In vivo toxicity, anti-hyperlipidaemic, antioxidant and anti-atherogenic activities of 'LIPO A' A traditional herbal product in rodents.

Hyperlipidemia accounts for about 17 million deaths worldwide each year. High cost and side effects have limited the use of conventional anti-lipidaemic agents in some cases, majority of whom resort to traditional medicine. The current research focused on validating the safety and efficacy of a herbal product, 'LIPO A' used in the management of hyperlipidaemia. Induction of hyperlipidaemia was achieved by oral administration of 3 mL of cholesterol in coconut oil for 4 weeks in male Sprague Dawley rats with water available as 40 % sucrose. Subsequently, the animals were treated with 100, 200 and 400 mg/kg of the product 'LIPO A' for 4 additional weeks with atorvastatin as reference drug (at 2 mg/kg body weight). Blood samples were taken for serum biochemistry and atherogenic ratios were then calculated. 2,2-Diphenyl-1-Picrylhydrazyl (DPPH) scavenging assay, total antioxidant capacity, physicochemical and phytochemical analysis were also carried out using standard methods. Treatment resulted in a dose-dependent reduction in total cholesterol with maximum reduction of 46.01 % at 400 mg/kg compared to atorvastatin with 49.30 %. There were significant changes in the low-density lipoprotein cholesterol and high-density lipoprotein cholesterol (LDL-c/HDL-c) and Total Cholesterol (TC/HDL-c) ratios which measures the atherogenic and coronary risk indices respectively. Acute and subacute toxicity studies did not reveal any signs of toxicity. High Performance Liquid Chromatography (HPLC) fingerprint revealed six well resolved peaks with two prominent compounds with retention times 24.88 and 23.95 min, which could serve as quality control markers for the product. The herbal product showed considerable antihyperlipidemic and antioxidant actions in rodent models and lend credence to its use in traditional medicine for hyperlipidaemia.

In vitro study of Nigella sativa and thymoquinone activity on endothelial activation and monocyte adhesion.

INTRODUCTION: Thymoquinone (TQ) is one of the bioactive compounds in Nigella sativa (NS). Also known as black seeds/cumin, it has been postulated to possess anti-atherogenic properties. However, research on the effects of NS oil (NSO) and TQ on atherogenesis remain scarce. The aim of this study is to determine gene and protein expression of Intercellular Adhesion Molecule-1 (ICAM-1), Vascular Cell Adhesion Molecule-1 (VCAM-1), and Endothelial-eukocyte adhesion molecule (E-selectin) in Human Coronary Artery Endothelial Cells (HCAECs). METHODS: HCAECs were stimulated for 24 hours (h) with 200 µg/ml of Lipopolysaccharides (LPS) and different concentrations of NSO (55, 110, 220, 440 µg/ml) or TQ (4.5, 9.0, 18.0, 36.0 µm). The effects of NSO and TQ on gene and protein expressions were measured using multiplex gene assay and ELISA assay, respectively. Rose Bengal assay was used to analyse monocyte binding activity. RESULTS: NSO and TQ significantly reduced ICAM-1 and VCAM-1 gene and protein expressions. TQ showed significant reduction activity of the biomarkers in dose dependent manner. HCAECs pre-treated with NSO and TQ for 24 h significantly lowered monocytes adherence compared to non-treated HCAECs. CONCLUSIONS: NSO and TQ supplementation have anti-atherogenic properties and inhibit monocytes' adherence to HCAECs via down-regulation of ICAM-1 expression. NSO could potentially be incorporated in standard treatment regimens to prevent atherosclerosis and its related complications.

Endothelial mechanobiology in atherosclerosis.

Cardiovascular disease (CVD) is a serious health challenge, causing more deaths worldwide than cancer. The vascular endothelium, which forms the inner lining of blood vessels, plays a central role in maintaining vascular integrity and homeostasis and is in direct contact with the blood flow. Research over the past century has shown that mechanical perturbations of the vascular wall contribute to the formation and progression of atherosclerosis. While the straight part of the artery is exposed to sustained laminar flow and physiological high shear stress, flow near branch points or in curved vessels can exhibit 'disturbed' flow. Clinical studies as well as carefully controlled in vitro analyses have confirmed that these regions of disturbed flow, which can include low shear stress, recirculation, oscillation, or lateral flow, are preferential sites of atherosclerotic lesion formation. Because of their critical role in blood flow homeostasis, vascular endothelial cells (ECs) have mechanosensory mechanisms that allow them to react rapidly to changes in mechanical forces, and to execute context-specific adaptive responses to modulate EC functions. This review summarizes the current understanding of endothelial mechanobiology, which can guide the identification of new therapeutic targets to slow or reverse the progression of atherosclerosis.

Anti-Atherogenic Protection by Oligomeric Proanthocyanidins via Regulating Collagen Crosslinking Against CC Diet-Induced Atherosclerosis in Rats.

The synthesis of collagen and its turnover remained as critical determinants for the progression of atherosclerosis. During this condition, proteases secreted by SMCs and foam cells in the necrotic core degrade collagen. Growing evidences demonstrated that consumption of antioxidant rich diet is highly associated with a reduced risk of atherosclerosis. Oligomeric proanthocyanidins (OPC) have been proved to possess promising antioxidant, anti-inflammatory and cardioprotective activity, based on our previous studies. The present study aims to investigate the efficacy of OPC isolated from Crataegus oxyacantha berries as a natural collagen crosslinker and anti-atherogenic agent. Spectral studies like FTIR, ultraviolet and circular dichroism analysis confirmed the in vitro crosslinking ability of OPC with rat tail collagen when compared to the standard epigallocatechin gallate. The administration of cholesterol:cholic acid (CC) diet induces proteases-mediated collagen degradation that could result in plaque instability. Further, the CC diet fed rats showed significantly increased levels of total cholesterol and triacylglycerols which, in turn, increases the activities of collagen degrading proteases-MMPs (MMP 1, 2 and 9) and Cathepsin S and D. Upon OPC treatment, marked reduction in the lipid content, activation of proteases with concomitant increase in the mRNA levels of collagen Type I and Type III as similar to atorvastatin treatment were observed .Thus, OPC supplementation may contribute to the prevention of atherosclerotic plaque instability by acting as a natural crosslinker of collagen.

Natural Monoterpenes as Potential Therapeutic Agents against Atherosclerosis.

Traditional herbal medicines based on natural products play a pivotal role in preventing and managing atherosclerotic diseases, which are among the leading causes of death globally. Monoterpenes are a large class of naturally occurring compounds commonly found in many aromatic and medicinal plants. Emerging evidence has shown that monoterpenes have many biological properties, including cardioprotective effects. Remarkably, an increasing number of studies have demonstrated the therapeutic potential of natural monoterpenes to protect against the pathogenesis of atherosclerosis. These findings shed light on developing novel effective antiatherogenic drugs from these compounds. Herein, we provide an overview of natural monoterpenes' effects on atherogenesis and the underlying mechanisms. Monoterpenes have pleiotropic and multitargeted pharmacological properties by interacting with various cell types and intracellular molecular pathways involved in atherogenesis. These properties confer remarkable advantages in managing atherosclerosis, which has been recognized as a multifaceted vascular disease. We also discuss limitations in the potential clinical application of monoterpenes as therapeutic agents against atherosclerosis. We propose perspectives to give new insights into future preclinical research and clinical practice regarding natural monoterpenes.

Interleukin-35 Mitigates ox-LDL-Induced Proatherogenic Effects via Modulating miRNAs Associated with Coronary Artery Disease (CAD).

PURPOSE: Recent emergence of miRNAs as important regulators of processes involving lesion formation and regression has highlighted miRNAs as potent therapeutic targets for the treatment of atherosclerosis. Few studies have reported the atheroprotective role of IL-35, a novel immunosuppressive and anti-inflammatory cytokine; however, miRNA-dependent regulation underlying the anti-atherosclerotic potential of IL-35 remains elusive. METHODS: THP-1 macrophages were incubated with human recombinant IL-35 (rIL-35) either in the presence or absence of ox-LDL. qRT-PCR was conducted to validate the expression levels of previously identified miRNAs including miR-197-5p, miR-4442, miR-324-3p, miR-6879-5p, and miR-6069 that were differentially expressed in peripheral blood mononuclear cells of coronary artery disease (CAD) patients vs. controls. Additionally, bioinformatic analysis was performed to predict miRNA-associated targets and their corresponding functional significance in CAD. RESULTS: Exogenous IL-35 significantly decreased the average area of ox-LDL-stimulated macrophages, indicating the inhibitory effect of IL-35 on lipid-laden foam cell formation. Furthermore, rIL-35 treatment alleviated the ox-LDL-mediated atherogenic effects by modulating the expression levels of aforementioned CAD-associated miRNAs in the cultured macrophages. Moreover, functional enrichment analysis of these miRNA-related targets revealed their role in the molecular processes affecting different stages of atheroslerotic plaque development, such as macrophage polarization, T cell suppression, lipoprotein metabolism, foam cell formation, and iNOS-mediated inflammation. CONCLUSION: Our observations uncover the novel role of IL-35 as an epigenetic modifier as it influences the expression level of miRNAs implicated in the pathogenesis of atherosclerosis. Thus, IL-35 cytokine therapy-mediated miRNA targeting could be an effective therapeutic strategy against the development of early atheromas in asymptomatic high-risk CAD patients.

Corrigendum: Effective management of atherosclerosis progress and hyperlipidemia with nattokinase: A clinical study with 1,062 participants.

[This corrects the article DOI: 10.3389/fcvm.2022.964977.].

Sesquiterpenoids from the Florets of Carthamus tinctorius (Safflower) and Their Anti-Atherosclerotic Activity.

(1) Background: The florets of Carthamus tinctorius L. are traditionally used as a blood-activating drug and can be used for the treatment of atherosclerosis, but no compounds with anti-atherosclerotic activity have been reported. (2) Methods: This study investigated the chemical compounds from the florets of C. tinctorius. Comprehensive spectroscopic techniques revealed their structures, and ECD calculations established their absolute configurations. Nile Red staining, Oil Red O staining, and cholesterol assessment were performed on these compounds and their aglycones for the inhibitory activity against the formation of foam cells induced by oxidized low-density lipoprotein (ox-LDL) in RAW264.7 macrophages. In addition, RAW264.7 macrophages were tested for their anti-inflammatory activity by measuring the inhibition of NO production caused by LPS. (3) Results: Five new sesquiterpenoids (1-5) isolated from the florets of C. tinctorius were identified as (-)-(1R,4S,9S,11R)-caryophyll-8(13)-en-14-ol-5-one (1), (+)-(1R,4R,9S,11R)-caryophyll-8(13)-en-14-ol-5-one (2), (-)-(3Z,1R,5S,8S,9S,11R)-5,8-epoxycaryophyll-3-en-14-O-ß-D-glucopyranoside (3), (+)-(1S,7R,10S)-guai-4-en-3-one-11-O-ß-D-fucopyranoside (4), and (-)-(2R,5R,10R)-vetispir-6-en-8-one-11-O-ß-D-fucopyranoside (5). All compounds except for compound 3 reduced the lipid content in ox-LDL-treated RAW264.7 cells. Compounds 3 and 4 and their aglycones were found to reduce the level of total cholesterol (TC) and free cholesterol (FC) in ox-LDL-treated RAW264.7 cells. However, no compounds showed anti-inflammatory activity. (4) Conclusion: Sesquiterpenoids from C. tinctorius help to decrease the content of lipids, TC and FC in RAW264.7 cells, but they cannot inhibit NO production, which implies that their anti-atherogenic effects do not involve the inhibition of inflammation.

Peptide-Based HDL as an Effective Delivery System for Lipophilic Drugs to Restrain Atherosclerosis Development.

Purpose: Peptide-based high-density lipoprotein (pHDL) structurally and functionally resembles the natural HDL as anti-atherosclerosis (AS) therapies. Since pHDL contains a large hydrophobic core, this study aims to evaluate the potentials of pHDL as a hydrophobic drug carrier and the efficiency of drug-loaded pHDL in the control of AS. Methods: The pHDL encapsulation of hydrophobic components from natural plants, including curcumin (Cur) and tanshinone IIA (TanIIA), was achieved using one-step microfluidics. Then, morphological features and loading efficiencies of pHDL-Cur and pHDL-TanIIA were determined by TEM and high-performance liquid chromatography (HPLC), respectively. Taking the fluorescence advantage of Cur, localizations of loaded Cur in pHDL were investigated by fluorescence quenchers, and recruitments of Cur to AS plaques were assessed with ex vivo imaging. Based on anti-inflammatory properties of TanIIA, pHDL-TanIIA was accordingly developed to evaluate the anti-AS effects through examinations of plasma lipid parameters and pathological alterations of plaque-associated regions. Results: Both lipophilic Cur and TanIIA can be efficiently loaded into pHDL carriers. The resultant pHDL-Cur and pHDL-TanIIA inherit the homogeneous nano-disk structure of pHDL. By using pHDL-Cur, the encapsulated hydrophobics are tracked in the core of pHDL, and incorporations of Cur with pHDL vehicles greatly improve the bioavailability and association of Cur with AS plaques. Moreover, when loaded with TanIIA, which has established its role in anti-AS as an anti-inflammatory candidate, synergistic effects in reducing AS lesions and improving pathological alterations of main organs related to AS were achieved. Conclusion: The pHDL system could potentially be applied for both imaging and therapy in animal models of AS. Benefits of pHDL-based drug delivery will potentially extend the application scenarios of bioactive chemicals from natural plants which are underutilized due to features like low bioavailability and facilitate the clinical translation of synthetic HDL therapies in HDL-associated disorders, including but not limited to AS.

Effective management of atherosclerosis progress and hyperlipidemia with nattokinase: A clinical study with 1,062 participants.

Nattokinase (NK), known as a potent fibrinolytic and antithrombotic agent, has been shown to have antiatherosclerotic and lipid-lowering effects. However, data on human clinical studies are limited. In this clinical study involving 1,062 participants, our objective was to examine the efficacy of NK in atherosclerosis and hyperlipidemia and safety at the dose of 10,800 FU/day after 12 months of oral administration. Various factors, including lower doses that influence NK pharmacological actions, were also investigated. We found that NK at a dose of 10,800 FU/day effectively managed the progression of atherosclerosis and hyperlipidemia with a significant improvement in the lipid profile. A significant reduction in the thickness of the carotid artery intima-media and the size of the carotid plaque was observed. The improvement rates ranged from 66.5 to 95.4%. NK was found to be ineffective in lowering lipids and suppressing atherosclerosis progression at a dose of 3,600 FU/day. The lipid-lowering effect of NK was more prominent in subjects who smoked, drank alcohol, and subjects with higher BMI. Regular exercise further improved the effects of NK. Co-administration of vitamin K2 and aspirin with NK produced a synergetic effect. No noticeable adverse effects associated with the use of NK were recorded. In conclusion, our data demonstrate that atherosclerosis progression and hyperlipidemia can be effectively managed with NK at a dose of 10,800 FU/day. The lower dose of 3,600 FU per day is ineffective. The dose of 10,800 FU/day is safe and well tolerated. Some lifestyle factors and the coadministration of vitamin K2 and aspirin lead to improved outcomes in the use of NK. Our findings provide clinical evidence on the effective dose of NK in the management of cardiovascular disease and challenge the recommended dose of 2,000 FU per day.

Biological Importance and Therapeutic Benefit of Rhamnocitrin: A Review of Pharmacology and Analytical Aspects.

BACKGROUND: Humans have a long history of the uses of plant based products, including extracts and pure phytoconstituents for the treatment of human diseases in the different system of medicine. In the developing countries, phytoproducts play an important role in the healthcare systems due to their medicinal importance and pharmacological activities. Flavonoids class phytochemicals are beneficial for human beings because of their free radical scavenging properties and trace metals chelating potential. Flavonoids have inhibitory potential for the growth of bacteria and virus mainly through enzyme inhibition functions and viral translation. Rhamnocitrin is also called 7- methyl-kaempferol is important flavonoids, which has been isolated from different medicinal plants and has pharmacological activities in the medicine. METHODS: Present paper describes the biological potential and health beneficial aspects of rhamnocitrin in the medicine through the data analysis of published papers in the recent years in the field of medicine and modern medical sciences. Scientific data on rhamnocitrin have been collected from electronic databases such as PubMed, Google Scholar, Google, Scopus and Science Direct in the present investigation and analyzed to know the biological importance and pharmacological activities of rhamnocitrin. Pharmacological scientific data of rhamnocitrin have been collected and analyzed in the present work with their analytical aspects. RESULTS: Literature data analysis of different scientific work on rhamnocitrin revealed the biological importance of rhamnocitrin in medicine. Rhamnocitrin is known to be a promising phytoconstituents found to be present in medicinal plants with a wide range of biological activities. Rhamnocitrin was found to have pharmacological activities, including anti-atherogenic, anti-oxidant, anti-cancer, anti-bacterial, anti-inflammatory, enzymatic and neuroprotective potential. Further biological effect of rhamnocitrin on adipocyte differentiation has been also studied in the present work. Analytical data on rhamnocitrin signified the application of different analytical techniques for the separation, isolation and identification of rhamnocitrin in medicine. CONCLUSION: Literature data analysis of different scientific research works revealed the biological importance and therapeutic benefit of rhamnocitrin in medicine.

Antioxidant and Anti-Atherogenic Activities of Essential Oils from Myrtus communis L. and Laurus nobilis L. in Rat.

Essential oils (EOs) from aromatic and medicinal plants, such as myrtle (Myrtus communis L.) and Laurel (Laurus nobilis L.), are gaining popularity as a potential ingredient in functional foods and nutraceuticals. This study aims to investigate whether the essential oils (EOs) could be effective in weight control, antioxidative and antilipidemic status of rats by affecting microbiota and its enzymes activity and whether changes in intestinal enzyme activity affect the health of rats. The intragastric application of laurel and myrtle EOs to rats for two weeks affects weight loss, reduces glycolytic activity, lipid parameters (cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C) and very low-density lipoprotein cholesterol (VLDL-C)) and atherogenic indicators, leading to cardiovascular protection. Laurel EO can be an excellent candidate for the treatment of drug-induced obesity and related diseases, since it affects lipid metabolism in the liver and inhibits the enzymes responsible for the metabolism of carbohydrates into glucose in the digestive tract, leading to weight loss. In contrast, myrtle EO shows a better antioxidant capacity in most tissues, except kidneys, where it causes a pro-oxidative effect, compared to laurel EO. Myrtle EO increases the permeability and instability of the erythrocyte membrane, resulting in a loss of selectivity for the entry of toxic substances into the cell. On the other hand, myrtle EO leads to intestinal inflammation by reducing the number of probiotic bacteria and increasing Enterobacter.

Antidyslipidemic Capacity of Cleome arabica (L.) in Streptozotocin-Induced Diabetic Rats.

AIMS: The aim of the study was to assess the effect of Cleome arabica on lipid metabolism. BACKGROUND: Cleome arabica (L.) is a medicinal plant used traditionally by the population of North Africa for managing diabetes mellitus. OBJECTIVE: This study was designed to evaluate the antidyslipidemic and antiatherogenic capacities of Cleome arabica (L.) in normal and streptozotocin(STZ)-induced diabetic rats. METHODS: The hypolipidemic, antihyperglycemic and antiatherogenic effects of oral administration of the aqueous extract of Cleome arabica (CAAE) (100 mg/kg) were evaluated in normal and diabetic rats. In addition, the quantification of polyphenols, flavonoids and tannins as well as the antioxidant activity were performed. RESULTS: The results showed that the extract (CAAE) revealed an antidyslipidemic action by attenuating plasma levels of Total Cholesterol (TC), Triglycerides (TGs), Low-Density Lipoprotein cholesterol (LDL-c), Very low-density lipoprotein cholesterol (VLDL-c) and glucose. Additionally, CAAE exhibited a potent antiatherogenic activity by reducing Atherogenic Coefficient (AC), Castelli's Risk index-I (cri-I), and Castelli's Risk Index-II (CRI-II). Furthermore, the findings indicated that CAAE is abundant with polyphenols, flavonoids and tannins, and exhibited an important antioxidant capacity. CONCLUSION: The study demonstrates that aqueous Cleome arabica extract was able to ameliorate lipid abnormalities associated with diabetes mellitus. This pharmacological activity might be due to the antioxidant capacities of phytochemical compounds.

Kansuinine A Ameliorates Atherosclerosis and Human Aortic Endothelial Cell Apoptosis by Inhibiting Reactive Oxygen Species Production and Suppressing IKKß/IκBα/NF-κB Signaling.

Reactive oxygen species (ROS)-induced vascular endothelial cell apoptosis is strongly associated with atherosclerosis progression. Herein, we aimed to examine whether Kansuinine A (KA), extracted from Euphorbia kansui L., prevents atherosclerosis development in a mouse model and inhibits cell apoptosis through oxidative stress reduction. Atherosclerosis development was analyzed in apolipoprotein E-deficient (ApoE-/-) mice fed a high-fat diet (HFD) using Oil Red O staining and H&E staining. Human aortic endothelial cells (HAECs) were treated with KA, followed by hydrogen peroxide (H2O2), to investigate the KA-mediated inhibition of ROS-induced oxidative stress and cell apoptosis. Oil Red O staining and H&E staining showed that atherosclerotic lesion size was significantly smaller in the aortic arch of ApoE-/- mice in the HFD+KA group than that in the aortic arch of those in the HFD group. Further, KA (0.1-1.0 µM) blocked the H2O2-induced death of HAECs and ROS generation. The H2O2-mediated upregulation of phosphorylated IKKß, phosphorylated IκBα, and phosphorylated NF-κB was suppressed by KA. KA also reduced the Bax/Bcl-2 ratio and cleaved caspase-3 expression, preventing H2O2-induced vascular endothelial cell apoptosis. Our results indicate that KA may protect against ROS-induced endothelial cell apoptosis and has considerable clinical potential in the prevention of atherosclerosis and cardiovascular diseases.

Progress in the Medicinal Value, Bioactive Compounds, and Pharmacological Activities of Gynostemma pentaphyllum.

Gynostemma pentaphyllum (Thunb.) Makino (GP), also named Jiaogulan in Chinese, was known to people for its function in both health care and disease treatment. Initially and traditionally, GP was a kind of tea consumed by people for its pleasant taste and weight loss efficacy. With the passing of the centuries, GP became well known as more than just a tea. Until now, numbers of bioactive compounds, including saponins (also named gypenosides, GPS), polysaccharides (GPP), flavonoids, and phytosterols were isolated and identified in GP, which implied the great medicinal worth of this unusual tea. Both in vivo and in vitro tests, ranging from different cell lines to animals, indicated that GP possessed various biological activities including anti-cancer, anti-atherogenic, anti-dementia, and anti-Parkinson's diseases, and it also had lipid-regulating effects as well as neuroprotection, hepatoprotective, and hypoglycemic properties. With the further development and utilization of GP, the research on the chemical constituents and pharmacological properties of GP were deepening day by day and had made great progress. In this review, the recent research progress in the bioactive compounds, especially gypenosides, and the pharmacological activities of GP were summarized, which will be quite useful for practical applications of GP in the treatment of human diseases.

Phenolic Compounds in Whole Grain Sorghum and Their Health Benefits.

Sorghum grain (Sorghum bicolor L. Moench) is a staple food grown across the globe, and is mainly cultivated in the semi-arid regions of Africa and Asia. Recently, sorghum grain is increasingly utilized for human consumption, due to the gluten-free nature and potential phenolic-induced health benefits. Sorghum grain is rich in bioactive phenolic compounds, such as ferulic acid, gallic acid, vanillic acid, luteolin, and apigenin, 3-deoxyanthocyanidins (3-DXA), which are known to provide many health benefits, including antioxidant, anti-inflammatory, anti-proliferative, anti-diabetic, and anti-atherogenic activities. Given an increasing trend of sorghum consumption for humans, this article reviews the content and profile of phenolics in sorghum. It covers aspects of their health benefits and explores their mechanisms of action. The impact of thermal processing, such as boiling, steaming, roasting, and extrusion on sorghum phenolics is also discussed. Compelling data suggest the biological functions of sorghum phenolics, however, further investigations appear warrant to clarify the gap in the current research, and identify promising research topics in future.

Effects of Gentiana lutea Root on Vascular Diseases.

BACKGROUND: Gentiana lutea (GL), commonly known as yellow gentian, bitter root, and bitterwort, belongs to family Gentianaceae. GL belongs to genus Gentiana, which is a rich natural source of iridoids, secoiridoids, xantones, flavonoids, triterpenoids, and carbohydrates. Medicinal plants from Gentiana species have anti-oxidant, anti-inflammatory, anti-mitogenic, anti-proliferative, and lipidlowering effects, as well as a cardioprotective, hypotensive, vasodilator and anti-platelet activities. OBJECTIVE: We reviewed the recent literature related to the effects of Gentiana species, and their active components on vascular diseases. METHODS: Data used for this review were obtained by searching the electronic database [PUBMED/ MEDLINE 1973 - February 2020]. The primary data search terms of interest were: Gentiana lutea, Gentienacea family, phytochemistry, vascular diseases, treatment of vascular diseases, antioxidant, anti-inflammatory, anti-atherogenic. CONCLUSION: Gentiana species and their constituents affect many different factors related to vascular disease development and progression. Therefore, Gentiana-based therapeutics represent potentially useful drugs for the management of vascular diseases.

The effects of Rosmarinus officinalis L. essential oil and its nanoemulsion on dyslipidemic Wistar rats.

Dyslipidemias are lipid metabolism alterations that cause increased levels of serum lipoprotein, cholesterol, and triglycerides. These alterations are associated with a higher incidence of cardiovascular diseases and are a risk factor for atherosclerosis development. This study aimed to evaluate the effect of Rosmarinus officinalis essential oil (EORO, 100 mg/kg) and its nanoemulsion (NEORO, 500 µg/kg) on Triton and coconut saturated-fat-induced (CSF) dyslipidemias using Wistar rats. The phytochemical evaluation of EORO performed by gas chromatography-mass spectroscopy (GC-MS) revealed 1,8-cineole (33.70%), camphor (27.68%), limonene (21.99%), and α-pinene (8.13%) as its major compounds. Triton-induced dyslipidemia significantly increased total cholesterol, LDL, and triglycerides levels. On the other hand, the groups treated with EORO and NEORO had significantly reduced total cholesterol, LDL, and triglycerides compared to the group treated only with Triton. Similar results were observed on the positive control treated with simvastatin. Dyslipidemia induced with coconut saturated-fat (CSF) caused abdominal fat gain, hypercholesterolemia, hypertriglyceridemia, increased LDL levels, and atherogenesis in the aorta. In contrast, the groups treated with EORO, NEORO, and simvastatin had significantly reduced hypercholesterolemia and hypertriglyceridemia, reduced abdominal fat gain, and absence of atherogenesis in the vascular endothelium. Overall, in the Triton-induced dyslipidemia model, EORO treatment had superior values than NEORO's (and simvastatin), although the differences were not too high, while in the CSF model, the values were mixed. In this manner, our results show an anti-dyslipidemic and anti-atherogenic activity effect by EORO and NEORO.

Diabetes-induced Alterations in HDL Subfractions Distribution.

INTRODUCTION: Diabetes mellitus (DM) due to its increasing prevalence and associated morbidity and mortality has become a serious public health problem. In DM, HDL may lose its beneficial features and become proatherogenic due to its altered biological activity thus increasing cardiovascular risk. The aim of this study was to assess the influence of the presence of diabetes mellitus type 2 and its duration on the distribution of HDL subfractions. Moreover, the effect of statin treatment on HDL subfraction share was analysed in this study. METHODS: The study group consisted of 50 patients with newly diagnosed DM and 50 persons with DM for longer than 10 years while the control group consisted of 50 healthy volunteers. HDL subfractions were analysed with the use of Lipoprint. RESULTS: We demonstrated progressive worsening of heart functioning and impairment of its structure in the course of diabetes mellitus. Moreover, we observed that HDL-6 subfraction and intermediate HDL fraction are lowest in the group with advanced DMt2 compared to the group with newly diagnosed DM and a healthy control group. Finally, the results of our study indicated the effect of statin treatment on HDL subfractions that seems not to be advantageous. CONCLUSION: It seems that in patients with diabetes mellitus compromised antiatherogenic properties of HDL, as a result of oxidative modification and glycation of the HDL protein as well as the transformation of the HDL proteome into a proinflammatory protein, increase cardiovascular risk.

In Vitro Antioxidant, Antithrombotic, Antiatherogenic and Antidiabetic Activities of Urtica dioica, Sideritis euboea and Cistus creticus Water Extracts and Investigation of Pasta Fortification with the Most Bioactive One.

BACKGROUND: The present work evaluated the in vitro antioxidant, antithrombotic, antiatherogenic and antidiabetic activities of Urtica dioica, Sideritis euboea and Cistus creticus and investigated pasta fortification with the most bioactive one. The methods employed were total phenolic content (TPC) in mg of gallic acid equivalents per g of dried-herb, 2,2'-azino-bis(3-ethylbenzothiazoline- 6-sulfonic acid) (ABTS) free radical scavenging in mg of dried-herb, cupric reducing antioxidant capacity (CUPRAC) in micromol trolox equivalent per g of dried-herb, platelet aggregation inhibition (PAF-PAI); plasma oxidation inhibition (POxI); and alpha glucosidase inhibition (a-GaseI) all in mg of dried-herb. Pasta fortified with the most bioactive herb was also studied for the above activities. METHODS: Cistus creticus extract was more bioactive (p < 0.05) compared to Sideritis euboea and Urtica dioica in all but antithrombotic assay, where Sideritis euboea was superior to the others (TPC: 37.9 ± 0.56 versus 9.6 ± 0.83 and 5.4 ± 0.70; SA50-ABTS: 0.040 ± 0.001 versus 0.400 ± 0.010 and 0.520 ± 0.008; ACUPRAC: 860 ± 6.23 versus 170 ± 4.25 and 80 ± 3.63; IA50-PAF: 1.8 ± 0.14 versus 1.2 ± 0.10 and 5.2 ± 0.21; POxI: 0.095 ± 0.016 versus 0.216 ± 0.021 and 0.534 ± 0.029; IA50-aGase: 0.2 ± 0.01 versus 2.1 ± 0.16 and 1.7 ± 0.12). RESULTS: Fortified pasta with cistus creticus extract exhibited significantly higher levels (p < 0.05) in all assays compared to plain pasta (TPC: 0.392 ± 0.064 versus 0.137 ± 0.020; SA50-ABTS: 9.4 ± 0.2 versus 126.9 ± 2.7; ACUPRAC: 5.4 ± 0.5 versus 0.9 ± 0.1; IA50-PAF: 1.87 ± 0.04 versus 2.28 ± 0.06; POxI: 3.21 ± 0.18 versus 12.2 ± 0.73; IA50-aGase: 8.9 ± 1.1 versus 18.2 ± 0.9). CONCLUSION: The current findings add to the mounting evidence on the potential health benefits to be derived from consuming pasta fortified with herbal extracts and indicate that Cistus creticus could form an ideal raw material towards the production of fortified pasta with increased nutritional value.