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Purpose of the Review <p>This review focuses on withanolides from <i>Withania somnifera</i> as neuroprotective agents against Alzheimer’s disease, highlighting their clinical, cellular and molecular mechanisms of action.</p> Recent Findings <p>Withanolides, natural steroidal lactones from <i>W. somnifera</i>, enhance memory and provide significant neuroprotection both in vitro and in vivo. They inhibit amyloid-β protein oligomer aggregation, prevent tau protein hyperphosphorylation, and exert antioxidant effects by modulating the Kaep-1/Nrf2 pathway. In addition, they inhibit acetylcholinesterase and pseudo-cholinesterase, thereby improving memory and cognition. Withanolides reduce inflammation by lowering pro-inflammatory markers, such as IL-1β, IL-6, MCP-1, and TNF-α, and prevent neuronal apoptosis by decreasing Bax/caspase-3 and cyto-c expression. They also enhance neuroplasticity by increasing the levels of brain-derived neurotropic factor (BDNF) and glial fibrillary protein (GFAP), providing neuroprotection. Clinical trials have confirmed cognitive enhancement, memory improvement, and stress relief in patients with Alzheimer’s disease.</p> Conclusion <p>Withanolides offer neuroprotection in Alzheimer’s disease through antioxidant and anti-inflammatory activities, inhibition of amyloid-β aggregation, tau hyperphosphorylation, and acetylcholine enhancement. Current in vitro and in vivo data indicate that withanolides have strong potential to be effective treatments for Alzheimer’s disease.</p>

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Exploring Withanolides from Withania somnifera: A Promising Avenue for Alzheimer’s Disease Treatment

  • 期刊论文

  • 发表日期：

    2025年2月7日

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  • Chitikela P Pullaiah,
  • Preethi Priyadharshini SP,
  • Phareedha SK,
  • Yamini Nemalapalli,
  • Geetha Birudala,
  • S Lahari,
  • Shanmugam Vippamakula,
  • R Shakila,
  • Muni Swamy Ganjayi,
  • Raghavendra Mitta

摘要

Purpose of the Review

This review focuses on withanolides from Withania somnifera as neuroprotective agents against Alzheimer’s disease, highlighting their clinical, cellular and molecular mechanisms of action.

Recent Findings

Withanolides, natural steroidal lactones from W. somnifera, enhance memory and provide significant neuroprotection both in vitro and in vivo. They inhibit amyloid-β protein oligomer aggregation, prevent tau protein hyperphosphorylation, and exert antioxidant effects by modulating the Kaep-1/Nrf2 pathway. In addition, they inhibit acetylcholinesterase and pseudo-cholinesterase, thereby improving memory and cognition. Withanolides reduce inflammation by lowering pro-inflammatory markers, such as IL-1β, IL-6, MCP-1, and TNF-α, and prevent neuronal apoptosis by decreasing Bax/caspase-3 and cyto-c expression. They also enhance neuroplasticity by increasing the levels of brain-derived neurotropic factor (BDNF) and glial fibrillary protein (GFAP), providing neuroprotection. Clinical trials have confirmed cognitive enhancement, memory improvement, and stress relief in patients with Alzheimer’s disease.

Conclusion

Withanolides offer neuroprotection in Alzheimer’s disease through antioxidant and anti-inflammatory activities, inhibition of amyloid-β aggregation, tau hyperphosphorylation, and acetylcholine enhancement. Current in vitro and in vivo data indicate that withanolides have strong potential to be effective treatments for Alzheimer’s disease.