Role of Lipid Accumulation and Inflammation in Atherosclerosis: Focus on Molecular and Cellular Mechanisms.

Atherosclerosis is a chronic lipid-driven and maladaptive inflammatory disease of arterial intima. It is characterized by the dysfunction of lipid homeostasis and signaling pathways that control the inflammation. This article reviews the role of inflammation and lipid accumulation, especially low-density lipoprotein (LDL), in the pathogenesis of atherosclerosis, with more emphasis on cellular mechanisms. Furthermore, this review will briefly highlight the role of medicinal plants, long non-coding RNA (lncRNA), and microRNAs in the pathophysiology, treatment, and prevention of atherosclerosis. Lipid homeostasis at various levels, including receptor-mediated uptake, synthesis, storage, metabolism, efflux, and its impairments are important for the development of atherosclerosis. The major source of cholesterol and lipid accumulation in the arterial wall is proatherogenic modified low-density lipoprotein (mLDL). Modified lipoproteins, such as oxidized low-density lipoprotein (ox-LDL) and LDL binding with proteoglycans of the extracellular matrix in the intima of blood vessels, cause aggregation of lipoprotein particles, endothelial damage, leukocyte recruitment, foam cell formation, and inflammation. Inflammation is the key contributor to atherosclerosis and participates in all phases of atherosclerosis. Also, several studies have shown that microRNAs and lncRNAs have appeared as key regulators of several physiological and pathophysiological processes in atherosclerosis, including regulation of HDL biogenesis, cholesterol efflux, lipid metabolism, regulating of smooth muscle proliferation, and controlling of inflammation. Thus, both lipid homeostasis and the inflammatory immune response are closely linked, and their cellular and molecular pathways interact with each other.

Mechanistic Aspects of Medicinal Plants and Secondary Metabolites against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

BACKGROUND AND OBJECTIVE: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a highly pathogenic virus, is responsible for a respiratory disease termed coronavirus disease 2019 (COVID-19). SARS-CoV-2 genome encodes various structural and non-structural proteins, which are necessary for viral entry and replication. Among these proteins, papain-like protease (PLpro), 3C-like protease (3CLpro), RNAdependent RNA polymerase (RdRp), helicase, serine protease, and spike protein are potential targets of herbal remedies and phytocompounds for inhibition of viral infection and replication. There is, at present, no confirmed cure for the COVID-19. Various plants and their components have been introduced against SARS-CoV-2. A number of review articles have also been published on them. This article is focused on the mechanistic aspects of these plants and their derivatives on SARS-CoV-2. METHODS: The material in this review article was prepared from significant scientific databases, including Web of Science, PubMed, Science Direct, Scopus and Google Scholar. RESULTS: Different medicinal plants and their phytocompounds interact with important structural and nonstructural of SARS-CoV-2 proteins. Natural compounds form strong bonds with the active site of SARS-CoV-2 protease and make large conformational changes. These phytochemicals are potential inhibitors of structural and non-structural SARS-CoV-2 proteins such as Spike protein, PLpro, and 3CLpro. Some important anti- SARS-CoV-2 actions of medicinal plants and their metabolites are: inhibition of the virus replication or entry, blocking the angiotensin-converting enzyme 2 (ACE-2) receptor and "Transmembrane protease, serine 2 (TMPRSS2), regulation of inflammatory mediators, inhibition of endothelial activation, toll-like receptors (TLRs) and activation of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2). Some of these important natural immune boosters that are helpful for the prevention and cure of various symptoms related to COVID-19 include Allium sativum, Nigella sativa, Glycyrrhiza glabra Zingiber officinalis, Ocimum sanctum, Withania somnifera, Tinospora cordifolia, and Scutellaria baicalensis. Also, Kaempferol, Quercetin, Baicalin, Scutellarin, Glycyrrhizin, Curcumin, Apigenin, Ursolic acid, and Chloroquine are the best candidates for treating the symptoms associated with SARS-CoV-2 infection. CONCLUSION: Medicinal plants and/or their bioactive compounds with inhibitory effects against SARS-CoV-2 support the human immune system and help in fighting against COVID-19 and rejuvenating the immune system.

Mechanisms of Medicinal Plant Activity on Nitric Oxide (NO) Bioavailability as Prospective Treatments for Atherosclerosis.

BACKGROUND AND OBJECTIVE: Atherosclerosis is one of the leading causes of human morbidity globally and reduced bioavailability of vascular nitric oxide (NO) has a critical role in the progression and development of the atherosclerotic disease. Loss of NO bioavailability, for example via a deficiency of the substrate (L-arginine) or cofactors for endothelial nitric oxide synthase (eNOS), invariably leads to detrimental vascular effects such as impaired endothelial function and increased smooth muscle cell proliferation, deficiency of the substrate (Larginine) or cofactors for eNOS. Various medicinal plants and their bioactive compounds or secondary metabolites with fewer side effects are potentially implicated in preventing cardiovascular disease by increasing NO bioavailability, thereby ameliorating endothelial dysfunction. In this review, we describe the most notable medicinal plants and their bioactive compounds that may be appropriate for enhancing NO bioavailability, and treatment of atherosclerosis. METHODS: The material in this article was obtained from noteworthy scientific databases, including Web of Science, PubMed, Science Direct, Scopus and Google Scholar. RESULTS: Medicinal plants and their bioactive compounds influence NO production through diverse mechanisms including the activation of the nuclear factor kappa B (NF-κB) signaling pathway, activating protein kinase C (PKC)-α, stimulating protein tyrosine kinase (PTK), reducing the conversion of nitrite to NO via nitrate-nitrite reduction pathways, induction of eNOS, activating the phosphatidylinositol 3-kinase (PI3K)/serine threonine protein kinase B (AKT) (PI3K/AKT/eNOS/NO) pathway and decreasing oxidative stress. CONCLUSION: Medicinal plants and/or their constituent bioactive compounds may be considered as safe therapeutic options for enhancing NO bioavailability and prospective preventative therapy for atherosclerosis.

Review of Phytochemical Compounds as Antiviral Agents Against Arboviruses from the Genera Flavivirus and Alphavirus.

Arboviruses are a diverse group of viruses that are among the major causes of emerging infectious diseases. Arboviruses from the genera flavivirus and alphavirus are the most important human arboviruses from a public health perspective. During recent decades, these viruses have been responsible for millions of infections and deaths around the world. Over the past few years, several investigations have been carried out to identify antiviral agents to treat these arbovirus infections. The use of synthetic antiviral compounds is often unsatisfactory since they may raise the risk of viral mutation; they are costly and possess either side effects or toxicity. One attractive strategy is the use of plants as promising sources of novel antiviral compounds that present significant inhibitory effects on these viruses. In this review, we describe advances in the exploitation of compounds and extracts from natural sources that target the vital proteins and enzymes involved in arbovirus replication.

Effective Antiviral Medicinal Plants and Biological Compounds Against Central Nervous System Infections: A Mechanistic Review.

BACKGROUND AND OBJECTIVE: Infectious diseases are amongst the leading causes of death in the world and central nervous system infections produced by viruses may either be fatal or generate a wide range of symptoms that affect global human health. Most antiviral plants contain active phytoconstituents such as alkaloids, flavonoids, and polyphenols, some of which play an important antiviral role. Herein, we present a background to viral central nervous system (CNS) infections, followed by a review of medicinal plants and bioactive compounds that are effective against viral pathogens in CNS infections. METHODS: A comprehensive literature search was conducted on scientific databases including: PubMed, Scopus, Google Scholar, and Web of Science. The relevant keywords used as search terms were: "myelitis", "encephalitis", "meningitis", "meningoencephalitis", "encephalomyelitis", "central nervous system", "brain", "spinal cord", "infection", "virus", "medicinal plants", and "biological compounds". RESULTS: The most significant viruses involved in central nervous system infections are: Herpes Simplex Virus (HSV), Varicella Zoster Virus (VZV), West Nile Virus (WNV), Enterovirus 71 (EV71), Japanese Encephalitis Virus (JEV), and Dengue Virus (DENV). The inhibitory activity of medicinal plants against CNS viruses is mostly active through prevention of viral binding to cell membranes, blocking viral genome replication, prevention of viral protein expression, scavenging reactive Oxygen Species (ROS), and reduction of plaque formation. CONCLUSION: Due to the increased resistance of microorganisms (bacteria, viruses, and parasites) to antimicrobial therapies, alternative treatments, especially using plant sources and their bioactive constituents, appear to be more fruitful.

Antioxidants and Atherosclerosis: Mechanistic Aspects.

Atherosclerosis is a chronic inflammatory disease which is a major cause of coronary heart disease and stroke in humans. It is characterized by intimal plaques and cholesterol accumulation in arterial walls. The side effects of currently prescribed synthetic drugs and their high cost in the treatment of atherosclerosis has prompted the use of alternative herbal medicines, dietary supplements, and antioxidants associated with fewer adverse effects for the treatment of atherosclerosis. This article aims to present the activity mechanisms of antioxidants on atherosclerosis along with a review of the most prevalent medicinal plants employed against this multifactorial disease. The wide-ranging information in this review article was obtained from scientific databases including PubMed, Web of Science, Scopus, Science Direct and Google Scholar. Natural and synthetic antioxidants have a crucial role in the prevention and treatment of atherosclerosis through different mechanisms. These include: The inhibition of low density lipoprotein (LDL) oxidation, the reduction of reactive oxygen species (ROS) generation, the inhibition of cytokine secretion, the prevention of atherosclerotic plaque formation and platelet aggregation, the preclusion of mononuclear cell infiltration, the improvement of endothelial dysfunction and vasodilation, the augmentation of nitric oxide (NO) bioavailability, the modulation of the expression of adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) on endothelial cells, and the suppression of foam cell formation.