Direct vagus nerve stimulation: A new tool to control allergic airway inflammation through α7 nicotinic acetylcholine receptor.

Background And Purpose: Asthma is characterized by airway inflammation, mucus hypersecretion, and airway hyperresponsiveness. The use of nicotinic agents to mimic the cholinergic anti-inflammatory pathway (CAP) controls experimental asthma. Yet, the effects of vagus nerve stimulation (VNS)-induced CAP on allergic inflammation remain unknown.

Natural Products for the Management of Asthma and COPD.

Chronic airway inflammatory diseases like asthma, chronic obstructive pulmonary disease (COPD), and their associated exacerbations cause significant socioeconomic burden. There are still major obstacles to effective therapy for controlling severe asthma and COPD progression. Advances in understanding the pathogenesis of the two diseases at the cellular and molecular levels are essential for the development of novel therapies.

Isthmin-1 attenuates allergic Asthma by stimulating adiponectin expression and alveolar macrophage efferocytosis in mice.

Background: Allergic asthma is a common respiratory disease that significantly impacts human health. Through in silico analysis of human lung RNASeq, we found that asthmatic lungs display lower levels of Isthmin-1 (ISM1) expression than healthy lungs. ISM1 is an endogenous anti-inflammatory protein that is highly expressed in mouse lungs and bronchial epithelial cells, playing a crucial role in maintaining lung homeostasis.

Dexamethasone protects against Aspergillus fumigatus-induced severe asthma via modulating pulmonary immunometabolism.

Severe asthma is a difficult-to-treat chronic airway inflammatory disease requiring systemic corticosteroids to achieve asthma control. It has recently been shown that drugs targeting immunometabolism have elicited anti-inflammatory effects. The purpose of this study was to investigate potential immunometabolic modulatory actions of systemic dexamethasone (Dex) in an Aspergillus fumigatus (Af)-induced severe asthma model.

Degradation of MK2 with natural compound andrographolide: A new modality for anti-inflammatory therapy.

The p38-MK2 signaling axis functions as an initiator of inflammation. Targeting the p38-MK2 signaling axis represents a direct therapeutic intervention of inflammatory diseases. We described here a novel role of andrographolide (AG), a small-molecule ent-labdane natural compound, as an inhibitor of p38-MK2 axis via MK2 degradation.

Multifunctional Antibacterial Nanonets Attenuate Inflammatory Responses through Selective Trapping of Endotoxins and Pro-Inflammatory Cytokines.

Extracellular lipopolysaccharide (LPS) released from bacteria cells can enter the bloodstream and cause septic complications with excessive host inflammatory responses. Target-specific strategies to inactivate inflammation mediators have largely failed to improve the prognosis of septic patients in clinical trials. By utilizing their high density of positive charges, de novo designed peptide nanonets are shown to selectively entrap the negatively charged LPS and pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6).

Calcaratarin D, a labdane diterpenoid, attenuates mouse asthma via modulating alveolar macrophage function.

Background And Purpose: Alveolar macrophages (AMs) contribute to airway inflammation and remodelling in allergic asthma. Calcaratarin D (CalD), a labdane diterpenoid from rhizomes of the medicinal plant Alpinia calcarata, has recently been shown to possess anti-inflammatory properties. The present study evaluated protective effects of CalD in a house dust mite (HDM)-induced asthma mouse model.

Angiotensin II type-2 receptor activation in alveolar macrophages mediates protection against cigarette smoke-induced chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally. Cumulative evidence has implicated renin-angiotensin system (RAS) in the pathogenesis of COPD. Alveolar macrophages (AMs) are the first line immune defense in the respiratory system and play a critical role in the lung homeostasis.

ISM1 suppresses LPS-induced acute lung injury and post-injury lung fibrosis in mice.

Background: Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) are clinical syndromes characterized by acute lung inflammation, pulmonary edema and hypoxemia, with up to 50% mortality rate without effective pharmacological therapy. Following the acute inflammation, repair and remodeling occurs which in some cases resulting in lung fibrosis. The pathophysiology of ALI/ARDS remains incompletely understood.

ISM1 protects lung homeostasis via cell-surface GRP78-mediated alveolar macrophage apoptosis.

Alveolar macrophages (AMs) are critical for lung immune defense and homeostasis. They are orchestrators of chronic obstructive pulmonary disease (COPD), with their number significantly increased and functions altered in COPD. However, it is unclear how AM number and function are controlled in a healthy lung and if changes in AMs without environmental assault are sufficient to trigger lung inflammation and COPD.

Activation of angiotensin II type-2 receptor protects against cigarette smoke-induced COPD.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally. Cumulative evidence has implicated renin-angiotensin system (RAS) in the pathogenesis of COPD. This study aimed to investigate potential protective effects of angiotensin II type-2 receptor (AT2R) activation in cigarette smoke (CS)-induced COPD models.

Restoration of HDAC2 and Nrf2 by andrographolide overcomes corticosteroid resistance in chronic obstructive pulmonary disease.

Background And Purpose: Corticosteroid resistance poses a major barrier to an effective anti-inflammatory therapy for chronic obstructive pulmonary disease (COPD). The present study aimed to investigate potential corticosteroid re-sensitization actions of andrographolide, a bioactive molecule from the herb Andrographis paniculata, in COPD models, particularly in peripheral blood mononuclear cells (PBMCs) from COPD patients.

Experimental Approach: Corticosteroid sensitivity in PBMCs collected from COPD patients, or in human monocytic U937 cells exposed to cigarette smoke extract (CSE), was determined by measuring LPS-induced IL-8 production, in the presence and absence of andrographolide.

Gene silencing of receptor-interacting protein 2 protects against cigarette smoke-induced acute lung injury.

Background And Purpose: Chronic obstructive pulmonary disease (COPD) is characterized by progressive alveolar damage and generally irreversible airflow limitation. Nuclear factor-κB (NF-κB) plays a critical role in COPD pathogenesis. Receptor-interacting protein 2 (Rip2), a 60 kDa adaptor protein, is a positive regulator of NF-κB pathway and also an inducible transcriptional product of NF-κB activation.

Andrographolide simultaneously augments Nrf2 antioxidant defense and facilitates autophagic flux blockade in cigarette smoke-exposed human bronchial epithelial cells.

Cigarette smoking is the leading cause of chronic obstructive pulmonary disease (COPD). Cigarette smoke heightens oxidative stress and impairs autophagy, advancing COPD progression. Andrographolide is a bioactive diterpenoid lactone isolated from the plant Andrographis paniculata which has been a traditional medicinal herb for respiratory diseases.

Ribosomal Protein S3 Gene Silencing Protects Against Cigarette Smoke-Induced Acute Lung Injury.

Chronic obstructive pulmonary disease (COPD) is estimated to be the third leading cause of death by 2030. Transcription factor NF-κB may play a critical role in COPD pathogenesis. Ribosomal protein S3 (RPS3), a 40S ribosomal protein essential for executing protein translation, has recently been found to interact with the NF-κB p65 subunit and promote p65 DNA-binding activity.

Targeting the renin-angiotensin system as novel therapeutic strategy for pulmonary diseases.

The renin-angiotensin system (RAS) plays a major role in regulating electrolyte balance and blood pressure. RAS has also been implicated in the regulation of inflammation, proliferation and fibrosis in pulmonary diseases such as asthma, acute lung injury (ALI), chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and pulmonary arterial hypertension (PAH). Current therapeutics suffer from some drawbacks like steroid resistance, limited efficacies and side effects.

Radiation-Induced Dermatitis is Mediated by IL17-Expressing γδ T Cells.

Radiation dermatitis is a serious cutaneous injury caused by radiation therapy or upon accidental nuclear exposure. However, the pathogenic immune mechanisms underlying this injury are still poorly understood. We seek to discover how the dysregulated immune response after irradiation orchestrates skin inflammation.

Is there a future for andrographolide to be an anti-inflammatory drug? Deciphering its major mechanisms of action.

Andrographis paniculata has long been part of the traditional herbal medicine system in Asia and in Scandinavia. Andrographolide was isolated as a major bioactive constituent of A. paniculata in 1951, and since 1984, andrographolide and its analogs have been scrutinized with modern drug discovery approach for anti-inflammatory properties.

Radiation-Induced Dermatitis is Mediated by IL17-Expressing γδ T Cells.

Radiation dermatitis is a serious cutaneous injury caused by radiation therapy or upon accidental nuclear exposure. However, the pathogenic immune mechanisms underlying this injury are still poorly understood. We seek to discover how the dysregulated immune response after irradiation orchestrates skin inflammation.

Oligonucleotide Therapy for Obstructive and Restrictive Respiratory Diseases.

Inhaled oligonucleotide is an emerging therapeutic modality for various common respiratory diseases, including obstructive airway diseases like asthma and chronic obstructive pulmonary disease (COPD) and restrictive airway diseases like idiopathic pulmonary fibrosis (IPF). The advantage of direct accessibility for oligonucleotide molecules to the lung target sites, bypassing systemic administration, makes this therapeutic approach promising with minimized potential systemic side effects. Asthma, COPD, and IPF are common chronic respiratory diseases, characterized by persistent airway inflammation and dysregulated tissue repair and remodeling, although each individual disease has its unique etiology.

Ribosomal protein S3 gene silencing protects against experimental allergic asthma.

Background And Purpose: Ribosomal protein S3 (RPS3) is a 40S ribosomal protein of the S3P family essential for implementing protein translation. RPS3 has recently been found to interact with the p65 subunit of the NF-κB complex and promote p65 DNA-binding activity. Persistent activation of the NF-κB pathway is evident in allergic asthma.

Andrographolide Restores Steroid Sensitivity To Block Lipopolysaccharide/IFN-γ-Induced IL-27 and Airway Hyperresponsiveness in Mice.

LPS and IFN-γ alone or in combination have been implicated in the development of steroid resistance. Combined LPS/IFN-γ strongly upregulates IL-27 production, which has been linked to steroid-resistant airway hyperresponsiveness (AHR). Andrographolide, a bioactive molecule isolated from the plant Andrographis paniculata, has demonstrated anti-inflammatory and antioxidant properties.

Cigarette Smoke-Induced Lung Disease Predisposes to More Severe Infection with Nontypeable Haemophilus influenzae: Protective Effects of Andrographolide.

Cigarette smoke (CS) is associated with many maladies, one of which is chronic obstructive pulmonary disease (COPD). As the disease progresses, patients are more prone to develop COPD exacerbation episodes by bacterial infection, particularly to nontypeable Haemophilus influenza (NTHi) infection. The present study aimed to develop a CS-exposed mouse model that increases inflammation induced by NTHi challenge and investigate the protective effects of andrographolide, a bioactive molecule with anti-inflammatory and antioxidant properties isolated from the plant Andrographis paniculata.

Vitamin E therapy beyond cancer: Tocopherol versus tocotrienol.

The discovery of vitamin E (α-tocopherol) began in 1922 as a vital component required in reproduction. Today, there are eight naturally occurring vitamin E isoforms, namely α-, β-, γ- and δ-tocopherol and α-, β-, γ- and δ-tocotrienol. Vitamin E is potent antioxidants, capable of neutralizing free radicals directly by donating hydrogen from its chromanol ring.