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Moxibustion ameliorates cerebral ischemia-reperfusion injury by regulating ferroptosis in rats
JingRuo Zhang1,2, Wa Cai1, Xifang Wei1
1Department of Acupuncture, Shanghai Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Abstract:
Moxibustion is an effective treatment for the clinical management of acute cerebral infarction. However, its exact mechanism of action is still not fully understood. This study aimed to investigate the protective effect of moxibustion on cerebral ischemia-reperfusion injury (CIRI) in rats. Middle cerebral artery occlusion/reperfusion (MCAO/R) was used to construct a CIRI rat model, all animals were randomly divided into four groups including sham operation group, MCAO/R group (MCAO/R), moxibustion therapy + MCAO/R (Moxi) and ferrostatin-1 + MCAO/R (Fer-1) group. In the Moxi group, moxibustion treatment was initiated 24 h after modeling, once a day for 30 mins each time for 7 days. Moreover, the Fer-1 group received intraperitoneal injections of Fer-1 12 h after modeling, once a day for a total of 7 days. The results showed that moxibustion could reduce nerve function damage and neuronal death. Additionally, moxibustion could reduce the production of lipid peroxides such as lipid peroxide, malondialchehyche and ACSL4 to regulate lipid metabolism, promote the production of glutathione and glutathione peroxidase 4 and reduce the expression of hepcidin by inhibiting the production of inflammatory factor interleukin-6, therefore, downregulating the expression of SLC40A1, reducing the iron level in the cerebral cortex, reducing the accumulation of reactive oxygen species and inhibiting ferroptosis. Based on our studies, it can be concluded that moxibustion has the ability to inhibit ferroptosis of nerve cells post CIRI and plays a protective role in the brain. This protective role can be attributed to the regulation of iron metabolism of nerve cells, reduction of iron deposition in the hippocampus and lowering the level of lipid peroxidation.
Insights
Moxibustion effectively treats acute cerebral infarction by inhibiting ferroptosis in nerve cells. This traditional therapy protects the brain by regulating iron metabolism and reducing oxidative stress after cerebral ischemia-reperfusion injury.
Area of Science:
- Neuroscience
- Traditional Chinese Medicine
- Biochemistry
Background:
- Acute cerebral infarction poses significant clinical challenges.
- The precise mechanisms underlying moxibustion's therapeutic effects remain unclear.
- Cerebral ischemia-reperfusion injury (CIRI) is a major complication of stroke.
Purpose of the Study:
- To investigate the protective effects of moxibustion against CIRI in a rat model.
- To elucidate the underlying molecular mechanisms, particularly focusing on ferroptosis and iron metabolism.
Main Methods:
- A rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) was established.
- Animals were divided into sham, MCAO/R, moxibustion + MCAO/R, and ferrostatin-1 + MCAO/R groups.
- Moxibustion was applied daily for 7 days post-MCAO/R.
Main Results:
- Moxibustion significantly reduced nerve function damage and neuronal death.
- It decreased lipid peroxidation markers (e.g., malondialdehyde) and ACSL4 expression.
- Moxibustion promoted antioxidant production (glutathione, GPx4), inhibited inflammation (IL-6), and reduced iron levels by downregulating hepcidin and SLC40A1, thereby inhibiting ferroptosis.
Conclusions:
- Moxibustion demonstrates a protective effect against CIRI in rats.
- This protection is mediated by the inhibition of ferroptosis in nerve cells.
- Key mechanisms involve regulating iron metabolism, reducing lipid peroxidation, and mitigating oxidative stress.
