Behl Tapan, Sharma Aditi, Sharma Lalit, Sehgal Aayush, Zengin Gokhan, Brata Roxana, Fratila Ovidiu, Bungau Simona
Chitkara College of Pharmacy, Chitkara University, Punjab 140401, India.
School of Pharmaceutical Sciences, Shoolini University, Solan, Himachal Pradesh 173229, India.
Biomedicines. 2020 Dec 6;8(12):571. doi: 10.3390/biomedicines8120571.
Withaferin A (WA), a manifold studied, C28-steroidal lactone withanolide found in . 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.
睡茄内酯A（WA）是一种在[具体来源未提及]中发现的经过多方面研究的C28甾体内酯类睡茄素。鉴于其独特的有益作用，它在现代科学时代受到了关注。癌症被认为是一种“不治之症”且是全球主要死因，而现有的传统疗法存在诸多以副作用形式出现的缺陷。这种多药合用的天然化合物——WA治疗，通过改变氧化应激、促进细胞凋亡和自噬、抑制细胞增殖、减少血管生成以及转移进展，显示出对各种癌症特征的缓解作用。还讨论了与抗肿瘤途径相关的细胞蛋白。WA的结构修饰作用于多个信号转导途径并提高在各种疾病中的治疗效果。此外，它通过抑制乙酰胆碱酯酶和丁酰胆碱酯酶的酶活性，显示出对多种神经退行性疾病的有效药理作用；通过上调脂联素并阻止过氧化物酶体增殖物激活受体（PPARγ）的磷酸化，具有抗糖尿病活性；通过激活AMP激活的蛋白激酶（AMPK）并抑制线粒体凋亡，具有心脏保护活性。本综述是对各种与WA相关的疾病靶点、其药代动力学、协同组合、修饰以及生物学活性的广泛调查。
