Effectiveness of gamma-oryzanol in glycaemic control and managing oxidative stress, inflammation, and dyslipidaemia in diabetes: a systematic review of preclinical studies.

Background: Diabetes mellitus (DM) and associated complications remain a global public health challenge despite many confrontational aspects of the disease, and its prevalence is projected to rise in the coming decades. Thus, there is an urgent need to intensify the current efforts to address both the prevalence and adverse effects of diabetes, including the use of natural products. Increasing evidence from the scientific literature has revealed the beneficial effects of gamma oryzanol for treating diabetes and its related complications.

Aim: To investigate the effectiveness of gamma oryzanol (γ-oryzanol) in managing hyperglycaemia, oxidative stress, inflammation, and dyslipidaemia in a rodent model of diabetes mellitus.

Methodology: The review was conducted by searching PubMed, ScienceDirect, Scopus, and Web of Science for articles published from inception to July 12, 2025, with the terms (Gamma-oryzanol OR γ-oryzanol OR Oryzanol OR Cycloartenyl ferulate OR Gammariza) AND (Diabetes mellitus OR Type 2 diabetes mellitus OR hyperglycemia OR oxidative stress OR inflammation OR dyslipidaemia). The review included only articles that used rat and mouse models of diabetes mellitus and γ-oryzanol as treatments; articles that did not meet these criteria were excluded. A total of nine articles were identified, encompassing a total population of 394 rodents. SyCLE's risk of bias tool was used to assess the methodological quality of the studies.

Results: Out of 1,989 records initially identified through the systematic search, nine studies met the eligibility criteria. All included studies were assessed to have an unclear to low risk of bias. The synthesised findings indicate that γ-oryzanol (γ-ORZ) exerts beneficial effects on glycaemic control by enhancing insulin secretion and sensitivity, as well as by reducing fasting blood glucose (FBG) levels. Additionally, γ-ORZ demonstrates antioxidant activity by elevating endogenous antioxidant enzyme levels and decreasing oxidative stress markers. Its lipid-modulatory effects include the elevation of beneficial lipid fractions and the reduction of atherogenic lipids, thereby alleviating diabetic dyslipidaemia. Moreover, γ-ORZ exhibits anti-inflammatory properties through the downregulation of proinflammatory biomarkers. Despite these promising results in preclinical models, further high-quality investigations, particularly well-designed clinical trials, are essential to validate these findings and support the potential integration of γ-ORZ into diabetes management strategies.

Conclusion: Most included studies reported that γ-ORZ positively affected hyperglycaemia, oxidative stress, dyslipidaemia, and inflammation under diabetic conditions. Further research, particularly rigorously designed clinical trials, is strongly recommended to confirm and translate these preclinical findings into clinical practice.