虾青素保护PC-3细胞免受H2O2氧化应激的作用机制

目的：研究虾青素对过氧化氢诱导PC-3细胞氧化应激的保护作用,探索其信号通路机制。方法：建立H2O2 氧化应激模型,采用不同浓度虾青素预处理PC-3细胞,检测细胞存活率、细胞凋亡、活性氧（reactive oxygen species, ROS）水平、B淋巴细胞瘤-2（B-cell lymphoma-2,Bcl-2）、Bcl-2相关X蛋白（Bcl-2-associated X protein,Bax）、 活化半胱天冬酶-3表达及丝裂原活化蛋白激酶-核因子E2相关基因2-血红素氧合酶1（mitogen-activated protein kinases nuclear factor erythroid-2-related factor 2-heme oxygenase 1,MAPK-Nrf2-HO-1）通路的变化。结果：20 μmol/L虾青 素预处理显著提高H2O2所降低的细胞存活率、降低ROS水平（P＜0.05）,同时通过抑制Bcl-2/Bax比率下降及半胱 天冬酶-3的激活,从而使细胞凋亡率从51.4%降低至14.8%,进一步研究发现虾青素能够促进Nrf2磷酸化,并促进 HO-1的表达,呈现浓度依赖性。通过细胞外调节蛋白激酶（extracellular regulated protein kinases,ERK）抑制剂 （U0126）和Akt抑制剂（LY294002）预处理,发现当ERK和磷脂酰肌醇激酶/蛋白激酶B（phosphoinositide 3-kinase/ protein kinase B,PI3K/Akt）通路被抑制后,Nrf2表达降低,表明HO-1上调受上游ERK和胞内PI3K/Akt通路的调 控。在对MAPK途径对细胞毒性影响的研究中,ERK通路被抑制后细胞存活率显著下降,而c-Jun氨基末端激酶 （c-Jun N-terminal kinase,JNK）和p38 MAPK通路被抑制后并不影响其保护作用,表明虾青素抑制细胞存活率下降 是通过MAPK途径中的ERK通路,而不是JNK和p38通路。结论：虾青素预处理PC-3细胞可以减轻H2O2诱导的氧化 应激,维持细胞生理活性。     

Saffron (Crocus sativus L.) increases glucose uptake and insulin sensitivity in muscle cells via multipathway mechanisms

Saffron (Crocus sativus Linn.) has been an important subject of research in the past two decades because of its various biological properties, including anti-cancer, anti-inflammatory, and anti-atherosclerotic activities. On the other hand, the molecular bases of its actions have been scarcely understood. Here, we elucidated the mechanism of the hypoglycemic actions of saffron through investigating its signaling pathways associated with glucose metabolism in C₂C₁₂ skeletal muscle cells. Saffron strongly enhanced glucose uptake and the phosphorylation of AMPK (AMP-activated protein kinase)/ACC (acetyl-CoA carboxylase) and MAPKs (mitogen-activated protein kinases), but not PI 3-kinase (Phosphatidylinositol 3-kinase)/Akt. Interestingly, the co-treatment of saffron and insulin further improved the insulin sensitivity via both insulin-independent (AMPK/ACC and MAPKs) and insulin-dependent (PI 3-kinase/Akt and mTOR) pathways. It also suggested that there is a crosstalk between the two signaling pathways of glucose metabolism in skeletal muscle cells. These results could be confirmed from the findings of GLUT4 translocation. Taken together, AMPK plays a major role in the effects of saffron on glucose uptake and insulin sensitivity in skeletal muscle cells. Our study provides important insights for the possible mechanism of action of saffron and its potential as a therapeutic agent in diabetic patients.     

果蔬中多酚类化合物双向调控Nrf2/Keap1信号通路的研究进展

果蔬中含有丰富的多酚类化合物,其含有的酚羟基中邻位酚羟基极易被氧化,有较强捕捉活性氧等自由 基的能力,因此能够清除自由基和淬灭活性氧。Nrf2（NF-E2-related factor 2）信号通路是增强机体抗氧化功能最 重要的保护性信号途径,在细胞抵御氧化应激机制中有着重要的地位,是抗氧化研究领域的热点。本文通过阐述 Nrf2/Keap1（Kelch-like ECH-associated protein 1）信号通路及其调节方式,讨论Nrf2在肿瘤化学预防和促进癌症发 生中的双重作用,重点介绍和归纳了果蔬中几种典型的多酚类物质对Nrf2/Keap1信号通路双向调控作用的分子机 制,以期为利用果蔬多酚开发健康绿色食品和药品提供一定的理论依据。     

Chemopreventive functions of sulforaphane: A potent inducer of antioxidant enzymes and apoptosis

Epidemiological and dietary studies have revealed an association between high intake of cruciferous vegetables and decreased cancer risk cancer. Sulforaphane, a phytochemical constituent of cruciferous vegetables, has received much attention as a potential cancer chemopreventive compound. Recent advances in the cellular and molecular biology of cancer have shed light on components of intracellular signaling cascades that can be molecular targets of chemoprevention by various anti-cancer agents. Metallothionein (MT), a primary antioxidant enzyme involved in the metabolism and detoxification of heavy metal, has been recognized as a molecular target for chemoprevention by natural anti-cancer agents, but the cellular signaling mechanisms that associate MT gene regulation are not yet clearly understood. Recent studies suggest that Nrf2-mediated signaling, which controls the expression of many of genes responsible for carcinogen detoxification and protection against oxidative stress, is regulated by sulforaphane. This contribution focuses on Nrf2-mediated signaling pathways, particularly in relation to MT gene induction and the apoptosis-inducing effects of sulforaphane.     

食品中亲电物质的最新研究进展

食品中的亲电物质是高效低毒的核转录因子NF-E2相关因子2(Nrf2)诱导剂,通过Keap1/Nrf2/ARE通路激活Ⅱ相酶和抗氧化酶的转录。Ⅱ相酶和抗氧化蛋白可发挥慢速、长效的抗氧化和解毒作用。目前已经发现食品中有9类亲电物质,它们具有相似的结构特征。研究和开发食品中的亲电物质,将成为功能性食品新的研究领域。     

A recent review of citrus flavanone naringenin on metabolic diseases and its potential sources for high yield-production

BackgroundMetabolic syndromes are the multi-metabolic abnormality characterized by hyperlipidemia, obesity, hyperglycemia, diabetes, hypertension, cardiovascular disease, and neuro-dysfunction. Naringenin, a naturally occurring flavanone compound, abundantly found in citrus fruit, has demonstrated diverse biological activities. In this context, the role of naringenin in the treatment of metabolic disease and alternative sources for high-yield production of naringenin have recently drawn full scientific attention and become an important issue in research.Scope and approachThis review focuses on recent findings of naringenin against metabolic disorders including oxidative stress, hyperlipidemia, obesity, diabetes, inflammation, and organ toxicity. Also, this review highlights the potential sources of naringenin production.Key findings and conclusionsNaringenin exerts its protective effect against metabolic diseases through multiple mechanisms including its antioxidant activity by scavenging free radicals, inducing antioxidant enzymes and targeting on phosphoinositide 3-kinase/protein Kinase B/nuclear factor (erythroid-derived 2)-like 2 (PI3K/Akt/Nrf2), nuclear factor (erythroid-derived 2)-like 2/antioxidant responsive element (NRf2/ARE), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), mitogen-activated protein kinase (MAPK), 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, peroxisome proliferator-activated receptor (PPAR), and nitric oxide-cGMP-protein kinase G-induced K_ATP channel (NO-cGMP-PKG-K_ATP). Moreover, microbial production is recommended as a promising alternative method for large-scale production of naringenin. In conclusion, naringenin is a promising compound for the prevention and management of metabolic diseases. Further clinical studies and trials are needed to prove its protective effects on metabolic syndrome in the human population.     

植物多酚通过Nrf2/ARE信号通路抗氧化作用研究进展

植物多酚是植物体内重要的次生代谢产物,是重要的天然抗氧化剂,能够清除自由基和淬灭活性氧。Nrf2（NF-E2-related factor 2）/抗氧化反应元件（antioxidant response element,ARE）信号通路是增强机体抗氧化功能最重要的保护性信号途径,在细胞抵御氧化应激机制中有着重要的地位,是抗氧化研究领域的热点。本文综述了Nrf2/ARE信号通路的组成及其调节机制,总结植物多酚通过该信号通路增强机体抗氧化应激能力,减少细胞凋亡、参与神经保护、延缓衰老和减少氧化损伤等的能力,以期为植物多酚应用于抗氧化保健食品和药品的开发提供一定依据。     

食品非营养成分发挥生物学作用的信号通路

来自饮食和药用植物的天然植物非营养成分(Phc)具有重要的健康保护和临床应用潜力,这已经得到了全世界的密切关注。主要来自果蔬的植物非营养成分是功能性食品的重要来源,而植物非营养成分已经证明在健康保护、抗癌、防癌,特别是预防现代文明病方面表现出巨大的应用潜力。研究证明,Phc 可以上调表达抗化作用的酶类,促进癌症和突变细胞凋亡、调节,特别是下调免疫应答,改变细胞相Ⅰ和相Ⅱ酶的表达,改变细胞因子网络,从而发挥重要的防病治病作用。大量研究表明,Phc 通过和受体相互作用向机体、组织和细胞传递信号。其信号途径主要涉及：丝裂原- 活化蛋白激酶(MAPK)、蛋白激酶C(PKC)、磷酸肌醇3 激酶(PI3K)、Toll 样受体(TLRs)、异常环氧酶-2(COX-2)、活化因子蛋白-1(AP-1)、核因子κB(NF-κB)等。其中,尤其是NF-κB 与AP-1 直接和炎症、免疫调节和癌症相联系。细胞信号的级联放大作用及不同信号途径之间的交谈和相互作用构成了一个非常复杂的调控网络。MAPK 途径异常,或者其下游转录因子的异常都会造成细胞的异常增殖、免疫功能过头、慢性炎症性疾病、现代文明病和细胞恶性转化。因此,抑制这些信号途径可以提供一个避免现代文明病、各种慢性病和癌症的有效战略。本文就这些信号途径进行综述,并提出自己的观点。     

单宁酸通过抑制TRAF6向细胞质膜的招募抑制Akt信号通路

目的：表皮生长因子受体（epidermal growth factor receptor,EGFR）/蛋白激酶B（protein kinase B, PKB,也称Akt）信号通路在大多数人类实体肿瘤中过度激活、表达失调,促进肿瘤细胞增殖。植物单宁属于植物 多酚类物质,能够抑制肿瘤细胞的增殖。然而,单宁酸通过何种机制调控肿瘤细胞中过度激活的Akt信号通路仍不 清楚。方法：本实验选用人胶质瘤U87细胞作为模型,研究单宁酸抑制人胶质瘤U87细胞EGFR/Akt信号通路的分子 机制。结果：单宁酸抑制人胶质瘤U87细胞Akt的磷酸化以及受Akt信号通路调控的相关蛋白4EBP-1和核糖体S6蛋 白的磷酸化。进一步研究发现,单宁酸抑制肿瘤坏死因子受体相关因子6（tumor necrosis receptor-associated factor 6,TRAF6）向细胞质膜的招募,导致与TRAF6相互作用的Akt蛋白减少,进而抑制人胶质瘤细胞中Akt的磷酸化 激活。利用EGFR组成型激活突变体EGFR vIII研究单宁酸对TRAF6向细胞质膜招募的影响发现：一方面单宁酸对 EGFR的抑制作用需要EGFR胞外区第2～7外显子区域的存在;另一方面单宁酸对EGFR磷酸化的抑制是导致TRAF6 向细胞质膜招募减少的原因。结论：EGFR是单宁酸发挥其抗肿瘤作用的受体蛋白,单宁酸通过抑制EGFR的磷酸 化改变TRAF6向细胞质膜的招募进而介导了单宁酸对肿瘤细胞中Akt磷酸化的抑制,从而控制蛋白质的翻译,为食 品来源单宁酸的抗肿瘤研究提供理论依据。     

Research progress on the regulation of oxidative stress by phenolics: the role of gut microbiota and Nrf2 signaling pathway

In recent years, the increase in high-calorie diets and sedentary lifestyles has made obesity a global public health problem. An unbalanced diet promotes the production of proinflammatory cytokines and causes redox imbalance in the body. Phenolics have potent antioxidant activity and cytoprotective ability. They can scavenge free radicals and reactive oxygen species, and enhance the activity of antioxidant enzymes, thus combating the body's oxidative stress. They can also improve the body's inflammatory response, enhance the enzyme activity of lipid metabolism, and reduce the contents of cholesterol and triglyceride. Most phenolics are biotransformed and absorbed into the blood after the action by gut microbiota; these metabolites then undergo phase I and II metabolism and regulate oxidative stress by scavenging free radicals and increasing expression of antioxidant enzymes. Phenolics induce the expression of genes encoding antioxidant enzymes and phase II detoxification enzymes by stimulating Nrf2 to enter the nucleus and bind to the antioxidant response element after uncoupling from Keap1, thereby promoting the production of antioxidant enzymes and phase II detoxification enzymes. The absorption rate of phenolics in the small intestine is extremely low. Most phenolics reach the colon, where they interact with the microbiota and undergo a series of metabolism. Their metabolites will reach the liver via the portal vein and undergo conjugation reactions. Subsequently, the metabolites reach the whole body to exert biological activity by traveling with the systemic circulation. Phenolics can promote the growth of probiotics, reduce the ratio of Firmicutes/Bacteroidetes (F/B), and improve intestinal microecological imbalance. This paper reviews the nutritional value, bioactivity, and antioxidant mechanism of phenolics in the body, aiming to provide a scientific basis for the development and utilization of natural antioxidants and provide a reference for elucidating the mechanism of action of phenolics for regulating oxidative stress in the body. © 2023 Society of Chemical Industry.     

南极磷虾油对硫酸葡聚糖钠盐诱导溃疡性结肠炎小鼠的抗氧化作用机制

目的:探讨南极磷虾油(Antarctic krill oil,AKO)对硫酸葡聚糖钠盐(dextran sulfate sodium,DSS)诱导溃疡性结肠炎(ulcerative colitis,UC)小鼠的抗氧化作用及其机制.方法:BALB/c小鼠随机分成4组:对照组、DSS组、低剂量AKO组(L-AKO,0.25...     

Ca~(2+)信号通路调控肌纤维类型转化的研究进展

Ca~(2+)信号通路包括钙调神经磷酸酶(calcineurin,CaN)和钙调蛋白激酶(calmodulin kinase,CaMK)两条Ca~(2+)依赖性信号传导途径,其被激活都会促进快肌纤维向慢肌纤维转化。本文综述了CaN和CaMK的组成结构、作用机理、影响Ca~(2+)信号通路调控的主要因素、Ca~(2+)信号通路在肌纤维类型转化中的作用以及与肉品品质的关系,并对其研究方向作出展望,以期为今后通过遗传、营养等措施改善肉品品质提供理论依据。     

巴氏灭活嗜黏蛋白阿克曼氏菌对ox-LDL诱导的HAEC细胞损伤的保护作用及机制初探

目的:本研究以巴氏灭活的嗜黏蛋白阿克曼氏菌（pasteurized Akkermansia muciniphila,PAKK）为研究对象,探究其对氧化低密度脂蛋白（oxidized low density lipoprotein,ox-LDL）诱导的人主动脉内皮细胞（human aortic endothelial cells,HAEC）损伤的保护作用。方法:首先利用MTT法评价PAKK对细胞活性的影响并确定合适的剂量。建立ox-LDL诱导的细胞损伤模型,并通过测定细胞乳酸脱氢酶、活性氧等评价PAKK对细胞损伤的保护作用,最后通过测定抗氧化酶活力以及Nrf2抗氧化通路相关基因及蛋白表达等,探讨PAKK改善HAEC细胞氧化损伤的可能机制。结果:菌数为105和106 CFU/mL的PAKK不影响HAEC细胞的活性;能显著降低ox-LDL诱导HAEC细胞的乳酸脱氢酶释放率;显著降低细胞内的活性氧水平,提高超氧化物歧化酶、过氧化氢酶的活力,以及细胞的总抗氧化能力;显著上调细胞内转录因子核因子-E2相关因子2（nuclear factor erythroid 2-related factor 2,Nrf2）、血红素氧合酶-1（hemeoxygenase-1, HO-1）、谷胱甘肽巯基转移酶（glutathione S-transferase,GST）以及NADPH醌氧化还原酶1 （NADPH quinine oxidoreductase-1,NQO1）的mRNA表达量;显著上调Nrf2、HO-1、NQO1蛋白的表达。结论:本研究表明巴氏灭活的嗜黏蛋白阿克曼氏菌可缓解ox-LDL对HAEC细胞造成的损伤,且其保护作用可能是通过调节Nrf2信号通路从而增强抗氧化相关基因表达。本研究为开发基于嗜黏蛋白阿克曼氏菌的可用于预防动脉粥样硬化的益生菌相关产品奠定理论基础。     

谷物花色苷功能活性与开发利用研究进展

花色苷是一种水溶性类黄酮物质,广泛分布于深色谷物、浆果及蔬菜中。花色苷具有较强的抗氧化和抗炎活性,摄入适量富含花色苷的谷物可降低患糖尿病、心血管疾病、年龄相关性黄斑变性等慢性病的风险。本文系统介绍了不同谷物来源的花色苷对慢性病的健康功效及作用机理,重点阐明花色苷在谷物中的分布与含量,对Nrf2、NF-κB、MAPK、PI3K/AKT等信号通路的调控作用机制,梳理了谷物花色苷的开发利用现状及发展趋势,为谷物花色苷在食品、药品等领域的基础研究及产品开发提供参考依据。