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Si-Wu-Tang improves liver fibrosis by restoring liver sinusoidal endothelial cell functionality and reducing communication with hepatic stellate cells. 四物汤通过恢复肝窦内皮细胞功能和减少与肝星状细胞的通讯来改善肝纤维化。
IF 5.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-12-31 DOI: 10.1186/s13020-024-01038-1
Le Wang, Jiaorong Qu, Jianan Li, Xiaoyong Xue, Lingling Qin, Yufei Li, Yuanfeng Dou, Xiaohong Mu, Xiaojiaoyang Li

Background: Liver fibrosis is a complex reparative process in response to chronic liver injuries, with limited effective therapeutic options available in clinical practice. During liver fibrosis, liver sinusoidal endothelial cells (LSECs) undergo phenotypic changes and also play a role in modulating cellular communications. Si-Wu-Tang (SWT), a traditional Chinese herbal remedy, has been extensively studied for its effectiveness in treating hematological, gynecological and hepatic diseases.

Materials and methods: The component of SWT were identified by ultra-high-performance liquid chromatography (UHPLC). After establishing bile duct ligation (BDL)-induced liver fibrosis mice model and VEGFA-stimulated LSEC model, we invested the mechanism of SWT through RNA sequencing combined with molecular biology techniques.

Results: SWT significantly improved the sinusoidal permeability and liver fibrosis induced by BDL and effectively regulated pathological processes in LSECs, such as angiogenesis, cell adhesion, basement membrane formation and defenestration. The anti-fibrosis effects of SWT were attributed to the inhibition on LSEC adhesion via COL8A1, on LSEC angiogenesis via IL-1β and the induction of LSEC defenestration by OLR1. Additionally, SWT disrupted the intercellular crosstalk between LSECs and hepatic stellate cells (HSCs) driven by IL-1β, thus alleviating liver fibrosis.

Conclusion: SWT collectively ameliorated liver fibrosis by inhibiting the COL8A1/IL-1β/OLR1 pathways associated with LSEC angiogenesis, adhesion and defenestration, as well as suppressing LSEC secretion of IL-1β to reduce HSC activation.

背景:肝纤维化是慢性肝损伤的复杂修复过程,临床实践中有效的治疗方案有限。在肝纤维化过程中,肝窦内皮细胞(LSECs)经历表型改变,并在调节细胞通讯中发挥作用。四物汤(SWT)是一种传统的中草药,因其治疗血液病、妇科和肝脏疾病的有效性而被广泛研究。材料和方法:采用超高效液相色谱法(UHPLC)鉴定SWT的成分。我们建立了胆管结扎(BDL)诱导的肝纤维化小鼠模型和vegfa刺激的LSEC模型,通过RNA测序结合分子生物学技术研究SWT的机制。结果:SWT显著改善BDL诱导的肝窦通透性和肝纤维化,有效调节LSECs血管生成、细胞粘附、基底膜形成和脱巢等病理过程。SWT的抗纤维化作用是通过COL8A1抑制LSEC粘附,通过IL-1β抑制LSEC血管生成,以及通过OLR1诱导LSEC脱巢。此外,SWT破坏了由IL-1β驱动的LSECs和肝星状细胞(hsc)之间的细胞间串扰,从而减轻了肝纤维化。结论:SWT通过抑制LSEC血管生成、粘附和脱内皮相关的COL8A1/IL-1β/OLR1通路,抑制LSEC IL-1β分泌,降低HSC活化,共同改善肝纤维化。
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引用次数: 0
Indole-3-carbinol alleviates allergic skin inflammation via periostin/thymic stromal lymphopoietin suppression in atopic dermatitis. 吲哚-3-甲醇通过抑制特应性皮炎患者的骨膜蛋白/胸腺基质淋巴生成素来缓解过敏性皮肤炎症。
IF 5.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-12-26 DOI: 10.1186/s13020-024-01042-5
Yun-Mi Kang, Hye-Min Kim, Junho Lee, Jong-Suep Baek, Minho Lee, Hyo-Jin An

Background: Atopic dermatitis (AD) is a chronic multifactorial inflammatory skin disorder with a complex etiology. Despite its increasing prevalence, treatment of AD is still limited. Indole-3-carbinol (I3C) is found in cruciferous vegetables and is formed when these vegetables are cut, chewed, or cooked; it exerts diverse pharmacological activities.

Methods: HaCaT keratinocytes stimulated with tumor necrosis factor-α and interferon-γ mixture and NC/Nga mice stimulated with 2,4-dinitrochlorobenzen (DNCB) were used for AD models, in vitro and in vivo, respectively.

Results: The results showed that I3C reduced the expression of pro-inflammatory cytokines, thymic stromal lymphopoietin (TSLP), and periostin in in vitro model. Oral administration of I3C alleviated AD-like skin inflammatory symptoms, including serum IgE levels, epidermal thickening, inflammatory cell infiltration, transepidermal water loss, and scratching behavior. Moreover, I3C decreased the expression of TSLP and periostin and recovered the expression of skin barrier proteins by regulating Aryl Hydrocarbon Receptor and inhibiting the mitogen-activated protein kinase and nuclear factor-κB pathways in the skin of DNCB-induced AD mice.

Conclusions: I3C is suggested as a potential therapeutic alternative for the treatment of AD by repressing allergic inflammatory pathways.

背景:特应性皮炎(AD)是一种病因复杂的慢性多因素炎症性皮肤病。尽管阿尔茨海默病的发病率越来越高,但治疗仍然有限。吲哚-3-甲醇(I3C)存在于十字花科蔬菜中,当这些蔬菜被切割、咀嚼或烹饪时形成;它具有多种药理活性。方法:采用肿瘤坏死因子-α和干扰素-γ混合物刺激HaCaT角质形成细胞和2,4-二硝基氯苯(DNCB)刺激NC/Nga小鼠分别建立AD模型。结果:I3C可降低体外模型中促炎细胞因子、胸腺基质淋巴生成素(TSLP)、骨膜素的表达。口服I3C可减轻ad样皮肤炎症症状,包括血清IgE水平、表皮增厚、炎症细胞浸润、经皮失水和抓伤行为。此外,I3C通过调节芳烃受体、抑制丝裂原活化蛋白激酶和核因子-κB通路,降低了dncb诱导AD小鼠皮肤中TSLP和periostin的表达,恢复了皮肤屏障蛋白的表达。结论:I3C可作为一种潜在的治疗方案,通过抑制过敏性炎症途径治疗AD。
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引用次数: 0
Lipid droplet formation induced by icaritin derivative IC2 promotes a combination strategy for cancer therapy. 淫羊藿苷衍生物IC2诱导的脂滴形成促进了癌症治疗的联合策略。
IF 5.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-12-26 DOI: 10.1186/s13020-024-01050-5
Guosheng Wu, Liang Ying, Qian Zhang, He Xiong, Jie Wang, Sitao Chen, Chen Yang, Yiyuan Jin, Zengwei Lai, Ninghan Feng, Yunjun Ge

Background: Lipid metabolism is crucial in cancer progression. Lipid droplets (LDs) generated in cancer cells can act as protective mechanisms through alleviating lipotoxicity under stress conditions. We previously developed IC2 from the Chinese medicine icaritin as an inhibitor of stearoyl-CoA desaturase 1 (SCD1). IC2 has been shown to disrupt lipid metabolism and inhibits cancer cell proliferation. However, the impact of IC2 on intracellular LDs and the potential of targeting LD formation for combination cancer therapy remain unexplored.

Methods: LD formation in cancer cells was analyzed with oil red O or BODIPY staining by microscopy. LD quantification was normalized to the cell number. IC2-induced cellular responses were revealed by transcriptional analysis, real-time PCR, and immunoblotting. Mitochondrial functions were assessed by measuring ATP production and oxygen consumption. The lipid source for LD formation was studied using lipid transporter inhibitors or lipid deprivation. The effect of inhibiting LD formation on IC2's anti-tumor effects was evaluated using MTT assays and apoptosis assays, which was subsequently validated in an in vivo xenografted tumor model.

Results: IC2 exerted anti-tumor effects, resulting in LD formation in various cancer cells. LD formation stimulated by IC2 was independent of extracellular lipid sources and did not result from increased de novo fatty acid (FA) synthesis within the cancer cells. Transcriptional analysis indicated that IC2 disturbed mitochondrial functions, which was confirmed by impaired mitochondrial membrane potential (MMP) and reduced capacity for ATP production and oxygen consumption. Moreover, IC2 treatment led to a greater accumulation of lipids in LDs outside the mitochondria compared with the control group. IC2 inhibited the proliferation of PC3 cells and promoted the apoptosis of the cancer cells. These effects were further enhanced after inhibiting the diacylglycerol acyltransferase 1 (DGAT1), a key intracellular enzyme involved in LD formation. In PC3-xenografted mice, the DGAT1 inhibitor augmented the IC2-induced reduction in tumor growth by modulating LD formation.

Conclusion: LD formation is a feedback response to IC2's anti-tumor effects, which compromises the anti-tumor actions. IC2's anti-tumor efficacy can be enhanced by combining it with inhibitors targeting LD formation. This strategy may be extended to other anti-tumor agents that regulate lipid metabolism.

背景:脂质代谢在癌症进展中起关键作用。在应激条件下,癌细胞中产生的脂滴可以作为一种保护机制,减轻脂肪毒性。我们之前从中药淫羊藿苷中开发了IC2,作为硬脂酰辅酶a去饱和酶1 (SCD1)的抑制剂。IC2已被证明可以破坏脂质代谢并抑制癌细胞增殖。然而,IC2对细胞内LD的影响以及针对LD形成的联合癌症治疗的潜力仍未被探索。方法:显微镜下采用油红O或BODIPY染色法观察癌细胞LD形成情况。LD定量归一化为细胞数。通过转录分析、实时PCR和免疫印迹分析显示ic2诱导的细胞反应。通过测量ATP生成和耗氧量来评估线粒体功能。通过脂质转运蛋白抑制剂或脂质剥夺来研究LD形成的脂质来源。通过MTT实验和细胞凋亡实验评估抑制LD形成对IC2抗肿瘤作用的影响,随后在体内异种移植肿瘤模型中验证。结果:IC2具有抗肿瘤作用,可在多种癌细胞中形成LD。IC2刺激的LD形成不依赖于细胞外脂质来源,也不是由于癌细胞内新生成脂肪酸(FA)合成增加所致。转录分析表明,IC2干扰了线粒体功能,线粒体膜电位(MMP)受损、ATP生成和氧气消耗能力降低证实了这一点。此外,与对照组相比,IC2处理导致线粒体外ld中的脂质积累更多。IC2抑制PC3细胞的增殖,促进癌细胞的凋亡。在抑制二酰基甘油酰基转移酶1 (DGAT1)后,这些作用进一步增强,DGAT1是参与LD形成的关键细胞内酶。在pc3异种移植小鼠中,DGAT1抑制剂通过调节LD的形成增强了ic2诱导的肿瘤生长的减少。结论:LD的形成是对IC2抗肿瘤作用的反馈反应,这种反馈反应损害了IC2的抗肿瘤作用。IC2与靶向LD形成的抑制剂联用可增强其抗肿瘤疗效。这一策略可能扩展到其他调节脂质代谢的抗肿瘤药物。
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引用次数: 0
Electroacupuncture ameliorates inflammatory pain through CB2 receptor-dependent activation of the AMPK signaling pathway. 电针通过CB2受体依赖性激活AMPK信号通路改善炎症性疼痛。
IF 5.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-12-24 DOI: 10.1186/s13020-024-01048-z
Yuye Lan, Xianghong Jing, Ziyu Zhou, Yiqing Rao, Kaichen Wang, Renjie Qin, Yisong Wu, Jingjing Sun, Ke Zhang, Xinyue Liu, Zixiao Wang, Jiahao Xu, Minzhen Zhao, Xiao Cui Yuan, Yongmin Liu, Hong Zhang, Xuefei Hu, Huilin Pan, Tengfei Hou, Man Li

Background: Chronic inflammatory pain is a pervasive condition, and electroacupuncture (EA) is an effective treatment, but its mechanisms are not fully understood. AMP-activated protein kinase (AMPK), a key energy sensor, is involved in pain relief and EA's effects. EA may work by increasing endocannabinoids, upregulating CB2 receptors (CB2R), and stimulating β-endorphin (β-END). This study tests if EA activates AMPK via CB2R to modulate β-END and reduce pain.

Methods: The inflammatory pain model was established with Complete Freund's adjuvant (CFA), and EA was administered daily for six consecutive days, targeting the acupoints "Zusanli" (ST36) and "Shangjuxu" (ST37). Pain sensitivity was evaluated using Von Frey filaments for mechanical thresholds and a hot plate for thermal thresholds. Ultra-high Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS) was used to quantitatively determine the levels of endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (AEA). The expression levels of the CB2R and β-END were measured by Western blotting, along with the activation of AMPK. Immunofluorescence double-labeling was applied to visualize AMPK activation and β-END expression within CD68-positive macrophages. The study encompassed both wild-type and CB2R gene knockout mice, elucidating the role of CB2R in EA-induced AMPK activation.

Results: CFA-induced inflammatory pain model mice exhibited mechanical allodynia and thermal hyperalgesia. EA activated AMPK in the inflamed skin tissue when it exerted analgesic effect on the inflammatory pain. Pre-administration of the AMPK inhibitor Compound C significantly inhibited the effect of EA on pain relief. EA elevated β-END expression in inflamed skin tissue, which was reversed by Compound C, indicating that AMPK has a regulatory role in EA inducing β-END expression. In addition, EA significantly upregulated the levels of 2-AG, AEA and the expression of CB2Rs in the inflamed skin tissue compared with the CFA group. In wild-type mice, EA activates AMPK in macrophages, while CB2 knockout reduced EA's ability to activate AMPK in these cells.

Conclusion: EA activates AMPK through CB2R, enhancing β-END expression in inflamed skin to alleviate inflammatory pain. This study reveals a new link between endocannabinoids, endorphins, and AMPK in analgesic effects of EA, highlighting the CB2R-AMPK-β-END pathway.

背景:慢性炎症性疼痛是一种普遍的疾病,电针(EA)是一种有效的治疗方法,但其机制尚不完全清楚。amp活化蛋白激酶(AMPK)是一种关键的能量传感器,参与疼痛缓解和EA的作用。EA可能通过增加内源性大麻素,上调CB2受体(CB2R)和刺激β-内啡肽(β-END)起作用。本研究检测EA是否通过CB2R激活AMPK,从而调节β-END,减轻疼痛。方法:采用完全弗氏佐剂(CFA)建立炎症性疼痛模型,每日给予足三里(ST36)、上巨枢(ST37)穴EA,连续6 d。采用Von Frey细丝作为机械阈值,热板作为热阈值来评估疼痛敏感性。采用超高效液相色谱-串联质谱法(UPLC-MS/MS)定量测定内源性大麻素2-花生四烯醇甘油(2-AG)和anandamide (AEA)的含量。Western blotting检测CB2R和β-END的表达水平,同时检测AMPK的激活。应用免疫荧光双标记技术观察cd68阳性巨噬细胞内AMPK活化和β-END表达情况。该研究包括野生型和CB2R基因敲除小鼠,阐明了CB2R在ea诱导的AMPK激活中的作用。结果:cfa诱导的炎性疼痛模型小鼠表现出机械性异常痛和热痛觉过敏。EA对炎症性疼痛有镇痛作用时,激活了炎症皮肤组织中的AMPK。预先给药AMPK抑制剂化合物C显著抑制EA对疼痛的缓解作用。EA升高了炎症皮肤组织中β-END的表达,化合物C逆转了这一变化,表明AMPK在EA诱导β-END表达中具有调节作用。此外,与CFA组相比,EA显著上调了炎症皮肤组织中2-AG、AEA水平和CB2Rs的表达。在野生型小鼠中,EA激活巨噬细胞中的AMPK,而CB2敲除降低了EA激活这些细胞中AMPK的能力。结论:EA通过CB2R激活AMPK,增强炎症皮肤中β-END的表达,减轻炎症性疼痛。本研究揭示了内源性大麻素、内啡肽和AMPK在EA镇痛作用中的新联系,强调了CB2R-AMPK-β-END通路。
{"title":"Electroacupuncture ameliorates inflammatory pain through CB2 receptor-dependent activation of the AMPK signaling pathway.","authors":"Yuye Lan, Xianghong Jing, Ziyu Zhou, Yiqing Rao, Kaichen Wang, Renjie Qin, Yisong Wu, Jingjing Sun, Ke Zhang, Xinyue Liu, Zixiao Wang, Jiahao Xu, Minzhen Zhao, Xiao Cui Yuan, Yongmin Liu, Hong Zhang, Xuefei Hu, Huilin Pan, Tengfei Hou, Man Li","doi":"10.1186/s13020-024-01048-z","DOIUrl":"10.1186/s13020-024-01048-z","url":null,"abstract":"<p><strong>Background: </strong>Chronic inflammatory pain is a pervasive condition, and electroacupuncture (EA) is an effective treatment, but its mechanisms are not fully understood. AMP-activated protein kinase (AMPK), a key energy sensor, is involved in pain relief and EA's effects. EA may work by increasing endocannabinoids, upregulating CB2 receptors (CB2R), and stimulating β-endorphin (β-END). This study tests if EA activates AMPK via CB2R to modulate β-END and reduce pain.</p><p><strong>Methods: </strong>The inflammatory pain model was established with Complete Freund's adjuvant (CFA), and EA was administered daily for six consecutive days, targeting the acupoints \"Zusanli\" (ST36) and \"Shangjuxu\" (ST37). Pain sensitivity was evaluated using Von Frey filaments for mechanical thresholds and a hot plate for thermal thresholds. Ultra-high Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS) was used to quantitatively determine the levels of endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (AEA). The expression levels of the CB2R and β-END were measured by Western blotting, along with the activation of AMPK. Immunofluorescence double-labeling was applied to visualize AMPK activation and β-END expression within CD68-positive macrophages. The study encompassed both wild-type and CB2R gene knockout mice, elucidating the role of CB2R in EA-induced AMPK activation.</p><p><strong>Results: </strong>CFA-induced inflammatory pain model mice exhibited mechanical allodynia and thermal hyperalgesia. EA activated AMPK in the inflamed skin tissue when it exerted analgesic effect on the inflammatory pain. Pre-administration of the AMPK inhibitor Compound C significantly inhibited the effect of EA on pain relief. EA elevated β-END expression in inflamed skin tissue, which was reversed by Compound C, indicating that AMPK has a regulatory role in EA inducing β-END expression. In addition, EA significantly upregulated the levels of 2-AG, AEA and the expression of CB2Rs in the inflamed skin tissue compared with the CFA group. In wild-type mice, EA activates AMPK in macrophages, while CB2 knockout reduced EA's ability to activate AMPK in these cells.</p><p><strong>Conclusion: </strong>EA activates AMPK through CB2R, enhancing β-END expression in inflamed skin to alleviate inflammatory pain. This study reveals a new link between endocannabinoids, endorphins, and AMPK in analgesic effects of EA, highlighting the CB2R-AMPK-β-END pathway.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"19 1","pages":"176"},"PeriodicalIF":5.3,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Gegen-Sangshen oral liquid and its active fractions mitigate alcoholic liver disease in mice through repairing intestinal epithelial injury and regulating gut microbiota. 葛根三参口服液及其有效组分通过修复肠道上皮损伤和调节肠道菌群减轻小鼠酒精性肝病。
IF 5.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-12-23 DOI: 10.1186/s13020-024-01049-y
Shulin Wei, Mingxing Li, Long Zhao, Tiangang Wang, Ke Wu, Jiayue Yang, Yubin Liu, Yueshui Zhao, Fukuan Du, Yu Chen, Shuai Deng, Jing Shen, Zhangang Xiao, Wanping Li, Xiaobing Li, Yuhong Sun, Li Gu, Mei Wei, Zhi Li, Xu Wu
<p><strong>Background: </strong>Liuweizhiji Gegen-Sangshen oral liquid (LGS), as a Chinese medicinal preparation, is developed from a Traditional Chinese medicinal formula consisting of six Chinese medicinal herbs, including Puerariae lobatae radix, Hoveniae semen, Imperatae rhizoma, Crataegi fructus, Mori fructus and Canarli fructus, and has been extensively utilized in the prevention and treatment of alcoholic liver disease (ALD) clinically. Previous study has demonstrated that LGS dose-dependently mitigated ALD in rat models. However, whether and how the main characteristic constituents of LGS (the flavonoid and polysaccharide fractions, LGSF and LGSP) contribute to the anti-ALD effect remains unclear. This study aimed to assess the anti-ALD effect of LGS and its main fractions (LGSF and LGSP) in a murine model of ALD and to explore the underlying mechanisms.</p><p><strong>Methods: </strong>ALD mouse model was constructed using the chronic and binge ethanol feeding method. Biochemical determinations of AST, ALT, TC, TG, ADH, ALDH, HDL, LDL, IL-1β, IL-6, and TNF-α were performed using corresponding kits. Histopathological examination of liver and intestinal sections was conducted based on the H&E staining. Lipid accumulation in hepatocytes was evaluated by oil red O staining. Ethanol metabolism was assessed by determining the activity of ADH and ALDH enzymes. Intestinal barrier function was analyzed based on immunohistochemistry analysis of ZO-1 and occludin and immunofluorescence analysis of epithelial markers, Lgr5, Muc2, and Lyz1. Intestinal epithelial apoptosis was detected by TUNEL staining. Mouse fecal microbiota alterations were analyzed by 16S rRNA sequencing. An in vitro epithelial injury model was established by developing TNF-α-induced 3D-cultured intestinal organoids. In vitro culture of specific bacterial strains was performed.</p><p><strong>Results: </strong>The results showed that LGS and its flavonoid and polysaccharide fractions (LGSF and LGSP) significantly alleviated ALD in mice through attenuating hepatic injury and inflammation, improving liver steatosis and promoting ethanol metabolism. Notably, LGS, LGSP, and LGSF mitigated intestinal damage and maintained barrier function in ALD mice. The intestinal barrier protection function of LGS, LGSP, and LGSF was generally more obvious than that of the positive drug meltadosine. Further study demonstrated that LGS, LGSP, and LGSF promoted intestinal epithelial repair via promoting Lgr5<sup>+</sup> stem cell mediated regeneration in TNF-α-induced intestinal organoids. LGS and LGSF, other than LGSP, had a better effect on repair of epithelial injury in vitro. Moreover, LGS, LGSP, and LGSF remarkably alleviated gut dysbiosis in ALD mice via at least partially recovery of alcohol-induced microbial changes and induction of specific bacterial groups. In vitro culture of bacterial strains indicated that LGS, LGSP, and LGSF had a specific impact on bacterial growth. LGS and LGSP, but not
背景:六味之基葛根三神口服液(LGS)是一种中药制剂,由葛根、黄芪、欧胡根、山楂、桑子、Canarli等六种中草药组成的中药配方研制而成,在临床上广泛应用于酒精性肝病(ALD)的防治。先前的研究表明,LGS剂量依赖性地减轻了大鼠模型中的ALD。然而,LGS的主要特征成分(类黄酮和多糖组分,LGSF和LGSP)是否以及如何参与抗ald作用尚不清楚。本研究旨在评估LGS及其主要组分(LGSF和LGSP)在小鼠ALD模型中的抗ALD作用,并探讨其作用机制。方法:采用慢性酒精狂饮法建立ALD小鼠模型。采用相应试剂盒进行AST、ALT、TC、TG、ADH、ALDH、HDL、LDL、IL-1β、IL-6、TNF-α生化检测。肝、肠切片采用H&E染色进行组织病理学检查。油红O染色评价肝细胞脂质积累。通过测定ADH和ALDH酶的活性来评估乙醇代谢。通过免疫组化分析ZO-1和occludin,免疫荧光分析上皮标志物Lgr5、Muc2和Lyz1,分析肠道屏障功能。TUNEL染色检测肠上皮细胞凋亡。通过16S rRNA测序分析小鼠粪便微生物群的变化。采用TNF-α-诱导的3d培养小肠类器官建立体外上皮损伤模型。对特定菌株进行体外培养。结果:黄芪多糖及其黄酮多糖组分(LGSF和LGSP)通过减轻小鼠肝损伤和炎症,改善肝脏脂肪变性,促进乙醇代谢,显著减轻小鼠ALD。值得注意的是,LGS、LGSP和LGSF减轻了ALD小鼠的肠道损伤并维持了屏障功能。LGS、LGSP、LGSF的肠道屏障保护作用普遍较阳性药物meltadosine更为明显。进一步研究表明,LGS、LGSP和LGSF通过促进Lgr5+干细胞介导的TNF-α-诱导的肠道类器官再生来促进肠上皮修复。LGS和LGSF在体外对上皮损伤的修复效果优于LGSP。此外,LGS、LGSP和LGSF通过至少部分恢复酒精诱导的微生物变化和诱导特定细菌群,显著缓解了ALD小鼠的肠道生态失调。菌株的体外培养表明,LGS、LGSP和LGSF对细菌生长有特定的影响。LGS和LGSP对乳酸菌的生长有显著的促进作用,LGSF对乳酸菌的生长没有显著的促进作用。同样,lggs和LGSP显著增加了缝氏拟杆菌的增殖,LGSF的作用最小。LGS、LGSP和LGSF均能促进凝固芽孢杆菌、青少年双歧杆菌和两歧双歧杆菌的生长。lggs和LGSP对纽约杜波氏菌的生长有促进作用,LGSF没有作用。结论:枸杞多糖通过调节小鼠肠肝轴发挥抗ald作用,其黄酮和多糖组分LGSF和LGSP可能是其保护作用的机制。
{"title":"Gegen-Sangshen oral liquid and its active fractions mitigate alcoholic liver disease in mice through repairing intestinal epithelial injury and regulating gut microbiota.","authors":"Shulin Wei, Mingxing Li, Long Zhao, Tiangang Wang, Ke Wu, Jiayue Yang, Yubin Liu, Yueshui Zhao, Fukuan Du, Yu Chen, Shuai Deng, Jing Shen, Zhangang Xiao, Wanping Li, Xiaobing Li, Yuhong Sun, Li Gu, Mei Wei, Zhi Li, Xu Wu","doi":"10.1186/s13020-024-01049-y","DOIUrl":"10.1186/s13020-024-01049-y","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Liuweizhiji Gegen-Sangshen oral liquid (LGS), as a Chinese medicinal preparation, is developed from a Traditional Chinese medicinal formula consisting of six Chinese medicinal herbs, including Puerariae lobatae radix, Hoveniae semen, Imperatae rhizoma, Crataegi fructus, Mori fructus and Canarli fructus, and has been extensively utilized in the prevention and treatment of alcoholic liver disease (ALD) clinically. Previous study has demonstrated that LGS dose-dependently mitigated ALD in rat models. However, whether and how the main characteristic constituents of LGS (the flavonoid and polysaccharide fractions, LGSF and LGSP) contribute to the anti-ALD effect remains unclear. This study aimed to assess the anti-ALD effect of LGS and its main fractions (LGSF and LGSP) in a murine model of ALD and to explore the underlying mechanisms.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;ALD mouse model was constructed using the chronic and binge ethanol feeding method. Biochemical determinations of AST, ALT, TC, TG, ADH, ALDH, HDL, LDL, IL-1β, IL-6, and TNF-α were performed using corresponding kits. Histopathological examination of liver and intestinal sections was conducted based on the H&E staining. Lipid accumulation in hepatocytes was evaluated by oil red O staining. Ethanol metabolism was assessed by determining the activity of ADH and ALDH enzymes. Intestinal barrier function was analyzed based on immunohistochemistry analysis of ZO-1 and occludin and immunofluorescence analysis of epithelial markers, Lgr5, Muc2, and Lyz1. Intestinal epithelial apoptosis was detected by TUNEL staining. Mouse fecal microbiota alterations were analyzed by 16S rRNA sequencing. An in vitro epithelial injury model was established by developing TNF-α-induced 3D-cultured intestinal organoids. In vitro culture of specific bacterial strains was performed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The results showed that LGS and its flavonoid and polysaccharide fractions (LGSF and LGSP) significantly alleviated ALD in mice through attenuating hepatic injury and inflammation, improving liver steatosis and promoting ethanol metabolism. Notably, LGS, LGSP, and LGSF mitigated intestinal damage and maintained barrier function in ALD mice. The intestinal barrier protection function of LGS, LGSP, and LGSF was generally more obvious than that of the positive drug meltadosine. Further study demonstrated that LGS, LGSP, and LGSF promoted intestinal epithelial repair via promoting Lgr5&lt;sup&gt;+&lt;/sup&gt; stem cell mediated regeneration in TNF-α-induced intestinal organoids. LGS and LGSF, other than LGSP, had a better effect on repair of epithelial injury in vitro. Moreover, LGS, LGSP, and LGSF remarkably alleviated gut dysbiosis in ALD mice via at least partially recovery of alcohol-induced microbial changes and induction of specific bacterial groups. In vitro culture of bacterial strains indicated that LGS, LGSP, and LGSF had a specific impact on bacterial growth. LGS and LGSP, but not ","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"19 1","pages":"175"},"PeriodicalIF":5.3,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Zi Shen Wan Fang repaired blood-brain barrier integrity in diabetic cognitive impairment mice via preventing cerebrovascular cells senescence. 滋肾万方通过防止脑血管细胞衰老修复糖尿病认知障碍小鼠血脑屏障完整性。
IF 5.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-12-19 DOI: 10.1186/s13020-024-01041-6
Qingsheng Yin, Genhui Yang, Runtao Su, Jie Bu, Ying Li, Han Zhang, Yanjun Zhang, Pengwei Zhuang
<p><strong>Background: </strong>Blood-brain barrier (BBB) integrity disruption is a key pathological link of diabetes-induced cognitive impairment (DCI), but the detailed mechanism of how the diabetic environment induces BBB integrity disruption is not fully understood. Our previous study found that Zi Shen Wan Fang (ZSWF), an optimized prescription consisting of Anemarrhenae Rhizoma (Anemarrhena asphodeloides Bge.), Phellodendri Chinensis Cortex (Phellodendron chinense Schneid.) and Cistanches Herba (Cistanche deserticola Y.C.Ma) has excellent efficacy in alleviating DCI, however, whether its mechanism is related to repairing BBB integrity remains unclear. This study aims to reveal the mechanism of BBB integrity destruction in DCI mice, and to elucidate the mechanism by which ZSWF repairs BBB integrity and improves cognitive function in DCI mice.</p><p><strong>Methods: </strong>Diabetic mouse model was established by feeding a 60% high-fat diet combined with a single intraperitoneal injection of 120 mg/kg streptozotocin (STZ). DCI mice were screened with morris water maze (MWM) after 8 weeks of sustained hyperglycemic stimulation. ZSWF was administered daily at doses of 9.36 and 18.72 g/kg for 8 weeks. Cognitive function was evaluated using MWM, blood-brain-barrier (BBB) integrity was tested using immunostaining and western blot, the underlying mechanisms were explored using single-cell RNA sequencing (scRNA-seq), validation experiments were performed with immunofluorescence analysis, and the potential active ingredients of ZSWF against cerebrovascular senescence were predicted using molecular docking. Moreover, cerebral microvascular endothelial cells were cultured, and the effects of mangiferin on the expression of p21 and Vcam1 were investigated by immunofluorescence staining and RT-qPCR.</p><p><strong>Results: </strong>ZSWF treatment significantly ameliorated cognitive function and repaired BBB integrity in DCI mice. Using scRNA-seq, we identified 14 brain cell types. In BBB constituent cells (endothelial cells and pericytes), we found that Cdkn1a and senescence-associated secretory phenotype (SASP) genes were significantly overexpressed in DCI mice, while ZSWF intervention significantly inhibited the expression of Cdkn1a and SASP genes in cerebrovascular cells of DCI mice. Moreover, we also found that the communication between brain endothelial cells and pericytes was decreased in DCI mice, while ZSWF significantly increased the communication between them, especially the expression of PDGFRβ in pericytes. Molecular docking results showed that mangiferin, the blood component of ZSWF, had a stronger affinity with the upstream proteins of p21. In vitro experiments showed that high glucose significantly increased the expression of p21 and Vcam1 in bEnd.3 cells, while mangiferin significantly inhibited the expression of p21 and Vcam1 induced by high glucose.</p><p><strong>Conclusion: </strong>Our study reveals that ZSWF can ameliorate cognitive
背景:血脑屏障(BBB)完整性破坏是糖尿病诱导认知障碍(DCI)的一个关键病理环节,但糖尿病环境诱导血脑屏障完整性破坏的详细机制尚不完全清楚。我们前期研究发现,由知母(anemarhena asphodeloides Bge.)、黄柏皮(Phellodendron chinense Schneid.)和肉苁蓉(Cistanche deserticola Y.C.Ma)组成的优化方紫参丸方(ZSWF .)对DCI有良好的缓解作用,但其机制是否与修复血脑屏障完整性有关尚不清楚。本研究旨在揭示DCI小鼠血脑屏障完整性破坏的机制,阐明ZSWF修复DCI小鼠血脑屏障完整性和改善认知功能的机制。方法:采用60%高脂饲料饲养,腹腔注射链脲佐菌素(STZ) 120 mg/kg,建立糖尿病小鼠模型。持续高血糖刺激8周后,采用morris水迷宫(MWM)筛选DCI小鼠。ZSWF每天以9.36和18.72 g/kg的剂量给药,持续8周。采用MWM评估认知功能,采用免疫染色和western blot检测血脑屏障(BBB)完整性,采用单细胞RNA测序(scRNA-seq)探索其潜在机制,采用免疫荧光分析进行验证实验,并通过分子对接预测ZSWF抗脑血管衰老的潜在有效成分。培养脑微血管内皮细胞,采用免疫荧光染色和RT-qPCR检测芒果苷对p21和Vcam1表达的影响。结果:ZSWF治疗可显著改善DCI小鼠的认知功能并修复血脑屏障完整性。使用scRNA-seq,我们鉴定了14种脑细胞类型。在血脑屏障组成细胞(内皮细胞和周细胞)中,我们发现Cdkn1a和衰老相关分泌表型(SASP)基因在DCI小鼠中显著过表达,而ZSWF干预显著抑制了DCI小鼠脑血管细胞中Cdkn1a和SASP基因的表达。此外,我们还发现DCI小鼠脑内皮细胞与周细胞之间的通讯减少,而ZSWF显著增加了它们之间的通讯,特别是PDGFRβ在周细胞中的表达。分子对接结果表明,ZSWF的血液成分芒果苷与p21上游蛋白具有较强的亲和力。体外实验表明,高糖显著提高了bEnd组织中p21和Vcam1的表达。芒果苷显著抑制高糖诱导的p21和Vcam1的表达。结论:我们的研究表明,ZSWF可通过修复血脑屏障完整性改善DCI小鼠的认知功能,其具体机制可能与防止脑血管细胞衰老有关,芒果苷是其关键活性成分。
{"title":"Zi Shen Wan Fang repaired blood-brain barrier integrity in diabetic cognitive impairment mice via preventing cerebrovascular cells senescence.","authors":"Qingsheng Yin, Genhui Yang, Runtao Su, Jie Bu, Ying Li, Han Zhang, Yanjun Zhang, Pengwei Zhuang","doi":"10.1186/s13020-024-01041-6","DOIUrl":"10.1186/s13020-024-01041-6","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Blood-brain barrier (BBB) integrity disruption is a key pathological link of diabetes-induced cognitive impairment (DCI), but the detailed mechanism of how the diabetic environment induces BBB integrity disruption is not fully understood. Our previous study found that Zi Shen Wan Fang (ZSWF), an optimized prescription consisting of Anemarrhenae Rhizoma (Anemarrhena asphodeloides Bge.), Phellodendri Chinensis Cortex (Phellodendron chinense Schneid.) and Cistanches Herba (Cistanche deserticola Y.C.Ma) has excellent efficacy in alleviating DCI, however, whether its mechanism is related to repairing BBB integrity remains unclear. This study aims to reveal the mechanism of BBB integrity destruction in DCI mice, and to elucidate the mechanism by which ZSWF repairs BBB integrity and improves cognitive function in DCI mice.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Diabetic mouse model was established by feeding a 60% high-fat diet combined with a single intraperitoneal injection of 120 mg/kg streptozotocin (STZ). DCI mice were screened with morris water maze (MWM) after 8 weeks of sustained hyperglycemic stimulation. ZSWF was administered daily at doses of 9.36 and 18.72 g/kg for 8 weeks. Cognitive function was evaluated using MWM, blood-brain-barrier (BBB) integrity was tested using immunostaining and western blot, the underlying mechanisms were explored using single-cell RNA sequencing (scRNA-seq), validation experiments were performed with immunofluorescence analysis, and the potential active ingredients of ZSWF against cerebrovascular senescence were predicted using molecular docking. Moreover, cerebral microvascular endothelial cells were cultured, and the effects of mangiferin on the expression of p21 and Vcam1 were investigated by immunofluorescence staining and RT-qPCR.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;ZSWF treatment significantly ameliorated cognitive function and repaired BBB integrity in DCI mice. Using scRNA-seq, we identified 14 brain cell types. In BBB constituent cells (endothelial cells and pericytes), we found that Cdkn1a and senescence-associated secretory phenotype (SASP) genes were significantly overexpressed in DCI mice, while ZSWF intervention significantly inhibited the expression of Cdkn1a and SASP genes in cerebrovascular cells of DCI mice. Moreover, we also found that the communication between brain endothelial cells and pericytes was decreased in DCI mice, while ZSWF significantly increased the communication between them, especially the expression of PDGFRβ in pericytes. Molecular docking results showed that mangiferin, the blood component of ZSWF, had a stronger affinity with the upstream proteins of p21. In vitro experiments showed that high glucose significantly increased the expression of p21 and Vcam1 in bEnd.3 cells, while mangiferin significantly inhibited the expression of p21 and Vcam1 induced by high glucose.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Our study reveals that ZSWF can ameliorate cognitive ","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"19 1","pages":"169"},"PeriodicalIF":5.3,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11657355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Zhishi Xiebai Guizhi Decoction modulates hypoxia and lipid toxicity to alleviate pulmonary vascular remodeling of pulmonary hypertension in rats. 枳实泻白桂枝汤调节缺氧和脂质毒性减轻肺动脉高压大鼠肺血管重构。
IF 5.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-12-19 DOI: 10.1186/s13020-024-01039-0
Min Fu, Yuan Li, Jingjing Liu, Junjie Liu, Jiaoxia Wei, Yuxin Qiao, Hanxin Zhong, Dongyang Han, Haitao Lu, Li Yao

Background: Pulmonary hypertension (PH) is a severe cardio-pulmonary vascular disease, involves complex molecular mechanism especially during the pathological process of pulmonary vascular remodeling, brings a significant challenge to clinical treatment and thus resulting in high mortality rates. Classic Traditional Chinese medicine formula, Zhishi Xiebai Guizhi Decoction (ZXGD), holds therapeutic potential for PH. In present study, we sought to explore therapeutic potential of ZXGD against PH in rats.

Methods: We employed a combination methods of chemical profiling, echocardiographic, morphologic measurements, molecular biology, rats models and cultured pulmonary artery smooth muscle cells (PASMCs) to achieve this.

Results: Eighteen compounds were precisely identified in ZXGD using UHPLC-QTOF-MS/MS. Our data demonstrated ZXGD could alleviate PH by reducing pulmonary artery pressure and alleviating pulmonary vascular remodeling in rats. Specifically, ZXGD was found to intervene in abnormal expansion of PASMCs, thereby attenuating pulmonary vascular remodeling. ZXGD was also observed to modulate expressions of HIF-1α, ROS, and Nrf2 to alleviate hypoxia and oxidative stress. Additionally, ZXGD significantly regulated disorders in pro-inflammatory cytokines, thus mitigating inflammation. Furthermore, ZXGD decreased levels of decadienyl-L-carnitine and LDL-C, while elevating HDL-C and lipid droplet counts, thereby reducing cholesterol and lipid toxicity and preserving mitochondrial function. Importantly, inhibition of HIF-1α reversed expression of key pathological triggers for pulmonary vascular remodeling. Neohesperidin and naringin in ZXGD extract were identified as the primary contributors to its pharmacological effects against PH.

Conclusion: Altogether, our study empirically explored therapeutic potential and pharmacological mechanisms of ZXGD in treating PH, offering a groundwork for the development of novel anti-PH drugs.

背景:肺动脉高压(Pulmonary hypertension, PH)是一种严重的心肺血管疾病,涉及复杂的分子机制,特别是在肺血管重塑的病理过程中,给临床治疗带来了巨大的挑战,导致了很高的死亡率。中药经典方剂枳实泻白桂枝汤(ZXGD)具有治疗PH的潜力。本研究旨在探讨枳实泻白桂枝汤对大鼠PH的治疗潜力。方法:采用化学分析、超声心动图、形态学测量、分子生物学、大鼠模型和培养肺动脉平滑肌细胞(PASMCs)相结合的方法。结果:采用UHPLC-QTOF-MS/MS技术,对18个化合物进行了精确鉴定。我们的数据表明,ZXGD可以通过降低大鼠肺动脉压和减轻肺血管重构来减轻PH。具体来说,ZXGD可以干预pasmc的异常扩张,从而减弱肺血管重构。ZXGD还可调节HIF-1α、ROS和Nrf2的表达,减轻缺氧和氧化应激。此外,ZXGD显著调节促炎细胞因子紊乱,从而减轻炎症。此外,ZXGD降低了十烯基左旋肉碱和LDL-C水平,同时提高了HDL-C和脂滴计数,从而降低了胆固醇和脂质毒性,并保持了线粒体功能。重要的是,抑制HIF-1α逆转了肺血管重构的关键病理触发因子的表达。结论:本研究通过实证研究,探索了枳实提取物对PH的治疗潜力和作用机制,为开发新型抗PH药物奠定了基础。
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引用次数: 0
Integrated analysis of metabolome, lipidome, and gut microbiome reveals the immunomodulation of Astragali radix in healthy human subjects. 综合分析代谢组、脂质组和肠道微生物组揭示了黄芪对健康人体的免疫调节作用。
IF 5.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-12-19 DOI: 10.1186/s13020-024-01045-2
Wan-Yu Gui, Jun-Gang Yin, Jian-Cheng Liao, Hui-Zhi Luo, Qing You, Jia-Hui Gong, Jie Xiang, Jian-Dong Zou, Chang-Yin Li

Background: As a typical medicinal food homology species, Chinese herbal medicine Astragali radix (AR) has been widely used to regulate the human immune system worldwide. However, the human immunomodulation of AR and its corresponding mechanisms remain unclear.

Methods: First, following a fortnight successive AR administration, the changes in immune cytokines and immune cells from 20 healthy human subjects were used as immune indicators to characterize the immunomodulatory effects of AR. Subsequently, ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) based lipidomics and metabolomics analysis was performed on human serum, urine, and feces samples to investigate the changes in metabolic profiles. Then, 16S rRNA gene sequencing of feces samples was adopted for the changes of human gut microbiota. Finally, correlation analysis was conducted on the gut microbiome, metabolome/lipidome data, and immune indicators.

Results: AR displayed good safety in clinical use and posed a minor impact on gut microbiota major genera, global metabolic profiles, and immune cells. Meanwhile, AR could significantly up-regulate anti-inflammatory cytokines, down-regulate serum creatinine and pro-inflammatory cytokines, promote the anabolism of arginine, glycerolipid, sphingolipid, and purine, and the catabolism of phenylalanine and glycerophospholipid. Moreover, these AR-induced changes were closely correlated with significantly decreased Granulicatella, slightly higher Bifidobacterium, Ruminococcus, and Subdoligranulum, and slightly lower Blautia.

Conclusion: The study clearly demonstrated that AR could modulate the human immune, by modifying the metabolism of amino acids, lipids, and purines in a microbiota-related way. Trial registration ChiCTR, ChiCTR2100054765. Registered 26 December 2021-Prospectively registered, https://www.chictr.org.cn/historyversionpub.html?regno=ChiCTR2100054765.

背景:中草药黄芪(Astragali radix, AR)作为一种典型的药用食品同源物种,在世界范围内被广泛用于调节人体免疫系统。然而,人类对AR的免疫调节及其相应的机制尚不清楚。方法:首先,在连续给药两周后,将20名健康受试者的免疫细胞因子和免疫细胞的变化作为免疫指标来表征AR的免疫调节作用。随后,基于超高效液相色谱-四极杆飞行时间质谱(UHPLC-Q-TOF/MS)的脂质组学和代谢组学分析对人血清、尿液、以及粪便样本来研究代谢谱的变化。然后,对粪便样本进行16S rRNA基因测序,了解人体肠道菌群的变化。最后,对肠道微生物组、代谢组/脂质组数据和免疫指标进行相关性分析。结果:AR在临床应用中表现出良好的安全性,对肠道微生物群、主要属、整体代谢谱和免疫细胞的影响较小。同时,AR能显著上调抗炎细胞因子,下调血清肌酐和促炎细胞因子,促进精氨酸、甘油脂、鞘脂和嘌呤的合成代谢,以及苯丙氨酸和甘油磷脂的分解代谢。此外,ar诱导的这些变化与Granulicatella显著减少,Bifidobacterium、Ruminococcus和Subdoligranulum略高,Blautia略低密切相关。结论:本研究清楚地表明,AR可以通过与微生物群相关的方式改变氨基酸、脂质和嘌呤的代谢来调节人的免疫。试验注册ChiCTR, ChiCTR2100054765。已注册2021年12月26日-已注册,https://www.chictr.org.cn/historyversionpub.html?regno=ChiCTR2100054765。
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引用次数: 0
Pulsatilla chinensis functions as a novel antihyperlipidemic agent by upregulating LDLR in an ERK-dependent manner. 白头草是一种新型的抗高脂血症药物,通过erk依赖性的方式上调LDLR。
IF 5.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-12-19 DOI: 10.1186/s13020-024-01044-3
Wei-Fang Song, Rui-Jun Wang, Rui-Xin Yao, Qiu-Yan Jiang, Juan Feng, Kun Luo, Zheng-Han Di, Cheng-Mei Ma, Lan Xie

Background: Pulsatilla chinensis (PC) is a traditional Chinese medicine (TCM) known for its beneficial activities. It has been historically used to treat dysentery, vaginal trichomoniasis, bacterial infections, and malignant tumors. The therapeutic potential of PC in the management of hypercholesterolemia remains largely unexplored.

Methods: A high-throughput screening based on high-throughput sequencing was conducted in HepG2 cells to construct gene expression profiles for several hundred TCMs. In vivo evaluation of the efficacy of PC was performed using rats with hypercholesterolemia. Transcriptome analysis was carried out on PC-treated rat livers and HepG2 cells to investigate the mechanism of action of PC in vitro. The findings were further validated using RT-qPCR and western blot techniques.

Results: PC was identified as similar to Rhizoma Coptidis based on signature genes related to metabolism. Administration of PC via gavage in rats with hypercholesterolemia for 11 weeks resulted in substantially reduced serum total cholesterol and low-density lipoprotein (LDL) cholesterol and ameliorated fatty liver. Transcriptome analysis revealed that PC regulated various pathways associated with lipid metabolism. The LDL receptor (LDLR), a key player in cholesterol metabolism, was upregulated by PC both in vivo and in vitro. It was discovered that PC achieved this upregulation by activating extracellular regulated protein kinase (ERK) signaling in HepG2 cells. To uncover the major bioactive components responsible for the anti- hypercholesterolemia effect of PC, two major saponins, named Pulsatilla saponin D (PCD) and PC anemoside B4 (PCB4), were assessed. PCD, but not PCB4, was identified as the active ingredient responsible for the upregulation of LDLR by PC.

Conclusion: These findings demonstrated that PC acts as an antihypercholesterolemic agent by upregulating LDLR in an ERK-dependent manner and holds potential in the treatment of hypercholesterolemia.

背景:白头翁(pulsatila chinensis, PC)是一种以其有益活性而闻名的传统中药。它历来被用于治疗痢疾、阴道滴虫病、细菌感染和恶性肿瘤。PC在治疗高胆固醇血症方面的治疗潜力仍未得到充分的探索。方法:采用高通量测序技术对HepG2细胞进行高通量筛选,构建数百种中药HepG2细胞基因表达谱。用高胆固醇血症大鼠进行体内评价。对PC处理的大鼠肝脏和HepG2细胞进行转录组分析,探讨PC的体外作用机制。使用RT-qPCR和western blot技术进一步验证了研究结果。结果:根据代谢相关的特征基因,鉴定出黄连与黄连相似。高胆固醇血症大鼠灌胃给予PC 11周,可显著降低血清总胆固醇和低密度脂蛋白(LDL)胆固醇,改善脂肪肝。转录组分析显示,PC调节与脂质代谢相关的多种途径。低密度脂蛋白受体(LDL receptor, LDLR)是胆固醇代谢的关键角色,在体内和体外均被PC上调。研究发现,PC通过激活HepG2细胞中的细胞外调节蛋白激酶(ERK)信号来实现这种上调。为了揭示白头翁抗高胆固醇血症作用的主要生物活性成分,对白头翁皂苷D (PCD)和白头翁皂苷B4 (PCB4)两种主要皂苷进行了评价。PCD,而不是PCB4,被确定为PC上调LDLR的活性成分。结论:这些发现表明,PC作为一种抗高胆固醇药物,通过erk依赖的方式上调LDLR,并在治疗高胆固醇血症方面具有潜力。
{"title":"Pulsatilla chinensis functions as a novel antihyperlipidemic agent by upregulating LDLR in an ERK-dependent manner.","authors":"Wei-Fang Song, Rui-Jun Wang, Rui-Xin Yao, Qiu-Yan Jiang, Juan Feng, Kun Luo, Zheng-Han Di, Cheng-Mei Ma, Lan Xie","doi":"10.1186/s13020-024-01044-3","DOIUrl":"10.1186/s13020-024-01044-3","url":null,"abstract":"<p><strong>Background: </strong>Pulsatilla chinensis (PC) is a traditional Chinese medicine (TCM) known for its beneficial activities. It has been historically used to treat dysentery, vaginal trichomoniasis, bacterial infections, and malignant tumors. The therapeutic potential of PC in the management of hypercholesterolemia remains largely unexplored.</p><p><strong>Methods: </strong>A high-throughput screening based on high-throughput sequencing was conducted in HepG2 cells to construct gene expression profiles for several hundred TCMs. In vivo evaluation of the efficacy of PC was performed using rats with hypercholesterolemia. Transcriptome analysis was carried out on PC-treated rat livers and HepG2 cells to investigate the mechanism of action of PC in vitro. The findings were further validated using RT-qPCR and western blot techniques.</p><p><strong>Results: </strong>PC was identified as similar to Rhizoma Coptidis based on signature genes related to metabolism. Administration of PC via gavage in rats with hypercholesterolemia for 11 weeks resulted in substantially reduced serum total cholesterol and low-density lipoprotein (LDL) cholesterol and ameliorated fatty liver. Transcriptome analysis revealed that PC regulated various pathways associated with lipid metabolism. The LDL receptor (LDLR), a key player in cholesterol metabolism, was upregulated by PC both in vivo and in vitro. It was discovered that PC achieved this upregulation by activating extracellular regulated protein kinase (ERK) signaling in HepG2 cells. To uncover the major bioactive components responsible for the anti- hypercholesterolemia effect of PC, two major saponins, named Pulsatilla saponin D (PCD) and PC anemoside B4 (PCB4), were assessed. PCD, but not PCB4, was identified as the active ingredient responsible for the upregulation of LDLR by PC.</p><p><strong>Conclusion: </strong>These findings demonstrated that PC acts as an antihypercholesterolemic agent by upregulating LDLR in an ERK-dependent manner and holds potential in the treatment of hypercholesterolemia.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"19 1","pages":"172"},"PeriodicalIF":5.3,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11657699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Temporal, spatial and demographic distributions characteristics of COVID-19 symptom clusters from chinese medicine perspective: a systematic cross-sectional study in China from 2019 to 2023. 基于中医视角的2019 - 2023年中国新冠肺炎症状聚类时空分布特征及人口统计学研究
IF 5.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-12-18 DOI: 10.1186/s13020-024-01043-4
Bin Liu, Tian Song, Mingzhi Hu, Zhaoyuan Gong, Qianzi Che, Jing Guo, Lin Chen, Haili Zhang, Huizhi Li, Ning Liang, Jing Wan, Kunfeng Wang, Yanping Wang, Nannan Shi, Luqi Huang
<p><strong>Background: </strong>The subtypes diagnosis of disease symptom clusters, grounded in the theory of "Treatment in Accordance with Three Categories of Etiologic Factors" and International Classification of Diseases 11th Revision (ICD-11), is a vital strategy for Chinese Medicine (CM) in treating unknown respiratory infectious diseases. However, the classification of disease symptom clusters continues to depend on empirical observations and lacks robust scientific evidence. Consequently, this study seeks to explore the temporal, spatial and demographic distributions characteristics of Corona Virus Disease 2019 (COVID-19) symptom clusters in China.</p><p><strong>Methods: </strong>PubMed, Web of Science, Science direct, WHO, Litcovid, CNKI databases were searched from inception until December 31, 2023. Optical character recognition technology and image recognition technology were employed to identify tables within the papers. Four researchers independently screened and extracted data, resolving conflicts through discussion. Heat mapping and hierarchical clustering techniques were utilized to analyze COVID-19 symptom clusters. Data analysis and visualization were conducted using R software (4.2.0), while the association analysis of symptom clusters was performed using Cytoscape (3.10.2).</p><p><strong>Results: </strong>A total of 366 COVID-19 clinical trials with 86,972 cases including 66 clinical symptoms of 7 disease systems and other clinical manifestations in China were included. In temporal distribution, 63 symptoms centered around fatigue and 44 symptoms focused on chest tightness are characteristic of symptom clusters in spring and winter, respectively. With the addition of spatial distribution, the symptom clusters in middle and low latitudes during spring are characterized by 53 symptoms centered around fatigue and cough, and 51 symptoms focused on fatigue, respectively. During winter, the symptom clusters in middle and low latitudes are characterized by 38 symptoms centered around chest tightness and 37 symptoms focused on fever, respectively. When considering demographic distribution, the symptom clusters for < 50 years are characterized by fatigue as the core symptom in middle (44 symptoms)/low (28 symptoms) latitudes during spring and middle latitude (25 symptoms) during winter. For ≥ 50 years, the symptom clusters in middle latitude (49 symptoms) during spring and low latitudes (35 symptoms) during winter are centered around cough, while in low latitude (27 symptoms) focuses on diarrhea during spring, and middle latitude (35 symptoms) emphasizes both diarrhea and chest tightness during winter.</p><p><strong>Conclusion: </strong>In summary, variations in symptom clusters and core symptoms of COVID-19 in temporal, spatial and demographic distributions in China offer a scientific rationale for the "Treatment in Accordance with Three Categories of Etiologic Factors" theory. These interesting findings prompt further investigation in
背景:基于“三因分治”理论和国际疾病分类第11版(ICD-11)的疾病症状群亚型诊断是中医治疗未知呼吸道传染病的重要策略。然而,疾病症状群的分类仍然依赖于经验观察,缺乏有力的科学证据。因此,本研究旨在探讨中国2019冠状病毒病(COVID-19)症状聚类的时间、空间和人口分布特征。方法:检索自建库至2023年12月31日的PubMed、Web of Science、Science direct、WHO、Litcovid、CNKI数据库。采用光学字符识别技术和图像识别技术对论文中的表格进行识别。四位研究者独立筛选和提取数据,通过讨论解决冲突。利用热图和分层聚类技术分析COVID-19症状聚类。采用R软件(4.2.0)进行数据分析和可视化,采用Cytoscape软件(3.10.2)进行症状聚类的关联分析。结果:全国共纳入新冠肺炎临床试验366项,病例86972例,包括7个疾病系统的66种临床症状及其他临床表现。在时间分布上,以疲劳为中心的症状有63种,以胸闷为中心的症状有44种,分别是春季和冬季症状群的特征。加上空间分布因素,春季中低纬度地区以疲劳、咳嗽为中心的症状群有53种,以疲劳为中心的症状群有51种。冬季中低纬度地区以胸闷为中心的症状群有38种,以发热为中心的症状群有37种。结论:综上所述,中国新冠肺炎症状群和核心症状在时间、空间和人口分布上的变化,为“三因分治”理论提供了科学依据。这些有趣的发现促使人们进一步研究ICD-11中的CM模式,并提出个性化精准治疗COVID-19的潜在策略。有必要对个体症状进行高质量的临床研究,以加强对呼吸道传染病的了解。
{"title":"Temporal, spatial and demographic distributions characteristics of COVID-19 symptom clusters from chinese medicine perspective: a systematic cross-sectional study in China from 2019 to 2023.","authors":"Bin Liu, Tian Song, Mingzhi Hu, Zhaoyuan Gong, Qianzi Che, Jing Guo, Lin Chen, Haili Zhang, Huizhi Li, Ning Liang, Jing Wan, Kunfeng Wang, Yanping Wang, Nannan Shi, Luqi Huang","doi":"10.1186/s13020-024-01043-4","DOIUrl":"10.1186/s13020-024-01043-4","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The subtypes diagnosis of disease symptom clusters, grounded in the theory of \"Treatment in Accordance with Three Categories of Etiologic Factors\" and International Classification of Diseases 11th Revision (ICD-11), is a vital strategy for Chinese Medicine (CM) in treating unknown respiratory infectious diseases. However, the classification of disease symptom clusters continues to depend on empirical observations and lacks robust scientific evidence. Consequently, this study seeks to explore the temporal, spatial and demographic distributions characteristics of Corona Virus Disease 2019 (COVID-19) symptom clusters in China.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;PubMed, Web of Science, Science direct, WHO, Litcovid, CNKI databases were searched from inception until December 31, 2023. Optical character recognition technology and image recognition technology were employed to identify tables within the papers. Four researchers independently screened and extracted data, resolving conflicts through discussion. Heat mapping and hierarchical clustering techniques were utilized to analyze COVID-19 symptom clusters. Data analysis and visualization were conducted using R software (4.2.0), while the association analysis of symptom clusters was performed using Cytoscape (3.10.2).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 366 COVID-19 clinical trials with 86,972 cases including 66 clinical symptoms of 7 disease systems and other clinical manifestations in China were included. In temporal distribution, 63 symptoms centered around fatigue and 44 symptoms focused on chest tightness are characteristic of symptom clusters in spring and winter, respectively. With the addition of spatial distribution, the symptom clusters in middle and low latitudes during spring are characterized by 53 symptoms centered around fatigue and cough, and 51 symptoms focused on fatigue, respectively. During winter, the symptom clusters in middle and low latitudes are characterized by 38 symptoms centered around chest tightness and 37 symptoms focused on fever, respectively. When considering demographic distribution, the symptom clusters for &lt; 50 years are characterized by fatigue as the core symptom in middle (44 symptoms)/low (28 symptoms) latitudes during spring and middle latitude (25 symptoms) during winter. For ≥ 50 years, the symptom clusters in middle latitude (49 symptoms) during spring and low latitudes (35 symptoms) during winter are centered around cough, while in low latitude (27 symptoms) focuses on diarrhea during spring, and middle latitude (35 symptoms) emphasizes both diarrhea and chest tightness during winter.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;In summary, variations in symptom clusters and core symptoms of COVID-19 in temporal, spatial and demographic distributions in China offer a scientific rationale for the \"Treatment in Accordance with Three Categories of Etiologic Factors\" theory. These interesting findings prompt further investigation in","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"19 1","pages":"171"},"PeriodicalIF":5.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11654152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Chinese Medicine
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