Yun Zhong,1– 3 Yufei Zhao,4 Xin Meng,2 Fan Wang,2 Lei Zhou1 

1Department of Dermatology, the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Department of Dermatology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 3Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 4Department of Gastrointestinal Surgery, Laboratory of Surgery, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China

Correspondence: Lei Zhou, Department of Dermatology, the Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong, 510630, People’s Republic of China, Tel +020-85253333, Fax +020-85253336, Email zhoulei53@mail.sysu.edu.cn

Background: Rosacea, a recurring dermatological disorder, demands effective therapeutic approaches. Traditional Chinese medicine, particularly Liangxue Siwu Decoction (LXSWD), has shown promise in managing inflammatory skin diseases, such as rosacea. This study focuses on uncovering LXSWD’s specific effects on the inflammatory symptoms of rosacea.
Objective: Our research investigates LXSWD’s therapeutic effectiveness in rosacea treatment and delves into its underlying mechanisms.
Methods: Network pharmacology was utilized to identify LXSWD’s key components and their targets in rosacea management, which were then validated by molecular docking. An in vivo rosacea-like model in LL-37-induced mice was developed, subdividing them into control, model, and LXSWD groups. The LXSWD group received oral administration (25.0 g/kg/day) for six days before model induction. Post-treatment evaluations included skin tissue analyses to verify our network pharmacology predictions.
Results: Key active ingredients in LXSWD, such as quercetin, kaempferol, and luteolin, were identified alongside central target proteins like TNF and MMPs. Our molecular docking study confirmed the interactions between these ingredients and targets. Analyses through GO and KEGG pathways indicated LXSWD’s role in mitigating inflammation, particularly influencing the TNF and IL-17 pathways. LXSWD treatment in vivo markedly alleviated LL-37-induced symptoms in mice, showing a marked reduction in inflammatory cytokines (p < 0.05) and modulation of crucial genes (p < 0.05). These results, supported by immunofluorescence analysis and Western blot, underline the modulatory effects of LXSWD on MMPs, offering significant protection against rosacea’s inflammation alterations (p < 0.05).
Conclusion: Integrating network pharmacology, molecular docking, and in vivo experiments, this study elucidates LXSWD’s potential mechanisms in rosacea treatment. It offers a novel theoretical framework for its clinical use in managing rosacea.

Keywords: Liangxue siwu decoction, molecular docking, network pharmacology, rosacea, skin inflammation