亡、将细胞周期阻滞在 G2/M 期、抑制上皮-间充质转化(EMT)相关标志物,并影响磷酸肌醇 3-激酶/蛋白激酶 B 信号通路。后续研究应侧重于细化剂量方案、探索创新的给药系统,并进行全面的临床试验,将这些发现转化为有效的治疗应用。

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