γ-Oryzanol, a unique ingredient specific to brown rice, effectively restores mild cognitive impairment (MCI) in obese aged mice by ameliorating microglial inflammation and promoting neurogenesis in hippocampus: Novel therapeutic insight into obesity-associated MCI

Ask your competent? doctor and hospital when research will determine if this also applies to humans and non-obese persons and stroke survivors with their higher risk of dementia?

Do you prefer your doctor, hospital and board of director's incompetence NOT KNOWING? OR NOT DOING? Your choice; let them be incompetent or demand action!

 γ-Oryzanol, a unique ingredient specific to brown rice, effectively restores mild cognitive impairment (MCI) in obese aged mice by ameliorating microglial inflammation and promoting neurogenesis in hippocampus: Novel therapeutic insight into obesity-associated MCI

Shiki Okamotoa,b , Ikumi Nomuraa, Ayano Kinjoc, Yuko Murayamaa, Chie Horiguchia, Chisayo Kozukad , Taiki Teruyaa, Tsugumi Uemaa Michio Shimabukuroe , Tomoko Nagaic, , Chitoshi Takayamaf Masayuki Matsushitag, Keiko Abeh , and Hiroaki Masuzakia* aDivision of Endocrinology, Diabetes and Metabolism, Hematology and Rheumatology, Second Department of Internal Medicine, Gradu ate School of Medicine, University of the Ryukyus, Okinawa 901-2720, Japan bLaboratory of Veterinary Physiology and Biochemistry, Yamaguchi University Joint Graduate School of Veterinary Medicine, Yamaguchi 753-8515, Japan cSENTAN Pharma Inc., R&D Department, Fukuoka 812-0027, Japan dLaboratory for Epigenome Inheritance, RIKEN Center for Integrative Medical Sciences, Kanagawa 230-0045, Japan eDepartment of Diabetes, Endocrinology and Metabolism, School of Medicine, Fukushima Medical University, Fukushima 960-1295, Japan fDepartment of Molecular Anatomy, School of Medicine, University of the Ryukyus, Okinawa 901-2720, Japan gDepartment of Molecular and Cellular Physiology, Graduate School of Medicine, University of the Ryukyus, Okinawa 901-2720, Japan hDepartment of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113-8657, Japan *Corresponding author: Hiroaki Masuzaki, Division of Endocrinology, Diabetes and Metabolism, Hematology and Rheumatology, Second Department of Internal Medicine, Graduate School of Medicine, University of the Ryukyus, Okinawa, 901-2720, Japan. E-mail: hiroaki@ cs.u-ryukyu.ac.jp DOI: 10.26599/JFB.20xx.000xx Received: January 17, 2026; Revised received & accepted: February 06, 2026 Abbreviations: CI, cognitive impairment; Orz, γ-oryzanol; Nano-Orz, nanoparticulated γ-oryzanol; FITC, fluorescein isothiocyanate; LCD, lab chow diet; HFD, high-fat diet; PO, per os Citation: Okamoto, S., Nomura, I., Kinjo, A., Murayama, Y., Horiguchi, C., Kozuka, C., Teruya, T., Uema, T., Nagai, T., Shimabukuro, M., Takayama, C., Matsushita, M., Abe, K., and Masuzaki, H. (2026). γ-Oryzanol, a unique ingredient specific to brown rice, effectively restores mild cognitive impairment (MCI) in obese aged mice by ameliorating microglial inflammation and promoting neurogenesis in hippocampus: Novel therapeutic insight into obesity-associated MCI. J. Food Bioact. 000: 000–000. 

Abstract 

Obesity-diabetes syndrome poses a considerable risk for mild cognitive impairment (MCI). Our study was designed to explore therapeutic potential of γ-oryzanol (Orz), a brown rice-specific oil composed of ferulic acid ester with several phytosterols, on MCI in high-fat diet (HFD) induced obese aged mice. After being housed on an HFD for 4 months, regular Orz or the nanoparticulated form of Orz (Nano-Orz), which markedly enhances its intestinal absorption, was administered to aged mice. Mice treated with regular Orz for 4 months exhibited significant improvement in spatial cognitive function. Impressively, mice treated with Nano-Orz demonstrated cognitive improvement as early as 1 month, with substantial recovery by 3 months. In the hippocampus, treatment with both regular Orz and Nano-Orz upregulated genes associated with neurogenesis and stem cell function accompanied by a significant increase in gene expressions of anti-inflammatory cytokines. Our data highlight a therapeutic potential of Orz for obesity-associated MCI. 1. Introduction Mild cognitive impairment (MCI) stems from a variety of factors, including aging, chronic inflammation, and beta-amyloid accumu lation in the hippocampus. Of note, obesity has recently been rec ognized as a considerable risk for MCI, highlighting that chronic over-ingestion of a high-fat diet (HFD) substantially impairs hip pocampus-dependent memory in both rodents and humans (Ka noski and Davidson, 2010; Kanoski et al., 2007; Nyaradi et al., 2014; Sharma, 2021). γ-Oryzanol (Orz), a brown rice-specific oil composed of ferulic acid ester with several phytosterols, is known to act preferentially on lipophilic organs and tissues (Masuzaki et al., 2019). A line of our studies showed that orally administered Orz accumulated considerably in the brain and pancreas, thereby reducing exaggerated endoplasmic reticulum (ER) stress by sup pressing mRNA expression of ER stress-associated genes (Chop, ERdj4, Xβp1) in both hypothalamus and pancreatic β-cells in HFD-induced obese diabetic mice (Kozuka et al., 2015; Kozuka, Shimizu-Okabe, et al., 2017). We also demonstrated in mouse ex periments that Orz potently inhibited DNA methyltransferases, thereby reducing animal fat preference via epigenetic modulation of dopamine receptor gene in brain reward system (Kozuka, Kan ame, et al., 2017). Moreover, a rat model of streptozotocin-induced sporadic Alzheimer’s disease showed that Orz was potent to delay the onset of MCI (Jha and Panchal, 2017). To date, detailed molecular mechanisms whereby Orz would improve MCI have been poorly elucidated. Furthermore, due to extremely poor solubility in water of Orz, oral administration of Orz in mice provided a weak impact on some effects (Kozuka et al., 2013). To overcome such a hazard, we previously reported that oral administration of nanoparticulated γ-oryzanol (Nano Orz) in mice markedly enhanced absorption efficiency from intestine by more than 1,000-fold (Kozuka, Shimizu-Okabe, et al., 2017). In this context, we here provide evidence that oral administration of Nano-Orz potently mitigates hippocampal dys function via novel mechanisms, thereby improving MCI in obese aged mice. 

More at link.