Inhibitory Role of Berberine, an Isoquinoline Alkaloid, on NLRP3 Inflammasome Activation for the Treatment of Inflammatory Diseases
TL;DR: The pyrin domain-containing multiprotein complex NLRP3 inflammasome plays a vital role in the pathophysiology of several inflammatory disorders, including neurological and metabolic disorders, chronic inflammatory diseases, and cancer.
Abstract: The pyrin domain-containing multiprotein complex NLRP3 inflammasome, consisting of the NLRP3 protein, ASC adaptor, and procaspase-1, plays a vital role in the pathophysiology of several inflammatory disorders, including neurological and metabolic disorders, chronic inflammatory diseases, and cancer. Several phytochemicals act as promising anti-inflammatory agents and are usually regarded to have potential applications as complementary or alternative therapeutic agents against chronic inflammatory disorders. Various in vitro and in vivo studies have reported the anti-inflammatory role of berberine (BRB), an organic heteropentacyclic phytochemical and natural isoquinoline, in inhibiting NLRP3 inflammasome-dependent inflammation against many disorders. This review summarizes the mechanism and regulation of NLRP3 inflammasome activation and its involvement in inflammatory diseases, and discusses the current scientific evidence on the repressive role of BRB on NLRP3 inflammasome pathways along with the possible mechanism(s) and their potential in counteracting various inflammatory diseases.
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TL;DR: In this article , the authors reviewed the current status of cachexia, the molecular mechanisms of primary events driving cachexia and state-of-the-art knowledge that reports the preventive and therapeutic activities of multiple families of phytochemical compounds and their pharmacological mode of action.
5 citations
TL;DR: In this article , a growing body of evidence has shown that many pathological processes, abnormal concentration of mechanical stress and chloride channel dysfunction in articular cartilage lead to microenvironment disorders, matrix and bone metabolism imbalances, which cause partial aseptic inflammation.
Abstract: Articular cartilage allows the human body to buffer and absorb stress during normal exercise. It is mainly composed of cartilage cells and the extracellular matrix and is surrounded by the extracellular microenvironment formed by synovial fluid and various factors in it. Studies have shown that chondrocytes are the metabolic center of articular cartilage. Under physiological conditions, the extracellular matrix is in a dynamic balance of anabolism and catabolism, and various factors and physical and chemical conditions in the extracellular microenvironment are also in a steady state. This homeostasis depends on the normal function of proteins represented by various ion channels on chondrocytes. In mammalian chondrocyte species, ion channels are mainly divided into two categories: cation channels and anion channels. Anion channels such as chloride channels have become hot research topics in recent years. These channels play an extremely important role in various physiological processes. Recently, a growing body of evidence has shown that many pathological processes, abnormal concentration of mechanical stress and chloride channel dysfunction in articular cartilage lead to microenvironment disorders, matrix and bone metabolism imbalances, which cause partial aseptic inflammation. These pathological processes initiate extracellular matrix degradation, abnormal chondrocyte death, hyperplasia of inflammatory synovium and bony. Osteoarthritis (OA) is a common clinical disease in orthopedics. Its typical manifestations are joint inflammation and pain caused by articular cartilage degeneration, but its pathogenesis has not been fully elucidated. Focusing on the physiological functions and pathological changes of chloride channels and pathophysiology of aseptic inflammation furthers the understanding of OA pathogenesis and provides possible targets for subsequent medication development.
4 citations
Journal Article•
01 Jan 2022TL;DR: In this article , Follistatin-like 1 (FSTL-1) has been reported to have anti-inflammatory and anti-apoptotic effects in a variety of diseases.
Abstract: Severe acute pancreatitis (SAP) is one of the most common abdominal conditions of digestive system that usually causes acute lung injury through systemic inflammation. Follistatin-like 1 (FSTL-1) has been reported to have anti-inflammatory and anti-apoptotic effects in a variety of diseases. The aim of this study was to investigate the effects of FSTL-1 on SAP-associated lung injury (SAPALI) and the underlying mechanism.SAP model was induced by intraperitoneal injection of the L-arginine in C57BL/6 mice. The haematoxylin and eosin (H&E) staining was applied to determine the severity of lung and pancreatic injury. ELISA kits were used to determine serum amylase and inflammatory cytokines levels. TUNEL staining was carried out to measure cell apoptosis. Western blotting was applied to analyze the related proteins of NLRP3 inflammasome and NF-κB pathways.FSTL-1 was significantly increased in the lung of SAP mice. Knockout of FSTL-1 ameliorated pancreatic injury, lung injury, inflammation and apoptosis in mice with SAP. Moreover, the protein levels of NLRP3, ASC, Caspase-1, p-p65 and p-IκBα were obviously reduced in the FSTL-1 KO+SAP group in comparison with SAP group, suggesting that inhibition of FSTL-1 repressed the activation of the NLRP3 inflammasome and NF-κB pathway.This study helps us understand the mechanism of FSTL-1 in SAPALI and might provide a potential new strategy for the treatment of SAPALI.
1 citations
TL;DR: In this paper , a review of well-known plant-derived biomolecules and their potential as immunomodulators for cancer treatment is presented. But, the authors do not discuss the potential of these biomolecular compounds as immunotherapies for cancer patients.
Abstract: Despite advancements in chemotherapy, the issue of resistance and non-responsiveness to many chemotherapeutic drugs that are currently in clinical use still remains. Recently, cancer immunotherapy has gathered attention as a novel treatment against select cancers. Immunomodulation is also emerging as an effective strategy to improve efficacy. Natural phytochemicals, with known anticancer properties, been reported to mediate their effects by modulating both traditional cancer pathways and immunity. The mechanism of phytochemical mediated-immunomodulatory activity may be attributed to the remodeling of the tumor immunosuppressive microenvironment and the sensitization of the immune system. This allows for improved recognition and targeting of cancer cells by the immune system and synergy with chemotherapeutics. In this review, we will discuss several well-known plant-derived biomolecules and examine their potential as immunomodulators, and therefore, as novel immunotherapies for cancer treatment.
1 citations
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TL;DR: The NLRP3 inflammasome mediates pro-inflammatory responses and pyroptotic cell death and how it is being targeted to treat inflammatory diseases is described.
Abstract: NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) is an intracellular sensor that detects a broad range of microbial motifs, endogenous danger signals and environmental irritants, resulting in the formation and activation of the NLRP3 inflammasome. Assembly of the NLRP3 inflammasome leads to caspase 1-dependent release of the pro-inflammatory cytokines IL-1β and IL-18, as well as to gasdermin D-mediated pyroptotic cell death. Recent studies have revealed new regulators of the NLRP3 inflammasome, including new interacting or regulatory proteins, metabolic pathways and a regulatory mitochondrial hub. In this Review, we present the molecular, cell biological and biochemical bases of NLRP3 activation and regulation and describe how this mechanistic understanding is leading to potential therapeutics that target the NLRP3 inflammasome.
2,097 citations
TL;DR: This Review discusses the recent developments in inflammasome research with a focus on the molecular mechanisms that govern inflammaome assembly, signalling and regulation.
Abstract: Inflammasomes are multiprotein signalling platforms that control the inflammatory response and coordinate antimicrobial host defences. They are assembled by pattern-recognition receptors following the detection of pathogenic microorganisms and danger signals in the cytosol of host cells, and they activate inflammatory caspases to produce cytokines and to induce pyroptotic cell death. The clinical importance of inflammasomes reaches beyond infectious disease, as dysregulated inflammasome activity is associated with numerous hereditary and acquired inflammatory disorders. In this Review, we discuss the recent developments in inflammasome research with a focus on the molecular mechanisms that govern inflammasome assembly, signalling and regulation.
2,084 citations
TL;DR: The functions of the different inflammasome complexes are reviewed and how aberrations in them are implicated in the pathogenesis of human diseases are discussed.
Abstract: Inflammasomes are a group of protein complexes built around several proteins, including NLRP3, NLRC4, AIM2 and NLRP6. Recognition of a diverse range of microbial, stress and damage signals by inflammasomes results in direct activation of caspase-1, which subsequently induces secretion of potent pro-inflammatory cytokines and a form of cell death called pyroptosis. Inflammasome-mediated processes are important during microbial infections and also in regulating both metabolic processes and mucosal immune responses. We review the functions of the different inflammasome complexes and discuss how aberrations in them are implicated in the pathogenesis of human diseases.
1,871 citations
Lawrence Berkeley National Laboratory1, Buck Institute for Research on Aging2, Lund University3, University of California, San Francisco4, National Institutes of Health5, University College London6, Harvard University7, Columbia University Medical Center8, Emory University9, University of Milan10, Humanitas University11, Queen Mary University of London12, Stanford University13, Albert Einstein College of Medicine14, Veterans Health Administration15, University of California, Los Angeles16, European University of Madrid17
TL;DR: The multi-level mechanisms underlying SCI and several risk factors that promote this health-damaging phenotype, including infections, physical inactivity, poor diet, environmental and industrial toxicants and psychological stress are described.
Abstract: Although intermittent increases in inflammation are critical for survival during physical injury and infection, recent research has revealed that certain social, environmental and lifestyle factors can promote systemic chronic inflammation (SCI) that can, in turn, lead to several diseases that collectively represent the leading causes of disability and mortality worldwide, such as cardiovascular disease, cancer, diabetes mellitus, chronic kidney disease, non-alcoholic fatty liver disease and autoimmune and neurodegenerative disorders. In the present Perspective we describe the multi-level mechanisms underlying SCI and several risk factors that promote this health-damaging phenotype, including infections, physical inactivity, poor diet, environmental and industrial toxicants and psychological stress. Furthermore, we suggest potential strategies for advancing the early diagnosis, prevention and treatment of SCI.
1,708 citations
TL;DR: Current understanding of the mechanisms ofNLRP3 inflammasome activation by multiple signaling events, and its regulation by post-translational modifications and interacting partners of NLRP3 are summarized.
Abstract: The NLRP3 inflammasome is a critical component of the innate immune system that mediates caspase-1 activation and the secretion of proinflammatory cytokines IL-1β/IL-18 in response to microbial infection and cellular damage. However, the aberrant activation of the NLRP3 inflammasome has been linked with several inflammatory disorders, which include cryopyrin-associated periodic syndromes, Alzheimer’s disease, diabetes, and atherosclerosis. The NLRP3 inflammasome is activated by diverse stimuli, and multiple molecular and cellular events, including ionic flux, mitochondrial dysfunction, and the production of reactive oxygen species, and lysosomal damage have been shown to trigger its activation. How NLRP3 responds to those signaling events and initiates the assembly of the NLRP3 inflammasome is not fully understood. In this review, we summarize our current understanding of the mechanisms of NLRP3 inflammasome activation by multiple signaling events, and its regulation by post-translational modifications and interacting partners of NLRP3.
1,486 citations