Stroke is one of the major diseases leading to human death and disability,and prevention and treatment of stroke have become difficult medical problems.A large number of studies have shown that estrogen has significant neuroprotective effect against stroke,but its clinical application has encountered many obstacles.Long-term use of estrogen,especially the activation of estrogen receptor α (ERα) will increase the risk of reproductive system tumors.Recent studies abroad and our previous research have found that activation of estrogen receptor β (ERβ) can significantly alleviate cerebral ischemic injury.In addition,activation of ERβ can also improve the learning and memory abilities of ovariectomized rats.At the same time,ERβ selective agonists lack the ability to stimulate the proliferation of breast or endometrial tissue as compared with estrogen or ERa agonists,so activation of ERβ is expected to be a more safe and effective method for the prevention and treatment of stroke in menopause women.In this paper,we briefly reviewed the neuroprotective effects associated with ERβ signaling pathway in order to provide new ideas and molecular targets for the clinical transformation of estrogen in prevention and treatment against stroke.

Twelve novel 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid(CDDO) derivatives were designed and synthesized(9a-91) by introducing different heterocyclic rings to 17-COOH of CDDO through various linkers.Their structures were determined by ESI-MS,IR and 1 H NMR.The antiproliferative activity of the synthetic derivatives against human cancer cells HCT-116,A549 and HepG2 was evaluated by MTT assay.Several compounds showed potent inhibitory activities against test cell lines.Among them,compound 9c showed more potent antiproliferative activity than the CDDO-imidazolide (CDDO-Im).Moreover,rat plasma stability assay showed that compound 9c was more stable than CDDO-Im.