Curcumin attenuates endothelial cell fibrosis through inhibiting endothelial–interstitial transformation

Curcumin (Cur) has various pharmacological activities, including anti-inflammatory, antiapoptotic and anticancer effects. However, there is no report on the effect of Cur on endothelial cell fibrosis. This study was designed to investigate the effect and mechanism of Cur on endothelial cell fibrosis. An endothelial cell fibrosis model was established by using transforming growth factor (TGF) induction. Proliferation assays, qRT-PCR, western blotting and immunostaining were performed to investigate the effects and mechanism of Cur on endothelial cell fibrosis. We found that in human umbilical vein endothelial cells (HUVECs), TGF-β1 treatment significantly decreased the expression of nuclear factor erythroid-2-related factor 2 (NRF-2), dimethylarginine dimethylaminohydrolase-1 (DDAH1), and VE-cadherin, the secretion of cellular nitric oxide (NO) and the activity of nitrous oxide synthase (NOS), while asymmetric dimethylarginine (ADMA) and the release of inflammatory factors were elevated. Immunofluorescence showed decreased CD31 and increased α-smooth muscle actin (α-SMA). Overexpression of NRF-2 significantly attenuated the effects of TGF-β1, while downregulation of DDAH1 potently counteracted the effect of NRF-2. In addition, ADMA treatment resulted in similar results to those of TGF-β1, and Cur significantly attenuated the effect of TGF-β1, accompanied by increased VE-cadherin, DDAH1 and NRF-2 and decreased matrix metalloproteinase-9 (MMP-9) and extracellular regulated protein kinases 1/2 (ERK1/2) phosphorylation. The NRF-2 inhibitor ML385 had the opposite effect as that of Cur. These results demonstrated that Cur inhibits TGF-β1-induced endothelial-to-mesenchymal transition (EndMT) by stimulating DDAH1 expression via the NRF-2 pathway, thus attenuating endothelial cell fibrosis.     

姜黄素逆转结直肠癌化疗耐药的药理作用机制研究进展

结直肠癌是世界上第3大常见癌症,化疗贯穿整个治疗过程,但其耐药的发生成为癌症死亡和复发的主要原因,亟需寻找辅助化疗药治疗的药物增加其疗效。姜黄素是美国国立肿瘤学会所承认的广谱抗癌药物,其作用机制是通过调控相关蛋白表达、上皮间充质转化分子标志物、结直肠癌干细胞识别标志物、相关信号通路、自噬和相关因子。综述姜黄素逆转逆转结直肠癌化疗耐药的机制,旨在为科研探索和临床治疗、预防提供更好的研究思路和应用价值。     

姜黄素体内外逆转结肠癌的5-氟尿嘧啶耐药研究及机制探讨

目的 探究姜黄素在体内外对结肠癌5-氟尿嘧啶（5-fluorouracil,5-FU）耐药的逆转作用及其相关机制。方法 以SW480结肠癌细胞为亲代细胞,构建5-FU耐药细胞株SW480R,采用MTT法检测SW480R细胞的耐药指数以及不同浓度的姜黄素对SW480R细胞增殖能力的影响;流式细胞术检测姜黄素对SW480R细胞周期和凋亡的影响;Western blotting检测姜黄素对SW480R细胞上皮-间充质转化（epithelial-mesenchymal transition,EMT）相关蛋白以及Wnt信号通路相关蛋白的影响;采用裸鼠移植瘤模型检测肿瘤体积变化情况,计算姜黄素的体内抑瘤率,Western blotting检测肿瘤组织中相关蛋白变化。结果 SW480R的耐药指数为12.16,姜黄素能够剂量依赖性地抑制SW480R细胞的增殖,阻滞SW480R细胞周期于G₀/G₁期,以及诱导SW480R细胞凋亡;Western blotting结果表明姜黄素能够在体内外抑制EMT和Wnt信号通路的活性;体内试验表明姜黄素能够有效抑制裸鼠移植瘤的生长。结论 姜黄素能够在体内外逆转结肠癌的5-FU耐药,可能是通过调控Wnt信号通路从而抑制EMT的发生。     

姜黄素对大鼠肠缺血再灌注后肠黏膜细胞凋亡及GRP78表达的影响

目的 观察姜黄素对大鼠肠缺血再灌注后肠黏膜细胞凋亡及GRP78表达的影响。方法 30只雄性SD大鼠随机分为假手术组、模型组、姜黄素组。采用无创性动脉夹夹闭肠系膜上动脉1 h后实施再灌注来建立肠缺血再灌注模型,姜黄素组在手术前5 d开始每天按200 mg/kg ig给药1次,假手术组仅分离肠系膜上动脉,不夹闭。采用HE染色观察肠黏膜损伤情况并进行病理评分;TUNEl法观察肠黏膜细胞凋亡情况并计算凋亡指数;Western blotting检测再灌注损伤3 h时肠黏膜GRP78及Caspase-12蛋白表达。结果 模型组肠黏膜损伤严重,绒毛上皮成块脱落,固有层破坏、溃疡,腺体破坏严重;姜黄素组肠黏膜绒毛上皮仅部分脱落,腺体排列紊乱,与模型组比较,病理评分显著降低（P<0.05）;模型组肠黏膜隐窝可见大量凋亡阳性细胞;与模型组比较,姜黄素组肠黏膜隐窝上皮细胞凋亡情况明显减轻,凋亡指数显著下降（P<0.05）;与模型组比较,姜黄素组GRP78蛋白表达量显著增加（P<0.05）,Caspase-12蛋白表达量显著下降（P<0.05）。结论 姜黄素有可能通过上调GRP78表达,减少内质网应激所致肠黏膜细胞凋亡,来减轻肠黏膜的再灌注损伤,达到保护肠黏膜作用。     

Green synthesis of gold nanoparticles modulates lipopolysaccharide-induced lung inflammation in Wistar rats

This study aimed to investigate the effect of intranasal treatment of gold nanoparticles (GNPs) and Curcumin (Cur) on the lipopolysaccharide (LPS)-induced acute pulmonary inflammatory response. A single intraperitoneal injection of LPS (0.5 mg/Kg) was performed, and the animals in the Sham group were injected with 0.9% saline. Treatment was daily intranasally with GNPs (2.5 mg/L), Cur (10 mg/kg) and GNP-Cur started 12 h after LPS administration and ended on the seventh day. The results show that the treatment performed with GNP-Cur was the most effective to attenuate the action of pro-inflammatory cytokines, and a lower leukocyte count in the bronchoalveolar lavage, in addition to positively regulating anti-inflammatory cytokines in relation to other groups. As a result, it promoted an oxirreductive balanced environment in the lung tissue, providing a histological outcome with a reduction in inflammatory cells and greater alveolar area. The group treated with GNPs-Cur was superior to the other groups, with better anti-inflammatory activity and reduced oxidative stress, resulting in less morphological damage to lung tissue. In conclusion, the use of reduced GNPs with curcumin demonstrates promising effects in the control of the acute inflammatory response, helping to protect the lung tissue at the biochemical and morphological levels.     

Arylnitro monocarbonyl curcumin analogues: Synthesis and in vitro antitubercular evaluation

Curcumin is a natural product that has been reported to exhibit myriad pharmacological properties, one of which is antitubercular activity. It demonstrates antitubercular activity by directly inhibiting Mycobacterium tuberculosis (M.tb) and also enhances immune responses that ultimately lead to the elimination of M.tb by macrophages. This natural product is, however, unstable, and several analogues, noticeably monocarbonyl analogues, have been synthesized to overcome this challenge. Curcumin and its monocarbonyl analogues reported so far exhibit moderate antitubercular activity in the range of 7 to 16 μM. Herein, we report a straightforward synthesis of novel monocarbonyl curcumin analogues, their antitubercular activity, and the structure–activity relationship. The hit compound from this study, 3a , exhibits potent MIC₉₀ values in the range of 0.2 to 0.9 μM in both ADC and CAS media.     

基于斑马鱼模型的水溶性姜黄素制剂抗血栓和抗炎活性研究

目的 基于斑马鱼模型探究水溶性姜黄素制剂对血栓形成和炎症消退的作用。方法 随机挑选受精后3 d的斑马鱼分为对照组、模型组、阳性药对照组、水溶性姜黄素制剂（姜黄素质量分数为10%,125、250、500、1 000、2 000 μg·mL^-1）组、普通姜黄素（姜黄素质量分数为95%,125、250、500、1 000、2 000 μg·mL^-1）组,每组30尾。除对照组外,其余组使用花生四烯酸、脂多糖、五水合硫酸铜分别诱导建立血栓、细菌性炎症和神经性炎症模型。通过观察分析斑马鱼红细胞染色强度和炎症部位中性粒细胞个数来评价水溶性姜黄素制剂抑制血栓形成和抗炎作用。结果 与对照组比较,模型组斑马鱼心脏红细胞染色强度明显减少（P<0.001）、炎症部位中性粒细胞个数明显增多（P<0.001）;与模型组比较,水溶性姜黄素制剂≥250 μg·mL^-1质量浓度时能显著抑制血栓形成、消退炎症,主要表现为斑马鱼心脏红细胞染色强度显著升高（P<0.001）、炎症部位中性粒细胞个数明显减少（P<0.05、0.01、0.001）;姜黄素在≥1 000 μg·mL^-1时能显著抑制血栓形成（P<0.01、0.001）,≥500 μg·mL^-1时能显著消退炎症（P<0.05、0.01、0.001）。姜黄素为水溶性姜黄素制剂给药浓度2～8倍的条件下,才能达到相同的抑制血栓和炎症形成的效果。结论 与普通姜黄素组比较,在相同给药浓度下,水溶性姜黄素制剂具有更好的抑制血栓形成和抗炎作用。     

姜黄素防治急性胰腺炎的作用机制研究进展

急性胰腺炎是常见的临床急性腹部疾病,其起病急、进展迅速、结局不良,限制炎症发展是急性胰腺炎治疗的有效策略。姜黄素是一种来自姜黄的黄色素,具有抗纤维化、抗癌、抗细胞凋亡和抗炎等多种活性。姜黄素可通过抑制核因子-κB(NF-κB)相关通路的活性,调控丝裂原活化蛋白激酶（MAPK）信号通路,抑制Janus激酶2(JAK2)/信号转导及转录激活蛋白3(STAT3)信号通路,激活肌醇磷脂-3-激酶（PI3K）/丝氨酸-苏氨酸激酶（Akt）信号通路,抑制炎症因子分泌,抑制趋化因子上皮中性粒细胞激活肽78(ENA-78)的表达,抑制环氧化酶2(COX-2)的表达,改善细胞自噬功能,抑制胰腺星状细胞活化,减轻氧化应激反应,发挥防治急性胰腺炎的作用。综述了姜黄素防治急性胰腺炎的作用机制,以期为姜黄素的临床研究提供参考。     

Curcumin and Its Potential Impact on Microbiota

Curcumin is one of the most frequently researched herbal substances; however, it has been reported to have a poor bioavailability and fast metabolism, which has led to doubts about its effectiveness. Curcumin has antioxidant and anti-inflammatory effects, and has demonstrated favorable health effects. Nevertheless, well-reported in vivo pharmacological activities of curcumin are limited by its poor solubility, bioavailability, and pharmacokinetic profile. The bidirectional interactions between curcumin and gut microbiota play key roles in understanding the ambiguity between the bioavailability and biological activity of curcumin, including its wider health impact.