2. Academic Validation
  3. Identification of Flavonoid Compounds in Treating Alzheimer's Disease Based on Network Medicine Framework Strategy

Identification of Flavonoid Compounds in Treating Alzheimer's Disease Based on Network Medicine Framework Strategy

  • Am J Chin Med. 2025 Aug 30:1-32. doi: 10.1142/S0192415X25500806.
Min-Rui Ding 1,  Cai-Yun Xia 2,  Yan-Jie Qu 3,  Li-Min Zhang 1,  Meng-Xue Zhang 1,  Rong-Rong Zhen 1,  Tong Zhang 1,  Jin-Fang Chen 4,  Bing Hu 4,  Hong-Mei An 5
Affiliations

Affiliations

  • 1 Department of Neurology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, P. R. China.
  • 2 Intensive Care Unit, Emergency Department, General Hospital of Ningxia Medical University, Yinchuan 750004, P. R. China.
  • 3 Department of Traditional Chinese Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, P. R. China.
  • 4 Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, P. R. China.
  • 5 Department of Science & Technology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, P. R. China.
PMID: 40884807 DOI: 10.1142/S0192415X25500806
Abstract

Alzheimer's disease (AD) currently lacks effective therapeutics, but blood-brain-barrier-penetrating Flavonoids show promising therapeutic potential. To address this critical need, we employed a novel network medicine framework to systematically identify flavonoid compounds for AD therapy by quantifying their network proximity to AD targets. Our systematic screening identified 48 potential anti-AD Flavonoids, of which luteolin, quercetin, apigenin (API), and baicalein demonstrated significant neuroprotective effects in A[Formula: see text]25-35-induced rat pheochromocytoma (PC12) cell models. Of these, API emerged as the most promising candidate. A network pharmacological analysis revealed that API likely exerts its anti-AD effects through modulating Apoptosis and inflammatory response, and Akt1 and NFKBIA were identified as key therapeutic targets. Experimental validation demonstrated that API treatment impeded the H2O2-induced decline in the mitochondrial membrane potential of PC12 cells, suppressed Apoptosis, and mitigated neuronal damage. Furthermore, API downregulated the Akt/NF-[Formula: see text]B signal pathway, promoted microglial M2 polarization, and attenuated LPS-induced neuroinflammation in BV2 cells. API also alleviated the toxic effects of M1 microglia on neurons. This network-based screening strategy provides an innovative approach for developing new AD therapeutics.

Keywords

Alzheimer’s Disease; Apigenin; Flavonoids; Network Medicine Framework.

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