Labdane diterpenoids as potential anti-inflammatory agents

Tran, Quy T.N.; Wong, W.S. Fred; Chai, Christina L. L.

doi:10.1016/j.phrs.2017.07.019

Cited by 74 publications

(41 citation statements)

References 142 publications

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“… 31 It has also been reported that labdane diterpenes bearing an α,β-unsaturated carbonyl group at the decalin unit or a γ-lactone ring (instead of a furan ring) possess high NF-κB inhibitory potential and, therefore, anti-inflammatory activity due to the covalent adduct formation with its Cys62 residue of the p50 subunit. 18 , 31 In one recent study, Khan et al reported that compound 7 can suppress LPS-induced NF-κB activation, which resulted in the downregulation of iNOS and COX-2 protein expression, and in addition, it suppressed TNF-α production. 18 …”

Section: Results and Discussionmentioning

confidence: 99%

Labdane-Type Diterpenes from the Aerial Parts of Rydingia persica: Their Absolute Configurations and Protective Effects on LPS-Induced Inflammation in Keratinocytes

et al. 2020

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Phytochemical investigations of an extract of the aerial parts of Rydingia persica led to the isolation of 14 labdane-type diterpenoids, of which compounds 1 – 5 , 8 , and 12 – 14 turned out to be new natural products, while the remaining compounds were isolated for the first time from the genus Rydingia . Their structures were elucidated using 1D- and 2D-NMR and mass spectrometry, and their absolute configurations were determined by quantum chemical calculation methods. Furthermore, DP4+ NMR chemical shift probability calculations were performed for compounds 12 – 14 , in order to elucidate the orientation of the ambiguous chiral center at C-15, prior to absolute configuration determination. The methanol extract of the aerial parts of R. persica along with subfractions obtained and selected isolated compounds were evaluated for their effects on inflammation-related factors such as nitrotyrosine formation, IL-6 release, and TNF-α release, along with tight-junction proteins claudin-1 and occludin expression in LPS-stimulated HaCaT cells. Occludin and claudin-1 are tight-junction proteins, which play a pivotal role in wound repair mechanisms. Overall, the subfractions and compounds isolated showed moderate to high activity, indicating that labdane-type diterpenoids contribute to the anti-inflammatory and wound-healing activity of R. persica .

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Section: Results and Discussionmentioning

confidence: 99%

Labdane-Type Diterpenes from the Aerial Parts of Rydingia persica: Their Absolute Configurations and Protective Effects on LPS-Induced Inflammation in Keratinocytes

et al. 2020

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“…Andrographolide is a naturally occurring labdane diterpenoid with known anti‐inflammatory activities. It possesses an inhibitory α,β‐unsaturated lactone to form a Michael acceptor system, which is an electrophilic structure that can covalently react with nucleophilic thiol groups in target proteins (Tran, Wong, & Chai, 2017). Andrographolide has been shown to form a covalent adduct with the reduced Cys62 residue of the p50 subunit of the transcription factor NF‐κB through Michael addition reaction, leading to inhibition of the NF‐κB transcriptional activity (Nguyen et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

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

Liao

Lim

Tan

et al. 2020

British J Pharmacology

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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. The mechanisms of corticosteroid re‐sensitization action of andrographolide were evaluated in a mouse cigarette smoke (CS)‐induced acute lung injury model. Key Results Impaired inhibition of IL‐8 production by dexamethasone was detected in PBMCs from COPD patients and in CSE‐exposed U937 cells, together with reduced levels of nuclear factor erythroid 2‐related factor 2 (Nrf2) and histone deacetylase‐2 (HDAC2). In both PBMCs and CSE‐exposed U937 cells, andrographolide restored dexamethasone inhibition of IL‐8 production, accompanied by the up‐regulation of Nrf2 and HDAC2 levels. In the U937 cells, andrographolide was able to block CSE‐induced Akt and reduce the level of c‐Jun. Besides, andrographolide also augmented dexamethasone actions on lowering total and neutrophil counts, cytokine levels, and oxidative damage markers in bronchoalveolar lavage fluid from CS‐exposed mice. Conclusion and Implications We report here for the first time a novel corticosteroid re‐sensitization property of andrographolide in human PBMCs and provide mechanistic evidence to support clinical evaluation of andrographolide in reversing steroid resistance in COPD.

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“…Labdane diterpenes, also known as labdane-like bicyclic diterpenes, are a group of natural products sharing the same structural core and are prolific in various plants, such as Clary sage in our study. A wide variety of biological activities in labdane diterpenes have been identified, such as antimicrobial, antifungal, anti-inflammatory, and immunomodulatory functions [ 7 , 8 , 9 , 10 ]. Sclareol (labd-14-ene-8, 13-diol) is a member of bioactive labdane-type diterpenes, extracted from the leaves and flowers of Clary sage ( Salvia sclarea L.) of the Lamiaceae family, one commonly cultivated for its essential oil that has been widely used as raw material for food, cosmetic products, and folk medicine.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Potential of Sclareol in Experimental Models of Rheumatoid Arthritis

Tsai

Hsieh

et al. 2018

IJMS

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Previous studies have shown that the natural diterpene compound, sclareol, potentially inhibits inflammation, but it has not yet been determined whether sclareol can alleviate inflammation associated with rheumatoid arthritis (RA). Here, we utilized human synovial cell line, SW982, and an experimental murine model of rheumatoid arthritis, collagen-induced arthritis (CIA), to evaluate the therapeutic effects of sclareol in RA. Arthritic DBA/1J mice were dosed with 5 and 10 mg/kg sclareol intraperitoneally every other day over 21 days. Arthritic severity was evaluated by levels of anti-collagen II (anti-CII) antibody, inflammatory cytokines, and histopathologic examination of knee joint tissues. Our results reveal that the serum anti-CII antibody, cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and IL-17, as well as Th17 and Th1 cell population in inguinal lymph nodes, were significantly lower in sclareol-treated mice compared to the control group. Also, the sclareol treatment groups showed reduced swelling in the paws and lower histological arthritic scores, indicating that sclareol potentially mitigates collagen-induced arthritis. Furthermore, IL-1β-stimulated SW982 cells secreted less inflammatory cytokines (TNF-α and IL-6), which is associated with the downregulation of p38-mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), and NF-κB pathways. Overall, we demonstrate that sclareol could relieve arthritic severities by modulating excessive inflammation and our study merits the pharmaceutical development of sclareol as a therapeutic treatment for inflammation associated with RA.

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Labdane diterpenoids as potential anti-inflammatory agents

Cited by 74 publications

References 142 publications

Labdane-Type Diterpenes from the Aerial Parts of Rydingia persica: Their Absolute Configurations and Protective Effects on LPS-Induced Inflammation in Keratinocytes

Labdane-Type Diterpenes from the Aerial Parts of Rydingia persica: Their Absolute Configurations and Protective Effects on LPS-Induced Inflammation in Keratinocytes

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

Therapeutic Potential of Sclareol in Experimental Models of Rheumatoid Arthritis

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