Matrine (MT) and Oxymatrine (OMT) are two natural alkaloids derived from plants. These bioactive compounds are notable for their diverse pharmacological effects and have been extensively studied and recognized in the treatment of cardiovascular diseases in recent years. The cardioprotective effects of MT and OMT involve multiple aspects, primarily including antioxidative stress, anti-inflammatory actions, anti-atherosclerosis, restoration of vascular function, and inhibition of cardiac remodeling and failure. Clinical pharmacology research has identified numerous novel molecular mechanisms of OMT and MT, such as JAK/STAT, Nrf2/HO-1, PI3 K/AKT, TGF-β1/Smad, and Notch pathways, providing new evidence supporting their promising therapeutic potential against cardiovascular diseases. Thus, this review aims to investigate the potential applications of MT and OMT in treating cardiovascular diseases, encompassing their mechanisms, efficacy, and safety, confirming their promise as lead compounds in anti-cardiovascular disease drug development.

OBJECTIVE: To investigate the involvement of the high mobility group box protein B1 (HMGB1)-Toll-like receptor 2 (TLR2)/TLR4-nuclear factor κB (NF-κB) pathway in the intestinal mucosal injury induced by Cryptosporidium parvum infection, and to examine the effect of oxymatrine (OMT) on C. parvum infection in mice.
METHODS: Forty SPF 4-week-old BALB/c mice were randomly divided into four groups, including the control group, infection group, glycyrrhizin (GA) group and OMT group. Each mouse was orally administered with 1 × 105 C. parvum oocysts one week in the infection, GA and OMT groups following dexamethasone-induced immunosuppression to model C. parvum intestinal infections in mice. Upon successful modeling, mice in the GA group were intraperitoneally injected with GA at a daily dose of 25.9 mL/kg for successive two weeks, and animals in the OMT group were orally administered OMT at a daily dose of 50 mg/kg for successive two weeks, while mice in the control group were given normal food and water. All mice were sacrificed two weeks post-treatment, and proximal jejunal tissues were sampled. The pathological changes of mouse intestinal mucosal specimens were observed using hematoxylin-eosin (HE) staining, and the mouse intestinal villous height, intestinal crypt depth and the ratio of intestinal villous height to intestinal crypt depth were measured. The occludin and zonula occludens protein 1 (ZO1) expression was determined in mouse intestinal epithelial cells using immunohistochemistry, and the relative expression of HMGB1, TLR2, TLR4, myeloid differentiation primary response gene 88 (MyD88) and NF-κB p65 mRNA was quantified in mouse jejunal tissues using quantitative real-time PCR (qPCR) assay.
RESULTS: HE staining showed that the mouse intestinal villi were obviously atrophic, shortened, and detached, and the submucosal layer of the mouse intestine was edematous in the infection group as compared with the control group, while the mouse intestinal villi tended to be structurally intact and neatly arranged in the GA and OMT groups. There were significant differences among the four groups in terms of the mouse intestinal villous height (F = 6.207, P = 0.000 5), intestinal crypt depth (F = 6.903, P = 0.000 3) and the ratio of intestinal villous height to intestinal crypt depth (F = 37.190, P < 0.000 1). The mouse intestinal villous height was lower in the infection group than in the control group [(321.9 ± 41.1) μm vs. (399.5 ± 30.9) μm; t = 4.178, P < 0.01] and the GA group [(321.9 ± 41.1) μm vs. (383.7 ± 42.7) μm; t = 3.130, P < 0.01], and the mouse intestinal crypt depth was greater in the infection group [(185.0 ± 35.9) μm] than in the control group [(128.4 ± 23.6) μm] (t = 3.877, P < 0.01) and GA group [(143.3 ± 24.7) μm] (t = 2.710, P < 0.05). The mouse intestinal villous height was greater in the OMT group [(375.3 ± 22.9) μm] than in the infection group (t = 3.888, P < 0.01), and there was no significant difference in mouse intestinal villous height between the OMT group and the control group (t = 1.989, P > 0.05). The mouse intestinal crypt depth was significantly lower in the OMT group [(121.5 ± 27.3) μm] than in the infection group (t = 4.133, P < 0.01), and there was no significant difference in mouse intestinal crypt depth between the OMT group and the control group (t = 0.575, P > 0.05). The ratio of the mouse intestinal villous height to intestinal crypt depth was significantly lower in the infection group (1.8 ± 0.2) than in the control group (3.1 ± 0.3) (t = 10.540, P < 0.01) and the GA group (2.7 ± 0.3) (t = 7.370, P < 0.01), and the ratio of the mouse intestinal villous height to intestinal crypt depth was significantly higher in the OMT group (3.1 ± 0.2) than in the infection group (t = 15.020, P < 0.01); however, there was no significant difference in the ratio of the mouse intestinal villous height to intestinal crypt depth between the OMT group and the control group (t = 0.404, P > 0.05). Immunohistochemical staining showed significant differences among the four groups in terms of occludin (F = 28.031, P < 0.000 1) and ZO1 expression (F = 14.122, P < 0.000 1) in mouse intestinal epithelial cells. The proportion of positive occluding expression was significantly lower in mouse intestinal epithelial cells in the infection group than in the control group [(14.3 ± 4.5)% vs. (28.3 ± 0.5)%; t = 3.810, P < 0.01], and the proportions of positive occluding expression were significantly higher in mouse intestinal epithelial cells in the GA group [(30.3 ± 1.3)%] and OMT group [(25.8 ± 1.5)%] than in the infection group (t = 7.620 and 5.391, both P values < 0.01); however, there was no significant differences in the proportion of positive occluding expression in mouse intestinal epithelial cells between the GA or OMT groups and the control group (t = 1.791 and 2.033, both P values > 0.05). The proportion of positive ZO1 expression was significantly lower in mouse intestinal epithelial cells in the infection group than in the control group [(14.4 ± 1.8)% vs. (24.2 ± 2.8)%; t = 4.485, P < 0.01], and the proportions of positive ZO1 expression were significantly higher in mouse intestinal epithelial cells in the GA group [(24.1 ± 2.3)%] (t = 5.159, P < 0.01) and OMT group than in the infection group [(22.5 ± 1.9)%] (t = 4.441, P < 0.05); however, there were no significant differences in the proportion of positive ZO1 expression in mouse intestinal epithelial cells between the GA or OMT groups and the control group (t = 0.037 and 0.742, both P values > 0.05). qPCR assay showed significant differences among the four groups in terms of HMGB1 (F = 21.980, P < 0.000 1), TLR2 (F = 20.630, P < 0.000 1), TLR4 (F = 17.000, P = 0.000 6), MyD88 (F = 8.907, P = 0.000 5) and NF-κB p65 mRNA expression in mouse jejunal tissues (F = 8.889, P = 0.000 7). The relative expression of HMGB1 [(5.97 ± 1.07) vs. (1.05 ± 0.07); t = 6.482, P < 0.05] 、TLR2 [(5.92 ± 1.29) vs. (1.10 ± 0.14); t = 5.272, P < 0.05] 、TLR4 [(5.96 ± 1.50) vs. (1.02 ± 0.03); t = 4.644, P < 0.05] 、MyD88 [(3.00 ± 1.26) vs. (1.02 ± 0.05); t = 2.734, P < 0.05] and NF-κB p65 mRNA [(2.33 ± 0.72) vs. (1.04 ± 0.06); t = 2.665, P < 0.05] was all significantly higher in mouse jejunal tissues in the infection group than in the control group. A significant reduction was detected in the relative expression of HMGB1 (0.63 ± 0.01), TLR2 (0.42 ± 0.10), TLR4 (0.35 ± 0.07), MyD88 (0.70 ± 0.11) and NF-κB p65 mRNA (0.75 ± 0.01) in mouse jejunal tissues in the GA group relative to the control group (t = 8.629, 5.830, 11.500, 4.729 and 6.898, all P values < 0.05), and the relative expression of HMGB1, TLR2, TLR4, MyD88 and NF-κB p65 mRNA significantly reduced in mouse jejunal tissues in the GA group as compared to the infection group (t = 7.052, 6.035, 4.084, 3.165 and 3.274, all P values < 0.05). In addition, the relative expression of HMGB1 (1.14 ± 0.60), TLR2 (1.00 ± 0.24), TLR4 (1.14 ± 0.07), MyD88 (0.96 ± 0.25) and NF-κ B p65 mRNA (1.12 ± 0.17) was significantly lower in mouse jejunal tissues in the OMT group than in the infection group (t = 7.059, 5.320, 3.510, 3.466 and 3.273, all P values < 0.05); however, there were no significant differences between the OMT and control groups in terms of relative expression of HMGB1, TLR2, TLR4, MyD88 or NF-κB p65 mRNA in mouse jejunal tissues (t = 0.239, 0.518, 1.887, 0.427 and 0.641, all P values > 0.05).
CONCLUSIONS: C. parvum infection causes intestinal inflammatory responses and destruction of intestinal mucosal barrier through up-regulating of the HMGB1-TLR2/TLR4-NF-κB pathway. OMT may suppress the intestinal inflammation and repair the intestinal mucosal barrier through inhibiting the activity of the HMGB1-TLR2/TLR4-NF-κB pathway.
［摘要］ 目的 探讨高迁移率族蛋白B1 (high mobility group box protein B1, HMGB1)-Toll样受体2 (Toll-like receptor 2, TLR2)/TLR4-核因子κB (nuclear factor κB, NF-κB) 通路在微小隐孢子虫感染致肠黏膜损伤中的作用, 以及氧化苦参碱 (oxymatrine, OMT) 对小鼠微小隐孢子虫感染的干预作用。方法 4周龄SPF级BALB/c小鼠40只随机分成4组, 分别为 对照组、感染组、甘草酸 (glycyrrhizin, GA) 组及OMT组。感染组、GA组及OMT组小鼠给予地塞米松免疫抑制1周后, 每 只灌胃1 × 105个微小隐孢子虫卵囊建立微小隐孢子虫肠道感染小鼠模型。模型建立成功后, GA组小鼠连续2周腹腔注 射GA 25.9 mL/(kg·d), OMT组连续2周经口灌胃OMT 50 mg/(kg·d); 对照组正常饮食、饮水。治疗2周后剖杀各组小鼠, 取空肠近端组织。采用苏木精-伊红 (hematoxylin-eosin, HE) 染色观察小鼠肠黏膜病理变化, 测量肠绒毛高度、肠隐窝深 度及两者比值; 采用免疫组织化学染色检测小鼠肠上皮细胞中闭合蛋白 (occludin) 和紧密粘连蛋白1 (zonula occludens protein 1, ZO1) 表达水平, 采用实时荧光定量PCR (quantitative real-time PCR, qPCR) 检测小鼠空肠组织中HMGB1、TLR2、 TLR4、髓样分化因子88 (myeloid differentiation primary response gene 88, MyD88) 、NF-κB p65mRNA相对表达量。结果 HE 染色结果显示, 与对照组比较, 感染组小鼠肠绒毛明显萎缩变短、脱落, 黏膜下层水肿; GA组和OMT组小鼠肠绒毛结构 趋于完整, 排列趋于整齐。各组小鼠肠绒毛高度 (F = 6.207, P = 0.000 5) 、肠隐窝深度 (F = 6.903, P = 0.000 3) 及两者比 值 (F = 37.190, P < 0.000 1) 差异均有统计学意义。感染组小鼠肠绒毛高度 [(321.9 ± 41.1) μm] 显著低于对照组 [(399.5 ± 30.9) μm] (t = 4.178, P < 0.01) 和GA组 [(383.7 ± 42.7) μm] (t = 3.130, P < 0.01), 感染组小鼠肠隐窝深度 [(185.0 ± 35.9) μm] 显著高于对照组 [(128.4 ± 23.6) μm] (t = 3.877, P < 0.01) 及GA组 [(143.3 ± 24.7) μm] (t = 2.710, P < 0.05) 。OMT组小 鼠肠绒毛高度 [(375.3 ± 22.9) μm] 显著高于感染组 (t = 3.888, P < 0.01), 与对照组差异无统计学意义 (t = 1.989, P > 0.05); OMT组小鼠肠隐窝深度 [(121.5 ± 27.3) μm] 显著低于感染组 [(185.0 ± 35.9) μm] (t = 4.133, P < 0.01), 与对照组差异无统 计学意义 (t = 0.575, P > 0.05) 。感染组小鼠肠绒毛高度与肠隐窝深度比值 [(1.8 ± 0.2) ] 显著低于对照组 [(3.1 ± 0.3) ] (t = 10.540, P < 0.01) 及GA组 [(2.7 ± 0.3) ] (t = 7.370, P < 0.01); OMT组小鼠肠绒毛高度与肠隐窝深度比值 [(3.1 ± 0.2) ] 显著 高于感染组 (t = 15.020, P < 0.01), 与对照组差异无统计学意义 (t = 0.404, P > 0.05) 。免疫组织化学染色结果显示, 各组 小鼠肠上皮细胞中occludin (F = 28.031, P < 0.000 1) 及ZO1表达水平差异均有统计学意义 (F = 14.122, P <0.0001) 。感染组 小鼠肠上皮细胞中occludin阳性表达率 [(14.3 ± 4.5) %] 低于对照组 [(28.3 ± 0.5) %] (t = 3.810, P < 0.01), GA组 [(30.3 ± 1.3) %] 、OMT组小鼠肠上皮细胞中occludin阳性表达率 [(25.8 ± 1.5) %] 显著高于感染组 (t = 7.620、5.391, P 均< 0.01), 但GA组、OMT组小鼠肠上皮细胞中occludin阳性表达率与对照组差异均无统计学意义 (t = 1.791、2.033, P 均> 0.05) 。 感染组小鼠肠上皮细胞中ZO1阳性表达率 [(14.4 ± 1.8) %] 显著低于对照组 [(24.2 ± 2.8) %] (t = 4.485, P < 0.01), GA组 [(24.1 ± 2.3) %] (t = 5.159, P < 0.01) 、OMT组小鼠肠上皮细胞中ZO1阳性表达率 [(22.5 ± 1.9) %] 显著高于感染组 (t = 4.441, P < 0.05), 但GA组、OMT组小鼠肠上皮细胞中ZO1阳性表达率与对照组差异均无统计学意义 (t = 0.037、0.742, P 均> 0.05) 。qPCR检测结果显示, 各组小鼠空肠组织中HMGB1 (F = 21.980, P < 0.000 1) 、TLR2 (F = 20.630, P < 0.000 1) 、 TLR4 (F = 17.000, P = 0.000 6) 、MyD88 (F = 8.907, P = 0.000 5) 、NF-κB p65 mRNA 表达水平差异均有统计学意义 (F = 8.889, P = 0.000 7) 。感染组小鼠空肠组织中HMGB1 [(5.97 ± 1.07) vs. (1.05 ± 0.07); t = 6.482, P < 0.05] 、TLR2 [(5.92 ± 1.29) vs. (1.10 ± 0.14); t = 5.272, P < 0.05] 、TLR4 [(5.96 ± 1.50) vs. (1.02 ± 0.03); t = 4.644, P < 0.05] 、MyD88 [(3.00 ± 1.26) vs. (1.02 ± 0.05); t = 2.734, P < 0.05] 、NF-κB p65 mRNA 相对表达量 [(2.33 ± 0.72) vs. (1.04 ± 0.06); t = 2.665, P < 0.05] 均 显著高于对照组。与对照组比较, GA组小鼠空肠组织中HMGB1 (0.63 ± 0.01) 、TLR2 (0.42 ± 0.10) 、TLR4 (0.35 ± 0.07) 、 MyD88 (0.70 ± 0.11) 、NF-κB p65 mRNA 相对表达量 (0.75 ± 0.01) 均显著下降 (t = 8.629、5.830、11.500、4.729、6.898, P 均< 0.05) 。与感染组比较, GA组小鼠空肠组织中HMGB1、TLR2、TLR4、MyD88、NF-κB p65 mRNA 相对表达量均显著降低 (t = 7.052、6.035、4.084、3.165、3.274, P 均< 0.05); OMT 组小鼠空肠组织中HMGB1 (1.14 ± 0.60) 、TLR2 (1.00 ± 0.24) 、TLR4 (1.14 ± 0.07) 、MyD88 (0.96 ± 0.25) 、NF-κB p65 mRNA 相对表达量 (1.12 ± 0.17) 亦显著低于感染组 (t = 7.059、5.320、3.510、 3.466、3.273, P 均< 0.05) 。OMT组与对照组小鼠空肠组织中HMGB1、TLR2、TLR4、MyD88、NF-κB p65 mRNA 相对表达量 差异均无统计学意义 (t = 0.239、0.518、1.887、0.427、0.641, P均> 0.05) 。结论 微小隐孢子虫感染小鼠后通过上调 HMGB1-TLR2/TLR4-NF-κB 通路表达引起肠道炎症反应、破坏肠黏膜屏障。OMT 可能通过抑制HMGB1-TLR2/TLR4-NF-κB 通路活性抑制小鼠肠道炎症, 并修复肠黏膜屏障。.

Ulcerative colitis (UC) is difficult to cure and easy to relapse, leading to poor quality of life for patients. Oxymatrine (OMT) is one of the main alkaloids of Sophora flavescens Aiton, which has many effects, such as anti-inflammation, anti-oxidative stress, and immunosuppression. This study aimed to investigate whether OMT could attenuate ulcerative colitis by inhibiting the NOD-like receptor family pyrin domain containing three (NLRP3) inflammasome-mediated pyroptosis. In this study, the UC rat models were established by 2,4,6-Trinitrobenzenesulfonic acid (TNBS) in vivo, while RAW264.7 cells and peritoneal macrophages were stimulated with Lipopolysaccharides/Adenosine Triphosphate (LPS/ATP) in vitro to simulate pyroptosis models, and Western blotting (WB) and other detection techniques were applied to analyze proteins involved in the NLRP3 inflammasome pathway. Our results showed that OMT alleviated colitis ulcers and pathological damage in the TNBS-induced UC rats and exhibited an inhibitory effect on pyroptosis at the early stage of UC. In the model group, the pyroptosis reached the peak at 24 h after modeling with the contents of active-cysteine-aspartic proteases-1 (caspase-1), Gasdermin D (GSDMD)-N, and cleaved-interleukin-1 beta (IL-1β) to the highest expression level. Meanwhile, we found that OMT (80 mg kg-1) remarkably decreased the expression levels of NLRP3, active-caspase-1, and cleaved-IL-1β at 24 h in the lesion tissue from UC rats. Further experiments on cells demonstrated that OMT at concentrations of 100 and 250 μM significantly inhibited cell death caused by NLRP3 inflammasome activation (p < 0.05), downregulated caspase-1, GSDMD, and decreased the levels of active-caspase-1, GSDMD-N, cleaved-IL-1β in RAW326.7 cells, and peritoneal macrophages. In summary, these results indicated that OMT could attenuate ulcerative colitis through inhibiting pyroptosis mediated by the NLRP3 inflammasome. The inhibition of the NLRP3 inflammasome may be a potential strategy for UC.

Cryptosporidiosis is a worldwide zoonotic disease. Oxymatrine, an alkaloid extracted and isolated from the plant bitter ginseng, has been reported to have therapeutic effects on cryptosporidiosis. However, the underlying mechanism of its action remains unclear. In this study, we utilized network pharmacology and experimental validation to investigate the mechanism of oxymatrine in the treatment of cryptosporidiosis. First, the potential targets of drugs and diseases were predicted by TCMSP, Gene Cards, and other databases. Following the intersection of drug-disease targets, the DAVID database was used to implement the enrichment analysis of GO functions and KEGG pathways, and then the network diagram of \"intersected target-KEGG\" relationship was constructed. Autodock 4.2.6 software was used to carry out the molecular docking of core targets to drug components. Based on the establishment of a mouse model of cryptosporidiosis, the validity of the targets in the TNF/NF-κB signaling pathway was confirmed using Western blot analysis and Quantitative Rea-ltime-PCR. A total of 41 intersectional targets of oxymatrine and Cryptosporidium were generated from the results, and five core targets were screened out by network analysis, including RELA, AKT1, ESR1, TNF, and CASP3. The enrichment analysis showed that oxymatrine could regulate multiple gene targets, mediate TNF, Apoptpsis, IL-17, NF-κB and other signaling pathways. Molecular docking experiments revealed that oxymatrine was tightly bound to core targets with stable conformation. Furthermore, we found through animal experiments that oxymatrine could regulate the mRNA and protein expression of IL-6, NF-κB, and TNF-α in the intestinal tissues of post-infected mice through the TNF/NF-κB signaling pathway. Therefore, it can be concluded that oxymatrine can regulate the inflammatory factors TNF-α, NF-κB, and IL-6 through the TNF/NF-κB signaling pathway for the treatment of cryptosporidiosis. This prediction has also been validated by network pharmacology and animal experiments.

Sepsis is a life-threatening organ dysfunction that endangers patient lives and is caused by an imbalance in the host defense against infection. Sepsis continues to be a significant cause of morbidity and mortality in critically sick patients. Oxymatrine (OMT), a quinolizidine alkaloid derived from the traditional Chinese herb Sophora flavescens Aiton, has been shown to have anti-inflammatory effects on a number of inflammatory illnesses according to research. In this study, we aimed to evaluate the therapeutic effects of OMT on sepsis and explore the underlying mechanisms. We differentiated THP-1 cells into THP-1 macrophages and studied the anti-inflammatory mechanism of OMT in a lipopolysaccharide (LPS)-induced THP-1 macrophage sepsis model. Activation of the receptor for advanced glycation end products (RAGE), as well as NF-κB, was assessed by Western blot analysis and immunofluorescence staining. ELISA was used to measure the levels of inflammatory factors. We found that OMT significantly inhibited HMGB1-mediated RAGE/NF-κB activation and downstream inflammatory cytokine production in response to LPS stimulation. Finally, an in vivo experiment was performed on septic mice to further study the effect of OMT on injured organs. The animal experiments showed that OMT significantly inhibited HMGB1-mediated RAGE/NF-κB activation, protected against the inflammatory response and organ injury induced by CLP, and prolonged the survival rate of septic mice. Herein, we provide evidence that OMT exerts a significant therapeutic effect on sepsis by inhibiting the HMGB1/RAGE/NF-κB signaling pathway.

Chronic pain often coincides with changes in gut microbiota composition. Yet, the role of gut microbiota in bone cancer pain (BCP) is still not fully understood. This study investigated the role of gut microbiota in BCP and the effect of oxymatrine (OMT) on gut microbiota in BCP. A BCP mice model was developed to assess gut microbiota composition, serum and brain tissue butyric acid levels, and blood-brain barrier (BBB) permeability. Microbiota transplantation was used to restore gut microbiota, and the effect of Clostridium butyricum or sodium butyrate (NaB) supplementation on pain-related behaviors and BBB integrity was evaluated. The potential benefits of OMT on gut microbiota composition, peroxisome proliferator-activated receptor gamma (PPARγ)/cyclooxygenase-2 (COX-2) signaling, BBB integrity, and pain-related behaviors were also explored. BCP significantly altered gut microbiota composition and reduced serum and brain tissue butyric acid levels. Additionally, BBB permeability increased considerably in the BCP group compared with sham and control mice. Microbiota transplantation, as well as C butyricum or NaB supplementation, ameliorated pain-related behaviors and BBB integrity; the supplementation of C butyricum or NaB boosted brain-tight-junction protein expression, potentially through modulating PPARγ/COX-2 signaling. OMT influenced gut microbiota composition and regulated PPARγ/COX-2 signaling in the BCP model, improving pain-related behaviors and BBB integrity. BCP affects gut microbiota composition and butyric acid levels. Modulating gut microbiota and butyric acid levels through transplantation or supplementation may alleviate BCP. OMT shows potential as a treatment by altering gut microbiota composition and regulating PPARγ/COX-2 signaling. These findings provide new insights into BCP pathophysiology and possible treatments. PERSPECTIVE: This study explores the impact of gut microbiota on BCP. Microbiota transplantation alleviates BCP and enhances BBB integrity. Also, C butyricum or NaB improves BBB via PPARγ/COX-2. OMT, a BCP treatment, modifies microbiota by regulating PPARγ/COX-2, in turn improving pain and BBB integrity. These findings suggest a therapeutic approach, emphasizing clinical relevance in targeting gut microbiota and restoring butyric acid levels.

BACKGROUND: Sophora flavescens is often used in traditional Chinese medicine for skin issues, diarrhea, and vaginal itching (Plant names have been checked with http://www.the/plant/list.org on Feb 22nd, 2024). Oxymatrine (OY), a major bioactive compound from Sophora flavescens, is commonly used in China to treat ulcerative colitis, but its mechanisms are still unclear.
OBJECTIVE: Recent studies have found that the crosstalk between ferroptosis and inflammation is an important mechanism in the pathogenesis of UC. The aim of this study was to investigate the potential underlying mechanisms of OY treatment on DSS-induced ulcerative colitis, specifically focusing on the processes of ferroptosis and inflammation.
METHODS: Bioinformatics methods were used to identify key targets of OY for ferroptosis and inflammation in ulcerative colitis, based on GEO data and FerrDb database. Then, 4% DSS solution was used to induce UC model. OY\'s impact on morphological changes was assessed using colon views, Hematoxylin and eosin (HE) staining, and transmission electron microscopy (TEM). Ferroptosis phenotype index and inflammations factors were detected by ELISA or chem-bio detection kits. The screen out hub related genes about ferroptosis and inflammation were verified by RT-PCR, immunohistochemistry (IHC), and western blotting (WB) respectively.
RESULTS: Bioinformatics results show that there are 16 key target genes involved in ferroptosis and inflammation interaction of OY treatment for UC, such as IL6, NOS2, IDO1, SOCS1, and DUOX. The results of animal experiments show that OY could depress inflammatory factors (IL-1β, IL-6, TNF-α, HMGB1, and NLRP3) and reduce iron deposition (Fe2+, GSH). Additionally, OY suppressed the hub genes or proteins expression involved in ferroptosis and inflammation, including IL-1β, IL-6, NOS2, HIF1A, IDO1, TIMP1, and DUOX2.
CONCLUSIONS: This present study combines bioinformatics, molecular biology, and animal experimental research evidently demonstrated that OY attenuates UC by improving ferroptosis and inflammation, mainly target to the expression of IL-1β, IL-6, NOS2, HIF1A, IDO1, TIMP1, and DUOX2.

BACKGROUND: The management of erythrodermic psoriasis (EP), a rare but severe type of psoriasis, is challenging, especially in patients with concomitant chronic hepatitis B (CHB). We previously demonstrated that oxymatrine treatment alleviated severe plaque psoriasis, but its therapeutic potential in treating EP remains unexplored. This study was to assess the efficacy and safety of oxymatrine for the treatment of EP, with attention to concomitant CHB.
METHODS: In this investigator-initiated clinical trial, four consecutive patients with EP, including two (A and B) with concomitant CHB, were treated with intravenous administration of oxymatrine as monotherapy for 8 weeks, and scheduled to be followed up for a minimum of 24 weeks. The primary outcome was at least 75% improvement in the psoriasis area and severity index (PASI 75) at week 32. Secondary outcomes included the body surface area (BSA) score, dermatology life quality index (DLQI)], and safety.
RESULTS: Patients A, B, and C achieved PASI 75 at treatment completion and week 32, demonstrating improvements of 77.4%, 97.2%, and 100% in PASI, respectively. Their BSA and DLQI were also improved significantly at week 32 and throughout follow-up of 37, 57, and 105 weeks, respectively. The viral loads in patients A and B with CHB decreased modestly. Patient D discontinued after follow-up for 19 weeks, and the primary outcome could not be analyzed. No adverse events were reported during treatment and follow-up.
CONCLUSIONS: Oxymatrine appears to be efficacious and safe for the treatment of patients with EP, including those with concomitant CHB.
BACKGROUND: This study was registered at the Chinese Clinical Trial Registry ( www.chictr.org.cn ; Registration number ChiCTR-TRC-14004301).

Sophora flavescens Aiton, a traditional Chinese medicine that was supposed to predominantly play an anti-inflammatory role, has been used to treat multiple diseases, including cancer, for over two thousand years. Recently, it has attracted increasing attention due to the anti-tumor properties of Oxymatrine, one of the most active alkaloids extracted from S. flavescens. This study aims to explore it\'s anti-tumor effects in non-small cell lung cancer (NSCLC) and the underlying mechanisms. We first investigated the effects of oxymatrine on cell apoptosis in lung cancer cell lines A549 and PC9 as well as explored related genes in regulating the apoptosis by transcriptome analysis. Subsequently, to further study the role of TRIM46, we constructed two types of TRIM46 over-expression cells (A549TRIM46+ and PC9TRIM46+ cells) and then investigated the effect of TRIM46 on oxymatrine-induced apoptosis. Moreover, we explored the effect of TRIM46 on downstream signaling pathways. Transcriptome analysis suggested that shared differentially expressed genes (DEGs) in A549 and PC9 cells treated with oxymatrine were CACNA1I, PADI2, and TRIM46. According to TCGA database analysis, the abundance of TRIM46 expression was higher than CACNA1I, and PADI2 in lung cancer tissues, then was selected as the final DEG for subsequent studies. We observed that oxymatrine resulted in down-expression of TRIM46 as well as induced the apoptosis of the cancer cells in a dose- and time-dependent manner. Meanwhile, we found that apoptosis induced by oxymatrine was inhibited by over-expressing TRIM46. Furthermore, our study indicated that the NF-κB signaling pathway was involved in apoptosis suppressed by TRIM46. We conclude that TRIM46 is the direct target of oxymatrine to induce anti-tumor apoptosis and may activate the downstream NF-κB signaling pathway.

Daruqi is a Traditional Mongolian medicine with anti-inflammatory, anti-bacterial, and immune-regulatory effects. However, the mechanisms of its activity were unclear. In the present study, we confirmed the anti-inflammation effect of Daruqi on inflammation induced by LPS using animal models. Then, THP-1 cells treated with LPS was used as a positive control to explore the effective component of Daruqi on inflammation. We identified that Oxymatrine was the essential effector of Daruqi. Furthermore, the mechanism of Oxymatrine on inflammation was verified through proteomics analyses and validation assays. Our results demonstrated that Oxymatrine significantly reduced the levels of inflammatory cytokine, including IL-8, IL-1α, and IL-1β, in LPS induced THP-1 cells. Based on tandem mass tag -labeled quantitative proteomics, 428 differentially expressed proteins were screened, involved in TNF signaling pathway, Ferroptosis, IL-17 signaling pathway, etc. Among these differential expressed proteins (DEPs), 23 proteins were verified with parallel reaction monitoring analysis. The results showed that LPS treatment potentiated the protein level of PLEK, ACSL5 and CYBB, which could be reversed by Oxymatrine. By contrast, the protein expression of SPRYD4 and EMR2 was suppressed after LPS treatment, which could be rescued by Oxymatrine. In summary, Oxymatrine has excellent protective effects in LPS induced THP-1 cells. The five proteins, including PLEK, ACSL5, CYBB, SPRYD4 and EMR2, might serve as the targets of Oxymatrine, and as candidates regulating inflammation in future therapies.