OBJECTIVE: To explore the possible mechanism of Tongdu Tiaoshen acupuncture combined with Xiaoxuming decoction ((sic)(sic)(sic), XXMD) in the treatment of Parkinson's disease (PD).METHODS: C57BL/6 mice were randomly divided into eight groups (n = 12), including blank group, model group, medication group, acupuncture group, high-dose XXMD group (XXMD-H), low-dose XXMD group (XXMD-L), acupuncture combined with high-dose XXMD group (A+H), and acupuncture combined with low-dose XXMD group (A+L). After treatment for 6 weeks, dopamine (DA) neurons and the pathological changes of tyrosine hydroxylase (TH) positive cells were observed. The enzyme-linked immunosorbent assay (ELISA) was used to measure the content of DA and the level of interleukin-1[3 ( IL-1[3), interleukin-6 ( IL-6), interleukin-10 (IL-10) and tumor necrosis factor alpha (TNF-alpha). The mRNA level ofPINK1 and Parkin and the protein expression of Nix, PINK1 and Parkin in the substantia nigra were also detected.RESULTS: Combination treatment effectively ameliorated the symptoms of PD. Compared with model group, combined treatment significantly up-regulated the protein expression of Nix, Parkin and PINK1 and the mRNA levels of PINK1 and Parkin in the substantia nigra (P < 0.0001, P < 0.001, P < 0.01 orP < 0.05). Furthermore, the levels of pro-inflammation cytokines were obviously decreased after combination therapy, while IL-10 content was increased remarkably (P < 0.01).CONCLUSION: Compared with each treatment alone, combination therapy improved the pathological damage of DA neurons of PD mice more effectively. The possible mechanism may be attributed to the up-regulated level of mitochondrial autophagy and improved mitochondrial function. These results provide fresh insight into the mechanism of co-treatment with Tongdu Tiaoshen acupuncture and XXMD for PD.(c) 2023 JTCM. All rights reserved.