LPS and ATP-induced Death of PMA-differentiated THP-1 Macrophages and its Validation.

Cell death is a fundamental process in all living organisms. The protocol establishes a lipopolysaccharide (LPS) and adenosine triphosphate (ATP)-induced phorbol-12-myristate-13-acetate (PMA)-differentiated lipid deposition in human monocyte (THP-1) macrophage model to observe cell death. LPS combined with ATP is a classic inflammatory induction method, often used to study pyroptosis, but apoptosis and necroptosis also respond to stimulation by LPS/ATP.

The Scutellaria-Coptis herb couple and its active small-molecule ingredient wogonoside alleviate cytokine storm by regulating the CD39/NLRP3/GSDMD signaling pathway.

Ethnopharmacological Relevance: A drug pair is a fundamental aspect of traditional Chinese medicine prescriptions. Scutellaria baicalensis Georgi and Coptis chinensis Franch, commonly used as an herb couple (SBCC), are representative heat-clearing and dampness-drying drugs. They possess functions such as clearing heat, drying dampness, purging fire, and detoxifying.

Traditional Chinese medicine in regulating macrophage polarization in immune response of inflammatory diseases.

Ethnopharmacological Relevance: Numerous studies have demonstrated that various traditional Chinese medicines (TCMs) exhibit potent anti-inflammatory effects against inflammatory diseases mediated through macrophage polarization and metabolic reprogramming.

Aim Of The Study: The objective of this review was to assess and consolidate the current understanding regarding the pathogenic mechanisms governing macrophage polarization in the context of regulating inflammatory diseases. We also summarize the mechanism action of various TCMs on the regulation of macrophage polarization, which may contribute to facilitate the development of natural anti-inflammatory drugs based on reshaping macrophage polarization.

Electroacupuncture Alleviates Lung Injury in CpG1826-Challenged Mice via Modulating CD39-NLRP3 Pathway.

Purpose: Cytokine storm secondary lung injury (CSSLI) is the leading death cause in COVID-19 virus infection, and CD39-dominated purinergic brake drives NLRP3 inflammasome activation and pyroptosis, which plays a crucial role in the pathogenesis of CSSLI. Though electroacupuncture (EA) can alleviate lung injury caused by a variety of inducers, its effect on CSSLI and the underlying mechanism needs further investigation.

Methods: We established a widely recognized CSSLI mice model with CpG1826 (CpG), a TLR-9 agonist agent.

Sepsis-Induced Acute Lung Injury Is Alleviated by Small Molecules from Dietary Plants via Pyroptosis Modulation.

Sepsis-induced acute respiratory distress syndrome (ARDS) has high morbidity and mortality, and it has three major pathogeneses, namely alveolar-capillary barrier destruction, elevated gut permeability, and reduced neutrophil extracellular traps (NETS), all of which are pyroptosis-involved. Due to limitations of current agents like adverse reaction superposition, inevitable drug resistance, and relatively heavier financial burden, naturally extracted small-molecule compounds have a broad market even though chemically modified drugs have straightforward efficacy. Despite increased understanding of the molecular biology and mechanism underlying sepsis-induced ARDS, there are no specific reviews concerning how small molecules from dietary plants alleviate sepsis-induced acute lung injury (ALI) via regulating pyroptotic cell death.

UDP-glucose sensing P2YR: A novel target for inflammation.

Uridine 5'-diphosphoglucose (UDP-G) as a preferential agonist, but also other UDP-sugars, such as UDP galactose, function as extracellular signaling molecules under conditions of cell injury and apoptosis. Consequently, UDP-G is regarded to function as a damage-associated molecular pattern (DAMP), regulating immune responses. UDP-G promotes neutrophil recruitment, leading to the release of pro-inflammatory chemokines.

CD73: Friend or Foe in Lung Injury.

Ecto-5'-nucleotidase (CD73) plays a strategic role in calibrating the magnitude and chemical nature of purinergic signals that are delivered to immune cells. Its primary function is to convert extracellular ATP to adenosine in concert with ectonucleoside triphosphate diphosphohydrolase-1 (CD39) in normal tissues to limit an excessive immune response in many pathophysiological events, such as lung injury induced by a variety of contributing factors. Multiple lines of evidence suggest that the location of CD73, in proximity to adenosine receptor subtypes, indirectly determines its positive or negative effect in a variety of organs and tissues and that its action is affected by the transfer of nucleoside to subtype-specific adenosine receptors.

The cardioprotective potentials and the involved mechanisms of phenolic acids in drug-induced cardiotoxicity.

Cardiotoxicity is one of the major safety concerns in the use of drug and is the most common reason for drug removal from the market. At present, several drugs that have been recognized as the clinically effective drug have been reported to be associated with a high risk of cardiotoxicity during clinical use. The most representative ones are doxorubicin, arsenic trioxide, isoproterenol, cyclophosphamide, etc.

Scutellaria baicalensis georgi is a promising candidate for the treatment of autoimmune diseases.

Autoimmune diseases a group of disorders elicited by unexpected outcome of lymphocytes self-tolerance failure, and the common members of which include multiple sclerosis, systemic lupus erythematosus, inflammatory bowel disease, rheumatoid arthritis, and type 1 diabetes mellitus, etc. The pathogenesis of autoimmune diseases is not fully understood and the current therapeutic regimen's inefficacy in certain cases coupled with low rates of success, exorbitant financial burden, as well as numerous side effects, which do open new avenues for the role of natural products as novel therapeutic agents for auto-inflammatory disorders. Scutellaria baicalensis Georgi is a well-known and widely-recognized herbal medicine with certain ameliorative effect on diverse inflammation-involved dysfunction.

Cytokine storm-calming property of the isoquinoline alkaloids in Franch.

Coronavirus disease (COVID-19) has spread worldwide and its effects have been more devastating than any other infectious disease. Importantly, patients with severe COVID-19 show conspicuous increases in cytokines, including interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, IL-8, tumor necrosis factor (TNF)-α, IL-1, IL-18, and IL-17, with characteristics of the cytokine storm (CS). Although recently studied cytokine inhibitors are considered as potent and targeted approaches, once an immunological complication like CS happens, anti-viral or anti-inflammation based monotherapy alone is not enough.

Sennoside A is a novel inhibitor targeting caspase-1.

The assembly of inflammasomes drives caspase-1 activation, which further promotes proinflammatory cytokine secretion and downstream pyroptosis. The discovery of novel caspase-1 inhibitors is pivotal to developing new therapeutic means for inflammasome-involved diseases. In our present study, sennoside A (Sen A), a popular ingredient in multiple weight-loss medicines and dietary supplements, is found to potently inhibit the enzymatic activity of caspase-1 .

Pivotal regulatory roles of traditional Chinese medicine in ischemic stroke via inhibition of NLRP3 inflammasome.

Ethnopharmacological Relevance: Many studies have demonstrated the powerful neuroprotection abilities of multiple traditional Chinese medicines (TCMs) against NLRP3 inflammasome-mediated ischemic cerebral injury. These TCMs may be in the form of TCM prescriptions, Chinese herbal medicines and their extracts, and TCM monomers.

Aim Of The Study: This review aimed to analyze and summarize the existing knowledge on the assembly and activation of the NLRP3 inflammasome and its role in the pathogenesis of ischemic stroke (IS).

Huang-Lian-Jie-Du decoction attenuates cognitive dysfunction of rats with type 2 diabetes by regulating autophagy and NLRP3 inflammasome activation.

Ethnopharmacological Relevance: Huang-Lian-Jie-Du decoction (HLJDD) is a traditional Chinese formula that is efficacious in treating diabetes mellitus, Alzheimer's disease, and diabetic encephalopathy; the underlying mechanisms of HLJDD in diabetes-associated cognitive dysfunction remain unclear.

Aim Of The Study: This study investigated the neuroprotective effects of HLJDD on cognitive function, and the possible underlying mechanisms in type 2 diabetes mellitus (T2DM) in a rat model of cognitive impairment.

Materials And Methods: Twelve active ingredients in HLJDD were detected using high-performance liquid chromatography analysis.

Updates and advances on pharmacological properties of Taraxacum mongolicum Hand.-Mazz and its potential applications.

As a well-recognized dietary and medicinal plant, Taraxacum mongolicum Hand.-Mazz (TMHM) has been used for making wines, candies, energy drinks, and other functional foods. The TMHM contains a diverse range of active phytoconstituents, including flavonoids, triterpenoids, phenolic acids, sesquiterpene lactones, pigments, coumarins and sterols.

Therapeutic potential of Scutellaria baicalensis Georgi in lung cancer therapy.

Background: Globally, lung cancer is the leading cause of cancer associated mortalities. The current conventional chemotherapy remains the preferred treatment option for lung cancer, as surgical resection plays little role in the treatment of over 75% of lung cancer patients. Therefore, there is a need to develop novel potential therapeutic drugs or adjuvants with a high efficiency and safety against lung cancer.

Assessment of the anti-inflammatory effects of three rhubarb anthraquinones in LPS-Stimulated RAW264.7 macrophages using a pharmacodynamic model and evaluation of the structure-activity relationships.

Ethnopharmacological Relevance: Rhubarb (Rhei Radix et Rhizoma) is a traditional Chinese medicine, has been used as a strong astringent in China to treat inflammation-related diseases, such as acute pancreatitis, acute cholecystitis, appendicitis and so on. Rhein, emodin and aloe-emodin are the important active anthraquinone in rhubarb, and are considered to be the main ingredients contributing to anti-inflammatory.

Aim Of The Study: Rhein, emodin and aloe-emodin, anthraquinones with the same parent structure that are found in rhubarb, have beneficial anti-inflammatory effects in vitro and in vivo.

Pyroptosis by caspase-11 inflammasome-Gasdermin D pathway in autoimmune diseases.

Inflammasomes are a group of supramolecular complexes primarily comprise a sensor, adaptor protein and an effector. Among them, canonical inflammasomes are assembled by one specific pattern recognition receptor, the adaptor protein apoptosis-associated speck-like protein containing a CARD and procaspase-1. Murine caspase-11 and its human ortholog caspase-4/5 are identified as cytosolic sensors which directly responds to LPS.

Therapeutic effect of berberine on metabolic diseases: Both pharmacological data and clinical evidence.

The increased incidence of metabolic diseases (e.g., diabetes and obesity) has seriously affected human health and life safety worldwide.

Nanoparticle-Enabled Dual Modulation of Phagocytic Signals to Improve Macrophage-Mediated Cancer Immunotherapy.

Activation of the phagocytosis of macrophages to tumor cells is an attractive strategy for cancer immunotherapy, but the effectiveness is limited by the fact that many tumor cells express an increased level of anti-phagocytic signals (e.g., CD47 molecules) on their surface.

Targeting foam cell formation and macrophage polarization in atherosclerosis: The Therapeutic potential of rhubarb.

Atherosclerosis, a chronic inflammatory disease associated with high morbidity and mortality, is characterized by the accumulation of foam cells in the arterial wall. It has long been acknowledged that the formation of foam cells is caused by excess lipid uptake and abnormal cholesterol metabolism function. And increasing evidence shows that inhibiting foam cell formation is a promising way to suppress the development of atherosclerotic lesions.

Phosphoproteomics and Proteomics Reveal Metabolism as a Key Node in LPS-Induced Acute Inflammation in RAW264.7.

To better understand the acute inflammatory mechanisms, the modulation, and to investigate the key node in predicting inflammatory diseases, high-sensitivity LC-MS/MS-based proteomics and phosphoproteomics approaches were used to identify differential proteins in RAW264.7 macrophages with lipopolysaccharide (LPS). Furthermore, differential proteins and their main biological process, as well as signaling pathways, were analyzed through bioinformatics techniques.

Apoptosis Exerts a Vital Role in the Treatment of Colitis-Associated Cancer by Herbal Medicine.

Colitis-associated cancer (CAC) is known as inflammatory bowel disease (IBD)-developed colorectal cancer, the pathogenesis of which involves the occurrence of apoptosis. Western drugs clinically applied to CAC are often single-targeted and exert many adverse reactions after long-term administration, so it is urgent to develop new drugs for the treatment of CAC. Herbal medicines commonly have multiple components with multiple targets, and most of them are low-toxicity.

The pharmacological properties of chrysophanol, the recent advances.

As a universal Chinese medicine, Rhei Radix et Rhizoma was used for centuries in different fields including pharmaceutical, health care and cosmetics. Chrysophanol (Chr) is one of the most important anthraquinone components isolated from plants of the Rheum genus. Current reports show that in Rheum officinale, Chr is the most abundant free anthraquinone compound [1] and exerts a number of beneficial effects, such as anti-inflammation, anti-cancer, and anti-depressive effects and offers neuroprotection.

Aloe-emodin induces hepatotoxicity by the inhibition of multidrug resistance protein 2.

Background: Aloe-emodin (AE) is among the primary bioactive anthraquinones present in traditional Chinese medicinal plants such as Rheum palmatum L. Multidrug resistance protein 2 (ABCC2/ MRP2) is an important efflux transporter of substances associated with cellular oxidative stress. However, the effects of traditional Chinese medicine on this protein remain unclear.

Vanillin enhances the passive transport rate and absorption of drugs with moderate oral bioavailability in vitro and in vivo by affecting the membrane structure.

Vanillin is a popular flavoring agent in the food, tobacco, and perfume industries. In this paper, we investigated the effect of vanillin on the transport rates of drugs with different levels of permeability (acyclovir, hydrochlorothiazide, propranolol and carbamazepine) through a Caco-2 cell bidirectional transport experiment. We also explored the underlying mechanism using an in silico technique and fluorescence anisotropy measurements.