In the present study, we investigated the mechanisms underlying the anti-inflammatory effects of rosmarinosin A in (LPS)-stimulated RAW 264.7 macrophages. The cells were pretreated with various concentrations of rosmarinosin A, and then stimulated with LPS. Rosmarinosin A reduced the production of nitric oxide (NO) and prostaglandin E₂ (PGE₂), possibly through the modulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, respectively. Additionally, it inhibited the production of pro-inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin (IL) 1β, and IL-6. The molecular mechanisms of rosmarinosin A involved the suppression of nuclear factor κB (NF-κB) p65 translocation into the nucleus. Furthermore, rosmarinosin A exhibited anti-inflammatory properties by suppressing the mitogen-activated protein kinase (MAPK) signaling pathway. These findings suggest that rosmarinosin A may exert its anti-inflammatory effects, at least in part, through the modulation of NF-κB and MAPK pathways in LPS-activated macrophages, offering the potential for therapeutic development.

The primary aim of this research was to identify the structural characteristics of three newly derived procyanidins from cold plasma-treated (–)-epicatechin, known for their anti-inflammatory properties. The newly generated compounds were isolated through column chromatography, and their chemical structures were elucidated through spectroscopic data analyses, including both one-dimensional and two-dimensional nuclear magnetic resonance (NMR) and mass spectrometry (MS) techniques. Furthermore, their absolute configurations were determined via circular dichroism (CD) spectroscopy. The inhibitory activity of the isolated compounds on nitric oxide (NO) production and expression levels of inducible NO synthase (iNOS) in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages was evaluated. Three new procyanidins—methylenetrisepicatechin (2), isomethylenetrisepicatechin (3), and methylenebisepicatechin (4)—along with two reported dimeric flavan-3-ols (5 and 6), were identified from plasma-treated (–)-epicatechin (1). The unique oligomerized products 2 and 3 linked by methylene bridges significantly suppressed both NO production and iNOS expression, demonstrating higher anti-inflammatory activities in LPS-stimulated RAW 264.7 cells compared with the parent compound. The newly oligomerized procyanidins have potential applications in the treatment of inflammatory diseases owing to their significant anti-inflammatory properties.

Radiation is widely used as a powerful tool for inducing molecular transformation and expanding chemical diversity; however, its application in clinically relevant antibiotics remains limited. Minocycline (1), a clinically used tetracycline antibiotic, was subjected to gamma irradiation at doses of up to 30 kGy, resulting in the formation of a previously unreported radiation-induced derivative, minocyclinosin A (2). The structure of the newly generated compound was elucidated by comprehensive spectroscopic analyses, including one- and two-dimensional nuclear magnetic resonance spectroscopy and high-resolution electrospray ionization mass spectrometry, which revealed extensive A-ring cleavage, degradation, and recyclization to form a unique cyclopenta[b]anthracene-type tetracycline scaffold. Biological evaluation revealed that minocyclinosin A exhibited enhanced anti-inflammatory activity by suppressing lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages, while maintaining antibacterial activity against skin inflammation-associated Staphylococcus species. High-performance liquid chromatography further demonstrated a clear dose-dependent molecular conversion, with irradiation at 30 kGy affording minocyclinosin A as the major product with a conversion efficiency of approximately 78.3%.

Rotenone, isolated from Derris, Lonchocarpus, and Tephrosia from the family Fabaceae, has been shown to have a variety of biological properties and is used in various agricultural industries as a potent biopesticide. However, recent reports have demonstrated that rotenone has the potential to cause several adverse effects such as a neurodegenerative disease. This study aimed to induce thermolysis of the biopesticide rotenone and enhance the functionality of the degraded products. Rotenone (1) was degraded after autoclaving for 12 h, and the thermolytic reactants showed enhanced anti-inflammatory capacity against nitric oxide (NO) production. The structures of the newly modified products were spectroscopically determined. The thermal reaction products included various isoflavonoid derivatives 2–6, whose structures were characterized as being produced via chemical reactions in rotenone at the C-12 positions. Among the degraded products, (−)-tubaic acid (6) exhibited significantly improved anti-inflammatory effects compared to the original rotenone. Quantitative LC-MS analysis of the major thermolysis products generated in Derris extract containing rotenone was performed using isolate 2–5 purified from autoclaved rotenone. These results suggest that the thermal transformation of rotenone can improve the functionality of anti-inflammatory agents.