Pinocembrin relieves lipopolysaccharide and bleomycin induced lung inflammation via inhibiting TLR4-NF-κB-NLRP3 inflammasome signaling pathway

Gan, Wenhua; Li, Xiaohe; Cui, Yunyao; Tu, Xiao; Li, Rui; Wang, Ming; Wei, Yiying; Cui, Mengqi; Ren, Shanfa; Helian, Kaiyue; Ning, Wen; Yang, Cheng

doi:10.1016/j.intimp.2020.107230

Cited by 24 publications

(11 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sepsis has long been regarded as the foremost precipitant of AKI, which is attributed to the high susceptibility of the kidney to sepsis ( 2 , 3 ). PINO, a bioactive flavonoid isolated from honey, propolis, wild marjoram and the roots of ginger, possesses multiple biological properties and is recognized as a promising natural small-molecule drug in inflammation-associated diseases ( 8 , 11 , 15 ). The present study was designed to determine the functional roles of PINO in septic AKI, and to investigate the underlying mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…It is worth noting that PINO has been approved by China Food and Drug Administration as a novel drug for ischemic stroke, and it is currently in phase II clinical trials (8)(9)(10). In addition, as a potential anti-inflammatory drug, its ability to control inflammation has been demonstrated in situations of lung injury, liver injury and intestinal injury (11)(12)(13). A previous study has uncovered a role for PINO in attenuating gentamicin-induced nephrotoxicity in rats, suggesting a protective effect for PINO against kidney injury (14).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pinocembrin ameliorates lipopolysaccharide‑induced HK‑2 cell apoptosis and inflammation by regulating endoplasmic reticulum stress

Feng

2022

Exp Ther Med

View full text Add to dashboard Cite

Pinocembrin (PINO) is a natural flavonoid drug that possesses a range of biological activities, including antimicrobial, antioxidant and anti-inflammatory activities. The specific aim of the present study was to examine the pharmacological role of PINO in sepsis-mediated acute kidney injury (AKI), as well as to investigate the potential underlying mechanism. Human renal tubular epithelial cells (of the HK-2 cell line) were stimulated with lipopolysaccharide (LPS) for 24 h to simulate septic AKI in vitro , after which the experiments were repeated and the cells were pretreated with increasing concentrations of PINO (0, 50, 100 and 200 µg/ml). Using an MTT cell viability assay, PINO was revealed to be non-toxic to HK-2 cells. In LPS-treated HK-2 cells, PINO alleviated the loss of cell viability. Western blotting was used to analyze the expression levels of pro-inflammatory cytokines, including IL-1β, IL-6 and TNF-α, and the results revealed that PINO decreased the expression levels of these cytokines in a concentration-dependent manner. Furthermore, malondialdehyde (MDA) and glutathione (GSH) activities were assessed using MDA and GSH assay kits and it was revealed that PINO decreased the significantly increased level of malondialdehyde, while it also decreased the reduction in the level of GSH in LPS-challenged HK-2 cells. In addition, a TUNEL assay and western blotting were performed to examine cell apoptosis, and PINO was identified to significantly inhibit the level of apoptosis in LPS-induced HK-2 cells. Subsequently, the expression levels of endoplasmic reticulum stress (ERS)-associated factors, including activating transcription factor 4, C/EBP homologous protein and phosphorylated/total eukaryotic translation initiation factor 2 subunit 1 were examined by western blotting and it was demonstrated that ERS was triggered in HK-2 cells exposed to LPS, although this was partly circumvented through PINO treatment in a concentration-dependent manner. Furthermore, after the addition of tunicamycin, which acts as an agonist of ERS, the aforementioned experiments were performed again. Tunicamycin led to partial abolition of the protective function of PINO against inflammation, oxidative stress and apoptosis in LPS-challenged HK-2 cells. Overall, the results of the present study demonstrated that PINO was able to ameliorate the injuries sustained by LPS-challenged HK-2 cells via modulating ERS to reduce inflammation, oxidative stress and apoptosis; therefore, PINO may be a novel candidate drug for treating septic AKI.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pinocembrin ameliorates lipopolysaccharide‑induced HK‑2 cell apoptosis and inflammation by regulating endoplasmic reticulum stress

Feng

2022

Exp Ther Med

View full text Add to dashboard Cite

show abstract

“…In animal models where pinocembrin had been found to effectively retard fibrosis that was induced in other organs, pinocembrin also inhibited pro-inflammatory cytokines TNF-α, IL-1β and IL-6 and dampened inflammatory responses via depression of the NF-κβ signalling pathway [ 9 , 10 ]. Further mechanistic studies with mouse LPS and bleomycin models suggested that TLR4 (toll-like receptor 4) and inflammasomes are causally linked to the pinocembrin suppression of NF-κβ inflammatory signalling [ 2 ]. As with all bleomycin-induced models of pulmonary fibrosis, the timing of the drug intervention is crucial for determining the relative anti-fibrotic and anti-inflammatory contributions of the treatment [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

The efficacy and safety of pinocembrin in a sheep model of bleomycin-induced pulmonary fibrosis

et al. 2021

View full text Add to dashboard Cite

The primary flavonoid, pinocembrin, is thought to have a variety of medical uses which relate to its reported anti-oxidant, anti-inflammatory, anti-microbial and anti-cancer properties. Some studies have reported that this flavonoid has anti-fibrotic activities. In this study, we investigated whether pinocembrin would impede fibrosis, dampen inflammation and improve lung function in a large animal model of pulmonary fibrosis. Fibrosis was induced in two localized lung segments in each of the 10 sheep participating in the study. This was achieved via two infusions of bleomycin delivered bronchoscopically at a two-week interval. Another lung segment in the same sheep was left untreated, and was used as a healthy control. The animals were kept for a little over 5 weeks after the final infusion of bleomycin. Pinocembrin, isolated from Eucalyptus leaves, was administered to one of the two bleomycin damaged lung segments at a dose of 7 mg. This dose was given once-weekly over 4-weeks, starting one week after the final bleomycin infusion. Lung compliance (as a measure of stiffness) was significantly improved after four weekly administrations of pinocembrin to bleomycin-damaged lung segments. There were significantly lower numbers of neutrophils and inflammatory cells in the bronchoalveolar lavage of bleomycin-infused lung segments that were treated with pinocembrin. Compared to bleomycin damaged lung segments without drug treatment, pinocembrin administration was associated with significantly lower numbers of immuno-positive CD8+ and CD4+ T cells in the lung parenchyma. Histopathology scoring data showed that pinocembrin treatment was associated with significant improvement in inflammation and overall pathology scores. Hydroxy proline analysis showed that the administration of pinocembrin did not reduce the increased collagen content that was induced by bleomycin in this model. Analyses of Masson’s Trichrome stained sections showed that pinocembrin treatment significantly reduced the connective tissue content in lung segments exposed to bleomycin when compared to bleomycin-infused lungs that did not receive pinocembrin. The striking anti-inflammatory and modest anti-fibrotic remodelling effects of pinocembrin administration were likely linked to the compound’s ability to improve lung pathology and functional compliance in this animal model of pulmonary fibrosis.

show abstract

“…Pinocembrin (5,7-dihydroxyflavanone) is a natural flavanone present in fruits, spices, propolis, tea, and red wine and has shown beneficial properties, including anti-inflammatory potential [ 13 , 14 ]. A recent in vivo study proved the ability of pinocembrin to inhibit the LPS-stimulated inflammatory response in macrophages and to regulate the TLR4-NF-κB signaling pathway [ 15 ]. Furthermore, pinocembrin is also found in pine species that are exploited for their wood [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Investigation of Flavanone Derivatives as Potential New Anti-Inflammatory Agents

et al. 2022

View full text Add to dashboard Cite

Flavonoids are polyphenols with broad known pharmacological properties. A series of 2,3-dihydroflavanone derivatives were thus synthesized and investigated for their anti-inflammatory activities. The target flavanones were prepared through cyclization of 2′-hydroxychalcone derivatives, the later obtained by Claisen–Schmidt condensation. Since nitric oxide (NO) represents an important inflammatory mediator, the effects of various flavanones on the NO production in the LPS-induced RAW 264.7 macrophage were assessed in vitro using the Griess test. The most active compounds were flavanone (4G), 2′-carboxy-5,7-dimethoxy-flavanone (4F), 4′-bromo-5,7-dimethoxy-flavanone (4D), and 2′-carboxyflavanone (4J), with IC50 values of 0.603, 0.906, 1.030, and 1.830 µg/mL, respectively. In comparison, pinocembrin achieved an IC50 value of 203.60 µg/mL. Thus, the derivatives synthesized in this work had a higher NO inhibition capacity compared to pinocembrin, demonstrating the importance of pharmacomodulation to improve the biological potential of natural molecules. SARs suggested that the use of a carboxyl-group in the meta-position of the B-ring increases biological activity, whereas compounds carrying halogen substituents in the para-position were less active. The addition of methoxy-groups in the meta-position of the A-ring somewhat decreased the activity. This study successfully identified new bioactive flavanones as promising candidates for the development of new anti-inflammatory agents.

show abstract

Pinocembrin relieves lipopolysaccharide and bleomycin induced lung inflammation via inhibiting TLR4-NF-κB-NLRP3 inflammasome signaling pathway

Cited by 24 publications

References 35 publications

Pinocembrin ameliorates lipopolysaccharide‑induced HK‑2 cell apoptosis and inflammation by regulating endoplasmic reticulum stress

Pinocembrin ameliorates lipopolysaccharide‑induced HK‑2 cell apoptosis and inflammation by regulating endoplasmic reticulum stress

The efficacy and safety of pinocembrin in a sheep model of bleomycin-induced pulmonary fibrosis

Synthesis and Investigation of Flavanone Derivatives as Potential New Anti-Inflammatory Agents

Contact Info

Product

Resources

About