Department of Pharmacy, Faculty of Biological Sciences, University of Malakand, Chakdara, 18000 Dir (L), KP, Pakistan.
Public health Department, Health Sciences College at Lieth, Umm Al Qura University, Makkah, KSA.
Phytomedicine. 2024 Feb;124:155272. doi: 10.1016/j.phymed.2023.155272. Epub 2023 Dec 12.
Alzheimer's diseases (AD) and dementia are among the highly prevalent neurological disorders characterized by deposition of beta amyloid (Aβ) plaques, dense deposits of highly phosphorylated tau proteins, insufficiency of acetylcholine (ACh) and imbalance in glutamatergic system. Patients typically experience cognitive, behavioral alterations and are unable to perform their routine activities. Evidence also suggests that inflammatory processes including excessive microglia activation, high expression of inflammatory cytokines and release of free radicals. Thus, targeting inflammatory pathways beside other targets might be the key factors to control- disease symptoms and progression.
This review is aimed to highlight the mechanisms and pathways involved in the neuroprotective potentials of lead phytochemicals. Further to provide updates regarding challenges associated with their use and their progress into clinical trials as potential lead compounds.
Most recent scientific literature on pre-clinical and clinical data published in quality journals especially on the lead phytochemicals including curcumin, catechins, quercetin, resveratrol, genistein and apigenin was collected using SciFinder, PubMed, Google Scholar, Web of Science, JSTOR, EBSCO, Scopus and other related web sources.
Literature review indicated that the drug discovery against AD is insufficient and only few drugs are clinically approved which have limited efficacy. Among the therapeutic options, natural products have got tremendous attraction owing to their molecular diversity, their safety and efficacy. Research suggest that natural products can delay the disease onset, reduce its progression and regenerate the damage via their anti-amyloid, anti-inflammatory and antioxidant potentials. These agents regulate the pathways involved in the release of neurotrophins which are implicated in neuronal survival and function. Highly potential lead phytochemicals including curcumin, catechins, quercetin, resveratrol, genistein and apigenin regulate neuroprotective signaling pathways implicated in neurotrophins-mediated activation of tropomyosin receptor kinase (Trk) and p75 neurotrophins receptor (p75NTR) family receptors.
Phytochemicals especially phenolic compounds were identified as highly potential molecules which ameliorate oxidative stress induced neurodegeneration, reduce Aβ load and inhibit vital enzymes. Yet their clinical efficacy and bioavailability are the major challenges which need further interventions for more effective therapeutic outcomes.
阿尔茨海默病（AD）和痴呆症是高度流行的神经退行性疾病，其特征是β淀粉样蛋白（Aβ）斑块沉积、高度磷酸化 tau 蛋白的密集沉积、乙酰胆碱（ACh）不足和谷氨酸能系统失衡。患者通常会出现认知、行为改变，无法进行日常活动。有证据表明，炎症过程包括过度的小胶质细胞激活、炎症细胞因子的高表达和自由基的释放。因此，除了其他靶点之外，靶向炎症途径可能是控制疾病症状和进展的关键因素。
本综述旨在强调植物化学物中铅的神经保护潜力所涉及的机制和途径。进一步提供有关其使用相关挑战及其作为潜在先导化合物进入临床试验的最新进展。
使用 SciFinder、PubMed、Google Scholar、Web of Science、JSTOR、EBSCO、Scopus 和其他相关网络资源，收集发表在高质量期刊上的有关铅植物化学物（包括姜黄素、儿茶素、槲皮素、白藜芦醇、染料木黄酮和芹菜素）的临床前和临床最新科学文献。
文献综述表明，针对 AD 的药物发现还不够，只有少数几种药物在临床上被批准，而且疗效有限。在治疗选择中，天然产物因其分子多样性、安全性和疗效而引起了极大的关注。研究表明，天然产物可以通过其抗淀粉样蛋白、抗炎和抗氧化潜力来延缓疾病的发生、减少其进展并再生损伤。这些药物调节涉及神经营养因子释放的途径，而神经营养因子参与神经元的存活和功能。包括姜黄素、儿茶素、槲皮素、白藜芦醇、染料木黄酮和芹菜素在内的高潜力铅植物化学物调节神经营养因子介导的原肌球蛋白受体激酶（Trk）和 p75 神经营养因子受体（p75NTR）家族受体的激活所涉及的神经保护信号通路。
植物化学物，特别是酚类化合物，被鉴定为具有改善氧化应激诱导的神经退行性变、减少 Aβ 负荷和抑制关键酶的高度有潜力的分子。然而，其临床疗效和生物利用度是主要挑战，需要进一步干预以获得更有效的治疗效果。
