Anti-inflammatory potential of Indonesian marine sponge Theonella sp.: Mechanisms via TNF-α, IL-6, and IL-12 inhibition

Inflammation is a complex biological response triggered by harmful stimuli and characterized by elevated levels of pro-inflammatory cytokines such as interleukin (IL)-6, IL-12, and tumor necrosis factor (TNF)-α. Although steroidal and non-steroidal anti-inflammatory drugs are commonly used, their side effects highlight the need for safer alternatives. This study evaluates the anti-inflammatory activity of the ethanol extract of Theonella sp. collected from Southeast Sulawesi, Indonesia, through in vitro, in vivo, and in silico approaches. To our knowledge, this is the first report evaluating the cytokine-modulating effects of Theonella sp. from this region. In vitro study was done using human red blood cell membrane stability and protein denaturation assays, whereas the in vivo study was done using carrageenan-induced paw edema in male Wistar rats. The edema volume was measured using a plethysmometer, and the levels of cytokines IL-6, IL-12, and TNF-α were measured using enzyme-linked immunosorbent assay, and its molecular docking. The extract stabilized cell membranes, inhibited protein denaturation, and significantly reduced paw edema and cytokine levels, indicating anti-inflammatory potential. Preliminary phytochemical screening identified alkaloids (peptides) and steroids. These findings highlight Theonella sp. as a promising source of natural anti-inflammatory agents.