In our search for bioactive components, various chromatographic separations of the organic fractions from Filipendula glaberrima leaves led to the isolation of a new ellagitannin and a triterpenoid, along with 26 known compounds. The structures of the isolates were determined based on their spectroscopic properties and chemical evidence, which were then evaluated for their antioxidant activities, inhibitory activities on 3-hydroxy-3-methylglutaryl-coenzyme A reductase, and foam cell formation in THP-1 cells to prevent atherosclerosis. Rugosin B methyl ester (1) showed the best HMG-CoA reductase inhibition and significantly reduced ox-low-density lipoprotein-induced THP-1 macrophage-derived foam cell formation at 25 µM. In addition, no cytotoxicity was observed in THP-1 cells at 50 μg/mL of all extracts in the macrophage foam cell formation assay. Therefore, F. glaberrima extract containing 1 is promising in the development of dietary supplements due to its potential behavior as a novel source of nutrients for preventing and treating atherosclerosis.

Tumor-associated macrophages (TAMs) play a critical role in the tumor microenvironment (TME), interacting with cancer cells and other components to promote tumor growth. Given the influence of TAMs on tumor progression and resistance to therapy, regulating the activity of these macrophages is crucial for improving cancer treatment outcomes. TAMs often exhibit immunosuppressive phenotypes (commonly referred to as M2-like macrophages), which suppress immune responses and contribute to drug resistance. Therefore, inhibiting immunosuppressive polarization offers a promising strategy to impede tumor growth. This study revealed retinoic acid receptor gamma (RARγ), a nuclear receptor, as a key regulator of immunosuppressive polarization in THP-1 macrophages. Indeed, the inhibition of RARγ, either by a small molecule or gene silencing, significantly reduced the expression of immunosuppressive macrophage markers. In a three-dimensional tumor spheroid model, immunosuppressive macrophages enhanced the proliferation of HCT116 colorectal cancer cells, which was significantly hindered by RARγ inhibition. These findings suggest that targeting RARγ reprograms immunosuppressive macrophages and mitigates the tumor-promoting effects of TAMs, highlighting RARγ as a promising therapeutic target for developing novel anti-cancer strategies.