Clinical Traditional Medicine and Pharmacology · Sep 2026
Tuina ameliorates age-related cognitive impairment in SAMP8 mice via the PGC-1α/SIRT3/FOXO3a pathway by restoring mitochondrial ROS homeostasis
By Xu Z, Sun X, Wang R et al.
Background As a non-invasive therapy in traditional Chinese medicine (TCM), Tuina maintains systemic homeostasis by stimulating acupoints, unblocking meridians, and regulating yin-yang balance. Objective This study was performed to explore the effects of Tuina on oxidative stress dysregulation in SAMP8 mice, and to clarify whether Tuina can serve as a non-pharmacological intervention to ameliorate age-related mild cognitive impairment (MCI) and retard cognitive decline. Methods Six-month-old SAMP8 mice were selected as aging models, and age-matched SAMR1 mice served as normal controls. Four groups were set: Control, Model, Tuina, and Tuina+SIRT3 inhibitor (3-TYP). Learning and memory were tested via the Morris water maze (MWM) and novel object recognition (NOR). Hippocampal pathology, neuronal apoptosis, and mitochondrial function were observed by immunohistochemistry, histochemistry, and transmission electron microscopy. Mitochondrial reactive oxygen species (ROS), respiratory chain complex activities, relative mtDNA content, and the protein expressions of PGC-1α, SIRT3, and p-FOXO3a were quantitatively analyzed. Results Tuina treatment significantly shortened the escape latency in the MWM ( P < 0.01) and increased the discrimination index in the NOR test ( P < 0.01) compared with the Model group. Biochemically, Tuina markedly reduced hippocampal ROS levels and MDA content ( P < 0.01), while elevating the activities of antioxidant enzymes, including SOD and CAT ( P < 0.01). Furthermore, Tuina restored mitochondrial respiratory chain complex activities and relative mtDNA content, and significantly upregulated the protein levels of PGC-1α, SIRT3, and p-FOXO3a ( P < 0.01). Notably, these beneficial effects were largely abrogated by the administration of the SIRT3 inhibitor 3-TYP. Conclusion Tuina exerts neuroprotective effects by activating the PGC-1α/SIRT3/FOXO3a pathway. This mechanism improves mitochondrial function, sustains ROS homeostasis, alleviates oxidative stress injury, and ameliorates hippocampal lesions, thereby delaying brain aging and cognitive decline.