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.

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).

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.

Discovery and development of labdane-oxindole hybrids as small-molecule inhibitors against chikungunya virus infection.

Chikungunya virus (CHIKV) infection, a febrile illness caused by a mosquito-transmitted alphavirus, has afflicted millions of people worldwide. There is currently no approved effective antiviral treatment for CHIKV infection. In this study, we report a new class of small-molecule CHIKV inhibitors, the oxindole-labdanes, that potently block the replication of CHIKV with good selectivity.

Polypharmacology of andrographolide: beyond one molecule one target.

Covering: 1951 to 2020Andrographolide is one of the most widely studied plant secondary metabolites, known to display diverse pharmacological actions. Current literature has documented a sizeable list of pharmacological targets for andrographolide, suggesting its multi-targeting nature. Many of these targets are central to the pathophysiology of highly prevalent diseases such as cardiovascular diseases, neurodegenerative disorders, autoimmunity, and even cancer.

From irreversible to reversible covalent inhibitors: Harnessing the andrographolide scaffold for anti-inflammatory action.

Covalent drugs with prolonged actions often show superior potency, yet integrated strategies for optimizing their structural and electronic features are lacking. Herein, we present our effort directed towards understanding the contribution of chemical reactivity to biological potency to rationally design new covalent inhibitors based on the ent-ladane andrographolide scaffold for anti-inflammatory action. Specifically, a series of andrographolide derivatives comprising various Michael acceptors was developed and their thiol reactivity was assayed under various chemical and biological conditions.

The identification of naturally occurring labdane diterpenoid calcaratarin D as a potential anti-inflammatory agent.

In this study we report, for the first time, the synthesis of the natural product calcaratarin D via a stereo- and regio-selective aldol condensation with (S)-β-hydroxy-γ-butyrolactone as key steps. A concise synthetic route (under 10 steps) to a series of structurally related normal-labdane diterpenes was also developed and their anti-inflammatory activities were evaluated in an in vitro model of inflammation. The structure-activity relationships (SARs) pertaining to the labdane scaffold were elucidated and results suggest that an α-alkylidene-β-hydroxy-γ-butyrolactone system is necessary for potent activity in the labdanes.

Labdane diterpenoids as potential anti-inflammatory agents.

The search for new anti-inflammatory agents is challenging due to the complexity of the inflammatory process and its role in host defense. Over the past few decades, a significant body of evidence has emerged, supporting the prominent role of labdane diterpenoids in therapeutic interventions of various inflammatory diseases. The anti-inflammatory activity of labdane diterpenoids has been attributed mainly to the inhibition of nuclear factor-κB (NF-κB) activity, the modulation of arachidonic acid (AA) metabolism and the reduction of nitric oxide (NO) production.