Triton-induced Hyperlipidemic Rats Research Articles

A comparative study of hypolipidemic effect of atorvastatin and Coriandrum sativum in triton-induced hyperlipidemic albino rat model

Background: Hyperlipidemia is the main factor responsible for coronary artery disease. Atorvastatin commonly used, as a competitive inhibitor of HMG-Co-A reductase, is known to reduce LDL and triglyceride levels and increase HDL levels. Coriandrum sativum (Coriander) belongs to the Apiaceae family and has hypolipidemic, antidiabetic, and antioxidant properties. Triton WR1339 has been used by several studies to induce hypercholesterolemia in animals which acts on both the synthesis and excretory phase. This study aimed to compare the hypolipidemic effect of Coriandrum sativum and atorvastatin in triton-induced hyperlipidemic rats. Methods: Following approval from the Institutional Animal Ethics committee, 36 Wistar albino rats were divided into 6 groups of 6 animals each. Triton 200mg IP was administered to all the groups except Group 1 (control). Groups 3 and 4 received Coriander extract 300mg/kg and Atorvastatin 80mg/kg orally with Triton. Groups 5 and 6 received Coriander extract and Atorvastatin respectively 22 hours later. Lipid profile was estimated 24 hours before, 24 and 48 hours after administering Triton. Results: In the synthesis phase, there is a statistically significant increase in the lipid levels in Groups 2, 5, and 6 compared to Groups 3 and, 4 indicating hypolipidemic effects of both Coriander extract and Atorvastatin. In the excretory phase, all groups have shown a decrease in lipid levels but a decrease in total cholesterol level in Group 5 compared to Group 3 was significant. Conclusions: Atorvastatin and Coriander extract both affect the lipid levels in the synthesis and excretory phase. Even though coriander cannot replace atorvastatin in the management of hyperlipidemia, it can be used as an adjuvant to atorvastatin to reduce the cost effects and adverse reactions caused by allopathic medicines.

Prediction by DFT and synthesis of new xanthene derivatives: Evaluation of their toxicity and antihyperlipidemic properties in-vivo and in-silico

The current research focuses on the synthesis of novel Xanthene-based heterocyclic compounds and the evaluation of their toxicity and antihyperlipidemic effect. Our approach consists of exploring this synthesis and its mechanism theoretically via DFT calculations, and carrying out the synthesis in the laboratory. The Xanthene derivatives were synthesized by O-p-methylbenzylation and O-benzoylation, and their structures were established using standard spectroscopic methods. The experimental results obtained are in good agreement with the theoretical data. Furthermore, the synthetized Xanthene compounds were evaluated for their acute oral toxicity, and the results suggest the safety of oral administration of these compounds at a dose equal to or less than 2000 mg/kg. These Xanthene derivatives were then evaluated in Triton-induced hyperlipidemic rats and their effects were compared to those of the norm. They were found to have good antihyperlipidemic activity, comparable to that of the marketed antihyperlipidemic drug. In addition to in vivo investigations, in silico studies involving molecular docking and molecular dynamics (MD) simulations, as well as ADME analyses, were carried out to support and explain the experimental results. Additionally, docking results showed that the compounds exhibited robust binding interactions with key residues of the target receptor. Furthermore, the stability of the formed ligand-protein complexes was demonstrated through 100 ns MD simulations. Lastly, the prediction of ADME properties shows that Xanthene compounds possess good and favorable pharmacokinetic profiles.

Design, Synthesis and Evaluation of Antioxidant and NSAID Derivatives with Antioxidant, Anti-Inflammatory and Plasma Lipid Lowering Effects.

Amides containing methyl esters of γ-aminobutyric acid (GABA), L-proline and L-tyrosine, and esters containing 3-(pyridin-3-yl)propan-1-ol were synthesized by conjugation with 3,5-di-tert-butyl-4-hydroxybenzoic, an NSAID (tolfenamic acid), or 3-phenylacrylic (cinnamic, (E)-3-(3,4-dimethoxyphenyl)acrylic and caffeic) acids. The rationale for the conjugation of such moieties was based on the design of structures with two or more molecular characteristics. The novel compounds were tested for their antioxidant, anti-inflammatory and hypolipidemic properties. Several compounds were potent antioxidants, comparable to the well-known antioxidant, Trolox. In addition, the radical scavenging activity of compound 6 reached levels that were slightly better than that of Trolox. All the tested compounds demonstrated remarkable activity in the reduction in carrageenan-induced rat paw edema, up to 59% (compound 2, a dual antioxidant and anti-inflammatory molecule, with almost 2.5-times higher activity in this experiment than the parent NSAID). Additionally, the compounds caused a significant decrease in the plasma lipidemic indices in Triton-induced hyperlipidemic rats. Compound 2 decreased total cholesterol by 75.1% and compound 3 decreased triglycerides by 79.3% at 150 μmol/kg (i.p.). The hypocholesterolemic effect of the compounds was comparable to that of simvastatin, a well-known hypocholesterolemic drug. Additionally, all compounds lowered blood triglycerides. The synthesized compounds with multiple activities, as designed, may be useful as potential candidates for conditions involving inflammation, lipidemic deregulation and oxygen toxicity.

Effects of Seed of Different Mango Cultivars in Triton X-100 Induced Hyperlipdemic Rats

Hyperlipidemia is the most prevalent indicator for susceptibility to atherosclerotic heart diseases. The present study investigated the hypolipidemic potential of Mangifera haden, Mangifera pirie and combined extracts of Mangifera haden and Mangifera pirie seeds in Triton X-100 induced hyperlipidemic rats. Before the starting of the experiment, the animals were acclimatized to the laboratory conditions for a period of seven days. At the end of the acclimatization period, each rat was weighed and randomly divided into twelve groups of five animals each, comprising of test animals and control groups. Proximate analysis, toxicity studies, lipid profile parameters were determined in the study. The research study took place in the animal house of Biochemistry Department, University of Nigeria, Nsukka from July 2020 to August 2022. Proximate composition of Mangifera haden and Mangifera pirie seed extracts revealed that the (%) values of protein, lipid, crude fibre, ash, moisture, and carbohydrate are (4.82, 17.18, 4.29, 2.77, 8.39, 62.55) and (3.81, 20.20, 3.0, 1.0, 34.0, 37.99) respectively. Mangifera haden and Mangifera pirie were administered at different doses (200 mg, 300 mg, 500 mg) of the extracts per kilogram body weight of the animals while combined extract of Mangifera haden and Mangifera pirie were administered at 300 mg and 500 mg of the extract per kilogram body weight of the animals in Triton –Induced hyperlipidemic rats. Simvastatin and Atorvastatin were used as reference standards. Simvastatin was found to be an effective drug to Atorvastatin in lowering lipid profiles. The statistical analyses were carried out using one way ANOVA followed by Dunnett’s Post Hoc Multiple Comparisons test. Mangifera haden, Mangifera pirie and combined extracts of both species show significant decrease (P = 0.05) in the levels of serum Total Cholesterol, triacylglycerols, VLDL-C, LDL-C, Atherogenic index (A.I) and significant increase (P = 0.05) of serum HDL-C against Triton-Induced hyperlipidemic rats. The result also suggest that at 200 mg/kg Mangifera pirie and 300 mg/kg Mangifera haden body weight concentrations are an excellent lipid lowering agent. Single administration of either Mangifera haden or Mangifera pirie effectively suppressed the Triton-Induced hyperlipidemia in rats than the combined extracts. The organic extracts (Mangifera haden or Mangifera pirie) exhibited quite hypolipidemic potential when compared with one of the reference drugs, Atorvastatin which indicates that the organic extracts could be explored as an alternative therapeutic agent in the treatment of hyperlipidemia.

Antidiabetic and antihyperlipidemic effects of Premna spinosa bark in experimental animal models.

The purpose of the study is to evaluate the antidiabetic and hyperlipidemic potential of stem bark extract of Premna spinosa (Lamiaceae), by using streptozotocin (STZ)-nicotinamide (NA)-induced diabetic and triton-induced hyperlipidemic models in albino rats. The blood glucose, total cholesterol, and triglyceride levels were determined in STZ-NA-induced diabetic and triton-induced hyperlipidemic rats, as per the respective protocols. It was found that there is the dose dependent and significant reduction in foregoing parameters on the administration of extract from Premna spinosa stem bark at the doses of 200, 400, and 800 mg/kg body weight to diabetic and hyperlipidemic rats. From these observed results it may be inferred that the stem bark of Premna spinosa possesses remarkable antidiabetic and antihyperlipidemic properties.

Antioxidant Serine-(NSAID) Hybrids with Anti-Inflammatory and Hypolipidemic Potency.

A series of L-serine amides of antioxidant acids, such as Trolox, (E)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)acrylic acid (phenolic derivative of cinnamic acid) and 3,5-di-tert-butyl-4-hydroxybenzoic acid (structurally similar to butylated hydroxytoluene), was synthesized. The hydroxy group of serine was esterified with two classical NSAIDs, ibuprofen and ketoprofen. The Trolox derivatives with ibuprofen (7) and ketoprofen (10) were the most potent inhibitors of lipid peroxidation (IC50 3.4 μΜ and 2.8 μΜ), several times more potent than the reference Trolox (IC50 25 μΜ). Most of the compounds decreased carrageenan-induced rat paw edema (37–67% at 150 μmol/kg). They were moderate inhibitors of soybean lipoxygenase, with the exception of ibuprofen derivative 8 (IC50 13 μΜ). The most active anti-inflammatory compounds exhibited a significant decrease in lipidemic indices in the plasma of Triton-induced hyperlipidemic rats, e.g., the most active compound 9 decreased triglycerides, total cholesterol and low-density lipoprotein cholesterol by 52%, 61% and 70%, respectively, at 150 μmol/kg (i.p.), similar to that of simvastatin, a well-known hypocholesterolemic drug. Since the designed compounds seem to exhibit multiple pharmacological actions, they may be of use for the development of agents against inflammatory and degenerative conditions.

A Preliminary Study on the Effect of Psyllium Husk Ethanolic Extract on Hyperlipidemia, Hyperglycemia, and Oxidative Stress Induced by Triton X-100 Injection in Rats.

Simple SummaryHyperlipidemia contributes to the emergence and development of circulatory diseases, which commonly causes morbidity and mortality. The present study evaluated the psyllium husk ethanolic extract (PHEE) effect on hyperlipidemia induced by Triton X-100. This study proved that Triton-induced hyperlipidemic rats with PHEE administration reduced hyperlipidemia by hepatic and pancreatic protective effects. The administration of PHEE lowered lipid peroxidation, increased antioxidant activity, and improved leptin and adiponectin hormone levels.The aim of this study is to assess the efficiency of psyllium husk ethanolic extract (PHEE) on Triton X-100 induced hyperlipidemic rats by studying the changes in hepatic and pancreatic function and histopathology. Forty male albino rats (bodyweight 175–188 g) were grouped randomly into four sets with ten rats. The experimental groups included: (1) control group (CON); (2) Triton X-100 induced hyperlipidemic group—rats were intraperitoneally injected with a single dose of Triton X-100 (100 mg/kg body weight) on the 21st day of Trial onset; (3) PHEE group—PHEE was orally administered (100 mg/kg body weight dissolved in 1 mL of distilled water) by gastric tube from the first day of the experiment until the fortieth day, once daily, (PHEE); (4) PHEE +Triton group, which received PHEE orally with the induction of hyperlipidemia. Treating hyperlipidemic rats with PHEE showed a decrease in the total serum lipids, triglyceride (TG), total cholesterol (TC), atherogenic index (AI), and malondialdehyde (MDA) with an increase in superoxide dismutase (SOD) and catalase (CAT) activities. PHEE administration alleviated the negative impact of Triton on the serum levels of glucose, insulin, glycated hemoglobin (HbA1c), homeostatic model assessment for insulin resistance (HOMA IR index), leptin hormone, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma-Glutamyl Transferase (GGT) and proteinogram. The Triton-induced hyperlipidemic rats showed extensive histopathological changes in the liver and pancreas, which were alleviated with PHEE administration. It could be concluded that PHEE has potent effects against hyperlipidemia, hyperglycemia, and oxidative stress due to its biologically active constituents detected by GC-MS analysis. This study’s findings may help develop a novel trial against the effects of hyperlipidemia in the future.

Evaluation of antihyperlipidemic activity of gugulipid alone and in combination with different dosage of atorvastatin in triton-induced hyperlipidemic rodent model: Exploring a possible synergistic activity

Background: Gugulipid obtained from Commiphora mukul carries a long history of safe and efficacious use in hyperlipidemia as per Ayurvedic literature. Statins like atorvastatin are a highly prescribed hypolipidemic drug but not free from potentially serious adverse effects. Aims and Objectives: The present study was designed to establish antihyperlipidemic activity of gugulipid in triton-induced hyperlipidemic rats in comparison to atorvastatin and simultaneously to explore the combination of gugulipid and atorvastatin for any synergistic activity. Materials and Methods: Male Wistar albino rats (20) were divided equally into vehicle (2% gum acacia) (Group I), gugulipid only 6.75 mg/kgbw (Group II), atorvastatin 7.2 mg/kgbw only (Group III), and gugulipid 6.75 mg/kgbw and atorvastatin in 7.2 mg/kgbw combination (Group IV) in Phase 1 study. In Phase 2, additional three groups were created with five rats in each receiving gugulipid 6.75 mg/kgbw with atorvastatin at 5.4 mg/kgbw, 3.6 mg/kgbw, and 1.8 mg/kgbw dosage, respectively (Groups V–VII). Hyperlipidemia was induced by single intraperitoneal injection (400 mg/kgbw) of triton after 7 days of feeding with respective agents dissolved in vehicle through oral route. Results: Regarding total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL), Gr II was found superior to Gr I but inferior to others (P < 0.01). Gr IV prevented the rise of TC and TG significantly in comparison to Gr V, VI, and VII (P < 0.01) whereas Groups V and VI having non-significant difference in between, both differed significantly (P < 0.01) with Gr VII. Groups IV, V, and VI prevented the rise of serum LDL significantly (P < 0.01) from Group VII. Conclusion: Gugulipid showed significant antihyperlipidemic activity and was found to be optimally efficacious and safe in combination with even reduced dose of atorvastatin.

Effect of cholesterol-lowering starter cultures in smoked sausages on the formation of bioactive peptides and lipid profile in triton-induced hyperlipidemic rats

Three types of sausages were studied: without starter cultures; with experimental starter cultures from Moscow State University of Food Production collection; with starter culture Bactoferm SM 194 (Chr. Hansen). No pathogenic bacteria in any sample were revealed. According to the results of PCR-RT, the number of lactic acid bacteria in all samples was about the same - 1x109-2×109 CFU/g. T-RFLP analysis shows the maximum number of lactobacilli sausages with experimental starter cultures averaged 69.59% of the total microbiota. The study of the protein profile of raw smoked sausages showed changes in protein fractions and presumably formation of biologically active peptides.A wide range of peptide mass peaks, with certain differences, was obtained by mass spectrometry. Feces of rats (groups 1-5) were studied by T-RFLP. The proportion of lactobacilli was 2.09% 2.65% and 2.35%, in groups 3-5 respectively. The serum atherogenic index did not differ significantly between the groups due to the low content of non-LDL and non-HDL cholesterol in control rats compared to the other groups. The greatest decrease of serum cholesterol concentration was measured in rats that consumed sausages with experimental starter cultures, mainly due to almost 3-fold (P<0.05) decrease in cholesterol of low-density lipoproteins compared with the control.

Antihyperlipidemic effect of a Rhamnus alaternus leaf extract in Triton-induced hyperlipidemic rats and human HepG2 cells

The Mediterranean buckthorn, Rhamnus alaternus L., is a plant used in traditional medicine in Mediterranean countries. We aimed at characterizing its phenolic compounds and explore potential antihyperlipidemic activity of this plant. The profile of phenolic compounds in R. alaternus leaf crude methanolic extract (CME) and its liquid-liquid extraction-derived fractions were analyzed by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ESI-MS2). Effects of CME on: circulating lipids in rats with Triton WR-1339-induced hyperlipidemia, intracellular lipid accumulation and expression of genes of fatty acid metabolism in human hepatoma HepG2 cells, and adipogenesis in the 3T3-L1 murine adipocyte cell model were assessed. The HPLC/ESI-MS2 analytical profile revealed a total of fifteen compounds, of which eleven were identified. Oral CME administration decreased blood levels of cholesterol and triacylglycerols in hyperlipidemic rats (by 60% and 70%, respectively, at 200 mg CME/kg). In HepG2 cells, CME exposure dose-dependently decreased intracellular lipids and up-regulated gene expression of carnitine palmitoyltransferase 1 involved in fatty acid oxidation. In the 3T3-L1 model, CME favored preadipocyte proliferation and adipogenesis, pointing to positive effects on adipose tissue expandability. These results suggest novel uses of R. alaternus by showing that its leaves are rich in flavonoids and flavonoid derivatives with an antihyperlipidemic effect in vivo and in hepatic cells.

Hypolipidemic Effect of EthanolicExtract of Cyperus esculentumis in TritonWR-1339-Induced Hyperlipidemic Rats

Currently, there has been an observed interest in phytochemicals as a new hypolipidemic agents to replace synthetic toxic hypolipidemic drugs. The investigation was carried out to evaluate the hypolipidemic effects of ethanolicextract of Cyperus esculentumis in triton-induced hyperlipidemic rats. The ethanolic extract of the plant was administered orally to rats at the doses of 300,400 and 600mg/kg body weight for a period of twenty nine days in accordance with the Ethical committee on experimental animals. Hyperlipidemia was developed by interaperitoneal injection of Triton at a dose 250mg/kg b.wt. to wistar rats . Intraperitoneal injection of Triton WR-1339 at a dose of 250mg/kg to rats resulted in the increase in serum triglyceride, total cholesterol , low density and very low density lipoproteins cholesterol accompanied by reduction in the high density lipoprotein cholesterol .The histopathological examination also revealed that there were remarkable histopathological changes in the aorta and artery of rats induced with Triton WR-1339 . The damages were manifested as ulceration and stenosis .Pretreatment with the ethanolic tuber extract of Cyperus esculentumis led to significant reduction of TC, TG, LDL and VLDL cholesterol in triton-induced hyperlipidemic rats as compared to the control. There was also an increased in HDL-cholesterol and attenuation of histopathological damages. Among the different doses administered, only 600 mg/kg exhited statistical significant effects. Other doses 300 and 400mg/kg showed mild toxicity. This finding suggests that the cholesterol-lowering effect of Cyperus esculentumis may be due to the enhancement of LDL-C metabolism which might be attributed to the presence of the valuable phytochemicals in the extract.

Evaluation of &lt;i&gt;In vitro&lt;/i&gt; Antioxidant and &lt;i&gt;In vivo&lt;/i&gt; Antihyperlipidemic Activities of Methanol Extract of Aerial Part of &lt;i&gt;Crassocephalum crepidioides&lt;/i&gt; (Asteraceae) Benth S Moore

Purpose: To evaluate the antioxidant and antihyperlipidemic activities of the methanol extract of aerial part of Crassocephalum crepidioides (Asteraceae) Benth. S. Moore. Methods: The methanol extract of Crassocephalum crepidioides was prepared by organic solvent extraction (Maceration) and assessed for in vitro antioxidant activity using various methods, namely, 2,2 diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, total phenol and flavonoid content and reducing capacity. The extract was also evaluated for antihyperlipidemic activity in high-fat diet and triton WR-100 (iso-octyl polyoxyethylene phenol)-induced hyperlipidemic albino rats by evaluating serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), triglycerides (TG), very low density lipoprotein cholesterol (VLDL-c), low-density lipoprotein cholesterol (LDL-c) level and atherogenic index (AI). Results: The plant extract showed significant antioxidant activity in a dose-dependent manner. In highfat diet hyperlipedemic rats, the extract significantly reduced ( p < 0.01 or 0.001) serum TC, TG, LDL-c and VLDL-c levels, but significantly increased ( p < 0.05) serum HDL c level. In triton-induced hyperlipidemic rats, the extract significantly reduced ( p < 0.05, p < 0.01, p < 0.001) serum TC, TG, LDLc, VLDL-c levels but significantly increased ( p < 0.05) serum HDL-c level. The extract showed significant reduction ( p < 0.01) in AI at 300 mg /kg/day dose in both high fat-induced (1.70 ± 0.25) and tritoninduced (1.5 ± 0.17) hyperlipidemic albino rats. Conclusion: Based on these findings, the extract of Crassocephalum crepidioides aids in lowering hyperlipidemia in rats. This is probably due to its antioxidant activity. Keywords: Antioxidant, Antihyperlipidemic, Crassocephalum crepidioides , Triton WR-100, Atherogenic index

A mechanism-based pharmacological evaluation of efficacy of Flacourtia indica in management of dyslipidemia and oxidative stress in hyperlipidemic rats.

Flacourtia indica (Burm. f.) Merr. is a medicinal plant indigenous to India and is broadly used worldwide for the treatment of a variety of health ailments. The present study was experimented on hyperlipidemic Charles Foster rats with the aim to explore the possible mechanism responsible for the antidyslipidemic activity of the hydromethanolic extract from F. indica leaves (FIL). Hyperlipidemia was induced by a single intraperitoneal dose of Triton WR-1339 in Charles Foster rats. The plasma lipid levels were estimated in control and treated groups. The antioxidant potential of F. indica was assessed in both enzymatic and non-enzymatic systems. An acute toxicity study of high-performance liquid chromatography (HPLC)-fingerprinted extract was carried out in Swiss albino mice. The F. indica extract at a dose of 150 mg/kg significantly lowers the plasma level of total cholesterol (17%), triglycerides (13%), and phospholipids (16%) by increasing post-heparin lipolytic activity (19%) and lecithin-cholesterol-acyltransferase activity (20%) in Triton-induced hyperlipidemic rats. In addition, the F. indica extract showed significant in vitro antioxidant and anti-adipogenic activity. HPLC analysis indicates the presence of flavanones and flavones in the extract, and the extract was found to be non-toxic up to a dose of 2000 mg/kg body weight in the acute oral toxicity study. These finding suggest that F. indica holds significant potential in preventing clinical deterioration induced by dyslipidemia along with oxidative stress.

Toxicological Assessment and Ameliorative Effects of Parinari curatellifolia Alkaloids on Triton-Induced Hyperlipidemia and Atherogenicity in Rats

In the present study, toxicity of the alkaloid extract and crude methanol extract of Parinari curatellifolia seeds and their anti-hyperlipidemic effect in Triton X-1339 intoxicated rats were investigated. Triton (200 mg/kg i.p)-induced hyperlipidemic rats were treated with nicotinic acid (500 mg/kg), alkaloid extract (15 mg/kg) or crude extract (150 mg/kg) by gavage for 10 days following which biochemical and histological analyses were carried out on heart, aorta and sera of the animals. Administration of triton led to increased levels of total cholesterol and triglycerides, low/very low density lipoproteins, and promoted cardiac oxidative stress. In addition, high density lipoprotein level was decreased while coronary and atherogenic risk indices were increased. The alkaloid extract (15 mg/kg) and crude methanol extract (150 mg/kg) significantly (P < 0.001) salvaged triton-induced effects on cardiac antioxidant status, total cholesterol (41 and 36 %), triglyceride (53 and 42 %), low density lipoprotein (80 and 79 %), very low density lipoprotein (53 and 41 %), high density lipoprotein (50 and 166 %), coronary risk index (97 and 86 %) and atherogenic risk index (90 and 94 %) as comparable to the reference compound, nicotinic acid. In addition, improved heart and aortic histological architecture were observed in rats treated with both extracts. The present results revealed the antihyperlipidemic, antiatherogenic and antioxidant effects of P. curatellifolia alkaloids in triton-induced hyperlipidemic rats and indicate their potential usefulness as a source of hypolipidemic and anti-atherogenic drugs.

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. Article history:

Efficacy of β-sitosterol isolated from Evolvulus alsinoides L. as anti-hyperlipidemic and anti-tumor agent: Evidence from animal studies.

To explore the anti-hyperlipidemic and anti-tumor effect of ethanolic extract of Evolvulus alsinoides, its chloroform fraction and isolated components in Triton-induced hyperlipidemic rats. Animals were administered with intraperitoneal (i.p.) injection of Triton WR 1339 at a dose of 400 mg/kg body weight. After 24 h of Triton administration the test drugs were administered orally at a dose of 200 mg/kg body weight in rats. The ethanolic extract and stigmast-5-en-3β-ol from Evolvulus alsinoides were further investigated for the tumor take inhibitory activity in hybrid mice (of C57BL strain + Swiss albino strain). Preventive group animals were injected daily with the extract and stigmast-5-en-3β-ol at dose of 50 mg/kg body weight i.p. for 10 consecutive days. The animals were observed for the growth of tumor after injection of B16F10 melanoma cells into the dorsal skin of mice. Stigmast-5-en-3β-ol showed a marked antihyperlipidemic potential by reducing the total cholesterol, triglycerides, low density lipoproteins level, and significantly increased high density lipoprotein level compared with other isolated component. Pretreatment with the drug showed delay tumor growth by increasing the volume doubling time and growth delay. The stigmast-5-en-3β-ol showed better mean survival time. The supplementation of antioxidants and phytosterols rich food Evolvulus alsinoides has significant tumor take inhibitory activity.

Hypolipidaemic potential of seaweeds in normal, triton-induced and high-fat diet-induced hyperlipidaemic rats

Numerous epidemiological studies have shown that long-term hyperlipidaemia is associated with coronary heart disease. The dietary and pharmacological lowering of elevated plasma LDL cholesterol appears to be one of the methods to reduce the development of atherosclerosis and related heart diseases. During this study, ethanol extracts of 13 seaweed species were tested for hypolipidaemic potential in normal rats, some of these caused positive effect by lowering the total cholesterol, triglyceride and LDL cholesterol with increase in HDL cholesterol. Efficacy of eight seaweeds Dictyota dichotoma var. intrica, Jolyna laminarioides, Melanothamnus afaqhusainii, Sargassum binderi, Sargassum swartzii, Halimeda tuna, Spatoglossum variabile, and Solieria robusta was also examined in triton-induced hyperlipidaemic rats. Three potential seaweeds J. laminarioides, S. binderi and M. afaqhusainii were further evaluated in high-fat diet-induced hyperlipidaemic rats. These seaweeds showed effective hypolipidaemic potential in triton-induced and high-fat diet-induced hyperlipidaemic rat models. Liver and cardiac enzymes like LDH, ALP, ASAT and ALAT were not adversely affected by seaweeds. Hypolipidaemic potential of some of the seaweeds is comparable with common hypolipidaemic drugs such as bezafibrate (Lipocor) and fenofibrate (Fenoget).

Isolation of Bioactive Phytoconstituent from Alpinia galanga L. with Anti-Hyperlipidemic Activity

ABSTRACTThe present study was undertaken to explore the antihyperlipidemic effect of ethanolic extract of rhizomes of Alpinia galanga L. and its chloroform fraction in Triton-induced hyperlipidemic rats. Bioactivity guided fractionation was followed by chromatographic studies. Flash chromatography was done for the most active fraction resulting in the isolation of 5-(hydroxymethyl) furfural. Animals were administered with i.p. injection of Triton WR 1339 at dose of 400 mg/kg body weight. After 24 hr of Triton administration, the ethanolic extract and its fraction were administered orally at doses of 200 and 400 mg/kg body weight in rats. The treatment was continued for 5 days with a view to see the effect on lipid profile. Serum samples were subjected to biochemical analysis. The study dose dependently inhibited the total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL) level, and significantly increased high-density lipoprotein (HDL) level. Phytochemical screening revealed the presence of tannins, coumarins, flavanoids, sterols, and glycosides. Phytochemical investigation of the chloroform fraction of A. galanga L. resulted in the isolation of 5-(hydroxymethyl) furfural. UV λmax was found to be 276 nm for the isolated component. Acute treatment caused a stimulatory effect on the HDL level and inhibition in TC and TG elevation induced by triton.

Effects of Senna didymobotrya Root Extract and Compounds on Tritoninduced Hyperlipidaemic Rats and Differentiation of 3T3-Li Preadipocytes

The lipid lowering effects of Senna didymobotrya (Leguminoceae) root extract (250 mg/kg) and pure isolates (100 mg/kg) were investigated for hypolipidemic activity on Triton-induced hyperlipidemic rats (in-vivo). The extracts and isolates showed significant (p≤0.01) reduction in serum lipid contents, and reactivation of the lipolytic enzymes, relative to the Triton-treated group. Ethyl acetate extract exhibited the highest lipid lowering (p≤0.01) compared to other fractions. Seven anthraquinones, obtusifolin (1), 1,6-di-O-methylemodin (2), nataloemodin-8-methyl ether (3), chrysophanol (4), physcion (5), chrysophanol-10,10'-bianthrone (6), physcion-10,10-bianthrone (7) and stigmasterol (8) were isolated from the ethyl acetate extract. Compounds 3, 5 and 7 displayed significant (p≤0.01) lipid lowering effects. The hypolipidaemic activities prompted the determination of inhibition of differentiation of 3T3-L1 preadipocytes into adipocytes by the compounds 3, 5 and 7. Only compound 7 exhibited potent anti-adipogenic activity without significant cytotoxicity. The result indicated that extracts of S. didymobotrya root extract can provide good antidyslipidaemic and adipocytes maturation inhibitors.

Lipid Lowering and Antioxidant Effect of Miglitol in Triton Treated Hyperlipidemic and High Fat Diet Induced Obese Rats

Miglitol, an anti-diabetic drug, has been shown to reduce plasma lipids and inhibit free radical generation. The anti-hyperlipidemic and antioxidant effects of miglitol were studied in triton-induced hyperlipidemic rats and high fat diet-fed obese rats. Plasma cholesterol and triglycerides levels were significantly lowered by miglitol at 100 mg/kg body weight doses. Miglitol inhibited generation of superoxide anion and hydroxyl free radicals by 14 and 31 % in enzymatic systems and 19 and 25 % in non-enzymatic systems, respectively. The in-vitro effect of the drug on adipogenesis using 3T3-L₁ preadipocytes at 2-, 5- and 10-μM concentrations showed significant inhibition of adipogenesis (34.2 %) at 10-μM concentration. High fat diet-fed rat model was used to investigate anti-hyperlipidemic, anti-obesity and antioxidant effect of miglitol. Miglitol increased the activities of lecithin-cholesterol-acyltransferase (19 %), post heparin lipolytic activity (26 %), lipoprotein lipase (26 %) and triglyceride lipase (31 %) which result in a decrease in plasma lipid levels. The antioxidant enzymes viz., catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and thioredoxin reductase were increased by the drug in the treated animals. The antihyperlipidemic and antioxidant effect of miglitol can be correlated to its effect on different enzymes and it can be used for inhibiting the development of cardiovascular diseases.