Metabolite Profiling, In vitro Evaluation of Cytotoxic, and Anti-atherosclerosis Effects of Fermented Sambal Lalapan Extract

The increasing incidence of coronary heart disease (CHD) worldwide, along with concerns over the long-term use of statins and low adherence to a healthy diet, highlights the potential of natural product-based alternatives. This study aimed to investigate the metabolite profiling, cytotoxicity, and anti-atherosclerotic effects of fermented sambal lalapan extract (FSLE). FSLE was derived from an ethanolic extract of fermented powder that underwent spontaneous fermentation for 14 days at 20°C. Results from LC-MS/MS demonstrated that capsaicin was the predominant among 29 metabolites determined in FSLE. The percentage of cell viability in Vero and MDCK cells treated with FSLE at 5 µg/mL was 90.14 ± 5.35% and 88.27 ± 0.97%, respectively. At the highest concentration of 1,280 µg/mL, cell viability of 99.79 ± 1.87% and 99.85 ± 9.19% was obtained in Vero and MDCK cells. The effect of FSLE on atherosclerosis was evaluated using an atherosclerosis animal model. The oral administration of FSLE at 200 mg/kg body weight resulted in lower total cholesterol (TC) (154.40 ± 34.13 mg/dL), lower low-density lipoprotein (LDL)-c (130.59 ±15.68 mg/dL) (P = 0.001 < 0.05), and higher high-density lipoprotein (HDL)-c (33.73 ± 1.67 mg/dL) compared to the HFD group (P = 0.001 < 0.05). Observation using HE staining revealed a lower number of foam cells in the aortic tissue of the FSLE compared to the HFD group (P = 0.045 < 0.05), which may be attributed to increased ATP Binding Cassette A (ABCA)1 expression, as determined by real-time PCR and ELISA. In conclusion, FSLE showed promise against CHD by attenuating atherosclerosis.