Neuroprotective Effects of a Novel Antioxidant Mixture Twendee X in Mouse Stroke Model
Introduction
Ischemic stroke is a leading cause of mortality and neurologic impairments worldwide.1 Therapeutic strategies against stroke remain limited, and further novel therapies are required in daily clinical practice.2 Oxidative stress and inflammation are important aggravating factors in acute ischemic stroke.3, 4 Reactive oxygen species (ROS) is gradually generated during cerebral ischemia, then excessively increased after reperfusion notably in the peri-ischemic area with oxidation of cellular DNA, lipids, and proteins,5, 6, 7, 8 and then often focused as a medical treatable target.9
We originally showed the strong neuroprotective effects of a free radical scavenger edaravone.8, 10, 11 Furthermore, we reported that dietary supplements such as ginkgo extract,12 platinum nanoparticle species,13 and antioxidativenutrient-rich enteral diet14 showed neuroprotective effects on the ischemic brains of mice. Dietary supplements did not show the strong effects on diseases as medicinal chemicals. However, they are safe and valuable for the prevention and treatment of various diseases.15
Twendee X (TwX) is an anti-aging supplement containing multiple antioxidants and a patented composition.16 TwX has strong antioxidant effects, and increases superoxide dismutase and cell protection effects.17 In the present study, we validated whether TwX could be helpful in ameliorating mouse brain damages and oxidative stress following experimental transient middle cerebral artery occlusion (tMCAO).
Section snippets
Animals and Focal Cerebral Ischemia
All experimental procedures were approved by the Animal Committee of the Okayama University Graduate School of Medicine (OKU-2015573). Adult male C57BL/6JJcl mice (23-27 g, 8 weeks old) were obtained from CLEA Japan (Tokyo, Japan). The mice were maintained in a temperature-regulated room (23-25°C) on a 12-hour light–dark cycle and allowed free access to food and water. From 9 weeks of age, the mice received vehicle (physiological saline, ip, n = 15) or TwX (20 mg/kg per day, ip, n = 16) for 14
Serum Oxidative Stress and the Antioxidative Activities
As compared with the vehicle (V-1d, 165 ± 21.3 CARR U), TwX did not reduce oxidative stress (d-ROMs) 1 day after tMCAO (TwX-1d, 164 ± 10.3 CARR U), but showed a slight reduction 5 days after (V-5d = 167.5 ± 27.8 versus TwX-5d = 149.5 ± 14.4 CARR U, not significant) (Fig 2). On the other hand, OXY-Adsorbent showed a reduction tendency in TwX both 1 day after tMCAO (V-1d, 319.0 ± 52.4 µmol HClO/mL; TwX-1d, 294.0 ± 33.4 µmol HClO/mL) and 5 days after (V-5d, 337.5 ± 51.3 µmol HClO/mL; TwX-5d,
Discussion
The present study demonstrated that a novel antioxidant mixture TwX showed neuroprotective effects on mice cerebral ischemia by reducing the infarct size (Fig 3), and reducing both oxidative stress markers (Fig 4) and inflammatory markers (Fig 5). ROS is incrementally generated during cerebral ischemia, then explosively increased after reperfusion particularly in the penumbra with oxidation of cellular DNA, lipids, and proteins.5, 6, 7, 8 Such oxidative stress is detrimental in the cerebral
Acknowledgments
We are grateful to Dr. Maruyama T of the Department of Preventive Dentistry at Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, especially for their technical assistance in d-ROMs tests and OXY-Adsorbent tests.
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Grant support: This work was partly supported by Grants-in-Aid for Scientific Research (B, 25293202 and C, 15K09316), Challenging Research (15K15527), and Young Research (15K21181), and by Grants-in-Aid from the Research Committees (Mizusawa H, Nakashima K, Nishizawa M, Sasaki H, and Aoki M) from the Ministry of Health, Labour and Welfare, Japan.