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Neuroprotection by the soy isoflavone, genistein, via inhibition of mitochondria-dependent apoptosis pathways and reactive oxygen induced-NF-κB activation in a cerebral ischemia mouse model.
Neurochem Int. 2012 Jun; 60(8):759-67.NI

Abstract

Recently, the treatment of stroke has focused on antioxidant therapies, where oxidative stress is implicated. The preventive and therapeutic potential of plant compounds on ischemic stroke has been intensively studied because many of them contain antioxidant properties. Genistein, one of the active ingredients in soybean, possesses many bioactivities. In this study, we investigated the potential neuroprotective effects of genistein and its possible mechanism of action in a cerebral ischemia mouse model. Mice were pretreated with genistein (2.5, 5, and 10mg/kg) or vehicle orally once daily for 14 consecutive days before transient middle cerebral artery occlusion was performed. Genistein at doses of 2.5-10mg/kg significantly reduced the infarct volume, improved the neurological deficit and prevented cell apoptosis after ischemia. In addition, genistein pretreatment was shown to inhibit the ischemia-induced reactive oxygen species (ROS) production, enhance the activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), and decrease levels of malondialdehyde (MDA) in stroke mice. Moreover, genistein reversed the mitochondria dysfunction after ischemia, as evidenced by decreasing mitochondria ROS levels, preventing cytochrome C release to the cytoplasm and inhibiting caspase-3 activation. Western blotting showed ischemia activated the ROS-dependent nuclear factor-κB (NF-κB) signaling pathway, and genistein suppressed phosphorylation and activation of the NF-κB p65 subunit, as well as the phosphorylation and degradation of the inhibitor protein of κBα (IκBα). Our findings suggested that genistein has a neuroprotective effect in transient focal ischemia, which may involve regulation of mitochondria-dependent apoptosis pathways and suppression of ROS-induced NF-κB activation.

Authors+Show Affiliations

National Center for Soybean Improvement, Nanjing Agricultural University, Nanjing, People's Republic of China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22490611

Citation

Qian, Yisong, et al. "Neuroprotection By the Soy Isoflavone, Genistein, Via Inhibition of Mitochondria-dependent Apoptosis Pathways and Reactive Oxygen induced-NF-κB Activation in a Cerebral Ischemia Mouse Model." Neurochemistry International, vol. 60, no. 8, 2012, pp. 759-67.
Qian Y, Guan T, Huang M, et al. Neuroprotection by the soy isoflavone, genistein, via inhibition of mitochondria-dependent apoptosis pathways and reactive oxygen induced-NF-κB activation in a cerebral ischemia mouse model. Neurochem Int. 2012;60(8):759-67.
Qian, Y., Guan, T., Huang, M., Cao, L., Li, Y., Cheng, H., Jin, H., & Yu, D. (2012). Neuroprotection by the soy isoflavone, genistein, via inhibition of mitochondria-dependent apoptosis pathways and reactive oxygen induced-NF-κB activation in a cerebral ischemia mouse model. Neurochemistry International, 60(8), 759-67. https://doi.org/10.1016/j.neuint.2012.03.011
Qian Y, et al. Neuroprotection By the Soy Isoflavone, Genistein, Via Inhibition of Mitochondria-dependent Apoptosis Pathways and Reactive Oxygen induced-NF-κB Activation in a Cerebral Ischemia Mouse Model. Neurochem Int. 2012;60(8):759-67. PubMed PMID: 22490611.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuroprotection by the soy isoflavone, genistein, via inhibition of mitochondria-dependent apoptosis pathways and reactive oxygen induced-NF-κB activation in a cerebral ischemia mouse model. AU - Qian,Yisong, AU - Guan,Teng, AU - Huang,Menghao, AU - Cao,Liangxun, AU - Li,Yunman, AU - Cheng,Hao, AU - Jin,Hangxia, AU - Yu,Deyue, Y1 - 2012/04/03/ PY - 2011/10/18/received PY - 2012/03/08/revised PY - 2012/03/19/accepted PY - 2012/4/12/entrez PY - 2012/4/12/pubmed PY - 2012/10/13/medline SP - 759 EP - 67 JF - Neurochemistry international JO - Neurochem Int VL - 60 IS - 8 N2 - Recently, the treatment of stroke has focused on antioxidant therapies, where oxidative stress is implicated. The preventive and therapeutic potential of plant compounds on ischemic stroke has been intensively studied because many of them contain antioxidant properties. Genistein, one of the active ingredients in soybean, possesses many bioactivities. In this study, we investigated the potential neuroprotective effects of genistein and its possible mechanism of action in a cerebral ischemia mouse model. Mice were pretreated with genistein (2.5, 5, and 10mg/kg) or vehicle orally once daily for 14 consecutive days before transient middle cerebral artery occlusion was performed. Genistein at doses of 2.5-10mg/kg significantly reduced the infarct volume, improved the neurological deficit and prevented cell apoptosis after ischemia. In addition, genistein pretreatment was shown to inhibit the ischemia-induced reactive oxygen species (ROS) production, enhance the activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), and decrease levels of malondialdehyde (MDA) in stroke mice. Moreover, genistein reversed the mitochondria dysfunction after ischemia, as evidenced by decreasing mitochondria ROS levels, preventing cytochrome C release to the cytoplasm and inhibiting caspase-3 activation. Western blotting showed ischemia activated the ROS-dependent nuclear factor-κB (NF-κB) signaling pathway, and genistein suppressed phosphorylation and activation of the NF-κB p65 subunit, as well as the phosphorylation and degradation of the inhibitor protein of κBα (IκBα). Our findings suggested that genistein has a neuroprotective effect in transient focal ischemia, which may involve regulation of mitochondria-dependent apoptosis pathways and suppression of ROS-induced NF-κB activation. SN - 1872-9754 UR - https://www.unboundmedicine.com/medline/citation/22490611/Neuroprotection_by_the_soy_isoflavone_genistein_via_inhibition_of_mitochondria_dependent_apoptosis_pathways_and_reactive_oxygen_induced_NF_κB_activation_in_a_cerebral_ischemia_mouse_model_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-0186(12)00113-1 DB - PRIME DP - Unbound Medicine ER -