Estrogenic effect of main components kakkalide and tectoridin of Puerariae Flos and their metabolites

To understand the relationship between the metabolism and estrogenic activity of kakkalide and tectoridin, main isoflavones in the flower of Pueraria thunbergiana (family Leguminosae), these isoflavones and their metabolites by human intestinal microflora as well as their estrogenic effects were investigated. All human fecal specimens metabolized kakkalide and tectoridin. All isolated kakkalide-hydrolyzing intestinal bacteria also hydrolyzed kakkalide and tectoridin to irisolidone and tectorigenin, respectively. When the estrogenic effects of kakkalide and tectoridin were compared with those of their metabolites irisolidone and tectorigenin, the metabolites more potently increased proliferation of MCF-7 cells than kakkalide and tectoridin. These metabolites also potently induced estrogen-response c-fos and pS2 mRNA expression. These results suggest that kakkalide and tectoridin may be metabolized mainly to irisolidone and tectorigenin, respectively, by intestinal microflora in the intestines, and which may be subsequently absorbed into the blood where they can express their estrogenic effect.     

Protective effects of kakkalide from Flos puerariae on ethanol-induced lethality and hepatic injury are dependent on its biotransformation by human intestinal microflora

When kakkalide, which was isolated from Flos Puerariae, was incubated with human fecal bacteria, kakkalide was metabolized to irisolidone via kakkalidone. When kakkalide (250 mg/kg) was orally administered to rats, irisolidone, but not kakkalide, was detected in the blood. The mortality associated with ethanol treatment was slightly reduced when the mice were intraperitoneally treated with kakkalide. Intraperitoneally administered kakkalide and kakkalidone did not reduce alcohol toxicity. However, orally administered kakkalide and intraperitoneally administered irisolidone significantly reduced the mortality. Orally administered kakkalide and intraperitoneally injected irisolidone greatly reduced serum alanine aminotransferase and aspartate aminotransferase activities in ethanol-intoxified mice. Orally administered kakkalide and intraperitoneally administered irisolidone significantly lowered the level of blood ethanol. The results indicate that kakkalide is a prodrug of irisolidone in protecting against ethanol-induced lethality and hepatic injury.     

Hepatoprotective effects of irisolidone on tert-butyl hyperoxide-induced liver injury

To clarify the hepatoprotective effects of kakkalide and its metabolite irisolidone by human fecal microflora, their effects on tert-butyl hydroperoxide (t-BHP)-injured HepG2 cells and mice were investigated. Irisolidone protected HepG2 cells against cytotoxicity induced by t-BHP. However, kakkalide did not protect cytotoxicity. When kakkalide 100 mg/kg was orally administered to mice injured by t-BHP, it significantly inhibited the increase in plasma alanine aminotransferase and aspartate aminotransferase activities by 84% and 85% of t-BHP-treated control group, respectively. The inhibitory effect of kakkalide is much more potent than that of silybin, a hepatoprotective agent. However, intraperitoneally administered kakkalide did not exhibit hepatoprotective activity. When irisolidone was intraperitoneally administered to mice, it exhibited potent hepatoprotective activity. Based on these findings, irisolidone can be hepatoprotective and kakkalide may be a prodrug transformed to irisolidone.     

薯藤多糖降血脂作用实验研究

目的:观察薯藤多糖(STDT)在高脂动物模型上的降血脂作用。方法:SD大鼠、新西兰家兔采用高脂饲料喂养法、ICR小鼠采用腹腔注射蛋黄乳法复制高脂模型,分别灌胃给予不同剂量的STDT,测定给药前或给药后不同时间血清TC、TG、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)等指标。结果:STDT250、500、1000mg/kg剂量灌胃给药4周可明显抑制食糜性高脂大鼠血清TC、TG以及LDL-C的升高;100、200、400mg/kg剂量灌胃给药4周,能明显降低食糜性高脂家兔的血脂水平,使其血清TC、TG、LDL-C明显下降;STDT400、800、1600mg/kg剂量给药3d,对腹腔注射蛋黄乳所致的高脂模型小鼠血脂也有一定的降低趋势。结论:STDT无论是预防给药或是治疗给药,对多种高脂模型动物均体现出一定的降脂作用。     

天麻粉对高脂小鼠降血脂和谷丙转氨酶的实验观察

目的 观察天麻粉对高脂小鼠降血脂和血清谷丙转氨酶（GPT）的作用.方法 采用C57BL/6雄性小鼠,以高脂饲料喂养.实验设正常对照组,高脂（模型）对照组,天麻粉125、250、525 mg/kg组（相当于人体推荐剂量的2.5、5、10倍）,共5组,治疗8周.实验后检测血清总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-C）及GPT指标.结果 与高脂对照组比较,天麻粉250、525 mg/kg对血清TG有明显的降低作用（P＜0.05,P＜0.01）;天麻粉525 mg/kg对血清TC 、LDL-C和GPT有明显的降低作用（P＜0.01）.结论 天麻粉525 mg/kg对高脂小鼠具有降血脂和GPT的作用.     

四氢普伐他汀钠对高血脂模型新西兰兔脂质代谢的影响

目的通过高脂饮食兔高血脂模型考察四氢普伐他汀钠(H4PV-Na)的降血脂和调节脂质代谢的作用。方法新西兰白兔,雄性,100只,适应性饲养2周后,随机分为空白对照组、高脂模型组、阳性对照组P(普伐他汀钠组2.5mg·kg~(-1))、阳性对照组A(阿托伐他汀钙组2.5mg·kg~(-1))和给药组(低剂量1.25mg·kg~(-1)、中剂量2.5mg·kg~(-1)、高剂量5mg·kg~(-1))。高脂饲料喂饲2周形成高脂模型后,阳性药物和供试药物强制经口灌胃给药,10mL·kg~(-1),每天上午给药1次,每周给药6d,连续10周。最后1次给药后24h,禁食过夜,取血和肝脏组织,进行血脂和肝脂相关指标检测:血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、全血超氧化物歧化酶(SOD)活力和血清丙二醛(MDA)含量。横纹肌溶解毒性检测指标:测定血清磷酸肌酸激酶(CK)含量。取心脏、肝脏、脾脏、肺脏、肾脏、肾上腺等器官经HE染色检测脂肪组织的病理学变化。结果新西兰兔用高脂饲料喂养10周后,TC,TG和LDL-C水平升高,HDL-C水平降低,给予H4PV-Na后,TC、TG和LDL-C水平降低,HDL-C水平升高。结论 H4PV-Na具有明确的降血脂和胆固醇作用,在肝脏组织中降低胆固醇能力高于在血液中,无横纹肌溶解毒性,但在同等剂量下,H4PV-Na降脂效果稍弱于普伐他汀钠和阿托伐他汀钙。     

中药首明降脂宁的调血脂作用研究

目的观察复方中药首明降脂宁对高脂大鼠血脂的影响。方法采用高脂饲料诱导大鼠高脂血症模型,对首明降脂宁的调血脂作用进行研究。结果大鼠喂饲高脂饲料30d后,其总胆固醇、甘油三酯、低密度脂蛋白胆固醇较基础饲料组明显升高（P〈0．01）,高密度脂蛋白胆固醇降低（P〈0．05）。首明降脂宁低、中、高3个剂量（3,6,12g／kg）及血脂康（120mg／kg）灌胃30d后能显著降低大鼠总胆固醇、甘油三酯、低密度脂蛋白胆固醇水平（P〈0．01或P〈0．05）。结论首明降脂宁对高脂饮食诱导的大鼠高脂血症有一定的治疗作用。     

白藜芦醇苷降血脂作用的实验研究

目的 研究白藜芦醇苷的降血脂活性.方法 通过饲喂高脂饲料建立高脂血症大鼠和家兔动物模型,分别连续给药7d和14 d,观察白藜芦醇苷对2种动物模型血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL)和低密度脂蛋白(LDL)水平的影响.结果 白藜芦醇苷显著降低高血脂家兔血清TC、TG和LDL水平,能明显对抗大鼠升高的血清TG含量.结论 白藜芦醇苷具有降血脂的作用.     

姜黄提取物对实验性动物高脂血症的防治作用研究

目的 :研究姜黄提取物对实验性动物高脂血症的预防和治疗作用。方法 :以正常大鼠和家兔为实验对象 ,以血清总胆固醇(TC)、甘油三酯 (TG)、高密度脂蛋白 (HDL)、低密度脂蛋白 (LDL)和LDL/HDL值为指标 ,观察姜黄提取物灌胃后对高脂血症大鼠的预防作用以及对高脂血症家兔的预防及治疗作用。结果 :大鼠预防给予不同剂量的姜黄提取物后 ,血脂呈剂量依赖性下降 ,TC、LDL降低 ,HDL升高 ,LDL/HDL值明显降低 ,且降脂作用强于阳性对照药洛伐他汀。家兔预防和治疗性给予姜黄提取物后 ,TC、TG、LDL和HDL呈剂量依赖性下降 ,LDL/HDL值降低不明显 ,其降脂作用弱于阳性对照药洛伐他汀。结论 :姜黄提取物可以显著降低大鼠和家兔的血脂水平 ,其对大鼠作用强于洛伐他汀 ,而对家兔则弱于洛伐他汀。     

Hypolipidemic effects of Sophora flavescens and its constituents in poloxamer 407-induced hyperlipidemic and cholesterol-fed rats

In this study, we investigated the hypolipidemic effects of Sophora flavescens in poloxamer 407-induced hyperlipidemic and cholesterol-fed rats. The MeOH extract and 4 fractions of S. flavescens were administered at doses of 250 and 100 mg/kg body weight, respectively, once a day for 3 d to the poloxamer 407-induced hyperlipidemic rats. Serum lipid levels such as total cholesterol (TC), triglycerides (TG), and low-density lipoprotein-cholesterol (LDL-C) were markedly elevated in the poloxamer 407-induced hyperlipidemic control rats, while lipid levels were significantly decreased in the rats administered the MeOH extract or 4 fractions of S. flavescens. In addition, serum high-density lipoprotein-cholesterol (HDL-C) was reduced in the poloxamer 407-induced hyperlipidemic control rats. However, oral administration of both the MeOH extract and 4 fractions significantly increased HDL-C levels. Of the tested fractions, the EtOAc fraction showed the strongest lipid-lowering effect, as well as a high antiatherogenic potential with atherogenic index (A.I.) values of less than 1.92. We also investigated the hypolipidemic effects of the main compounds of the EtOAc fraction, kurarinol and kuraridinol, using the hyperlipidemic and hypercholesterolemic animal models. Here, elevated TC, TG, and LDL-C levels in the poloxamer 407-induced hyperlipidemic and cholesterol-fed rats were significantly reduced after oral administration of the compounds, and HDL-C levels had a significant increase. Furthermore, A.I. values were lowered by administering kurarinol and kuraridinol. In particular, kuraridinol exhibited stronger protective activities against hyperlipidemia than kurarinol. These results suggest that S. flavescens and its constituents may be effective cholesterol-lowering agents and useful for preventing hypercholesterolemic atherosclerosis.     

大鼠实验性高脂血症和高脂血症性脂肪肝模型研究

目的　建立高脂血症和高脂血症性脂肪肝实验动物模型。方法　采用SD大鼠 30只 ,随机分为对照组 (n =10 )和模型组 (n =2 0 )。对照组喂普通饲料 ,模型组喂普通饲料并给予脂肪乳剂灌胃 (10ml·kg-1)。动态观察一般情况和血清TG、TC、ALT、AST、MDA、SOD和肝脏TG、TC、MDA、SOD的变化 ,并行病理检查。结果　 1wk后 ,模型组血清TG和TC明显高于正常组 ,形成了高脂血症模型。 2wk后 ,随机处死模型中的 10只 ,与正常组相比 ,发现血清TG、TC、ALT和肝脏MDA均明显升高 ,而肝脏SOD则明显降低 ,病理显示有 2只轻度脂肪变性。在第 3wk处死剩余动物 ,发现肝指数、血清脂质、ALT、AST、MDA和肝脏TG、MDA与对照组相比显著升高 ,而SOD则明显降低 ;光镜下所见模型组均出现弥漫性肝细胞脂肪变性 ,并有炎症病灶。结论　通过 1wk脂肪乳剂的喂养 ,形成了高脂血症模型 ;继续给予脂肪乳剂 ,2wk后形成高脂血症性脂肪肝模型。     

Pharmacological investigation of bezafibrate, a hypolipidemic agent (1). Effects of bezafibrate on normal and experimental hyperlipidemia in rats

The hypolipidemic effects of bezafibrate were examined in normal rats and an experimentally induced hyperlipidemic model of rats. Oral administration of bezafibrate at 1 mg/kg/day or more to normal rats for 7 days significantly decreased serum triglyceride (TG) and at 3 mg/kg/day or more for 7 days caused significant reduction of serum total cholesterol (TC). A single oral dose of 100 mg/kg of bezafibrate significantly inhibited the increase of serum TC and TG in hyperlipidemic rats induced by Triton WR-1339. When normal rats were given 75% fructose solution for 7 days, serum TG increased in concentration about four times. Oral administration of bezafibrate for 7 days at 1 mg/kg/day or more inhibited the increase of serum TG in this model. Serum TC increased in concentration about twice in 1% cholesterol diet-fed rats for 8 weeks. Oral administration of bezafibrate at 30 mg/kg/day or more inhibited the increase of serum TC. These results suggest that bezafibrate is effective in the treatment of hyperlipidemia.     

高脂饲料诱发非酒精性脂肪肝实验研究

目的探讨正常饮食和高脂肪饮食对小鼠体重、血糖、葡萄糖耐受、血脂、脂肪肝的影响。方法雄性C57BL/6小鼠随机分为MD10%和MD45%脂肪含量饲料组,喂养3个月,检测动物体重、血糖、葡萄糖耐受、血脂,以及主要脏器重量及肝脏脂质含量。结果与正常组（MD10%脂肪含量）相比,高脂组（MD45%脂肪含量）动物体重显著增加,出现明显的糖耐量异常和血脂水平升高,同时伴有肝脏脂质含量增加。结论高脂饮食对非酒精性脂肪肝有较强的诱导作用。     

Anti-hyperlipidemic effect of an edible brown algae, Ecklonia stolonifera, and its constituents on poloxamer 407-induced hyperlipidemic and cholesterol-fed rats

We conducted this study to isolate novel anti-hyperlipidemic agents derived from natural marine products. To accomplish this, we investigated the effects of ethanolic (EtOH) extracts of Ecklonia stolonifera and its phlorotannin constituents, eckol and dieckol, on serum lipid levels in rats with hyperlipidemia that was induced by a high-cholesterol diet or poloxamer 407. Treatment with the EtOH extracts of E. stolonifera and its phlorotannin-rich ethyl acetate (EtOAc) and n-butanol (n-BuOH) fractions induced a significant reduction in triglycerides (TG), total cholesterol (TC), and low-density lipoprotein-cholesterol (LDL-C) levels, as well as a significant increase in the high-density lipoprotein-cholesterol (HDLC) level in hyperlipidemic rats. However, treatment with the water (H₂O) fraction did not exert any significant effects on the serum levels of hyperlipidemic rats. In addition, eckol and dieckol isolated from the active EtOAc fraction induced a significant reduction in serum TG, TC, and LDL-C levels, as well as in the atherogenic index (A.I.). Furthermore, treatment with dieckol induced a greater decrease in the serum TG, TC, and LDL-C levels of hyperlipidemic rats than eckol or lovastatin, as well as an increase in the serum HDL-C levels. Taken together, these results suggest that phlorotannins such as eckol and dieckol have the potential for use for the prevention of hyperlipidemic atherosclerosis.     

Paeonol inhibits NLRP3 mediated inflammatory reaction in rat endothelial cells by elevating hyperlipidemic rats plasma exosomal miRNA-223

OBJECTIVE Atherosclerosis(AS) is featured as a chronic inflammatory disease of vascular stenosis.Paeonol(Pae) is a natural phenolic compounds isolated from a traditional Chinese medicine, Cortex Moutan, which exhibits anti-AS effects in vitro and in vivo. In this study, we aimed to investigate whether the anti-AS efficacy of Pae was regulated through inhibiting NLRP3 inflammasome activityvia elevating hyperlipidemic rats plasma exosomalmicro RNA-223(miR-223). METHODS The Sprague-Dawley rats was induced by a high-fat diet, which was used as AS models.AS aortic pathological morphological in AS mice was examined by HE staining, and serum TC and TG levels were determined by automatic chemistry analyzer. Rat aortic endothelial cells(RAECs) were used during the whole study. After oral administration of Pae, we isolated exosomes from hyperlipidemic rats plasma(Pae-Exos) by ultracentrifugation and characterized by transmission electron, nanoparticle tracking analysis, dynamic light scattering and Western blotting.The activity of RAECs was detected by CCK-8 and trypan blue staining method. IL~(-1)β and IL-6 levels were detected by ELISA method. The expression of miR-223 was detected by q PCR, and the expression of NLRP3, ASC, caspase-1, and ICAM-1 was detected by Western blotting. RESULTS In vivo experiments confirmed that Pae could effectively reduce serum TC and TG levels and decrease serum IL~(-1)β and IL-6 levels, which demonstrated that Pae restricted AS development in hyperlipidemia rats. Both CCK-8 and trypan blue staining showed that the survival rate of RAECs in the PaeExos co-incubation group was higher than that in the model group. We also confirmed via real-time q PCR that Pae-Exos suppressed the expression of the inflammatory cytokines IL~(-1)β and IL-6. Accordingly, Pae-Exos dose-dependently increased the survival rate of RAECs and reduced inflammatory response. Furthermore, compared with the model group, Pae-Exos more successfully increased the expression of miR-223 and inhibited IL~(-1)β and IL-6 expression, which implied that Pae-exo may inhibited the inflammatory response of RAECs by increasing the content of miR-223. Subsequently, we found that Pae-Exos reduced the expressions of NLRP3, ASC, caspase-1 and ICAM-1, which indicated that Pae-Exos may reduced RAECs inflammation by suppressing NLRP3 signaling pathway via promoting miR-223 expression.CONCLUSION Pae can inhibit the downstream NLRP3 inflammatory corpuscle signaling pathway by increasing the level of miR-223 in plasma Exos of hyperlipidemic rats, providing new insights into the anti-atherosclerosis activity of Pae.     

胆石六号颗粒对高脂血症小鼠调脂保肝的作用研究

目的：观察胆石六号颗粒对高脂血症小鼠调脂保肝的作用。方法：将60只小鼠随机分成正常组（K）、模型组（M）、给药组（胆石六号颗粒,D）和阳性对照组（辛伐他汀,Y）,每组15只,采用高脂饮食法建立高脂血症小鼠模型;用试剂盒检测各组小鼠血清天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）水平;采用比色法检测肝脏组织丙二醛（MDA）含量和超氧化物歧化酶（SOD）活力;肝脏HE染色观察肝组织形态变化。结果：高脂饮食可引起小鼠腹部脂肪堆积,使肝脏明显发生脂肪变性;与正常组相比,模型组小鼠血清转氨酶、TC、TG、LDL-C明显升高（P<0.05）,HDL-C明显降低（P<0.05）;与模型组比较,胆石六号颗粒能明显降低小鼠肝指数,降低血清TC、TG、LDL-C、AST、ALT及肝脏MDA（P<0.01）水平,提高血清HDL-C含量及肝脏SOD活力（P<0.01）,明显改善肝脏组织中脂肪浸润;与阳性对照组比较,胆石六号颗粒组小鼠肝指数,血清TC、TG、LDL-C、AST、ALT、HDL-C,以及肝脏MDA和SOD没有明显差异。结论：胆石六号颗粒对高脂血症小鼠具有调脂保肝作用,有可能作为治疗高脂血症的有效药物。     

复方螺旋藻片对高血脂症小鼠血脂的影响

目的：观察复方螺旋藻片（FST）对高脂血症小鼠血脂的影响。方法：用FST1.5mg/kg,3g/kg分别灌胃给予高脂血症小鼠,连续14d后,眼眶取血测血脂。结果：与高脂血症模型对照组相比,FST高、低剂量能显著降低血清TC、TG和LDL－C水平,明显升高血清HDL－C水平与HDL－C／TC比值。同时FST还能升高血清apoAI并降低apoB(但FST 1.5g/kg对apoB无明显影响）。结论：FST能明显降低高脂血症小鼠血脂水平,并对载脂蛋白有一定的调节作用。     

Antihyperlipidemic effect of crocin isolated from the fructus of Gardenia jasminoides and its metabolite Crocetin

The pancreatic lipase inhibitors were isolated from the fructus of Gardenia jasminoides ELLIS, and their antihyperlipidemic activities were measured. Gardeniae fructus (GF) water extract inhibited pancreatic lipase activity. Crocetin and crocin were isolated from GF water extract as inhibitors of pancreatic lipase with an IC50 value of 2.1 and 2.6 mg/ml (triolein as a substrate). Crocin and crocetin significantly inhibited the increase of serum TG level in corn oil feeding-induced triglyceridemic mice, as well as that of serum triglyceride and total and LDL cholesterol levels in Triton WR-1339-induced hyperlipidemic mice. These compounds also showed hypolipidemic activity in hyperlipidemic mice induced by high cholesterol, high fat or high carbohydrate diets for 5 weeks. The results suggest that the hypolipidemic activity of GF and its component crocin may be due to the inhibition of pancreatic lipase and crocin, and its metabolite, crocetin, can improve hyperlipidemia.     

鹰嘴豆芽素A对高脂血症大鼠的降血脂作用

目的研究鹰嘴豆芽素A对高脂血症大鼠的降血脂作用。方法健康雄性SD大鼠60只,三月龄,随机分为正常组、模型组、血脂康组、鹰嘴豆芽素A低、中、高剂量组,每组10只。除正常组给予普通饲料外,其他5组灌胃给予10 mL/(kg.d)高脂乳剂,一周后,在每天灌胃高脂乳剂的基础上,血脂康组灌胃0.1 g/(kg.d)的血脂康;鹰嘴豆芽素A低、中和高剂量组分别灌胃0.3,0.6和1.2 g/(kg.d)鹰嘴豆芽素,给药30 d后测定血总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)水平、全血黏度和血浆黏度;凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)和纤维蛋白原含量(FIB)。结果鹰嘴豆芽素A能明显降低TC、TG和LDL-C水平及升高HDL-C水平(P<0.05),显著降低全血黏度和血浆黏度(P<0.05),同时能显著性延长PT、APTT及降低FIB(P<0.05)。结论鹰嘴豆芽素A能降低高脂血症大鼠的血脂水平、血液黏度及FIB,改善血液循环,抑制因血脂升高和脂质代谢紊乱引起的血液凝血系统指标的改变。