Absolute configuration of tetrandrine and isotetrandrine influences their anti-proliferation effects in human T cells via different regulation of NF-κB.

Autor: Xu W; Department of Pharmacy, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, P. R. China.; Institute of Traditional Chinese Medicine, Hubei Province Academy of Traditional Chinese Medicine, Wuhan, P. R. China., Kusano J; Division of Pharmacy, Kanagawa-ken Keiyukai Keiyu Hospital, Yokohama, Kanagawa, Japan., Chen S; Department of Pharmacy, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, P. R. China.; Institute of Traditional Chinese Medicine, Hubei Province Academy of Traditional Chinese Medicine, Wuhan, P. R. China., Yamamoto R; Division of Pharmacy, Kanagawa-ken Keiyukai Keiyu Hospital, Yokohama, Kanagawa, Japan., Matsuda H; Division of Nephrology, Kanagawa-ken Keiyukai Keiyu Hospital, Yokohama, Kanagawa, Japan., Hara Y; Division of Nephrology, Kanagawa-ken Keiyukai Keiyu Hospital, Yokohama, Kanagawa, Japan., Fujii Y; Division of Nephrology, Kanagawa-ken Keiyukai Keiyu Hospital, Yokohama, Kanagawa, Japan., Hayashi S; Division of Pharmacy, Kanagawa-ken Keiyukai Keiyu Hospital, Yokohama, Kanagawa, Japan., Tanaka S; Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan., Sugiyama K; Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan., Yamada H; Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan., Hirano T; Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
Jazyk: angličtina
Zdroj: Zeitschrift fur Naturforschung. C, Journal of biosciences [Z Naturforsch C J Biosci] 2020 Oct 30; Vol. 76 (1-2), pp. 21-25. Date of Electronic Publication: 2020 Oct 30 (Print Publication: 2021).
DOI: 10.1515/znc-2020-0064
Abstrakt: Natural compound tetrandrine was reported to inhibit the proliferation of T cells by inhibiting activation of NF-κB. Chemically, isotetrandrine differs from tetrandrine only in the stereochemistry at the chiral centers. The present study aimed to compare their anti-proliferation effects on human T cells with a focus on NF-κB. The IC 50 values of tetrandrine against MOLT-4 cells, MOLT-4/DNR cells, and concanavalin A-activated peripheral blood mononuclear cells of healthy subjects and dialysis patients were 4.43 ± 0.22, 3.62 ± 0.22, 1.91 ± 0.22 and 3.03 ± 0.28 μM, respectively. Whereas, the IC 50 values of isotetrandrine against the above immune cells were 2.19 ± 0.27, 2.28 ± 0.33, 1.29 ± 0.14 and 1.55 ± 0.26 μM, respectively. The inhibitory effect of isotetrandrine against the proliferation of T cells was stronger than that of tetrandrine significantly ( p  < 0.05). Molecular mechanism investigation showed that 10 μM of isotetrandrine largely decreased the expression of p-NF-κB and NF-κB in both MOLT-4 and MOLT-4/DNR T cells ( p  < 0.05), whereas 10 μM of tetrandrine slightly inhibited the phosphorylation of p-NF-κB with little influence on the expression of NF-κB. Taken together, absolute configurations of tetrandrine and isotetrandrine are suggested to influence on their anti-proliferation effects in human T cells via different regulation of NF-κB.
(© 2020 Walter de Gruyter GmbH, Berlin/Boston.)
Databáze: MEDLINE
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