Anti-atherosclerotic Activity Research Articles

Advancements in Litchi chinensis Peel Processing: A Scientific Review of Drying, Extraction, and Isolation of Its Bioactive Compounds.

This article systematically reviews the advancements in processing litchi peel (Litchi chinensis), emphasizing drying, extraction, purification methods, and the potential of bioactive compounds obtained from litchi peel. This work also highlights the impact of various drying techniques on phytochemical profiles, focusing on how methods such as hot air and freeze-drying affect the preservation of bioactive compounds. The study delves into extraction methods, detailing how different solvents and techniques influence the efficiency of extracting bioactive compounds from litchi peel. Furthermore, the purification and characterization of active compounds, showcasing the role of chromatographic techniques in isolating specific bioactive molecules, is discussed. Biological properties and mechanisms of action, such as antioxidant, antihyperglycemic, cardioprotective, hepatoprotective, anti-atherosclerotic, and anticancer activities, are reviewed, providing insight into the potential health benefits of litchi peel compounds. This review highlights the importance of optimizing and selecting accurate drying and extraction methods to maximize the therapeutic effects of litchi peel and its bioactive compounds. This review also reveals the broad pharmacological potential of the isolated compounds, underscoring the need for further research to discover their specific actions and health benefits.

Xintongtai Granule: Investigating the serum pharmacology and mechanisms of action against atherosclerosis

PurposeA serum medicinal chemistry analysis was performed to investigate the pharmacological basis of Xintongtai granule and to predict the potential mechanism of anti-atherosclerotic action based on the blood components. MethodsUPLC-Q-TOF-MS/MS was used to analyze the in vitro chemical composition and in vivo blood components of Xintongtai granule, and to detect the blood drug concentration. The PPI network was constructed by collecting blood components and disease targets through the network pharmacology method, and the key targets were subjected to GO and KEGG functional enrichment analyses, so as to construct the topology network of drug-component-target-disease, and to validate the network by molecular docking. ResultsThe UPLC-Q-TOF-MS/MS analysis identified 69 chemical components in Xintongtai granule, including 19 prototype circulating components and 9 metabolites in the bloodstream. Network pharmacology analysis revealed 115 intersecting targets for the circulating components, from which 10 core targets were selected. GO and KEGG analyses unveiled associated signaling pathways and biological processes. The construction of a topology network and preliminary molecular docking provided insights into its mechanism of action. ConclusionThe mechanism underlying the anti- atherosclerosis effect of Xintongtai granule may be associated with the intervention of active components such as Cryptotanshinone, Kaempferitrin, and Puerarin in pathways targeting CXCL8, STAT3, TNF, and other related targets.

Expression and Purification of Recombinant Bowman-Birk Trypsin Inhibitor from Foxtail Millet Bran and Its Anticolorectal Cancer Effect In Vitro and In Vivo.

Trypsin inhibitors derived from plants have various pharmacological activities and promising clinical applications. In our previous study, a Bowman-Birk-type major trypsin inhibitor from foxtail millet bran (FMB-BBTI) was extracted with antiatherosclerotic activity. Currently, we found that FMB-BBTI possesses a prominent anticolorectal cancer (anti-CRC) activity. Further, a recombinant FMB-BBTI (rFMB-BBTI) was successfully expressed in a soluble manner in host strain Escherichia coli. BL21 (DE3) was induced by isopropyl-β-d-thiogalactoside (0.1 mM) at 37 °C for 3.5 h by the pET28a vector system. Fortunately, a purity greater than 93% of rFMB-BBTI with anti-CRC activity was purified by nickel-nitrilotriacetic acid affinity chromatography. Subsequently, we found that rFMB-BBTI displays a strikingly anti-CRC effect, characterized by the inhibition of cell proliferation and clone formation ability, cell cycle arrest at the G2/M phase, and induction of cell apoptosis. It is interesting that the rFMB-BBTI treatment had no obvious effect on normal colorectal cells in the same concentration range. Importantly, the anti-CRC activity of rFMB-BBTI was further confirmed in the xenografted nude mice model. Taken together, our study highlights the anti-CRC activity of rFMB-BBTI in vitro and in vivo, uncovering the clinical potential of rFMB-BBTI as a targeted agent for CRC in the future.

Effects of Anthocyanins on Components of Metabolic Syndrome-A Review.

Metabolic syndrome (MetS) is a significant health problem. The co-occurrence of obesity, carbohydrate metabolism disorders, hypertension and atherogenic dyslipidaemia is estimated to affect 20-30% of adults worldwide. Researchers are seeking solutions to prevent and treat the conditions related to MetS. Preventive medicine, which focuses on modifiable cardiovascular risk factors, including diet, plays a special role. A diet rich in fruits and vegetables has documented health benefits, mainly due to the polyphenolic compounds it contains. Anthocyanins represent a major group of polyphenols; they exhibit anti-atherosclerotic, antihypertensive, antithrombotic, anti-inflammatory and anticancer activities, as well as beneficial effects on endothelial function and oxidative stress. This review presents recent reports on the mechanisms involved in the protective effects of anthocyanins on the body, especially among people with MetS. It includes epidemiological data, in vivo and in vitro preclinical studies and clinical observational studies. Anthocyanins are effective, widely available compounds that can be used in both the prevention and treatment of MetS and its complications. Increased consumption of anthocyanin-rich foods may contribute to the maintenance of normal body weight and modulation of the lipid profile in adults. However, further investigation is needed to confirm the beneficial effects of anthocyanins on serum glucose levels, improvement in insulin sensitivity and reduction in systolic and diastolic blood pressure.

Disulfiram Reduces Atherosclerosis and Enhances Efferocytosis, Autophagy, and Atheroprotective Gut Microbiota in Hyperlipidemic Mice.

Pyroptosis executor GsdmD (gasdermin D) promotes atherosclerosis in mice and humans. Disulfiram was recently shown to potently inhibit GsdmD, but the invivo efficacy and mechanism of disulfiram's antiatherosclerotic activity is yet to be explored. We used human/mouse macrophages, endothelial cells, and smooth muscle cells and a hyperlipidemic mouse model of atherosclerosis to determine disulfiram antiatherosclerotic efficacy and mechanism. The effects of disulfiram on several atheroprotective pathways such as autophagy, efferocytosis, phagocytosis, and gut microbiota were determined. Atomic force microscopy was used to determine the effects of disulfiram on the biophysical properties of the plasma membrane of macrophages. Disulfiram-fed hyperlipidemic apolipoprotein E-/- mice showed significantly reduced interleukin-1β release upon invivo Nlrp3 (NLR family pyrin domain containing 3) inflammasome activation. Disulfiram-fed mice showed smaller atherosclerotic lesions (~27% and 29% reduction in males and females, respectively) and necrotic core areas (~50% and 46% reduction in males and females, respectively). Disulfiram induced autophagy in macrophages, smooth muscle cells, endothelial cells, hepatocytes/liver, and atherosclerotic plaques. Disulfiram modulated other atheroprotective pathways (eg,efferocytosis, phagocytosis) and gut microbiota. Disulfiram-treated macrophages showed enhanced phagocytosis/efferocytosis, with the mechanism being a marked increase in cell-surface expression of efferocytic receptor MerTK. Atomic force microscopy analysis revealed altered biophysical properties of disulfiram-treated macrophages, showing increased order-state of plasma membrane and increased adhesion strength. Furthermore, 16sRNA sequencing of disulfiram-fed hyperlipidemic mice showed highly significant enrichment in atheroprotective gut microbiota Akkermansia and a reduction in atherogenic Romboutsia species. Taken together, our data show that disulfiram can simultaneously modulate several atheroprotective pathways in a GsdmD-dependent as well as GsdmD-independent manner.

Formulation and evaluation of nanobiotherapeutics of Terminalia arjuna through plant tissue culture for atherosclerosis

Abstract Background The study seeks to investigate the therapeutic potential of Terminalia arjuna callus in addressing atherosclerosis. In order to get maximum beneficial phytoconstituents from Terminalia arjuna, it is recommended to harvest the bark from Arjuna trees that are at least 15 years old and a gap of minimum 2 years should be kept before harvesting bark from the same plant. The callus culture technique was employed to expedite the process. The callus culture extract was subsequently converted into a nanosuspension with the aim of improving the efficacy of its phytoconstituents. It was then subjected to a comprehensive series of in vitro and in vivo evaluations to ascertain its potential for treatment of atherosclerosis. Results Liquid chromatography–mass spectrometry analysis of the callus extract confirmed the presence of flavonoids and terpenoids, known for their antioxidant and anti-inflammatory activities. Some terpenoids were even absent in Arjuna tree naturally. TEM images validated successful entrapment of the extract within the nanoparticles. In vitro analysis for antilipase and antioxidant assay confirmed the antiatherosclerotic potential of the extract. In vivo tests on rat blood serum demonstrated a significant reduction in total cholesterol, low-density lipoprotein, triglycerides, high-density lipoprotein, and very low-density lipoprotein. Histopathological analysis of rat aortas showed additional confirmation of antiatherosclerotic action. Conclusion In conclusion, the study highlights the potential of nanosuspension derived from Terminalia arjuna callus extract as a comprehensive therapeutic strategy for atherosclerosis treatment. The research highlights antioxidant, anti-inflammatory, and antiatherosclerotic properties of the callus, hinting at its viability as a potential treatment for atherosclerosis. This interdisciplinary investigation emphasizes the promising role of traditional medicinal plants within modern medical paradigms.

Integrated network pharmacology, molecular docking and pharmacodynamic study reveals protective effects and mechanisms of corilagin against cerebral ischemia-induced injury

BackgroundStroke is one of the leading causes of death and long-term disability worldwide. Previous studies have found that corilagin has antioxidant, anti-inflammatory, anti-atherosclerotic and other pharmacological activities and has a protective effect against cardiac and cerebrovascular injury. ObjectivesThe aim of this study was to investigate the protective effects of corilagin against ischemic stroke and to elucidate the underlying molecular mechanisms using network pharmacology, molecular docking, and animal and cell experiments. MethodsWe investigated the potential of corilagin to ameliorate cerebral ischemia–reperfusion injury using in vivo rat middle cerebral artery occlusion/reperfusion (MCAO/R) and in vitro oxygen–glucose deprivation/reoxygenation (OGD/R) models. ResultsOur results suggest that corilagin may exert its anti-ischemic stroke effect by interacting with 92 key targets, including apoptosis-associated proteins (Bcl-2, Bax, caspase-3) and PI3K/Akt signaling pathway-related proteins. In vivo and in vitro experiments showed that corilagin treatment improved neurological deficits, attenuated cerebral infarct volume, and mitigated neuronal damage in MCAO/R rats. Corilagin treatment also enhanced the survival of PC12 cells exposed to OGD/R, reduced the rate of LDH leakage, inhibited cell apoptosis, and activated the PI3K/Akt signaling pathway. Importantly, the effects of corilagin on the PI3K/Akt signaling pathway and apoptosis-associated proteins were reversed by the PI3K-specific inhibitor LY294002. ConclusionsThese results indicate that the molecular mechanism of the anti-ischemic effect of corilagin involves inhibiting neuronal apoptosis and activating the PI3K/Akt signaling pathway. These findings provide a theoretical and experimental basis for the further development and application of corilagin as a potential anti-ischemic stroke agent.

Mitochondrial Melatonin: Beneficial Effects in Protecting against Heart Failure.

Cardiovascular disease is the cause of physical infirmity and thousands of deaths annually. Typically, during heart failure, cardiomyocyte mitochondria falter in terms of energy production and metabolic processing. Additionally, inflammation and the accumulation of non-contractile fibrous tissue contribute to cardiac malfunction. Melatonin, an endogenously produced molecule, experimentally reduces the initiation and progression of atherosclerotic lesions, which are often the basis of coronary artery disease. The current review critically analyzes published data related to the experimental use of melatonin to forestall coronary artery pathologies. Collectively, these studies document melatonin's anti-atherosclerotic actions in reducing LDL oxidation and triglyceride levels, lowering endothelial malfunction, limiting adhesion molecule formation, preventing macrophage polarization to the M1 pro-inflammatory phenotype, changing cellular metabolism, scavenging destructive reactive oxygen species, preventing the proliferation and invasion of arterial smooth muscle cells into the lesioned area, restricting the ingrowth of blood vessels from the vasa vasorum, and solidifying the plaque cap to reduce the chance of its rupture. Diabetic hyperglycemia, which aggravates atherosclerotic plaque formation, is also inhibited by melatonin supplementation in experimental animals. The potential value of non-toxic melatonin as a possible inhibitor of cardiac pathology in humans should be seriously considered by performing clinical trials using this multifunctional molecule.

Nutritional Profiling and Characterization of Developed Cake Premix Using Finger Millets (Eleusine coracana) and Sweet Potato (Ipomea batatas L.)

Research in the areas of nutrition and health care, as well as the growing public knowledge of these subjects, support the potential of phytochemicals like dietary fibre on their health-beneficial properties. Finger millet (FM) rates higher in terms of nutritional composition than other cereal grains. When absorbed by the body, FM's nutritional composition lowers the chance of developing type 2 diabetes, hypertension, and gastrointestinal tract disorders. Due to the high levels of calcium (0.38%), dietary fibre (18%), and phenolic compounds (0.3–3%) in it, its usefulness in terms of nutrition is well understood. Additionally, they have been found to have anti-diabetic, anti-tumor, anti-atherosclerotic, antioxidant, and antibacterial activities. The study focused on the development, Physiochemical Analysis, Nutritional Profiling and Microbial analysis of Cake Premix using Finger Millet and Sweet Potato in Different Ratio. A porous shape of the premix powder was shown by Scanning Electron Microscope-Energy Dispersive Spectroscopy. The structure of the Premix was mainly pore-free, uniform, and compact. showed that the Premix's surface was also smooth. Presumption powder's Fourier-transform infrared spectroscopy (FTIR) spectra were essentially identical within the wave-number range of 4000–400 cm−1. the six-month period's microbiological proliferation (count of mould and yeast). The findings showed that during the storage period, there was no discernible variation in the microbiological load (yeast and mould count) in the created goods, suggesting that they were safe for ingestion for up to six months. The objective of the present research was intended to develop Cake premix by using Finger Millet and Sweet Potato in different Ratio which could be utilized as nutritional supplement and also helps in lowering the risks of lifestyle disorders.

In-silico studies on structural function of ampk through docking approach toward design drug for atherosclerosis

Atherosclerosis poses significant health risks, driving cardiovascular issues like heart attacks and strokes. Shortage of appropriate pathophysiological models and a suitable algorithm for the discovery of drugs and para-pharmaceuticals with direct anti-atherosclerotic action are major barriers to the effective pathogenetic medication for atherosclerosis. This study focused on using bioinformatics tools and molecular docking techniques to identify novel molecular agonists for the Activated Monophosphate Kinase (AMPK) enzyme via the AMPK/PP2A/NF-κB/LOX-1 pathway. Virtual screening and molecular docking were performed for activation and phosphorylation of AMPK and stimulation of Protein Phosphostase-2A (PP2A) which results in down-regulation of lectin-like oxLDL (LOX-1) receptor to reduce the internalization of oxidized low-density lipoprotein (oxLDL). Enkephalin (ZINC000014952116) emerged as a potent AMPK agonist, triggering a cascade of interactions leading to reduced LOX-1 expression and which inhibits the Nuclear Factor kappa betta (NF-κβ) transcriptional activity for inflammatory atherosclerosis.

Thymus atlanticus (Ball) Roussine Aqueous Extract Exerts Lipid-lowering and Anti-atherosclerotic Effects in Hyperlipidemic Guinea Pigs.

Thymus atlanticus (Ball) Roussine (T. atlanticus) is traditionally used in the Moroccan high Atlas Mountains to treat several disorders, including cardiovascular disease. In the present study, the lipid-lowering and anti-atherosclerotic activities of the traditionally used aqueous extract of T. atlanticus were evaluated on guinea pigs subjected to chronic hyperlipidemia. Animals were given a diet containing 2% cholesterol and 20% lard for 12 weeks. Moreover, thyme extract was given daily at 400 mg/kg. At the end of the experiment, lipid levels and paraoxonase arylesterase activity were measured, and aorta histology was studied. Our findings revealed that there was an important elevation of blood lipids in the HFD group along with a significant decrease in paraoxonase arylesterase activity (-40.06%). Moreover, the consumption of fat altered the histology of aorta by thickening the intima media and forming atherosclerotic lesions and foam cells in these tissues. However, the administration of thyme extract attenuated HFD-caused alterations by decreasing blood lipids, elevating paraoxonase activity (+24.04%), and limiting the progression of atherosclerotic lesions. We conclude that the supplementation with the aqueous extract of T. atlanticus could potentially protect against hyperlipidemia and consequently, the development of atherosclerosis.

Pterostilbene: A Review on its Pharmacological Activities

Pterostilbene is a type of stilbenoids, a phenolic compound found in various plant species. It is an antimicrobial phytoalexins produced in plants to protect against fungal infection and toxins. In this review, the biological effects of pterostilbene are discussed. It is reported to have wide array of actions including anticancer, neuroprotective, antidiabetic, antiobesity, antihyperlipidemic, anti-atherosclerotic, cardioprotective, antihypertensive, anti-inflammatory, anti-arthritic, antioxidant, anti-allergic, anti-anxiety, anti-androgenic and antifungal activity. Its anticancer potential is more widely explored. These results are seen in-vitro, in-vivo including animal studies as well as clinical human trials.

Acute aflatoxin B1-induced hepatic and cardiac oxidative damage in rats: Ameliorative effects of morin

Aflatoxins (AFs) are secondary metabolites produced by the fungus Aspergillus flavus, of which Aflatoxin-B1 (AFB1) appears to be the most cancerogenic and of the highest toxicity. AFB1 causes serious effects on several organs including the liver. Morin is a flavonol that exists in many fruits and plants and has diverse biological properties including anticancer, anti-atherosclerotic, antioxidant, anti-inflammatory, immunomodulatory, and multi-organ protective activities. The present study aims to evaluate the potential protective effects of morin against acute AFB1-induced hepatic and cardiac toxicity in rats. Forty rats were divided into five groups (n = 8) as follows: control received the vehicle, morin was orally administered 30/mg/kg body weight (MRN30), the AFB1 was administered orally at a dose of 2.5 mg/kg, twice on days 12 and 14 of the experiment for the 3rd, 4th, and 5th groups., AFB1-MRN15 was orally given morin at a dose of 15 mg/kg body weight, and AFB1-MRN30 orally received morin at 30 mg/kg body weight. The results indicated a significant decrease in serum AST, ALP, LDH, GGT, CK, CK-MB, 8-OHdG, IL-1β, IL-6, TNF-a levels in MRN30 compared to AFB1, and AFB1-MRN15 groups. However, the results indicated non-significant differences in the serum levels between MRN30, control, and AFB1-MRN30 groups. Meanwhile, regarding the hepatic and cardiac parameters, there were significant differences in the levels of MDA, NO, GSH, GSH-Px, SOD, and CAT in MRN30 compared to AFB1, and AFB1-MRN15 groups, overall implying the protective effects of morin. To conclude, morin at a dose of 30 mg/kg b. wt. showed significant enhancements in acute AFB1-induced hepatic and cardiac toxicity in rats, which could play a role in limiting the public health hazards of AFs.

Microarray analysis identifies human apoA-IMilano and apoA-II as determinants of the liver gene expression related to lipid and energy metabolism

The phenotype of individuals carrying the apolipoprotein A-IMilano (apoA-IM), the mutant form of human apoA-I (apoA-I), is characterized by very low concentrations of HDL and apoA-I, and hypertriglyceridemia. Paradoxically, these subjects are not found to be at increased risk of premature cardiovascular disease compared to controls. Besides, various in vitro and in vivo studies have demonstrated that apoA-IM possesses greater anti-atherosclerotic activity compared to apoA-I. The molecular mechanisms explaining the apoA-IM carrier's phenotype and the apoA-IM higher efficacy are still not fully elucidated. To investigate such mechanisms, we crossed previously generated apoA-I (A-I k-in) or apoA-IM knock-in mice (A-IM k-in) with transgenic mice expressing human apoA-II but lacking murine apoA-I (hA-II) to generate hA-II/A-I k-in, and hA-II/A-IM k-in, respectively. These genetically modified mice completely reproduced the apoA-IM carrier's phenotype, including hypoalphalipoproteinemia and hypertriglyceridemia. Furthermore, by using the microarray methodology, we investigated the intrinsic differences in hepatic gene expression among these k-in mouse lines. The expression of 871, 1,018, 1129 and 764 genes was significantly altered between 1) hA-II/A-I and hA-II/A-IM k-in; 2) A-IM and hA-II/A-IM k-in; 3) A-I and A-IM; 4) A-I and hA-II/A-I k-in liver samples, respectively. Bioinformatics analysis highlighted that the hepatic expression of two genes, Elovl6 and Gatm, related to fatty acid/lipid and energy metabolism, respectively, is influenced by the presence of the apoA-IM natural variant and/or apoA-II.

Anti-Atherosclerosis and Anti-Hyperlipidemia Functions of Terminalia catappa Fruit.

Background: Atherosclerosis is a chronic pathological condition that has remained clinically silent for decades, and the epidemic has continued to be on the rise due to risk factors, including diet, lifestyle, hyperlipidemia, pathogenic microorganisms, and aging. Using various synthetic drugs in treating atherosclerosis is associated with a high risk of myositis, angioedema, myoglobinuria, and acute renal failure. Various side effects of the available drugs have been reported; attempts are underway to explore natural sources with antiatherosclerotic activity. Aim and objective: Using a diet-induced atherosclerosis rat model, the current study tested the hypothesis of antiatherosclerotic and antihyperlipidemic roles of Terminalia catappa fruit extracts. Materials and Methods: Atherosclerosis in Wistar rats was induced using an atherogenic diet. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (AP), creatine kinase (CK), and lactate dehydrogenase (LDH) were determined using analytical kits. Results: Quantitative phytochemical analysis of the extracts demonstrated that the plant had flavonoids, saponins, tannins, terpenoids, alkaloids, cardiac glycosides, sterols, phenols, and anthraquinones. Diet-induced atherogenic Wistar rats showed a significant (p < 0.05) increase in total cholesterol, triglyceride, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol compared to the healthy control group; however, the atherogenic lipid profile was reversed by the treatment of T. catappa fruit extracts. The biochemical experiments demonstrate that T. catappa fruit extracts have an antihyperlipidaemic effect, shown by a decreased coronary risk index and the atherogenic index, and an increased cardioprotective index, compared to disease control. Conclusion: The current study indicates that T. catappa fruit extracts may contain bioactive molecules to treat atherosclerosis.

Rosmarinic acid as a potential anti-hyperlipidemic agent

Rosmarinic acid (RA) is a natural phytochemical that occurs in numerous plants, including Rosmarinus officinalis. This bioactive compound is widely reported to exert various pharmacological effects, including anti-hyperlipidemic activity. In this study, we reviewed the literature data on RA and hyperlipidemia research. In silico, in vitro, and in vivo studies were retrieved from Scholar, PubMed, ScienceDirect, Web of Science, and Scopus. The In silico studies revealed that RA possesses squalene synthase and 3-hydroxy-3-methylglutaryl–coenzyme A reductase enzymes inhibiting effect. Additionally, in vitro reports revealed that RA exerts remarkable lipid-lowering effects and also exhibits anti-adipogenic and anti-atherosclerotic activities. The lipid-lowering action was modulated by numerous mechanisms including the regulation of anti-inflammatory and antioxidant signaling pathways. Moreover, in vivo studies revealed that RA alleviates hyperlipidemia in animal models by modulating the expression of genes involved in hyperlipidemia as well as the regulation of gut microbiota and anti-inflammatory pathways. We conclude that RA is a multi-target anti-hyperlipidemic agent. Moreover, we suggest that the use of this bioactive compound as an anti-hyperlipidemic drug would be an effective pharmacological strategy that could provide promising options for the treatment and prevention of hyperlipidemia and its related disorders including atherosclerosis.

Crocin improves the renal autophagy in rat experimental membranous nephropathy via regulating the SIRT1/Nrf2/HO-1 signaling pathway

Membranous nephropathy (MN) is a glomerular disease. Crocin is isolated from saffron and gardenia. Its antioxidant, anti-inflammatory, anti-hyperlipidemic, anti-atherosclerotic, anti-tumor, free-radical scavenging and neuroprotective activities have been well established. We investigated the biological functions of crocin and its related mechanisms in MN. We established an experimental passive Heymann nephritis (PHN) rat model induced by anti-Fx1A antiserum. The rats were divided into sham, sham + crocin, PHN, PHN + crocin, and PHN + enalapril groups. Blood samples and kidneys of rats were collected for estimation of biochemical parameters in serum and oxidative stress indicators in kidney tissues. Histopathological changes of renal tissues were evaluated by hematoxylin and eosin, periodic acid-Schiff (PAS) and Masson staining. The podocyte number was estimated by immunohistochemistry staining of Wilms tumor type 1 (WT1). The deposition of rat anti-rabbit IgG antibodies, complement C3 and C5b-9 was detected by immunofluorescence staining. Western blotting was performed to measure the levels of Sirtuin 1 (Sirt1), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1) and apoptosis-related proteins. The total cholesterol, triglycerides, creatinine, blood urea nitrogen, urine volume and urine albumin of PMN rats were significantly reduced by crocin. Additionally, crocin attenuated the renal histopathological changes. Moreover, the oxidative stress damage and podocyte loss and immune injury were relieved by crocin in PHN rats. Mechanistically, crocin administration activated the Sirt1/Nrf2/HO-1 pathways. The results provide a scientific basis that crocin could alleviate MN by inhibiting immune injury and podocyte damage through activating the Sirt1/Nrf2/HO-1 pathways.

COMPARATIVE LEAF ANATOMY OF SOME ASYNEUMA GRISEB. &amp; SCHENK TAXA

Objective: The Asyneuma Griseb. &amp;amp; Schenk is represented by 34 accepted species worldwide and its native range covers a wide area from East Central Europe to Japan and Northern Indo-china. The plants of Asyneuma are characterized by herbaceous, simple or branched inflorescences, purple, violet or blue corolla and capsule fruits. Studies show that the Campanulaceae family contains bioactive compounds phenylethanoid (phenylproponoid), alkaloids, cyanogenetic heteroside, flavonoid, triterpene, anthocyanin, phenolic acid, essential oil, coumarin and polysaccharide. In addition, it is known that plants in the family have antioxidant, wound healing, anti-inflammatory, analgesic, antiobesity, expectorant antihepatotoxic, antitumoral, antiatherosclerotic, neuroprotective, antidepressant, tonic and α-glucosidase inhibitory activities. In this study, the anatomical structures of Asyneuma limonifolium subsp. limonifolium, A. limonifolium subsp. pestalozzae (Boiss.) Damboldt, A. linifolium subsp. linifolium and A. linifolium subsp. nallihanicum Kit Tan &amp;amp; Yıldız leaves were examined. Material and Method: Asyneuma limonifolium subsp. limonifolium, A. limonifolium subsp. pestalozzae (Boiss.) Damboldt, A. linifolium subsp. nallihanicum Kit Tan &amp;amp; Yıldız were collected from Ankara. A. linifolium subsp. linifolium was collected from Antalya. Plant parts preserved in alcohol (70%). Microscopic sections were taken using a razor blade. Tissues were stained with Sartur's reagent and examined with a light microscope. Microphotographs were taken with a camera attached to a light microscope. Result and Discussion: The results showed that, the anatomical structures of the basal and cauline leaves of Asyneuma limonifolium subsp. limonifolium and A. limonifolium subsp. pestalozzae were similar. The leaves are bifacial and the palisade parenchyma 1-2 rows. In addition, the unicellular, non-glandular hairs and anomocytic stomata were observed on both epidermal surfaces. Besides, the leaf of A. linifolium subsp. linifolium is monofacial while that of A. linifolium subsp. nallihanicum is bifacial. Also, unicellular hairs were present on epidermal layer of A. linifolium subsp. linifolium while A. linifolium subsp. nallihanicum were not. The anomocytic stomata were determined on the upper and lower leaf surfaces of both subspecies.

Design, optimization, and in vivo evaluation of invasome-mediated candesartan for the control of diabetes-associated atherosclerosis

Atherosclerosis is an inflammatory disease characterized by the accumulation of arterial plaque. Diabetes mellitus stands out as a major risk factor for atherosclerosis. Candesartan is a potent angiotensin II receptor antagonist that enhances arterial blood flow and reduces insulin resistance. However, oral candesartan has limited activity because of its low bioavailability, water solubility, hepatic first-pass degradation, and efficacy. The current study aims to develop nasal candesartan-loaded invasome (CLI) drops to improve candesartan’s permeation, release, and bioavailability as a potential treatment for diabetes-associated atherosclerosis. Design expert software was used to prepare various CLI formulations to determine the impact of the concentrations of ethanol, cineole, and phospholipid. The desirability index was used to estimate the optimized formulation composition to maximize entrapment efficiency and minimize vesicle size. The optimized formulation had a 1% ethanol concentration, a 1.5% cineole concentration, and a 2.32% phospholipid concentration. The selected optimized formulation was then tested in a rat model of diabetes and atherosclerosis to evaluate its activity. The results showed that nasal CLI drops significantly raised serum HDL levels by a ratio of 1.42 and lowered serum glucose, cholesterol, triglycerides, LDL, and VLDL levels by 69.70%, 72.22%, 36.52%, 58.0%, and 65.31%, respectively, compared with diabetic atherosclerotic rats, throwing an insight on the potential for promising anti-diabetic and anti-atherosclerotic activities. Additionally, atherosclerotic lesions were improved in rats treated with CLI, as shown in histopathology. In conclusion, the results of this investigation showed that treatment with nasal CSN-loaded invasome formulation drops prevented the initiation and progression of diabetes-associated atherosclerosis.Graphical

Emergence of Nano-Based Formulations for Effective Delivery of Flavonoids against Topical Infectious Disorders.

Flavonoids are hydroxylated phenolic substances in vegetables, fruits, flowers, seeds, wine, tea, nuts, propolis, and honey. They belong to a versatile category of natural polyphenolic compounds. Their biological function depends on various factors such as their chemical structure, degree of hydroxylation, degree of polymerization conjugation, and substitutions. Flavonoids have gained considerable attention among researchers, as they show a wide range of pharmacological activities, including coronary heart disease prevention, antioxidative, hepatoprotective, anti-inflammatory, free-radical scavenging, anticancer, and anti-atherosclerotic activities. Plants synthesize flavonoid compounds in response to pathogen attacks, and these compounds exhibit potent antimicrobial (antibacterial, antifungal, and antiviral) activity against a wide range of pathogenic microorganisms. However, certain antibacterial flavonoids have the ability to selectively target the cell wall of bacteria and inhibit virulence factors, including biofilm formation. Moreover, some flavonoids are known to reverse antibiotic resistance and enhance the efficacy of existing antibiotic drugs. However, due to their poor solubility in water, flavonoids have limited oral bioavailability. They are quickly metabolized in the gastrointestinal region, which limits their ability to prevent and treat various disorders. The integration of flavonoids into nanomedicine constitutes a viable strategy for achieving efficient cutaneous delivery owing to their favorable encapsulation capacity and diminished toxicity. The utilization of nanoparticles or nanoformulations facilitates drug delivery by targeting the drug to the specific site of action and exhibits excellent physicochemical stability.