Analysis of the mechanism of action of “Half Lotus White Hedyotis diffusa” medicine in the treatment of psoriasis based on network pharmacology and molecular docking technology
Psoriasis, commonly known as “psoriasis” or “dry psoriasis”, is clinically characterized by red papules or patches covered with silver white scales or thin films, and punctate appearance. Its histological features include excessive proliferation and abnormal differentiation of epidermal keratinocytes. Psoriasis is a destructive disease, and data shows that the prevalence of psoriasis in China is about 0.47%. The mechanism of this disease is not yet clear, mainly related to dendritic cells, T lymphocytes, and keratinocytes. The treatment of psoriasis ranges from local phototherapy to combination therapy of systemic drugs, establishing a wide range of conventional medical therapies. However, most of them have limited efficacy and many side effects, including skin atrophy, organ toxicity, carcinogenicity, and immunosuppression, making their treatment difficult. Traditional Chinese medicine has unique advantages in treating psoriasis, which can significantly reduce the recurrence rate and have clear therapeutic effects.
Yinxie Ping Wan is an in-house preparation of the Department of Dermatology at the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine. Many clinical cases have confirmed its definite therapeutic effect on psoriasis, among which “Half Lotus White Hedyotis diffusa” is its main drug pair. Half Lotus has a bitter taste, pungent nature, and coldness, and has the effects of clearing heat and detoxifying, removing blood stasis and stopping bleeding, and diuresis; White Hedyotis diffusa has a sweet taste, a slightly bitter nature, and is cold. It can clear heat, detoxify, disperse blood stasis, and eliminate carbuncles. The combination of the two requires mutual use. In order to explore its mechanism of intervention in psoriasis, traditional Chinese medicine mechanism research mostly follows the model of “one medicine, one target, one disease”, which cannot reflect the intervention characteristics of Chinese medicine with multiple components, targets, and pathways. Network pharmacology is the combination of multiple pharmacokinetic parameters for predicting active compounds, mining different drug targets, and macroscopic network analysis to predict drug component targets and signaling pathways of action, which is in line with the model of traditional Chinese medicine intervention in diseases. This study utilizes network pharmacology to predict and analyze the potential mechanism of the drug “Half Lotus White Hedyotis diffusa” in the treatment of psoriasis, providing reference for future experimental research and diagnosis and treatment ideas of psoriasis.

Psoriasis, the pathogenesis of traditional Chinese medicine, is attributed to deficiency of blood circulation, internal accumulation of blood heat, transformation of dryness and generation of wind, and loss of skin nourishment. The Complete Book of Surgical Treatment states: “White dagger, dry and itchy skin, thick skin between the ten fingers, and no itching. The basic treatment principles include cooling blood and promoting blood circulation, nourishing blood and moistening dryness, clearing heat and detoxifying. Psoriasis is a skin inflammatory disease caused by the dysregulation of multiple signaling pathways, with chronic inflammation mediated by T cells and epidermal cells being its main cause of onset. Modern research has shown that plant polysaccharides in half lotus have biological activity in regulating immune function. They can increase cell proliferation, phagocytosis, regulate nitric oxide production and cytokine secretion in a dose-dependent manner. Water extract of Hedyotis diffusa can affect the proliferation of T and B cells to affect immune response. Some studies have also shown that it can enhance macrophage phagocytic activity and increase NK cell activity to promote immune response in normal mice. However, a search of domestic and foreign literature in recent years has found that there is currently no research on the specific mechanisms of the effective chemical components, targets, signaling pathways, and biological pathways of the “Half Lotus White Hedyotis diffusa” medicine for psoriasis. Therefore, the aim of this study is to clarify the mechanism, specific targets, and pathways of action of the “Half Lotus White Hedyotis diffusa” drug on psoriasis based on network pharmacology.
According to the results of this study, it can be concluded that the main active ingredients that play a key role in the treatment of psoriasis in the “Half Lotus White Hedyotis diffusa” medicine are quercetin, luteolin, kaempferol, Robinia pseudoacacia, β – sitosterol, cyclotriol, etc. Among them, quercetin is an effective active ingredient shared by Half Lotus and White Hedyotis diffusa, with the highest degree value in the network topology of “active ingredient intersection target”. It is a dietary flavonoid rich in many natural plants. Studies have shown that Src family tyrosine kinases are highly expressed in the pathogenesis of psoriasis, and quercetin can significantly inhibit their upregulation during the course of the disease. It can also inhibit the expression of NF – κ B, IKK α, NIK in psoriasis like mouse models. Promoted the expression of TRAF3 and reduced the levels of TNF – α in serum The levels of IL-6 and IL-17 increase the activity of glutathione, catalase, and superoxide dismutase to inhibit the progression of psoriasis. Osmanthus extract has antioxidant and anti-inflammatory activities on keratinocytes, fibroblasts, and various immune cells. It also plays an important role in delaying skin aging and treating inflammatory skin diseases, especially in alleviating psoriatic lesions induced by imiquimod in BALB/c mice. Its mechanism is not only related to the inhibition of inflammatory mediators IL-17A, IL-6, TNF – α, IL-23, as well as the NF – κ B signaling pathway, but also regulates immune responses. For the immune cells of psoriasis mice, verbascoside reduces the ratio of Th1/Th2 and Th17/Treg, inhibits the increase of peripheral blood Th1 and Th17, suppresses the expression of HSP90 protein and exosome secretion, and regulates the proportion of immune cells to alleviate psoriasis lesions and symptoms. The intervention of salvianolic acid in psoriasis lesions mainly focuses on the regulation of immune cells. It can significantly reduce the infiltration of CD3+T cells and the expression of major pro-inflammatory cytokines (including IL-6, IL-17A, and TNF) in psoriasis lesions. Moreover, salvianolic acid also reduces the percentage of IL17A+/CD4+T cells in the spleen and lymph nodes of psoriasis mice. The key active ingredients of “Half Lotus White Hedyotis diffusa” predicted by this network pharmacology exert intervention effects on psoriasis through multiple pathways such as regulating immunity and inhibiting inflammatory mediators. Relevant literature has been reviewed and confirmed by basic research, indicating that this prediction has high accuracy.
Ten core target proteins, including AKT1, JUN, MAPK1, RELA, HSP90AA1, IL6, ESR1, MAPK8, EGFR, and MAPK14, were screened out, which may play an important role in the treatment of psoriasis with “Half Lotus White Hedyotis diffusa” medicine. AKT1 is a downstream key structure of the PI3K pathway. AKT1 is highly activated in the epidermal layer of psoriasis lesions, and its phosphorylation activates a series of protein complexes with different functions, including mTOR. Upregulation of mTOR kinase has been confirmed in the lesions of psoriasis patients. Mitogen activated protein kinase (MAPK) is a serine threonine protein kinase that plays an important role in many inflammatory and autoimmune diseases, among which c-Jun N-terminal kinase is an important sub pathway. The activation of c-Jun can stimulate the production of inflammatory factor IL-6, thereby exacerbating the inflammatory response in psoriasis lesions. The RELA transcription factor plays a central role in the stress response process of keratinocyte proliferation and differentiation. The phosphorylation of RELA promotes the expression of p65 and enhances the activation of NF κ B, thereby strengthening the excessive proliferation of lymphocytes, endothelial cells, dendritic cells, and keratinocytes. In the results of molecular simulation docking, half of the screened active target proteins showed excellent activity docking with the key active ingredients of “Half Lotus White Hedyotis diffusa”, indicating that reverse validation supports the prediction results. This study has certain reference value, among which HSP90AA1 receptor protein exhibited the best average docking activity, HSP90AA1 is an important member of the shock protein family, closely related to cell apoptosis, division, and angiogenesis. However, there is currently a lack of sufficient literature support for basic research related to the pathogenesis of psoriasis. Studies have shown that heat shock proteins can affect innate and adaptive immune responses, and their antibodies have a direct stimulating effect on regulatory T cells and an anti proliferative effect on keratinocytes, making them a potential therapeutic target for autoimmune skin diseases such as psoriasis.
In the KEGG pathway enrichment analysis of this study, the gene functions of the common targets of the “Half Lotus White Hedyotis diffusa” drug for intervening in psoriasis were mainly enriched in signaling pathways related to hypoxia inducible factor pathway, PI3K Akt, tumor necrosis factor (TNF) pathway, IL-17, Th17 cell differentiation, VEGF related signaling pathway, Th1 and Th2 cell differentiation, and signaling pathways closely related to angiogenesis, inflammatory response, and immune mediation. The increase of hypoxia inducible factor (HIF-1 α) is involved in the pathogenesis of psoriasis, and the increase in epithelial keratinocytes may help promote angiogenesis and skin inflammation. The PI3K/Akt pathway constitutes an important intracellular signaling pathway, including the skin, and plays a crucial role in the development of psoriasis. The PI3K/Akt pathway also plays a key role in inducing the expression of HIF-1 α in keratinocytes. From the perspective of immune regulation related predictive pathways, psoriasis is a chronic skin disease associated with inflammation mediated by Th17 cells and IL-17A. The activation of Th1 and Th17 promotes the proliferation, migration, and invasion of keratinocytes, accelerating the progression of the disease. Most monoclonal antibody biologics target it, thereby blocking downstream inflammatory mediators such as IL-17 and TNF – α and delaying the onset of the disease. Vascular endothelial growth factor plays a crucial role in the pathogenesis of various inflammatory immune-mediated diseases. In recent years, some scholars have proposed anti angiogenic therapies and found that certain psoriasis therapies can reduce the circulating VEGF-A levels in the papillary dermis of lesions and normalize related vascular pathology. VEGF-A and its signaling through its receptors may be potential intervention pathways for psoriasis. Psoriasis is a chronic inflammatory skin disease with an unclear etiology. Overproliferation of the epidermis and angiogenesis are widely recognized pathogenesis mechanisms, which overlap with the predicted signaling pathways in this study.
In summary, this study is based on the methods of network pharmacology and molecular simulation docking, using the “Half Lotus White Hedyotis diffusa” drug pair as the research object. The active ingredients and targets were screened based on oral bioavailability, and the biological pathways and pathways of its intervention in psoriasis were comprehensively analyzed. Reverse molecular docking was used for verification, and it was found that the intervention of active ingredients in psoriasis involves multiple pathways and pathways. Most of the results were supported by relevant evidence-based research, and some targets currently have insufficient evidence and potential for further experimental verification. However, limitations also exist. This study is based on screening active ingredients in drug databases, and the accuracy of predictions depends on the integrity of the database. Secondly, the results of this study are only a theoretical exploration of the mechanism of action, and further experiments are still needed to verify the specific mechanism of drug action.