天然物クルシアノンによるラット肝ミトコンドリア脱共役およびHepG2細胞死誘導
Clusianone belongs to the polycyclic polyprenylated acylphloroglucinol class of natural compounds and is a structural isomer of nemorosone, a known mitochondrial uncoupler with cytotoxic properties. This study examined its effects on mitochondrial function and cancer cell viability. In HepG2 hepatocarcinoma cells, clusianone caused dissipation of mitochondrial membrane potential, depletion of ATP, and externalization of phosphatidylserine, the last of which signals apoptotic induction. Experiments with isolated rat liver mitochondria demonstrated protonophoric uncoupling, evidenced by elevated resting respiration, suppressed calcium influx, enhanced calcium efflux from calcium-loaded organelles, reduced ATP and NAD(P)H levels, reactive oxygen species generation, and swelling in valinomycin-treated preparations under hyposmotic potassium acetate conditions. The magnitude of both uncoupling and cytotoxic effects was notably lower than that of nemorosone, an outcome attributed to an intramolecular hydrogen bond formed with the adjacent carbonyl group at the C15 position, which likely limits protonophoric activity.
Clusianone acts as a protonophoric uncoupler, dissipating mitochondrial membrane potential and triggering ROS generation and ATP depletion, ultimately inducing apoptosis; an intramolecular hydrogen bond at the C15 carbonyl position attenuates its potency relative to nemorosone.
This is basic research at the cellular or molecular level. For human application, inhalation is the most promising delivery route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration devices are not recommended).
See also:
https://h2-papers.org/en/papers/24491676