翘鳞伞胞外多糖的抗肿瘤活性和对荷瘤小鼠免疫功能的影响

为考察翘鳞伞胞外多糖对荷瘤小鼠体内肿瘤的抑制及其免疫功能的影响;采用无机陶瓷膜从翘鳞伞(Pholiota squarrosa)AS 5.245液体发酵醪中分离得到的胞外粗多糖(Crude Extracellular Polysaccharide,CEP),以荷瘤S180小鼠为试验对象,用免疫器官重量法,进行高、中、低剂量CEP的腹腔注射试验;试验结果表明,CEP具有较高的抑瘤活性,并呈剂量相关性;中、高剂量组与对照组相比较,小鼠胸腺指数和脾脏指数均有显著增加(P0.05);与低剂量组相比较,亦均有显著增加;表明CEP可以增强荷瘤小鼠的免疫功能对肿瘤进行抑制。     

酶法修饰绿茶多糖对免疫低下模型小鼠免疫活性的影响

以糖苷酶溶液为工具酶,研究酶法修饰茶多糖对环磷酰胺抑制的免疫低下模型小鼠的免疫功能的影响。结果表明,原多糖TPS与改性后的茶多糖ETPS在免疫低下模型小鼠的细胞免疫功能、体液免疫功能、单核-巨噬细胞功能和NK细胞活性4个方面的实验中,结果均呈阳性,说明它们均具有明显的增强免疫功能的作用,酶法修饰改性能显著提高绿茶多糖的免疫活性。在同等剂量下,ETPS与TPS相比能提高脾指数、腹腔巨噬细胞吞噬率和吞噬指数,能显著提高DTH试验耳肿程度、血清HC50、NK细胞活性。绿茶多糖通过酶法修饰免疫活性得到增强。     

安吉白茶多糖对实验性糖尿病小鼠的降血糖作用研究

通过制备去甲肾上腺素致糖尿病小鼠模型及四氧嘧啶致高血糖小鼠模型,给正常小鼠、去甲肾上腺素致高血糖小鼠及四氧嘧啶致糖尿病小鼠连续灌胃安吉白茶多糖14 d后,取血测定血糖水平,以探讨安吉白茶多糖对正常小鼠、去甲肾上腺素致高血糖小鼠及四氧嘧啶致高血糖小鼠血糖水平及糖耐量（GT）的影响。结果显示,灌胃2周后,安吉白茶多糖对正常小鼠血糖水平影响较小,低、中、高剂量组与正常对照组相比均无显著意义(P>0.05);安吉白茶多糖能明显降低去甲肾上腺素所致糖尿病小鼠的血糖水平,低、中、高剂量组的血糖值与肾上腺素模型组比较,差异极显著(P<0.01)。且高剂量组降血糖效果优于低剂量组;安吉白茶多糖明显降低四氧嘧啶所致高血糖小鼠的血糖水平,三剂量组的血糖值与四氧嘧啶模型组比较,差异极显著(P<0.01)。三剂量均能降低实验性高血糖小鼠血糖,且随剂量增大,降血糖作用增强,以高剂量降糖作用最强。安吉白茶多糖在缓解糖尿病小鼠糖耐量降低方面作用显著,达到了药物组的治疗水平,但并不影响正常小鼠的血糖和糖耐量。     

春石斛品种Dendrobium Second Love‘Tokimeki’与金钗石斛多糖免疫活性的比较研究

为比较春石斛栽培品种Dendrobium Second Love‘Tokimeki’与金钗石斛的粗多糖、精多糖(除蛋白多糖)和多糖水洗组分(过层析柱分离的水洗组分)的免疫活性差异,分别对昆明小鼠灌胃上述6种不同纯度的多糖,观察其对小鼠脏体指数、迟发性变态反应、抗体积数和小鼠腹腔巨噬细胞吞噬百分比与吞噬指数等免疫学指标的影响。结果表明:2种石斛的免疫活性随多糖纯度的提高而增强,纯度最高的多糖水洗组分免疫活性最强,且各指标均显著高于对照。D.Second Love‘Tokimeki’和金钗石斛同等纯度的多糖在胸腺指数、脾脏指数、小鼠耳肿胀率及小鼠抗体积数上均无显著差异,而D.Second Love‘Tokimeki’的3种不同纯度多糖的吞噬指数均达到了与金钗石斛多糖水洗组分无显著差异的水平。综合来看,栽培品种D.Second Love‘Tokimeki’的多糖免疫活性与金钗石斛多糖相近,具有良好的药用开发价值。     

中国绿茶的抗肿瘤作用 Ⅱ.龙雾茶提取物抗癌和免疫动物实验

龙雾茶提取物对荷瘤小鼠艾氏腹水癌、肝癌、肉瘤180等实体瘤,以每公斤体重50毫克剂量给药为最佳,抑瘤率分别为45%、57%和61%;艾氏腹水型荷瘤小鼠生命延长率为128%。免疫实验证明,茶叶提取物对小鼠因荷瘤而导致的 T 淋巴细胞和自然杀伤细胞免疫活性反应下降具有显著的回升作用,T 淋巴细胞~(125)IUDR 参入值(cpm)由对照组的932±27提高到2998±210,自然杀伤细胞活性由对照组10.7%提高到41%,恢复到了正常实验小鼠的水平。     

大豆异黄酮和皂甙对H_(22)小鼠肝癌移植瘤的生长抑制及促细胞凋亡作用

为了探讨大豆异黄酮和皂甙对H_(22)小鼠肝癌移植瘤的生长抑制及促细胞凋亡作用,建立小鼠皮下H_(22)移植瘤模型,将其分为模型组、5-氟尿嘧啶组、大豆异黄酮组和大豆皂甙组。大豆异黄酮和大豆皂甙组分别按200 mg·kg~(-1)剂量每日灌胃给药,共10次;5-Fu组按25 mg·kg~(-1)剂量隔日腹腔注射给药,共5次。实验末期处死动物,计算抑瘤率、胸腺指数和脾脏指数,苏木素-伊红(HE)染色法观察肿瘤组织病理学变化,比色法检测肿瘤组织Caspase-3和Caspase-8相对活性以及血清还原型谷胱甘肽(GSH)含量、总抗氧化活力(T-AOC)和丙二醛(MDA)含量。结果表明:与模型组比较,大豆异黄酮和皂甙处理均能显著降低H_(22)小鼠肝癌移植瘤组织的瘤重,提高抑瘤率,其抑癌率分别为36.3%和34.8%。同时,大豆异黄酮和皂甙均显著升高荷瘤小鼠脾脏指数,增高肿瘤组织Caspase-3和Caspase-8相对活性,降低小鼠血清MDA水平,增高血清GSH和T-AOC水平。试验说明大豆异黄酮和皂甙对H_(22)小鼠肝癌移植瘤具有明显的抑瘤作用,其作用可能与其促细胞凋亡和抗氧化作用有关。     

人参地黄桑葚片对小鼠免疫功能的影响

目的探索人参地黄桑葚片对小鼠免疫功能的影响。方法将雄性ICR小鼠随机分为对照组、人参地黄桑葚片高剂量组(2.250g/kg)、人参地黄桑葚片中剂量组(0.750g/kg)、人参地黄桑葚片低剂量组(0.375g/kg),每组15只,连续灌胃人参地黄桑葚片30天,称量各组小鼠免疫重量并计算器官指数、测定绵羊红细胞(SRBC)诱导的迟发型变态反应(DTH)、自然杀伤(NK)细胞的活性、脾淋巴细胞增殖能力、腹腔巨噬细胞对鸡红细胞(CRBC)的吞噬能力。结果人参地黄桑葚片高、中、低剂量组均能显著增加小鼠胸腺指数及脾脏指数(P0.05);人参地黄桑葚片高、中剂量组能显著增强小鼠NK细胞活性及SRBC诱导的小鼠DTH(P0.05);人参地黄桑葚片高剂量组能显著提高腹腔巨噬细胞对CRBC的吞噬作用及Con A诱导的脾淋巴细胞的增殖力(P0.05)。结论人参地黄桑葚片对小鼠的免疫器官指数、NK细胞活性、腹腔巨噬细胞对CRBC的吞噬作用、Con A诱导脾淋巴细胞的增殖能力以及SRBC诱导的小鼠DTH具有的提高作用。     

人参皂苷M1硬脂酸酯抗肿瘤活性的研究

研究人参皂苷M1硬脂酸酯(SM1)对小鼠肝癌腹水型(HepA)细胞和小鼠胃癌(MFC)细胞的生长抑制作用。采用动物移植瘤模型,以生理盐水组、阳性药环磷酰胺组作对照,对SM1抗癌活性进行筛选评价。对于小鼠肝癌(HepA)细胞,SM1给药组瘤重为1.44±0.57克,其肿瘤抑制率为51.66%,与生理盐水处理的对照组瘤重(2.97±0.54克)比较差异具有极显著统计学意义(P0.001);对于小鼠胃癌(MFC)细胞,SM1给药组瘤重为1.60±0.68克,其肿瘤抑制率为52%,与生理盐水处理的对照组瘤重(3.32±1.39克)比较差异具有显著统计学意义(P0.05)。SM1能显著抑制小鼠体内肝癌细胞和胃癌细胞的生长,具有显著的抗肿瘤作用。     

茶多糖对肉仔鸡免疫功能和抗氧化能力的影响

在AA肉鸡的饮水中分别加入0%、0.2%和0.4%的茶多糖,研究其对肉仔鸡免疫功能和抗氧化能力的影响。试验结果表明,茶多糖能显著促进肉仔鸡胸腺的生长发育(P<0.05),可以明显升高血清中免疫球蛋白IgG的含量(P<0.05),提高T-淋巴细胞数和淋巴细胞转化率(P<0.05),增强白细胞吞噬功能(P<0.05),但对法氏囊的生长发育没有明显作用;同时,茶多糖能显著提高肉仔鸡血清中SOD活力(P<0.05)、GSH-Px活力(P<0.05)和CAT活力(P<0.05),并能明显降低血清中MDA含量(P<0.05)。     

园参与林下山参对小鼠免疫功能影响的比较

目的考察园参与林下山参对小鼠免疫功能的影响。方法将正常的小鼠随机分成7组,即:对照组,园参原粉小、中、大剂量(0.17、0.34、0.51g生药/kg)组,10年以上林下山参原粉小、中、大剂量(0.17、0.34、0.51g生药/kg)组,每组10只,连续灌胃给药30天后,处死小鼠。观察各组小鼠胸腺指数和脾脏指数、脾淋巴细胞增殖能力、巨噬细胞吞噬功能。结果园参原粉和林下山参原粉高剂量组显著增加正常成年小鼠的胸腺指数和脾脏指数:园参原粉和林下山参原粉大、中剂量显示出提高巨噬细胞对鸡红细胞的吞噬率。结论人参对于免疫器官重量及指数、脾淋巴细胞的增殖、腹腔巨噬细胞吞噬率有一定的提高作用,并且林下山参活性强于园参。     

大豆异黄酮对小鼠肝癌移植瘤血管生成的抑制作用

为了探讨大豆异黄酮对肝癌移植瘤血管生成的抑制作用,建立小鼠H22肝癌皮下移植瘤模型。用大豆异黄酮干预10 d,利用免疫组化染色法检测肿瘤组织内微血管密度,利用免疫印迹法检测肿瘤组织内血管内皮细胞生长因子(VEGF)、血管内皮细胞生长因子受体2(VEGFR2)和缺氧诱导因子-1α(HIF-1α)的表达,酶联免疫吸附测定(ELISA)法检测转化生长因子-β1(TGF-β1)和基质金属蛋白酶2(MMP2)的水平。结果显示,大豆异黄酮组移植瘤细胞生长受到抑制,细胞坏死较严重。与模型组比较,大豆异黄酮组肿瘤组织内微血管密度降低;VEGF、VEGFR2和HIF1α的蛋白表达降低;TGF-β1及MMP2蛋白表达下降。提示,大豆异黄酮对小鼠H_(22)移植瘤组织的血管生成具有抑制作用,机制可能与下调移植瘤组织VEGF和TGF-β1蛋白表达有关。     

Immunomodulatory Properties of Highly Viscous Polysaccharide Extract from the Gagome Alga (<Emphasis Type="Italic">Kjellmaniella crassifolia</Emphasis>)

Marine brown algae are rich in sulfated polysaccharides, which have the ability to form gels and viscous solution. Sulfated polysaccharides exhibit many biological activities; however, little is known whether the viscoelastic property in the polysaccharide extract is correlated with biological activities. We examined the immunomodulatory properties of highly viscous polysaccharide extract (HVPE) from Gagome Kjellmaniella crassifolia in a murine model, and the effects were compared with those of a less viscous polysaccharide extract (LVPE). HVPE or LVPE (10, 30, and 100 mg/kg/day) were orally administered to C57BL/6 mice for 14 days. Secretions of cytokine and IgA in Con A-stimulated spleen and Peyer’s patch (PP) cells and phagocytic activity of peritoneal macrophages was determined. IFN-γ, IL-12, IL-6, and IgA secretions showed high levels in spleen cell cultures from mice administered HVPE, whereas these effects were diminished in the LVPE-administered mice. The phagocytic activity of peritoneal macrophages was enhanced by the continuous oral administration of HVPE, and these effects were higher than those of LVPE. Furthermore, an increase in IgA secretion by administration of HVPE was observed in Con A-stimulated PP cells. These results suggest that the polysaccharide extract from K. crassifolia has immunomodulatory activities, which depend on the viscosity.     

Antitumor Effect of a Polypeptide Fraction from Arca subcrenata in Vitro and in Vivo

Arca subcrenata Lischke is a marine traditional Chinese medicine. The study investigated the antitumor effects of P2, a polypeptide fraction from A. subcrenata, and its toxicity in vitro and in vivo. The results showed that P2 could inhibit the proliferation of seven tumor cell lines, especially in HeLa and HT-29 cell lines. The IC₅₀ values were 11.43 μg/mL for HeLa and 13.00 μg/mL for HT-29 treated by P2 for 48 h. P2 had little cytotoxicity on normal liver cells (L-02). The maximum tolerated dose (MTD) of P2 on KM mice was 1000 mg/kg by i.p. or i.v. The tumor growth inhibitory ratios of P2 were 26.4%, 41.4% and 46.4% for H-22, and 34.0%, 45.8% and 60.1% for S-180 tumor-bearing mice. The results demonstrated that P2 might be a potential antitumor agent with high efficiency in dose-dependent and time-dependent manners and low toxicity.     

Purification, characterization and antitumor activities of a new protein from Syngnathus acus, an officinal marine fish

Discovery and development of new antitumor agents from abundant marine fish are attracting an increasing interest. In the present study, we extracted and purified a novel antitumor protein Syngnathusin from the whole body of Syngnathus acus L., a precious marine fish traditionally used for tumors. Syngnathusin was comprised of 16 kinds of amino acids, mainly acidic amino acids. Its molecular weight was 67.3 kDa and its isoelectric point was 4.57. The N-terminal amino acid sequence of Syngnathusin was determined to be Lys-Arg-Asp-Leu-Gly-Phe-Val-Asp-Glu-Ile-Ser-Ala-His-Tyr and showed no significant homology with the known proteins. Syngnathusin could significantly inhibit the growth of A549 and CCRF-CEM cells. However, the obvious proliferation inhibition against human non-tumor cell lines was not observed. Flow cytometry, morphologic assessment and comet assay revealed that Syngnathusin could induce apoptosis in A549 and CCRF-CEM cells and strongly cooperated with MTX. Syngnathusin could inhibit the growth of S180 tumor transplanted in mice. Syngnathusin may be developed as a novel, selective and effective antineoplastic agent.     

Laminaria japonica Peptides Suppress Liver Cancer by Inducing Apoptosis: Possible Signaling Pathways and Mechanism

The anticancer properties of Laminaria japonica peptides (LJPs) have never been studied. Here, we extracted LJPs from fresh seaweed and explored their anti-liver cancer activity (in vivo and in vitro). LJPs were isolated/purified by HPLC-ESI-MS. HepG2 cell apoptosis and cell cycle were evaluated. MTT assays were used to examine the cytotoxicity of LJPs. Caspase activation of caspases 3 and 9, cleaved caspases 3 and 9, and cleaved PARP was examined by Western blotting. The PI3K/AKT pathway and the phosphorylation states of MAPKs (p38 and JNK) were examined. We found that the LJP-1 peptide had the most antiproliferative activity in H22 cells in vitro. LJP-1 blocked H22 cells in the G0/G1 phase, accompanied by inhibition of cyclin expression. LJP-1 induced apoptosis through caspase activation and regulation of the ASK1/MAPK pathway. Concurrent in vivo studies demonstrated that LJP-1 significantly inhibited tumor growth and induced tumor cell apoptosis/necrosis. In conclusion, LJPs, particularly LJP-1, exert strong inhibitory effects on liver cancer growth in vivo and in vitro. LJP-1 induces HCC cell apoptosis through the caspase-dependent pathway and G0/G1 arrest. LJP-1 induces caspase-dependent apoptosis, in part by inhibiting PI3K, MAPK signaling pathways, and cell cycle proteins. LJP-1 has the potential to be a novel candidate for human liver cancer therapeutics.     

In Vivo Induction of Apoptosis by Fucoxanthin, a Marine Carotenoid, Associated with Down-Regulating STAT3/EGFR Signaling in Sarcoma 180 (S180) Xenografts-Bearing Mice

Previous in vitro researches have showed that fucoxanthin, a natural carotenoid isolated from sargassum, can inhibit proliferation or induce apoptosis in human neuroblastoma, hepatoma, leukemia, colon carcinoma, prostate cancer or urinary bladder cancer cells. But the precise mechanism by which fucoxanthin exerts anticarcinogenic effects is not yet fully understood. In this study, we performed an in vivo study to investigate the anti-tumor effect and mechanisms of fucoxanthin on xenografted sarcoma 180 (S180) in mice. Results revealed that fucoxanthin significantly inhibited the growth of sarcoma at the dose of 50 or 100 mg/kg. TUNEL analysis showed that the number of positive cells in the fucoxanthin-treated group was higher than that in the control group. Western blotting analysis also revealed the suppressed expression of bcl-2 and enhanced expression of cleaved caspase-3 by fucoxanthin. In addition, immunohistochemistry analysis and Western blotting analysis showed that fucoxanthin significantly decreased the expressions of survivin and vascular endothelial growth factor (VEGF). Most importantly, fucoxanthin inhibited the expressions of the epidermal growth factor receptor (EGFR) and STAT3 and phosphorylated STAT3 proteins. These results indicated that in vivo induction of apoptosis by fucoxanthin is associated with down-regulating STAT3/EGFR signaling in S180 xenografts-bearing mice.