Moxibustion Protects Dopaminergic Neurons in Parkinson's Disease through Antiferroptosis.

Ferroptosis is associated with neural degeneration of dopaminergic neurons in Parkinson's disease (PD). However, how to control the level of ferroptosis in PD remains unclear. Clinically, moxibustion has been used to treat PD and has an apparent therapeutic effect on improving the motor symptoms of PD. In the present study, the PD rat model was constructed by two-point stereotactic 6-hydroxydopamine injection. Then, moxibustion was used to treat the PD rats. The expression of glutathione peroxidase 4 (GPX4) and Ferritin Heavy Chain 1 (FTH1), the level of reactive oxygen species (ROS), and the morphology of mitochondrial were detected to evaluate the level of ferroptosis. The results showed that moxibustion treatment of Shi's moxa sticks could reduce the behavioral score, alleviate the level of ferroptosis, decrease mitochondrial damage, and improve dopaminergic neuron survival. In conclusion, the present study results indicated that Shi's moxa sticks could effectively suppress the level of ferroptosis, thereby improving the survival of dopaminergic neurons in the SNpc of PD rats, which may provide a promising complementary and alternative therapy for PD patients.

[Effect and mechanism of moxibustion on oxidative stress injury in rats with Parkinson's disease by activating Nrf2/ARE pathway].

OBJECTIVE: To observe the effect of moxibustion on oxidative stress injury of nigrostriatal system in rats with Parkinson's disease (PD) based on nuclear factor erythroid 2-related factor (Nrf2)/antioxidant response element (ARE) pathway, and to explore its mechanism. METHODS: A total of 48 SD rats were randomized into a blank group, a sham-operation group, a model group and a moxibustion group, 12 rats in each group. Unilateral two-point injection with 6-hydroxydopamine (6-OHDA) was adopted in the model group and the moxibustion group to establish the PD model; the operation manipulation in the sham-operation group was the same as the model group and the moxibustion group, and the same volume of 0.9% sodium chloride solutions was given by unilateral two-point injection. Moxibustion was adopted at "Baihui" (GV 20) and "Sishencong" (EX-HN 1) in the moxibustion group for 20 min, once a day, 6 times a week for 6 weeks. No intervention was given in the other 3 groups. Morphology of right mesencephalon substantia nigra was observed by HE staining, the expression of tyrosine hydroxylase (TH) in right mesencephalon substantia nigra was detected by immunohistochemistry method, the expression of reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and glutathione peroxidase (GSH-Px) in corpus striatum was detected by colorimetry method, and the expression of Nrf2 and heme oxygenase-1 (HO-1) proteins was detected by Western blot in the 4 groups. RESULTS: Clear tissue structure and complete dopaminergic neurons of right mesencephalon substantia nigra were observed in the blank group and the sham-operation group; unclear tissue structure, decreased and swelling dopaminergic neurons were observed in the model group; compared with the model group, more neurons were observed and the swelling of cyton was reduced in the moxibustion group. Compared with the sham-operation group, the expression of TH in right mesencephalon substantia nigra was decreased in the model group (P<0.01); compared with the model group, the expression of TH in right mesencephalon substantia nigra was increased in the moxibustion group (P<0.05). Compared with the sham-operation group, the expression of ROS, MDA was increased (P<0.01), the expression of GSH, GSH-Px, Nrf2 and HO-1 was decreased in the model group (P<0.01, P<0.05); compared with the model group, the expression of ROS, MDA was decreased (P<0.05, P<0.01), the expression of GSH, GSH-Px, Nrf2 and HO-1 was increased in the moxibustion group (P<0.05, P<0.01). CONCLUSION: Moxibustion can alleviate oxidative stress injury of nigrostriatal system in rats with Parkinson's disease by activating the Nrf2/ARE pathway, and protect the dopamine neurons.

Moxibustion Exerts a Neuroprotective Effect through Antiferroptosis in Parkinson's Disease.

The objective of this study was to explore the neuroprotective effect of moxibustion on rats with Parkinson's disease (PD) and its mechanism. A Parkinson's disease model was established in rats using a two-point stereotactic 6-hydroxydopamine injection in the right substantia nigra (SN) and ventral tegmental area. The rats received moxibustion at the Baihui (GV20) and Sishencong (EX-HN1) acupoints for 20 minutes, six times a week, for 6 weeks. The right SN tissue was histologically and immunohistochemically examined. Differentially expressed genes (DEGs) were identified through RNA sequencing. In addition, the levels of tyrosine hydroxylase (TH), glutathione peroxidase 4 (GPX4), and ferritin heavy chain 1 (FTH1) in SN were measured. In comparison to the model group, the moxibustion group showed a significantly greater TH immunoreactivity and a higher behavioural score. In particular, moxibustion led to an increase in the number and morphological stability of SN neural cells. The functional pathway analysis showed that DEGs are closely related to the ferroptosis pathway. GPX4 and FTH1 in the SN were significantly overexpressed in the moxibustion-treated rats with PD. Moxibustion can effectively reduce the death of SN neurons, decrease the occurrence of ferroptosis, and increase the TH activity to protect the neurons in rats with PD. The protective mechanism may be associated with suppression of the ferroptosis.