Dexamethasone

Inflammatory bowel disease (IBD), encompassing chronic relapsing gastrointestinal disorders, remains a profound clinical challenge because conventional therapeutics are often impeded by systemic off-target toxicities and suboptimal retention at inflamed mucosal sites. Herein, an inflammation-activated and retentive injectable hydrogel is presented, which leverages pathological nitric oxide (NO) overproduction as both a therapeutic target and an autonomous release trigger. An NO-responsive and NO-scavenging polymer (NRSP) incorporating an NO-cleavable o-phenylenediamine (o-PD) motif is formulated into cationic, dexamethasone-encapsulating micelles and electrostatically assembled with anionic hyaluronic acid (HA) to form a shear-thinning hydrogel that facilitates minimally invasive rectal administration and ensures prolonged, localized retention at the inflamed mucosal interface. Upon exposure to the NO-rich inflammatory microenvironment, structural disruption of NO-responsive and NO-scavenging micelles (NRSM) compromises the electrostatic integrity of the HA-micelle network, thereby reducing the storage modulus and accelerating cargo release. In vitro evaluations using lipopolysaccharide-stimulated macrophages demonstrate that NRSM hydrogels effectively reduce intracellular and extracellular NO levels and attenuate pro-inflammatory cytokine secretion. Furthermore, the HA matrix mediates disease-adaptive localization through CD44 receptor recognition and preferential electrostatic adhesion to positively charged inflammatory interfaces, resulting in enhanced colonic retention in DSS-induced colitis models ex vivo. Following rectal administration in DSS-induced mice, NRSM-based hydrogels significantly alleviate disease severity, reduce colonic NO and inflammatory cytokine levels, and rescue mucosal architecture and mucin-associated features. Notably, dexamethasone-loaded NRSM hydrogel exerted the most potent synergistic therapeutic benefit. Overall, this disease-responsive hydrogel platform establishes an effective localized intervention for IBD, merging intrinsic pathological NO scavenging with controlled drug delivery.

Acute lung injury (ALI) is a respiratory disease with a high mortality rate. Shionone, derived from the Chinese herbal medicine Aster tataricus, has anti-inflammatory and antioxidant effects. However, its protective effect on ALI remains unclear. In this study, we aimed to assess the protective effect of shionone on lipopolysaccharide (LPS)-induced ALI and to elucidate its underlying mechanisms. In this study, male C57BL/6 mice aged 8-10 weeks were randomly divided into five groups (10 mice per group) including control group, LPS group, LPS + shionone (50 mg/kg) group, LPS + shionone (100 mg/kg) group, and LPS + Dexamethasone (1 mg/kg) group. In mice with LPS-induced ALI, shionone significantly reduced lung index, lung wet/dry weight ratio, production of inflammatory cytokines, nitric oxide (NO) content, malondialdehyde (MDA) production, and increased superoxide dismutase (SOD) activity and nicotinamide adenine dinucleotide phosphate (NADPH) level. Shionone improved lung histopathological injury by inhibiting inflammatory cell infiltration and edema in LPS-induced ALI in mice. In vitro, shionone inhibited oxidative stress and inflammation in LPS-induced BEAS-2B cells. Shionone improved the protein expression of anti-ferroptosis proteins, including glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), in mice lung tissues and BEAS-2B cells. Additionally, GC-MS-based metabolomic analysis showed that shionone increased the levels of various metabolites, such as fructose, glucose, and lactic acid. Shionone ameliorated LPS-induced ALI by downregulating Kelch-like ECH-associated protein 1 (Keap1) and upregulating Nuclear factor erythroid 2-related factor 2 (Nrf2), Heme oxygenase-1 (HO-1), and quinone oxidoreductase 1 (NQO1) in both in vivo and in vitro study. In conclusion, this study demonstrated that shionone mitigated LPS-induced ALI by inhibiting ferroptosis through regulation of Keap1/Nrf2/SLC7A11/GPX4 pathway, indicating that shionone may be a promising agent for ALI.