Hypolipidemic Effects Research Articles

The study on synthesis and vitro hypolipidemic activity of novel berberine derivatives nitric oxide donors

Berberine was used as the lead compound in the present study to design and synthesize novel berberine derivatives by splicing bromine bridges of different berberine carbon chain lengths coupled nitric oxide donors, and their lipid lowering activities were assessed in a variety of ways. This experiment synthesized 17 new berberine nitric oxide donor derivatives. Compared with berberine hydrochloride, most of the compounds exhibited certain glycerate inhibitory activity, and compounds 6a, 6b, 6d, 12b and 12d showed higher inhibitory activity than berberine, with 6a, 6b and 6d having significant inhibitory activity. In addition, compound 6a linked to furazolidone nitric oxide donor showed better NO release in experiments; In further mechanistic studies, we screened and got two proteins, PCSK9 and ACLY, and docked two proteins with 17 compounds, and found that most of the compounds bound better with ATP citrate lyase (ACLY), among which there may be a strong interaction between compound 6a and ACLY, and the interaction force was better than the target drug Bempedoic Acid, which meaning that 6a may exert hypolipidemic effects by inhibiting ACLY; moreover, we also found that 6a may had the better performance in gastrointestinal absorption, blood-brain barrier permeability, Egan, Muegge class drug principle model calculation and bioavailability.

Mitigation of letrozole induced polycystic ovarian syndrome associated inflammatory response and endocrinal dysfunction by Vitex negundo seeds

BackgroundPolycystic ovary syndrome (PCOS) is a complex endocrine disorder in women that necessitates effective and safe treatment alternatives. This study aimed to evaluate the therapeutic efficacy of Vitex negundo seed in a letrozole-induced PCOS rat model.ResultsFindings of the present study demonstrated that administration of hydro-ethanolic extract of Vitex negundo (VNE) effectively restored endocrino-metabolic imbalances associated with PCOS, along with correction of antioxidant enzymes level, proinflammatory cytokines, and apoptotic bio-markers. LC-MS analysis confirmed the presence of cinnamic acid, plumbagin and nigundin B as the prominent phytochemicals in VNE. The observed beneficial effects could be attributed to the active compounds in Vitex negundo extract, which exhibited hypoglycemic, hypolipidemic, and catabolic effects on body weight. Additionally, the extract contributed to hormonal balance regulation by modulating the steroidogenic enzymes, specifically by tuning gonadotropins level and correcting the LH:FSH ratio, through the modulation of ERα signalling and downregulation of NR3C4 expression. The antioxidant properties of phytochemicals in Vitex negundo seed were apparent through the correction of SOD and catalase activity. While it’s anti-inflammatory and antiapoptotic action were associated with the regulation of mRNA expression of TNF-α, IL-6, BAX, Bcl2. Molecular docking study further indicated the molecular interaction of above mentioned active phytocompounds of VNE with ERα, NR3C4 and with TNFα that plays a critical mechanistic gateway to the regulation of hormone signalling as well as synchronizing the inflammation cascade. Furthermore, the histomorphological improvement of the ovaries supported the ameliorative action of Vitex negundo extract in the letrozole-induced PCOS model.ConclusionsThis study indicates the potential of Vitex negundo seed as a multifaceted therapeutic option for PCOS. VNE offers a holistic strategy for PCOS with antiandrogenic, anti-inflammatory, and antioxidant properties, driven by its major compounds like cinnamic acid, plumbagine, and nigundin B.

A combination of gliclazide and metformin attenuates obesity-induced polycystic ovary syndrome in female Wistar rats

Presently, it is known that the progression of obesity concomitantly leads to polycystic ovary syndrome and infertility. This study aimed to evaluate the potential effects of metformin (M; insulin secretagogues) and gliclazide (G; insulin sensitizer) alone and their combination at different doses to treat obesity-induced PCOS. High high-fat diet was given to all female Wistar rats for nine weeks to induce obesity except for the normal control group which received a normal chow diet. Estradiol valerate (0.8 mg/kg) was also given to all obese rats to induce polycystic ovarian syndrome. After the induction, M (100, 300 mg/kg) and G (5, 10 mg/kg) were given orally either individually or in combination for 28 days. The notable (p < 0.0001) reduction in body weight and blood glucose level was observed in treatment groups in contrast to disease control (DCG). The marked (p < 0.05–0.0001) decrease in hemocylated hemoglobin, serum insulin, cholesterol, triglycerides, and testosterone was observed in treated groups, notably in combination groups (M100+G10 mg/kg) in contrast to DCG. There was a considerable (p < 0.01–0.0001) increase in progesterone E2, estradiol, luteinizing, and follicle-stimulating hormones in treated groups as compared to DCG. Treatment with M and G treated groups also exhibited marked (p < 0.05–0.0001) increases in SOD, CAT, and GSH while decreased in NO and MDA levels in ovary tissue as evidenced by the histological study of the ovary. Treatment with M and G alone and in combination significantly (p < 0.0001) restored the serum IL-6, NrF2, and NF-κB levels as compared to DCG. The results inveterate that the M and G combination (M100+G10, and M300+G10) was useful in treating obesity-induced infertility due to antioxidant properties, hypolipidemic effects, and modulation of inflammatory markers.

A Mini-review on the Chemical Composition, Extraction and Isolation Techniques, and Pharmacological Activity of Rosmarinus officinalis L.

Abstract: Rosmarinus officinalis L. belongs to the genus Rosemary in the family Labiatae, which is a perennial evergreen subshrub. It is currently cultivated in certain areas of Yunnan, Guangxi, and Guizhou. At present, in food, cosmetics, healthcare products, and other domains, R. officinalis has a wide range of applications; it has received widespread attention, and is also a hot topic of research today. Using modern spectroscopic techniques, it has been found that the main chemical components of rosemary can be divided into two major groups, including volatile components (essential oils) and non-volatile components (diterpenes, triterpenes, flavonoids, phenolic acids, sterols, etc.). Among them, carnosic acid, carnosol, rosemary phenol, and 1,8-cineole are the main components acting as antioxidants and they are highly regarded. The main methods for extracting the active ingredients of R. officinalis include water distillation, ultrasonic-assisted microwave method, supercritical CO2 extraction method, enzyme-assisted extraction method, and microwaveassisted extraction method. Modern research has shown that rosemary has anti-inflammatory, antioxidant, antibacterial, antiviral, antitumor, hepatoprotective, hypolipidemic, immunomodulatory, antiseptic, and antithrombotic effects, and is widely used in medical applications.

Hepatoprotective Activity of Ezetimibe Against Risperidone-Induced Liver Injury in Rats

Abstract Background: Drug-induced hepatic injury is an unfavorable reaction to medications and/or their byproducts, which can result in ongoing harm to liver function and even death. Risperidone, the second most prescribed antipsychotic drug, has been linked to weight gain, abnormal hepatic enzyme levels, and further damage to liver cells. On the other hand, ezetimibe is an antihyperlipidemic agent that reduces serum cholesterol levels by inhibiting its absorption in the gastrointestinal tract. Additionally, it possesses antioxidant, hepatoprotective, and nephroprotective properties. Objectives: The purpose of this study is to evaluate the hepatoprotective and hypolipidemic effects of ezetimibe in mitigating liver damage induced by risperidone. Materials and Methods: A total of 24 adult male Swiss albino rats aged 6–7 weeks and weighing 170–180 g each were randomly divided into four groups, with 6 rats in each group. The first group served as a control and received vehicles only (0.5 mL of corn oil). Rats in the second group were administered risperidone alone at a dose of 2 mg/kg. In the last two groups, rats received a combination of risperidone (2 mg/kg) and ezetimibe at doses of 3 and 5 mg/kg, respectively. After sacrificing the rats, serum samples were collected to measure parameters related to lipid profile and liver enzymes. Additionally, liver tissue was immediately gathered for histopathological assessment using the NAS scoring system. Results: Ezetimibe exhibited marked hepatoprotective effects in rats exposed to risperidone-induced hepatic injury. This was achieved by significantly (P &lt; 0.05) lowering adverse lipid profile components (TCHO, TG, LDL, and VLDL) and liver enzymes (ALT and AST), while at the same time significantly (P &lt; 0.05) elevating the beneficial lipid profile (HDL). Moreover, Ezetimibe demonstrated remarkable liver protection by mitigating hepatic lobule destruction, inflammatory cell infiltration, and the presence of steatotic cells. Conclusion: Ezetimibe exhibited notable hepatoprotective and hypolipidemic properties in countering hepatic injury induced by risperidone.

Comparative of Antioxidant property of Actinidia Deliciosa extracts by DPPH Assay

Introduction: The kiwi fruit is the edible berry of a cultivar group of the woody vine of several Actinidia species. The most common commercially available, green-fleshed kiwi fruit is the cultivar 'Hayward', which belongs to the Actinidia deliciosa species. Various chemical tests such Quantitative and Qualitative analysis have been carried out on kiwi extract. Methods: The antioxidant activity was evaluated by DPPH, an antioxidative screening of kiwi fruit components (pulp) crude extracts were carried out using specific assay media characterized for the presence of highly reactive species such as 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH). In-vitro the antioxidant enzymes study of DPPH. Result: In our study we have evaluated the antioxidant capacity of flesh of kiwi fruit and also evaluated the antioxidant activity of kiwi fruit constituents along with the array detector for curcumin and piperine. Conclusion: The Kiwi fruit which is highly antioxidant in nature was found to have activity against asthma. It also acts as an anti-oxidant, antidiabetic, anti-ulcer, anti-tumour, hypoglycaemic, hypolipidemic effects, anti-inflammatory and many more. Recent studies show that phytoconstituent such as curcumin and piperine have used to treat asthma.

The cytotoxicity of 1,4-bis(3,4,5-trimethoxyphenyl)-tetrahydro-furo(3,4-c) furan isolated from Swietenia macrophylla King seed extract on 3T3-L1 and RAW 264.7 cells

The exploration of natural products as anti-obesity candidates needs to be performed urgently since obesity has become a worldwide epidemic and many drugs for this health condition were withdrawn due to their serious adverse events such as psychiatric disorders and drug dependence. The 1,4-bis(3,4,5-trimethoxyphenyl)-tetrahydro-furo(3,4-c) furan, a saponin isolated from Indonesian Swietenia macrophylla seeds extract has the potential to modulate obesity because it acts as a potent PPAR-γ agonist in silico and the seeds’ hypolipidemic effect has been proven. The cytotoxicity study is a crucial part of the early pharmaceutical development stage, whilst, the exploration of 1,4-bis(3,4,5- trimethoxyphenyl)-tetrahydro-furo(3,4-c) furan to ensure the compound’s safety in preadipocytes and macrophage cells which play a crucial role in obesity pathogenesis is still limited. This study aims to explore the cytotoxicity of saponin isolate on 3T3-L1 (preadipocytes) and RAW 264.7 (macrophages) cell lines to ensure its safety profile in vitro. Both cell lines were exposed to various concentrations of the isolate (3.125-200 µg/mL), then metformin was used as the standard drug and DMSO as solvent control for 24 hrs. The cytotoxicity test was conducted by MTT assay and IC50 was determined by probit analysis. Most of the 1,4-bis(3,4,5-trimethoxyphenyl)-tetrahydro-furo(3,4-c) furan did not affect the viability of 3T3-L1 and RAW 264.7 with the IC50 148.90±12.22 and 84.78±1.69 µg/mL, respectively. Metformin and DMSO also did not alter the viability of both cells. These results were promising as a basis for further development since the isolates’ IC50 value was more than the cytotoxic threshold of NCI guidelines.

Dyslipidemic effect of aqueous and ethanolic extracts of raw and roasted xoconostle (Opuntia joconostle) peel

The aim of the present study was to assess the impacts of roasting and the type of extraction solvent (ethanol or water) on the hypolipidemic activity of xoconostle fruit peel extracts in a tyloxapol-induced model of hyperlipidemia. Water and ethanol extracts from raw and roasted Opuntia joconostle peels were obtained to quantify the phytochemicals contained within and assess their hypolipidemic activity in rats (n=5) against tyloxapol-induced dyslipidemia (400 mg/kg). The raw ethanol and water extracts, as well as the roasted water extract (200 mg/kg), showed hypolipidemic activity in the tyloxapol-treated group (p&lt;0.05). In contrast, the roasted sample extracted with ethanol did not show this effect. The concentrations of phenolic compounds (39.80 mg GAE/g) and flavonoids (16.42 ±0.14 mg QE/g) were higher in the ethanolic extracts than in the aqueous extracts. Conversely, the concentration of betalains (115.51 ±1.66 mg/100 g) was higher in the water extracts than in the ethanol extracts. It was concluded that the roasting process modified the concentration of some phytochemicals and their antioxidant capacity in vitro, producing a hypolipidemic effect in tyloxapol-induced hyperlipidemic rats.

A Comparative Analysis between Whole Chinese Yam and Peeled Chinese Yam: Their Hypolipidemic Effects via Modulation of Gut Microbiome in High-Fat Diet-Fed Mice.

Chinese yam is a "medicine food homology" food with medical properties, but little is known about its health benefits on hyperlipidemia. Furthermore, the effect of peeling processing on the efficacy of Chinese yam is still unclear. In this study, the improvement effects of whole Chinese yam (WY) and peeled Chinese yam (PY) on high-fat-diet (HFD)-induced hyperlipidemic mice were explored by evaluating the changes in physiological, biochemical, and histological parameters, and their modulatory effects on gut microbiota were further illustrated. The results show that both WY and PY could significantly attenuate the HFD-induced obesity phenotype, accompanied by the mitigative effect on epididymis adipose damage and hepatic tissue injury. Except for the ameliorative effect on TG, PY retained the beneficial effects of WY on hyperlipemia. Furthermore, 16S rRNA sequencing revealed that WY and PY reshaped the gut microbiota composition, especially the bloom of several beneficial bacterial strains (Akkermansia, Bifidobacterium, and Faecalibaculum) and the reduction in some HFD-dependent taxa (Mucispirillum, Coriobacteriaceae_UCG-002, and Candidatus_Saccharimonas). PICRUSt analysis showed that WY and PY could significantly regulate lipid transport and metabolism-related pathways. These findings suggest that Chinese yam can alleviate hyperlipidemia via the modulation of the gut microbiome, and peeling treatment had less of an effect on the lipid-lowering efficacy of yam.

Effect of quinoa (Chenopodium quinoa W.) flour supplementation in breads on the lipid profile and glycemic index: an in vivo study.

Quinoa is a gluten-free pseudocereal, with an excellent nutrient profile containing considerable amounts of fiber and minerals and rich in antioxidants such as polyphenols. The purpose of this research was to investigate the effects of quinoa bread on physical, chemical, bioactive components, glycaemic index (GI), and biochemical parameters. Human subjects aged between 20 and 50 years with the absence of morbid factors were fed daily with quinoa bread for 3 months in order to study its pre-and post-treatment effects on blood glucose, glycosylated haemoglobin, and lipid profile. The effort was made to incorporate the maximum amount of quinoa into the bread without compromising the acceptability of the bread. Of the 14 formulations, TQ13, containing 20% quinoa flour with 3% wheat bran, was selected for further analysis. The GI study revealed that quinoa bread peaked at 45 min with a gradual increase after ingestion of the bread and a steady decline thereafter. The observed value for blood glucose levels, before and after supplementation with quinoa-incorporated bread, was 86.96 ± 15.32 mg/dL and 84.25 ± 18.26 mg/dL, respectively. There was a statistically significant (p ≤ 0.05) decrease in levels of triglycerides, total cholesterol, low-density lipoprotein (LDL), and very-LDL (VLDL) level before and after supplementation. However, non-significant changes were observed for high-density lipoprotein levels from the pre- and post-treatment with the quinoa-incorporated bread. Quinoa-incorporated bread possessed low GI (42.00 ± 0.83) compared to control (69.20 ± 1.84) and long-term consumption proved to contain functional efficacies in terms of hypolipidemic effect.

Phenolic Acids, Steroids, and Triterpenoids Isolated from Platycodon grandiflorus (Jacq.) A. DC.

Platycodon grandiflorus (Jacq.) A. DC. is a precious medicinal plant, which is one of 54 medicinal species selected by the Vietnamese government for development in specialized areas of medicinal herbs. Currently, P. grandiflorus has been planted in some regions in Vietnam. Although P. grandiflorus has been commonly used in traditional Vietnamese medicine, the reports on the chemical composition and biological activity of this plant are limited in our country. As a part of our research on the hypolipidemic effect of P. grandiflorus, six compounds including ferulic acid (1), caffeic acid (2), p-hydroxy benzoic acid (3), spinasterol (4), sitostenone (5), and betulin (6) were isolated from the ethyl acetate and n-hexane extracts of the roots of P. grandiflorus. The structures of these compounds were determined based on NMR and MS spectral data and comparison with those reported in the literature. Compound 5 has been found in P. grandiflorus for the first time.&#x0D;

Hypolipidemic effect and gut microbiota regulation of Gypenoside aglycones in rats fed a high-fat diet

Ethnopharmacological relevanceGynostemma pentaphyllum (Thunb.) Makino has traditional applications in Chinese medicine to treat lipid abnormalities. Gypenosides (GPs), the main bioactive components of Gynostemma pentaphyllum, have been reported to exert hypolipidemic effects through multiple mechanisms. The lipid-lowering effects of GPs may be attributed to the aglycone portion resulting from hydrolysis of GPs by the gut microbiota. However, to date, there have been no reports on whether gypenoside aglycones (Agl), the primary bioactive constituents, can ameliorate hyperlipidemia by modulating the gut microbiota. Aim of the studyThis study explored the potential therapeutic effects of gypenoside aglycone (Agl) in a rat model of high-fat diet (HFD)-induced hyperlipidemia. MethodsA hyperlipidemic rat model was established by feeding rats with a high-fat diet. Agl was administered orally, and serum lipid levels were analyzed. Molecular techniques, including RT-polymerase chain reaction (PCR) and fecal microbiota sequencing, were used to investigate the effects of Agl on lipid metabolism and gut microbiota composition. ResultsAgl administration significantly reduced serum levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) and mitigated hepatic damage induced by HFD. Molecular investigations have revealed the modulation of key lipid metabolism genes and proteins by Agl. Notably, Agl treatment enriched the gut microbiota with beneficial genera, including Lactobacillus, Akkermansia, and Blautia and promoted specific shifts in Lactobacillus murinus, Firmicutes bacterium CAG:424, and Allobaculum stercoricanis. ConclusionThis comprehensive study established Agl as a promising candidate for the treatment of hyperlipidemia. It also exhibits remarkable hypolipidemic and hepatoprotective properties. The modulation of lipid metabolism-related genes, along with the restoration of gut microbiota balance, provides mechanistic insights. Thus, Agl has great potential for clinical applications in hyperlipidemia management.

A Proof-of-Concept for a Hypolipidemic Brown Trout Model.

The impacts of hypolipidemic pharmaceuticals on fish lipid metabolism remain unexplored. However, data points to similar effects and mechanisms of action between fish and humans. Therefore, fish may be a strong model for screening hypolipidemic drug candidates and water pollution by lipid-modulating agents. This study aimed to test a new hypolipidemic model assay with juvenile brown trout using atorvastatin (ATV)-a hypolipidemic chemical. We selected 17α-ethinylestradiol (EE2), known to cause hyperlipidemia in fish, to ensure model functionality. Fish received intramuscular injections of 4 μL/g for two weeks under the following experimental conditions: control-C (0.7% NaCl), solvent control-SC (0.7% NaCl, 0.9% ethanol, 0.1% dimethyl sulfoxide), ATV (0.3 μg/g), EE2 (2 μg/g), and a mixture of both compounds-MIX (0.3 μg/g ATV and 2 μg/g EE2). Endpoints included blood lipid biochemistry, hepatic lipid droplet quantification, and liver mRNA expression of lipid-related target genes (related to lipogenesis, lipid transport, and β-oxidation pathways). ATV lowered blood total cholesterol, high-density lipoproteins (HDL), and low-density lipoproteins (LDL) levels, whilst triglycerides and very-low-density lipoproteins (VLDL) were highest under EE2. Hepatic lipid droplet deposition significantly increased in the ATV, EE2, and MIX groups. ATV and MIX caused a significant downregulation of the peroxisome proliferator-activated receptor γ (pparγ) and acetyl Co-A oxidase 3 (acox3). EE2 upregulated acyl-CoA long-chain synthetase 1 (acsl1) and downregulated both fatty acid binding protein 1 (fabp1) and acetyl Co-A oxidase 1-3I (acox1-3I). ATV caused hypolipidemic effects in juvenile brown trout and could even counteract EE2-stimulated hyperlipidemia, reinforcing the potential of fish hypo- and hyperlipidemic models.

The anti-cholestatic effects of Coptis chinensis Franch. alone and combined with Tetradium ruticarpum (A. Jussieu) T. G. Hartley: dual effects on fecal metabolism and microbial diversity.

Introduction: Drug dosages and combinations are the main factors that affect the efficacy of pleiotropic traditional Chinese medicine (TCM). Coptis chinensis Franch. (CF) is a representative TCM with multiple effects and is often combined with Tetradium ruticarpum (A. Jussieu) T. G. Hartley (TR) to treat cholestasis. The present study assessed the influence of CF dose and its combination with TR on the efficacy of CF in cholestasis treatment, including their effects on fecal metabolism and fecal microorganisms. Methods: Rats with α-naphthylisothiocyanate (ANIT, 50mg/kg)-induced cholestasis were administered low (0.3g/kg) and high (0.6g/kg) doses of CF, as well as CF combined with TR at doses of 0.6g/kg and 0.9g/kg, respectively. The anti-cholestatic effects of these treatments were assessed by determining their anti-inflammatory, hypolipidemic, and anti-oxidative stress properties. Additionally, fecal metabolomics and fecal microorganisms were analyzed. Results: Low dose CF had a more potent hypolipidemic effect than high dose CF, whereas high dose CF had more potent anti-inflammatory and anti-oxidative stress effects. Combination with TR enhanced the hypolipidemic effect, but antagonized the anti-inflammatory effect, of CF. Analyses of fecal metabolomics and fecal microorganisms showed differences in the regulation of lipid- and amino acid metabolism-related pathways, including pathways of linoleic acid, tyrosine, and arachidonic acid metabolism, and amino acid biosynthesis between different doses of CF as well as between different doses of CF in combination with TR. These differences may contribute to differences in the anti-cholestatic effects of these preparations. Conclusion: CF dose influences its anti-cholestatic efficacy. The combination with TR had synergistic or antagonistic effects on the properties of CF, perhaps by altering fecal metabolism and fecal microbial homeostasis.

Evaluating the hypolipidemic effect of garlic essential oil encapsulated in a novel double-layer delivery system

The limited application of garlic essential oil (GEO) is attributed to its pungent taste, poor water solubility and low bioavailability. Liposomes are nontoxic, biodegradable and biocompatible, and β-cyclodextrin can inhibit undesirable odors and improve the stability and bioavailability. Thus a promising dual-layer GEO β-cyclodextrin inclusion compound liposome (GEO-DCL) delivery system with both advantages was designed and prepared in this study. Experimental results indicated that the encapsulation efficiency of GEO-DCLs was 5% higher than that of GEO liposomes (GEO-CLs), reaching more than 88%. In vitro release experiment showed that the release rate of GEO in GEO-DCLs was 40% lower than that of GEO-CLs after incubation in gastric juice for 6-h, indicating that the stability of GEO-DCLs was better than GEO-CLs. Evaluation of the effects of GEO-DCLs on lowering blood lipid levels in hypercholesterolemia mice. GEO-DCLs could reduce the weight and fat deposition in hypercholesterolemia mice. Inhibiting the increase of TC, LDL-C, and decrease of HDL-C in mice. The degree of liver injury was decreased, the number of round lipid droplets in liver cytoplasm was reduced, and the growth of fat cells was inhibited. The lipid-lowering effects of GEO-DCLs were dose-dependent. GEO-DCL can improve the bioavailability of GEO and improve dyslipidemia. Based on GEO's efficacy in lowering blood lipids, this study developed a kind of GEO-DCL compound pomegranate juice beverage with good taste, miscibility and double effect of reducing blood lipids. This study lays a foundation for the application of GEO in the field of functional food.

Hypolipidemic Effect of Rice Bran Oil Extract Tocotrienol in High-Fat Diet-Induced Hyperlipidemia Zebrafish (Danio Rerio) Induced by High-Fat Diet.

In recent years, the potent influence of tocotrienol (T3) on diminishing blood glucose and lipid concentrations in both Mus musculus (rats) and Homo sapiens (humans) has been established. However, the comprehensive exploration of tocotrienol's hypolipidemic impact and the corresponding mechanisms in aquatic species remains inadequate. In this study, we established a zebrafish model of a type 2 diabetes mellitus (T2DM) model through high-fat diet administration to zebrafish. In the T2DM zebrafish, the thickness of ocular vascular walls significantly increased compared to the control group, which was mitigated after treatment with T3. Additionally, our findings demonstrate the regulatory effect of T3 on lipid metabolism, leading to the reduced synthesis and storage of adipose tissue in zebrafish. We validated the expression patterns of genes relevant to these processes using RT-qPCR. In the T2DM model, there was an almost two-fold upregulation in pparγ and cyp7a1 mRNA levels, coupled with a significant downregulation in cpt1a mRNA (p < 0.01) compared to the control group. The ELISA revealed that the protein expression levels of Pparγ and Rxrα exhibited a two-fold elevation in the T2DM group relative to the control. In the T3-treated group, Pparγ and Rxrα protein expression levels consistently exhibited a two-fold decrease compared to the model group. Lipid metabolomics showed that T3 could affect the metabolic pathways of zebrafish lipid regulation, including lipid synthesis and decomposition. We provided experimental evidence that T3 could mitigate lipid accumulation in our zebrafish T2DM model. Elucidating the lipid-lowering effects of T3 could help to minimize the detrimental impacts of overfeeding in aquaculture.

Optimization of Naringenin-loaded nanoparticles for targeting of Vanin-1, iNOS, and MCP-1 signaling pathway in HFD-induced obesity

Naringenin, a natural dihydrochalcone flavonoid, exhibits diverse pharmacological properties. This study investigates the hypolipidemic effects of Nar-NPs on obese mice. The characteristics of Nar-NPs, including morphology, particle size, zeta potential, UV–vis, and FT-IR spectra, were examined. The anti-obesity properties of Nar-NPs were evaluated in obese rats, considering LD50, 1/20 LD50, and 1/50 LD50 for treatment preparation. Results indicated that synthesized Nar-NPs were uniform, spherical, and well-dispersed, with a size of 130.06 ± 1.98 nm and with a zeta potential of −25.6 ± 0.8 mV. Nar-NPs exhibited enhancement in the cumulative release of naringenin (56.87 ± 2.45 %) as compared to pure naringenin suspension 87.83 ± 1.84 % in 24 h of the study. The LD50 of Nar-NPs was determined as 412.5 mg/kg.b.w. HFD induced elevated glycemic, oxidative stress, and inflammatory biomarkers while reducing HDL-C, GSH, and superoxide dismutase (SOD) levels. Administration of Nar-NPs significantly mitigated body weight, glucose, insulin, leptin, TC, TG, SREBP1c, pAMPK, PPAR-α, as well as vanin-1, MCP-1, and iNOS mRNA gene expression. Histological investigations supported the biochemical and PCR findings. In a nutshell, the study suggests that the Nar-NPs could serve as a promising and viable pharmacological strategy for the treatment of obesity-related disorders.

Exploring Scientific Validation of Millets in Contemporary Healthcare: A Traditional Food Supplement.

Millets, small-seeded grasses, are gaining interest for their nutrition and health benefits. This abstract provides a comprehensive overview of millets' pharmacological activities, highlighting their rich bioactive compounds. These compounds, including phenolic compounds, flavonoids, and dietary fibers, contribute to antioxidant effects, safeguarding against chronic diseases. Millets also possess anti-inflammatory properties, potentially alleviating conditions, like arthritis and asthma. They show anti-carcinogenic potential, possibly preventing various cancers' development through mechanisms, like apoptosis induction and inhibiting tumor growth. Moreover, millets offer hypolipidemic and hypoglycemic effects, beneficial for managing conditions, such as dyslipidemia and diabetes. Their high dietary fiber and resistant starch content regulate blood lipids and glucose, reducing the cardiovascular risk. Additionally, millets act as antimicrobials, inhibiting pathogens and serving as natural alternatives to synthetic antimicrobials. They exhibit immunomodulatory effects, enhancing immune function and response. Overall, millets' pharmacological properties, including antioxidant, antiinflammatory, anti-carcinogenic, hypolipidemic, hypoglycemic, antimicrobial, and immunomodulatory traits, position them as functional foods with varied health benefits. Further research can integrate millets into preventive and therapeutic approaches for diverse diseases.

Investigation of acute and sub-chronic oral toxicity and effects of Allium ascalonicum L. extract on Triton WR1339-induced hyperlipidemia on Swiss albino mice

IntroductionMetabolic disorders are increasingly rapidly becoming a burden on global healthcare systems. Among these, hyperlipidemia frequently leads to cardiovascular diseases such as myocardial infarction and cerebral stroke, posing significant life-threatening risks. The pharmacological drugs, which are often costly and may cause a range of adverse side effects detrimental to health. Allium ascalonicum L., a member of the Alliaceae family, a widely used species of the Allium genus, is commonly employed as a spice and food ingredient in Asia. Allium ascalonicum (AS) is rich in triterpenoids, phenolic acids, flavonoids, thiosulfates, and anthocyanins, whose therapeutic effects have been documented. In Chinese, Allium ascalonicum L. is known as 葱 (Cōng), which is used for various types of onions and similar plants in Chinese, including shallots. Ancient Chinese medicine documented that AS has a sweet and mildly spicy taste with a slight astringency and is warm in nature. In traditional Chinese medicine, AS is prepared as infusions, juices, and poultices to harness their health benefits, and commonly used in cooking for their nutritional and medicinal purposes. Modern medicine has discovered that this type of bulb possesses antibacterial and anti-inflammatory properties, acts as a diuretic, treats diarrhea, reduces blood sugar levels, lowers blood pressure, reduces cholesterol, and among its other roles. Currently, there is a lack of in vivo study on the cholesterol-regulating potential of AS. MethodsFor our experiments, 24 and 32 Swiss albino mice were employed to investigate the acute and sub-chronic oral toxicity according to the Guidelines for preclinical and clinical trials of Traditional Medicine and Herbal Medicines by the Vietnam Ministry of Health and OECD. To investigate the effects on hyperlipidemia, 40 mice of both sexes were divided into five groups (n = 6–8 each). Tyloxapol (Triton WR1339, 400 mg/kg, i.p.) was used to induce hyperlipidemia. Atorvastatin (60 mg/kg, p.o.) was used as the standard, and AS extract was conducted at the doses of 500 mg/kg and 1000 mg/kg. Hyperlipidemic activity was assessed using a variety of parameters. ResultsAllium ascalonicum (AS) extract showed no acute toxicity and sub-chronic toxicity. The AS showed a significant decrease in total cholesterol, triglycerides and LDL-c but showed no changes in HDL-c. ConclusionOur results indicated that AS is safe to use for a longtime and has a potential as an antihyperlipidemic agent, possibly due to its ability to inhibit the elevation of total cholesterol, triglycerides and LDL-c. The AS is rich in phytochemicals like triterpenoids, flavonoids and saponins, which may contribute to its hypolipidemic effect.

Impact of statins in the liver: A bane or a boon?

Treatment of hypercholesterolemia with statins is considered one of the cornerstones in the management of atherosclerotic cardiovascular diseases. Statins exert their hypolipidemic effects by inhibiting HMG-CoA reductase, the key enzyme in cholesterol biosynthesis. Beyond cholesterol reduction, statins exhibit pleiotropic effects, including anti-inflammatory, antioxidant, and antiproliferative actions, making them valuable in mitigating atherosclerotic and non-atherosclerotic diseases. Though concerns of hepatotoxicity have been associated with the use of statins, extensive evidence suggests that the risk of statin-induced liver injury (SILI) is rare, with an incidence of &lt;1%. Hepatic adverse effects include reversible asymptomatic transaminase elevation (most frequent), hepatitis, cholestasis, and rarely acute liver failure. While hepatotoxicity concerns should not be dismissed, the evidence overwhelmingly supports the safety of statins. Contrary to the myth of statin hepatotoxicity, real-world data and extensive research emphasize the safety and benefits of statins. They are therapeutic in various liver-related conditions, mainly non-alcoholic fatty liver disease. This scientific review aims to provide a comprehensive overview of statins, shedding light on their mechanism of action, hepatotoxicity concerns, and therapeutic potential in various liver-related conditions.