Arginase activity in the peritoneal macrophages of BN6Lewis F1 progeny is higher than that in Lewis but lower than that in BN rats

. Resveratrol inhibits EMMPRIN expression via P38 and ERK1/2 pathways in PMA-induced THP-1 cells. Biochem Biophys Res Commun 374: 517521. 46. Kundu JK, Shin YK, Kim SH, Surh YJ Resveratrol inhibits phorbol ester-induced expression of COX-2 and activation of NF-kappaB in mouse skin by blocking IkappaB kinase activity. Carcinogenesis 27: 14651474. 47. Venkatesan B, Ghosh-Choudhury N, Das F, Mahimainathan L, Kamat A, et al. Resveratrol inhibits PDGF receptor mitogenic signaling in mesangial cells: role of PTP1B. FASEB J 22: 34693482. 48. Chen L, Fischle W, Verdin E, Greene WC Duration of nuclear NFkappaB action regulated by reversible acetylation. Science 293: 16531657. 49. Gu W, Roeder RG Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell 90: 595606. 50. Martinez-Balbas MA, Bauer UM, Nielsen SJ, Brehm A, Kouzarides T Regulation of E2F1 activity by acetylation. EMBO J 19: 662671. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 13 Chirality is a quite common feature for both biomacromolecules and small-molecules in nature and in our daily life. Biomacromolecules have the potential to stereoselectively recognize and dispose the ligands. For example, it has been shown that S-verapamil is significantly different from R-verapamil in plasma protein binding and systemic clearance. On the other hand, small-molecules also stereoselectively take their biological actions. Taking propoxyphene as an example, MedChemExpress LY341495 dextropropoxyphene is an analgesic, whereas levopropoxyphene is an antitussive agent. Warfarin is another example. At physiological concentrations, R-warfarin interacts with pregnane X receptor and significantly induces CYP3A4 and CYP2C9 mRNAs, while S-warfarin does not show such effects. As mentioned above, it is interesting and important to explore the interactions between chiral small molecules and stereoselective biomacromolecules, with pre-clinical and clinical significances. Ginsenosides, the main effective constituents of ginseng, have a broad range of therapeutic applications. The basic structure of ginsenoside is tetracyclic triterpenoid, with many chiral carbones in the molecule. Particularly, the chirality of carbon-20 contributes to the two stereoisomers of each ginsenoside. They “1678014 are called epimers. It is very likely that the two epimers of ginsenoside have different biological characteristics. 20-ginsenoside Rg3 but not 20-ginsenoside Rg3 inhibited the Ca2+, K+ and Na+ channel currents in a dose- and voltage-dependent manner. In human fecal microflora, the amount of 20-ginsenoside Rg3 transforming to 20-ginsenoside Rh2 was 19-fold higher than that of 20-ginsenoside Rg3 transforming to 20-ginsenoside Rh2. On the other hand, as the deglycosylation metabolite of Rg3, ginsenoside Rh2 also exhibited stereoselective activities. 20-ginsenoside Rh2 but not 20-ginsenoside Rh2 inhibited the proliferation of both androgen-dependent and independent prostate cancer cells. Interestingly, 20-ginsenoside Rh2 is a selective osteoclastgenesis inhibitor without any cytotoxicity, while 20-ginsenoside Rh2 showed weak osteoclastgenesis inhibition but had strong cytotoxicity in osteoclasts. We have previously examined the pharmacokinetic profile of ginsenoside Rh2 and observed its poor bioavailability . We found that stereochemistry was one of the causes to poor oral absorption, because 20-ginsenoside Rh2 and 20ginsenoside Rh2 exhibited different membrane permeabilit