Study on the mechanism of action of Tibetan medicine Weng Bu on ulcerative colitis
Wengbu is a traditional Tibetan medicine, which originates from the tender leaves of various plants of Myricaria, Tamaricaceae, and is widely distributed in Xizang, Qinghai, Yunnan and other places. Modern research has shown that the main chemical components of Wenbu are flavonoids and polyphenolic compounds. Its medicinal parts are tender branches, green in color, with a flat nature and a slightly bitter taste. It is used to treat yellow water disease, internal cavity toxic heat, and scattered rash. It is also used for diseases such as plague, blood heat, toxic heat syndrome, measles opacity, and sore throat. The basic pathogenesis of “chronic diarrhea” is the accumulation of spleen deficiency, damp heat, and disharmony between qi and blood, while “blood heat” is an important pathogenic factor in the active stage of ulcerative colitis. Modern pharmacological research has shown that Onbu also has antibacterial, anti-inflammatory, analgesic, anti rheumatic, anti fatigue, and antioxidant effects.
Ulcerative colitis (UC) is a chronic inflammatory disease of the colon with an unclear etiology. The lesions are limited to the mucosa and submucosa of the large intestine, and the main symptoms are abdominal pain, diarrhea, mucous purulent bloody stools, etc. The condition is prone to recurrence and difficult to cure. Immunosuppressants, corticosteroids, and sodium aminosalicylate preparations are currently the main means of treating UC, with significant short-term treatment effects, but there are problems such as large adverse reactions and inability to maintain. It is not yet clear whether Onbu has a therapeutic effect on UC. This study aims to explore the effect and mechanism of Tibetan medicine Ongbu in treating UC through UHPLC-Q-Exactive-Orbitrap-MS technology, network pharmacology, molecular docking, and animal experiments, providing reference for the rational development and utilization of Ongbu.

This study used UHPLC-Q-Exactive-Orbitrap-MS technology to analyze 171 components of Wenbu, and screened 23 active components of Wenbu through the TCMSP platform. According to the “Weng Bu Active Ingredient UC” network diagram, the top 5 components with the most matching targets are pyrethroid, demethylated pyrethroid, rhein, isorhamnetin, and tannic acid. He et al.’s research shows that tannic acid has pharmacological effects such as antioxidant and anti-inflammatory properties. Zheng et al. found that tannic acid significantly reduces the release of TNF – α, IL-1 β, and NO by inhibiting pathways such as MAPK/I κ B – α/NF – κ B/COX, thereby improving UC. Rhein has anti-tumor, antibacterial, and anti-inflammatory activities, and studies have shown that it can inhibit the transmission of inflammatory signals by inhibiting target proteins such as JAK2, reduce the release of inflammatory factors, and alleviate the inflammatory response caused by abnormal immune function in UC. Isorhamnetin (ISO) is a natural small molecule flavonoid compound widely present in various plants, with multiple biological functions such as anti-inflammatory and antiviral effects. ISO can exert anti-inflammatory and therapeutic effects on inflammatory enteritis by inhibiting the activity of MPO, inhibiting the release of pro-inflammatory mediators (TNF – α, IL-2, IL-6), and downregulating the NF – κ B signaling pathway. Scutellaria lactone can inhibit the activation of NLRP3 inflammasome and cell pyroptosis, thereby exerting anti-inflammatory effects in vivo.
Through network pharmacology technology screening, 285 targets of Onbu were identified, including 2415 targets for ulcerative colitis disease. After intersection, 111 potential targets for treating ulcerative colitis were obtained. By constructing the “Onbu Active Ingredient UC” network, the molecular mechanism of Onbu in treating ulcerative colitis was revealed; By predicting the key targets of Onbu in the treatment of ulcerative colitis through protein interaction networks, PPI network analysis revealed that Onbu may exert therapeutic effects on ulcerative colitis by regulating target proteins such as TNF, CASP3, EGFR, PTGS2, and HSP90AA1. These genes directly or indirectly participate in processes such as cellular inflammation, apoptosis, and oxidative stress. TNF – α is a key target for the treatment of ulcerative colitis. Studies have shown that the levels of TNF – α are elevated in fecal samples and colon mucosal biopsy specimens of patients with ulcerative colitis. Anti TNF – α monoclonal antibodies can achieve anti-inflammatory effects by blocking their biological activity. Anti TNF – α monoclonal antibodies have good therapeutic effects in the treatment of ulcerative colitis. Caspases are involved in cell apoptosis, and caspase 3 (CASP3) plays an important role in the process of cell apoptosis. The occurrence of ulcerative colitis is closely related to cell apoptosis. Animal studies have shown that the CASP3 content in the intestinal mucosa of the ulcerative colitis model group is significantly increased, and after effective drug treatment, its expression level is downregulated, and the apoptosis rate of colon cells is significantly reduced. The prostacyclin endoperoxide synthase (PTGS2) protein is involved in multiple inflammatory signaling pathways, and inhibiting this protein can reduce the production of inflammatory mediators. The EGFR signaling pathway, as a key signaling pathway in the human body, mediates cell apoptosis and proliferation, and is associated with the occurrence of colonic mucosal injury. Therefore, intervening in the EGFR signaling pathway provides the possibility for treating UC. There are studies showing that damage to the intestinal mucosa of ulcerative colitis can affect EGFR expression, thereby reducing its protective and reparative effects on the colonic mucosa, and it has been found that EGFR levels are closely related to UC recurrence. HSP90AA1 is closely related to inflammation and can regulate cell proliferation and apoptosis. Inhibiting HSP90AA1 can induce autophagy and improve ulcerative colitis.
It is speculated that Weng Bu may exert therapeutic effects on UC by regulating the five target proteins mentioned above for anti-inflammatory, antioxidant, and reducing cell apoptosis. The molecular docking results also showed that Weng Bu has good binding activity with the five core genes mentioned above.
The KEGG results showed that the main pathways of Onbu treatment for ulcerative colitis include the core pathways of cellular immune research, such as T cell receptor signaling pathway, MAPK signaling pathway, and TNF – α signaling pathway. IL-6, tumor necrosis factor alpha, and interleukin-1 beta are three common inflammatory factors in the inflammatory response. TNF – α and IL-1 β are important pro-inflammatory factors in the early stage of acute UC. The inhibitory effect of pro-inflammatory factors on T cell apoptosis plays a sustained pro-inflammatory role, thereby participating in the occurrence and development of UC. There are studies showing that the pathological damage of lung and intestinal tissues can be improved through the TNF – α/NF – κ B signaling pathway, achieving the effect of treating both lungs and intestines together. The mitogen activated protein kinase signaling pathway includes ERK and p38 MAPK signaling pathways, which can participate in regulating various physiological and pathological processes such as inflammation, oxidative stress, cell differentiation, and apoptosis. MAPK signaling transduction is closely related to the inflammatory response of UC.
TNF – α is the first cytokine released by harmful stimuli in the body, and IL-1 β can be induced by TNF – α. The increase of IL-1 β can synergistically stimulate the production of IL-6 with TNF – α. Therefore, this study used network pharmacology and molecular docking techniques to predict the potential therapeutic targets and signaling pathways of Onbu on ulcerative colitis. A mouse model of ulcerative colitis was replicated by free consumption of DSS for pharmacological evaluation. Onbu can improve the colon length and colon mucosal damage induced by DSS in UC mice, reduce the levels of TNF – α and IL-6 in the colon and serum, and alleviate the inflammatory response of ulcerative colon.
In summary, this study systematically analyzed the mechanism of action of Onbu in treating UC through network pharmacology methods, and preliminarily validated its target using molecular docking technology. At the same time, the efficacy of Onbu in treating UC was tested through in vivo experiments in C57BL-6 mice. The preliminary research results indicate that Onbu can treat UC through “multi-target, multi pathway” therapy and alleviate DSS induced inflammatory response, but its mechanism is still unclear. Subsequent research will be conducted on it in order to provide reference for the mechanism of action of Onbu in the treatment of ulcerative colitis.