Synthesis and In Vivo Hypolipidemic Effect of Some N-(Benzoylphenyl)-Carboxamide Derivatives in Triton WR-1339-Induced Hyperlipidemic Rats

A series of N-(benzoylphenyl)-carboxamide derivatives (2a, 2b, 3a, 3b, 4a, 4b, 5a, 5b, 6a and 6b) was prepared with good yields by reacting the corresponding carbonyl chlorides with aminobenzophenones at room temperature. This was followed by evaluating the hypotriglyceridemic and hypocholesterolemic effects of 3b, 5a and 5b. Triton WR-1339 (300 mg/kg) was intraperitoneally administered to overnight-fasted rats to induce hyperlipidemia. Rats were divided into six groups: control, hyperlipidemic, hyperlipidemic plus compounds 3b, 5a and 5b and hyperlipidemic plus bezafibrate. Results showed that after 18 h of treatment at a dose of 15 mg/kg body weight of each of the test compounds, the elevated plasma levels of triglycerides (TG) and total cholesterol (TC) were significantly lowered by compounds 5b and 3b (p < 0.001) and by 5a (p < 0.0001), compared to the hyperlipidemic control group. Compounds 3b and 5a significantly increased levels of high-density lipoprotein cholesterol (HDL-C) by 58 and 71%, respectively. In addition, compounds 3b and 5a caused significant reduction (p < 0.0001) of low-density lipoprotein cholesterol (LDL-C) levels compared to the control group. These results suggest a promising potential for compounds 3b, 5a and 5b as lipid-lowering agents, which may contribute to reducing the risk of atherosclerosis and cardiovascular disease

Knockout of NLRP3 enhances hypolipidemic effect and anti-inflammative effect of apigenin in Triton-WR 1339-induced hyperlipidemia mice / 中国药理学通报

Aim To investigate the role and mechanism of NLRP3 on hypolipidemic effect and anti-inflammative effect of apigenin. Methods Triton-WR 1339-induced hyperlipidemia was applied to wide type C57BL/6 and NLRP3"'" mice, which was treated with apigenin of 6.25 mg • kg"1 • day"1 for five days. Blood and liver tissueswere collected for detecting TC, TG, HDL, LDL, IL-1B, IL-6, MCP-1 and the liver underwent HE staining. The expressions of NLRP3, I L 4, ASC, CD36, CYP7A1 and FGF21 were tested using RT-qPCR. Results Compared with NLRP3 "'" model group, serum contents of TC, TG, HDL, LDL, IL-1B, IL-6, MCP-1 were reduced in NLPR3"'" treated with apigenin of 6. 25 mg • kg"1 (P < 0. 05). The percentage of hepatic steatosis wasdown-regulated by apigenin in pathogenesis observation. However, all these phenotype changes were not observed in WT mice treated with apigenin. Moreover, up-regulation of CD36 and vLDLR and down-regualtion of ASC and IL-4 were founded in both WT and NLRP3"'" model group (P < 0. 05), while down-regulation of FGF21 and up-regulation of CYP7A1 were only seen in NLRP3"/ _ model group but not in WT group. Conclusions Knockout of NLRP3 enhances hypolipidemic effect and anti-inflammative effect of apigenin in triton-1339 IP-induced hyperlipidemia mice, which may be associated with apigenin-regulated FGF21/CYP7A1 pathway without NLRP3 inflammasome interruption.

Antihyperlipidemic activity of Chloroxylon swietenia in triton WR1339 induced hyperlipidemia

Background: Medicinal herbs are beneficial and effective either in the management and prevention of several metabolic disorders, associated with hyperlipidemia, hypertension and insulin resistance which increases the cardio-metabolic risk and demands for the life time therapy. Current allopathic medicines are expensive and reported with several adverse effects and hence, finding of a suitable herbal medicine for hyperlipidemic disorders is very important.Methods: Thirty albino rats weighing 200-230g were randomly divided into 5 groups were rendered hyperlipidemia with a single dose of triton WR 1339. Normal control, positive control, standard, aqueous and ethanolic extract groups were treated with tween-80, tween-80, atorvastatin, aqueous and ethanolic extracts of Chloroxylon swietenia respectively for seven days. At the end of the study, blood was collected for estimation of the lipid profile.Results: Both the aqueous and ethanolic extract groups significantly reduced the TG and VLDL levels.Conclusions: The extracts exhibited remarkable activity on one or either parameter of the lipid profile. It could be due to the presence of alkaloids, steroids, flavonoids, coumarins and phenols in the extracts.

Lipid-lowering effect of propolis in mice with Triton-WR1339-induced hyperlipidemia and its mechanism for regulating lipid metabolism / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the therapeutic effect of propolis against Triton-WR1339-induced hyperlipidemia in mice and explore the underlying mechanism.</p><p><b>METHODS</b>C57BL/6 mice were randomly divided into 7 groups (=10), including the control group, hyperlipidemia model group, fenofibrate (30 mg/kg) treatment group, and 4 treatment groups treated with low- (30 mg/kg) or high-dose (60 mg/kg) propolis HB01 or HB02. In all but the control group, acute hyperlipidemia models were established by intramuscular injection of Triton WR-1339, and corresponding treatments were administered via gastric lavage for 7 days. After the treatments, blood samples were collected for testing the levels of total cholesterol (TC), triglycerides (TG), highdensity lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), malondialdehyde (MDA), superoxide dismutase (SOD), alanine aminotransferase (GPT), and aspartate aminotransferase (GOT); Western blotting was used to detect the expressions of the proteins involved in lipid metabolism in the liver tissues including ABCA1, ABCG8, LDLR, and SR-B1.</p><p><b>RESULTS</b>Compared with the normal control group, the mice with Triton-WR1339-induced hyperlipidemia showed significantly increased levels of TC, TG, LDL, MDA, GPT, and GOT and lowered HDL-C levels and SOD activity ( < 0.05). Treatments with fenofibrate and the 2 propolis at either low or high dose significantly reversed Triton-WR1339-induced changes in blood lipids ( < 0.05), and the effects of propolis were more potent. Triton-WR1339 injection also significantly decreased the expressions levels of ABCA1, ABCG8, LDLR, and SR-B1 in the liver ( < 0.05), and these changes were obviously reversed by treatments with fenofibrate and propolis ( < 0.05), especially by the latter.</p><p><b>CONCLUSIONS</b>The lipid-lowering effects of propolis are mediated by improving lipid metabolism and regulating the expressions of lipid transport proteins in the liver tissue.</p>

Evaluation of phenolic compounds and lipid-lowering effect of Morus nigra leaves extract

ABSTRACT Morus nigra L. (Moraceae) is a tree known as black mulberry and the leaves are used in folk medicine in the treatment of diabetes, high cholesterol and menopause symptoms. The aim of this study was to evaluate the M. nigra leaves phytochemical profile in different extractions and the hypolipidemic effect of the infusion comparing to the fenofibrate. Morus nigra infusion (MN) showed higher amounts of phenolics and flavonoids (83.85 mg/g and 79.96 µg/g, respectively), as well as antioxidant activity (83.85%) than decoction or hydromethanolic extracts. Although, decoction showed the best result for ascorbic acid (4.35 mg/100 g) than hydromethanolic or infusion (2.51 or 2.13 mg/100 g, respectively). The phenolic acids gallic, chlorogenic and caffeic and the flavonoids quercetin, rutin and catechin were found in the M. nigra extracts. Hyperlipidemic rats treated with 100, 200 or 400 mg/kg of MN decreased serum cholesterol, triglycerides and normalized lipoproteins. Furthermore, MN inhibited lipid peroxidation in liver, kidney and brain of hyperlipidemic rats. This study provides evidence that M. nigra leaves extracts are rich in polyphenols, mainly chlorogenic acid, which normalized hyperlipidemic disturbance. The results suggest a potential therapeutic effect of the M. nigra leaves infusion on dislipidemic condition and related oxidative stress.

Changes of Poison Data Characteristics Collected from Telephone Response in 1339 and 119: Discrepancy in Characteristics of Post-toxin Exposure Data Obtained through Telephone Counselling Provided by 1339 and 119

PURPOSE: The aim of this study was to compare the toxicologic profiles and outcome of poisoned patients by comparing the data obtained through telephone counselling, each provided by emergency medical information center (1339) and emergency dispatch center (119). METHODS: We analyzed the telephone-based poison exposure data before and after Seoul 1339 merged to 119. We compared the Seoul 1339 call response data in 2008 with Seoul and Busan 119 call response data between 2014 and 2016. We analyzed the changes in the trend and quality of data obtained, as well as the quality of service provided by each center before and after this reallocation, by comparing the data each obtained through telephone counselling. RESULTS: The data was collected for a total of 2260 toxin exposure related calls made to Seoul 1339 in 2009, and 1657 calls to 119 in Seoul and Busan between 2014 and 2016. Significant difference was observed for age, sex, and reason for exposure to toxic substance between the two groups. CONCLUSION: After the integration of 1339 with 119, 119 focused on role of field dispatch and hospital transfer, lacking the consulting on drug poisoning. Moreover, data on exposure to toxic substances at the pre-hospital stage indicate that drug information and counseling are missing or unknown. In addition, first aid or follow-up instructions are not provided. Thus, systematic approach and management are required.

Construction of Rat Extracellular Signal-regulated Kinase 1 Gene 3' Untranslated Regions Dual-luciferase Reporter Plasmids and Effect of rno-miR-15b-5p on Its Activitiy / 中国康复理论与实践

@#Objective To construct dual-luciferase reporter plasmids containing the wild type and mutant rat extracellular signal-regulat-ed kinase 1 (ERK1) gene 3' untranslated regions (UTR) which were used to detect rno-miR-15b-5p's putative target gene. Methods The rat ERK1 gene 3' UTR fragment was amplified by polymerase chain reaction (PCR) from PC12 cell cDNA and cloned into pmiR-RB-ReportTM vector. The mutant rat ERK1 gene 3' UTR fragment was obtained by overlap PCR and inserted into pmiR-RB-ReportTM vector. Successful wild type and mutant recombinant plasmids were confirmed by DNA sequencing. PC12 cells were co-transfected with rno-miR-15b-5p mim-ic and pmiR-ERK13' UTR or pmiR-ERK1-mut 3' UTR and then analyzed by dual-luciferase reporter assay system. The achieved mutation sequence of the target site TGCTGCT was mutated to CGAACGT and GTACACG, respectively. Results The wild-type reporter vector pmiR-ERK13' UTR and the mutant reporter vector pmiR-ERK1-mut 3' UTR were successfully constructed. The rno-miR-15b-5p mimic de-creased the activity of pmiR-ERK13' UTR plasmid (P<0.001) but did not decrease the activity of pmiR-ERK1-mut 3' UTR plasmid. Conclu-sion The recombinant pmiR-ERK13' UTR and pmiR-ERK1-mut 3' UTR plasmids were constructed successfully, and luciferase activities demonstrated that the 3' UTR of ERK1 gene might be a potential target of rno-miR-15b-5p.

Hypolipidemic activity of friedelin isolated from Azima tetracantha in hyperlipidemic rats

Abstract The hypolipidemic activity of friedelin isolated from Azima tetracantha Lam., Salvadoraceae, was studied in Triton WR-1339 and high-fat diet-induced hyperlipidemic rats. In Triton WR-1339 induced hyperlipidemic rats, treatment with friedelin (50 and 70 mg/kg) showed a significant (p < 0.01) lipid-lowering effect as assessed by reversal of plasma levels of total cholesterol (TC), triacylglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). In high-fat diet fed hyperlipidemic rats, treatment with friedelin (50 and 70 mg/kg) caused lowering of lipid levels in plasma and liver. The hypolipidemic activity of friedelin was compared with fenofibrate, a known lipid-lowering drug, in both models.

Weight losing, antihyperlipidemic and cardioprotective effects of the alkaloid fraction of Hunteria umbellata seed extract on normal and triton-induced hyperlipidemic rats

OBJECTIVE: To investigate the weight losing, antihyperlipidemic and cardioprotective effects of the alkaloid fraction of Hunteria umbellata (H. umbellata) seed. METHODS: Adult female Wistar rats (weight range: 120-150 g) were randomly divided into 4 and 5 treatment groups in the normal and triton-induced hyperlipidemic models, respectively. and were daily treated for 14 d before they were humanely sacrificed under inhaled diethyl ether anesthesia. About 5 mL of whole blood was obtained by cardiac puncture from each treated rat, from which serum for lipids assay was subsequently separated. Tissue samples of livers of treated rats were harvested and processed for histopathological analysis. RESULTS: Repeated daily oral treatments of normal rats with 25 and 50 mg/kg/day of alkaloid fraction of H. umbellata resulted in significant (P<0.05 and P<0.001) and dose-dependent weight loss, and decreases in the serum triglyceride, total cholesterol and low density lipoprotein cholesterol, while significantly (P<0.001) increased the serum levels of high density lipoprotein cholesterol fraction. Similarly, oral pre-treatments with 25 and 50 mg/kg/day of alkaloid fraction of H. umbellata for 14 d before induction of hyperlipidemia with triton WR-1339 significantly (P<0.01, P<0.001) and dose-dependently attenuated increases in the average body weights, serum levels of triglyceride, total cholesterol and low density lipoprotein cholesterol while also significantly (P<0.01, P<0.001) and dose-dependently attenuated significant (P<0.001) decrease in the serum high-density lipoproteincholesterol levels when compared to the untreated control values. However, the results obtained for 50 mg/kg of alkaloid fraction of H. umbellata in both normal and triton WR-1339-induced hyperlipidemic rats were comparable to that recorded for 20 mg/kg of simvastatin. Similarly, oral pretreatments with 25 and 50 mg/kg/day of alkaloid fraction of H. umbellata significantly improved the histological lesions of fatty hepatic degeneration induced by triton WR-1339 treatment. CONCLUSIONS: Overall, results of this study showed that repeated oral treatments with 25 and 50 mg/kg/day of alkaloid fraction of H. umbellata elicited weight losing, antihyperlipidemic and cardioprotective effects in triton WR-1339 induced hyperlipidemic rats that were mediated via de novo cholesterol biosynthesis inhibition.

The hypolipidemic activity of Ayurvedic medicine, Arogyavardhini vati in Triton WR-1339-induced hyperlipidemic rats: A comparison with fenofi brate.

Background: Hyperlipidemia is a major risk factor of coronary heart disease. Currently available hypolipidemic drugs have been associated with number of side effects. Arogyavardhini vati, an Ayurvedic polyherbal formulation has been used for liver disorders. Therefore, present study was designed to evaluate the effect of Arogyavardhini vati in Triton WR-1339-induced hyperlipidemia in rats. Objectives: Anti-hyperlipidemic activity evaluation of Arogyavardhini vati against Triton WR-1339-induced hyperlipidemia in rats. Materials and Methods: Overnight fasted male Wistar rats (150-200 g) were randomly divided into normal control group [4% Dimethyl Sulfoxide (DMSO), i.p.], positive control group (Triton WR-1339 in 4% DMSO, 400 mg/kg, i.p.), standard drug treated (fenofi brate 65 mg/kg, p.o. for 7 days after inducing hyperlipidemia) and Arogyavardhini vati treated (50, 100, 200 mg/kg, p.o. for 7 days after inducing hyperlipidemia). Rat doses were calculated by extrapolating the equivalent human dose (therapeutic dose, sub-maximum, and maximum dose). Serum total cholesterol, triglyceride, low-density lipoprotein (LDL), high-density lipoprotein HDL, liver malondialdehyde (MDA), and glutathione (GSH) levels were estimated at end of experiments. Results: Arogyavardhini vati signifi cantly decreased serum cholesterol, triglyceride, LDL, and C-reactive protein (CRP) and signifi cantly increased serum HDL in a dose-dependent manner. Decreased MDA and increased GSH levels in liver were observed at all doses of Arogyavardhini vati (50, 100, 200 mg/kg) and fenofi brate-treated groups when compared with Triton-treated group. Atherogenic Index (AI) level was signifi cantly decreased in fenofi brate and Arogyavardhini vati (200 mg/kg) treated rats when compared with normal control. Conclusion: Arogyavardhini vati, a traditionally used Ayurvedic medicine may be a useful therapy for hypercholesterolemia through reducing oxidative stress (decreasing MDA and increasing GSH) and lipid levels.

Anti-hyperlipidemic activity of oryzanol, isolated from crude rice bran oil, on Triton WR-1339-induced acute hyperlipidemia in rats

Experimental studies carried out for evaluating the anti-hyperlipidemic properties of rice bran components have given interesting but often contrasting results. Therefore, the current study was initiated to investigate the anti-hyperlipidemic activity of oryzanol (OZ), a commercially-important bioactive phytochemical, isolated from crude rice bran oil (cRBO). OZ was isolated by a two-step solvent crystallization process from cRBO, which was extracted from fresh rice bran by hexane mediated soxhlet extraction. Subsequently, OZ (50 and 100 mg/kg, p.o.) was evaluated for anti-hyperlipidemic activity in Triton WR-1339-induced acute hyperlipidemic albino rats by estimating serum triacylglyceride (TG), total cholesterol (TC), very low density lipoprotein-cholesterol (VLDL-C), low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) levels with atorvastatin as the reference standard. The degree of protection was also assessed by measuring the levels of various hepatic anti-oxidant enzymes. OZ evoked a significant decrease in the levels of serum cholesterol, triacylglycerides, LDL, VLDL and a significant increase in the level of serum HDL and hepatic anti-oxidant enzymes. It also showed a significant ameliorative action on elevated atherogenic index (AI) and LDL/HDL-C ratios. These findings indicate that OZ possesses the potential to lower plasma lipid concentrations and might be of therapeutic benefit in hyperlipidemia and atherosclerosis.

Antihyperlipidaemic Activity of Spermacoce Hispida Ethanolic Extract in Triton WR-1339 Induced Hyperlipidaemic Rats.

Hyperlipidaemia is the greatest risk factor of coronary heart disease. Currently available hypolipidaemic drugs have been associated with number of side effects. Herbal treatment for hyperlipidaemia has no side effects and is relatively cheap and locally available. Literature claims that Saponins are able to reduce hyperlipidemia. Based on high saponin content in herbal plants, Spermacoce hispida (S. hispida) was selected and the present study focus on the antihyperlipidaemic activity of ethanolic seed extract of S. hispida against triton-WR-1339 induced hyperlipidaemia in rats. Hyperlipidaemia was induced in Wistar rats by intraperitoneal (i.p) injections of Triton WR-1339 at a dose of 400 mg/kg body weight. S. hispida was administered orally at a dose of 200 mg/kg to triton WR-1339 induced hyperlipidaemic rats. After administration of S. hispida shows a significant decrease in the levels of cholesterol, phospholipids, triglycerides, LDL, VLDL and significant increase in the level of HDL in serum and liver tissues against triton induced hyperlipidaemic in rats. Therefore it effectively suppressed the triton induced hyperlipidemia in rats, suggesting the potential protective role in Coronary heart disease.