Peimine

Indigo, Aliso B acetate, gentiopicroside, peimine, perillaldehyde, wedelolactone, bergapten, picroside I, berberine, cinnamaldehyde, ephedrine, p-synephrine, 6-shogao, and 6-gingerol were purchased from Sigma-Aldrich. Phellodendrine was purchased from Abcam. Baicalein, baicalin, wogonin, wogonoside, and Ephedra sinica were kindly provided by Y.L. Leu (Chang Gung University, Taiwan). Scutellaria baicalensis (precursor of Baicalein, baicalin, wogonin, wogonoside) and Ephedra sinica were supplied and authenticated by Department of Pharmacy Services, Chang Gung Memorial Hospital at Taoyuan, Taiwan. See Supplementary Information for more details on compound preparation.

The following compounds were used in our experiments: fisetin (F; Cayman, Ann Arbor, MI, USA), peimine (P; Sigma‒Aldrich, St Louis, USA), artemisinin (Ar; Sigma‒Aldrich, St. Louis, MI, USA), astaxanthin (A; Sigma‒Aldrich, St Louis, USA), bardoxolone methyl (BM, Sigma‒Aldrich, St. Louis, MI, USA), 740 Y-P (7; Med Chem Express, Monmouth Junction, NJ, USA), morphine hydrochloride (M; Fagron, Krakow, Poland), buprenorphine (B; Polfa S.A., Warsaw, Poland) and oxycodone hydrochloride (O; Molteni Farmaceutici, Scandicci, Italy). All of these substances were administered via intrathecal injection (i.t.), a standard procedure in our laboratory [109 (link),111 (link)]. It is performed by using a Hamilton syringe with a thin needle in accordance with instructions described previously [112 (link)]. The injections were performed in the lumbar segment of the spinal cord (between the L5 and L6 vertebrae) with a volume of 5 µL, and the tail reflex was an indicator of correct administration.