Exploring the Multifaceted Therapeutic Potential of Withaferin A and Its Derivatives.
Exploring the Multifaceted Therapeutic Potential of Withaferin A and Its Derivatives.
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DOI：
10.3390/biomedicines8120571
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发表时间：
2020-12-06
期刊：
影响因子：
4.7
通讯作者：
Bungau S
中科院分区：
文献类型：
--
作者：
Behl T;Sharma A;Sharma L;Sehgal A;Zengin G;Brata R;Fratila O;Bungau S
Withaferin A(Wa)，一种被研究的多种多样的化合物，C28-类固醇内酯和双内酯，从睡莲中发现。由于其独特的有益效果，它在现代科学时代引起了人们的关注。癌症被认为是一个“无可救药的病例，也是全世界主要的死亡原因，而现有的传统疗法以副作用的形式存在许多漏洞。多药天然化合物WA Treatment通过改变氧化应激、促进细胞凋亡和自噬、抑制细胞增殖、减少血管生成和转移进展，显示出各种癌症特征的减弱。并对与抗肿瘤途径相关的细胞蛋白进行了讨论。Wa结构修饰可攻击多条信号转导通路，提高各种疾病的治疗效果。此外，它还通过抑制乙酰胆红素酶和丁酰胆碱酯酶的活性，通过上调脂联素和阻止过氧化物酶体增殖物激活受体(PPARγ)的磷酸化来抗糖尿病，通过激活AMP激活蛋白激酶(AMPK)来保护心脏，抑制线粒体凋亡，从而显示出有效的药理作用。目前的综述是对不同的与WA相关的疾病靶点、其药代动力学、协同结合、修饰和生物活性进行广泛的综述。
Withaferin A (WA), a manifold studied, C28-steroidal lactone withanolide found in Withania somnifera. Given its unique beneficial effects, it has gathered attention in the era of modern science. Cancer, being considered a “hopeless case and the leading cause of death worldwide, and the available conventional therapies have many lacunae in the form of side effects. The poly pharmaceutical natural compound, WA treatment, displayed attenuation of various cancer hallmarks by altering oxidative stress, promoting apoptosis, and autophagy, inhibiting cell proliferation, reducing angiogenesis, and metastasis progression. The cellular proteins associated with antitumor pathways were also discussed. WA structural modifications attack multiple signal transduction pathways and enhance the therapeutic outcomes in various diseases. Moreover, it has shown validated pharmacological effects against multiple neurodegenerative diseases by inhibiting acetylcholesterinases and butyrylcholinesterases enzyme activity, antidiabetic activity by upregulating adiponectin and preventing the phosphorylation of peroxisome proliferator-activated receptors (PPARγ), cardioprotective activity by AMP-activated protein kinase (AMPK) activation and suppressing mitochondrial apoptosis. The current review is an extensive survey of various WA associated disease targets, its pharmacokinetics, synergistic combination, modifications, and biological activities.
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发表时间：
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