Genipin has attracted much attention for its hepatoprotective, anti-inflammatory, and neuroprotection activities. However, poor water solubility and active chemical properties limit its application in food and pharmaceutical industries. This article aimed to develop a lipid-based microemulsion delivery system to improve the stability and bioavailability of genipin. The excipients for a genipin microemulsion (GME) preparation were screened and a pseudo-ternary phase diagram was established. The droplet size (DS), zeta potential (ZP), polydispersity index (PDI), physical and simulated gastrointestinal digestion stability, and in vitro drug release properties were characterized. Finally, the effect of the microemulsion on its cellular uptake by Caco-2 cells and the protective effect on PC12 cells were investigated. The prepared GME had a transparent appearance with a DS of 16.17 ± 0.27 nm, ZP of −8.11 ± 0.77 mV, and PDI of 0.183 ± 0.013. It exhibited good temperature, pH, ionic strength, and simulated gastrointestinal digestion stability. The in vitro release and cellular uptake data showed that the GME had a lower release rate and better bioavailability compared with that of free genipin. Interestingly, the GME showed a significantly better protective effect against amyloid-β (Aβ1-42)-induced PC12 cell cytotoxicity than that of the unencapsulated genipin. These findings suggest that the lipid-based microemulsion delivery system could serve as a promising approach to improve the application of genipin.

Gardeniae fructus is a common neuroprotective medicinal food in China, however the extraction efficiency and mixture activities are rarely mentioned. In this study, accelerated solvent extraction (ASE) parameters were optimized by a response surface methodology to extract antioxidants from Gardeniae fructus. Neuroprotective activity was evaluated using H₂O₂ and amyloid-β_25–35 peptide-treated PC12 cells. By comparing with three other extract methods (i.e., heated refluxing extraction (HRE), ultrasound-assisted extraction (UAE), microwave-assisted extraction (MAE)), it was found that the yield (35.10%), total iridoids (27.69%), total flavonoid (6.12%) content, antioxidant activities (IC₅₀ on DPPH, 164.46 µg/mL; FRAP value 4703.54 μmol/L), and acetylcholinesterase inhibitory ability (IC₅₀ 92.58 µg/mL) of ASE extract under the optimal condition (150 °C temperature, 10 min static time, 60% ethanol, 2 extract cycles) were significantly higher than other extract methods. The strongest ability to protect PC12 cells from damage was also present in ASE extract, as evidenced by decreasing lactate dehydrogenase and malondialdehyde levels, elevating superoxide dismutase and glutathioneperoxidase activities. Compositional analysis indicated that the extremely high crocetin level in ASE extract (1.30 μg/mg) may offer great potential. Our results indicated that ASE is a proper extraction method that could offer great potential for finding the neuroprotective ability of Gardeniae fructus for the treatment of AD.

In our previous study, AI-3, a mixture of isoflavones, was obtained from Apios Americana Medik tuber and showed strong protective ability on oxidative damaged RIN-m5F cells. This study aimed to identify the main compounds of AI-3 and elucidate their activities and underlying mechanism. In results, eleven compounds were purified from AI-3. Among them, Compound 8 (2'-Hydroxy, 5-methoxy genistein-7-O-glucoside, HMG) was the most effective compound against H₂O₂-induced injury in RIN-m5F cells (stronger than positive control α-LA). Further RNA-seq analysis found that compared with H₂O₂ group, 388 differentially expressed genes (DEGs) were identified in HMG group. The enrichment analyses revealed fluid shear stress and atherosclerosis pathway and hepatocellular carcinoma pathway enriched the most DEGs, in which HOX-1, GST, NQO1, SQSTM, TrxR1 were significantly up-regulated. The finding indicated Keap1-Nrf2-ARE signaling pathway may play essential role in the protective effect of HMG on oxidative damaged RIN-m5F cells.

Gardenia fruit, a medicinal and edible resource rich in bioactive compounds, faces several limitations, including low extraction efficiency, poor stability, and intense bitterness. In this study, gardenia fruit powder at varying concentrations (2.5%, 5.0%, 7.5%, 10.0%, and 12.5%) was mixed with a kombucha inoculum and fermented for 8 days to develop functional beverages. The results demonstrated that fermentation with gardenia fruit powder effectively supported SCOBY growth. The 5.0% addition of gardenia fruit (G5Fer) produced thicker bacterial cellulose, higher total titratable acidity (10.43 g/L), and increased total polyphenols (37.12 mg GAE/100 mL) after 8 days of fermentation. G5Fer also achieved the highest sensory scores, especially in aroma, flavor, and overall acceptance. Higher doses of gardenia fruit (≥7.5%) caused turbidity, dark color, and strong sourness, leading to lower sensory scores. Non-targeted metabolomics revealed that kombucha fermentation reshaped the metabolic profile, enriching phenolic acids (e.g., gallic acid and caffeic acid) and flavonol glycosides (e.g., kaempferol-3-O-rutinoside) via the biosynthesis of phenylpropanoid pathways while antioxidant activity (DPPH and ABTS⁺ scavenging rate) was well maintained. Overall, G5Fer achieved the best balance among acidity, bioactive compounds, and consumer preference. In conclusion, gardenia fruit represents a promising substrate for developing a functional, palatable kombucha-like beverage, aligning with the growing demand for value-added fermented products.