Abstract
<jats:p>Background/Objectives: Oxidative stress and chronic inflammation are critical pathophysiological drivers of over 100 degenerative diseases and malignancies. Beta-Sitosterol (BS) and pteropodine (PT) are plant-derived bioactive compounds implicated in fatty acid metabolism and tissue homeostasis. This study aimed to evaluate the immunomodulatory capacity, selective cytotoxicity, acute anti-inflammatory effects, and antimutagenic potential of BS and PT using complementary in vivo and in vitro models.Methods: Male and female BALB/c mice were orally treated with BS (100–200 mg/kg) or PT (25–50 mg/kg). Humoral immunity against thymus-dependent antigens was assessed via a modified Jerne/Cunningham hemolytic plaque assay (SRBC immunization). Acute inflammation was evaluated using a TPA-induced mouse ear edema model. In vitro selective cytotoxicity was determined by exposing human hepatocellular carcinoma cells (HepG2) and normal human liver cells (Chang liver) to both compounds, evaluating cell adhesion and morphology. Results: Both BS and PT significantly enhanced the humoral immune response by increasing plaque-forming cells (IgM-producing B-lymphocytes) and elevated peripheral lymphocyte counts in BALB/c mice. Topically, both compounds effectively reduced TPA-induced acute ear edema. Furthermore, BS exhibited potent selective cytotoxicity, inducing complete cell detachment (CT100) and apoptotic morphological changes in HepG2 cancer cells, while leaving normal Chang liver cells unaffected (CT0). Conclusions: Pteropodine and beta-sitosterol exert significant immunomodulatory, anti-inflammatory, and antioxidant activities in vivo, alongside a remarkable tumor-selective cytotoxic profile in vitro, representing promising natural scaffolds for multi-target chemopreventive therapies.</jats:p>