Distinct immunosuppressive effect by Isodon serra extracts.
Distinct effect of ent-Kaurene Diterpenoids from Isodon serra on abnormal proliferation of murine lymphocytes was examined with MTT assay and Flow Cytometry Analyses (FCAS). After choosing the most appropriate monomer from these Diterpenoids, we introduced mouse tumescence model to investigate whether it could impact cytokine production in vivo with ELISA assay. The result of MTT assay showed that four ent-Kaurene Diterpenoids could effectively suppress the murine splenic T lymphocytes overproduction stimulated by Concanavalin A, while inhibitive effect was softer on normal sleep lymphocytes than the stimulated ones. Among four ent-Kaurene Diterpenoids, Enmein was the most sensitive one with IC50/EC50 equaling to 1.55. This inhibitive activity was due to interfering DNA replication in G1-S stage and to regulating cell cycle according to flow cytometry analyses (FCAS) result. Xylene-induced mouse tumescence model result further suggested that Enmein depressed the murine ear swelling extent and the level of Interleukin-2 in blood serum in a dose-dependent manner. In conclusion, it demonstrated that four ent-Kaurene Diterpenoids from I. serra had distinct immunosuppressive effect in vitro and in vivo systems, which primarily differentiated Enmein from the others. The experimental results provided insight into a potential immunosuppressive action of Enmein as a promising drug, though profound mechanism remained to be further studied.
Zhang
Yan
Y
State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, PR China.
Liu
Jianwen
J
Jia
Wei
W
Zhao
Aihua
A
Li
Ting
T
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D045786:Diterpenes, Kaurane / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D004487:Edema / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D005260:Female; D007166:Immunosuppressive Agents / Q000302:isolation & purification / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D018664:Interleukin-12 / Q000097:blood; D037602:Isodon; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects*; D051379:Mice; D013154:Spleen / Q000166:cytology / Q000187:drug effects*; D014992:Xylenes
D004224:Diterpenes; D045786:Diterpenes, Kaurane; D004365:Drugs, Chinese Herbal; D007166:Immunosuppressive Agents; D014992:Xylenes; D018664:Interleukin-12; C007594:enmein