Garlic extract attenuates brain mitochondrial dysfunction and cognitive deficit in obese-insulin resistant rats

2014 ◽  
Vol 39 (12) ◽  
pp. 1373-1379 ◽  
Author(s):  
Hiranya Pintana ◽  
Jirapas Sripetchwandee ◽  
Luerat Supakul ◽  
Nattayaporn Apaijai ◽  
Nipon Chattipakorn ◽  
...  
Keyword(s):  
Body Weight ◽  
Cognitive Function ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Visceral Fat ◽  
Cognitive Deficit ◽  
Garlic Extract ◽  
Insulin Resistant ◽  
Mitochondrial Functions ◽  
Brain Mitochondrial Function

Oxidative stress in the obese-insulin resistant condition has been shown to affect cognitive as well as brain mitochondrial functions. Garlic extract has exerted a potent antioxidant effect. However, the effects of garlic extract on the brain of obese-insulin resistant rats have never been investigated. We hypothesized that garlic extract improves cognitive function and brain mitochondrial function in obese-insulin resistant rats induced by long-term high-fat diet (HFD) consumption. Male Wistar rats were fed either normal diet or HFD for 16 weeks (n = 24/group). At week 12, rats in each dietary group received either vehicle or garlic extract (250 and 500 mg·kg–1·day–1) for 28 days. Learning and memory behaviors, metabolic parameters, and brain mitochondrial function were determined at the end of treatment. HFD led to increased body weight, visceral fat, plasma insulin, cholesterol, and malondialdehyde (MDA) levels, indicating the development of insulin resistance. Furthermore, HFD rats had cognitive deficit and brain mitochondrial dysfunction. HFD rats treated with both doses of garlic extract had decreased body weight, visceral fat, plasma cholesterol, and MDA levels. Garlic extract also improved cognitive function and brain mitochondrial function, which were impaired in obese-insulin resistant rats caused by HFD consumption.

scholarly journals Energy restriction combined with dipeptidyl peptidase-4 inhibitor exerts neuroprotection in obese male rats

2016 ◽  
Vol 116 (10) ◽  
pp. 1700-1708 ◽  
Author(s):  
Hiranya Pintana ◽  
Pongpan Tanajak ◽  
Wasana Pratchayasakul ◽  
Piangkwan Sa-nguanmoo ◽  
Titikorn Chunchai ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Synaptic Plasticity ◽  
Cognitive Function ◽  
Insulin Sensitivity ◽  
Mitochondrial Function ◽  
Male Rats ◽  
Insulin Resistant ◽  
Hippocampal Synaptic Plasticity ◽  
Brain Insulin ◽  
Brain Mitochondrial Function

AbstractDipeptidyl peptidase-4 (DDP-4) inhibitors and energy restriction (ER) are widely used to treat insulin resistance and type 2 diabetes mellitus. However, the effects of ER or the combination with vildagliptin on brain insulin sensitivity, brain mitochondrial function, hippocampal synaptic plasticity and cognitive function in obese insulin-resistant rats have never been investigated. We hypothesised that ER with DDP-4 inhibitor exerts better efficacy than ER alone in improving cognition in obese insulin-resistant male rats by restoring brain insulin sensitivity, brain mitochondrial function and hippocampal synaptic plasticity. A total of twenty-four male Wistar rats were divided into two groups and fed either a normal diet or a high-fat diet (HFD) for 12 weeks. At week 13, the HFD rats were divided into three subgroups (n 6/subgroup) to receive one of the following treatments: vehicle, ER (60 % of energy received during the previous 12 weeks) or ER plus vildagliptin (3 mg/kg per d, p.o.) for 4 weeks. At the end of the treatment, cognitive function, metabolic parameters, brain insulin sensitivity, hippocampal synaptic plasticity and brain mitochondrial function were determined. We found that HFD-fed rats demonstrated weight gain with peripheral insulin resistance, dyslipidaemia, oxidative stress, brain insulin resistance, impaired brain mitochondrial function and cognitive dysfunction. Although HFD-fed rats treated with ER and ER plus vildagliptin showed restored peripheral insulin sensitivity and improved lipid profiles, only ER plus vildagliptin rats had restored brain insulin sensitivity, brain mitochondrial function, hippocampal synaptic plasticity and cognitive function. These findings suggest that only a combination of ER with DPP-4 inhibitor provides neuroprotective effects in obese insulin-resistant male rats.

scholarly journals DPP-4 inhibitors improve cognition and brain mitochondrial function of insulin-resistant rats

2013 ◽  
Vol 218 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Hiranya Pintana ◽  
Nattayaporn Apaijai ◽  
Nipon Chattipakorn ◽  
Siriporn C Chattipakorn
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Dipeptidyl Peptidase 4 ◽  
Cognitive Behaviors ◽  
Insulin Resistant ◽  
Stress Levels ◽  
To Receive ◽  
Brain Mitochondrial Function

Recent evidence has demonstrated that insulin resistance is related to the development of type 2 diabetes mellitus. Our previous study found that high-fat diet (HFD) consumption caused not only peripheral and brain insulin resistance but also brain mitochondrial dysfunction and cognitive impairment. Vildagliptin and sitagliptin, dipeptidyl-peptidase-4 inhibitors, are recently developed anti-diabetic drugs. However, the effects of both drugs on cognitive behaviors and brain mitochondrial function in HFD-induced insulin-resistant rats have not yet been investigated. Sixty male Wistar rats were divided into two groups to receive either normal diet or HFD for 12 weeks. Rats in each group were then further divided into three treatment groups to receive either vehicle, vildagliptin (3 mg/kg per day), or sitagliptin (30 mg/kg per day) for 21 days. The cognitive behaviors of the rats were tested using the Morris Water Maze test. Blood samples were collected to determine metabolic parameters and plasma oxidative stress levels. Upon completion of the study, the animals were killed and the brains were removed to investigate brain and hippocampal mitochondrial function as well as to determine oxidative stress levels. We demonstrated that both drugs significantly improved the metabolic parameters and decreased circulating and brain oxidative stress levels in HFD-induced insulin-resistant rats. In addition, both drugs completely prevented brain and hippocampal mitochondrial dysfunction and equally improved the learning behaviors impaired by the HFD. Our findings suggest that the inhibition of dipeptidyl-peptidase-4 enzymes with vildagliptin or sitagliptin in insulin-resistant rats not only increases peripheral insulin sensitivity but also decreases brain dysfunction.

Hyperbaric oxygen therapy attenuates D-galactose-induced-age-related cardiac dysfunction through mitigating cardiac mitochondrial dysfunction in pre-diabetic rats

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Bo-Htay ◽  
T Shwe ◽  
S Palee ◽  
T Pattarasakulchai ◽  
K Shinlapawittayatorn ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
High Fat Diet ◽  
Diabetic Rats ◽  
Normal Diet ◽  
Lv Function ◽  
High Fat ◽  
Insulin Resistant ◽  
Lv Dysfunction ◽  
Age Related ◽  
Mitochondrial Functions

Abstract Background D-galactose (D-gal) induced ageing has been shown to exacerbate left ventricular (LV) dysfunction via worsening of apoptosis and mitochondrial dysfunction in the heart of obese rats. Hyperbaric oxygen therapy (HBOT) has been demonstrated to exert anti-inflammatory and anti-apoptotic effects in multiple neurological disorders. However, the cardioprotective effect of HBOT on inflammation, apoptosis, LV and mitochondrial functions in D-gal induced ageing rats in the presence of obese-insulin resistant condition has never been investigated. Purpose We sought to determine the effect of HBOT on inflammation, apoptosis, mitochondrial functions and LV function in pre-diabetic rats with D-gal induced ageing. We hypothesized that HBOT attenuates D-gal induced cardiac mitochondrial dysfunctions and reduces inflammation and apoptosis, leading to improved LV function in pre-diabetic rats. Methods Forty-eight male Wistar rats were fed with either normal diet or high-fat diet for 12 weeks. Then, rats were treated with either vehicle groups (0.9% NSS, subcutaneous injection (SC)) or D-gal groups (150 mg/kg/day, SC) for 8 weeks. At week 21, rats in each group were equally divided into 6 sub-groups: normal diet fed rats treated with vehicle (NDV) sham, normal diet fed rats treated with D-gal (NDDg) sham, high fat diet fed rats treated with D-gal (HFDg) sham, high fat diet fed rats treated with vehicle (HFV) + HBOT, NDDg + HBOT and HFDg + HBOT. Sham treated rats were given normal concentration of O2 (flow rate of 80 L/min, 1 ATA for 60 minutes), whereas HBOT treated rats were subjected to 100% O2 (flow rate of 250 L/min, 2 ATA for 60 minutes), given once daily for 2 weeks. Results Under obese-insulin resistant condition, D-gal-induced ageing aggravated LV dysfunction (Fig 1A) and impaired cardiac mitochondrial function, increased cardiac inflammatory and apoptotic markers (Fig 1B). HBOT markedly reduced cardiac TNF-α level and TUNEL positive apoptotic cells, and improved cardiac mitochondrial function as indicated by decreased mitochondrial ROS production, mitochondrial depolarization and mitochondrial swelling, resulting in the restoration of the normal LV function in HFV and NDDg rats, compared to sham NDDg rats. In addition, in HFDg treated rats, HBOT attenuated cardiac TNF-α level, TUNEL positive apoptotic cells and cardiac mitochondrial dysfunction, compared to sham HFDg rats, leading to improved cardiac function as indicated by increased %LV ejection fraction (LVEF) (Figure 1). Conclusion HBOT efficiently alleviates D-gal-induced-age-related LV dysfunction through mitigating inflammation, apoptosis and mitochondrial dysfunction in pre-diabetic rats. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): 1. The National Science and Technology Development Agency Thailand, 2. Thailand Research Fund Grants

scholarly journals HuoXue QianYang QuTan Recipe attenuates left ventricular hypertrophy in obese hypertensive rats by improving mitochondrial function through SIRT1/PGC-1α deacetylation pathway

2019 ◽  
Vol 39 (12) ◽  
Author(s):  
Jing Wang ◽  
Zhen-Hua Dong ◽  
Ming-Tai Gui ◽  
Lei Yao ◽  
Jian-Hua Li ◽  
...  
Keyword(s):  
Body Weight ◽  
Left Ventricular Hypertrophy ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Ventricular Hypertrophy ◽  
Vital Role ◽  
Left Ventricular ◽  
Therapeutic Effects ◽  
Glycolipid Metabolism ◽  
Obesity Hypertension

Abstract Mitochondrial dysfunction plays a vital role in the progression of left ventricular hypertrophy (LVH). Previous studies have confirmed that the disorder of SIRT1/PGC-1α deacetylation pathway aggravated mitochondrial dysfunction. HuoXue QianYang QuTan Recipe (HQQR) is a commonly used prescription that has shown therapeutic effects on obesity hypertension and its complications. However, the potential mechanisms are still unclear. In the present study, obesity hypertension (OBH) was established in rats and we investigated the efficacy and mechanisms of HQQR on LVH. Rats were divided into the five groups: (1) WKY-ND group, (2) SHR-ND group, (3) OBH-HF group, (4) OBH-HF/V group and (5) OBH-HF/H group. We evaluated body weight, Lee index and blood pressure (BP) before and every 2 weeks after treatment. After 10 weeks of treatment, we mainly detected glycolipid metabolic index, the severity of LVH, mitochondrial function along with SIRT1/PGC-1α deacetylation pathway. Our results showed that HQQR significantly lowered body weight, Lee index, BP and improved the disorder of glycolipid metabolism in OBH rats. Importantly, we uncovered HQQR could alleviate mitochondrial dysfunction in OBH rats by regulating SIRT1/PGC-1α deacetylation pathway. These changes could be associated with the inhibition of LVH.

Protocatechuic acid protects brain mitochondrial function in streptozotocin-induced diabetic rats

2015 ◽  
Vol 40 (10) ◽  
pp. 1078-1081 ◽  
Author(s):  
Yoswaris Semaming ◽  
Jirapas Sripetchwandee ◽  
Piangkwan Sa-nguanmoo ◽  
Hiranya Pintana ◽  
Patchareewan Pannangpetch ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Glycemic Control ◽  
Mitochondrial Dysfunction ◽  
Stress Reduction ◽  
Mitochondrial Function ◽  
Protocatechuic Acid ◽  
Diabetic Rats ◽  
Brain Oxidative Stress ◽  
The Brain ◽  
Brain Mitochondrial Function

Brain mitochondrial dysfunction has been demonstrated in diabetic animals with neurodegeneration. Protocatechuic acid (PCA), a major metabolite of anthocyanin, has been shown to exert glycemic control and oxidative stress reduction in the heart. However, its effects on oxidative stress and mitochondrial function in the brain under diabetic condition have never been investigated. We found that PCA exerted glycemic control, attenuates brain mitochondrial dysfunction, and contributes to the prevention of brain oxidative stress in diabetic rats.

scholarly journals Zhen-Wu-Tang Induced Mitophagy to Protect Mitochondrial Function in Chronic Glomerulonephritis via PI3K/AKT/mTOR and AMPK Pathways

2021 ◽  
Vol 12 ◽  
Author(s):  
Bihao Liu ◽  
Yiwen Cao ◽  
Dejuan Wang ◽  
Yuan Zhou ◽  
Peichun Zhang ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Mitochondrial Membrane ◽  
Periodic Acid ◽  
Underlying Mechanism ◽  
Chronic Glomerulonephritis ◽  
Heat Shock Protein 60 ◽  
Periodic Acid Schiff ◽  
Pi3k Inhibitor Ly294002 ◽  
Mitochondrial Functions

Chronic glomerulonephritis (CGN) is one of the major causes of end-stage kidney disease. Zhen-wu-tang (ZWT), as a famous Chinese herbal prescription, is widely used in China for CGN therapy in clinic. However, the mechanism of ZWT in CGN has not been fully understood. The present study explored the therapeutic effect and the underlying mechanism of ZWT on mitochondrial function in cationic bovine serum albumin (C-BSA)-induced CGN model rats and tumor necrosis factor (TNF-α)-damaged mouse podocytes. The renal functions were measured by serum creatinine (Scr) and blood urea nitrogen (BUN). Renal pathological changes and ultrastructure of kidney tissues were evaluated by periodic acid-Schiff (PAS) staining and transmission electron microscopy. The levels of antioxidases, including mitochondrial catalase (CAT), superoxide dismutase 2 (SOD2), and peroxiredoxin 3 (PRDX3), in CGN rats were examined by real-time PCR. The mitochondrial functions of podocytes were measured by ATP concentration, mitochondrial membrane potential (MMP), and mitochondrial ROS (mtROS). For mitophagy level detection, the expressions of mitophagy-related proteins, including LC3, p62, heat shock protein 60 (HSP60), and translocase of outer mitochondrial membrane 20 (TOMM20), were measured by Western blot, as the colocation of LC3 and mitochondrial marker COX IV were evaluated by immunofluorescence. Our results manifested that ZWT ameliorated CGN model rats by a remarkable decrease in Scr and BUN, inhibition of mesangial matrix proliferation, protection against foot processes fusion, and basement membrane thickening. More importantly, ZWT protected against mitochondrial dysfunction by increasing the expressions of CAT, SOD2, and PRDX3 in CGN model rats, increased ATP content and MMP in podocytes, and decreased excessive mtROS. Furthermore, ZWT induced mitophagy in CGN through increasing the expression of LC3, and decreasing p62, HSP60, TOMM20, and ZWT also enhanced the colocation of LC3 to the mitochondria. We found that ZWT inhibited the PI3K/AKT/mTOR pathway, which could be disturbed by PI3K inhibitor LY294002 and agonist insulin-like growth factor 1. Moreover, ZWT reversed the inhibition of the AMPK pathway in CGN. Overall, ZWT ameliorated renal mitochondrial dysfunction probably by inducing mitophagy via the PI3K/AKT/mTOR and AMPK pathways.

scholarly journals Avocado Oil Improves Mitochondrial Function and Decreases Oxidative Stress in Brain of Diabetic Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Omar Ortiz-Avila ◽  
Mauricio Esquivel-Martínez ◽  
Berenice Eridani Olmos-Orizaba ◽  
Alfredo Saavedra-Molina ◽  
Alain R. Rodriguez-Orozco ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Diabetic Complication ◽  
Diabetic Rats ◽  
Complex Iii ◽  
Diabetic Encephalopathy ◽  
Avocado Oil ◽  
Brain Mitochondrial Function

Diabetic encephalopathy is a diabetic complication related to the metabolic alterations featuring diabetes. Diabetes is characterized by increased lipid peroxidation, altered glutathione redox status, exacerbated levels of ROS, and mitochondrial dysfunction. Although the pathophysiology of diabetic encephalopathy remains to be clarified, oxidative stress and mitochondrial dysfunction play a crucial role in the pathogenesis of chronic diabetic complications. Taking this into consideration, the aim of this work was to evaluate the effects of 90-day avocado oil intake in brain mitochondrial function and oxidative status in streptozotocin-induced diabetic rats (STZ rats). Avocado oil improves brain mitochondrial function in diabetic rats preventing impairment of mitochondrial respiration and mitochondrial membrane potentialΔΨm, besides increasing complex III activity. Avocado oil also decreased ROS levels and lipid peroxidation and improved the GSH/GSSG ratio as well. These results demonstrate that avocado oil supplementation prevents brain mitochondrial dysfunction induced by diabetes in association with decreased oxidative stress.

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