scholarly journals Therapeutic Potential of β-Caryophyllene: A Dietary Cannabinoid in Diabetes and Associated Complications

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2963 ◽  
Author(s):  
Hebaallah Mamdouh Hashiesh ◽  
M.F. Nagoor Meeran ◽  
Charu Sharma ◽  
Bassem Sadek ◽  
Juma Al Kaabi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Receptor Subtypes ◽  
Natural Occurrence ◽  
Bioactive Constituents ◽  
Therapeutic Benefits ◽  
Anti Inflammatory

Diabetes mellitus (DM), a metabolic disorder is one of the most prevalent chronic diseases worldwide across developed as well as developing nations. Hyperglycemia is the core feature of the type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), following insulin deficiency and impaired insulin secretion or sensitivity leads insulin resistance (IR), respectively. Genetic and environmental factors attributed to the pathogenesis of DM and various therapeutic strategies are available for the prevention and treatment of T2DM. Among the numerous therapeutic approaches, the health effects of dietary/nutraceutical approach due to the presence of bioactive constituents, popularly termed phytochemicals are receiving special interest for pharmacological effects and therapeutic benefits. The phytochemicals classes, in particular sesquiterpenes received attention because of potent antioxidant, anti-inflammatory, and antihyperglycemic effects and health benefits mediating modulation of enzymes, receptors, and signaling pathways deranged in DM and its complications. One of the terpene compounds, β-caryophyllene (BCP), received enormous attention because of its abundant occurrence, non-psychoactive nature, and dietary availability through consumption of edible plants including spices. BCP exhibit selective full agonism on cannabinoid receptor type 2 (CB2R), an important component of endocannabinoid system, and plays a role in glucose and lipid metabolism and represents the newest drug target for chronic inflammatory diseases. BCP also showed agonist action on peroxisome proliferated activated receptor subtypes, PPAR-α and PPAR-γ, the main target of currently used fibrates and imidazolidinones for dyslipidemia and IR, respectively. Many studies demonstrated its antioxidant, anti-inflammatory, organoprotective, and antihyperglycemic properties. In the present review, the plausible therapeutic potential of BCP in diabetes and associated complications has been comprehensively elaborated based on experimental and a few clinical studies available. Further, the pharmacological and molecular mechanisms of BCP in diabetes and its complications have been represented using synoptic tables and schemes. Given the safe status, abundant natural occurrence, oral bioavailability, dietary use and pleiotropic properties modulating receptors and enzymes, BCP appears as a promising molecule for diabetes and its complications.

Antarctic Freshwater Microalga, Micractinium simplicissimum, Suppresses Inflammation

2021 ◽  
Vol 21 (7) ◽  
pp. 4098-4103
Author(s):  
Hae-Jung Chae ◽  
Jong Bae Seo ◽  
Sung-Hak Kim ◽  
Ei Joung Youn ◽  
Sanghee Kim ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Dermal Fibroblast ◽  
Human Dermal Fibroblast ◽  
Bioactive Molecules ◽  
Protective Mechanism ◽  
Anti Inflammatory ◽  
Underlying Mechanisms

Inflammation mediated by the innate immune system is the organism’s protective mechanism against infectious environmental risk factors. Uncontrolled acute inflammation can become chronic, contributing to various chronic inflammatory diseases such as arthritis, asthma, autoimmune diseases, and atherosclerosis. Although microalgae are increasingly receiving attention as a source of bioactive molecules with therapeutic potential for various human diseases, the underlying mechanisms are not yet well understood. In the present study, we investigated the molecular mechanisms underlying the anti-inflammatory and anti-aging activities of ethanol extracts of Antarctic freshwater microalga Micractinium simplicissimum. Using RAW 264.7 macrophages, microalgal extracts exerted anti-inflammatory activity by regulating the major inflammatory indicators including cyclooxy-genase (COX)-2, interleukin (IL)-6, inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α and nitric oxide (NO). Besides, we observed the anti-aging activity of the microalgal extract by suppressing MMP-1 production in human dermal fibroblast. Taken together, these data suggest that anti-inflammatory and anti-aging activities of Antarctic freshwater microalga, Micractinium simplicissimum, can provide new clues to understanding the molecular link between inflammation and diseases, and be a potential anti-inflammatory agent.

scholarly journals Glucocorticoid Resistance: Interference between the Glucocorticoid Receptor and the MAPK Signalling Pathways

2021 ◽  
Vol 22 (18) ◽  
pp. 10049
Author(s):  
Lisa M. Sevilla ◽  
Alba Jiménez-Panizo ◽  
Andrea Alegre-Martí ◽  
Eva Estébanez-Perpiñá ◽  
Carme Caelles ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Cell Types ◽  
Inflammatory Conditions ◽  
Therapeutic Benefits ◽  
Therapeutic Outcomes ◽  
Mapk Signalling ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory

Endogenous glucocorticoids (GCs) are steroid hormones that signal in virtually all cell types to modulate tissue homeostasis throughout life. Also, synthetic GC derivatives (pharmacological GCs) constitute the first-line treatment in many chronic inflammatory conditions with unquestionable therapeutic benefits despite the associated adverse effects. GC actions are principally mediated through the GC receptor (GR), a ligand-dependent transcription factor. Despite the ubiquitous expression of GR, imbalances in GC signalling affect tissues differently, and with variable degrees of severity through mechanisms that are not completely deciphered. Congenital or acquired GC hypersensitivity or resistance syndromes can impact responsiveness to endogenous or pharmacological GCs, causing disease or inadequate therapeutic outcomes, respectively. Acquired GC resistance is defined as loss of efficacy or desensitization over time, and arises as a consequence of chronic inflammation, affecting around 30% of GC-treated patients. It represents an important limitation in the management of chronic inflammatory diseases and cancer, and can be due to impairment of multiple mechanisms along the GC signalling pathway. Among them, activation of the mitogen-activated protein kinases (MAPKs) and/or alterations in expression of their regulators, the dual-specific phosphatases (DUSPs), have been identified as common mechanisms of GC resistance. While many of the anti-inflammatory actions of GCs rely on GR-mediated inhibition of MAPKs and/or induction of DUSPs, the GC anti-inflammatory capacity is decreased or lost in conditions of excessive MAPK activation, contributing to disease susceptibility in tissue- and disease- specific manners. Here, we discuss potential strategies to modulate GC responsiveness, with the dual goal of overcoming GC resistance and minimizing the onset and severity of unwanted adverse effects while maintaining therapeutic potential.

scholarly journals Therapeutic Potential of Volatile Terpenes and Terpenoids from Forests for Inflammatory Diseases

2020 ◽  
Vol 21 (6) ◽  
pp. 2187 ◽  
Author(s):  
Taejoon Kim ◽  
Bokyeong Song ◽  
Kyoung Sang Cho ◽  
Im-Soon Lee
Keyword(s):  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Biological Activities ◽  
Beneficial Effects ◽  
Forested Areas ◽  
Inflammatory Processes ◽  
Respiratory Inflammation ◽  
Volatile Terpenes ◽  
Anti Inflammatory

Forest trees are a major source of biogenic volatile organic compounds (BVOCs). Terpenes and terpenoids are known as the main BVOCs of forest aerosols. These compounds have been shown to display a broad range of biological activities in various human disease models, thus implying that forest aerosols containing these compounds may be related to beneficial effects of forest bathing. In this review, we surveyed studies analyzing BVOCs and selected the most abundant 23 terpenes and terpenoids emitted in forested areas of the Northern Hemisphere, which were reported to display anti-inflammatory activities. We categorized anti-inflammatory processes related to the functions of these compounds into six groups and summarized their molecular mechanisms of action. Finally, among the major 23 compounds, we examined the therapeutic potentials of 12 compounds known to be effective against respiratory inflammation, atopic dermatitis, arthritis, and neuroinflammation among various inflammatory diseases. In conclusion, the updated studies support the beneficial effects of forest aerosols and propose their potential use as chemopreventive and therapeutic agents for treating various inflammatory diseases.

scholarly journals The Action of Polyphenols in Diabetes Mellitus and Alzheimer's Disease: A Common Agent for Overlapping Pathologies

2019 ◽  
Vol 17 (7) ◽  
pp. 590-613 ◽  
Author(s):  
Ana C. Silveira ◽  
Jane Pires Dias ◽  
Vanessa M. Santos ◽  
Pedro Fontes Oliveira ◽  
Marco G. Alves ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Fruits And Vegetables ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Genetic Alterations ◽  
Therapeutic Alternatives ◽  
The Relationship

:Diabetes Mellitus (DM) and Alzheimer's disease (AD) are two prevalent diseases in modern societies, which are caused mainly by current lifestyle, aging and genetic alterations. It has already been demonstrated that these two diseases are associated, since individuals suffering from DM are prone to develop AD. Conversely, it is also known that individuals with AD are more susceptible to DM, namely type 2 diabetes (T2DM). Therefore, these two pathologies, although completely different in terms of symptomatology, end up sharing several mechanisms at the molecular level, with the most obvious being the increase of oxidative stress and inflammation.:Polyphenols are natural compounds widely spread in fruits and vegetables whose dietary intake has been considered inversely proportional to the incidence of DM and AD. So, it is believed that this group of phytochemicals may have preventive and therapeutic potential, not only by reducing the risk and delaying the development of these pathologies, but also by improving brain’s metabolic profile and cognitive function.:The aim of this review is to understand the extent to which DM and AD are related pathologies, the degree of similarity and the relationship between them, to detail the molecular mechanisms by which polyphenols may exert a protective effect, such as antioxidant and anti-inflammatory effects, and highlight possible advantages of their use as common preventive and therapeutic alternatives.

scholarly journals Columbianadin Suppresses Lipopolysaccharide (LPS)-Induced Inflammation and Apoptosis through the NOD1 Pathway

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 549 ◽  
Author(s):  
Chao Zhang ◽  
Alan Hsu ◽  
He Pan ◽  
Yinuo Gu ◽  
Xu Zuo ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Therapeutic Agent ◽  
Inflammatory Diseases ◽  
Mechanisms Of Action ◽  
Bioactive Constituents ◽  
Cellular Apoptosis ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Columbianadin (CBN) is one of the main bioactive constituents isolated from the root of Angelica pubescens. Although the anti-inflammatory activity of CBN has been reported, the underpinning mechanism of this remains unclear. In this study, we investigated the anti-inflammatory effect of CBN on lipopolysaccharide (LPS)-stimulated THP-1 cells and explored the possible underlying molecular mechanisms. The results showed that CBN suppressed LPS-mediated inflammatory response mainly through the inactivation of the NOD1 and NF- κ B p65 signaling pathways. Knockdown of NOD1 reduced the degree to which inflammatory cytokines decreased following CBN treatment, whereas forced expression of NOD1 and CBN treatment reduced NF- κ B p65 activation and the secretion of inflammatory cytokines. Furthermore, CBN significantly reduced cellular apoptosis by inhibiting the NOD1 pathway. Collectively, our results indicate that CBN suppressed the LPS-mediated inflammatory response by inhibiting NOD1/NF- κ B activation. Further investigations are required to determine the mechanisms of action of CBN in the inhibition of NOD signaling: However, CBN may be employed as a therapeutic agent for multiple inflammatory diseases.

scholarly journals The Landscape of microRNAs in βCell: Between Phenotype Maintenance and Protection

2021 ◽  
Vol 22 (2) ◽  
pp. 803
Author(s):  
Giuseppina Emanuela Grieco ◽  
Noemi Brusco ◽  
Giada Licata ◽  
Daniela Fignani ◽  
Caterina Formichi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Metabolic Disorders ◽  
Molecular Mechanisms ◽  
Β Cell ◽  
Physiological Mechanisms ◽  
Effective Strategies ◽  
Chronic Hyperglycaemia ◽  
Shed Light

Diabetes mellitus is a group of heterogeneous metabolic disorders characterized by chronic hyperglycaemia mainly due to pancreatic β cell death and/or dysfunction, caused by several types of stress such as glucotoxicity, lipotoxicity and inflammation. Different patho-physiological mechanisms driving β cell response to these stresses are tightly regulated by microRNAs (miRNAs), a class of negative regulators of gene expression, involved in pathogenic mechanisms occurring in diabetes and in its complications. In this review, we aim to shed light on the most important miRNAs regulating the maintenance and the robustness of β cell identity, as well as on those miRNAs involved in the pathogenesis of the two main forms of diabetes mellitus, i.e., type 1 and type 2 diabetes. Additionally, we acknowledge that the understanding of miRNAs-regulated molecular mechanisms is fundamental in order to develop specific and effective strategies based on miRNAs as therapeutic targets, employing innovative molecules.

scholarly journals Insulin Resistance and Diabetes Mellitus in Alzheimer’s Disease

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1236
Author(s):  
Jesús Burillo ◽  
Patricia Marqués ◽  
Beatriz Jiménez ◽  
Carlos González-Blanco ◽  
Manuel Benito ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Type 2 Diabetes Mellitus ◽  
Insulin Signaling ◽  
Molecular Mechanisms ◽  
Progressive Disease

Type 2 diabetes mellitus is a progressive disease that is characterized by the appearance of insulin resistance. The term insulin resistance is very wide and could affect different proteins involved in insulin signaling, as well as other mechanisms. In this review, we have analyzed the main molecular mechanisms that could be involved in the connection between type 2 diabetes and neurodegeneration, in general, and more specifically with the appearance of Alzheimer’s disease. We have studied, in more detail, the different processes involved, such as inflammation, endoplasmic reticulum stress, autophagy, and mitochondrial dysfunction.

scholarly journals Diabetes and Thrombosis: A Central Role for Vascular Oxidative Stress

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 706
Author(s):  
Aishwarya R. Vaidya ◽  
Nina Wolska ◽  
Dina Vara ◽  
Reiner K. Mailer ◽  
Katrin Schröder ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Molecular Mechanisms ◽  
Vascular System ◽  
Cell Damage ◽  
National Health System ◽  
Vascular Damage ◽  
Circulating Cells ◽  
Environmental Causes ◽  
Vascular Oxidative Stress

Diabetes mellitus is the fifth most common cause of death worldwide. Due to its chronic nature, diabetes is a debilitating disease for the patient and a relevant cost for the national health system. Type 2 diabetes mellitus is the most common form of diabetes mellitus (90% of cases) and is characteristically multifactorial, with both genetic and environmental causes. Diabetes patients display a significant increase in the risk of developing cardiovascular disease compared to the rest of the population. This is associated with increased blood clotting, which results in circulatory complications and vascular damage. Platelets are circulating cells within the vascular system that contribute to hemostasis. Their increased tendency to activate and form thrombi has been observed in diabetes mellitus patients (i.e., platelet hyperactivity). The oxidative damage of platelets and the function of pro-oxidant enzymes such as the NADPH oxidases appear central to diabetes-dependent platelet hyperactivity. In addition to platelet hyperactivity, endothelial cell damage and alterations of the coagulation response also participate in the vascular damage associated with diabetes. Here, we present an updated interpretation of the molecular mechanisms underlying vascular damage in diabetes, including current therapeutic options for its control.

MAPK/AP-1-Targeted Anti-Inflammatory Activities of Xanthium strumarium

2016 ◽  
Vol 44 (06) ◽  
pp. 1111-1125 ◽  
Author(s):  
Muhammad Jahangir Hossen ◽  
Mi-Yeon Kim ◽  
Jae Youl Cho
Keyword(s):  
Mouse Model ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Elevated Serum ◽  
Human Monocyte ◽  
Serum Levels ◽  
Mitogen Activated Protein Kinase ◽  
Xanthium Strumarium ◽  
U937 Cells ◽  
Anti Inflammatory

Xanthium strumarium L. (Asteraceae), a traditional Chinese medicine, is prescribed to treat arthritis, bronchitis, and rhinitis. Although the plant has been used for many years, the mechanism by which it ameliorates various inflammatory diseases is not yet fully understood. To explore the anti-inflammatory mechanism of methanol extracts of X. strumarium (Xs-ME) and its therapeutic potential, we used lipopolysaccharide (LPS)-stimulated murine macrophage-like RAW264.7 cells and human monocyte-like U937 cells as well as a LPS/D-galactosamine (GalN)-induced acute hepatitis mouse model. To find the target inflammatory pathway, we used holistic immunoblotting analysis, reporter gene assays, and mRNA analysis. Xs-ME significantly suppressed the up-regulation of both the activator protein (AP)-1-mediated luciferase activity and the production of LPS-induced proinflammatory cytokines, including interleukin (IL)-1[Formula: see text], IL-6, and tumor necrosis factor (TNF)-[Formula: see text]. Moreover, Xs-ME strongly inhibited the phosphorylation of mitogen-activated protein kinase (MAPK) in LPS-stimulated RAW264.7 and U937 cells. Additionally, these results highlighted the hepatoprotective and curative effects of Xs-ME in a mouse model of LPS/D-GalN-induced acute liver injury, as assessed by elevated serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and histological damage. Therefore, our results strongly suggest that the ethnopharmacological roles of Xs-ME in hepatitis and other inflammatory diseases might result from its inhibitory activities on the inflammatory signaling of MAPK and AP-1.

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