Millingtonia hortensis L.F. (Bignoniaceae), commonly referred to as the tree jasmine or Indian cork tree, is indigenous to South Asia and South East Asia (Jumnongprakhon et al., 2021). Traditionally, the stem bark of this plant is employed as a pulmonary tonic with anti-asthmatic and antimicrobial activities. Both its leaves and roots are utilized for their anti-asthmatic and antimicrobial properties. The flowers of M. hortensis are utilized in the treatment of asthma and sinusitis (Kumari and Sharma, 2013). Moreover, recent studies have extensively explored M. hortensis, focusing particularly on its diverse extract components and their associated biological activities. M. hortensis is rich in flavonoids that exert hepatoprotective effects. The antioxidative properties inherent in the flower extract of M. hortensis may contribute to this hepatoprotective effect (Babitha et al., 2012). In addition, M. hortensis has demonstrated potential efficacy in addressing neurodegenerative diseases associated with aging (Jumnongprakhon et al., 2021). Notably, M. hortensis extract exhibited antibacterial activity (Mondal and Rai, 2019), as well as anti-proliferative and pro-apoptotic properties against colon cancer (Tansuwanwong et al., 2006, 2009), and larvicidal activities against Anopheles stephensi, Culex quinquefasciatus and Aedes aegypti (Kaushik and Saini, 2008). Furthermore, M. hortensis can alleviate indigestion (Chander et al., 2015). In addition, traditional medical literature has explicitly acknowledged its anti-inflammatory effects, as well as preventive effects against allergies, stomach trouble, cough, and phlegm (Paibon et al., 2011). However, its underlying anti-inflammatory mechanisms remain relatively unexplored.

Inflammation is a series of defense responses protecting our body from external stimuli, such as injury or pathogen infections. In recent years, inflammation has garnered significant attention in biomedical research, given reports of its intimate association with various chronic diseases, such as cancer, (Pang et al., 2023; Sutopo et al., 2023), cardiovascular diseases (Liu et al., 2023; You et al., 2022a), and neurodegenerative diseases (Zhao et al., 2023). During inflammation, circulating monocytes infiltrate tissues and differentiate into macrophages, which are pivotal in inflammatory responses (Tang et al., 2023). Lipopolysaccharide (LPS) is a principal constituent of the outer wall of Gram-negative bacteria, and it is recognized by Toll-like receptor 4 (TLR4) present on the surface of macrophage membranes (Ghasemi-Dehnoo et al., 2023). When LPS binds to TLR4, it activates myeloid differentiation primary response 88 (MyD88)- or TIR domain-containing adaptor protein (TRIF)-dependent signaling pathways (Ratan et al., 2022). This intracellular signaling prompts macrophages to express inflammatory factors, including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2), thereby leading to the production of inflammatory mediators such as nitric oxide (NO), and consequent inflammation (Zhang et al., 2021).

Among various signal molecules, tyrosine kinase family proteins are principal effector molecules in the orchestration of inflammatory responses (Yi et al., 2014). Syk, a nonreceptor tyrosine kinase, interacts with TLR4 to activate nuclear factor-κB (NF-κB) signaling (Yi et al., 2021). NF-κB, which is ubiquitously present across diverse animal cell types, serves a transcription factor pivotal in diverse cellular responses, including cell growth, proliferation, differentiation, apoptosis, and carcinogenesis. In the context of inflammatory responses, NF-κB activation leads to the expression of pro-inflammatory factors, thereby perpetuating a cascade of inflammatory processes (Mitra et al., 2022).

In this research, we explored the impacts of M. hortensis ethanol extract (Mh-EE) on inflammatory responses in LPS-induced macrophages and a HCl/EtOH-induced gastritis mouse model and evaluated the underlying molecular mechanisms.