Nine new gingerols, including three 6-oxo-shogaol derivatives [(Z)-6-oxo-[6]-shogaol (1), (Z)-6-oxo-[8]-shogaol (2), (Z)-6-oxo-[10]-shogaol (3)], one 6-oxoparadol derivative [6-oxo-[6]-paradol (4)], one isoshogaol derivative [(E)-[4]-isoshogaol (5)], and four paradoldiene derivatives [(4E,6Z)-[4]-paradoldiene (8), (4E,6E)-[6]-paradoldiene (9), (4E,6E)-[8]-paradoldiene (10), (4E,6Z)-[8]-paradoldiene (11)], together with eight known analogues, were isolated from the rhizoma of Zingiber officinale. Their structures were elucidated on the basis of spectroscopic data. It was noted that the isolation of 6-oxo-shogaol derivatives represents the first report of gingerols containing one 1,4-enedione motif. Their structures were elucidated on the basis of spectroscopic and HRESIMS data. All the new compounds were evaluated for their cytotoxic activities against human cancer cells (MCF-7, HepG-2, KYSE-150).

Background/Objectives: The blood–brain barrier (BBB) is compromised in many neurological disorders, yet in vitro models rarely reproduce graded inflammatory stimulation of brain endothelial cells in vivo. This study developed a detachable, modular BBB-on-a-chip for stepwise inflammation modeling with multi-marker readout, and compared the anti-inflammatory efficacy of quercetin (QUER) and kaempferol (KAE). Methods: The chip combines a Christmas-tree concentration gradient generator with a four-channel culture module, fabricated separately and assembled on demand for stepwise seeding, exposure, dosing, and sampling. hCMEC/D3 cells were exposed to a TNF-α gradient (0–30 ng/mL); extracellular ATP, ROS, NO, cytokines, ZO-1, and ICAM-1 were monitored over 48 h. Transcriptomics and network pharmacology were integrated with molecular docking and 100 ns molecular dynamics simulations; QUER and KAE were administered gradient-wise (0–20 μM), with dexamethasone as a control. Results: The TNF-α gradient induced time- and concentration-dependent injury, with ATP and IL-8 responding at 8 h, ROS and NO at 12 h, and IL-1β, IL-6, and tight-junction impairment later, yielding spatiotemporally resolved readouts across four parallel channels. Ten hub inflammatory genes, including ICAM1, were identified, and network pharmacology nominated QUER. QUER was predicted to bind ICAM-1 more strongly than KAE, its structural analog differing by one B-ring hydroxyl group; gradient administration confirmed QUER suppressed ICAM-1 expression and inflammatory mediator release at lower concentrations. Conclusions: The detachable modular design makes multi-step inflammation modeling and gradient-based anti-inflammatory evaluation convenient on a single chip; QUER’s consistent advantage over KAE across binding calculations and functional assays supports a structure-activity relationship consistent with ICAM-1 engagement.

Fusel oil is a by-product during the fermentation of alcoholic beverage, mainly including n-propanol, isobutanol, isopentanol, and others. Long-term or excessive intake of them may cause potential harm to human health. In the present work, we preliminarily evaluated the cytotoxicity of n-propanol and isobutanol, main components of fusel oil, in human fetal astrocytes (SVGp12), human microvascular endothelial cells (HMEC-1), and human microglial cells (HMC3). The results showed that both n-propanol and isobutanol exhibited cytotoxicity in all three types of cells, and the release of proinflammatory cytokines (IL-6 and IL-8) significantly increased in the cells exposed to fusel oil components. The transepithelial electrical resistance (TEER) values were decreased and the permeability was increased in HMEC-1 cells exposed to fusel oil components. These results indicate that fusel oil components may cause potential harm to human health.