The leaves of the seasoning plant Litsea cubeba inhibit the NLRP3 inflammasome and ameliorate dextran sulfate sodium-induced colitis in mice

Abstract

The intracellular sensor NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome controls caspase-1 activity and the maturation and release of the cytokines interleukin (IL)−1β and IL−18. The NLRP3 inflammasome has attracted the attention of the pharmaceutical industry because it promotes the pathogenesis of many diseases, making it a promising target for drug development. Litsea cubeba (Lour.) is a plant traditionally used as a seasoning in Taiwan and in other Asian countries. In this study, we investigated the inhibitory activity of the leaves of L. cubeba against the NLRP3 inflammasome. We found that the ethanol extract of L. cubeba leaves (MLE) inhibited the NLRP3 inflammasome in macrophages by reducing caspase−1 activation and IL−1β secretion. MLE reduced pyroptosis in macrophages and inhibited the release of NLRP3 and apoptosis-associated speck-like protein containing a CARD (ASC). In a mechanistic study, MLE reduced mitochondrial reactive oxygen species (ROS) production and preserved mitochondrial integrity, which led to reduced mitochondrial DNA release into the cytosol. MLE did not reduce the expression levels of NLRP3, IL−1β precursor or TNF-α in lipopolysaccharide (LPS)-activated macrophages. These results indicated that MLE inhibited the NLRP3 inflammasome by suppressing the activation signals of the NLRP3 inflammasome but not by reducing the priming signal induced by LPS. In addition, oral administration of MLE (20−80 mg/kg) ameliorated dextran sulfate sodium (DSS)−induced colitis in a mouse model. Notably, mice that received MLE (1 and 2 g/kg) daily for 7 days did not exhibit visible side effects. Gas chromatography-mass spectrometry (GC-MS) analysis found that α-Terpinyl acetate (27.2%) and 1,8−Cineole (17.7%) were the major compounds in MLE. These results indicated that L. cubeba leaves have the potential to be a nutraceutical for preventing and improving NLRP3 inflammasome-related diseases.

Modes of Action of 1,8-Cineol in Infections and Inflammation

“…Further detailed analysis of the anti-inflammatory mechanism of L. nobilis extract revealed that the observed inhibition of NLRP3 inflammasome activation was correspondingly associated with an inhibition of caspase-1 activation and apoptosis-associated speck-like protein containing a CARD (ASC) pyroptosome complex formation [ 89 ]. The 1,8-Cineol containing leaves of the plant Litsea cubeba were also shown to inhibit the NLRP3 inflammasome activation and to ameliorate the dextran-sulfate-induced colitis [ 90 ] and pro-inflammatory cell infiltrations in ankle tissues in mouse models [ 91 ].…”

Surfactin Containing Bacillus licheniformis-Fermented Products Alleviate Dextran Sulfate Sodium-Induced Colitis by Inhibiting Colonic Inflammation and the NLRP3 Inflammasome in Mice

“…Because food enters the digestive system first, diet is thought to influence the prevalence of IBD, making it a potential adjunctive therapy in IBD [ 30 ]. Recently, we demonstrated that Litsea cubeba leaves ameliorate colitis in DSS-treated mice by inhibiting the NLRP3 inflammasome [ 31 ]. Other studies have also indicated that natural products or dietary supplements have the potential to improve IBD by inhibiting the NLRP3 inflammasome.…”

Profil Kandungan Kimia, Fenolik Total, dan Aktivitas Antioksidan Ekstrak Etanol Tumbuhan Litsea firma (Blume) Hook F

“…Pelarut etanol digunakan karena merupakan pelarut universal yang dapat melarutkan hampir semua senyawa organik yang ada pada suatu sampel, baik senyawa polar maupun senyawa non polar dan relatif aman dibandingkan metanol (Noviyanti, 2016). Perbandingan rendemen ekstrak etanol daun L. firma dengan ekstrak etanol dari spesies Litsea lainnya menunjukkan bahwa rendemen ekstrak etanol daun L. firma relatif lebih besar daripada ekstrak etanol dari daun L. elliptica (10,4% w/w) (Mariani et al, 2021), L. monopetala (4% w/w) (Hasan et al, 2014), dan L. cubeba (20% w/w) (Wong et al, 2022). Selain faktor efisiensi ekstraksi, faktor kandungan senyawa metabolit sekunder pada L. firma diduga lebih memengaruhi besarnya rendemen ini.…”