Protective effects of naringin against drugs and chemical toxins induced hepatotoxicity: A review

The liver is a vital metabolic organ for drug and xenobiotic metabolism which is influenced by chemical and natural toxins. Liver injury is associated with systemic oxidative stress, which leads to cellular necrosis, fibrosis, tissue lipid peroxidation, and depletion in glutathione levels. Considering the lack of reliable hepato‐protective drugs in modern medicine, plant‐derived phytoconstituents seem to be a noteworthy option. Naringin is an abundant flavonoid found in citrus fruits with various pharmacological benefits such as antioxidant, anti‐inflammatory, and antiapoptotic, activities. In this review, we summarize available data from recent studies about the hepatoprotective effects of naringin against chemical toxicants and discuss the possible mechanisms of actions.     

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??Based on overseas and domestic data bank mainly as Scifinder, ACS publication, CNKI, and CQVIP. The relationships between the types of natural products and their anti-allergic activities have been summarized. The advances of anti-allergic natural products over the past ten years have been reviewed. The pathogenesis of allergic diseases and the diversity of anti-allergy components and natural products were summarized, together with their origins and mechanisms of anti-allergy activities. Many natural products show multiple anti-allergy targets and few side effects, while the research is still far from enough. Several suggestions were proposed for further research on anti-allergy natural medicines on the basis of our review.     

Selected Secondary Plant Metabolites for Cancer Therapy

Secondary plant metabolites reveal numerous biological activities making them attractive as resource for drug development of human diseases. As the majority of cancer drugs clinically established during the past half century is derived from nature, cancer researchers worldwide try to identify novel natural products as lead compounds for cancer therapy. Natural products are considered as promising cancer therapeutics, either as single agents or in combination protocols, to enhance the antitumor activity of additional therapeutic modalities. Most natural compounds exert pleotrophic effects and modulate various signal transduction pathways. A better understanding of the complex mechanisms of action of natural products is expected to open new perspectives in coming years for their use alone or in combination therapies in oncology. Two major strategies to identify novel drug candidates from nature are the bioactivity-guided fractionation of medicinal plant extracts to isolate cytotoxic chemicals and the identification of small molecules inhibiting specific targets in cancer cells. In the present review, we report on our own efforts to unravel the molecular modes of action of phytochemicals in cancer cells and focus on resveratrol, betulinic acid, artesunate, dicentrine and camptothecin derivatives.     

Natural compounds in the chemoprevention of alcoholic liver disease

Alcoholic liver disease (ALD), caused by excessive consumption of alcohol, is a major cause of chronic liver disease worldwide. Much effort has been expended to explore the pathogenesis of ALD. Hepatic cell injury, oxidative stress, inflammation, regeneration, and bacterial translocation are all involved in the pathogenesis of ALD. Immediate abstinence is the most important therapeutic treatment for affected individuals. However, the medical treatment for ALD had not advanced in a long period. Intriguingly, an increasing body of research indicates the potential of natural compounds in the targeted therapy of ALD. A plethora of dietary natural products such as flavonoids, resveratrol, saponins, and β‐carotene are found to exert protective effects on ALD. This occurs through various mechanisms composed of antioxidative, anti‐inflammatory, iron chelation, pro‐apoptosis, and/or antiproliferation of hepatic stellate cells and hepatocellular carcinoma cells. In this review, we will summarize current knowledge about the pathogenesis and treatments of ALD and focus on the potential of natural compounds in ALD therapies and underlying mechanisms.     

Advances in traditional Chinese medicine for liver disease therapy in 2020

Liver diseases are gradually becoming a serious threat to human health worldwide.Although a number of medications have been introduced for the prophylaxis,diagnosis,and treatment of liver diseases,several limitations and challenges remain.Traditional Chinese medicine is frequently used to treat liver diseases and well known to protect hepatocytes and inhibit inflammation,oxidative stress,and fibrosis.However,given the complex composition of traditional Chinese medicine,clarifying the mechanisms behind its curative and protective effects is difficult.In this review,research progress on traditional Chinese medicine for the treatment of liver diseases in 2020 is summarized on the basis of the literature available in the PubMed database.Herbal extracts derived from traditional Chinese medicine,including flavonoids,polysaccharides,saponins,and alkaloids,and Chinese medicinal formulas,such as the classic decoctions Chaihu Shugan powder,Linggui Zhugan decoction,and Huanglian Jiedu decoction,have shown promising therapeutic efficacy in liver disease treatment.We summarized the findings of several studies on the active ingredients of traditional Chinese herbs used for liver disease treatment in 2020,focusing mainly on their ability to confer antiviral effects to treat hepatitis,regulate antioxidant levels and apoptosis to treat liver injury,inhibit inflammation and improve dysfunctions in amino acids and energy metabolism to treat alcoholic liver disease,reduce hepatic lipid deposition to treat nonalcoholic fatty liver disease,promote activated hepatic stellate cells to treat liver fibrosis,inhibit the proliferation or promote the apoptosis of liver cancer cells to treat hepatocellular carcinoma,and improve bile acid metabolism to treat cholestasis.     

Paeoniflorin ameliorates ANIT‐induced cholestasis by activating Nrf2 through an PI3K/Akt‐dependent pathway in rats

Cholestasis causes hepatic accumulation of bile acids leading to liver injury, fibrosis and liver failure. Paeoniflorin, the major active compound isolated from the roots of Paeonia lactiflora pall and Paeonia veitchii Lynch, is extensively used for liver diseases treatment in China. However, the mechanism of paeoniflorin's hepatoprotective effect on cholestasis has not been investigated yet. In this study, we administered paeoniflorin to rats for 3 days prior to alpha‐naphthylisothiocyanate (ANIT) administration for once, then went on administering paeoniflorin to rats for 3 days. The data demonstrated that paeoniflorin significantly prevented ANIT‐induced change in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphates (ALP), serum total bilirubin (TBIL), direct bilirubin (DBIL), total bile acid (TBA) and gamma‐glutamyl transpeptidase (γ‐GT). Histology examination revealed that paeoniflorin treatment rats relieved more liver injury and bile duct proliferation than ANIT‐administered rats. Moreover, our data indicated that paeoniflorin could restore glutathione (GSH) and its related synthase glutamate‐cysteine ligase catalytic subunit (GCLc) and glutamate‐cysteine ligase modifier subunit (GCLm) in ANIT‐treated group. In addition, the RNA and protein expression of Akt and nuclear factor‐E2‐related factor‐2 (Nrf2) were also activated by paeoniflorin in ANIT‐induced rats. These findings indicated that paeoniflorin protected ANIT‐induced cholestasis and increased GSH synthesis by activating Nrf2 through PI3K/Akt‐dependent pathway. Therefore, paeoniflorin might be a potential therapeutic agent for cholestasis. Copyright © 2015 John Wiley & Sons, Ltd.     

Stilbenoids from Rheum undulatum Protect Hepatocytes Against Oxidative Stress Through AMPK Activation

Oxidative stress promotes several diseases, including liver disease. We have isolated several stilbenoids from Rheum undulatum to investigate their hepatoprotective activities and mechanism. Stilbenoids from R. undulatum protects hepatocytes against arachidonic acid + iron (AA + Fe) induced oxidative stress. Pterostilbene (compound 5) shows stronger activity than the others. Trimethoxystilbenoid (compound 6) shows best activity on protection of HepG2 cells from AA + Fe‐induced oxidative stress, and trans‐stilbenoid (compound 7) shows weak activity. These stilbenoids suppress ROS generation in AA + Fe‐treated HepG2 cells and also suppress AA + Fe‐induced MMP disruption. Their protective effects on AA + Fe‐induced MMP disruption were abrogated by treatment of AMP‐activated protein kinase (AMPK) inhibitor, compound C or transfection of dominant negative form of AMPK. Taken together, stilbenoids from R. undulatum protect hepatocytes against AA + Fe‐induced oxidative stress through AMPK activation. And the methoxy groups in the aryl groups are important for their cytoprotective activity. Copyright © 2015 John Wiley & Sons, Ltd.     

枸杞多糖的神经保护作用机制研究进展

枸杞多糖是从茄科枸杞属植物宁夏枸杞的果实中提取分离得到的多糖类化合物,是枸杞中的主要有效成分之一,具有增强免疫、抗氧化、抗衰老、抗肿瘤、保护视网膜、保护肝脏、保护神经系统、降血糖降血脂等多种药理作用。目前,枸杞多糖在临床上广泛用于多种疾病的治疗,包括肿瘤及免疫类疾病,高血压高血脂,急性肝损伤,脑缺血及脑中风等。尤其对于阿尔茨海默症,脑缺血等神经系统疾病的治疗具有显著的临床疗效,使枸杞多糖在中枢神经系统方面的应用受到越来越多的重视。近年来,有关枸杞多糖保护神经系统的研究成果不断涌现,为了推进枸杞多糖在防治中枢神经系统疾病方面的作用机制研究,本文结合国内外最新报道,对近年来枸杞多糖发挥神经保护作用的途径进行系统总结和陈述,主要包括改善神经退行性病变、视神经保护、抑制氧化应激、抑制细胞凋亡、抑制炎症反应、降低谷氨酸毒性作用、抑制神经细胞非正常分化等几个方面。虽然枸杞多糖保护神经系统的作用机制主要涉及以上几种途径,但对于枸杞多糖神经保护作用机制的某些部分研究不够深入,枸杞多糖的神经保护作用机制仍然非常复杂,需从现代分子生物学和基因分析技术入手,为枸杞多糖对神经系统保护作用的深入研究提供依据和思路。     

Isobavachalcone attenuates myotube atrophy induced by TNF‐α through muscle atrophy F‐box signaling and the nuclear factor erythroid 2‐related factor 2 cascade

Skeletal muscle atrophy is a condition characterized by damaged muscle fibers and reduced numbers of muscle cells due to various causes. Muscle atrophy is associated with chronic diseases, such as heart failure, diabetes, and aging‐related diseases. Isobavachalcone (IBC) is a flavonoid found in various foods and natural products, and studies have investigated its diverse effects, including its neuroprotective and anticancer effects. However, no studies have evaluated the effects of IBC on muscle atrophy. Thus, in this study, we assessed the effects of IBC on prevention of muscle atrophy. To evaluate the preventive effects of IBC on muscle atrophy, we used C2C12 myoblasts and induced muscle atrophy by tumor necrosis factor (TNF)‐α. IBC regulated the expression levels of muscle atrophy F‐box and muscle RING finger‐1 in response to damaged muscle cells, thereby restoring the expression of myosin heavy chain and myogenin. Moreover, IBC regulated the phosphorylation of the nuclear factor‐κB and p38 and upregulated the expression of nuclear factor erythroid 2‐related factor 2 and heme oxygenase‐1, which are involved in regulating oxidative stress. Our results indicated that IBC acted to relieve TNF‐α‐induced skeletal muscle atrophy by regulating the factors related to inflammation and oxidative stress.     

基于网络药理学探讨清肝化瘀颗粒对非酒精性脂肪性肝病和肝癌“异病同治”的作用机制

目的:基于网络药理学研究方法,探讨清肝化瘀颗粒治疗非酒精性脂肪性肝病(NAFLD)和肝癌的有效成分、作用靶点及可能作用机制,并为其对NAFLD和肝癌"异病同治"的合理性阐释提供依据。方法:通过多个中药与疾病数据库,运用网络药理学筛选清肝化瘀颗粒治疗NAFLD和肝癌的主要有效成分与作用靶点。通过STRING 11.0分析作用靶点之间的相互作用,使用cytoHubba插件从作用靶点中筛选出核心作用靶点。使用Metascape数据库对作用靶点进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析。同时,利用体外试验验证清肝化瘀颗粒主要有效成分之一山柰酚对肝癌细胞模型与NAFLD细胞模型的作用。结果:共筛选出清肝化瘀颗粒治疗NAFLD及肝癌的作用靶点43个,对应8味中药中的136种有效成分。富集分析结果显示作用靶点共涉及20种生物过程,13种分子功能,9种细胞组分及15条信号通路。利用构建的"中药-成分-靶点-疾病"网络图发现清肝化瘀颗粒主要通过以山柰酚、槲皮素及木犀草素为代表的主要有效成分对胱天蛋白酶-3(CASP3),肿瘤蛋白p53(TP53),血管内皮生长因子A(VEGFA)等枢纽基因参与细胞凋亡抑制等与肝癌有关的肿瘤生物学行为进行调节,同时对氧化应激等与NAFLD相关的生物学行为进行调节。体外试验发现山柰酚可以剂量依赖性地抑制肝癌细胞的增殖,并对NAFLD细胞模型氧化应激标志物丙二醛(MDA)及谷胱甘肽过氧化物酶(GPx)的浓度进行调节;同时,山柰酚还可对肝癌与NAFLD细胞模型中枢纽基因CASP3蛋白水平的表达量进行调节。结论:清肝化瘀颗粒对NAFLD与肝癌"异病同治"的主要机制涉及以槲皮素、木犀草素及山柰酚为代表的多成分,以VEGFA,TP53及CASP3为代表的多靶点,以及以氧化应激及细胞凋亡为代表的多通路。     

Antioxidant and Anti‐Inflammatory Properties of the Citrus Flavonoids Hesperidin and Hesperetin: An Updated Review of their Molecular Mechanisms and Experimental Models

Inflammation and oxidative stress are two major causes of various life‐threatening diseases. Hesperidin (Hsd) and its aglycone, hesperetin (Hst), are two flavonoids from citrus species that have numerous biological properties, particularly antioxidant and anti‐inflammatory. New findings showed that the antioxidant activity of Hsd/Hst was not only limited to its radical scavenging activity, but it augmented the antioxidant cellular defenses via the ERK/Nrf2 signaling pathway as well. Various in vitro and in vivo studies have been conducted to evaluate Hsd, its metabolites, or its synthetic derivatives at reducing inflammatory targets including NF‐κB, iNOS, and COX‐2, and the markers of chronic inflammation. In this review, new findings regarding the molecular targets of Hsd and Hst in the reduction of oxidative stress are discussed. Also, in the anti‐inflammatory section, we provide a summary of significant investigations concerning the mechanisms of action based on the studied inflammation models. Copyright © 2014 John Wiley & Sons, Ltd.     

黄酮类成分抗肝纤维化作用及其机制的研究进展

肝纤维化是肝脏对各种急慢性肝损伤进行的一种创伤修复过程,以细胞外基质的过度增生与异常沉积为主要病理特征,其持续发展会恶化为肝硬化、肝癌等疾病。肝纤维化具有可逆性,减轻或逆转肝纤维化被认为是预防肝硬化、肝癌的重要手段。研究表明,黄酮类成分具有抗肝纤维化的作用,其作用机制与抗炎、抗氧化应激、抗凋亡、抑制细胞外基质的异常堆积等有关。黄酮类成分通过多通路、多靶点减轻或逆转肝纤维化进程,近年来备受学者重视。对近10年来国内外报道的具有抗肝纤维化活性的黄酮类成分及其作用机制进行总结,以期为开发黄酮类抗肝纤维化药物提供参考。     

Overview of biological effects of Quercetin on ovary

Over the last few decades, using natural products has been increased to treat different diseases. Today, great attention has been pointed toward the usage of natural products such as flavonoids, especially Quercetin (QUR), in the treatment of diseases. QUR as a natural antioxidant has been traditionally used to prevent or treat a variety of diseases such as cancer, cardiovascular disease, polycystic ovary syndrome (PCOS), obesity, chronic inflammation, and reproductive system dysfunction. Several studies demonstrated that QUR acts as an anti‐inflammatory, anti‐apoptotic, antioxidant, and anticancer agent. With this in view, in this study, we intended to describe an overview of the biological effects of QUR on the ovary. QUR improves the quality of oocytes and embryos. It affects the proliferation and apoptosis and decreases the oxidative stress in granulosa cells (GCs). Furthermore, QUR can be used as a complementary and alternative therapy in ovarian cancer and it has beneficial effects in the treatment of PCOS patients. It seems that QUR as a supplementary factor has different activities for the treatment of different disorders and it also has bidirectional activities. However, further investigations are needed for understanding the efficacy of QUR in the treatment and improvement of gynecological patients.     

补肾类方药及中药有效成分抗衰老的作用机制研究进展

衰老是一个涉及多个方面包括脏腑器官、细胞组织以及多种年龄相关性疾病的生命阶段。中医认为肾虚与衰老密切相关,补肾在延缓衰老方面发挥着重要作用,中药可以多途径、多靶点、多功效地起到延缓衰老的作用,文章查阅文献归纳了补肾类方药及中药有效成分在延缓衰老研究中的作用机制,包括调节氧化应激、调节内质网应激、调节细胞凋亡、调节免疫反应、促进干细胞增殖与分化、神经保护作用等,以期为中药抗衰老的研究提供借鉴。     

Therapeutic potential of rutin in male infertility: A mini review

Male infertility has become a problem worldwide, and recent research has emphasized the development of more effective therapy options. Among natural compounds, rutin has been widely studied for its potential to treat dysfunction related to male infertility, including a reduction in sperm quality, spermatogenesis disruption and structural disruption in the testis. A thorough review of scientific literature published in several databases, including Google Scholar, PubMed/MEDLINE and Scopus, was us...     

基于调控法尼醇X受体的中药治疗肝内胆汁瘀积的研究进展

肝内胆汁瘀积是临床常见病、多发病,其形成机制十分复杂。熊脱氧胆酸和奥贝胆酸是目前FDA批准的仅有的2个用于治疗胆汁瘀积的药物。法尼醇X受体(FXR)是胆汁酸合成和转运的关键调节因子,其高表达对于维持胆汁酸的内环境稳态、降低胆汁酸对肝脏的毒性具有重要意义。中药可以通过多靶点、多途径发挥作用,针对主要发病机制的同时,兼顾次要发病机制,相互协同,在治疗肝内胆汁瘀积方面疗效显著。多种中药及其提取物或有效成分被证明能够通过激活FXR靶点而发挥保肝利胆作用,引起国内外广泛关注。对胆汁酸的体内代谢过程和FXR在肝内胆汁瘀积治疗中的作用进行概述,总结了基于调控FXR的中药治疗肝内胆汁瘀积的研究进展,以期为中药新药的开发提供参考。     

鼠尾草酸的体内氧化应激调节作用研究进展

氧化应激会破坏核酸、蛋白质和脂质等多种生物分子的结构和功能,导致基因表达调控、细胞信号转导、物质摄取及胞内运输等重要生命活动受到影响,是多种组织器官发生病变的主要因素。鼠尾草酸富含于迷迭香等植物中,能够活化细胞内抗氧化系统[如核转录因子E2相关因子2-BTB-Kelch样ECH相关蛋白1(nuclear factor erythroid-2 related factor 2-BTB-Kelch-like ECH-associated protein 1,Nrf2-Keap1)、沉默交配型信息调节因子2同源蛋白1(silent mating type information regulation 2 homolog 1,Sirt1)等信号通路]清除活性氧,同时抑制其他促进氧化应激的信号通路[如核转录因子κB(nuclear factor-kappa B,NF-κB)、糖基化终末产物(advanced glycation end products,AGE)等],抑制活性氧的作用,最终减缓甚至阻止氧化应激,有效预防和治疗如神经系统、视网膜、心血管、肝脏等组织器官的病变。笔者整理归纳了鼠尾草酸对氧化应激相关疾病的调节机制,为推进鼠尾草酸临床应用的转化提供参考。