Hua-Zhuo-Ning-Fu Decoction Ameliorates Psoriasis by Inhibiting TNF-Α/IL-6 and PI3K/AKT Signaling Pathway: A Network Pharmacology Approach and Experimental Validation.

Introduction: Hua-Zhuo-Ning-Fu decoction (HZD) is a traditional Chinese medicine prescription that has been clinically used by Chinese medical master Wang Xinlu for treating psoriasis. However, the specific molecular mechanisms remain unclear.

Methods: To identify the effective compounds of HZD and psoriasis-related genes, we conducted comprehensive searches in public databases, including TCMSP, SwissTargetPrediction, Gene Cards, and OMIM. Based on the degree values, core genes of HZD against psoriasis were determined. Furthermore, the affinity energy between the active compounds of HZD and their core targets was validated via molecular docking. Finally, the anti-psoriasis effects and potential mechanisms of HZD were examined in M5-stimulated HaCaT cells in vitro and IMQ-induced psoriasis mice in vivo.

Results: Network pharmacological analysis of HZD for psoriasis treatment identified 43 active components and 243 targets. Topological and molecular docking analyses identified interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) as core targets for its anti-psoriasis effects. Specifically, the docking energy of isovitexin with IL-6 was lower (-7.30 kcal/mol), and that of baicalin with TNF-α was lower (-6.70 kcal/mol). KEGG analysis revealed that the main pathway was the PI3K/AKT pathway. HZD inhibited cell viability, inflammation, and oxidative stress in M5- induced HaCaT cells. Animal experiments demonstrated that HZD alleviated psoriatic dermatitis, histopathological features, and inflammation in IMQ-induced mice with psoriatic plaques. Notably, HZD inhibited the expression of TNF-α and IL-6 and the activation of the PI3K/AKT pathway both in vivo and in vitro.

Discussion: Specific upstream/downstream regulators of the PI3K/AKT axis regulated by HZD still need to be explored. Further investigation is essential to clarify the functional relationship between the predicted targets and active components.

Conclusion: In summary, HZD potentially mitigated inflammatory responses by targeting the TNF-α and IL-6 proteins, interfered with the PI3K/AKT pathway, and consequently drove the anti-psoriatic effect in IMQ-induced mice. Our findings provide a theoretical basis for HZD's clinical use in psoriasis treatment.