Brown and beige adipocytes dissipate energy to generate heat through uncoupled respiration, and the hormone norepinephrine plays an important role in stimulating brown fat thermogenesis and beige adipocyte development in white adipose depots. Increasing energy expenditure by promoting the function and development of brown and beige fat is a potential approach to treat obesity and diabetes. Here, we investigated the effects of macrophage sirtuin 6 (SIRT6) on the regulation of the norepinephrine content of brown adipose tissue (BAT) and on obesity in mice. Myeloid SIRT6 deficiency impaired the thermogenic function of BAT, thereby decreasing core body temperatures because of reduced norepinephrine concentrations in BAT and subsequently leading to cold sensitivity. In addition, the oxygen consumption rate was reduced, resulting in severe insulin resistance and obesity. Furthermore, macrophage SIRT6 deficiency inhibited BAT thermogenesis after cold exposure or norepinephrine treatment and cold exposure-induced increases in markers of lipid metabolism and thermogenesis in white adipose tissue. Myeloid-specific SIRT6 deficiency promoted H3K9 acetylation in the promoter regions and the expression of genes encoding the norepinephrine-degrading enzyme MAOA and the norepinephrine transporter SLC6A2 in macrophages in BAT, leading to norepinephrine degradation and obesity. Our findings indicate that SIRT6 in macrophages is essential for maintaining norepinephrine concentrations in BAT in mice.

Non-alcoholic fatty liver disease (NAFLD) has emerged as the leading cause of chronic liver disease worldwide. Caspase 8 and FADD-like apoptosis regulator (CFLAR) has been identified as a potent factor in mitigating non-alcoholic steatohepatitis (NASH) by inhibiting the N-terminal dimerization of apoptosis signal-regulating kinase 1 (ASK1). While arginine methyltransferase 1 (PRMT1) was previously reported to be associated with increased hepatic glucose production, its involvement in hepatic lipid metabolism remains largely unexplored. The interaction between PRMT1 and CFLAR and the methylation of CFLAR were verified by Co-IP and immunoblotting assays. Recombinant adenoviruses were generated for overexpression or knockdown of PRMT1 in hepatocytes. The role of PRMT1 in NAFLD was investigated in normal and high-fat diet-induced obese mice. In this study, we found a significant upregulation of PRMT1 and downregulation of CFLAR after 48h of fasting, while the latter significantly rebounded after 12h of refeeding. The expression of PRMT1 increased in the livers of mice fed a methionine choline-deficient (MCD) diet and in hepatocytes challenged with oleic acid (OA)/palmitic acid (PA). Overexpression of PRMT1 not only inhibited the expression of genes involved in fatty acid oxidation (FAO) and promoted the expression of genes involved in fatty acid synthesis (FAS), resulting in increased triglyceride accumulation in primary hepatocytes, but also enhanced the gluconeogenesis of primary hepatocytes. Conversely, knockdown of hepatic PRMT1 significantly alleviated MCD diet-induced hepatic lipid metabolism abnormalities and liver injury in vivo, possibly through the upregulation of CFLAR protein levels. Knockdown of PRMT1 suppressed the expression of genes related to FAS and enhanced the expression of genes involved in FAO, causing decreased triglyceride accumulation in OA/PA-treated primary hepatocytes in vitro. Although short-term overexpression of PRMT1 had no significant effect on hepatic triglyceride levels under physiological conditions, it resulted in increased serum triglyceride and fasting blood glucose levels in normal C57BL/6J mice. More importantly, PRMT1 was observed to interact with and methylate CFLAR, ultimately leading to its ubiquitination-mediated protein degradation. This process subsequently triggered the activation of c-Jun N-terminal kinase 1 (JNK1) and lipid deposition in primary hepatocytes. Together, these results suggested that PRMT1-mediated methylation of CFLAR plays a critical role in hepatic lipid metabolism. Targeting PRMT1 for drug design may represent a promising strategy for the treatment of NAFLD.

Abstract Studies had revealed that Immune related genes play an important role in Chronic hepatic injury (CHI), which is the main cause of liver fibrosis. Differentially expressed genes (DEGs) between CHI including Alcoholic hepatitis (AH), Nonalcoholic fatty liver disease (NAFLD), Hepatitis C (HC), and Hepatitis B (HB) and related Control samples were detected by differential analysis. Then, 77 latent genes of CHI were intersected with IRGs to obtain DEGs for generating a Protein-protein interaction (PPI) network to screen out 5 key genes consisting of secreted phosphor protein 1 (SPP1), Chemokine (C-X-C motif) ligand (CXCL10), Chemokine (C-C motif) ligand 20 (CCL20), Annexin A2 (ANXA2), and lectin galactoside-binding soluble 3 (LGALS3). Besides, we found that CXCL10 was regulated by a natural compound named quercetin, and there were 187 herbs with it as the main component. TFs-mRNA network identified that Forkhead box C1 (FOXC1) could regulate 4 key genes including CCL20, SSP1, ANXA2, and LGALS3. Therefore, this could provide references for CHI treatments and further studies.

BackgroundDihydromyricetin (DMY) is a natural flavonoid with anti-nonalcoholic steatohepatitis (NASH) activity. However, the effects of DMY on the composition of lipids and bile acids (BAs) in serum, and gut microbiota (GM) in ileum of mice with NASH are not clear.MethodsAfter male C57BL/6 mice was fed with methionine and choline deficiency (MCD) diet and simultaneously administered with DMY (300 mg/kg/day) by gavage for 8 weeks, the pathological changes of liver tissue were observed by Oil Red O, hematoxylin eosin and Masson staining, the levels of serum alaninea minotransferase, aspartate aminotransferase and liver triglyceride, malonic dialdehyde were detected by the detection kits, the composition and contents of serum lipids and BAs were detected by Liquid Chromatograph-Mass Spectrometry, the mRNA levels of hepatic BAs homeostasis-related genes were detected by RT-qPCR, and microbiological diversity in ileum was analyzed by 16S rDNA sequencing.ResultsThe results showed that the significant changes including 29 lipids, 4 BAs (23-nor-deoxycholic acid, ursodeoxycholic acid, 7-ketodeoxycholic acid and cholic acid), 2 BA transporters (Mrp2 and Oatp1b2) and 8 GMs between MCD and DMY groups. Among them, DMY treatment significantly down-regulated 21 lipids, 4 BAs mentioned above, the ratio of Firmicutes/Bacteroidota and the abundance of Erysipelotrichaceae, Faecalibacuium, significantly up-regulated 8 lipids and 5 GMs (Verrucomicrobiota, Bacteroidota, Actinobacteria, Akkermansiaceae and Akkermansia).ConclusionsThe results suggested that DMY may alleviate MCD diet-induced NASH through decreasing the serum levels of toxic BAs which regulated by liver Oatp1b2 and Mrp2, regulating the metabolism of related lipids, and up-regulating intestinal probiotics (Actinobacteria and Verrucomicrobiota at the phylum level; Akkermansiaceae at the family level; Akkermansiaat at the genus level) and inhibiting intestinal harmful bacteria (Firmicutes at the phylum level; Erysipelotrichaceae at the family level; Faecalibaculum at the genus level).

Abstract We present an interesting case where severe pulmonary arterial hypertension (PAH) developed in a 30-year-old male systemic lupus erythematosus (SLE) patient after achieving complete remission of class V lupus nephritis (LN) complicated with overlooked podocytic infolding glomerulopathy (PIG). Despite rapid renal response to conventional therapy, emergent PAH failed to improve with SLE immunosuppression, suggesting the predominance of pulmonary vascular remodeling over immunological activity in PAH persistence. Notably, glucocorticoid resulted in avascular necrosis without PAH remission. However, belimumab combined with pulmonary vasculature-targeting agents effectively lowered pulmonary pressure. This case highlights that PAH requires ongoing surveillance even after apparent LN/SLE resolution, and directly rectifying vascular changes, rather than immunosuppression alone, is key to optimal PAH control. It also provides clues to potent treatment strategies for this refractory SLE complication. The association between PIG and PAH warrants further research.

对细圆藤(Pericampylus glaucus)醇提取物的急性毒性进行初步研究,筛选出细圆藤抗炎、镇痛有效部位,为新药的开发提供理论依据.采用最大给药量测定法,小鼠灌胃给药测定藤水提取物和醇提物的半数致死量(LD50)或最大耐受量(MTD)研究其安全性;采用冰醋酸致小鼠疼痛和小鼠热刺激反应考察细圆藤不同提取部位的镇痛作用;采用琼脂肉芽肿胀法观察细圆藤不同提取部位的抗炎作用.结果显示,在急性毒性中,未测得半数致死量LD50,细圆藤醇提取物的MTD>94 g/kg,最大耐受量倍数相当成人(60 kg)用量的376倍;细圆藤不同部位组均能减轻小鼠肉芽湿重,细圆藤石油醚部位、乙酸乙酯部位、正丁醇部位、水部位的抑制率分别为13.74％、21.35％、16.35％、32.27％,其差异均具有统计学意义;与空白对照组比较,细圆藤石油醚部位、水部位在给药后90、120 min痛阈值显著提高;细圆藤乙酸乙酯部位、正丁醇部位在给药后120 min痛阈值显著提高,细圆藤不同部位组均能减轻醋酸引起小鼠疼痛,其中细圆藤石油醚部位、乙酸乙酯部位、正丁醇部位、水部位的镇痛率分别为51.74％、37.63％、32.13％、40.55％,与空白组比较其差异具有统计学意义;细圆藤无明显毒性,临床常用量安全可行;在抗炎镇痛有效部位筛选发现,细圆藤不同部位均具有一定的抗炎镇痛作用,细圆藤石油醚部位镇痛效果最强,水部位抗炎效果最强.

秤钩风属植物在壮药、苗药、傣族药等少数民族医药中,作为治疗外伤感染、风湿痹痛、肿痛等疾病的传统用药应用广泛.文章通过查阅相关国内外文献,对防已科植物秤钩风属的研究进展和研究现状进行综述,综述了秤钩风属植物在化学成分、药理作用方面的研究进展,总结出秤钩风属植物在各方面研究中可能存在的空白,为苍白秤钩风的进一步研究提供参考依据.

目的 建立瑶药水石榴的质量标准.方法 建立瑶药水石榴的性状、显微特征、薄层鉴别及含量测定方法;根据中国药典2015年版第四部通则中的方法对瑶药水石榴的水分、灰分、酸不溶性灰分及浸出物等项目进行测定.结果 瑶药水石榴在性状、显微特征和薄层色谱方面均具有专属性特征.药材水分含量为7.38％?12.25％,灰分含量为5.81％～10.69％,酸不溶物含量为0.09％～3.87％,浸出物为18.91％?32.29％.异荭草苷在2.750 4～45.8μg?mL-1(r=0.99997)内线性关系良好,平均加样回收率为104.6％.10批药材样品中异荭草苷的含量为0.0105％?0.139 0％.结论 建立的水石榴药材质量标准具有很好的专属性和准确性,研究结果可为瑶药水石榴质量标准的建立及其药材的推广使用提供科学依据.

铁线草[Cynodon dactylon (L.) Pers.]具有清热利尿、散瘀止血、舒经活络等功效,且分布较广,具有广阔的开发和利用前景.综述了铁线草易混淆品、化学成分、药理作用及应用等方面的研究现状,以期为进一步开发和利用好该草药资源提供依据.

三七总皂苷(Panax notoginseng saponins,PNS)是三七(Panax notoginseng)的主要活性成分,具有抗炎、降血脂、抗氧化和抗肿瘤等药理作用.在查阅近年来国内外文献的基础上,对三七总皂苷的药理作用和临床应用进行了综述,为其进一步研究和应用提供参考.

对瑶浴散剂的水分、灰分、酸不溶性灰分及水溶性浸出物按2015版《中华人民共和国药典》(四部)通则中的方法进行测定;观察瑶浴散剂粉末显微鉴别特征,并对其进行薄层鉴别检查;采用HPLC法测定瑶浴散剂中β-细辛醚的含量.结果表明,瑶浴散剂中的水分含量不得超过9.00％;灰分含量不得大于10.00％,酸不溶性灰分含量不得大于1.30％;水溶性浸出物含量不得低于19.00％;瑶浴散剂中合欢皮、鸡血藤及石菖蒲药材的显微特征明显;TLC鉴别中斑点清晰,阴性无干扰;瑶浴散剂中β-细辛醚的含量在0.71％～0.85％,RSD为2.48％,各批次含量大致相同.所建立瑶浴散剂质量控制方法重复性好,专属性强,可对瑶浴散剂质量进行控制.

目的 建立风湿骨痛胶囊HPLC指纹图谱,并对其批间一致性进行评价.方法 该药物70％甲醇提取液的分析采用Agilent Zorbax SB-C18色谱柱(250 mm×4.6 mm,5μm);流动相乙腈-0.2％磷酸,梯度洗脱;体积流量1.0 mL/min;检测波长210、235、310 nm;柱温30℃,通过中药色谱指纹图谱相似度评价系统(2012版)进行相似度分析,通过SIMCA13.0软件进行偏最小二乘法、判别分析、聚类分析.结果 20批样品指纹图谱中有31个共有峰,相似度0.957～0.985,鉴定出原儿茶酸、盐酸麻黄碱、盐酸伪麻黄碱、绿原酸、芹糖甘草苷、甘草苷、苯甲酰新乌头原碱、甘草素、异甘草苷、甘草酸.20批样品所含成分较一致,但共有峰峰面积存在差异.结论 该方法专属性强,高效快速,可为风湿骨痛胶囊的质量控制提供依据.

生物碱类是一类含氮碱性有机化合物,具有很好的抗病毒活性,是发现抗病毒药物的重要源泉.查阅相关文献发现生物碱具有多种抗病毒活性,主要包括抗流感病毒、抗乙型肝炎病毒、抗丙型肝炎病毒、抗登革病毒、抗寨卡病毒、抗基孔肯雅病毒、抗艾滋病病毒、抗柯萨奇病毒及抗疱疹病毒等,且效果良好.文章总结了近年来国内外生物碱类化合物对抗常见病毒的相关文献,为开发新型生物碱类抗病毒药物的进一步深入研究提供理论参考.

川乌在治疗风湿性关节炎方面有较好的效果,现代药理发现它还具有抗肿瘤作用,但其毒性较强,能引起严重的心脏毒性和神经毒性.目前,液质谱联用、一测多评等现代分析检测技术和数据处理方法越来越多应用到川乌安全性、有效性的质量控制中.本文对川乌药理、毒性、质量控制方法的文献进行综述,以期为该药材深入研究提供参考.

运用中药系统药理学分析平台(TCMSP)数据库,以化合物口服利用度(OB ＞30％、药物相似性(DL)＞0.18为条件,检索得到三七(Panax notoginseng)的主要有效成分;通过Drugbank、UniProt数据库进行活性成分靶点提取并用GeneCards、OMIM数据库筛选出关节炎的相关靶点,制作三七治疗关节炎的相关靶点的Veen图,进而使用Cytoscape 3.6.0软件、String数据库分别绘制三七-有效活性成分-靶基因-关节炎的中药网络调控图和蛋白互作(PPI)网络图,最后以R语言为工具,筛选关键靶点并分析其生物过程和重要信号通路,利用网络药理学方法探究三七治疗关节炎的作用机制.结果 表明,检索到三七的8个主要成分,得到β-谷甾醇、豆甾醇、人参皂苷rh2等;预测三七治疗关节炎的相关靶点131个;三七关键靶点主要涉及蛋白质异二聚活性、DNA结合转录激活活性,RNA聚合酶Ⅱ特异性、细胞因子受体结合等生物过程;主要通过糖尿病并发症AGE-RAGE信号通路、流体剪切应力与动脉粥样硬化、乙型肝炎等重要信号通路发挥治疗关节炎的作用.

目的 探讨磨盘草乙酸乙酯部位提取物对肝硬化腹水的影响及利尿作用.方法 采用四氯化碳(CCl4)-橄榄油致大鼠肝腹水模型观察磨盘草乙酸乙酯部位提取物对肝硬化腹水的影响,测定血清谷草转氨酶(AST)、谷丙转氨酶(ALT)、白蛋白(ALB)、醛固酮(ALD)水平及钾离子(K+)浓度并做病理检查;通过大鼠水负荷实验探讨利尿作用以及采用高效液相色谱法(HPLC)对磨盘草乙酸乙酯部位含药血清和空白血清,含药尿液和空白尿液进行初步成分分析.结果 磨盘草乙酸乙酯部位可降低ALT、AST及ALD水平,可引起大鼠尿量增加且与药量呈现量效关系,发现并标定了 12个入血成分及7个代谢产物.结论 磨盘草乙酸乙酯部位具有消退腹水、改善肝功能及利尿作用,入血成分初步判定来源于磨盘草乙酸乙酯部位原药材或是其次级代谢产物.

目的:研究不同产地当归藤的挥发油化学成分,为当归藤的质量标准建立提供依据.方法:通过水蒸气蒸馏法提取13个不同产地当归藤中挥发油成分,运用气相色谱-质谱联用仪(GC-MS)分析13个产地当归藤挥发油成分的组成差异,并将10个产地的当归藤挥发油总离子图谱导入中药色谱指纹图谱相似度评价系统2012版软件对其进行分析,建立其指纹图谱.结果:不同产地的当归藤挥发油成分中共鉴定出124种化合物,共有的成分有正十三烷、十六烷、十八烷、2,4-二叔丁基苯酚.10个不同产地当归藤挥发油指纹图谱有18个共有峰,10个产地当归藤药材指纹图谱与对照指纹相似度＞0.9.结论:不同产地的当归藤挥发油成分差异较大,不同产地的当归藤挥发油成分指纹图谱也存在差异.

鼠李科属植物翼核果(Ventilago leiocarpa Benth.)的根及根茎红穿破石是一种民族药,红穿破石可清热利湿、利尿通淋,对泌尿系统结石具有特殊作用,主要归纳了民族药红穿破石的化学成分、鉴别特征、含量测定及其药理作用,为红穿破石药材的更深一步的研究开发和应用提供依据.

目的 通过研究当归藤不同极性部位对脂多糖(LPS)诱导RAW264.7细胞NO、TNF-α、IL-6表达的影响及其对DPPH和ABTS自由基的清除作用来表明其抗炎作用机制和抗氧化作用的强弱.方法 利用LPS(25μg/mL)诱导RAW264.7细胞建立炎症模型,用MTT法检测当归藤不同部位药物浓度毒性,用Griess试剂法和ELISA法检测体外炎症模型分泌一氧化氮(N0)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)等炎性细胞因子的影响;通过DPPH和ABTS自由基考察当归藤的抗氧化能力.结果 当归藤不同极性部位在0～0.5 mg/mL范围内对小鼠RAW264.7细胞无不良反应;其对LPS诱导RAW 264.7细胞产生的炎症因子NO、TNF-α和IL-6具有抑制的作用,并具有浓度依赖性;乙酸乙酯部位的DPPH和ABTS的IC50值均＜0.04 mg/mL.结论 LPS诱导小鼠RAW264.7细胞能使TNF-α、IL-6、IL-1β的蛋白含量增加,当归藤可抑制该生物反应,发挥间接抗炎作用;乙酸乙酯部位具有较强的抗氧化活性.

目的 建立不同产地当归藤HPLC指纹图谱.方法 当归藤85％甲醇提取物的分析采用Phenomenex C18色谱柱(4.6 mm× 250 mm,5μm);流动相乙腈-0.1％磷酸水,梯度洗脱;体积流量0.8 mL/min;柱温30℃;检测波长225 nm.对结果进行聚类分析和主成分分析.结果 12批样品指纹图谱中有12个共有峰,相似度均大于0.940,并指认了没食子酸,儿茶素;聚类分析将12批样品分为2类.结论 该方法准确稳定,重复性好,可用于当归藤药材的质量控制.