BACKGROUND:Due to the absence of disease-modifying treatments and mysterious molecular causes, metabolic dysfunction-associated steatotic liver disease (MASLD) poses an urgent and unmet clinical need. The active ingredient in Fructus gardenia, geniposidic acid (GPA), has anti-inflammatory, antioxidant, and hepato-protective properties. However, its effects on MASLD are still unknown. PURPOSE:This study aimed to determine how diet-induced hepatic steatosis in mice is affected by GPA. METHODS:Dietary induction developed the mouse model of hepatic steatosis. The influence of GPA on hepatic steatosis, inflammation, and fibrosis were examined using the mouse primary hepatocyte lipid overload model. The mechanism of GPA in preventing and treating MASLD was explored through RNA-seq, and the activation of the SIRT6 signal by GPA was verified by molecular docking, pull-down, etc. Hepatocyte-specific Sirt6-deletion mice were established, and cellular and animal studies were performed to assess SIRT6 functions in inhibiting and treating MASLD by GPA. RESULTS:GPA therapy significantly enhanced hepatic fat accumulation, oxidative stress, inflammatory infiltration, and fibrosis in mice subjected to high fat diet (HFD) and methionine choline deficient (MCD) diets. In the meantime, GPA can reduce oxidative stress in hepatocyte metabolic stress and fat buildup brought on by oleic acid (OA) and palmitic acid (PA). RNA sequencing revealed that GPA exerts its protective effects against MASLD primarily by stimulating SIRT6 and triggering the downstream PPARα signaling cascade. Furthermore, GPA was found to interact directly with SIRT6 through specific binding sites. This interaction enables SIRT6 activation under both normal and disease conditions. However, without SIRT6, the liver-protective benefits of GPA under metabolic stress are lost. CONCLUSION:It was found that GPA binds directly to SIRT6 and enhances its activity, thereby inhibiting the progression of diet-induced MASLD. The findings suggest the potential of GPA as a therapeutic target for treating MASLD.

ETHNOPHARMACOLOGICAL RELEVANCE:The Timosaponin BⅡ (TBⅡ) is one of the main active components of the traditional Chinese medicine Anemarrhena asphodeloides, and it is a steroidal saponin with various pharmacological activities such as anti-oxidation, anti-inflammatory and anti-apoptosis. However, its role in acute ulcerative colitis remains unexplored thus far. AIM OF THE STUDY:This study aims to investigate the protective effect of TBⅡ against dextran sulfate sodium (DSS)-induced ulcerative colitis in mice and elucidate its underlying mechanisms. METHODS:Wild-type (WT) and NLRP3 knockout (NLRP3-/-) mice were applied to evaluate the protective effect of TBⅡ in DSS-induced mice colitis. Pharmacological inhibition of NLRP3 or adenovirus-mediated NLRP3 overexpression in bone marrow-derived macrophages (BMDM) from WT mice and colonic epithelial HCoEpiC cells was used to assess the role of TBⅡ in LPS + ATP-induced cell model. RNA-seq, ELISA, western blots, immunofluorescence staining, and expression analysis by qPCR were performed to examine the alterations of colonic NLRP3 expression in DSS-induced colon tissues and LPS + ATP-induced cells, respectively. RESULTS:In mice with DSS-induced ulcerative colitis, TBⅡ treatment attenuated clinical symptoms, repaired the intestinal mucosal barrier, reduced inflammatory infiltration, and alleviated colonic inflammation. RNA-seq analysis and protein expression levels demonstrated that TBⅡ could prominently inhibit NLRP3 signaling. TBⅡ-mediated NLRP3 inhibition was associated with alleviating intestinal permeability and inflammatory response via the blockage of communication between epithelial cells and macrophages, probably in an NLRP3 inhibition mechanism. However, pharmacological inhibition of NLRP3 by MCC950 or Ad-NLRP3 mediated NLRP3 overexpression significantly impaired the TBⅡ-mediated anti-inflammatory effect. Mechanistically, TBⅡ-mediated NLRP3 inhibition may be partly associated with the suppression of NF-κB, a master pro-inflammatory factor for transcriptional regulation of NLRP3 expression in the priming step. Moreover, co-treatment TBⅡ with NF-κB inhibitor BAY11-7082 partly impaired TBⅡ-mediated NLRP3 inhibition, and consequently affected the IL-1β mature and secretion. Importantly, TBⅡ-mediated amelioration was not further enhanced in NLPR3-/- mice. CONCLUSION:TBⅡ exerted a prominent protective effect against DSS-induced colitis via regulation of alleviation of intestinal permeability and inflammatory response via the blockage of crosstalk between epithelial cells and macrophages in an NLRP3-mediated inhibitory mechanism. These beneficial effects could make TBⅡ a promising drug for relieving colitis.

[目的]运用网络药理学及分子对接探讨黄芪散治疗2型糖尿病(T2DM)的作用机制.[方法]通过中药系统药理学分析平台(TCMSP)查找黄芪散组方中黄芪、葛根、桑白皮的的活性成分和作用靶点,通过GeneCards和OMIM数据库查询与T2DM相关的疾病靶点,通过UniProt数据库查询成分和疾病靶点对应的基因名,利用Cytoscape 3.6.1软件构建黄芪散活性成分-靶点网络、蛋白相互作用(PPI)网络,并通过Merge功能构建疾病-成分-靶点网络,筛选出黄芪散治疗T2DM的核心靶点,最后通过DAVID数据库对核心靶点蛋白进行基因本体论(GO)生物过程分析及京都基因与基因组百科全书(KEGG)通路富集分析,预测其作用机制,并绘制GO和KEGG气泡图进行数据可视化.[结果]研究得到包括槲皮素、山柰酚、刺芒柄花素等在内的38个活性成分和ESR1、JUN、PTGS2、AKT1和MAPK1等75个关键靶点.GO功能富集分析得到113个GO条目(P<0.05),主要包括蛋白酪氨酸激酶活性、生长因子活性和核受体活性等生物过程,KEGG富集得到157条信号通路(P<0.05),主要涉及晚期糖基化终末产物(AGEs)-晚期糖基化终末产物受体(RAGE)信号通路、肿瘤坏死因子(TNF)信号通路、磷脂酰肌醇3-激酶(PI3K)/Akt信号通路等.[结论]黄芪散治疗T2DM可能的机制是通过抑制炎症因子分泌,参与抗炎反应,降低氧化应激,激活PI3K/Akt通路等来改善胰岛素抵抗,提高胰岛素敏感性,降低血糖.

BACKGROUND Some studies have reported the correlation between Helicobacter pylori and celiac disease (CD), but the results lack consistency. This meta-analysis aimed to quantify the relationship between H. pylori and CD. In addition, the study also analyzed the impact of H. pylori on the symptoms and classification of CD. METHODS Studies published up to September 1, 2020 on 3 databases - EMBASE, MEDICINE, and PubMed - were searched. The statistical data of articles which met the requirements were collated and extracted. RESULTS Twenty-five papers and 141 355 participants were finally enrolled. The results showed that the H. pylori infection rate of CD patients was 0.57 times greater compared to controls (OR = 0.57, 95% CI [0.44, 0.75]), while statistical differences were also seen in the subgroups of children (OR = 0.53, 95% CI [0.33, 0.85]) and adults (OR = 0.63, 95% CI [0.49, 0.81]). Furthermore, patients having CD with H. pylori were more likely to have symptoms of abdominal pain, diarrhea, and distension (OR = 2.5, 95% CI [1.35, 4.62]) (OR = 1.56, 95% CI [1.09, 2.24]) (OR = 2.75, 95% CI [1.74, 4.35]). However, H. pylori has no effect on CD classification. CONCLUSION The study confirmed that there is a correlation between H. pylori and CD, but the causality cannot be clarified. A demonstration of a causal role of H. pylori in CD in future prospective studies could have important therapeutic implications.

目的 观察补阳还五汤（BYHWD）黄芪不同配比组方对动脉粥样硬化（atherosclerosis, AS）大鼠主动脉组织炎性因子及血管细胞黏附分子（vascular cell adhesion molecule, VCAM-1）、细胞间黏附分子（intercellular adhesion molecules, ICAM-1）、基质金属蛋白酶（matrix met alloproteinase, MMP）-2、MMP-9蛋白表达的影响。方法 70只SD大鼠随机分为A组：正常对照组；B组：模型组；C组：BYHWD黄芪低剂量组（黄芪30 g）;D组：BYHWD黄芪中剂量组（60 g）;E组：BYHWD黄芪高剂量组（90 g）;F组：BYHWD黄芪超高剂量组（120 g）;G组：辛伐他汀组；每组10只。除正常对照组外其余各组采用维生素D 3 与高脂饲料联合喂养法复制AS模型。造模成功后，各治疗组给予药物干预28 d。行苏木素-伊红（HE）染色检测各组大鼠主动脉组织病理形态变化；全自动生化分析仪测定各组大鼠血清中血脂水平；酶联免疫吸附测定法（ELISA）检测大鼠主动脉组织白细胞介素（interleukin, IL）-6、IL-1β、肿瘤坏死因子（tumor necrosis factor-α,TNF-α）和血清C-反应蛋白（C-reactive protein, CRP）含量；蛋白免疫印迹法（Western blot）检测大鼠主动脉组织VCAM-1、ICAM-1和MMP-2、MMP-9蛋白相对表达水平。结果 HE结果显示模型组可见大量脂质及坏死物质沉积，各治疗组的AS病理改变均有不同程度改善。与A组比较，B组主动脉组织IL-6、IL-1β、TNF-α及血清CRP的水平显著增高，VCAM-1、ICAM-1、MMP-2、MMP-9蛋白相对表达水平均升高（均P＜0.05）。与B组比较，经辛伐他汀及各补阳还五汤黄芪不同配比组干预后，各治疗组大鼠IL-6、IL-1β、TNF-α、CRP水平及VCAM-1、ICAM-1、MMP-2、MMP-9蛋白相对表达水平均显著降低（均P＜0.05）。各补阳还五汤黄芪不同配比组组间比较，C、D、E、F组IL-6、IL-1β、TNF-α、CRP含量梯度递减，VCAM-1、ICAM-1、MMP-2、MMP-9蛋白相对表达水平梯度递减，F组降低AS大鼠炎性相关因子含量、抑制AS大鼠主动脉VCAM-1、ICAM-1、MMP-2、MMP-9表达水平的效果优于其他补阳还五汤黄芪不同配比组（均P＜0.05）。F、G组组间比较，F组IL-6、IL-1β、TNF-α、CRP水平及VCAM-1、ICAM-1、MMP-2、MMP-9蛋白相对表达水平较G组均降低（均P＜0.05）。结论 补阳还五汤黄芪低、中、高、超高剂量组可能通过下调VCAM-1、ICAM-1、MMP-2、MMP-9蛋白表达水平，减少炎性因子释放，抑制主动脉炎性反应防治动脉粥样硬化，其中BYHWD黄芪超高剂量组（120 g）疗效最优。

中医药对亚健康人群的调理、中老年或体质虚弱人群日常保健及女性美容养颜具有独特的优势.对于中医院校来说,急需培养标准化、专业化、规范化、实用型的养生保健人才以适应社会需求.教学过程中笔者结合古代中医药养生理论,以思维导图的形式将药食两用中药系统梳理,化繁为简,层层递进,引导学生掌握既是食物又是药物品种在不同体质和常见病中的食养调补知识,为学习制定个体化中药养生保健方案提供基础.

Ethnopharmacological relevance: Anemarrhena asphodeloides is the dry rhizome of Anemarrhena asphodeloides Bge. Anemarrhena Saponins isolated from Anemarrhena asphodeloides are one of the pharmacologically active components of this plant and have blood lipid reduction and blood glucose reduction properties. These facts suggest that these saponins might be helpful in the treatment of insulin resistance. Aim of the study: To determine the therapeutic effect of anemarrhena saponins on insulin resistance and the probable underlying mechanism. Materials and methods: Insulin-resistant rats were used as the experimental subject, to observe the therapeutic effect of anemarrhena saponins. The blood glucose and blood lipid parameters were determined using the relevant kits. We used hematoxylin and eosin (H&E) staining to observe the protective effect of anemarrhena saponins on the livers of insulin-resistant rats and reverser transcripition polymerase chain reaction (RT-PCR) to analyze the mRNA expressions patterns of genes related to glucose metabolism and inflammatory factors. The toxicity of anemarrhena saponins to HepG2 cells was calculated using the MTT assay. Further, we conducted in vivo and in vitro experiments, and Western-blot analysis to study the effects of anemarrhena saponins on the IRS1/PI3K/AKT pathway. Results: Anemarrhena saponins were found to improve dyslipidemia, reduce obesity and inflammation, and alleviate liver injury in insulin-resistant rats. Anemarrhena saponins also reduced the mRNA expression of gluconeogenesis-related genes sunch as G6pase, PEPCK, and GSK3 beta in the liver. Moreover, anemarrhena saponins up-regulated the phosphorylation levels of IRS-1, PI3K and AKT, promoted insulin signal transduction, and reduced liver injury induced by insulin resistance. Conclusions: These findings suggest that anemarrhena saponins could promote insulin signal transduction through the IRS-1/PI3K/AKT pathway, thereby reducing the damage caused by insulin resistance.

目的:研究桑根酮C对游离脂肪酸诱导的人肝癌HepG2细胞脂质蓄积的改善作用.方法:将HepG2细胞分为对照组、模型组、非诺贝特组(10μmol/L)和桑根酮C低、中、高浓度组(2、4、8μmol/L),除对照组外,其余各组细胞加入1 mmol/L游离脂肪酸以诱导建立脂质蓄积模型,且各给药组加入相应含药培养基进行培养.采用油红O染色法观察细胞中脂质蓄积情况,并测定脂质水平和三酰甘油(TG)含量;采用实时荧光定量聚合酶链式反应法和Western blot法检测细胞中过氧化物酶体增殖物激活受体α(PPARα)、肉碱棕榈酰转移酶1(CPT-1)、成脂甾醇元件结合蛋白固醇调节元件结合蛋白1c(SREBP-1c)、脂肪酸合成酶(FAS)、沉默信息调节因子1(SIRT1)、过氧化物酶体增殖物激活受体γ辅助激活物1α(PGC-1α)的mRNA和蛋白表达水平.结果:与对照组比较,模型组细胞核明显萎缩、体积变小,脂滴数明显增加;细胞中脂质水平、TG含量以及SREBP-1c、FAS的mRNA和蛋白表达水平均显著升高(P<0.05或P<0.01),PPARα、CPT-1、SIRT1、PGC-1α的mRNA和蛋白表达水平均显著降低(P<0.01).与模型组比较,桑根酮C各浓度组细胞核萎缩不明显、体积大小正常,脂滴数明显减少;细胞中脂质水平、TG含量以及上述PPARα通路相关基因的mRNA和蛋白(桑根酮C低浓度组的SREBP-1c蛋白除外)表达水平均显著逆转(P<0.05或P<0.01).结论:桑根酮C可改善HepG2细胞的脂质蓄积;其作用机制可能与调节PPARα信号通路、提高细胞脂质氧化能力、抑制脂质合成有关.

Anemarrhena asphodeloides originated from the rhizome of Liliaceae Anemarrhena asphodeloides. One of the active pharmacological components of Anemarrhena asphodeloides is timosaponin (TSA), which reduces blood lipids and shows antioxidation and anti-inflammatory effects, but its mechanism is unclear. The objective of this study was to investigate the effect of TSA on oxidative stress induced by a long-term high-fat diet in obese rats. Body weight and the obesity index of the rats were measured during the experiment. Total antioxidant capacity (T-AOC), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) were used to detect oxidative stress indexes in serum and liver tissue. To observe the effect of TSA on the liver and adipose tissue of rats with oxidative stress, hematoxylin & eosin (H&E) staining was used. The p-NF-κB, NAD(P)H: quinone oxidoreductase 1 (NQO-1), Heme oxygenase 1 (HO-1), and Nrf2 in Nrf2/HO-1 and NF-κB pathways were assayed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. TSA was found to improve oxidative stress in obese rats by reducing MDA levels and increasing T-AOC and GSH-Px levels. Histological examination revealed that TSA effectively attenuated liver damage and improved obesity in rats. TSA was found to down-regulate the protein level of p-NF-κB and up-regulate the protein level of Nrf2/HO-1. These results suggested that TSA could effectively block inflammation and dyslipidemia in obese rats, thus improving oxidative stress, and its mechanism could be related to the Nrf2/HO-1 and NF-κB pathways.

后循环缺血性眩晕(posterior circulation ischemia vertigo,PCIV)是后循环缺血中的常见疾病之一,多由后循环动脉系统的狭窄或闭塞而引发,发病率高,病情复杂.PCIV在中医上属于"眩晕"范畴,发病的病理因素包括风、火、痰、瘀、虚等方面.历代医家对于PCIV有较多的研究,在"虚致眩晕"和"瘀致眩晕"观点上均有建树,认为二者在眩晕的治疗中常起到重要作用,临床上也取得了较好的疗效.益气活血的治疗思想早在《黄帝内经》中便有记载,张仲景、李东垣等大家对此法多有临证发挥,后由王清任创立"益气活血法",用以治疗气虚血瘀类疾病,临床效果显著.目前"益气活血法"已经被广泛应用于治疗气虚血瘀型PCIV,除却益气活血经典用方外,还出现了以此法为指导而创立的自拟方及中西医结合治疗方法,呈现出百花齐放之态.该文以气血理论为基础,从"虚瘀致眩"的角度,对益气活血法治疗气虚血瘀型PCIV的理论及应用方面进行归纳总结,以期为PCIV的未来研究提供思路与方向.

目的:探讨桑白皮总黄酮联合知母总皂苷对高脂血伴骨质疏松症大鼠的改善作用及其可能的机制.方法:40只SPF级雄性SD大鼠适应性喂养7d后,随机分为正常组、模型组、骨化三醇组(45 ng·kg-1),桑白皮总黄酮-知母总皂苷1∶2组(0.6g·kg-1+04g·kg-1)和桑白皮总黄酮-知母总皂苷2∶1组(1.2g·kg-1+02g·kg-1).除正常组外,其余各组大鼠高脂饲喂造模9周;正常组与模型组灌胃给予生理盐水,其他组灌胃给予相应药物;给药12周后,除正常组外,其余各组给药的同时肌肉注射糖皮质激素,给药22周后测定各组大鼠的体质量,生化法检测血清中总胆固醇(TC),甘油三酯(TG),低密度脂蛋白胆固醇(LDL-C),骨钙素(BGP)及骨碱性磷酸酶(BALP)的含量;苏木素-伊红(HE)染色观察大鼠胫骨病理形态变化;实时荧光定量聚合酶链式反应(Real-time PCR)检测大鼠骨组织中过氧化物酶体增殖物激活受体γ(PPARy),Runt相关转录因子2(Runx2)mRNA的表达水平;免疫荧光法检测大鼠PPARy,Runx2的表达.结果:与正常组比较,模型组大鼠体质量显著升高(P＜0.01),血清中TC,TG,LDL-C含量显著增加(P＜0.01);与模型组比较,桑白皮总黄酮-知母总皂苷1:2组和桑白皮总黄酮-知母总皂苷2∶1组大鼠体质量显著降低(P＜0.01),血清中TC,TG,LDL-C含量显著降低(P＜0.01),BGP,BALP含量显著升高(P＜0.01).HE染色结果表明,与正常组比较,模型组大鼠胫骨脂肪空泡增多,成骨细胞数量减少;与模型组比较,桑白皮总黄酮-知母总皂苷1:2组和桑白皮总黄酮-知母总皂苷2:1组大鼠胫骨脂肪空泡减小,成骨细胞数量增加.免疫荧光与Real-time PCR结果表明,与正常组比较,模型组大鼠Runx2表达减少,PPARγ表达增加(P＜0.01),与模型组比较,桑白皮总黄酮-知母总皂苷1∶2组和桑白皮总黄酮-知母总皂苷2:1组上调Runx2的表达,下调PPARy的表达(P＜0.05,P＜0.01).结论:桑白皮总黄酮联合知母总皂苷可上调Runx2,下调PPARγ mRNA和蛋白的表达,从而影响了血液中TG和TC代谢,达到对骨质疏松的治疗作用,为临床防治高脂血症伴骨质疏松症的治疗提供了实验依据.

目的:利用网络药理学从整体水平探讨补阳还五汤治疗动脉粥样硬化的作用机制.方法:通过中药系统药理学数据库与分析平台(TCMSP)筛选补阳还五汤中的有效活性成分及相关靶点.利用GeneCards数据库检索动脉粥样硬化疾病相关靶点,获取补阳还五汤与动脉粥样硬化的共同靶点.应用DAVID对共同靶点进行东京基因组百科全书(KEGG)通路富集分析.结果:由7种中药组成的补阳还五汤共有86个活性成分和4346个潜在靶点,其中该方与动脉粥样硬化97个共同靶点,富集到143条KEGG相关通路,涉及白介素-17(IL-17)信号通路、T细胞受体信号通路、肿瘤坏死因子(TNF)信号通路、Th17细胞分化、乏氧诱导因子-1(HIF-1)信号通路等炎症通路,与自噬相关的PI3K-Akt信号通路等.结论:补阳还五汤发挥多成分、多靶点、多途径的作用特点,通过免疫调节、抗炎、激活自噬等干预动脉粥样硬化进程.

Context Poria coco F.A.Wolf (Polyporaceae) dispels dampness and promotes diuresis implying hypouricaemic action. Objective To examine hypouricaemic action of Poria coco. Materials and methods Ethanol extract (PCE) was prepared by extracting the sclerotium of P. cocos with ethanol, and the water extract (PCW) was produced by bathing the remains with water. PCE and PCW (50, 100 and 200 mg/kg, respectively) were orally administered to hyperuricemic Kunming mice (n = 8) to examine its hypouricaemic effect. Also, molecular docking was performed. Results P. cocos showed excellent hypouricaemic action, decreasing the serum uric acid of hyperuricaemia (HUA) control (526 ± 112 μmol/L) to 178 ± 53, 153 ± 57 and 151 ± 62 μmol/L (p < 0.01) by PCE and 69 ± 23, 63 ± 15 and 62 ± 20 μmol/L (p < 0.01) by PCW, respectively. According to SCrs, BUNs and H&E staining, PCE and PCW partially attenuated renal dysfunction caused by HUA. They presented no negative effects on ALT, AST and ALP activities. They elevated ABCG2 (ATP-binding cassette super-family G member 2) mRNA and protein expression in comparison to HUA control. In molecular docking, compound 267, 277, 13824, 15730 and 5759 were predicted as the top bioactives of P. cocos against HUA, which even presented better scores than the positive compound, oestrone 3-sulfate. Discussion and conclusions This paper demonstrated the hypouricaemic and nephroprotective effects of P. cocos in hyperuricemic mice by up-regulating ABCG2. These results may be useful for the development of a hypouricaemic agent.

Background:There have been various articles reporting relationship between Vitamin D (VitD) and celiac disease (CeD), but results remain controversial. This study aimed to conduct a meta-analysis to systematically review and quantify the relationship between VitD and CeD. Moreover, difference in Vitamin D Receptor (VDR) genotypes between CeD patients and controls was also analyzed. Methods:Articles published until July 20, 2019 in the PubMed, MEDLINE, and EMBASE databases were searched. According to the inclusion and exclusion criteria, relevant statistical data were collated and extracted, which were finally analyzed by STATA15.1. Results:27 articles and 28 sets of data were included. It showed that average 25(OH)D level in CeD patients was 8.36 nmol/L lower than controls (Weighted Mean Difference (WMD) = -8.36, 95% CI = [-14.63, -2.09] nmol/L). After gluten-free diet treatment, we found that average 25(OH)D level in treated patients was 15.6 nmol/L higher than untreated patients (WMD = 15.6, 95% CI = [5.96, 25.23] nmol/L). In addition, 25(OH)D level in treated patients was close to healthy controls (WMD = -2.82, 95% CI = [-6.45, 0.73] nmol/L). However, genetic polymorphism analysis showed that there is no difference in VDR genotypes between CeD and control. Conclusions:CeD had decreased serum 25(OH)D levels, which returned to normal after treatment, suggesting that VitD may play a role in the development of CeD. The directionality of this association cannot be confirmed from cross-sectional studies. Demonstration of a causal role of VitD deficiency in CeD development in future studies could have important therapeutic implications.

目的 通过运用益气活血法的代表方剂补阳还五汤对血管平滑肌细胞的干预,观察各组血管平滑肌细胞Rho激酶及TFmRNA、基质金属蛋白酶MMP-2mRNA、MMP-9mRNA的表达等指标的变化.方法 将30只SD大鼠随机分为3组,一组为正常对照组,另两组为补阳还五汤低剂量对照组(10 g·kg-1)和补阳还五汤高剂量对照组(20g·kg-1);AS模型大鼠30只随机分为模型组,补阳还五汤低剂量治疗组(10 g·kg-1)和补阳还五汤高剂量治疗组(20 g·kg-1).给SD正常大鼠和AS模型大鼠口服不同浓度的补阳还五汤以制备含药大鼠血清,并在用合药大鼠血清保护体外培养的血管平滑肌细胞之后,检测血管平滑肌细胞Rho激酶mRNA、TFmRNA、MMP-2mRNA、MMP-gmRNA的表达.结果 与模型对照组相比,各组补阳还五汤高剂量治疗组血管平滑肌细胞Rho激酶、TFmRNA、MMP-2mRNA、MMP-9mRNA的表达均降低.差异均有统计学意义(P ＜0.05,P＜0.01).结论 补阳还五汤含药鼠血清可以通过抑制Rho激酶的活性,下调ROCK1、TF、MMP-2、MMP-9的mRNA的表达水平抑制血管平滑肌细胞增殖,从而抑制AS病变的形成和发展.

通过检索近年来运用益气活血法治疗糖尿病周围神经病变(DPN)的相关文献,探析气血的概念及功能,认为DPN总体归属本虚标实,故气血失调是DPN的发病根源,气虚、血瘀作为糖尿病周围神经病变基本病机贯穿始终.益气活血法能有效提高神经传导速度、改善临床症状.临床以益气活血法为治疗本病的基本思路,配合滋阴、温阳、祛湿、化痰等治法,灵活运用中药、针灸推拿、中药足浴、穴位贴敷、中西药联用等手段,可达到缓解DPN临床症状、延缓DPN病程发展的目的 .参考文献33篇.

Parkinson disease autosomal recessive, early onset 7 (PARK7 or DJ-1) is involved in multiple physiological processes and exerts anti-apoptotic effects on multiple cell types. Increased intestinal epithelial cell (IEC) apoptosis and excessive activation of the p53 signaling pathway is a hallmark of inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD). However, whether DJ-1 plays a role in colitis is unclear. To determine whether DJ-1 deficiency is involved in the p53 activation that results in IEC apoptosis in colitis, here we performed immunostaining, real-time PCR, and immunoblotting analyses to assess DJ-1 expression in human UC and CD samples. In the inflamed intestines of individuals with IBD, DJ-1 expression was decreased and negatively correlated with p53 expression. DJ-1 deficiency significantly aggravated colitis, evidenced by increased intestinal inflammation and exacerbated IEC apoptosis. Moreover, DJ-1 directly interacted with p53, and reduced DJ-1 levels increased p53 levels both in vivo and in vitro and were associated with decreased p53 degradation via the lysosomal pathway. We also induced experimental colitis with dextran sulfate sodium in mice and found that compared with DJ-1-/- mice, DJ-1-/-p53-/- mice have reduced apoptosis and inflammation and increased epithelial barrier integrity. Furthermore, pharmacological inhibition of p53 relieved inflammation in the DJ-1-/- mice. In conclusion, reduced DJ-1 expression promotes inflammation and IEC apoptosis via p53 in colitis, suggesting that the modulation of DJ-1 expression may be a potential therapeutic strategy for managing colitis.

BACKGROUND:Brown adipose tissue (BAT) activation is a promising therapeutic target to treat hyperlipidemia with obesity. Huang-Qi San (HQS), an traditional Chinese medicine, can ameliorate hyperlipidemia with obesity, but its mechanism of action (MOA) is not understood. PURPOSE:To articulate the MOA for HQS with animal models. METHODS:The main chemical constituents of HQS were identified by high-performance liquid chromatography (HPLC) based assay. Hyperlipidemia with obesity rat models induced by high-fat diet were employed in the study. The levels of the fasting plasma glucose (FPG), triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) were measured to evaluate the ability of HQS to ameliorate hyperlipidemia with obesity. Pathological analyses of organs were conducted with Oil Red O staining, hematoxylin-eosin (H&E) staining and transmission electron microscopy. The expression of mRNAs related to thermogenic genes, fatty acid oxidation-related genes and mitochondria biogenic genes were examined by quantitative real-time PCR. The protein expressions of uncoupling protein 1 (UCP1) were investigated by immunohistochemistry and western blot. Simultaneously, the protein expression of PR domain containing 16 (PRDM16), ATP synthase F1 subunit alpha (ATP5A) was detected by western blot. RESULTS:HQS ameliorates metabolic disorder, lipid ectopic deposition, obesity and maintained glucose homeostasis in hyperlipidemia with obesity rats. HQS can significantly increase the number of mitochondria and reduced the size of the intracellular lipid droplets in BAT, and increase the expression of BAT activation-related genes (UCP1, PGC1α, PGC1β, Prdm16, CD137, TBX1, CPT1a, PPARα, Tfam, NRF1 and NRF2) in vivo. Furthermore, UCP1, PRDM16 and ATP5A proteins of BAT were increased. CONCLUSION:HQS can activate BAT and browning of S-WAT (subcutaneous white adipose tissue) through activating the PRDM16/PGC1α/UCP1 pathway, augmenting mitochondrial biogenesis and fatty acid oxidation to increase thermogenesis and energy expenditure, resulting in a significant amelioration of hyperlipidemia with obesity. Therefore, HQS is an effective therapeutic medicine for the treatment of hyperlipidemia with obesity.

Structural modification of active natural compoundswhichwereoriginated fromTraditional Chinese Medicine (TCM) have showedgreat advantagesin thedevelopmentof new drugs. In TCM, “Huangqin-Huanglian” is a classic “medicine couple”thathas been used to treat intestinal diseases for thousands ofyears, while baicalinand berberine are the major active compoundsof Huangqin and Huanglianrespectively. Based onthis“medicine couple”,wedesignedand synthesizeda newbaicalin and berberine hybrid compound (BBH).Its molecular structure wasconfirmedby spectroscopy.The antibacterial activity of BBH was detected in vitro.Results indicatedthat the new hybrid compound exhibited the best antibacterial activity forproteobacteria as compared with its original synthetic materials (baicalin andberberine). In vivo, the effect of BBHon ulcerative colitiswas alsoinvestigated.BBH treatment significantly ameliorated the disease symptoms andpreventedthe colon damage of ulcerative colitis. Furthermore, BBH showed asignificant anti-inflammatory effect through regulating activities of SOD, MPOandexpressions of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) in colontissue. Data also suggested that BBH was more superior than baicalin and berberine inameliorating colonic damage. This indicated that the new hybrid compound BBHshowed enhanced efficacy in treating ulcerative colitis.

目的:观察桑根酮C (SanC)对地塞米松(DEX)作用下小鼠MC3T3-E1成骨细胞增殖与分化的影响,并探讨其作用机制.方法:将SanC与同源建模所得的Runt-相关转录因子2(Runx2)蛋白结构进行分子对接.不同浓度SanC(8,16,32 μmol·L-1)和1 μmol·L-1 DEX共同作用MC3T3-E1细胞,而后采用细胞增殖-毒性检测试剂盒(CCK-8)法检测SanC对MC3T3-E1成骨细胞增殖影响.试剂盒测定MC3T3-E1成骨细胞碱性磷酸酶(ALP)活性和茜素红染色检测骨矿化结节的形成.采用实时荧光定量聚合酶链反应(Real-time PCR)检测Runt-相关转录因子2(Runx2),ALP,和锌指结构转录因子(Osterix) mRNA的表达水平.蛋白免疫印迹法(Western blot)检测Runx2蛋白表达.结果:SanC与Runx2对接打分为-9.78.与正常组比较,DEX组显著降低细胞存活率(P＜0.01),其中7d存活率差异达到最大;与DEX组比较,SanC能显著促进MC3T3-E1的细胞增值(P＜0.01),其中32μmol·L-SanC作用细胞7d增殖率差异达到最大.与正常组比较,DEX组Runx2,ALP和Osterix mRNA的表达均有一定程度升高(P＜0.05);与DEX组比较,不同浓度SanC组依赖性上调Runx2,ALP和Osterix mRNA的表达(P＜0.01).与正常组比较,DEX组Runx2蛋白表达明显下降(P＜0.05);与DEX组比较,SanC干预下细胞Runx2蛋白表达显著升高(P＜O.01).结论:桑根酮C能促进MC3T3-E1成骨细胞增殖、分化和矿化,其机制可能与上调Runx2表达有关.