Sulfate conjugation of daphnetin by the human cytosolic sulfotransferases

Abstract

Ethnopharmacological relevance In Turkey, daphnetin-containing Daphne oleoides is used as a folk medicine for treating rheumatic pain and lumbago. A daphnetin-containing traditional Chinese medicine tablet, named Zushima-Pian, is available in China for treating rheumatoid arthritis. The present study aimed to investigate the metabolism of daphnetin through sulfation in cultured human cells and to identify the human cytosolic sulfotransferase(s) (SULT(s)) that is(are) capable of mediating the sulfation of daphnetin. Materials and methods Cultured HepG2 human hepatoma cells and Caco-2 human colon carcinoma cells were labeled with [35S]sulfate in the presence of different concentrations of daphnetin. Thirteen known human SULTS, previously expressed and purified, as well as cytosols of human kidney, liver, lung, and small intestine, were examined for daphnetin-sulfating activity using an established sulfotransferase assay. Results [35S]sulfated daphnetin was found to be generated and released by HepG2 cells and Caco-2 cells labeled with [35S]sulfate in the presence of daphnetin. Among the 13 known human SULTs, SULT1A1, SULT1A2, SULT1A3, SULT1B1, and SULT1C4 displayed significant sulfating activity toward daphnetin. Of the four human organ samples later tested, small intestine and liver cytosols displayed considerably higher daphnetin-sulfating activity than those of lung and kidney. Conclusion The results derived from the present study showed unequivocally that daphnetin could be sulfated in cultured human cells and by purified human SULT enzymes as well as human organ cytosols. The information obtained provided a basis for further studies on the metabolism of daphnetin through sulfation in vivo.

Daphnetin, a Coumarin in Genus Stellera Chamaejasme Linn: Chemistry, Bioactivity and Therapeutic Potential

“…Additionally, there are some research areas including: 3D-binding model/simulation of daphnetin to biotargets, structure-activity relationships of daphnetin and its derivatives/analogs, combination of daphnetin and other therapeutics for synergistic chemotherapy, as well as daphnetin-based functional drug formulations, need to be deeply and extensively investigated. The sulfation metabolism pathway [117]…”

“…In 2016, Han et al. studied the supersession of daphnetin by sulfation in cultured human cells and identified the human cytosolic sulfotransferase(s) (SULT(s)), which could mediate the sulfation of daphnetin [117] . The results indicated that daphnetin sulfating activity was the strongest in SULT1A1 (30.37±0.36 nmol/min/mg).…”