Plant-based remedies have been employed since ancient times to manage and prevent a wide range of diseases. Background: Their bioactive constituents provide natural alternatives to synthetic anti-inflammatory drugs, often with reduced toxicity and multiple biological benefits. Mandragora autumnalis, a medicinal plant rich in secondary metabolites, has not been extensively investigated for its anti-inflammatory properties. Methods: The anti-inflammatory activity of Mandragora autumnalis ethanolic extract (MAE) was evaluated using in vitro biochemical assays, including heat-induced protein denaturation (casein and bovine serum albumin) and red blood cell membrane stabilization. Cellular anti-inflammatory effects were assessed in LPS-stimulated RAW 264.7 macrophages by measuring nitric oxide production, pro-inflammatory cytokine levels, macrophage migration, gene and protein expression of inflammatory mediators, and the activation status of NF-κB, STAT3, and MAPK signaling pathways. Results: Preliminary screening revealed that MAE effectively inhibited heat-induced protein denaturation (casein and bovine serum albumin) and heat-induced red blood cell (RBC) hemolysis, indicating strong protein- and membrane-stabilizing properties associated with anti-inflammatory activity. In lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, MAE markedly suppressed the inflammatory response by downregulating the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), leading to a significant reduction in nitric oxide (NO) production and pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Furthermore, MAE inhibited macrophage migration and attenuated key inflammatory signaling pathways, notably nuclear factor kappa B (NF-κB), signal transducer and activator of transcription 3 (STAT3), and mitogen-activated protein kinases (MAPKs). Molecular docking analysis was conducted to explore the potential interactions between the most abundant chemical compounds and key proteins involved in inflammatory signaling pathways, including ERK and iNOS. Conclusions: Overall, these results indicate that MAE exhibits strong anti-inflammatory activity by stabilizing proteins, protecting cellular membranes, and inhibiting key inflammatory mediators and signaling pathways. These findings highlight its potential as a natural therapeutic candidate for the prevention and management of chronic inflammation-related disorders, such as arthritis, cardiovascular diseases, and cancer. However, further mechanistic investigations and in vivo studies are required to confirm its therapeutic potential and clinical relevance.

Background/Objectives: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with poor prognosis and limited targeted therapeutic options. Natural products, rich in bioactive phytochemicals, represent a potential source of novel anticancer agents. This study examined the phytochemical profile and anticancer activity of an ethanolic bulb extract of Cyclamen persicum (CPE), with a primary focus on TNBC. Methods: The phytochemical composition of CPE was analyzed by liquid chromatography–mass spectrometry (LC–MS). Antioxidant activity was evaluated using DPPH radical scavenging assay. The anticancer effects of CPE were assessed mainly in MDA-MB-231 TNBC cells using MTT cell viability assays, Ki-67 immunoblotting, Western blot analysis of signaling proteins, wound healing migration assays, Matrigel invasion assays, adhesion assays and cell–cell aggregation assays. Antiproliferative activity was also examined in 22RV1 (prostate), Capan-2 (pancreatic), and HCT116 (intestinal) cancer cell lines using MTT assays. Results: LC–MS analysis indicated that the extract contains multiple polyphenolic and organic acid constituents commonly associated with bioactivity. Consistent with this profile, CPE demonstrated strong antioxidant activity. In MDA-MB-231 cells, CPE significantly reduced cell viability and proliferation, accompanied by decreased Ki-67 expression. Treatment was associated with modulation of proteins involved in proliferative and survival signaling, induction of apoptosis-related markers, and reduced migratory and invasive capacities. CPE also promoted cell–cell homotypic aggregation, suggesting a shift toward a less aggressive phenotype. These effects were associated with reduced phosphorylation of p65, indicating possible modulation of NF-κB signaling. Additionally, CPE decreased proliferation in 22RV1, Capan-2, and HCT116 cancer cell lines. Conclusions: Collectively, these findings indicate that C. persicum bulb extract exerts multimodal anticancer effects in vitro, particularly in TNBC cells, and highlights its potential as a source of bioactive compounds warranting further mechanistic and translational investigation.