Ursolic-Acid-Enriched Herba Cynomorii Extract Protects against Oxidant Injury in H9c2 Cells and Rat Myocardium by Increasing Mitochondrial ATP Generation Capacity and Enhancing Cellular Glutathione Redox Cycling, Possibly through Mitochondrial Uncoupling

Chen, Jihang; Ko, Kam Ming

doi:10.1155/2013/924128

Cited by 16 publications

(20 citation statements)

References 45 publications

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“…Furthermore, several studies have suggested that UA attenuated ischemia and reperfusion injury in regions other than the brain such as the heart and the kidney. 20 – 24 UA may also hold potential as a therapeutic agent to prevent muscle ischemic injury; this evidence may provide new insight into the effects of UA on ischemic vascular diseases. 24 …”

Section: Discussionmentioning

confidence: 98%

Ursolic acid reduces the metalloprotease/anti-metalloprotease imbalance in cerebral ischemia and reperfusion injury

Wang

Deng

2016

DDDT

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BackgroundActivators of PPARs, particularly PPARγ, may be effective neuroprotective drugs against inflammatory responses in cerebral ischemia and reperfusion injury. Ursolic acid (UA) may act as a PPARγ agonist and serve as an anti-inflammatory agent. In this study, we used a rat middle cerebral artery occlusion and reperfusion model to examine how UA acts as a neuroprotective agent to modulate the metalloprotease/anti-metalloprotease balance.MethodsThe middle cerebral artery occlusion and reperfusion model (occlusion for 2 hours followed by reperfusion for 48 hours) was induced in male Sprague Dawley rats. UA was administered intragastrically 0.5, 24, and 47 hours after reperfusion. Bisphenol A diglycidyl ether (a PPARγ antagonist) was intraperitoneally administered 1, 24.5, and 47.5 hours after reperfusion. Forty-eight hours after reperfusion, neurological deficits and infarct volume were estimated. The PPARγ level and the metalloprotease/anti-metalloprotease balance were examined by Western blotting and immunohistochemistry. The activation of MAPK signaling pathways was also assessed.ResultsUA-treated (5, 10, or 20 mg/kg) rats showed significant improvement in neurological deficit score, infarct volume, and the number of intact neurons compared with control rats (P<0.01). Both the PPARγ protein level and the percentage of PPARγ-positive cells were increased in the UA-treated groups (P<0.01). Compared with the control group, the UA-treated groups exhibited reduced protein levels of MMP2, MMP9, and activated MAPKs (P<0.01) but an increased level of TIMP1 (P<0.01). UA exerted its protective effects in a dose-dependent manner. Co-treatment with UA and bisphenol A diglycidyl ether completely abolished the UA-induced changes in PPARγ expression; however UA continued to exert a significant but partial neuroprotective effect.ConclusionUA can act as a PPARγ agonist to improve the metalloprotease/anti-metalloprotease balance, possibly by inhibiting the activation of the MAPK signaling pathway, thereby attenuating cerebral ischemia and reperfusion injury. Therefore, UA may serve as a novel neuroprotective therapeutic agent.

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Section: Discussionmentioning

confidence: 98%

Ursolic acid reduces the metalloprotease/anti-metalloprotease imbalance in cerebral ischemia and reperfusion injury

Wang

Deng

2016

DDDT

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“…Ursolic acid (UA) is an isomer of oleanolic acid and a lipophilic triterpenoid compound primarily found in apples and many herbs [ 20 ]. Recently, UA has been demonstrated to have important biological roles including anti-fat accumulation [ 21 ], anti-insulin resistance via IGF-1 [ 6 ], anti-muscle atrophy [ 22 ], anti-cancer [ 23 ], anti-oxidation [ 24 ], and anti-inflammatory effects [ 25 ]. Above all, the underlying mechanism of UA is the enhancement or maintenance of skeletal muscle mass and function in vivo and vitro [ 22 , 25 , 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

Ursolic Acid-Induced Elevation of Serum Irisin Augments Muscle Strength During Resistance Training in Men

Bang

Seo

Chung

et al. 2014

Korean J Physiol Pharmacol

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Ursolic acid (UA), a type of pentacyclic triterpenoid carboxylic acid purified from natural plants, can promote skeletal muscle development. We measured the effect of resistance training (RT) with/without UA on skeletal muscle development and related factors in men. Sixteen healthy male participants (age, 29.37±5.14 years; body mass index=27.13±2.16 kg/m2) were randomly assigned to RT (n=7) or RT with UA (RT+UA, n=9) groups. Both groups completed 8 weeks of intervention consisting of 5 sets of 26 exercises, with 10~15 repetitions at 60~80% of 1 repetition maximum and a 60~90-s rest interval between sets, performed 6 times/week. UA or placebo was orally ingested as 1 capsule 3 times/day for 8 weeks. The following factors were measured pre-and post-intervention: body composition, insulin, insulin-like growth factor-1 (IGF-1), irisin, and skeletal muscle strength. Body fat percentage was significantly decreased (p<0.001) in the RT+UA group, despite body weight, body mass index, lean body mass, glucose, and insulin levels remaining unchanged. IGF-1 and irisin were significantly increased compared with baseline levels in the RT+UA group (p<0.05). Maximal right and left extension (p<0.01), right flexion (p<0.05), and left flexion (p<0.001) were significantly increased compared with baseline levels in the RT+UA group. These findings suggest that UA-induced elevation of serum irisin may be useful as an agent for the enhancement of skeletal muscle strength during RT.

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“…14 In brief, following incubation with UA, cells were collected by trypsinization and suspended in assay buffer (120 mM KCl, 5 mM KH 2 PO 4 , 2 mM EGTA, 10 mM HEPES, 0.1 mM MgCl 2 , 0.5% BSA, pH 7.4). An aliquot of suspended cells (1.5 × 10 6 cells) was placed in the electrode chamber.…”

Section: Measurement Of Mitochondrial Respiration In H9c2 Cellsmentioning

confidence: 99%

Mitochondrial reactive oxygen species production mediates ursolic acid-induced mitochondrial uncoupling and glutathione redox cycling, with protection against oxidant injury in H9c2 cells

Chen

Wong

2015

Food Funct.

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Ursolic acid (UA), a natural pentacyclic triterpenoid carboxylic acid, is a ubiquitous compound widely distributed in many plants, fruits and medicinal herbs worldwide. A previous study in our laboratory has shown that UA can increase the mitochondrial ATP generation capacity (ATP-GC) and a glutathione-dependent antioxidant response, thereby protecting against oxidant injury in H9c2 cells in vitro and rat hearts ex vivo. However, the mechanism underlying the cellular protective effects induced by UA remains largely unknown. The present study has shown that pre-incubation with UA produces a transient increase in the mitochondrial membrane potential in H9c2 cells, which was accompanied by increases in mitochondrial reactive oxygen species (ROS) production. Studies using an antioxidant (dimethylthiourea) indicated that the suppression of mitochondrial ROS completely abrogated the UA-induced enhancement of mitochondrial uncoupling and glutathione reductase (GR)-mediated glutathione redox cycling, as well as protection against menadione cytotoxicity in H9c2 cells. Co-incubation with specific inhibitors of uncoupling proteins and GR almost completely prevented the cytoprotection afforded by UA against menadione-induced cytotoxicity in H9c2 cells. The results obtained so far suggest that UA-induced mitochondrial ROS production can elicit mitochondrial uncoupling and glutathione-dependent antioxidant responses, which offer cytoprotection against oxidant injury in H9c2 cells.

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Ursolic-Acid-Enriched Herba Cynomorii Extract Protects against Oxidant Injury in H9c2 Cells and Rat Myocardium by Increasing Mitochondrial ATP Generation Capacity and Enhancing Cellular Glutathione Redox Cycling, Possibly through Mitochondrial Uncoupling

Cited by 16 publications

References 45 publications

Ursolic acid reduces the metalloprotease/anti-metalloprotease imbalance in cerebral ischemia and reperfusion injury

Ursolic acid reduces the metalloprotease/anti-metalloprotease imbalance in cerebral ischemia and reperfusion injury

Ursolic Acid-Induced Elevation of Serum Irisin Augments Muscle Strength During Resistance Training in Men

Mitochondrial reactive oxygen species production mediates ursolic acid-induced mitochondrial uncoupling and glutathione redox cycling, with protection against oxidant injury in H9c2 cells

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