T-2 toxin is a mycotoxin that has harmful effects on the immune system and cognitive function. Betulinic acid (BA) is a plant-derived pentacyclic lupane-type triterpenoid which possesses a wide spectrum of bioactivities. The study was aimed to explore whether BA has a protective effect on cognitive impairment and oxidative stress caused by T-2 toxin. BA was suspended in 1% soluble starch by continuous intragastric administration for 14 days, then the brain damage in mice was induced by a single intraperitoneal injection of T-2 toxin (4 mg/kg). It was found that BA alleviated the reduction of discrimination index in T-2 toxin-treated mice, and enhanced dopamine (DA), 5-hydroxytryptamine (5-HT), and acetylcholine (ACH) levels of brain neurotransmitter. Meanwhile, BA pretreatment ameliorated oxidative stress through increase of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione (GSH) levels, and inhibition of the generation of reactive oxygen species (ROS) and malondialdehyde (MDA) in the brain of mice exposed to T-2 toxin. Moreover, BA reduced brain hemorrhage and ecchymosis, improved the mitochondrial morphology, enriched the number of organelles, and inhibited cell apoptosis in brain challenged with T-2 toxin. Furthermore, BA inhibited mRNA expression of pro-inflammatory cytokines such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) as well as enhanced mRNA expression of anti-inflammatory cytokine such as IL-10 in the brain of T-2 toxin-triggered mice. Therefore, BA could improve the cognitive function, enhance the antioxidant capacity, and inhibit the secretion of proinflammatory cytokines in brain, thereby playing a preventive and protective role against brain damage caused by T-2 toxin.

Betulinic acid (BA), an occurring pentacyclic triterpenoid, has various biological activities, such as anti-inflammation and antioxidation. Previous studies found that BA attenuated cyclophosphamide (CYP)-induced intestinal mucosal damage by inhibiting intestinal mucosal barrier dysfunctions and cell apoptosis. However, the effects and regulation mechanisms of BA on CYP-induced renal damage has not been reported in literature. Here, we found that BA pretreatment alleviated the elevation of serum urea level and inhibited the increase in serum neutrophil gelatinase-associated lipocalin level induced by CYP. Meanwhile, BA ameliorated renal tubular epithelial cell edema, and vacuolization of renal cortical tubular and renal glomerulus. Moreover, pretreatment with BA inhibited the mRNA expressions of pro-inflammatory cytokines interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α, and increased mRNA expressions of anti-inflammatory cytokines such as IL-10 and transforming growth factor-β by inactivation nuclear factor kappa-B. Simultaneously, BA decreased the accumulation of reactive oxygen species and malondialdehyde, and lowered the levels of superoxide dismutase and glutathione, while increased the activity of glutathione peroxidase in CYP-induced kidney damage mice. Besides, BA reduced the phosphorylation of extracellular signal-regulated kinases (ERK), inhibited the ratio of Bcl-2/Bax and cell apoptosis in CYP-triggered kidney damage. Furthermore, BA and/or PD98059 (an inhibitor of ERK) regulated mitigation of CYP-elicited renal injury and deactivation of the ERK pathway and mitochondrial apoptotic pathway, indicating that the protective effect of BA on CYP-induced renal damage may be associated with the down-regulation of ERK-mediated mitochondrial apoptotic pathway. Thus, BA could be a candidate agent against chemotherapy drug-induced nephrotoxicity by reducing inflammation and oxidative stress through suppression of ERK-mediated mitochondrial apoptotic pathway.

T-2 toxin, a trichothecene mycotoxin produced by Fusarium, is widely distributed in crops and animal feed and frequently induces intestinal damage. Betulinic acid (BA), a plant-derived pentacyclic lupane-type triterpene, possesses potential immunomodulatory, antioxidant and anti-inflammatory biological properties. The current study aimed to explore the protective effect and molecular mechanisms of BA on intestinal mucosal impairment provoked by acute exposure to T-2 toxin. Mice were intragastrically administered BA (0.25, 0.5, or 1 mg/kg) daily for 2 weeks and then injected intraperitoneally with T-2 toxin (4 mg/kg) once to induce an intestinal impairment. BA pretreatment inhibited the loss of antioxidant capacity in the intestine of T-2 toxin-treated mice by elevating the levels of CAT, GSH-PX and GSH and reducing the accumulation of MDA. In addition, BA pretreatment alleviated the T-2 toxin-triggered intestinal immune barrier dysregulation by increasing the SIgA level in the intestine at dosages of 0.5 and 1 mg/kg, increasing IgG and IgM levels in serum at dosages of 0.5 and 1 mg/kg and restoring the intestinal C3 and C4 levels at a dosage of 1 mg/kg. BA administration at a dosage of 1 mg/kg also improved the intestinal chemical barrier by decreasing the serum level of DAO. Moreover, BA pretreatment improved the intestinal physical barrier via boosting the expression of ZO-1 and Occludin mRNAs and restoring the morphology of intestinal villi that was altered by T-2 toxin. Furthermore, treatment with 1 mg/kg BA downregulated the expression of p-NF-κB and p-IκB-α proteins in the intestine, while all doses of BA suppressed the pro-inflammatory cytokines expression of IL-1β, IL-6 and TNF-α mRNAs and increased the anti-inflammatory cytokine expression of IL-10 mRNA in the intestine of T-2 toxin-exposed mice. BA was proposed to exert a protective effect on intestinal mucosal disruption in T-2 toxin-stimulated mice by enhancing the intestinal antioxidant capacity, inhibiting the secretion of inflammatory cytokines and repairing intestinal mucosal barrier functions, which may be associated with BA-mediated inhibition of the NF-κB signaling pathway activation.

T-2 toxin, the most toxic of the trichothecenes, is widely found in grains and feeds, and its intake poses serious risks to the health of humans and animals. An important cytotoxicity mechanism of T-2 toxin is the production of excess free radicals, which in turn leads to oxidative stress. Betulinic acid (BA) has many biological activities, including antioxidant activity, which is a plant-derived pentacyclic triterpenoid. The protective effects and mechanisms of BA in blocking oxidative stress caused by acute exposure to T-2 toxin in the thymus of mice was studied. BA pretreatment reduced ROS production, decreased the MDA content, and increased the content of IgG in serum and the levels of SOD and GSH in the thymus. BA pretreatment also reduced the degree of congestion observed in histopathological tissue sections of the thymus induced by T-2 toxin. Besides, BA downregulated the phosphorylation of the p38, JNK, and ERK proteins, while it upregulated the expression of the Nrf2 and HO-1 proteins in thymus tissues. The results indicated that BA could protect the thymus against the oxidative damage challenged by T-2 toxin by activating Nrf2 and suppressing the MAPK signaling pathway.

为了探究桦木酸(betulinic acid,BA)对环磷酰胺(cyclophosphamide,CYP)导致的肝脏损伤的影响.将50只昆明小鼠随机分为5个组,即空白组、CYP组以及BA低、中、高剂量组.空白组和CYP组用1％(质量分数,下同)的可溶性淀粉灌胃,而其余各组按0.25、0.50、1.00?mg/kg?mb?BA剂量混悬在1％可溶性淀粉糊中灌胃,连续灌胃14?d后,除空白组腹腔注射生理盐水外,其余各组连续2?d腹腔注射CYP(50 mg/kg mb)诱导肝损伤模型.检测血清中谷丙转氨酶(alanine aminotransferase,ALT)和谷草转氨酶(aspartate aminotransferase,AST)活力;检测肝脏超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)、过氧化氢酶(catalase,CAT)活力,以及还原型谷胱甘肽(glutathione,GSH)和丙二醛(malondialdehyde,MDA)含量;荧光定量聚合酶链式反应检测肝脏促炎因子白细胞介素(interleukin,IL)-6、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、IL-1β和抗炎因子IL-10?mRNA的相对表达量.结果表明:1)与CYP组相比,BA预处理使小鼠体质量增加,其中0.50?mg/kg?mb?BA组显著增加(P<0.05),同时使肝脏指数降低,其中0.50?mg/kg?mb和1.00?mg/kg?mb?BA组显著降低(P<0.05);2)BA呈剂量依赖性降低AST的活力,其中1.00?mg/kg?mb?BA组显著降低(P<0.05),0.50?mg/kg?mb?BA组显著降低ALT活力(P<0.05);3)BA预处理缓解由CYP导致的空泡样变性;4)BA预处理降低肝脏SOD活力,其中0.25?mg/kg?mb?BA组显著降低(P<0.05),BA对肝脏GSH-Px、CAT、GSH和MDA水平无明显影响(P>0.05);5)0.25?mg/kg?mb和1.00?mg/kg?mb?BA缓解CYP引起的IL-1β?mRNA表达升高(P<0.05,P<0.01),BA极显著增加肝脏中IL-6(P<0.01)和IL-10?mRNA的表达(P<0.01),0.25?mg/kg?mb?BA增加肝脏TNF-α?mRNA的表达,但0.50?mg/kg?mb和1.00?mg/kg?mb?BA降低肝脏TNF-α?mRNA的表达(P<0.01).结论:BA能抑制CYP引起的血清酶活力改变,改善小鼠肝脏的脂质过氧化,抑制促炎因子分泌,促进抗炎因子的分泌,对CYP诱导的肝脏损伤具有预防性保护作用.

γ-Oryzanol, a mixture of ferulic acid esters of plant sterols and triterpene alcohols existed in rice bran oil, can ameliorate lipid metabolism and enhance antioxidant activity. In this study, we used hydrogen peroxide (H2O2)-induced injury in human hepatic L02 cells to investigate the mechanisms involved in the hepatoprotective activity of γ-oryzanol. The injuries produced by H2O2 in L02 cells include increased levels of malondialdehyde (MDA) and intracellular reactive oxygen species (ROS), decreased activities of superoxide dismutase (SOD) and catalase (CAT), loss of mitochondrial membrane potential (MMP), increased protein expressions of caspase-9 and caspase-3, and induced apoptosis. Pretreatment with γ-oryzanol enhanced the ROS scavenging activity of endogenous antioxidant enzymes and decreased lipid peroxidation in H2O2 treated cells. Moreover, pretreatment with γ-oryzanol inhibited H2O2-induced apoptosis by restoring MMP, upregulating the expression ratio of Bcl-2/Bax, and inhibiting the activation of caspase-9 and caspase-3. These findings show that γ-oryzanol can prevent H2O2-induced apoptosis by suppressing intracellular accumulation of ROS and impeding ROS-activated mitochondrial apoptotic pathway.

λ-Carrageenan (Carr), a seaweed polysaccharide, is used as a proinflammatory agent in research. Betulinic acid (BA), a naturally occurring pentacyclic triterpenoid, exerts immunomodulatory, antioxidant, anti-inflammatory, antitumor, anti-malarial and anti-HIV effects. The aim of this study was to investigate whether BA exerts anti-inflammatory effect against Carr-induced paw edema in mice, and how BA could mediate the expression of inflammation-associated MAPK-COX-2-PGE2 signal pathway. BA pretreatment significantly reduced the inflammatory response to Carr-induced paw edema, especially at 4 h after injection. BA reduced the serum levels of pro-inflammatory cytokines, such as IL-1α, IL-1β, IL-5, IL-6, GM-CSF, KC, MCP-1 and PGE2 in Carr-treated mice, and increased those of anti-inflammatory cytokines, such as IL-12. It also increased SOD, CAT and GSH-Px activities, and GSH content, and reduced MDA content in the liver of Carr-treated mice. Besides, BA reduced neutrophil infiltration in the basal and subcutaneous layers of the paw of Carr-treated mice, decreased the expression of COX-2 protein, and reduced the phosphorylation of JNK, p38 and ERK1/2. These results indicated that the protective effect of BA on Carr-induced paw edema might be due to its alleviation of inflammatory response and inhibition of oxidative stress, possibly by inhibiting MAPK-COX-2-PGE2 signaling pathway activation.

The objective of this research was to evaluate the effects of betulinic acid (BA) on immune organs of oxidative damaged mice induced by cyclophosphamide (Cy).Fifty male healthy Kunming mice were randomly divided into 5 groups,which were control group,Cy group,and 0.05,0.50 and 5.00 mg/kg BW BA groups.Control and Cy groups were orally administered with 1％ starch solution,and the other groups were orally administered with different doses of BA for 14 days.Except control group,mice in the other groups were intraperitoneal injected Cy at the dosage of 50 mg/kg BW to set up oxidative damage model.Serum,spleen and thymus of mice were collected.Activities of alanine aminotransferase (ALT) and aspartate transaminase (AST),contents of total protein (TP) and albumin (ALB) in serum,as well as activities of superoxide dismutase (SOD),glutathione peroxidase (GSH-Px) and catalast (CAT),and contents of glutathione (GSH) and malondialdehyde (MDA) in spleen and thymus were determined.The results showed as follows:1) about body weight,control group and Cy group had no significant difference (P＞0.05),and BA groups had no significant difference with Cy group (P＞0.05).2) Compared with control group,Cy significantly increased serum AST and ALT activities (P＜0.01),and 0.05 mg/kg BW BA significantly relieved the effects of Cy (P＜ 0.01).3)Compared with control group,Cy significantly decreased thymus index (P＜0.05),and 0.05 mg/kg BW BA significantly relieved the effects of Cy (P＜0.05).4)Compared with control group,Cy significantly decreased SOD and CAT activities in thymus,and GSH content in spleen (P＜0.05 or P＜0.01),significantly increased spleen MDA content (P＜0.01);compared with Cy group,0.05 mg/kg BW BA group had significantly higher GSH-Px and CAT activities in spleen and thymus (P＜0.05 or P＜0.01),and significantly lower MDA content in spleen (P＜0.01),but had significantly lower SOD activity in thymus (P＜0.01);compared with Cy group,5.00 mg/kg BW BA group had significantly higher GSH-Px and CAT activities in spleen and thymus(P＜0.05 or P＜0.01),and significantly lower MDA content in spleen (P＜0.01).The results suggest that BA can effectively improve oxidative stress of immune organs and shows preventive protection of oxidative damage in mice induced by Cy.

为了探讨桦木酸对大鼠胃溃疡的保护作用及可能机制,采用无水乙醇灌胃法建立大鼠胃黏膜损伤模型,检测桦木酸对大鼠胃黏膜组织中丙二醛(MDA)含量、超氧化物歧化酶(SOD)与谷胱甘肽过氧化物酶(GSH-Px)活性的影响.结果表明,桦木酸能降低大鼠胃黏膜组织中MDA含量,提高SOD和GSH-Px活性.说明桦木酸对大鼠胃黏膜损伤的保护作用与增强胃黏膜抗氧化能力、抑制自由基生成密切相关.

研究桦木酸对胃黏膜的保护作用.采用无水乙醇灌胃法建立大鼠胃黏膜损伤模型,以溃疡指数和溃疡抑制率表示大鼠胃黏膜损伤程度.结果表明,桦木酸能显著降低胃黏膜损伤模型的溃疡指数,提高其溃疡抑制率和胃内容物pH值(P＜0.01).说明枰木酸对大鼠乙醇胃黏膜损伤具有保护作用,该作用可能与其减少胃酸分泌以及增强组织自身生长和修复能力等有关.

"卓越农林人才培养计划"实施的主要目的是加强学生实践能力培养,突出德育为先、能力为重.文章以湖南农业大学动物医(药)学专业卓越农林人才创业班为例,对其在探索实践中存在的主要现实问题进行了分析,提出了改进策略.

研究桦木酸(betulinic acid,BA)对小鼠细胞因子的影响.取健康昆明系小鼠28只,随机分为4组,即空白对照组,BA低、中、高剂量组(0.25 mg/kg、0.5 mg/kg、1 mg/kg),灌胃给药,1次/d,连续14 d.检测BA对小鼠血清白细胞介素-2(IL-2)、IL-6和IL-10以及对腹腔巨噬细胞肿瘤坏死因子(TNF-α)水平的影响.结果表明,BA可降低小鼠血清IL-2和IL-6的分泌量,提高腹腔巨噬细胞TNF-α的分泌量.说明BA在治疗机体肿瘤、感染和炎症的过程中发挥着重要作用.

In order to extract protein from brewer＇ s spent grain,the alkali protease was used in hydrolyzing brewer＇ s spent grain.Brewer＇s spent grain was pretreated by cellulose enzyme,which reduced protein extraction rate in single-factor experiment.It was shown that increasing enzyme volume, heightening pH and prolonging enzymolysis time,were helpful to improve protein extraction rate,meanwhile,error term great influenced on protein extraction rate in the first uniform design experiment by path analysis. Based on path analysis results, the second uniform design experiment was adopted, through quadratic polynomial stepwise regression analysis, optimal enzymatic hydrolysis condition was obtained ： enzyme volume 3400u/g, ratio of material and water 1 ~ 13, time 5.0h,.pH 8.5, protein extraction rate was 64.15% ,improved by 28.04% than the first uniform design experiment.

To reduce the toxic substance and raise the protein content of the rapeseed hull,the rapeseed husk power treated with Aspergillus niger was fermented with the yeast strain broth.The feed protein yield were compared with those fermented by Saccharomyces cerevisiae and Candida dattila.The protein content in the dry products of final fermentation by the yeast strain A was 22.48%,which was 73.2% higher than that in the original rice husk powder(12.98%).In addition,it was 53.45% higher than that in the final fermentation products by Saccharomyces cerevisiae(14.65%),and 9.02% higher than that by Candida dattila(20.62%).