Dihuangzicao Granules Regulate the AGE/RAGE/NF-κB Signaling Pathway to Inhibit Inflammation in Psoriatic Mice via Network Pharmacology
and Experimental Validation
Authors: Lv Chong , Qiao Xianhua , Shi Zhe , Gao Juanjuan , Li Xiao , Jiang Shibin , Wang Chengcheng 
Published: October 2024

Aim:

Psoriasis is an immune-mediated skin disease that occurs worldwide and is
characterized by high prevalence and chronicity. Psoriasis has a complex pathogenesis and is difficult
to cure. Therefore, continuous exploration of the pathogenesis of psoriasis and the search
for new drug treatment methods are crucial for improving treatment efficiency and reducing psychological
damage to psoriasis patients. The active ingredients in Dihuang Zicao granules
(DHZCG) can effectively treat psoriasis. Therefore, this study aimed to analyze the active ingredients
of DHZCG and their potential mechanisms for treating psoriasis.

Methods:

The effective components of DHZCG were screened via the Traditional Chinese Medicine
Systems Pharmacology Database and Analysis Platform (TCMSP). Genetic information for
psoriasis was retrieved from the GeneCards, OMIM and DisGENET databases. Protein-Protein
Interaction (PPI) analysis was performed, and component‒target‒disease networks were constructed.
Important molecular biological processes and signaling pathways were screened via GO
and KEGG analyses. Molecular docking of the active ingredients and key targets was performed
via AutoDock Vina (1.1.2). A mouse model of psoriasis was established and divided into a control
group, model group, low-dose DHZCG group (L-DHZCG), medium-dose DHZCG group
(M-DHZCG), and high-dose DHZCG group (H-DHZCG). Hematoxylin and Eosin (HE) staining
was performed to determine the pathological changes in the skin of each group of mice, and the
Psoriasis Area Severity Index (PASI) score was used to assess skin damage. ELISA and RT‒
PCR were used to measure the levels of the inflammatory factors TNF-a, IL-17A, and IL-23 in
the serum and skin tissue of the mice, respectively. Western blotting was used to analyze the expression
of proteins related to the AGE/RAGE signaling pathway. Immunofluorescence was
used to examine the expression of the inflammatory factor NF-kB. Immunohistochemistry was
used to measure IL-1β and TNF-a expression in skin tissues.

Results:

Sixty genes associated with psoriasis treatment by DHZCG, including core genes encoding
IL-6, TNF-a, AKT1, IL-1β, TP53, NFKB1, BCL2, and MAPK3, were identified.
Through the construction of a psoriasis mouse model, DHZCG treatment effectively reduced
skin damage and significantly decreased the levels of the validated factors TNF-a, IL-17A, IL-
23, IL-1b, and NF-kB in the serum and damaged skin. Furthermore, the reduction in the levels of
these inflammatory factors by DHZCG is associated with the downregulation of the AGE/RAGE
signaling pathway.

Conclusion:

DHZCG reduces inflammation and alleviates psoriasis by downregulating the
AGE/RAGE/NF-kB signaling pathway. This study is beneficial for providing a theoretical basis
for the development of drugs for psoriasis and for offering personalized treatment strategies for
the clinical management of psoriasis.