桦木酸抗乳腺癌的作用机制研究进展

乳腺癌是影响全球女性的最常见恶性肿瘤之一,化疗药物的耐药性已成为乳腺癌治疗中最常见的挑战之一。桦木酸是一种天然存在的三萜类化合物,具有多种药理作用。桦木酸能通过抑制乳腺癌肿瘤细胞增殖和生长、促使肿瘤细胞凋亡、抑制肿瘤细胞侵袭和转移、抑制炎症反应以及与其他药物协同抗肿瘤等多个作用机制发挥抗乳腺癌的作用,因此综述了桦木酸抗乳腺癌的作用机制,以期为桦木酸的临床使用提供参考。     

近年来国内外中药抗炎作用机制研究概况

中药抗炎是一个重要的研究领域。大量实验研究表明,很多中药都有很好的抗炎作用,而其抗炎作用机制表现为多种不同的途径。笔者对近年来国内外关于中药通过抑制外源及内源性炎症介质发挥抗炎作用的报道进行综述。     

复方鱼腥草胶囊抗炎作用及机制实验研究

目的研究复方鱼腥草胶囊 (FYC)的抗炎作用并探讨其作用机制。方法采用组胺致大鼠皮肤渗透性增高模型、蛋清足肿胀模型研究FYC的抗炎作用 ,同时采用去双侧肾上腺小鼠耳肿胀模型 ,测定大鼠肾上腺中Vc含量及小鼠炎性渗出物中PGE2 、MDA含量研究FYC的抗炎机制。结果FYC可显著降低组胺所致的皮肤通透性增高 ,减轻蛋清足肿胀 ,使肾上腺中Vc含量降低 ,对去肾上腺小鼠不拮抗二甲苯所致小鼠耳肿胀 ,降低炎性渗出物中PGE2 和MDA含量。结论FYC具有明显抗炎作用 ,其机制可能与激动下丘脑 垂体 肾上腺轴 ,减少PGE2 和MDA含量增加有关     

泻心汤在急性炎症动物模型上的抗炎效应

目的研究泻心汤的抗炎效应及抗炎作用的机制。方法采用4种急性炎症模型,包括大鼠角叉菜胶及蛋清足肿胀、2%冰醋酸小鼠腹腔渗出和小鼠内毒素急性肺损伤模型,观察泻心汤对动物实验性急性炎症模型的影响;并观察小鼠内毒素急性肺损伤模型中,泻心汤对血浆一氧化氮合成酶、一氧化氮、肿瘤坏死因子-α及自由基产物丙二醛的影响。结果泻心汤ig给药后对上述4种炎症模型都具有良好的抗炎效果;并可以抑制内毒素炎症过程中诱生型一氧化氮合成酶的活性,抑制一氧化氮、肿瘤坏死因子-α等炎症因子的产生,减少自由基产物丙二醛生成。结论泻心汤具有良好的抗炎效应,且可以通过多途径产生抗炎作用。     

中草药的抗炎作用成分及其机制

目的对中草药的抗炎成分及其作用机制进行了综述。方法查阅近15年国内外资料并进行汇总、综述。结果大量研究表明中草药具有很好的抗炎作用,有效成分主要集中在苷类、多糖及生物碱类化合物,作用机制明确。结论中草药的抗炎作用具有较好的应用前景。     

中药抗炎作用机制研究进展

目的：为了对中药抗炎机制有一个系统了解，以便更好指导临床用药。方法：综述近年来对中药抗炎作用机制献研究。结果：发现有些中药具有很好的抗炎作用，其抗炎作用有与团体类抗炎药作用相似的，也有类似于非团体类抗炎药的。结论：通过对下丘脑—垂体—肾上腺轴的影响和对炎症介质的抑制是中药发挥其抗炎作用的主要途径。     

中药活性成分抗炎作用研究进展

目的：综述了近年来中药活性成分抗炎作用的研究进展.方法：检索近年来国内相关文献并进行了分析和归纳.结果：许多中药的活性成分对炎症有较好的治疗作用,而且对其抗炎机制的研究也越来越深入.结论：通过对中药活性成分的抗炎作用及其作用机制的研究,可为进一步研究与开发中药抗炎新药提供信息.     

网络药理学挖掘丹参-苦参药对提取物的抗炎药效及分子机制研究

目的通过网络药理学预测丹参-苦参药对的潜在靶点,探索其对于炎症模型的抗炎药效,为新药开发以及药对的抗炎作用机制研究提供依据。方法运用网络药理学预测药对抗炎作用的潜在靶点;采用小鼠二甲苯致耳肿胀模型研究药对提取物的抗炎药效;基于Luminex液相芯片分析技术,探究丹参-苦参提取物经皮给药后外周血清促炎细胞因子分泌的改变;采用伊文思蓝腹腔注射实验模拟炎性因子的渗出,探究药对提取物对小鼠毛细血管通透性的影响。结果网络药理学预测药对提取物发挥抗炎作用主要与免疫过程和血管内皮生长因子(VEGF)信号通路相关,说明机制与抑制促炎因子,改善血管通透性等相关。结论本文通过实验验证了网络药理学的预测结果,确证了抗炎作用涉及降低STAT3通路中IL-6、G-CSF水平及血管通透性,此作用与丹参苦参药对中主要成分丹参酮、苦参碱和氧化苦参碱相关。     

桦木属植物三萜类化合物研究进展

植物次生代谢产物是天然药物的重要来源。桦木属植物具有丰富的药用价值,药理作用机制复杂,这与其中的三萜类化合物具有密不可分的关系。桦木属植物三萜类化合物主要分为达玛烷型、奥克梯隆型、齐墩果烷型、羽扇豆烷型和环阿屯烷型;桦木属植物提取物具有抗肿瘤、抗炎、抗氧化、抗菌等多种活性;桦木属植物三萜类化合物的生物合成途径自2,3-氧化鲨烯之后根据环氧角鲨烯环化酶的不同分为达玛烯二醇Ⅱ、羽扇豆醇、环阿屯醇和香树酯四个分支。本文对桦木属植物三萜类化学成分、药理活性和生物合成途径解析三个方面进行了综述,以期为利用桦木属植物三萜类化合物进行新药研发及利用合成生物学方法在微生物细胞工厂中生产这类化合物提供参考。     

清凉巴布剂的抗炎作用及机制研究

目的研究清凉巴布剂的抗炎作用及作用机制。方法采用二甲苯所致小鼠耳肿胀及角叉菜胶所致大鼠足肿胀,考察清凉巴布剂的抗炎作用,试剂盒检测足肿胀大鼠炎性组织中SOD、MDA、IL-1的含量。结果清凉巴布剂中剂量和高剂量对小鼠耳肿胀及大鼠足肿胀均有显著的抑制作用,可明显降低炎性组织中IL-1、MDA含量,提高SOD活性。结论清凉巴布剂具有良好的抗炎作用,其机制与抑制炎性细胞因子、抗自由基损伤有关。     

Anti-Influenza Activity of Betulinic Acid from Zizyphus jujuba on Influenza A/PR/8 Virus

Betulinic acid, a pentacyclic triterpene isolated from Jujube tree (Zizyphus jujuba Mill), has been known for a wide range of biological and medicinal properties such as antibacterial, antimalarial, anti-inflammatory, antihelmintic, antinociceptive, and anticancer activities. In the study, we investigated the antiviral activity on influenza A/PR/8 virus infected A549 human lung adenocarcinoma epithelial cell line and C57BL/6 mice. Betulinic acid showed the anti-influenza viral activity at a concentration of 50 μM without a significant cytotoxicity in influenza A/PR/8 virus infected A549 cells. Also, betulinic acid significantly attenuated pulmonary pathology including increased necrosis, numbers of inflammatory cells and pulmonary edema induced by influenza A/PR/8 virus infection compared with vehicle- or oseltamivir-treated mice in vivo model. The down-regulation of IFN-γ level, which is critical for innate and adaptive immunity in viral infection, after treating of betulinic acid in mouse lung. Based on the obtained results, it is suggested that betulinic acid can be the potential therapeutic agent for virus infection via anti-inflammatory activity.     

白桦酸及其衍生物的研究进展

对白桦酸衍生物的构效关系及其中的YK-FH312、RPR103611和IC9564等的作用机制及活性进行述评。天然产物白桦酸是有抗HIV和抗肿瘤活性，且具有新型结构和新型作用机制的化合物，其天然来源广泛，半合成方法成熟，是寻找抗HIV和抗肿瘤药物的优秀的先导物。通过对白桦酸的结构修饰，大量白桦酸衍生物已被合成。     

Betulinic acid inhibits the migration and invasion of fibroblast-like synoviocytes from patients with rheumatoid arthritis

The aggressive phenotype displayed by fibroblast-like synoviocytes (FLSs) contributes to cartilage and bone destruction in rheumatoid arthritis (RA). Betulinic acid has been demonstrated to have a positive therapeutic effect on tumor, inflammation and immune disorder, however, the effects of betulinic acid on RA FLSs have not been verified. Therefore, in the present study, we observed the effect of betulinic acid on the migration and invasion of RA FLSs and explored its underlying signal mechanisms. Our results showed that betulinic acid treatment suppressed the migration, invasion and reorganization of the actin cytoskeleton of RA FLSs. In addition, we found that the mRNA expression of IL-1β, IL-6, IL-8 and IL-17A were markedly down-regulated by treatment with betulinic acid in TNF-α-induced RA FLSs. To gain insight into the molecular mechanisms, we evaluated the effect of betulinic acid on NF-κB activation in RA FLSs. The results indicated that betulinic acid treatment reduced the TNF-α-induced activation of NF-κB signal pathway and the NF-κB nuclear accumulation. We also observed that treatment with betulinic acid attenuated synovial inflammation and joint destruction in mice with CIA. Taken together, these results suggest that betulinic acid inhibits the migration and invasion of RA FLSs by blocking NF-κB signal pathway activation.     

Advances in the study of structural modifications and biological activities of betulinic acids

Betulinic acids are lupine-type pentacyclic triterpenoid saponins commonly found in some plants of Betulaceae family, especially in the bark of betula alba (birch). The potent anti-HIV and anti-tumor activities of betulinic acids have been greatly concerned. The natural betulinic acids include betulinic acid, 23-hydroxy betulinic acid, betulin and so on. Some investigations on the structural modifications of betulinic acids were carried out, and many derivatives with excellent biological activity have been obtained nowadays. In this paper, the research advances of the structural modification of betulinic acids, as well as their anti-HIV and anti-tumor activities are reviewed.     

Pharmacological properties of the ubiquitous natural product betulin.

Betulin (lup-20(29)-ene-3beta,28-diol) is an abundant naturally occurring triterpene and it is found predominantly in bushes and trees forming the principal extractive (up to 30% of dry weight) of the bark of birch trees. Presently, there is no significant use for this easily isolable compound, which makes it a potentially important raw material for polymers and a precursor of biologically active compounds. Betulin can be easily converted to betulinic acid, which possesses a wide spectrum of biological and pharmacological activities. Betulinic acid has antimalarial and anti-inflammatory activities. Betulinic acid and its derivatives have especially shown anti-HIV activity and cytotoxicity against a variety of tumor cell lines comparable to some clinically used drugs. A new mechanism of action has been confirmed for some of the most promising anti-HIV derivatives, which makes them potentially useful additives to the current anti-HIV therapy. Betulinic acid is specifically cytotoxic to several tumor cell lines by inducing apoptosis in cells. Moreover, it is non-toxic up to 500 mg/kg body weight in mice. The literature concerning derivatization of betulin for structure-activity relationship (SAR) studies and its pharmacological properties is reviewed.     

白桦酸类化合物的研究进展

白桦酸类化合物是一类可以从多种植物中分离得到的天然产物，包括白桦酸、23-羟基白桦酸、白桦素及其衍生物等，是一类结构及作用机制相对新颖、具有抗HIV-1和抗肿增活性的天然化合物。对这类化合物的结构修饰和改造，目前已经获得大量具有良好生物活性的衍生物。现对这方面的研究进展进行综述。     

Betulinic acid derivatives as anticancer agents: structure activity relationship

Betulinic acid, a pentacyclic triterpene, is widely distributed throughout the tropics. It possesses several biological properties such as anticancer, anti-inflammatory, antiviral, antiseptic, antimalarial, spermicidal, antimicrobial, antileshmanial, antihelmentic and antifeedent activities. However, betulinic acid was highly regarded for its anticancer and anti-HIV activities. Anticancer role of betulinic acid appeared by inducing apoptosis in cells irrespective of their p53 status. Due to high order safety in betulinic acid, a number of structural modifications carried out to improve its potency and efficacy. The C-1, C-2, C-3, C-4, C-20 and C-28 positions are the diversity centers in betulinic acid, and the derivatives resulted on various structural modifications at these positions screened for their anticancer activity. This review presents the structure activity relationship carried out on C-1, C-2, C-3, C-4, C-20, C-28, A-ring, D-ring and E-ring modified betulinic acid derivatives. We have compiled the most active betulinic acid derivatives along with their activity profile in each series. Structure activity relationship studies revealed that C-28 carboxylic acid was essential for the cytotoxicity. The halo substituent at C-2 position in betulinic acid enhanced the cytotoxicity. Though the relation of the cytotoxicity with the nature of substituents at C-3 position could not be generalized but the ester functionality appeared to be a better substituent for enhancing the cytotoxicity. An interesting observation is that the three rings skeleton (A, B and C rings) had played an important role in eliciting anticancer activity, which could be a new molecular skeleton to design new anticancer drugs.     

Betulinic acid,a bioactive pentacyclic triterpenoid,inhibits skeletal-related events induced by breast cancer bone metastases and treatment

Many breast cancer patients experience bone metastases and suffer skeletal complications. The present study provides evidence on the protective and therapeutic potential of betulinic acid on cancer-associated bone diseases. Betulinic acid is a naturally occurring triterpenoid with the beneficial activity to limit the progression and severity of cancer, diabetes, cardiovascular diseases, atherosclerosis, and obesity. We first investigated its effect on breast cancer cells, osteoblastic cells, and osteoclasts in the vicious cycle of osteolytic bone metastasis. Betulinic acid reduced cell viability and the production of parathyroid hormone-related protein (PTHrP), a major osteolytic factor, in MDA-MB-231 human metastatic breast cancer cells stimulated with or without tumor growth factor-β. Betulinic acid blocked an increase in the receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin ratio by downregulating RANKL protein expression in PTHrP-treated human osteoblastic cells. In addition, betulinic acid inhibited RANKL-induced osteoclastogenesis in murine bone marrow macrophages and decreased the production of resorbed area in plates with a bone biomimetic synthetic surface by suppressing the secretion of matrix metalloproteinase (MMP)-2, MMP-9, and cathepsin K in RANKL-induced osteoclasts. Furthermore, oral administration of betulinic acid inhibited bone loss in mice intra-tibially inoculated with breast cancer cells and in ovariectomized mice causing estrogen deprivation, as supported by the restored bone morphometric parameters and serum bone turnover markers. Taken together, these findings suggest that betulinic acid may have the potential to prevent bone loss in patients with bone metastases and cancer treatment-induced estrogen deficiency.