title: Chronic Treatment with a Water-Soluble Extract from the Culture Medium of Ganoderma lucidum Mycelia Prevents Apoptosis and Necroptosis in Hypoxia/Ischemia-Induced Injury of Type 2 Diabetic Mouse Brain.
abstract: Type 2 diabetes mellitus has been known to increase systemic oxidative stress by chronic hyperglycemia and visceral obesity and aggravate cerebral ischemic injury. On the basis of our previous study regarding a water-soluble extract from the culture medium of Ganoderma lucidum mycelia (designed as MAK), which exerts antioxidative and neuroprotective effects, the present study was conducted to evaluate the preventive effects of MAK on apoptosis and necroptosis (a programmed necrosis) induced by hypoxia/ischemia (H/I) in type 2 diabetic KKAy mice. H/I was induced by a combination of unilateral common carotid artery ligation with hypoxia (8% O2 for 20 min) and subsequent reoxygenation. Pretreatment with MAK (1 g/kg, p.o.) for a week significantly reduced H/I-induced neurological deficits and brain infarction volume assessed at 24 h of reoxygenation. Histochemical analysis showed that MAK significantly suppressed superoxide production, neuronal cell death, and vacuolation in the ischemic penumbra, which was accompanied by a decrease in the numbers of TUNEL- or cleaved caspase-3-positive cells. Furthermore, MAK decreased the expression of receptor-interacting protein kinase 3 mRNA and protein, a key molecule for necroptosis. These results suggest that MAK confers resistance to apoptotic and necroptotic cell death and relieves H/I-induced cerebral ischemic injury in type 2 diabetic mice.
authors.affiliation: Laboratory of Immunobiochemistry, Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan ; Laboratory of Organic and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan.
authors.forename: Meiyan
authors.initials: M
authors.lastname: Xuan
authors.affiliation: Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Okazaki
authors.affiliation: Laboratory of Immunobiochemistry, Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Iwata
authors.affiliation: Department of Pharmaceutical Sciences, International University of Health and Welfare, Tochigi 324-8501, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Asano
authors.affiliation: Laboratory of Immunobiochemistry, Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Kamiuchi
authors.affiliation: Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Matsuzaki
authors.affiliation: Laboratory of Organic and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sakamoto
authors.affiliation: Noda Shokukin-kogyo Co. Ltd., 295 Nanakohdai Noda, Chiba 278-0051, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Miyano
authors.affiliation: Noda Shokukin-kogyo Co. Ltd., 295 Nanakohdai Noda, Chiba 278-0051, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iizuka
authors.affiliation: Laboratory of Immunobiochemistry, Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Hibino