A Polyphenolic Complex Attenuates Inflammatory Response and Blood- Brain Barrier Disruption.

BACKGROUND: Cerebral ischemia causes a strong inflammatory response. Neumentix is a dietary supplement containing 14.9% rosmarinic acid and 29.9% total phenolic content, which has been proved to be beneficial against inflammatory response. Therefore, Neumentix's effect on anti-inflammatory and blood brain barrier (BBB) disruption in transient middle cerebral artery occlusion (tMCAO) model mice is investigated in this study. METHODS: After the pretreatment of vehicle or Neumentix 134 mg/kg/d, intraperitoneal injection (i.p.) (containing rosmarinic acid 20 mg/kg/d) for 14 days, mice were subjected to tMCAO for 60 min and kept receiving vehicle or Neumentix daily 5 days afterward. RESULTS: Neumentix treatment ameliorated neurobehavioral impairment in the corner test (5d after tMCAO, **P<0.01), reduced infarct volume (#P<0.05), suppressed expression of ionized calciumbinding adapter molecule-1 (Iba-1), tumor necrosis factor alpha (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) (###P<0.001), and improved the integrity of BBB (§P<0.05) at 5 days after tMCAO. CONCLUSION: The present study provided an evidence of Neumentix's anti-inflammatory and neuroprotection effect against BBB disruption on experimental tMCAO model mice, suggesting that Neumentix could be a potential therapeutic agent for stroke.

Antioxidative effects of a novel dietary supplement Neumentix in a mouse stroke model.

BACKGROUND: During an acute stroke, reactive oxygen species are overproduced and the endogenous antioxidative defense systems are disrupted. Therefore, antioxidative therapy can be a promising scheme to reduce the severity of stroke. Neumentix is a novel antioxidative supplement produced from a patented mint line and contains a high content of rosmarinic acid (RA). Although Neumentix has proven diverse efficacy and safety in clinical trials, its effect on strokes is unclear. METHODS: Mice that were treated with Neumentix or vehicle for 14 days underwent transient middle cerebral artery occlusion (tMCAO) for 60 min. Mice were sacrificed 5 days after tMCAO. RESULTS: Neumentix preserved body weight after tMCAO, showed a high antioxidative effect in serum, and reduced infarction volume compared to the vehicle. The expression of 4-hydroxy-2-nonenal, Nε-(carboxymethyl) lysine, and 8-hydroxy-2'-deoxyguanosine was reduced in Neumentix-treated mice. CONCLUSION: The antioxidative effect of Neumentix was confirmed. This is the first report to demonstrate the antioxidative effect of Neumentix on strokes.

Yoga-plus exercise mix promotes cognitive, affective, and physical functions in elderly people.

Objectives: Increased attention is being paid to Asian medicine in balanced total health care. We investigated the effects of mixed exercise including yoga ('Yoga-plus') among elderly individuals. Methods: A total of 385 subjects (72 males and 313 females, 75.5 ± 8.7 years old) participated in a 12-month (M) exercise program at a health and welfare center, a day service center, and a nursing home. Cognitive, affective, and physical functions, and activities of daily living (ADL), were compared at baseline (0M), 6M and 12M of exercise intervention. Results: Mean scores on the frontal assessment battery, clock drawing test, cube copying test, letter fluency, and category fluency significantly improved after the Yoga-plus intervention, while mini-mental state examination, Hasegawa dementia score-revised, and trail-making test performance were relatively stable. Affective scores on the geriatric depression scale (GDS), apathy scale (AS) and Abe's behavioral and psychological symptoms of dementia were not significantly affected by exercise therapy, but subgroups with higher baseline GDS (GDS ≥ 5) and AS (AS ≥ 16) scores showed a significant improvement after intervention. One-leg standing time and 3-m timed up and go test performance significantly improved after 12M intervention. Discussion: Yoga-plus improved cognitive, affective, ADL, and physical functions in a local elderly population, particularly among below-baseline individuals, indicating the benefits of dementia prevention among elderly individuals.

Clinical Benefits of Antioxidative Supplement Twendee X for Mild Cognitive Impairment: A Multicenter, Randomized, Double-Blind, and Placebo-Controlled Prospective Interventional Study.

Oxidative stress is part of the entire pathological process that underlies the development of Alzheimer's disease (AD), including the mild cognitive impairment (MCI) stage. Twendee X (TwX) is a supplement containing a strong antioxidative mix of eight antioxidants, which has been shown to have a clinical and therapeutic benefit in AD model mice. Here, we conducted a multicenter, randomized, double-blind, and placebo-controlled prospective interventional study to evaluate the efficacy of TwX in mitigating MCI. The primary outcomes were differences in Mini-Mental State Examination (MMSE) and Hasegawa Dementia Scale-revised (HDS-R) scores between baseline and six months for placebo and TwX groups. Seventy-eight subjects with MCI were randomized into placebo (n = 37) and TwX (n = 41) groups. MMSE scores at six months differed significantly between the TwX and placebo groups (p = 0.018), and HDS-R scores for the TwX group exhibited a significant improvement at six months relative to baseline (p = 0.025). The TwX group did not show any change in affective or activities of daily living scores at six months. The present study indicates that strong antioxidative supplement TwX is clinical beneficial for cognitive function in subjects with MCI.

Twendee X Ameliorates Phosphorylated Tau, α-Synuclein and Neurovascular Dysfunction in Alzheimer's Disease Transgenic Mice With Chronic Cerebral Hypoperfusion.

BACKGROUND: The pathological impact of chronic cerebral hypoperfusion (CCH) on Alzheimer's disease (AD) is still poorly understood. In the present study, we investigated the role of CCH on an AD mouse model in phosphorylated tau and α-synuclein pathology, neurovascular unit, cerebrovascular remodeling, and neurovascular trophic coupling. Moreover, examined protective effect of a new antioxidant Twendee X (TwX). METHODS: APP23 mice were implanted to bilateral common carotid arteries stenosis with ameroid constrictors to gradually decrease the cerebral blood flow. The effects of the administration of TwX were evaluated by immunohistochemical analysis and Immunofluorescent histochemistry. RESULTS: The present study revealed that the expressions of phospho-tau and phospho-α-synuclein were significantly increased in the APP23 + CCH mice group as compared with wild type and APP23 mice groups (*P < .05 and ⁎⁎P < .01 versus WT; #P < .05 and ##P < .01 versus APP23). In addition, CCH significantly exacerbated MMP-9 activation relating to blood-brain barrier destruction (⁎⁎P < .01 versus WT; #P < .05, and ##P < .01 versus APP23), enhanced neurovascular remodeling, and impaired a neurovascular trophic coupling in the vascular endothelial BDNF expression of the APP23 + CCH group. TwX treatment (20 mg/kg/day, from 4.5 to 12 months) significantly reduced tau and α-synuclein pathologies, ameliorated neurovascular dysfunction compared with APP23 + CCH group. CONCLUSIONS: Our findings indicate that administration of a new antioxidative mixture TwX substantially reduced the above neuropathologic abnormalities, suggesting a potential therapeutic benefit of TwX for AD with CCH.

Clinical and Pathological Benefit of Twendee X in Alzheimer's Disease Transgenic Mice with Chronic Cerebral Hypoperfusion.

BACKGROUND: Multiple pathogeneses are involved in Alzheimer's disease (AD), such as amyloid-ß accumulation, neuroinflammation, and oxidative stress. The pathological impact of chronic cerebral hypoperfusion on Alzheimer's disease is still poorly understood. METHODS: APP23 mice were implanted to bilateral common carotid arteries stenosis with ameroid constrictors for slowly progressive chronic cerebral hypoperfusion (CCH). The effects of the administration of Twendee X (TwX) were evaluated by behavioral analysis, immunohistochemical analysis, and immunofluorescent histochemistry. RESULTS: In the present study, chronic cerebral hypoperfusion, which is commonly found in aged Alzheimer's disease, significantly exacerbated motor dysfunction of APP23 mice from 5 months and cognitive deficit from 8 months of age, as well as neuronal loss, extracellular amyloid-ß plaque and intracellular oligomer formations, and amyloid angiopathy at 12 months. Severe upregulations of oxidative markers and inflammatory markers were found in the cerebral cortex, hippocampus, and thalamus at 12 months. Twendee X treatment (20 mg/kg/d, from 4.5 to 12 months) substantially rescued the cognitive deficit and reduced the above amyloid-ß pathology and neuronal loss, alleviated neuroinflammation and oxidative stress. CONCLUSIONS: The present findings suggested a potential therapeutic benefit of Twendee X for Alzheimer's disease with chronic cerebral hypoperfusion.

Therapeutic Effects of Pretreatment with Tocovid on Oxidative Stress in Postischemic Mice Brain.

BACKGROUND: Dietary supplement is an attempt to reduce the risk of ischemic stroke in high-risk population. A new mixed vitamin E-Tocovid that mainly contains tocotrienols other than tocopherol, attenuated the progression of white matter lesions by oral in humans. However, the effect of Tocovid on ischemic stroke has not been examined. In the present study, we assessed the therapeutic effects of Tocovid pretreatment on transient middle cerebral artery occlusion (tMCAO) in mice. MATERIALS AND METHODS: After pretreatment with Tocovid (200 mg/kg/d) or vehicle for 1 month, 60-minute tMCAO was performed, and these mice were examined at 1 day, 3 days, and 7 days after reperfusion. We histologically assessed the effects of Tocovid pretreatment on the expressive changes of oxidative stress markers, cleaved caspase-3, and LC3-II after tMCAO in mice. RESULTS: We observed that Tocovid pretreatment significantly improved the rotarod time, reduced infarct volume, decreased the number of 4-HNE, nitrotyrosine, and 8-OhdG positive cells, inhibited advanced glycation end products biomarkers RAGE, CMA, and CML expressions, and increased Nrf2 and MRP1 levels with GSSG/GSH ratio decrease. Furthermore, Tocovid pretreatment greatly decreased cleaved caspase-3 and LC3-II expressions after tMCAO. CONCLUSIONS: The present study obviously demonstrated that Tocovid pretreatment showed neuroprotective effects against oxidative stress and at least in part by antiapoptotic/autophagic cell death in ischemic mice brain.