Cucurbita ficifolia regulates the secretomes of adipocytes and macrophages in co-culture, breaking meta-inflammation

Abstract Cucurbita ficifolia’s fruit aqueous extract has been attributed with antidiabetic and anti-inflammatory properties, offering a promising alternative in addressing meta-inflammation. Meta-inflammation plays a pivotal role in the development of metabolic dysfunction, contributes to conditions such as obesity, diabetes mellitus, and metabolic syndrome. The interactions between adipocytes and macrophages within adipose tissue cause the onset of meta-inflammation, leading to disruptions in the secretomes and transcriptomes of inflammatory cytokines among other factors. We evaluated the effects of the aqueous extract from the fruit of Cucurbita ficifolia on the secretomes and transcriptomes of 3T3-L1 adipocytes and RAW-264.7 macrophages, by exchange of their conditioned mediums and in co-culture conditions. Adipocytes incubated with conditionate medium from macrophages treated with the extract exhibited an increase in GLUT-4 expression, and the protein release of TNFα, accompanied by a reduction in IL-1β. In contrast, macrophages incubated with conditionate medium from adipocytes treated with the extract exhibited inhibition the release of TNFα, IL-6, and IL-10, with TLR-4 expression reduction. Interestingly, under the conditions of indirect simultaneous co-culture, the release of TNFα, IL-6, and IL-1β was disrupted, increasing PPARγ expression in 3T3-L1 adipocytes. The salicin, compound reported in Cucurbita ficifolia extract, had a similar effect in this last model. The aqueous extract of Cucurbita ficifolia demonstrates the ability to suppress meta-inflammation by correcting the secretion patterns of TNFα and IL-6 in co-culture conditions. It effectively modulates the interactions between 3T3-L1 adipocytes and RAW-264.7 macrophages, leading to an improvement in the inflammatory cytokines profile.