The Chinese herbal formula Xiong Pi Fang relieves depression in coronary heart disease

Background: Coronary heart disease and depression are very common and often co-existing disorders. Xiong Pi Fang (XPF), a therapeutic classical traditional Chinese medicine (TCM) formula, has shown satisfactory efficacy in treating coronary heart disease associated with depression. However, its mechanism of action is still unknown.

Purpose: To employ a systematic pharmacology approach for identifying the action mechanisms of Xiong Pi Fang in treating coronary heart disease associated with depression.

Methods: We used a systematic pharmacology approach to identify the potential active mechanisms of Xiong Pi Fang in treating coronary heart disease with depression. Potential active compounds in XPF and the diseases targets were screened using relevant databases to build corresponding pathways, following the experiments that were conducted to confirm whether the presumptive results of systemic pharmacology were correct.

Results: Network pharmacology predicted 42 key targets and 20 signaling pathways involved in Xiong Pi Fang-mediated treatment, with IL-6/JAK2/STAT3/HIF-1α/VEGF-A pathway significantly affected. The common influences were hypothalamic-pituitary-adrenal axis (HPA axis) and glucocorticoid signaling, validated through chronic unexpected mild stress (CUMS) with isoprenaline (ISO) for inducing coronary heart disease within the depression model in rats. In addition, Xiong Pi Fang intake reduced depressive-like behaviors and improved ECG ischemic changes. Furthermore, Xiong Pi Fang exerted some anti-inflammatory effects by inhibiting the interleukin-6 (IL-6) induced phosphorylation of janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), ultimately downregulating hypoxia-inducible factor 1-α (HIF-1α) and vascular endothelial growth factor-A (VEGF-A) activation. The dysfunctional HPA axis feedback loop was also regulated, which enhanced the glucocorticoid receptor (GR) expression. In contrast, it improved glucocorticoid resistance by reducing the mineralocorticoid receptor expression.

Conclusions: Suppressing IL-6 release and maintaining the HPA feedback loop balance could be the primary mechanism of Xiong Pi Fang against coronary heart disease with depression. The significance of the IL-6 and HPA axis identified indicates their potential as essential targets for coronary heart disease therapy with depression.

Reference: https://pubmed.ncbi.nlm.nih.gov/35987411/

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About Attilio

Doctor of Chinese medicine, acupuncture expert and author of My Fertility Guide and My Pregnancy Guide.

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