This study aimed to explore the potential mechanism of Xiexin Tang in improving type 2 diabetes mellitus from the perspective of intestinal barrier function. The results indicated that Xiexin Tang could notably promote the expression of GPRs while suppressing the expression of HDACs in colon epithelial cells, then significantly elevate the levels of TGF-β1 and IL-18 to regulate the differentiation of T cells and further maintain the intestinal immune homeostasis. Meanwhile, it could markedly inhibit the inflammatory signaling pathway to improve intestinal barrier function, relieving type 2 diabetes mellitus.

Evidence regarding Chinese herbal medicine for facial rash related to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is limited. Therefore, this study aimed to investigate whether ex ternal application of a Xiaozhen zhiyang (XZZY) decoction is effective for EGFR-TKI-related facial rash in Chinese patients. In this prospective cohort study, 123 participants with EGFR-TKI-related facial rash were recruited from July 18, 2019 to May 20, 2021. The intervention was external application of the XZZY decoction twice daily for 2 weeks using a facial mask. Treatment efficacy, change in the WoMo score, and quality of life were evaluated as endpoints. The average age of the 123 enrolled participants was 54.83 ± 12.45 years, and 48.78% were female. The total efficiency of treatment was 93.5%, including 12 (10%) cases were cured, 20 (16.26%) cases were markedly improved and 83 (67.48%) cases were improved. The generalized estimating equations showed decreased WoMo scores, itching, and pain, as well as an improved quality of life after the treatment. Only 1 participant reported skin allergies, and no other adverse effects were reported. This study showed the effectiveness and safety of a XZZY decoction for EGFR-TKI-related rash.

Multiple organs are affected by the complex autoimmune illness known as systemic sclerosis (SSc), which has a high fatality rate. Genes linked to autophagy have been linked to the aetiology of SSc. It is yet unknown, though, whether autophagy-related genes play a role in the aetiology of SSc. After using bioinformatics techniques to examine two databases (the GSE76885 and GSE95065 datasets) and autophagy-related genes, we were able to identify 12 autophagy-related differentially expressed genes that are linked to the pathophysiology of SSc. Additional examination of the receiver operating characteristic curve revealed that SFRP4 (AUC = 0.944, P < 0.001) and CD93 (AUC = 0.904, P < 0.001) might be utilized as trustworthy biomarkers for the diagnosis of SSc. The SSc group’s considerably greater CD93 and SFRP4 expression levels compared to the control group were further confirmed by qRT-PCR results. The autophagy-related genes SFRP4 and CD93 were found to be viable diagnostic indicators in this investigation. Our research sheds light on the processes by which genes linked to autophagy affect the pathophysiology of SSc.

Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disease. Vascular damage is one of the important features of SSc, which affects the progression and prognosis of the disease. MiR-126-3p is an important microRNA (miRNA) that regulates vascular structure and function, which can be transported through exosomes. However, the role of miR-126-3p in vascular damage in SSc is still unclear. Therefore, we focused on the connection between miR-126-3p and vascular damage in SSc, as well as investigated the potential role of miR-126-3p in vascular damage in SSc. First, this study successfully extracted extracellular vesicles from clinical plasma samples and characterized the exosomes within them. Then, we predicted and screened the target pathway mammalian/mechanistic target of rapamycin (mTOR) and the target gene SLC7A5 of miR-126-3p through online databases. Next, we constructed SSc mice for in vivo studies. The results showed that the expression of miR-126-3p was decreased in the plasma exosomes, while the SLC7A5 expression, autophagy, and lipid peroxidation were increased in the aorta. Luciferase reporter gene assays demonstrated that miR-126-3p can bind to SLC7A5, resulting in a decrease in its expression. In vitro experiments have shown that exosomal miR-126-3p can be internalized by human umbilical vein endothelial cells (HUVECs). The miR-126-3p group exhibited enhanced cell viability and tube formation ability, along with increased expression of the vascular formation marker CD31. Additionally, miR-126-3p downregulated the protein expression of SLC7A5 and LC3 in HUVECs, while upregulating the protein expression of mTOR, P62, PPAR gamma, and CPT-1. However, the effects of miR-126-3p on HUVECs were counteracted by mTOR inhibitors and enhanced by mTOR activators. The results indicated that exosomal miR-126-3p has the potential to protect against vascular injury in SSc by regulating the SLC7A5/mTOR signalling pathway in HUVECs.

ETHNOPHARMACOLOGY RELEVANCE:Traditional herbal medicines have been considered as a novel and effective way to treat many diseases. Lizhong decoction (LZD), a classical prescription composed of Zingiber officinale Rosc., Panax ginseng C. A. Mey., Atractylodes macrocephala Koidz., and Glycyrrhiza uralensis Fisch., has been used to treat gastrointestinal disorders in clinical practices for thousands of years. However, the mechanism of LZD in alleviating ulcerative colitis (UC) is still unclear.AIM OF THE STUDY:The purpose of this study was to clarify the potential molecular mechanism of LZD in improving UC.MATERIALS AND METHODS:The amelioration of LZD on dextran sodium sulfate (DSS)-induced UC mice was evaluated by body weight, colon length, pathology of colon tissues, pro-inflammatory cytokines, and intestinal tight junction (TJ) proteins. Moreover, the gene expression profiles of UC patients were extracted to investigate potential pathological mechanisms of UC. The influence of LZD on ferroptosis was analyzed by iron load, malondialdehyde (MDA), and the expression of ferroptosis-associated proteins. Meanwhile, the inhibition of LZD on oxidative stress (OS) was assessed by the superoxide dismutase (SOD) activity, as well as the expression levels of glutathione (GSH) and glutathione disulfide (GSSG). Furthermore, the influence of LZD on ferroptosis was assessed by inhibiting nuclear factor (erythroid-derived-2)-like 2 (Nrf2).RESULTS:LZD showed significant therapeutic effects in UC mice, including reduction of intestinal injury and inflammation. Moreover, LZD treatment notably upregulated the expression of TJ proteins. Further investigation indicated that LZD significantly inhibited the ferroptosis of enterocytes by decreasing iron load and MDA, and increasing the expression levels of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in colon tissues. Furthermore, the decreased activity of SOD, reduced level of GSH, and increased content of GSSG in UC mice were notably reversed by LZD. Consistent with in vivo results, LZD could markedly inhibit ferroptosis and OS in RSL3-induced Caco-2 cells. Mechanistically, LZD alleviated ferroptosis by suppressing OS through the activation of Nrf2 signaling.CONCLUSIONS:Collectively, LZD remarkably improved intestinal pathological injury in UC mice, and its potential mechanism was the suppression of ferroptosis in enterocytes by the Nrf2/SLC7A11/GPX4 pathway.

Objective To analyze the effects and molecular mechanisms of AhR signaling pathway in the treatment of scleroderma with Bushen Yijing Decoction. Methods The active ingredients of Bushen Yijing Decoction and its target genes, AhR signaling pathway genes and the genes related to scleroderma were searched through TCMSP and other databases, and LC-MS results. Target gene network diagram of scleroderma, AhR pathway and the key active ingredients in Bushen Yijing Decoction were constructed. The protein-protein interaction network was constructed with STRING database, and GO and Genome KEGG were also performed. Finally, the molecular docking of the active ingredients and AhR were verified. Results Ferulic acid, quercetin, kaempferol, isoferulic acid and luteolin were key active ingredients in Bushen Yijing Decoction for the treatment of scleroderma by targeting AhR signaling pathway. These active ingredients possibly regulated AhR signaling pathway molecules, including IL-6, CTNNB1, HSP90AA1, TNF and PTGS2, which were involved in the pathogenesis of scleroderma. Molecular docking showed that the binding energies of ferulic acid, kaempferol, quercetin, isoferulic acid and luteolin with AhR were lower than -6.0 kcal/mol, indicating a good binding activity. Conclusions The mechanisms by which Bushen Yijing Decoction treats scleroderma can be attributed to the active ingredients such as ferulic acid, quercetin, kaempferol, isoferulic acid, luteolin, which target AhR signaling pathway and regulate core targets, including IL-6, CTNNB1, HSP90AA1, TNF and PTGS2.

目的:基于皮肤镜检测技术观察火针对重度痤疮的临床疗效.方法:将2021年3月-2022年3月广州中医药大学第一附属医院皮肤科就诊的100例重度痤疮患者纳入研究,随机分为对照组及观察组,每组50例.对照组给予口服阿奇霉素片联合复方黄柏涂剂外用;观察组在对照组的基础上再予以火针治疗.治疗周期共6周,治疗期间定期评估全球痤疮分级系统(Global acne grading system,GAGS)评分,采用皮肤镜观察皮疹变化情况,记录不良反应.结果:治疗结束后,治疗组及观察组均取得较好治疗效果.观察组有效率72.00％,显著高于对照组52.00％;观察组GAGS评分为(10.64±8.30)分低于对照组(15.02±10.62)分,差异具有统计学意义(P＜0.05)且皮肤镜下皮损改变情况直观显著.结论:火针联合口服阿奇霉素及外用复方黄柏涂剂治疗重度痤疮疗效确切.皮肤镜可作为客观评估痤疮病情变化的有效工具,用于其临床疗效评估及相关研究.

Xiexin Tang (XXT) is a classic prescription for treating diabetes in clinical practices for thousands of years in China, which has been also proved by a large number of modern pharmacological studies. However, due to its complex composition, the bioactive ingredients of XXT is still unclear. In present researches, spectrum-effect relationship analysis is widely used to explore the material basis of traditional medical herbs, so this method was adopted in this study. Firstly, the extract of XXT was separated and enriched into 5 fractions by macroporous adsorption resin. Then, UPLC-Q-TOF/MS method was used for qualitative identification of components in each eluting part, and efficacy of each fraction was assessed by the T2DM rat model. Based on grey relational analysis and pearson bivariate correlation analysis, it was found that the components such as berberine, gallic acid, catechin, epicatechin, acteoside, berberastine and 1-O-galloyl-β-D-glucose might be the main effective basis of XXT to improve T2DM.

Abstract Background: Systemic sclerosis (SSc) is a chronic autoimmune disease characterised by fibroblast activation and vascular and immune cell dysfunction. Autophagy-related genes are speculated to be involved in the development of SSc. However, the involvement of autophagy-related genes in SSc remains unexplored. This study aimed to explore the explicit mechanism of autophagy in SSc using bioinformatics analysis. Methods: GSE76885 and GSE95065 datasets were downloaded from the Gene Expression Omnibus database, and human autophagy genes were acquired from GeneCards. Following this, 12 autophagy-related differentially expressed genes (autophagy-related DEGs) were obtained using the Venn package of R software. The Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichments and Gene Set Enrichment Analysis were performed to annotate the biological function of autophagy-related DEGs. Receiver operating characteristic (ROC) analyses were performed to explore the diagnostic value of Autophagy-related DEGs in SSc. Finally, regulatory network analysis and single-sample Gene-set Enrichment Analysis (ssGSEA) were performed. Results: A total of 12 autophagy-related DEGs were identified related to the pathogenesis of SSc. Enrichment analysis identified that metabolism-related pathways were remarkably enriched along with classical PI3K/AKT signaling. ROC curve analysis showed that CD93 (AUC = 0.904, P < 0.001) and SFRP4 (AUC = 0.944, P < 0.001) could serve as reliable biomarkers in the diagnosis and treatment of SSc. Regulatory networks analysis identified 126 transcription factors, 93 miRNA molecules and 106 drugs or molecular compounds related to Autophagy-related DEGs. Finally, ssGSEA demonstrated that Autophagy-related DEGs were mainly associated with CCR, macrophages, Treg cells and Type I IFN Response. Conclusion: We identified CD93 and SFRP4 as valuable diagnosis biomarkers for SSc. Moreover, autophagy-related DEGs could affect the development of SSc through autophagy-related pathways, metabolic processes and immune cell infiltration.

In the present study, it was aimed to evaluate whether there is an objective tongue image indicator that could be used to evaluate malignant risk of thyroid nodules through a cross sectional study. From December 2018 to December 2020, the TFDA-1 digital tongue-face diagnostic instrument was used to collect the tongue images. TDAS 2.0 software was used for tongue image analysis. A standardized database was constructed by combining patient physical examination results and tongue image analysis results. The relationship between tongue image index and TI-RADS classification of thyroid nodules was tested. A total of 5,900 cases were collected and 4,615 cases were included in the present study after excluding 154 cases due to incomplete information, 1,221 cases with thyroid nodules were separated into 417 cases TI-RADS 2 group, 693 cases in TI-RADS 3 group and 111 cases in TI-RADS 4 group. Without considering confounding factors, tongue image indexes zhiCon, zhiASM, zhiENT, zhiMEAN, zhiClrB, zhiClrR, zhiClrG, zhiClrI, zhiClrL and zhiClrY were significantly different among the three groups (P<0.05). Excluding the influence of age, sex, body mass index, smoking and drinking, the results of one-way variance linear trend analysis showed that the values of zhiCon, zhiENT and zhiMEAN increased with the increasing TI-RADS category, while the values of zhiASM decreased with the increase of TI-RADS category. Tongue texture index may be helpful for differentiating the benign and malignant of thyroid nodules.

Zingiber officinale and Panax ginseng, as well-known traditional Chinese medicines, have been used together to clinically treat ulcerative colitis with synergistic effects for thousands of years. However, their compatibility mechanism remains unclear. In this study, the shift of gut microbiome and fecal metabolic profiles were monitored by 16S rRNA sequencing technology and ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry analysis, respectively, which aimed to reveal the synergistic mechanism of Zingiber officinale and Panax ginseng on the amelioration of ulcerative colitis. The results showed that the relative abundance of beneficial bacteria (such as Muribaculaceae_norank, Lachnospiraceae NK4A136 group and Akkermansia) was significantly increased and the abundance of pathogenic bacteria (such as Bacteroides, Parabacteroides and Desulfovibrio) was markedly decreased after the intervention of Zingiber officinale-Panax ginseng herb pair. And a total of 16 differential metabolites related to ulcerative colitis were identified by the metabolomics analysis, which were majorly associated with the metabolic pathways, including arachidonic acid metabolism, tryptophan metabolism, and steroid biosynthesis. Based on these findings, it was suggested that the regulation of the gut microbiota-metabolite axis might be a potential target for the synergistic mechanism of Zingiber officinale-Panax ginseng herb pair in the treatment of ulcerative colitis. Furthermore, the integrated analysis of microbiome and metabolomics used in this study could also serve as a useful template for exploring the mechanism of other drugs.

Rhubarb, a traditional herb, has been used in clinical practice for hundreds of years to cure constipation, but its mechanism is still not clear enough. Currently, growing evidence suggests that intestinal flora might be a potential target for the treatment of constipation. Thus, the aim of this study was to clarify the laxative effect of rhubarb via systematically analyzing the metagenome and metabolome of the gut microbiota. In this study, the laxative effects of rhubarb were investigated by loperamide-induced constipation in rats. The gut microbiota was determined by high-throughput sequencing of 16S rRNA gene. Ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used for fecal metabolomics analysis. The data showed that rhubarb could significantly shorten gastrointestinal transit time, increase fecal water content and defecation frequency, improve gastrointestinal hormone disruption, and protect the colon mucus layer. Analysis of 16S rRNA gene sequencing indicated that rhubarb could improve the disorder of intestinal microbiota in constipated rats. For example, beneficial bacteria such as Ligilactobacillus, Limosilalactobacillus, and Prevotellaceae UCG-001 were remarkably increased, and pathogens such as Escherichia-Shigella were significantly decreased after rhubarb treatment. Additionally, the fecal metabolic profiles of constipated rats were improved by rhubarb. After rhubarb treatment, metabolites such as chenodeoxycholic acid, cholic acid, prostaglandin F2α, and α-linolenic acid were markedly increased in constipation rats; in contrast, the metabolites such as lithocholic acid, calcidiol, and 10-hydroxystearic acid were notably reduced in constipation rats. Moreover, correlation analysis indicated a close relationship between intestinal flora, fecal metabolites, and biochemical indices associated with constipation. In conclusion, the amelioration of rhubarb in constipation might modulate the intestinal microflora and its metabolism. Moreover, the application of fecal metabolomics could provide a new strategy to uncover the mechanism of herbal medicines. Key points • Rhubarb could significantly improve gut microbiota disorder in constipation rats. • Rhubarb could markedly modulate the fecal metabolite profile of constipated rats.

Glycyrrhizinic acid (GL) is clinically applied to treat liver injury, and the bioavailability of orally administered GL is closely related to the gut microbiota. Therefore, the dysbiosis of gut flora in liver injury could significantly influence GL bioavailability. Still, less is known about the impact of probiotic supplementation on the bio-absorption process of oral medication, especially under a pathological state. Herein, probiotic L. rhamnosus R0011 (R0011) with a high viability in the harsh gastrointestinal environment was selected, and the effect of R0011 on the GL bioavailability in rats was investigated. Four groups of rats (n = 6 per group) were included: the normal group (N group), the normal group supplemented with R0011 (NLGG group), CCl4-induced chronic liver injury model (M group), and the model group supplemented with R0011 (MLGG group). Our results showed that liver injury was successfully induced in the M and MLGG groups via an intraperitoneal injection of 50% (v/v) CCl4 solution. Healthy rats supplemented with R0011 could increase the bioavailability of GL by 1.4-fold compared with the normal group by plasma pharmacokinetic analysis. Moreover, the GL bioavailability of MLGG group was significantly increased by 4.5-fold compared with the model group. R0011 directly improved gut microbial glucuronidase and downregulated the host intestinal drug transporter gene expression of multidrug resistance protein 2 (MRP2). More critically, R0011 restored the gut microbiota composition and regulated the metabolic function, significantly enhancing the microbial tryptophan metabolic pathway compared with the pathological state, which may indirectly promote the bioavailability of GL. Overall, these data may provide possible strategies by which to address the low bioavailability of traditional medicine through probiotic intervention.

Zingiberis Rhizoma and Ginseng Radix et Rhizoma are usually used together for the treatment of ulcerative colitis in clinical practices. However, their compatibility mechanism remains unclear. In this study, a rapid and sensitive liquid chromatography with tandem mass spectrometry method was developed for simultaneous quantification of ginsenoside Re, ginsenoside Rg1, ginsenoside Rb1, and 6‐gingerol in rat plasma after oral administration of Zingiberis Rhizoma–Ginseng Radix et Rhizoma herb pair and its single herb extracts. The calibration curves exhibited good linearity, with correlation coefficients of more than 0.993. The precision deviations of intra‐ and interday analysis were within 10.66%, and accuracy error ranged from −12.74 to 11.56%. The average recoveries of analytes were higher than 76.60% and the matrix effects were minimal. Thus, the validated method was successfully applied to a pharmacokinetic study of four ingredients in normal and ulcerative colitis rat plasma. The results indicated that the pharmacokinetic parameters of four analytes in normal and model groups showed significant differences. The larger exposure (the mean AUC 0‐t of ginsenoside Re, ginsenoside Rg1, ginsenoside Rb1, and 6‐gingerol were increased by 50.93, 141.90, 3.68, and 37.25%, respectively) and slower elimination (the CL z/F of ginsenoside Re, ginsenoside Rg1, and 6‐gingerol were decreased by 52.94, 83.64, and 32.18%, respectively) were observed in ulcerative colitis rats. Furthermore, compared with single herbs, the analytes in rat plasma after oral administration of combined extracts presented relatively high systemic exposure levels with AUC 0‐t > 2000 h·ng/mL and C max > 200 ng/mL. Collectively, the differences of pharmacokinetic characteristics revealed the synergistic effect of Zingiberis Rhizoma–Ginseng Radix et Rhizoma herb pair, which provided a valuable and reliable basis for its clinical application in the treatment of ulcerative colitis.

外治法治疗皮肤疾病可直接作用于皮肤,使药物直达病所,收效明显.陈汉章教授认为在中药内服基础上联合运用中药外洗法治疗皮肤疾病,临床效果显著,且简单易行;其临床应用中药外洗法诊治皮肤疾病辨证多从风、湿热以及血分论治皮肤疾病,外洗中药处方以祛风止痒、清热燥湿、活血化瘀药物为主,常选用防风、荆芥、地肤子、白鲜皮、乳香、没药等,并根据皮损的性质辨证选择外洗药物的种类.陈汉章教授临床治疗皮肤疾病所应用的外洗方,其药物组成精简,善用岭南中草药,并酌情运用虫类药以及中药散剂,收效显著.

[目的]观察经补肾益精法处理后人脐静脉内皮细胞(HUVEC)来源的外泌体对系统性硬皮病血管损伤的治疗作用.[方法]①体外研究:制备大鼠补肾益精中药复方含药血清,通过血管内皮细胞成管实验观察含药血清与对照血清对HUVEC成管的影响,细胞免疫荧光染色法检测血小板内皮细胞黏附分子1(CD31)表达.采用超速离心法提取HUVEC细胞上清液中外泌体,透射电镜观察外泌体形态,Nano Analyzer法检测外泌体径粒与浓度,Western Blot法检测外泌体标志物的表达.设置对照血清干预HUVEC来源的外泌体组(对照血清-外泌体组)和含药血清干预HUVEC来源的外泌体组(含药血清-外泌体组),用外泌体处理HUVEC后,通过成管实验观察HUVEC成管能力,细胞免疫荧光染色法检测CD31表达.②体内研究:设置正常组、模型组及外泌体组.采用皮下注射博来霉素(100μL·mg-1·d-1)28 d构建硬皮病小鼠模型.此外,模型组及外泌体组小鼠在造模第1、7天分别额外给予外泌体悬液及含药血清-外泌体局部皮下注射.4周后,观察小鼠皮肤组织病理变化,免疫组织化学法检测小鼠皮肤组织血管生成素1(ANG-1)、血管内皮细胞生长因子(VEGF)、血管性假血友病因子(vWF)、CD31表达水平.[结果]与对照组比较,含药血清组与含药血清-外泌体组的HUVEC成管能力及CD31表达均显著增强.电镜下可见类圆形高亮膜性微囊泡,外泌体的标志物表达增强.HE染色结果显示,与模型组比较,外泌体组小鼠皮肤胶原纤维含量有所减少,胶原间隙增宽,血管数量增多;免疫组织化学结果显示外泌体组小鼠皮肤ANG-1、VEGF、vWF、CD31表达水平显著高于模型组,较正常组有所降低.[结论]补肾益精法可通过HUVEC来源的外泌体途径发挥对系统性硬皮病的血管保护作用.

随着现代信息时代的快速发展,在"互联网+"的背景下,高校的教学教育模式也需要不断地改革及创新,以更好地提高教学效率.其中皮肤性病学是一门形态学特别强的学科,但是高校中皮肤与性病学课时少、教学内容多是皮肤科教学的主要难点,因此可以充分利用微信平台操作性强、学习时间空间灵活、学习资源丰富等优势开展皮肤科教学,高效优质地完成教学活动.

Systemic sclerosis (SSc) refers to a group of autoimmune rheumatic diseases. Bushen Yijing decoction (BSYJ) is used for treating SSc. However, its underlying mechanism remains unknown. The present study aims to investigate potential roles of Friend leukemia integration factor 1 (FLI1) and microRNA in the beneficial effects of BSYJ on SSc. Primary skin fibroblasts were isolated from healthy individuals and SSc patients through tissue-explant technique and validated by immunocytochemistry. mRNA and microRNA levels were determined by quantitative RT-PCR. Protein expression was measured by western blotting. MiR-26a mimics or inhibitor were transfected to induce miR-26a overexpression or knockdown in vitro and in vivo, respectively. Histological changes of skin tissues from SSc mouse were evaluated by H&E and Masson trichrome staining. Results showed that FLI1 expression significantly decreased in primary skin fibroblasts of SSc patients. MiR-26a was predicted to target FLI1 untranslated region. Transfection of miR-26 mimics in SSc skin fibroblasts (SFB) leads to decrease in FLI1 expression and increase in collagen I gene expression and fibronectin accumulation. On the other hand, miR-26a knockdown increased FLI1 expression and decreased collagen I and fibronectin expression in SFB. In addition, BSYJ-containing rat serum suppressed miR-26a expression, while it elevated FLI1 expression and inhibited fibronectin and collagen I accumulation in SFB. In the mouse SSc model, BSYJ-containing serum inhibited dermal fibrosis by suppressing miR-26a expression and restoring FLI1 protein levels. Overall, our study demonstrates that BSYJ decoction exerts anti-dermal fibrosis in SSc patients via suppressing miR-26a level and thus to increase FLI1 expression in fibroblasts.

The present study aimed to investigate the functional components from Bushen Yijing Formula and their inhibition of endothelial–mesenchymal transition (EndMT) and fibrosis in human umbilical vascular endothelial cells (HUVECs). HUVEC fibrosis was induced by treatment of transforming growth factor β (TGF-β) as the cellular model. Expression of EndMT biomarker gene and cofactors were determined by quantitative real-time-PCR, western blotting, and immunofluorescence. Angiogenesis capacity of vein endothelial cells was evaluated using tube formation assay. Ursolic acid and drug-contained serum ameliorated EndMT biomarker gene expression changes and angiogenesis capacity suppression induced by TGF-β treatment. Slug, Snail, and Twist gene expression and phosphorylation of mammalian target of rapamycin (mTOR) and AKT altered by TGF-β in HUVECs were suppressed by ursolic acid and drug-contained serum. Treatment with the mTOR signaling pathway inhibitor, rapamycin, inhibited the phosphorylation of mTOR and AKT, decreased Snail and Vimentin protein levels, and increased VE-cad protein levels. Overexpression of Snail gene promoted expression of EndMT-related genes and suppressed angiogenesis in HUVECs, which were attenuated by application of ursolic acid and drug-contained serum. Ursolic acid from Bushen Yijing Formula inhibits human umbilical vein endothelial cell EndMT and fibrosis, mediated by AKT/mTOR signaling and Snail gene expression.