Costunolide inhibits inflammation in LPS-induced RAW264.7 cells and ameliorates gastric acid reflux-induced esophageal injury in rat model

Abstract

As one of the gastroesophageal reflux disease (GERD), reflux esophagitis (RE) severely affects patients' daily lives. Costunolide (Cos), pertains to a sesquiterpene lactone, performs multiple pharmacological activities including inhibited acute liver injury, anti-inflammation and anti-oxidant. We carried out our study to investigate the anti-inflammatory effect and protective effects of Cos against esophageal tissue damage caused by gastric acid refluxing. The determination of anti-inflammatory effects of Cos were conducted using lipopolysaccharide (LPS)-induced RAW 264.7 cell inflammatory model. The ameliorative effects of Cos on RE were confirmed on RE controlled rats model. The results indicated that Cos reduced nitrite production and inhibited cellular inflammation via regulating the activation of NF-κB. In addition, gastric acid reflux increased expression levels of inflammatory proteins (COX-2, TNF-α and IL-1β) in esophageal tissues, while Cos treatment significantly downregulated the expression of these proteins by inhibiting activation of NF-κB. Furthermore, through observing histological stain, Cos significantly improved esophageal damage caused by gastric acid reflux. Therefore, we suggested that Cos has the potential to be a material of natural drug for the treatment of reflux esophagitis caused by acid reflux.

Antioxidant‐rich fraction of Amomum subulatum fruits mitigates experimental methotrexate‐induced oxidative stress by regulating TNF‐α, IL‐1β, and IL‐6 proinflammatory cytokines

“…One of our previous studies has reported the anti-inflammatory potential of A. subulatum (Drishya et al, 2021). Results of the present study showed acid (Kilic & Yesiloglu, 2013;Pragasam et al, 2013), syringic acid (Li et al, 2018), ferulic acid (Mahmoud et al, 2020), gallic acid (Badhani et al, 2015;Kroes et al, 1992), catechin (Fan et al, 2017), naringenin (Chung et al, 2019;Rashmi et al, 2018), rutin (Selloum et al, 2003;Yang et al, 2008), costunolide (Eliza et al, 2010;Nan et al, 2020), betulin (Lee et al, 2019), villosin (Li et al, 2016), n-hexadecanoic acid (Aparna et al, 2012), and so forth are some of the bioactive phytoconstituents in MEAS, which were reported to exhibit antioxidant/ anti-inflammatory potential. Hence, it can be concluded that the presence of these bioactive phytoconstituents confers A. subulatum the protective effect against MTX toxicities, suggesting the possibility of a combined therapeutic approach with MEAS so as to subside severe toxicities of MTX therapy.…”

“…Mitigating effect of MEAS against MTX‐induced toxicities is attributed to the antioxidant and anti‐inflammatory properties exhibited by bioactive phytoconstituents in MEAS. Vanillic acid (Calixto‐Campos et al., 2015; Kumar et al., 2011), p‐coumaric acid (Kilic & Yesiloglu, 2013; Pragasam et al., 2013), syringic acid (Li et al., 2018), ferulic acid (Mahmoud et al., 2020), gallic acid (Badhani et al., 2015; Kroes et al., 1992), catechin (Fan et al., 2017), naringenin (Chung et al., 2019; Rashmi et al., 2018), rutin (Selloum et al., 2003; Yang et al., 2008), costunolide (Eliza et al, 2010; Nan et al., 2020), betulin (Lee et al, 2019), villosin (Li et al., 2016), n‐hexadecanoic acid (Aparna et al., 2012), and so forth are some of the bioactive phytoconstituents in MEAS, which were reported to exhibit antioxidant/anti‐inflammatory potential. Hence, it can be concluded that the presence of these bioactive phytoconstituents confers A .…”

Epithelial Cell Adhesion Molecule (EpCAM) Expression Can Be Modulated via NFκB

“…Costunolide significantly reduced NFκB transcription in a concentration-dependent manner. Several studies have reported dose-dependent NFκB reduced expression by costunolide [ 52 ]. The inhibitory effect of costunolide on the transcriptional activity of NFκB and the translocation of p65 from cytoplasm to nucleus was also evident from previous studies [ 17 , 53 ].…”

Recent development on COX-2 inhibitors as promising anti-inflammatory agents: The past 10 years

“…17 ) were found from the leaves of Artemisia lavandulaefolia 98 , the biological evaluation results showed that compounds 152 – 156 had weak COX-2 inhibitory activity with IC 50 values of 43.29–236.33 μmol/L. In 2020, Choo group 99 investigated the potential activity of a sesquiterpene lactone, costunolide 157 . Compound 157 decreased the expression level of COX-2 protein and have good anti-inflammatory activity through NF- κ B signaling pathway.…”