白黎芦醇体外抗肝纤维化实验研究

目的:探讨白黎芦醇体外抗肝纤维化的作用机制。方法:原位灌流分离大鼠肝细胞,以维生素E作阳性对照,检测不同浓度白黎芦醇对四氯化碳(CCl4)损伤后肝细胞中丙二醛(MDA)、丙氨酸氨基转移酶(ALT)活性和肝细胞存活率的影响;并用肝星状细胞(HSC)与次氮基三醋酸铁共同培养产生氧应激后,检测不同浓度白黎芦醇对HSC增殖和Ⅰ型胶原生成的影响,并测定细胞培养液中MDA、超氧化物歧化酶(SOD)活性。结果:白黎芦醇明显改善CCl4损伤后肝细胞存活率,抑制CCl4引起的ALT、MDA活性升高,并能明显抑制HSC氧应激后MDA活性升高和SOD活性的降低,抑制HSC增殖和Ⅰ型胶原的生成。结论:白黎芦醇抗肝纤维化作用可能与其抗脂质过氧化有关。     

白黎芦醇的研究现状

白黎芦醇是一种天然的抗氧化物和自由基廓清剂,笔者通过白黎芦醇的来源、一般特性及药理作用的总结分析,探讨分析了白黎芦醇的研究现状。     

虎杖药理作用研究进展

虎杖含有多种药理活性成分,其主要有效成分白黎芦醇苷,具有扩血管、抗血栓、抗休克、降血脂及抗氧化等作用;另外,虎杖还具有抗菌、抗病毒及保肝等作用。临床用于治疗高血压、动脉粥样硬化、高脂血症及各种病毒感染等疾病。     

虎杖苷在心血管方面作用的研究

虎杖苷（polydatin。PD）,也称为白黎芦醇苷,是从蓼科蓼属虎杖的干燥根茎中提取的第4种单体,故又名虎杖结晶4号。它是白藜芦醇与葡萄糖结合的产物,属于芪类化合物,即羟基二苯乙烯类化合物,化学名称为3,4’,5-三羟基芪-3-B-单-D-葡萄糖苷。虎杖苷具有较强的生物活性,研究表明,虎杖苷能调节心肌细胞收缩性、抑制血小板聚集、降血脂、抗脂质过氧化、抗休克等作用,此外还能减轻多种因素造成的组织器官损伤。     

白藜芦醇和乙醇对内毒素诱导小鼠腹腔巨噬细胞炎性因子产生的作用

目的:研究白藜芦醇和乙醇对细菌内毒素活化的小鼠腹腔巨噬细胞炎性因子产生的相互作用.方法:Griess试剂法检测NO产生;小鼠胸腺细胞增殖法检测IL-1的产生;ELISA检测IL-6,TNF-α的生成.结果:自藜芦醇(6.25,12.5,25 μmol/L)和乙醇(0.2％,0.8％)剂量依赖性和协同性地抑制24小时LPS(1 mg/L)和IFN-γ(5 kU/L)刺激的NO的产生;25μmol/L的白黎芦醇还抑制IL-6的产生,此作用可被乙醇加强;乙醇单独对24小时IL-1的产生无影响,但可提高自藜芦醇促进IL-1产生的作用;低剂量乙醇抑制巨噬细胞TNF-α产生,但两种浓度的乙醇与白黎芦醇共用时均增强白黎芦醇对TNF-α的产生的促进作用.结论:白黎芦醇和乙醇对巨噬细胞功能分子的产生有调控作用.     

逆没食子酸抗突变、防癌研究概况

逆没食子酸是一种天然多元酚化合物,具有抗突变和防癌作用。本文综述了近30年来逆没食子酸抗突变、防癌的机理研究,以及对皮肤、肝、肠、肺与支气管、食道等多种器官的化学保护作用。     

鞣质的药理作用（Ⅱ）—抗肿瘤作用

鞣质具有广泛的药理活性，其中在化学致癌过程中的拮抗作用已引起人们的普遍关注。本文着重介绍在防癌抑癌体内外实验研究中的作用，并概述其作用机理和化学结构与抗肿瘤作用的构效关系，提示植物药中的鞣质类物质是一种具有抗肿瘤潜能的活性成分。     

不同工艺的虎杖提取物中白黎芦醇甙含量的比较

虎伏提取物分别用水与不同浓度（３０％，５０％，７０％）乙醇处理，通过反相高效液相色谱法，测定不同工艺的虎杖提取物中的白黎芦醇甙的含量。综合比较分析得出以水作为溶媒能更有效地将白黎芦醇甙提取出来。     

大戟科黄酮类化合物的研究进展

大戟科植物具有抗肿瘤、抗病毒、抗氧化、抗炎等多种生物学活性,根据其化学结构又可分为黄酮类、黄酮醇类、二氢黄酮（醇）类和花色素类等4种结构类型。大戟科黄酮类化合物结构新颖,药用前景广阔,值得深入研究及开发。本文综述了大戟科黄酮类化合物的化学结构及其药理活性研究概况。     

大蒜提取物抗肿瘤作用研究进展

癌是严重威胁人类生命和健康的恶性肿瘤,中药大蒜含有多种抗癌活性成分,其抗癌、防癌作用已被国内外大量实验研究结果证实。本文就大蒜提取物的抗癌、防癌作用及在这方面的研究进展作一综述。     

Targeting multiple signal pathways by chemopreventive agents for cancer prevention and therapy

In recent years, growing interest has been focused on the field of cancer prevention. Cancer prevention by chemopreventive agents offers significant promise for reducing the incidence and mortality of cancer. Chemopreventive agents may exert their effects either by blocking or metabolizing carcinogens or by inhibiting tumor cell growth. Another important benefit of chemopreventive agents is their nontoxic nature. Therefore, chemopreventive agents have recently been used for cancer treatment in combination with chemotherapeutics or radiotherapy, uncovering a novel strategy for cancer therapy. This strategy opens a new avenue from cancer prevention to cancer treatment. In vitro and in vivo studies have demonstrated that chemopreventive agents could enhance the antitumor activity of chemotherapeutics, improving the treatment outcome. Growing evidence has shown that chemopreventive agents potentiate the efficacy of chemotherapy and radiotherapy through the regulation of multiple signaling pathways, including Akt, NF-κB, c-Myc, cyclooxygenase-2, apoptosis, and others, suggesting a multitargeted nature of chemopreventive agents. However, further in-depth mechanistic studies, in vivo animal experiments, and clinical trials are needed to investigate the effects of chemopreventive agents in combination treatment of cancer with conventional cancer therapies. More potent natural and synthetic chemopreventive agents are also needed to improve the efficacy of mechanism-based and targeted therapeutic strategies against cancer, which are likely to make a significant impact on saving lives. Here, we have briefly reviewed the role of chemopreventive agents in cancer prevention, but most importantly, we have reviewed how they could be useful for cancer therapy in combination with conventional therapies.     

Resveratrol as an Inhibitor of Carcinogenesis

Abstract

Given the high probability of developing cancer over the period of a normal life span, cancer chemoprevention provides an attractive therapeutic strategy for the delay or reversal of this process. A variety of phytochemicals, such as sulfides, isothiocyanates, glucosinolates, flavonoids, carotenoids, phenols, and diarylhepanoids, are known to mediate chemopreventive responses. Resveratrol, a ubiquitous stilbene found in the diet of human beings (e.g., as a component of grapes and wine), was uncovered by bioassay-guided fractionation and found to mediate cancer chemopreventive activity in a murine model with mechanisms involving various stages of the carcinogenic process. This work spurred a myriad of studies that are summarized in this article. As demonstrated with in vitro. and cell culture models, resveratrol functions through a plethora of mechanisms, which can vary from model to model. Results from differential gene expression studies are daunting. Irrespective of the precise mechanism, however, efficacy has been demonstrated in some animal models, and a critical evaluation of resveratrol data relative to the characteristics of a promising cancer chemopreventive agent leads to favorable consideration. Animal studies have shown cancer inhibitory activity in a number of models, including adenoma, skin, breast, colon, esophagus, glioma, intestinal, liver, and neuroblastoma. Biomarkers are known, and ample quantities of compound can be produced. Dietary administration is feasible. Several small-scale human trials are under way, and human intervention trials may follow. As learned by past experience, data from these trials are necessary prior to drawing any conclusions, but the current cancer chemopreventive profile of resveratrol provides promise for widespread use in the future.     

Garlic [Allium sativum]: a review of its potential use as an anti-cancer agent

Garlic [Allium sativum] is among the oldest of all cultivated plants. It has been used as a medicinal agent for thousands of years. It is a remarkable plant, which has multiple beneficial effects such as antimicrobial, antithrombotic, hypolipidemic, antiarthritic, hypoglycemic and antitumor activity. In this review, we will discuss particularly the largely preclinical use of this agent in the treatment and prevention of cancer. A number of studies have demonstrated the chemopreventive activity of garlic by using different garlic preparations including fresh garlic extract, aged garlic, garlic oil and a number of organosulfur compounds derived from garlic. The chemopreventive activity has been attributed to the presence of organosulfur compounds in garlic. How this is achieved is not fully understood, but several modes of action have been proposed. These include its effect on drug metabolizing enzymes, antioxidant properties and tumor growth inhibition. Most of these studies were carried out in the animal models. Also, recent research has focused on the antimutagenic activity of garlic. Recently, it has been observed that aged garlic extract, but not the fresh garlic extract, exhibited radical scavenging activity. The two major compounds in aged garlic, S-allylcysteine and S-allylmercapto-L-cysteine, had the highest radical scavenging activity. In addition, some organosulfur compounds derived from garlic, including S-allylcysteine, have been found to retard the growth of chemically induced and transplantable tumors in several animal models. Therefore, the consumption of garlic may provide some kind of protection from cancer development.     

Efficacy of chemopreventive agents in mouse mammary gland organ culture (MMOC) model: a comprehensive review

Currently, breast cancer is considered as one of the leading causes for death in women in the United States. Consumption of natural products has received considerable attention in recent years as a possible approach for cancer prevention in general population. There are numerous cancer preventive agents present in the natural products, which may contribute to their chemopreventive properties. During the past two decades, numerous chemopreventive agents have been isolated and/or synthesized and evaluated for their efficacy in a variety of biological assays. To this end, we have established and utilized mouse mammary gland organ culture model (MMOC) as a bioassay for identifying chemopreventive agents. Mammary glands respond to growth promoting hormones and the physiological differentiation can be reproduced in MMOC in chemically defined medium by altering hormonal milieu. Both estrogen and progesterone dependent (mammary ductal lesions, MDL) and independent (mammary alveolar lesions, MAL) precancerous lesions can be induced in response to a 24 hour exposure to DMBA in MMOC. Suppression of the incidence and multiplicity of these lesions by a possible chemopreventive agent can serve as a tool to evaluate efficacy of potential experimental agents. Using this approach, we have evaluated more than 200 synthetic and natural product-derived chemopreventive agents in this model as a part of the National Cancer Institute-supported projects. Many of these chemopreventive agents expressing significant activity have progressed to the in vivo experimental mammary carcinogenesis studies. Thus, this bioassay has proven to be a valuable tool for screening cancer chemopreventive agents for breast cancer prevention and for understanding molecular mechanism(s) of action of these agents. In this comprehensive review, we provide a complete list of chemopreventive agents evaluated for the efficacy against development of mammary alveolar lesions (MAL) in MMOC along with the recent developments in this area. The structure-activity relationships for many chemopreventive agents evaluated in the MMOC model have been discussed.     

Developing curcumin into a viable therapeutic for lymphoma

Background: Emerging evidence suggests that natural plant ingredients have played an important role in the healthcare of many countries. Several of these natural plant products possess therapeutic potential for various diseases including cancer. Curcumin is the pigment of turmeric, a well-known chemopreventive agent that has been shown to suppress the proliferation of a wide variety of tumor cells, including lymphoma. Curcumin has been shown to have cancer chemopreventive potential against a variety of tumors via targeting key survival pathways that are aberrantly activated in cancer cells. Methods: This review discusses therapeutic potential of curcumin in malignancies of lymphoma as well as therapeutic implications of the recent advances in the field. Results/conclusion: Dietary-compound curcumin hardwires to multiple cellular processes. Suppression of cell proliferation, induction of apoptosis, and inhibition of metastasis are considered to be the major mechanisms underlying its anticancer properties.     

Biological effects of curcumin and its role in cancer chemoprevention and therapy

Curcumin, a natural component of the rhizome of curcuma longa has emerged as one of the most powerful chemopreventive and anticancer agents. Its biological effects range from antioxidant, anti-inflammatory to inhibition of angiogenesis and is also shown to possess specific antitumoral activity. The molecular mechanism of its varied cellular effects has been studied in some details and it has been shown to have multiple targets and interacting macromolecules within the cell. Curcumin has been shown to possess anti-angiogenic properties and the angioinhibitory effects of curcumin manifest due to down regulation of proangiogenic genes such as VEGF and angiopoitin and a decrease in migration and invasion of endothelial cells. One of the important factors implicated in chemoresistance and induced chemosensitivity is NFkB and curcumin has been shown to down regulate NFkB and inhibit IKB kinase thereby suppressing proliferation and inducing apoptosis. Cell lines that are resistant to certain apoptotic inducers and radiation become susceptible to apoptosis when treated in conjunction with curcumin. Besides this it can also act as a chemopreventive agent in cancers of colon, stomach and skin by suppressing colonic aberrant crypt foci formation and DNA adduct formation. This review focuses on the various aspects of curcumin as a potential drug for cancer treatment and its implications in a variety of biological and cellular processes vis-à-vis its mechanism of action.     

Resveratrol and cancer: chemoprevention,apoptosis, and chemo-immunosensitizing activities

The polyphenolic compound Resveratrol is a naturally occurring phytochemical and can be found in many plant species, including grapes, peanuts and various herbs. Several studies have established that Resveratrol can exert anti-oxidant and anti-inflammatory activities. It also has activity in the regulation of multiple cellular events associated with carcinogenesis. This review describes the general properties of Resveratrol including its relationship to estrogen, its effect on lipid metabolism, its cardiovascular effects, and its role on gene expression. Resveratrol has also been examined in several model systems for its potential effect against cancer. Its anti-cancer effects include its role as a chemopreventive agent, its ability to inhibit cell proliferation, its direct effect in cytotoxicity by induction of apoptosis and on its potential therapeutic effect in pre-clinical studies. In addition, Resveratrol has been shown to exert sensitization effects on cancer cells that will result in a synergistic cytotoxic activity when Resveratrol is used in combination with cytotoxic drugs in drug-resistant tumor cells. Clearly, the studies with Resveratrol provide support for the use of Resveratrol in human cancer chemoprevention and combination with chemotherapeutic drugs or cytotoxic factors in the treatment of drug refractory tumor cells.     

Modulating Polo-Like Kinase 1 as a Means for Cancer Chemoprevention

Naturally occurring agents have always been appreciated for their medicinal value for both their chemopreventive and therapeutic effects against cancer. In fact, the majority of the drugs we use today, including the anti-cancer agents, were originally derived from natural compounds, either in their native form or modified to enhance their bioavailability or specificity. It is believed that for maximum effectiveness, it will useful to design novel target-based agents for chemoprevention as well as the treatment of cancer. Recent studies have shown that the serine/threonine kinase polo-like kinase (Plk) 1 is widely overexpressed in a variety of cancers and is being increasingly appreciated as a target for cancer management. Additionally, several chemopreventive agents have been shown to inhibit Plk1 in cancer cells. In this review, we will discuss if Plk1 could also be a target for designing novel strategies for cancer chemoprevention.     

Antiproliferative and antioxidant activities of Juglans regia fruit extracts

Context: Cancer chemopreventive action of walnut [Juglans regia L. (Juglandaceae)] has been explored.

Objective: This study evaluated antiproliferative and antioxidant activities of walnut.

Materials and methods: Various fractions of walnut extract have been screened for antiproliferative activity against human cancer cell lines using the MTT assay. All these fractions have also been evaluated for total phenolic content, antioxidant activity, and reducing power capacity.

Results and discussion: Chloroform and ethyl acetate fractions exhibited a high level of antiproliferation against HepG-2, liver cancer cell line (IC₅₀?=?9 and 15 µg/mL, respectively).

Conclusion: Exhibiting high phenolic content, antioxidant activity, and potent antiproliferative activity, walnut may act as a cancer chemopreventive agent.     

Phase II study of Fenretinide (N-[4-Hydroxyphenyl]retinamide) in advanced breast cancer and melanoma

Summary Retinoids, the natural and synthetic analogs of vitamin A, are growth-inhibiting and differentiation-inducing agents and show clinical promise as chemopreventive and antineoplastic agents. Fenretinide, a new synthetic retinoid, has antitumor activity in certain in vitro and in vivo model systems and was relatively nontoxic in phase I trials. Based on these data, we designed a phase II study of Fenretinide involving 31 patients with advanced breast cancer [15] and melanoma [16], two cancers shown to be responsive to this agent in preclinical models. Fenretinide was inactive in patients with advanced disease. Toxicity was mild, and reversible. Mucocutaneous side effects occurred in 16 (52%) patients. Nyctalopia developed in three patients one of whom developed decreased B-wave amplitude of the scotopic electroretinogram. The minimal toxicity and significant activity in preclinical studies make this an attractive agent for future breast cancer chemoprevention studies.