Nutritional, metabolic, and cardiovascular parameters: (a) caloric intake (kcal/day); (b) adiposity index (%); (c) glucose (mg/dL); (d) HOMA-IR; (e) triglycerides (mg/dL); (f) systolic blood pressure (mmHg). Data expressed in mean ± standard deviation or median. Comparison by one-way ANOVA with Tukey post hoc. HSF: high sugar-fat diet; γOz: gamma oryzanol. ∗ indicates p<0.05; n=8 animals/group.

Nutritional, metabolic, and cardiovascular parameters: (a) caloric intake (kcal/day); (b) adiposity index (%); (c) glucose (mg/dL); (d) HOMA-IR; (e) triglycerides (mg/dL); (f) systolic blood pressure (mmHg). Data expressed in mean ± standard deviation or median. Comparison by one-way ANOVA with Tukey post hoc. HSF: high sugar-fat diet; γOz: gamma oryzanol. ∗ indicates p<0.05; n=8 animals/group.

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The kidney is an important organ in the maintenance of body homeostasis. Dietary compounds, reactive metabolites, obesity, and metabolic syndrome (MetS) can affect renal filtration and whole body homeostasis, increasing the risk of chronic kidney disease (CKD) development. Gamma oryzanol ( γ Oz) is a compound with antioxidant and anti-inflammatory...

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... Gamma-oryzanol (γOz) is a nutraceutical obtained from rice bran oil and composed of a mixture of ferulic acid esters of phytosterols and triterpenoids, cycloartenyl ferulate, 24-methylenecycloartanyl ferulate, and campesteryl ferulate [7]. The positive effects of γOz include antioxidant and anti-inflammatory action, effects on the immune system, and treatment or attenuation of dyslipidemia, diabetes, obesity, and neurological disorders, as demonstrated in preclinical experiments, models, and observations [8][9][10][11]. However, there is a lack of studies about the effects of γOz as a possible modulator of the physiopathological process involved in NAFLD. ...
... Body weight was measured weekly. To estimate animal body fat, the adiposity index (AI) was used and obtained by the formula: [(VAT + EAT + RAT)/FBW] × 100 [10]. ...
... Glycemia was determined in a blood drop using a glucometer (Accu-Chek Performa; Roche Diagnostics Brazil Limited, São Paulo, Brazil). The insulin level was measured using the enzyme-linked immunosorbent assay (ELISA) method (EMD Millipore Corporation, Billerica, MA, USA) and the HOMA-IR was calculated by the following formula: HOMA-IR = (fasting glucose (mmol/L) × fasting insulin (µU/mL))/22.5 [10]. ...
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Nonalcoholic fatty liver disease (NAFLD) is the main cause of liver disease. The physiopathological processes involved in the disease are metabolic syndrome (MetS) components (central obesity, dyslipidemia, insulin resistance/type 2 diabetes, hypertension), genetic, and dietary factors, including unsaturated fats and sweetened beverages, which are able to lead to inflammation and oxidative stress, conditions associated with progression and severity of NAFLD. Gamma-oryzanol (γOz) is a nutraceutical obtained from rice brain oil with many benefits to health, from immunological to metabolic. The aim of this study is to test the preventive effect of γOz on the physiopathological process related to nonalcoholic fatty liver disease in animals submitted to high sugar/fat diet. Male Wistar rats (±187 g) were randomly divided into four experimental groups to receive: control diet (C, n = 6), control diet plus γOz (C + γOz, n = 6), high sugar/fat diet (HSF, n = 6), or high sugar/fat diet plus γOz (HSF + γOz, n = 6) during 30 weeks. HSF groups also received water plus sucrose (25%). γOz was added to diets to reach 0.5% of final concentration. The HSF group presented MetS, liver inflammation and oxidative stress, and micro and macrovesicular steatosis. HSF plus γOz was protected against these changes. It is possible to conclude that gamma-oryzanol was effective in modulating the physiopathological process related to nonalcoholic fatty liver disease in animals submitted to a high sugar/fat diet.
... This antioxidant and antinflammatory effect can also explain the protection against heart and kidney dysfunction even in the presence of hypertension, an independent factor for CRMS. Some studies of our research group showed a local antioxidant and antinflammatory effect of lycopene in the heart of obese animals and the same positive effect of gamma-oryzanol in the kidney of obese animals, preserving renal function (Ferron et al., 2020;Francisqueti et al., 2018). This same effect may be exerted BLE in the heart and kidney of animals from this study. ...
Article
Bergamot citrus (Citrus bergamia Risso et Poiteau), have been used as a strategy to prevent or treat comorbidities associated with metabolic syndrome parameters, such as cardiorenal metabolic syndrome (CRMS). The aim was to test the effect of bergamot leaf extract on CRMS and associated pathophysiological factors in rats fed with a high sugar-fat diet. Animals were divided into two experimental groups with control diet (Control, n = 30) and high sugar-fat diet (HSF, n = 30) for 20 weeks. Once CRMS was detected, animals were redivided to begin the treatment with Bergamot Leaf Extract (BLE) by gavage (50mg/Kg) for 10 weeks: control diet + placebo (Control, n = 09), control diet + BLE (Control + BLE, n = 09), HSF diet + placebo (HSF, n = 09), HSF + BLE (n = 09). Evaluation included nutritional, metabolic and hormonal analysis; and renal and cardiac parameters. HSF groups presented obesity, dyslipidemia, hypertension, hyperglycemia, hyperinsulinemia, insulin resistance. BLE showed protection against effects on hypertriglyceridemia, insulin resistance, renal damage, and structural and functional alterations of the heart. Conclusion: Bergamot leaf extract shows potential as a therapeutic to treat CRMS in animals fed with a high sugar-fat diet.
... HSF animals 0.5 w/w (10 weeks) Increased protein expression of adiponectin receptor 2 and PPAR-α. [66] HFFD rat 0.16% (13 weeks) ...
... Numerous studies have shown that γ-oryzanol reduces obesity. It has been reported that (0.5 w/w) γ-oryzanol can increase the protein expression of adiponectin receptor 2 and peroxisomal proliferator-activated receptor-α (PPAR-α) and then suppress ROS production and inflammation response, also ameliorated the obesity-induced renal injuries in animals fed with high sugar-fat diet (HSF) after 10 weeks [66]. Wang et al. (2015) surveyed the effects of γ-oryzanol (0.16% of regular rodent diet) in a high-fat fructose diet (HFFD)-induced obesity, hyperlipidemia, hyperglycemia, and insulin resistance (IR) for 13 weeks in rats. ...
Article
Alpha-bisabolol (α-bisabolol), an unsaturated monocyclic sesquiterpene alcohol, is known as one of the "most-used herbal constituents" in the world. Various therapeutic and biological properties of α-bisabolol in preventing oxidative stress, inflammatory disorders, infections, neurodegenerative diseases, cancers, and metabolic disorders have been reported. In this review, we evaluated new findings regarding the molecular mechanisms of α-bisabolol published from 2010 until 2021 in PubMed, Science Direct, and Scopus. The antioxidant mechanism of α-bisabolol is mainly associated with the reduction of ROS/RNS, MDA, and GSH depletion, MPO activity, and augmentation of SOD and CAT. Additionally, upregulating the expression of bcl-2 and suppression of bax, P53, APAF-1, caspase-3, and caspase-9 activity indicates the anti-apoptotic effects of α- bisabolol. It possesses anti-inflammatory effects via reduction of TNF-α, IL-1β, IL-6, iNOS, and COX-2 and suppresses the activation of ERK1/2, JNK, NF-κB, and p38. The antimicrobial effect is mediated by inhibiting the viability of infected cells and improves cognitive function via downregulation of bax, cleaved caspases-3 and 9 levels, β-secretase, cholinesterase activities, and upregulation of bcl-2 levels. Finally, due to multiple biological activities, α-bisabolol is worthy to be subjected to clinical trials to achieve new insights into its beneficial effects on human health.
... Due to the increased global obesity prevalence, it is important to find alternatives that can minimize the obesity-related disorders. Several researches have shown that the introduction of bioactive compounds with antioxidant and anti-inflammatory effects in eating habits have controlled the emergence of several diseases (Costa et al., 2019;Ferron et al., 2019;Francisqueti et al., 2018;Sengupta et al., 2011). Gamma-oryzanol (γOz) is a compound present in the whole grain of rice and consists of a mixture of sterile ferulates or triterpene alcohol with the carboxylic group of ferulic acid (Minatel et al., 2014). ...
Article
Background Skeletal muscle is the most important organ for whole-body glucose homeostasis. However, it has been suggested that obesity-related inflammation could be involved in insulin resistance and diabetes mellitus type 2 (DM2) development due several mechanisms, among them, the reduced expression of the glucose transporter type 4 (GLUT-4). Gamma-oryzanol (γOz) is a compound present in the whole grain of rice that presents anti-inflammatory and antioxidant activities. The aim of this study was to verify if the effect antioxidant and anti-inflammatory of yOz attenuate insulin resistance in skeletal muscle of obese rats by increasing GLUT- 4 expression. Methods Male Wistar rats (±187g) were initially randomly distributed into 2 experimental groups (control, n = 6, and high sugar-fat diet (HSF), n = 12) for 20 weeks. At week 20th of this study, once obesity and insulin resistance were detected in the HSF group, animals were divided to begin the treatment with γOz or continue receiving HSF for 10 more weeks. At the end it was analyzed nutritional, metabolic, inflammatory and oxidative stress parameters and GLUT-4 protein expression. Results The treatment improved insulin resistance, reduced inflammation, increased antioxidant response and GLUT-4 expression. Conclusion It is possible to conclude that the antioxidant and anti-inflammatory activity of yOz attenuates insulin resistance by increasing GLUT-4 expression in skeletal muscle of obese animals.
... Since obesity and its related disorders are becoming increasingly prevalent, several researchers have been using high-fat diet models to induce obesity, typically characterized by weight gain and increased body fat. 7,15,22,23 In the present study, we chose ~40% of kcal from fat, as we believe this is closer to what is consumed by humans. However, some individuals remain resistant to becoming obese, a condition also observed in some animals' fed with high-fat diets, which are defined as obesity-resistant animals. ...
... 8 Several experiments have demonstrated that obese rats due to a high-fat diet intake develop obesity-related disorders that are similar to human disorders, such as glucose intolerance, insulin resistance, hypertension, and dyslipidemia. 16,22,26 However, in ROb models, there are controversies regarding the presence of comorbidities. 9,10,23,27 In the current study, the ROb group presented relevant metabolic, hormonal, and cardiovascular changes commonly found in obesity and associated with increased adiposity. ...
... Increased leptin and insulin are common in obesity. 16,22 However, the present study also observed this condition in the ROb animals. Increased insulin can be due to insulin resistance or elevated gastric inhibitory polypeptide levels induced by high-saturated fatty acid intake. ...
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Background: As some individuals present resistance to obesity development, experiments have been trying to understand their susceptibility to cardiometabolic diseases. Objective: To evaluate if the cardiac remodeling was related to collagen protein expression change. Methods: Male Wistar rats were randomized into two experimental groups: control diet (CD, n=15) or high-fat diet (HFD, n=15) for 30 weeks. Rats fed with HFD were ranked based on their adiposity indexes and classified as obese (Ob, n = 8) or obesity-resistant (ROb, n = 6). Rats that failed to present the normal characteristic of the control group while fed with CD were excluded (Control, n = 8). Nutritional profile, comorbidities (dyslipidemia, hypertension, glucose metabolism, hyperleptinemia), cardiac remodeling, and collagen protein expression were evaluated. The groups were compared by One-Way ANOVA, together the Tukey post hoc test, with p<0.05 considered significant.Results: The Ob rats presented an increased adiposity index when compared to C and ROb. Both groups Ob and ROb presented increased low-density lipoprotein (LDL), insulin, homeostatic model assessment of insulin resistance (HOMA- IR) and systolic blood pressure (SBP), and low high-density lipoprotein (HDL) levels when compared to the control group. The levels of triglycerides, non-esterified fatty acid (NEFA), and leptin were lower in ROb as compared to Ob, but higher than the control group. The Ob and ROb groups presented cardiac remodeling, evidenced by echocardiographic and post-mortem analysis. The collagen protein expression did not differ among the groups. Conclusion: The ROb animals present cardiac remodeling that is not related to collagen type I and III protein expression change. (1) (PDF) Cardiac Remodeling in Obesity-Resistance Model is not Related to Collagen I and III Protein Expression. Available from: https://www.researchgate.net/publication/353256712_Cardiac_Remodeling_in_Obesity-Resistance_Model_is_not_Related_to_Collagen_I_and_III_Protein_Expression [accessed Jul 15 2021].
... This calculation considered the adiposity index of previous studies published by our group. [22][23][24] The animals were randomly divided into two experimental groups: the control group (C, n= 8 animals) that received standard diet/water and the obese group (OB, n= 8 animals) that received high sugar-fat (HSF) diet and water plus 25% of sucrose for 30 weeks. The diet model is a well-established model to induce obesity previously published by our research group. ...
... At the end of the experimental period, the results show that these animals presented higher adiposity index and several disorders, such as hyperglycemia, increased uric acid, insulin resistance, hypertriglyceridemia, elevated SBP, increased TNF-α and IL-6 levels in both heart and adipose tissue, confirming the efficacy of the diet model used. [22][23][24][25] The coexistence of obesity-related disorders -such as insulin resistance, diabetes, and dyslipidemia -associated with adipose tissue dysfunction, characterized by adipokine imbalance, promote maladaptive responses in the heart, such as myocyte hypertrophy, contractile dysfunction, and cardiac remodeling, which contribute to both the development and progression of chronic heart failure. [31][32][33] This condition was confirmed in this study, since the echocardiogram evaluation showed cardiac remodeling and diastolic dysfunction in the OB group. ...
Article
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Background: Obesity is a chronic low-grade inflammation condition related to cardiac disorders. However, the mechanism responsible for obesity-related cardiac inflammation is unclear. The toll-like receptor 4 (TLR-4) belongs to a receptor of the transmembrane family responsible for the immune response whose activation stimulates the production of proinflammatory cytokines. Objective: To test whether the activation of the TLR-4 receptor participates in the obesity cardiomyopathy process, due to cytokine production through NF-ĸB activation. Methods: Male Wistar rats were randomized into two groups: the control group (C, n= 8 animals) that received standard diet/water and the obese group (OB, n= 8 animals) that were fed a high sugar-fat diet and water plus 25% of sucrose for 30 weeks. Nutritional analysis: body weight, adiposity index, food, water, and caloric intake. Obesity-related disorders analysis: plasma glucose, uric acid and triglycerides, HOMA-IR, systolic blood pressure, TNF-α in adipose tissue. Cardiac analysis included: TLR-4 and NF-ĸB protein expression, TNF-α and IL-6 levels. Comparison by unpaired Student's t-test or Mann- Whitney test with a p-value < 0.05 as statistically significant. Results: The OB group showed obesity, high glucose, triglycerides, uric acid, HOMA, systolic blood pressure, and TNF-α in adipose tissue. OB group presented cardiac remodeling and diastolic dysfunction. TLR-4 and NF-ĸB expression and cytokine levels were higher in OB. Conclusion: Our findings conclude that, in an obesogenic condition, the inflammation derived from cardiac TLR-4 activation can be a mechanism able to lead to remodeling and cardiac dysfunction.
... In this way, the search for strategies to lower the ligand burden (AGEs and other RAGE ligands) and strategies to dampen RAGE activation have received attention, such as the use of natural compounds as a promising pool of substances to treat diseases 10,11 . Gamma-oryzanol (γOz) comprises a mixture of ferulic acid (FA) esters and phytosterols (sterols and triterpene alcohols) mainly found in rice, a very important grain in the human diet. ...
... Very recently, Sobhy et al. (2020) 15 found that oryzanols inhibit glycation and AGEs formation by a direct anti-glycation effect and by scavenging the free radicals generated during the glycation reactions. Furthermore, the antioxidant activity of γOz has been reported in both in vitro and in vivo experiments by several groups 10,36,37 . ...
Article
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Introduction: The receptor for AGEs (RAGE) is a multiligand member of the immunoglobulin superfamily of cell surface receptors expressed in many organs, among them, the kidneys. When activated, RAGE leads to a sequence of signaling that results in inflammation and oxidative stress, both involved in kidney disease pathogenesis. Gamma-oryzanol (γOz) comprises a mixture of ferulic acid (FA) esters and phytosterols (sterols and triterpene alcohols) mainly found in rice, with antioxidant and anti-inflammatory activities. Aim: To evaluate the effect of γOz to reduce renal inflammation and oxidative stress by modulating AGEs/RAGE axis in animals submitted to a high sugar-fat diet. Methods: Male Wistar rats (±187g) were randomly divided into two experimental groups: control (n = 7 animals) and high sugar-fat diet (HSF, n = 14 animals) for 20 weeks. After this period, when the presence of renal disease risk factors was detected in the HSF group (insulin resistance, dyslipidemia, increased systolic blood pressure and obesity), the HSF animals were divided to begin the treatment with γOz or continue receiving only HSF for 10 more weeks. Results: No effect of γOz on obesity and metabolic parameters was observed. However, kidney inflammation and oxidative stress decreased as soon as RAGE levels were reduced in HSF + γOz. Conclusion: It is possible to conclude that the gamma- oryzanol was effective in reducing inflammation and oxidative stress in the kidney by modulating the AGEs/RAGE axis.
... However, the HSF + RB group presented protection against kidney damage, which can be explained by the effect on inflammation and oxidative stress. The main bioactive compound in RB is gamma-oryzanol, which has demonstrated antioxidative and antiinflammatory effects 25,32 also in kidneys of obese animals 20 . ...
Article
Obesity, diabetes, and hypertension are common risk factors for chronic kidney disease (CKD). CKD arises due to many pathological insults, including inflammation and oxidative stress, which affect renal function and destroy nephrons. Rice bran (RB) is rich in vitamins and minerals, and contains significant amount of antioxidants. The aim of this study was to evaluate the preventive effect of RB on renal disease risk factors. Methods: Male Wistar rats (±325 g) were divided into two experimental groups to received a high sugar-fat diet (HSF, n = 8) or high sugar-fat diet with rice bran (HSF + RB, n = 8) for 20 weeks. At the end, renal function, body composition, metabolic parameters, renal inflammatory and oxidative stress markers were analyzed. Results: RB prevented obesity [AI (HSF= 9.92 ± 1.19 vs HSF + RB= 6.62 ± 0.78)ENT#093;, insulin resistance [HOMA (HSF= 83 ± 8 vs. HSF + RB= 42 ± 11)ENT#093;, dyslipidemia [TG (HSF= 167 ± 41 vs. HSF + RB=92 ± 40)ENT#093;, inflammation [TNF-α (HSF= 80 ± 12 vs. HSF + RB=57 ± 14), IL-6 (903 ± 274 vs. HSF + RB=535 ± 277)], oxidative stress [protein carbonylation (HSF= 3.38 ± 0.18 vs. HSF + RB=2.68 ± 0.29), RAGE (HSF=702 ± 36 vs. RSF + RB=570 ± 190)], and renal disease [protein/creatinine ratio (HSF=1.10 ± 0.38 vs. HSF + RB=0.49 ± 0.16)]. Conclusion: In conclusion, rice bran prevented renal disease by modulating risk factors.
... However, the HSF + RB group presented protection against kidney damage, which can be explained by the effect on inflammation and oxidative stress. The main bioactive compound in RB is gamma-oryzanol, which has demonstrated antioxidative and antiinflammatory effects 25,32 also in kidneys of obese animals 20 . ...
Article
Full-text available
Introduction: Obesity, diabetes, and hypertension are common risk factors for chronic kidney disease (CKD). CKD arises due to many pathological insults, including inflammation and oxidative stress, which affect renal function and destroy nephrons. Rice bran (RB) is rich in vitamins and minerals, and contains significant amount of antioxidants. The aim of this study was to evaluate the preventive effect of RB on renal disease risk factors. Methods: Male Wistar rats (±325 g) were divided into two experimental groups to received a high sugar-fat diet (HSF, n = 8) or high sugar-fat diet with rice bran (HSF + RB, n = 8) for 20 weeks. At the end, renal function, body composition, metabolic parameters, renal inflammatory and oxidative stress markers were analyzed. Results: RB prevented obesity [AI (HSF= 9.92 ± 1.19 vs HSF + RB= 6.62 ± 0.78)ENT#093;, insulin resistance [HOMA (HSF= 83 ± 8 vs. HSF + RB= 42 ± 11)ENT#093;, dyslipidemia [TG (HSF= 167 ± 41 vs. HSF + RB=92 ± 40)ENT#093;, inflammation [TNF-α (HSF= 80 ± 12 vs. HSF + RB=57 ± 14), IL-6 (903 ± 274 vs. HSF + RB=535 ± 277)], oxidative stress [protein carbonylation (HSF= 3.38 ± 0.18 vs. HSF + RB=2.68 ± 0.29), RAGE (HSF=702 ± 36 vs. RSF + RB=570 ± 190)], and renal disease [protein/creatinine ratio (HSF=1.10 ± 0.38 vs. HSF + RB=0.49 ± 0.16)]. Conclusion: In conclusion, rice bran prevented renal disease by modulating risk factors.
... Natural compounds as γOz, the main bioactive from rice bran and germ, is a compound with anti-inflammatory and antioxidant activities (Minatel et al., 2016). Studies have shown that the γOz has a positive action in the treatment of some obesity-related comorbidities and attenuation of proinflammatory cytokines (Wang et al., 2015;Francisqueti et al., 2017aFrancisqueti et al., , 2018Son et al., 2011). However, little is known about the γOz action as a possible agonist of PPAR-γ. ...
... Body weight was measured weekly. After euthanasia, the fat deposits (visceral (VAT), epididymal (EAT) and retroperitoneal (RAT) were used to calculate the adiposity index (AI) by the following formula: Francisqueti et al., 2018). ...
... The insulin level was measured using the enzyme-linked immunosorbent assay (ELISA) method using commercial kits (EMD Millipore Corporation, Billerica, MA, USA). The homeostatic model of insulin resistance (HOMA-IR) was used as an insulin resistance index, calculated according to the formula: HOMA-IR = (fasting glucose (mmol/L) × fasting insulin (μU/mL))/22.5 (Francisqueti et al., 2018). ...
Article
The literature has reported a higher prevalence of negative clinical outcomes due to Coronavirus disease 19 (COVID-19) in obese individuals. This can be explained by the cytokine storm, result from the cytokine production from both obesity and viral infection. Gamma-oryzanol (γOz) is a compound with anti-inflammatory and antioxidant activities. However, little is known about the γOz action as a possible agonist of peroxisome proliferator-activated receptor gamma (PPAR-γ). The aim of this study was to test the hypothesis that γOz attenuates the cytokine storm by stimulating PPAR-γ in the adipose tissue. Methods: Male Wistar rats were randomly divided into three experimental groups and fed ad libitum for 30 weeks with control diet (C, n = 6), high sugar-fat diet (HSF, n = 6) or high sugar-fat diet + γOz (HSF + γOz, n = 6). HSF groups also received water + sucrose (25%). The γOz dose was 0.5% in the chow. Evaluation in animals included caloric intake, body weight, adiposity index, plasma triglycerides, and HOMA-IR. In adipose tissue was evaluated: PPAR-γ gene and protein expression, inflammatory and oxidative stress parameters, and histological analysis. Results: Adipose tissue dysfunction was observed in HSF group, which presented remarkable PPAR-γ underexpression and increased levels of cytokines, other inflammatory markers and oxidative stress. The γOz treatment prevented adipose tissue dysfunction and promoted PPAR-γ overexpression. Conclusion: Natural compounds as γOz can be considered a coadjutant therapy to prevent the cytokine storm in COVID-19 patients with obesity conditions.