Blackened Panax quinquefolius L. Saponins and Their Cytotoxic Effect on HepG2 Cells

In the present work, the blackening process of Panax quinquefolius L. (PQ) was systematically investigated at temperatures of 70–90 °C, relative humidities (RHs) of 70–85%, and treatment times of 0–14 days. Ginsenoside compositions and transformation pathways were analyzed by high-performance liquid chromatography (HPLC) and liquid chromatography coupled with ion trap time-of-flight tandem mass spectrometry (LC-IT-TOF-MS/MS). The results demonstrated that blackening treatment significantly increased total saponin content from 2.72% to 5.73% after being treated at 80 °C and 70% RH for 12 days, accompanied by the highest conversion efficiencies for newly generated ginsenosides Rk1 (8.89 mg/g) and Rg5 (17.69 mg/g). Furthermore, compared with untreated PQ saponins (PQS), the blackened PQ saponins treated under optimal conditions (BPQS) exhibited superior 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) cation (ABTS+) radical scavenging activities, with IC50 values of 0.2999 mg/mL and 0.2640 mg/mL, respectively, as well as stronger reducing power. Meanwhile, BPQS exhibited higher cytotoxicity toward HepG2 cells and effectively inhibited cell survival and proliferation by promoting the expression of apoptosis-related proteins, including caspase 3 and caspase 9. Our findings indicate that BPQS may be a functional ingredient suitable for use in dietary supplements and disease chemoprevention.