Shengmaisan combined with Liuwei Dihuang Decoction alleviated CIH-induced glutamate excitotoxicity by IGF1/IGFR signaling pathway

  • Fitoterapia. 2025 Oct 26:187:106941. doi: 10.1016/j.fitote.2025.106941.
Xue Chen  1 ,  Xintong Fan  1 ,  Qingqing Liu  1 ,  Kerong Qi  1 ,  Jianchao Si  1 ,  Dongli Li  2 ,  Ensheng Ji  3
Affiliations
  • 1. Hebei University of Chinese Medicine, Shijiazhuang 050200, China.
  • 2. Hebei University of Chinese Medicine, Shijiazhuang 050200, China; Hebei Technology Innovation Center of TCM Combined Hydrogen Medicine, Shijiazhuang 050200, China. Electronic address: [email protected].
  • 3. Hebei University of Chinese Medicine, Shijiazhuang 050200, China; Hebei Technology Innovation Center of TCM Combined Hydrogen Medicine, Shijiazhuang 050200, China. Electronic address: [email protected].
PMID: 41151699 DOI: 10.1016/j.fitote.2025.106941
Abstract

Background: Chronic intermittent hypoxia (CIH) is the primary pathological feature of obstructive sleep apnea (OSA), and plays a key role in glutamate excitotoxicity-induced cognitive impairment.

Aims: This study aimed to investigate the effects of SMS-LD and explore the potential underlying mechanisms of cognitive dysfunction in CIH-induced glutamate excitotoxicity.

Methods: Mice were exposed to CIH (21 %-5 % O2, 20 times/h, 8 h/d) for 35 days and SMS-LD was administered intragastrically (10, 20, or 30 g/kg) during CIH exposure. Cognitive levels, neuronal damage, mitochondrial damage, and glutamate excitotoxicity were measured. In addition, intracerebral ventricular injections of IGF1 siRNA (4 μL) and AG1024 (10 mM, 4 μL) were adopted to confirm the role of the IGF1/IGFR signalling pathway in SMS-LD therapy for CIH-induced glutamate excitotoxicity.

Results: In mice exposed to CIH, SMS-LD therapy ameliorated CIH-induced glutamate excitotoxic damage and mitochondrial dysfunction, increased the expression of IGF1 and IGFR (0.75-1.17 fold and 0.82-1.24 fold, respectively), activated the renin-angiotensin system (Ras)/rapidly accelerated fibrosarcoma (Raf) and phosphatidyqinositol-3 kinase (PI3K)/ protein kinase B (Akt) signalling pathways, and ameliorated cognitive impairment.

Conclusions: These results showed that SMS-LD ameliorated CIH-induced glutamate excitotoxicity by activating the IGF1/IGFR pathway.

Keywords
Chronic intermittent hypoxia; Glutamate excitotoxicity; IGF1/IGFR signalling pathway; Mitochondrial dysfunction; Shengmaisan combined with Liuwei Dihuang decoction.
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