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.

Triglycerides: A Sensitizer but Not a Trigger for Hypertriglyceridemic Acute Pancreatitis.

BACKGROUND: The incidence of hypertriglyceridemic acute pancreatitis (HTG-AP) is increasing. Although the guideline defines the diagnostic criteria as triglyceride (TG) greater than 11.3 mmol/L, there is actually no specific threshold. Many people with hypertriglyceridemia (HTG) or obvious chyloid blood do not develop acute pancreatitis (AP). AIMS: To explore the role of HTG in the pathogenesis of AP. METHODS: Thirty-six male SD rats were randomly assigned into normal control, AP, HTG, HTG-AP, low-dose fenofibrate and high-dose fenofibrate groups. Serum indices and cytokine levels in serum, and pathological changes in pancreatic tissues were observed. The expression levels of TLR4 and NF-κBp65 in pancreatic tissues were detected by immunohistochemistry and Western blot. RESULTS: In normal rats, HTG alone did not induce AP. However, after establishing the HTG-AP model with Poloxam 407 and L-arginine, serum-free fatty acid and TG levels were positively correlated with the levels of lipase, amylase, IL-1ß, IL-6, pancreatic inflammation scores, and the expressions of TLR4 and NF-κBp65 (all P < 0.001). Expressions of TLR4 and NF-κBp65 were significantly increased in the pancreatic tissues of HTG-AP rats. Fenofibrate effectively decreased TG levels in HTG-AP rats and reduced the expression of TLR4 and NF-κBp65 (all P < 0.001). CONCLUSIONS: HTG does not directly cause AP, but rather increases the susceptibility to AP or aggravates the inflammatory response. It is more like a sensitizer of inflammation rather than an activator.

Antioxidant and antihyperlipidemic effects of hawthorn extract (Crataegus oxyacantha) in broiler chickens.

BACKGROUND: One of the main problems in the poultry industry is excess body fat, and the anti-fat effect of Cratagus extract has been confirmed in several studies. OBJECTIVES: The present study was carried out to investigate the effects of hawthorn extract (Crataegus oxyacantha) on growth performance, haematological variables and hepatic gene expression in broiler chickens reared at high altitude (2100 m). METHODS: A total of 225-day-old chicks (Ross 308) were randomly distributed into three treatments. Experimental treatments were prepared by adding 0.0, 0.2 and 0.4 mL of hawthorn extract per litre of consumption of water. RESULTS: The results showed that weight gain and feed conversion ratio were significantly improved and abdominal fat decreased by consumption of two levels of Crateagus extract when compared to the control (p < 0.05). Consumption of hawthorn extract decreased circulatory levels of malondialdehyde, triacylglycerol, total cholesterol and low-density lipoproteins cholesterol but increased ferric reducing antioxidant power and high-density lipoproteins cholesterol (p < 0.05). Hawthorn extract caused an up-regulation of catalase, superoxide dismutase1, glutathione peroxidase1 and peroxisome proliferator-activated receptor alpha but reduced the expression of key lipogenic enzymes (p < 0.05). CONCLUSIONS: Overall, consumption of 0.4 mL hawthorn extract per litre of drinking water, improved growth performance, suppressed lipogenesis and enhanced antioxidant response.

Aqueous extract of fermented Eucommia ulmoides leaves alleviates hyperlipidemia by maintaining gut homeostasis and modulating metabolism in high-fat diet fed rats.

BACKGROUND: As a traditional Chinese medicinal herb, the lipid-lowing biological potential of Eucommia ulmoides leaves (EL) has been demonstrated. After fermentation, the EL have been made into various products with lipid-lowering effects and antioxidant activity. However, the anti-hyperlipidemic mechanism of fermented Eucommia ulmoides leaves (FEL) is unclear now. PURPOSE: To evaluate the effects of FEL on hyperlipidemia and investigate the mechanism based on regulating gut homeostasis and host metabolism. METHODS: Hyperlipidemia animal model in Wistar rats was established after 8 weeks high-fat diet (HFD) fed. The administered doses of aqueous extract of FEL (FELE) were 128, 256 and 512 mg/kg/d, respectively. Serum biochemical parameters detection, histopathological sections analysis, 16S rDNA sequencing of gut microbiota and untargeted fecal metabolomics analysis, were performed to determine the therapeutic effects and predict related pathways of FELE on hyperlipidemia. The changes of proteins and genes elated to lipid were detected by Immunofluorescence (IF) and quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: 56 Components in FELE were identified by UPLC-MS, with organic acids, flavonoids and phenolic acids accounting for the majority. The intervention of FELE significantly reduced the body weight, lipid accumulation and the levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein-cholesterol (LDL-C) in hyperlipidemia rats, while increased the level of High-density lipoprotein-cholesterol (HDL-C). Meanwhile, FELE improved the inflammatory makers and oxidative stress factors, which is tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT). These results demonstrated that FETE can effectively reduce blood lipids and alleviate inflammation and oxidative damage caused by hyperlipidemia. Mechanistically, FELE restore the homeostasis of gut microbiota by reducing the Firmicutes/Bacteroidetes ratio and increasing the abundance of probiotics, especially Lactobacillus, Rombousia, Bacteroides, Roseburia, Clostridia_UCG-014_Unclassified, while modulated metabolism through amino acid, bile acid and lipid-related metabolism pathways. In addition, the Pearson correlation analysis found that the upregulated bilirubin, threonine, dopamine and downregulated lipocholic acid, d-sphingosine were key metabolites after FELE intervention. IF and qRT-PCR analysis showed that FELE upregulated the expression of fatty acid oxidation proteins and genes (PPARα, CPT1A), bile acid synthesis and excretion proteins and genes (LXRα, CYP7A1, FXR), and downregulated the expression of adipogenic gene (SREBP-1c) by regulating gut microbiota to improve metabolism and exert a lipid-lowering effect. CONCLUSION: This work filled the lipid-lowering mechanism gap of FEL. FELE can improve HFD-induced hyperlipidemia by regulating the gut microbiota homeostasis and metabolism. Thus, FEL has the potential to develop into the novel raw material of lipid-lowering drugs.

Antihyperglycemic and antihyperlipidemic effects of fruit extract of Hodgsonia heteroclita (Roxb.) Hook. f. & Thomson in diabetic mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Hodgsonia heteroclita has been known as an important traditionally consumed medicinal plant of North-East India known to have antidiabetic properties. This study aims to investigate the effects of the ethanolic fruit extract of Hodgsonia heteroclita against hyperglycemia and hyperlipidemia by using streptozotocin (STZ) treated diabetic mice. MATERIALS AND METHODS: The fruits of H. heteroclita were collected from the various parts of Kokrajhar district, Assam India (Geographic coordinates: 26°24'3.85″ N 90°16'22.30″ E). Basic morphological evaluations were carried out by the Botanical Survey of India, Eastern circle, Shillong, who also certified and identified the plant. Hexane, chloroform, and ethanolic extracts of the fruit of H. heteroclita were investigated for α-amylase inhibition assay as a rapid screening tool for examining anti-diabetic activity. The efficacy of ethanolic extract at a dose of 100, 200, and 300 mg/kg body weight was tested for 21 days in STZ-induced diabetic mice. The body weight, fasting plasma glucose and serum lipids, and hepatic glycogen levels were measured in experimental animals to examine the antihyperglycemic and antihyperlipidemic efficacy of the extract. Both HPTLC and LC-MS analysis was performed to examine the phyotochemicals present in the ethanolic extract of H. heteroclita. RESULTS: It has been observed that treatment with the ethanolic extract dose-dependently reduced the plasma glucose levels, total cholesterol, low density lipoprotein-cholesterol, very low-density lipoprotein-cholesterol, triglyceride, and increased the body weight, liver glycogens and high-density lipoprotein-cholesterol in STZ treated diabetic mice. HPTLC demonstrated the presence of triterpene compounds and LC-MS analysis revealed the presence Cucurbitacin I, Cucurbitacin E, and Kuguacin G as the triterpene phytoconstituents. CONCLUSION: The present study demonstrated that ethanolic fruit extract of H. heteroclita improved both glycemic and lipid parameters in mice model of diabetes.

Beneficial Effects of Spirulina Supplementation in the Management of Cardiovascular Diseases.

In recent decades, as a result of rising mortality rates due to cardiovascular diseases (CVDs), there has been a growing urgency to find alternative approaches to conventional pharmaceutical treatment to prevent the onset of chronic diseases. Arthrospira platensis, commonly known as Spirulina, is a blue-green cyanobacterium, classified as a "superfood", used worldwide as a nutraceutical food supplement due to its remarkable nutritional value, lack of toxicity, and therapeutic effects. Several scientific studies have evaluated the cardioprotective role of Spirulina. This article presents a comprehensive review of the therapeutic benefits of Spirulina in improving cardio- and cerebrovascular health. It focuses on the latest experimental and clinical findings to evaluate its antihypertensive, antidiabetic, and antihyperlipidemic properties. The objective is to highlight its potential in preventing and managing risk factors associated with cardiovascular disease (CVD).

The impact of forearm immobilization and acipimox administration on muscle amino acid metabolism and insulin sensitivity in healthy, young volunteers.

Although the mechanisms underpinning short-term muscle disuse atrophy and associated insulin resistance remain to be elucidated, perturbed lipid metabolism might be involved. Our aim was to determine the impact of acipimox administration [i.e., pharmacologically lowering circulating nonesterified fatty acid (NEFA) availability] on muscle amino acid metabolism and insulin sensitivity during short-term disuse. Eighteen healthy individuals (age: 22 ± 1 years; body mass index: 24.0 ± 0.6 kg·m-2) underwent 2 days forearm immobilization with placebo (PLA; n = 9) or acipimox (ACI; 250 mg Olbetam; n = 9) ingestion four times daily. Before and after immobilization, whole body glucose disposal rate (GDR), forearm glucose uptake (FGU; i.e., muscle insulin sensitivity), and amino acid kinetics were measured under fasting and hyperinsulinemic-hyperaminoacidemic-euglycemic clamp conditions using forearm balance and l-[ring-2H5]-phenylalanine infusions. Immobilization did not affect GDR but decreased insulin-stimulated FGU in both groups, more so in ACI (from 53 ± 8 to 12 ± 5 µmol·min-1) than PLA (from 52 ± 8 to 38 ± 13 µmol·min-1; P < 0.05). In ACI only, and in contrast to our hypothesis, fasting arterialized NEFA concentrations were elevated to 1.3 ± 0.1 mmol·L-1 postimmobilization (P < 0.05), and fasting forearm NEFA balance increased approximately fourfold (P = 0.10). Forearm phenylalanine net balance decreased following immobilization (P < 0.10), driven by an increased rate of appearance [from 32 ± 5 (fasting) and 21 ± 4 (clamp) preimmobilization to 53 ± 8 and 31 ± 4 postimmobilization; P < 0.05] while the rate of disappearance was unaffected by disuse or acipimox. Disuse-induced insulin resistance is accompanied by early signs of negative net muscle amino acid balance, which is driven by accelerated muscle amino acid efflux. Acutely elevated NEFA availability worsened muscle insulin resistance without affecting amino acid kinetics, suggesting increased muscle NEFA uptake may contribute to inactivity-induced insulin resistance but does not cause anabolic resistance.NEW & NOTEWORTHY We demonstrate that 2 days of forearm cast immobilization in healthy young volunteers leads to the rapid development of insulin resistance, which is accompanied by accelerated muscle amino acid efflux in the absence of impaired muscle amino acid uptake. Acutely elevated fasting nonesterified fatty acid (NEFA) availability as a result of acipimox supplementation worsened muscle insulin resistance without affecting amino acid kinetics, suggesting increased muscle NEFA uptake may contribute to inactivity-induced insulin resistance but does not cause anabolic resistance.

A new integrated strategy for high purity pinolenic acid production from Pinus koraiensis Sieb. et Zucc seed oil and evaluation of its hypolipidemic activity in vivo.

Pinolenic acid is a polyunsaturated fatty acid present only in Pinus koraiensis Sieb. et Zucc seed oil. In order to solve the structural instability problem of polyunsaturated fatty acids, pinolenic acid of P. koraiensis seed oil was effectively isolated and purified by the integrated strategy of ethyl esterification followed by urea inclusion for the first time. Under the optimal conditions after the Box-Benhnken Design experimental, ethyl pinolenate with high purity 94.95% could be obtained, and the average content of PNAEE can still reach 86.18%. Then ethyl pinolenate was characterized by Gas chromatography-mass spectrometry, Fourier transform infrared, and Nuclear magnetic resonance spectra, results showed that ethyl pinolenate was successfully prepared. In addition, the hypolipidemic activity of ethyl pinolenate had been tested in vivo and showed that ethyl pinolenate had obvious hypolipidemic activity. The new strategy for high purity ethyl pinolenate production from P. koraiensis seed oil possesses great potential in food healthy field in the future.

Methanolic extract of S. securidaca flowers, leaves, and seeds' antihyperlipidemic effects on high fat diet-induced hyperlipidemia in Wistar rats.

Significant risk factors for atherosclerosis include hyperlipidemia and oxidative stress, which together rank as three of the most significant risk factors for cardiovascular diseases. Securigera securidaca lowers cholesterol levels in diabetic rats' blood. This investigation's objective was to determine how methanolic extracts affected the flowers, leaves, and seeds of plants in rats that were fed a high-fat diet (HFD). Five groups of animals were created (n = 5). A total of 35 days, divided into two intervals, were used for the study. Rats received HFD during the first 15-day interval, while during the second 20-day interval, they also received extracts or the Atorvastatin reference drug. The extract of seeds has a high phenol content as well as DPPH radical antioxidant activity. Extracts were given at a dose of 200 mg/kg; p.o. Methanolic treatment of S. securidaca flowers, leaves, and seeds in HFD-induced hyperlipidemic rats resulted in significant reductions in total cholesterol, triglycerides, LDLC, and VLDL-C levels. HDL-C levels increased significantly because of the leaves. While in hyperlipidemic rats, seeds significantly reduced the activities of the enzymes ALT and ALP. The findings showed that, to a certain extent, seeds, flowers, and leaves may have benefits in reducing hyperlipidemia brought on by HFD in terms of lipid profiles and liver function enzymes. The findings of this study indicate a promising application prospect, but more research is needed to determine the exact mechanism of these novel compounds as antihyperlipidemic agents and to clarify their potential combination effect with synthetic drugs such as Atorvastatin. Combinations can reduce the dose of chemical medications required, which lowers the risk of side effects.

Exploring the hypolipidemic effects of bergenin from Saxifraga melanocentra Franch: mechanistic insights and potential for hyperlipidemia treatment.

OBJECTIVE: The goal of this study was to explore the hypolipidemic effects of bergenin extracted from Saxifraga melanocentra Franch (S. melanocentra), which is a frequently utilized Tibetan medicinal plant known for its diverse bioactivities. Establishing a quality control system for black stem saxifrage is crucial to ensure the rational utilization of its medicinal resources. METHODS: A one-step polyamide medium-pressure liquid chromatography technique was applied to isolate and prepare bergenin from a methanol extract of S. melanocentra. A zebrafish model of hyperlipidemia was used to investigate the potential hypolipidemic effects of bergenin. RESULTS: The results revealed that bergenin exhibited substantial hypo efficacy in vivo. Specifically, bergenin significantly reduced the levels of triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-c) while simultaneously increasing high-density lipoprotein cholesterol (HDL-c) levels. At the molecular level, bergenin exerted its effects by inhibiting the expression of FASN, SREBF1, HMGCRα, RORα, LDLRα, IL-1ß, and TNF while promoting the expression of IL-4 at the transcriptional level. Molecular docking analysis further demonstrated the strong binding affinity of bergenin to proteins such as FASN, SREBF1, HMGCRα, RORα, LDLRα, IL-4, IL-1ß, and TNF. CONCLUSIONS: Findings indicate that bergenin modulates lipid metabolism by regulating lipid and cholesterol synthesis as well as inflammatory responses through signaling pathways associated with FASN, SREBF1, and RORα. These results position bergenin as a potential candidate for the treatment of hyperlipidemia.

Natural products in non-alcoholic fatty liver disease (NAFLD): Novel lead discovery for drug development.

With changing lifestyles, non-alcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease worldwide. A substantial increase in the incidence, mortality, and associated burden of NAFLD-related advanced liver disease is expected. Currently, the initial diagnosis of NAFLD is still based on ultrasound and there is no approved treatment method. Lipid-lowering drugs, vitamin supplementation, and lifestyle improvement treatments are commonly used in clinical practice. However, most lipid-lowering drugs can produce poor patient compliance and specific adverse effects. Therefore, the exploration of bio-diagnostic markers and active lead compounds for the development of innovative drugs is urgently needed. More and more studies have reported the anti-NAFLD effects and mechanisms of natural products (NPs), which have become an important source for new drug development to treat NAFLD due to their high activity and low side effects. At present, berberine and silymarin have been approved by the US FDA to enter clinical phase IV studies, demonstrating the potential of NPs against NAFLD. Studies have found that the regulation of lipid metabolism, insulin resistance, oxidative stress, and inflammation-related pathways may play important roles in the process. With the continuous updating of technical means and scientific theories, in-depth research on the targets and mechanisms of NPs against NAFLD can provide new possibilities to find bio-diagnostic markers and innovative drugs. As we know, FXR agonists, PPARα agonists, and dual CCR2/5 inhibitors are gradually coming on stage for the treatment of NAFLD. Whether NPs can exert anti-NAFLD effects by regulating these targets or some unknown targets remains to be further studied. Therefore, the study reviewed the potential anti-NAFLD NPs and their targets. Some works on the discovery of new targets and the docking of active lead compounds were also discussed. It is hoped that this review can provide some reference values for the development of non-invasive diagnostic markers and new drugs against NAFLD in the clinic.

Potential Effect of Baobab's Polyphenols as Antihyperlipidemic Agents: In Silico Study.

Adansonia digitata L. is an African tree commonly called baobab. This tree is effectively used in traditional medicine to treat cardiovascular disorders. Hyperlipidemia is a well-known cardiovascular risk factor associated with the increased incidence of mortality worldwide. This study aimed to demonstrate the mechanism of baobab polyphenols in the activities of hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and pancreatic lipase as lipid metabolic enzymes. Molecular docking and an incentive for drug design showed that all the polyphenols in baobab bound to the proteins with higher affinity and a lower binding energy compared with simvastatin as the positive control (ΔG: from -5.5 kcal/mol to -6.5 kcal/mol). The same polyphenols exhibited a considerable binding affinity to pancreatic lipase (ΔG: from -7.5 kcal/mol to -9.8 kcal/mol) in comparison with the control and HMG-CoA reductase. Quercetin showed the best docking score from the selected Baobab polyphenols (ΔG = -9.8 kcal/mol). The root mean square deviation (RMSD) results indicated that stable epicatechin and quercetin complexes were demonstrated with HMG-CoA reductase, and other less stable complexes were developed using rutin and chlorogenic acid. Moreover, the analysis of the root mean square fluctuation (RMSF) simulation results was consistent with that of the RMSD. The RMSF value for all the baobab polyphenols, including the crystal control ligand, was kept between 0.80 and 8.00 Å, similarly to simvastatin, and less than 4.8 Å for pancreatic lipase. Chlorogenic acid, quercetin, epicatechin, and rutin had negative ΔG binding scores from highest to lowest. The same ligands displayed more negative ΔG binding scores than those observed in HMG-CoA reductase and crystal control ligand (methoxyundecyl phosphinic acid) in their simulation with pancreatic lipase. In conclusion, baobab polyphenols interact with HMG-CoA reductase and pancreatic lipase to inhibit their substrate binding and block their activity.

Antihyperlipidemic mechanisms of a formula containing Curcuma xanthorrhiza, Sechium edule, and Syzigium polyanthum: In silico and in vitro studies.

Herbal medicines are multi-component and can exhibit synergistic effects in the treatment of diseases. Sechium edule, Syzigium polyanthum, and Curcuma xanthorrhiza have been used in traditional medicine to reduce serum lipid levels. However, the molecular mechanism was not described clearly, especially as a mixture. Thus, we performed a network pharmacology study combined with molecular docking to find a rational explanation regarding the molecular mechanisms of this antihyperlipidemic formula. According to the network pharmacology study, we predicted that this extract mixture would act as an antihyperlipidemic agent by modulating several pathways including insulin resistance, endocrine resistance, and AMP-activated protein kinase (AMPK) signaling pathway. Based on the topology parameters, we identified 6 significant targets that play an important role in reducing lipid serum levels: HMG-CoA reductase (HMGCR), peroxisome proliferator-activated receptor alpha (PPARA), RAC-alpha serine/threonine-protein kinase (AKT1), epidermal growth factor receptor (EGFR), matrix metalloproteinase-9 (MMP9), and tumor necrosis factor-alpha (TNF). Meanwhile, 8 compounds: ß-sitosterol, bisdesmethoxycurcumin, cucurbitacin D, cucurbitacin E, myricetin, phloretin, quercitrin, and rutin were the compounds with a high degree, indicating that these compounds have a multitarget effect. Our consensus docking study revealed that HMGCR was the only protein targeted by all potential compounds, and rutin was the compound with the best consensus docking score for almost all targets. The in vitro study revealed that the extract combination could inhibit HMGCR with an IC50 value of 74.26 µg/mL, indicating that HMGCR inhibition is one of its antihyperlipidemic mechanisms.

Evaluation of Antidiabetic Effect of Combined Leaf and Seed Extracts of Moringa oleifera (Moringaceae) on Alloxan-Induced Diabetes in Mice: A Biochemical and Histological Study.

Moringa oleifera (Moringaceae) is a medicinal plant rich in biologically active compounds. The aim of the present study was to screen M. oleifera methanolic leaf (L) extract, seed (S) extract, and a combined leaf/seed extract (2L : 1S ratio) for antidiabetic and antioxidant activities in mice following administration at a dose level of 500 mg/kg of body weight/day. Diabetes was induced by alloxan administration. Mice were treated with the extracts for 1 and 3 months and compared with the appropriate control. At the end of the study period, the mice were euthanized and pancreas, liver, kidney, and blood samples were collected for the analysis of biochemical parameters and histopathology. The oral administration of the combined L/S extract significantly reduced fasting blood glucose to normal levels compared with L or S extracts individually; moreover, a significant decrease in cholesterol, triglycerides, creatinine, liver enzymes, and oxidant markers was observed, with a concomitant increase in antioxidant biomarkers. Thus, the combined extract has stronger antihyperlipidemic and antioxidant properties than the individual extracts. The histopathological results also support the biochemical parameters, showing recovery of the pancreas, liver, and kidney tissue. The effects of the combined L/S extracts persisted throughout the study period tested. To the best of our knowledge, this is the first study to report on the antidiabetic, antioxidant, and antihyperlipidemic effects of a combined L/S extract of M. oleifera in an alloxan-induced diabetic model in mice. Our results suggest the potential for developing a natural potent antidiabetic drug from M. oleifera; however, clinical studies are required.

Adjunctive therapy with lipid-lowering agents in COVID-19: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Many commonly used drugs were evaluated as repurposed treatment options since the emergence of the COVID-19 pandemic. The benefit of lipid-lowering agents has been controversial in this regard. In this systematic review, we assessed the effect of these medications as adjunctive therapy in COVID-19 by the inclusion of randomized controlled trials (RCTs). METHODS: We searched four international databases including PubMed, the Web of Science, Scopus, and Embase for RCTs in April 2023. The primary outcome was mortality, while other efficacy indices were considered secondary outcomes. In order to estimate the pooled effect size of the outcomes, considering the odds ratio (OR) or standardized mean difference (SMD) and 95% confidence interval (CI), random-effect meta-analyses was conducted. RESULTS: Ten studies involving 2,167 COVID-19 patients using statins, omega-3 fatty acids, fenofibrate, PCSK9 inhibitors, and nicotinamide as intervention compared to control or placebo, were included. No significant difference was found in terms of mortality (OR 0.96, 95% CI 0.58 to 1.59, p-value = 0.86, I2 = 20.4%) or length of hospital stay (SMD -0.10, 95% CI -0.78 to 0.59, p-value = 0.78, I2 = 92.4%) by adding a statin to the standard of care. The trend was similar for fenofibrate and nicotinamide. PCSK9 inhibition, however, led to decreased mortality and an overall better prognosis. Omega-3 supplementation showed contradicting results in two trials, suggesting the need for further evaluation. CONCLUSION: Although some observational studies found improved outcomes in patients using lipid-lowering agents, our study found no benefit in adding statins, fenofibrate, or nicotinamide to COVID-19 treatment. On the other hand, PCSK9 inhibitors can be a good candidate for further assessment. Finally, there are major limitations in the use of omega-3 supplements in treating COVID-19 and more trials are warranted to evaluate this efficacy.

Physicochemical characterization, rheological properties, and hypolipidemic and antioxidant activities of compound polysaccharides in Chinese herbal medicines by fractional precipitation.

This study aimed to investigate the effects of different compound polysaccharides (CPs) extracted from Folium nelumbinis, Fructus crataegi, Fagopyrum tataricum, Lycium barbarum, Semen cassiae, and Poria cocos (w/w, 2:4:2:1:1.5:1) by gradient ethanol precipitation on the physicochemical properties and biological activities. Three CPs (CP50, CP70, and CP80) were obtained and comprised rhamnose, arabinose, xylose, mannose, glucose, and galactose in different proportions. The CPs contained different amounts of total sugar, uronic acid, and proteins. These also exhibited different physical properties, including particle size, molecular weight, microstructure, and apparent viscosity. Scavenging abilities of 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS), 1,1'-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl, and superoxide radicals of CP80 were more potent compared to those of the other two CPs. Furthermore, CP80 significantly increased serum levels of high-density lipoprotein cholesterol (HDL-C) and lipoprotein lipase (LPL), and hepatic lipase (HL) activity in the liver, while decreasing the serum levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C), along with LPS activity. Therefore, CP80 may serve as a natural novel lipid regulator in the field of medicinal and functional food.

Determination of Hypoglycemic, Hypolipidemic and Nephroprotective Effects of Berberis Calliobotrys in Alloxan-Induced Diabetic Rats.

Many plants of the Berberis genus have been reported pharmacologically to possess anti-diabetic potential, and Berberis calliobotrys has been found to be an inhibitor of α-glucosidase, α-amylase and tyrosinase. Thus, this study investigated the hypoglycemic effects of Berberis calliobotrys methanol extract/fractions using in vitro and In vivo methods. Bovine serum albumin (BSA), BSA-methylglyoxal and BSA-glucose methods were used to assess anti-glycation activity in vitro, while in vivo hypoglycemic effects were determined by oral glucose tolerance test (OGTT). Moreover, the hypolipidemic and nephroprotective effects were studied and phenolics were detected using high performance liquid chromatography (HPLC). In vitro anti-glycation showed a significant reduction in glycated end-products formation at 1, 0.25 and 0.5 mg/mL. In vivo hypoglycemic effects were tested at 200, 400 and 600 mg/kg by measuring blood glucose, insulin, hemoglobin (Hb) and HbA1c. The synergistic effect of extract/fractions (600 mg/kg) with insulin exhibited a pronounced glucose reduction in alloxan diabetic rats. The oral glucose tolerance test (OGTT) demonstrated a decline in glucose concentration. Moreover, extract/fractions (600 mg/kg) exhibited an improved lipid profile, increased Hb, HbA1c levels and body weight for 30 days. Furthermore, diabetic animals significantly exhibited an upsurge in total protein, albumin and globulin levels, along with a significant improvement in urea and creatinine after extract/fractions administration for 42 days. Phytochemistry revealed alkaloids, tannins, glycosides, flavonoids, phenols, terpenoids and saponins. HPLC showed the presence of phenolics in ethyl acetate fraction that could be accountable for pharmacological actions. Therefore, it can be concluded that Berberis calliobotrys possesses strong hypoglycemic, hypolipidemic and nephroprotective effects, and could be a potential therapeutic agent for diabetes treatment.

[Proposal for a diagnostic and therapeutic care pathway of the Piedmont Region on lipid-lowering and antithrombotic treatment in patients with peripheral arterial disease]. / Proposta di percorso diagnostico-terapeutico assistenziale della Regione Piemonte sulla terapia ipolipemizzante ed antitrombotica in pazienti con malattia delle arterie periferiche.

The aim of this paper is to present the diagnostic and therapeutic care pathway on peripheral arterial disease, recently developed in the Piedmont Region, Italy. It proposes a combined approach between the cardiologist and vascular surgeon for optimizing the treatment of patients with peripheral artery disease, which includes the most recently approved antithrombotic and lipid-lowering drugs. The goal is to promote a greater awareness on peripheral vascular disease, in order to implement its treatment patterns and consequently to perform an effective secondary cardiovascular prevention.

Antidiabetic, antihyperlipidemic and protective effects of Gladiolus psittacinus on hyperglycemia-mediated oxidative stress in streptozotocin-induced diabetic rats.

OBJECTIVES: Gladiolus psittacinus (GP) is an important medicinal plant in folk medicine where its corm is used for treatment of diabetes mellitus. Despite this, there is paucity of scientific information to justify its use as antidiabetic drug. Hence, this study was designed to explore antidiabetic, antihyperlipidemic and effects of aqueous extract of Gladiolus psittacinus (AGP) on hyperglycemia-associated oxidative stress in pancreas, kidney and liver of diabetic rats. METHODS: Diabetes mellitus (DM) was induced in rats using streptozotocin 50 mg/kg (i.p.). Normal and diabetic rats were treated orally with AGP once a day for 14 days. Antidiabetic effects were evaluated on body weight, fasting blood glucose concentration (FBGC), lipid profiles and serum chemistry. Also, protective effects of AGP were also determined on markers of oxidative stress, antioxidant enzymes and histopathology of pancreas, kidney and liver of diabetic rats. RESULTS: Treatment with AGP emanated to significant decrease of FBGC (552.67-157.33 mg/dL), increase in body weight (100.01-133.76 g) and positive modulation of lipid parameters in diabetic rats. The alteration in the contents of markers of liver and kidney function were significantly modulated in the diabetic rats upon treatment. Also, oxidative damage and antioxidant depletions in pancreas, kidney and liver were significantly mitigated in treated diabetic rats. Structural aberrations in the histopathology slides of pancreas, kidney and liver were improved upon treatment. CONCLUSIONS: It can be concluded that AGP could be used in the treatment of diabetes mellitus and its related ailments, thereby justifying its usage in traditional medicine.