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DOI: 10.12201/bmr.202601.00070

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  Abstract: Objective: To investigate the mechanism by which the Chinese herbal formula Bushen Zhichan Decoction inhibits ferroptosis of dopaminergic (DA)-ergic neurons in rats with Parkinsons disease (PD) by regulating the expression of Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2), Interleukin-4 (IL-4), and Interleukin-13 (IL-13).Methods: Seventy Sprague-Dawley (SD) rats were randomly divided into 7 groups (10 rats per group): control group, model group, Nrf2 inhibitor group, Bushen Zhichan Decoction low-dose group (15 g·kg?1·d?1), Bushen Zhichan Decoction medium-dose group (30 g·kg?1·d?1), Bushen Zhichan Decoction high-dose group (60 g·kg?1·d?1), and Levodopa and Benserazide group (2 g·kg?1·d?1). PD models were established using the proteasome inhibitor (PSI). Subsequently, rats in the Nrf2 inhibitor group were intraperitoneally injected with 50 mg/kg Nrf2 inhibitor (ML385), while rats in the other groups were injected with the same volume of normal saline; these injections were performed 3 times (on Mondays, Wednesdays, and Fridays) within 1 week. After the models were stabilized for 1 week, the model group and control group were given normal saline via gavage, and the remaining groups were given the corresponding drugs via gavage for 3 consecutive weeks. Behavioral tests were conducted during the treatment period. After treatment, the midbrain substantia nigra tissue was collected from the rats. Western blotting was used to detect the protein expression of Nrf2, IL-4, and IL-13; quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression of Nrf2; and enzyme-linked immunosorbent assay (ELISA) was used to measure the content of malondialdehyde (MDA).Results: After model establishment, compared with the control group, the other groups showed significantly decreased motor coordination, increased behavioral scores (P<0.05), significantly reduced Nrf2 mRNA and protein expression levels (P<0.05), significantly increased expression of IL-4 and IL-13 (P<0.05), and significantly elevated MDA content (P<0.05). After treatment, compared with the model group and Nrf2 inhibitor group, the Bushen Zhichan Decoction low-, medium-, and high-dose groups exhibited significantly improved motor coordination, decreased behavioral scores (P<0.05), significantly increased Nrf2 mRNA and protein expression in the substantia nigra (P<0.05), reduced expression of IL-4 and IL-13 (P<0.05), and decreased MDA content (P<0.05). Among these, the high-dose Bushen Zhichan Decoction group showed the most significant improvements (P<0.05). Compared with the model group, the Nrf2 inhibitor group had significantly lower Nrf2 mRNA and protein expression levels in the substantia nigra (P<0.05), higher expression of IL-4 and IL-13 (P<0.05), and significantly increased MDA content (P<0.05).

  Key words: Bushen Zhichan Formula; Parkinsons disease; Iron death; Nrf2

  Submit time: 26 January 2026

  Copyright: The copyright holder for this preprint is the author/funder, who has granted biomedRxiv a license to display the preprint in perpetuity.
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  1	2025-12-30	10.12201/bmr.202601.00070V1	Download

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