Dose-Response on the Chemopreventive Effects of Sarcophine-Diol on UVB-Induced Skin Tumor Development in SKH-1 Hairless Mice

Sarcophine-diol (SD) is a lactone ring-opened analogue of sarcophine. It has shown chemopreventive effects on chemically-induced skin tumor development in female CD-1 mice, as well as in a UVB-induced skin tumor development model in hairless SKH-1 mice at a dose of 30 μg SD applied topically and 180 mJ/cm² UVB. The objective of this study was to determine the dose-response on the chemopreventive effects of SD on SKH-1 hairless mice when exposed to a UVB radiation dose of 30 mJ/cm². This UVB dose better represents chronic human skin exposure to sunlight leading to skin cancer than previous studies applying much higher UVB doses. Carcinogenesis was initiated and promoted by UVB radiation. Female hairless SKH-1 mice were divided into five groups. The control group was topically treated with 200 μL of acetone (vehicle), and the SD treatment groups were topically treated with SD (30 μg, 45 μg, and 60 μg dissolved in 200 μL of acetone) 1 h before UVB radiation (30 mJ/cm²). The last group of animals received 60 μg SD/200 μL acetone without UVB exposure. These treatments were continued for 27 weeks. Tumor multiplicity and tumor volumes were recorded on a weekly basis for 27 weeks. Weight gain and any signs of toxicity were also closely monitored. Histological characteristics and the proliferating cell nuclear antigen (PCNA) were evaluated in the mice skin collected at the end of the experiment. The dose-response study proved a modest increase in chemopreventive effects with the increase in SD dose. SD reduced the number of cells positively stained with PCNA proliferation marker in mice skin. The study also showed that SD application without UVB exposure has no effect on the structure of skin. The results from this study suggest that broader range doses of SD are necessary to improve the chemopreventive effects.     

A Possible Mechanism of Action of the Chemopreventive Effects of Sarcotriol on Skin Tumor Development in CD-1 Mice

Sarcophine derivatives have been suggested to be chemopreventive in nature. One of its derivatives, Sarcotriol (ST), was investigated to study the skin cancer chemopreventive effects in female CD-1 mice. Three groups (control, promotion, initiation) of 30 female CD-1 mice each were taken. Carcinogenesis was initiated with 7, 12- dimethylbenz (a) anthracene (DMBA) and promoted with 12-O-tetradecanoylphorbol-13- acetate (TPA). One hour before treating with DMBA (200 nmol/100 μl acetone), control and promotion groups were treated with acetone (100 μl) and initiation group with ST (30μg/100μl of acetone). Beginning one week after initiation with DMBA, control and initiation groups were treated with acetone and promotion group with ST (30μg/100μl of acetone), one hour before treating with TPA (5 nmol/100 μl acetone). This was carried out twice a week for the next 20 weeks. The effects of ST on ³H-thymidine incorporation in epidermal DNA, the possible role of apoptotic proteins and COX-2 involved in the prevention of skin tumor development of CD-1 mice were investigated. Tumor incidence and multiplicity was found to be 100%, 73%, 100% and 8.2, 4.8, 9.7 in control, promotion and initiation groups respectively. ST treatment resulted in a significant (P < 0.05) inhibition in the incorporation of ³H-thymidine in epidermal DNA. The promotion group showed higher levels of caspase-3, -8 and –9 compared to the control. COX-2 expression was significantly lower (P < 0.05) in the promotion group as compared to the control. No significant difference in caspase-3, -8, -9 and COX-2 levels were observed in the initiation group compared to control. Together, this study confirms the chemopreventive effects of ST, and for the first time identifies the stage of carcinogenesis at which ST exerts its chemopreventive effect, and elucidates the mechanism possibly by inducing apoptosis and decreasing the COX-2 levels, contributing to its overall cancer chemopreventive effects in the mouse skin cancer model.     

Chemopreventive effects of sarcotriol on ultraviolet B-induced skin tumor development in SKH-1 hairless mice

Sarcotriol (ST) has been shown to be chemopreventive on 7,12-dimethyl-benz(a)anthracene (DMBA) initiated and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted skin tumor development in CD-1 mice in recent studies from our laboratory. The objective of this study was to determine the chemopreventive effects of ST on ultraviolet B (UVB)-induced skin tumor development in female SKH-1 hairless mice, an experimental model relevant to human skin cancer development, and its possible mechanisms of action. Female SKH-1 mice were divided into two groups: Control and ST treated. Control was topically treated with 100 μL acetone and ST treated group administered with 30 μg ST in 100 μL acetone one hour before UVB exposure. For UVB-induced tumorigenesis, carcinogenesis was initiated and promoted by UVB (180 mJ/cm²). Group weights and tumor counts were taken once every week. After 30 weeks, mice were sacrificed and dorsal skin samples were collected. The proteins from the skin sample were further used for SDS-PAGE and Western blotting using specific antibodies against caspase-3, caspase-8, caspase-9 and p53. Tumor multiplicity was found 19.6, 5.2 in the control and ST treated groups respectively. Caspase-3, -8, -9 and p53 were significantly (P < 0.05) upregulated in ST treated group compared to Control group. Together, this study for the first time identifies the chemopreventive effects of ST in UVB-induced carcinogenesis possibly by inducing apoptosis and upregulating p53.     

Echinochrome A Protects against Ultraviolet B-induced Photoaging by Lowering Collagen Degradation and Inflammatory Cell Infiltration in Hairless Mice

Echinochrome A (Ech A, 7-ethyl-2,3,5,6,8-pentahydroxy-1,4-naphthoquinone) has been known to exhibit anti-oxidative and anti-inflammatory effects. However, no study has been carried out on the efficacy of Ech A against skin photoaging; this process is largely mediated by oxidative stress. Six-week-old male SKH-1 hairless mice (n = 36) were divided into five groups. Except for a group that were not treated (n = 4), all mice underwent ultraviolet-B (UVB) exposure for 8 weeks while applying phosphate-buffered saline or Ech A through intraperitoneal injection. UVB impaired skin barrier function, showing increased transepidermal water loss and decreased stratum corneum hydration. UVB induced dermal collagen degeneration and mast cell infiltration. Ech A injection was found to significantly lower transepidermal water loss while attenuating tissue inflammatory changes and collagen degeneration compared to the control. Furthermore, Ech A was found to decrease the relative expression of matrix metalloproteinase, tryptase, and chymase. Taken together, these results suggest that Ech A protects against UVB-induced photoaging in both functional and histologic aspects, causing a lowering of collagen degradation and inflammatory cell infiltration.     

Dieckol Isolated from Eisenia bicyclis Ameliorates Wrinkling and Improves Skin Hydration via MAPK/AP-1 and TGF-β/Smad Signaling Pathways in UVB-Irradiated Hairless Mice

Repetitive exposure to ultraviolet B (UVB) is one of the main causes of skin photoaging. We previously reported that dieckol isolated from Eisenia bicyclis extract has potential anti-photoaging effects in UVB-irradiated Hs68 cells. Here, we aimed to evaluate the anti-photoaging activity of dieckol in a UVB-irradiated hairless mouse model. In this study, hairless mice were exposed to UVB for eight weeks. At the same time, dieckol at two doses (5 or 10 mg/kg) was administered orally three times a week. We found that dieckol suppressed UVB-induced collagen degradation and matrix metalloproteinases (MMPs)-1, -3, and -9 expression by regulating transforming growth factor beta (TGF-β)/Smad2/3 and mitogen-activated protein kinases (MAPKs)/activator protein-1 (AP-1) signaling. In addition, dieckol rescued the production of hyaluronic acid (HA) and effectively restored the mRNA expression of hyaluronan synthase (HAS)-1/-2 and hyaluronidase (HYAL)-1/-2 in UVB-irradiated hairless mice. We observed a significant reduction in transepidermal water loss (TEWL), epidermal/dermal thickness, and wrinkle formation in hairless mice administered dieckol. Based on these results, we suggest that dieckol, due to its anti-photoaging role, may be used as a nutricosmetic ingredient for improving skin health.     

艾纳香油对晒伤小鼠皮肤氧化应激及DNA损伤的影响

观察艾纳香油对UVB照射后Blab/C小鼠晒伤皮肤氧化应激及DNA损伤的影响。通过建立4组小鼠晒伤模型,在5个不同时间相点测定小鼠皮肤晒伤组织厚度和含水量,利用可见光分光光度法测各组皮肤组织中超氧化物岐化酶(SOD)、丙二醛(MDA)、还原型谷胱甘肽(GSH)和8-羟基脱氧鸟苷(8-OHdG)的含量。结果表明：艾纳香油可明显加快晒伤创面处结痂脱落,抑制晒伤皮肤组织增厚(P＜0.05),减少晒伤组织皮肤含水量的丧失(P＜0.05,P＜0.01);在整个治疗过程,能明显提高小鼠血清SOD活性(P＜0.05,P＜0.01),降低皮肤MDA含量(P＜0.05),升高皮肤GSH的水平(P＜0.05),降低皮肤8-OHdG含量(P＜0.01)。艾纳香油可抵抗UVB晒伤后小鼠表皮增厚,减少光产物表达,并通过清除氧自由基,提高抗氧化酶活性而发挥抗氧化作用。     

茶多酚对直链烷基苯磺酸钠致小鼠皮肤损伤的保护作用

本研究主要探讨茶多酚(Tea polyphenol,TP)对直链烷基苯磺酸钠(Linear alkylbenzene sulfonate,LAS)引起小鼠皮肤组织损伤的保护作用。将50只健康昆明种雄性小鼠随机分为5组,每组10只,分别为正常对照组、TP对照组(TP 100 mg·L~(-1))、LAS损伤组(LAS 300 mg·L~(-1))、TP干预组1(LAS 300 mg·L~(-1),TP 100 mg·L~(-1))与干预组2(LAS 300 mg·L~(-1),TP 200 mg·L~(-1))。分别用蒸馏水及不同剂量的LAS及TP涂抹小鼠的背部剃毛处,连续涂抹60 d,观察各组小鼠的饮食、日常活动及体质量变化情况;取背部涂抹皮肤进行HE及Masson染色观察皮肤组织结构及胶原纤维变化情况;检测皮肤中丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、羟脯氨酸(Hyp)及小鼠血清中乳酸脱氢酶(LDH)、一氧化氮(NO)水平。结果表明,TP干预可拮抗LAS引起的小鼠皮肤组织氧化应激及胶原改变;从第6周开始,干预组小鼠体质量增长显著高于LAS损伤组(P0.01);皮肤形态结构有所改善,表皮厚度增加且较为完整,胶原纤维含量增加,纤维排列杂乱、松散、模糊的现象得到改善;皮肤中SOD、GSH-Px及Hyp水平明显增加,MDA含量显著减少(P0.01);血清中LDH、NO水平显著低于LAS损伤组(P0.01)。实验结果表明TP在一定程度上对LAS所致小鼠皮肤的损伤有保护作用。     

不同微生物菌剂对芒萁秸秆腐熟过程中腐殖质构成的影响

以芒萁秸秆为材料,采用室内培养试验,研究了4种微生物菌剂对芒萁秸秆发酵腐熟过程中腐殖质形成的影响。结果表明:发酵30 d后4种微生物菌剂处理均显著降低发酵物全碳量、提高胡敏酸含量、降低胡敏素含量,使PQ值和HA/EA比值显著提高,说明微生物菌剂处理对芒萁秸秆腐殖质形成和组分有显著影响,其中木霉菌处理的效果最为显著,适宜作为芒萁秸秆的腐熟菌。     

儿茶素单体对小鼠急性高尿酸血症的作用

通过腹腔注射300 mg·kg-1氧嗪酸钾盐建立小鼠急性高尿酸血症模型,观察儿茶素单体对模型小鼠血清尿酸水平的影响;进一步进行血清、肝脏黄嘌呤氧化酶(XOD)活性实验和体外XOD抑制试验。结果显示,表儿茶素(EC)、表儿茶素没食子酸酯(ECG)和表没食子儿茶素(EGC)的灌胃剂量均为600 mg·kg-1时,在体内具有极显著降尿酸的作用,与模型对照组相比分别下降了23%(P0.001)、35%(P0.001)和37%(P0.001);ECG可降低小鼠血清和肝脏XOD活性,分别降低了31%(P0.01)和32%(P0.05);在体外ECG和EGCG具有抑制XOD活性的作用。因此,EC、ECG和EGC具有降低高尿酸血症小鼠血清尿酸水平的作用,其中ECG的降尿酸效果与抑制小鼠体内XOD活性有关。     

HND1生物种衣剂防治大豆胞囊线虫药效研究

采用厚垣轮枝菌HDQ18活性产物制备的生物种衣剂HND1原液、稀释5×、10×、20×、50×处理大豆胞囊线虫J2.研究其对大豆胞囊线虫的防效.结果表明:HND1对J2有较高的毒性,其死亡率分别为94.0%、83.3%、61.0%、54.3%、29%.用不同剂量的75% HND1生物种衣剂包衣大豆种子,在大豆出苗1个月后,调杳大豆根系胞囊线虫数量.结果表明:施用HND1种衣剂的3种不同处理的平均防效分别为45.5%、57.5%、60.5%,均好于对照药剂35%多克福种衣剂.对大豆株高和根瘤数等的调查结果表明,HND1种衣剂对大豆的生长和发育安全.     

脑灵素胶囊对小鼠中枢神经系统的影响

通过小鼠自主活动、戊巴比妥钠阈剂量及阈下剂量催眠作用及电刺激强直性惊厥反应,观察脑灵素胶囊对中枢神经系统的影响。结果表明,脑灵素胶囊能明显减少小鼠自主活动次数,可协同戊巴比妥钠阈下剂量的催眠作用,缩短戊阈剂量巴比妥钠小鼠的入睡时间,并延长睡眠持续时间,但对小鼠电刺激强直性惊厥无明显影响。     

Inhibitory Effect of Dihydroaustrasulfone Alcohol on the Migration of Human Non-Small Cell Lung Carcinoma A549 Cells and the Antitumor Effect on a Lewis Lung Carcinoma-Bearing Tumor Model in C57BL/6J Mice

There are many major causes of cancer death, including metastasis of cancer. Dihydroaustrasulfone alcohol, which is isolated from marine coral, has shown antioxidant activity, but has not been reported to have an anti-cancer effect. We first discovered that dihydroaustrasulfone alcohol provided a concentration-dependent inhibitory effect on the migration and motility of human non-small cell lung carcinoma (NSCLC) A549 cells by trans-well and wound healing assays. The results of a zymography assay and Western blot showed that dihydroaustrasulfone alcohol suppressed the activities and protein expression of matrix metalloproteinase (MMP)-2 and MMP-9. Further investigation revealed that dihydroaustrasulfone alcohol suppressed the phosphorylation of ERK1/2, p38, and JNK1/2. Dihydroaustrasulfone alcohol also suppressed the expression of PI3K and the phosphorylation of Akt. Furthermore, dihydroaustrasulfone alcohol markedly inhibited tumor growth in Lewis lung cancer (LLC)-bearing mice. We concluded that dihydroaustrasulfone alcohol is a new pure compound with anti-migration and anti-tumor growth activity in lung cancer and might be applied to clinical treatment in the future.     

L-茶氨酸对小鼠肠道形态结构及游离氨基酸的影响

将50只KM雄性小鼠按每组10只随机分为正常组、谷氨酰胺组及L-茶氨酸低、中、高剂量组,连续灌喂28 d,探究L-茶氨酸对小鼠肠道形态结构及游离氨基酸的影响。结果表明,与正常组相比,小鼠肠道绒毛高度随L-茶氨酸剂量的增大而增加,各剂量组的十二指肠绒毛高度和中、高剂量组的空肠绒毛高度及其绒毛高度与隐窝深度的比值均达显著水平(P<0.05),血清游离氨基酸含量及中、高剂量组的尿素氮含量显著降低(P<0.05),高剂量组的碱性磷酸酶、总蛋白含量显著升高(P<0.05);L-茶氨酸对不同肠道游离氨基酸含量的影响随剂量的增大而升高,其中,十二指肠中的各茶氨酸剂量组的全部必需氨基酸和大部分非必需氨基酸显著升高(P<0.05),且高剂量组的必需氨基酸含量显著高于低剂量组(P<0.05);空肠中的低剂量组的必需氨基酸Thr、Lys、Ile及中、高剂量组的全部必需氨基酸含量显著升高,且中、高剂量组中除Cit外的其他氨基酸含量均显著高于低剂量组(P<0.05);回肠中的低、中、高剂量组的全部必需氨基酸及大部分非必需氨基酸含量显著降低,且中、高剂量组中除GABA外的其他氨基酸含量显著高于低剂量组(P<0.05)。结果表明,L-茶氨酸可通过增加肠道绒毛高度、提高绒毛高度与隐窝深度比值来改善小鼠肠道形态结构,同时可促进十二指肠、空肠对氨基酸的吸收利用。     

Ameliorative Effects of Oyster Protein Hydrolysates on Cadmium-Induced Hepatic Injury in Mice

Cadmium (Cd) is a widespread environmental toxicant that can cause severe hepatic injury. Oyster protein hydrolysates (OPs) have potential effects on preventing liver disease. In this study, thirty mice were randomly divided into five groups: the control, Cd, Cd + ethylenediaminetetraacetic acid (EDTA, 100 mg/kg), and low/high dose of OPs-treatment groups (100 mg/kg or 300 mg/kg). After continuous administration for 7 days, the ameliorative effect of OPs on Cd-induced acute hepatic injury in Cd-exposed mice was assessed. The results showed that OPs significantly improved the liver function profiles (serum ALT, AST, LDH, and ALP) in Cd-exposed mice. Histopathological analysis showed that OPs decreased apoptotic bodies, hemorrhage, lymphocyte accumulation, and inflammatory cell infiltration around central veins. OPs significantly retained the activities of SOD, CAT, and GSH-Px, and decreased the elevated hepatic MDA content in Cd-exposed mice. In addition, OPs exhibited a reductive effect on the inflammatory responses (IL-1β, IL-6, and TNF-α) and inhibitory effects on the expression of inflammation-related proteins (MIP-2 and COX-2) and the ERK/NF-κB signaling pathway. OPs suppressed the development of hepatocyte apoptosis (Bax, caspase-3, and Blc-2) and the activation of the PI3K/AKT signaling pathway in Cd-exposed mice. In conclusion, OPs ameliorated the Cd-induced hepatic injury by inhibiting oxidative damage and inflammatory responses, as well as the development of hepatocyte apoptosis via regulating the ERK/NF-κB and PI3K/AKT-related signaling pathways.     

抗草甘膦转基因大豆饲料对雄性小鼠脾淋巴细胞体外增殖的影响

以雄性昆明鼠为动物模型,对亲本(F0)和子一代(F1)短期(30 d)及长期(90 d)喂食抗草甘膦转基因大豆饲料后,取其脾脏,MTT法检测脾淋巴细胞增殖情况。结果表明:短期喂食实验过程中,在0、2、7、14和30 d取样时,转基因大豆饲料对亲本(F0)实验的雄性小鼠脾脏淋巴细胞体外增殖均无显著性影响(P>0.05),在长期(90 d)喂食实验过程中,抗草甘膦转基因大豆饲料对亲本(F0)小鼠脾脏淋巴细胞体外增殖也无显著影响(P>0.05)。同样,在30 d的短期和90 d的长期喂食实验过程中,抗草甘膦转基因大豆饲料对子一代(F1)雄性小鼠脾脏淋巴细胞体外增殖也均无显著抑制作用(P>0.05)。表明短期(30 d)及长期(90 d)喂食含抗草甘膦转基因大豆饲料对亲本及子一代雄性小鼠脾脏淋巴细胞体外增殖均无显著性影响,且无遗传积累效应。     

UV-B辐射增强对3种湿地植物叶片紫外吸收物质含量的影响

以香蒲、芦苇、鸢尾3种湿地植物为材料,采用模拟人工湿地的方法,研究植物叶片紫外吸收物质含量对3个UV-B辐射强度的响应。结果表明:3种植物叶片类黄酮含量变化趋势为高辐射处理下先增加后降低,低辐射处理条件下持续增加,高辐射处理显著大于低辐射处理、低辐射处理显著大于对照,增强UV-B处理下叶片类黄酮含量平均增幅为鸢尾(21.88%)>芦苇(14.23%)>香蒲(6.16%)。增强UV-B辐射条件下,香蒲和鸢尾叶片类胡萝卜素(Car)含量显著(p<0.05)低于对照,且高辐射处理低于低辐射处理;芦苇叶片Car含量则表现为低辐射处理大于对照、对照大于高辐射处理,两个辐射剂量之间差异显著(p<0.05)。增强UV-B处理下叶片Car含量平均降幅为香蒲(51.00%)>芦苇(26.63%)>鸢尾(17.95%)。说明3种湿地植物对增强UV-B辐射的防御能力为:鸢尾>芦苇>香蒲。     

转Bt基因玉米的生殖毒性评价

将昆明种小鼠按照体重随机分为5组(分别为高、中、低剂量组、阳性对照组和正常对照组),进行显性致死试验和精子畸形试验,评价转Bt基因玉米的生殖毒性。结果显示,饲喂转基因玉米的3组小鼠各项指标间的差异不显著(P0.05),与正常对照组相比亦无显著差别(P0.05),与阳性对照组差别显著(P0.05)。说明使用添加不同剂量转Bt基因玉米的饲料饲喂小鼠不会造成对雄性小鼠的生殖毒性。     

红茶提取物对高尿酸血症小鼠血尿酸的影响

研究红茶提取物对高尿酸血症小鼠血尿酸的影响。将36只雄性KM小鼠随机分为空白组、模型组、红茶提取物低、中、高剂量组及别嘌呤醇组。空白组和给茶组连续1周分别灌胃生理盐水和红茶提取物,给茶组第7天造模后1 h给茶;模型组在第7天腹腔注射氧嗪酸钾并灌胃酵母膏造模。测定结果显示:与模型组相比,各给茶组血尿酸(UA)水平均降低;与模型组相比,给茶组血尿素氮(BUN)水平均降低,其中、高剂量给茶组BUN水平显著降低(P0.05),高剂量组差异极显著(P0.01);各给茶组血肌酐(Cr)值与模型组相比极显著下降(P0.001)。高剂量组黄嘌呤氧化酶(XOD)活性较模型组显著降低(P0.05),低、中剂量组有一定的抑制作用,但无显著差异。研究表明,红茶提取物对氧嗪酸钾和酵母膏导致的小鼠高尿酸血症有明显的改善作用。     

狭叶茶提取物对小鼠氧化应激性肝损伤的保护作用

研究狭叶茶(Camellia angustifolia Chang)提取物对拘束负荷诱发小鼠应激性肝损伤的保护作用。采用拘束负荷小鼠应激性肝损伤模型,18h拘束负荷诱发小鼠应激性肝损伤,分别用赖氏法测定小鼠血浆和肝组织丙氨酸转移酶(ALT)活性、硫代巴比妥酸法测定丙二醛(MDA)含量、HPLC法测定谷胱甘肽(GSH)水平、比色法测定黄嘌呤氧化酶(XOD)、谷胱甘肽过氧化物酶(GPX)和谷胱甘肽S转移酶(GST)活性,荧光酶标仪测定血浆、肝组织及狭叶茶提取物体外抗氧化能力指数(ORAC)。与拘束模型组相比,狭叶茶提取物可以明显提高拘束负荷小鼠血浆与肝组织匀浆的ALT活性和抗氧化能力指数,提高GSH水平,增强GPX和GST活性,有效降低肝组织中MDA含量和XOD活性,并在体外显示出较强的抗氧化能力。说明狭叶茶提取物对拘束应激引起的小鼠肝损伤具有一定的保护作用,其作用机制可能部分来自于减少拘束负荷小鼠氧化应激水平,清除自由基和抑制脂质过氧化过程。     

丸化剂对水稻种子出苗和秧苗生长的影响

以早稻品种金优974、湘早籼31号和晚稻品种新香优80、湘早籼10号为材料,比较研究了自研的丸化剂与进口种衣剂对水稻萌发、出苗、秧苗素质、苗期抗病虫能力的效应.结果表明,用丸化种衣剂包衣有利于种子发芽和出苗,提高秧苗综合素质.其中,成秧率提高6.8%～9.4%,秧苗根系活力提高7.1%～32.4%,病虫害防治效果分别达到95.7%～98.5%和77.5%～90.35%.