The antiaging property of aqueous extract of Millingtonia hortensis flowers in aging neuron.

Cellular senescence is the key mediator of cellular dysfunction before undergoing degenerative disease such as Alzheimer's disease. The aging process was mainly by the overactivation of senescence associated ß-galactosidase (SA-ß-gal) enzyme before mediated several negative responses, including intracellular reactive oxygen species (ROS) production, cellular senescence regulation, and death prior encourage synaptic loss. Thus, in the recent work, we evaluated the in vitro effects of aqueous extract of Millingtonia hortensis L. (MH) from flower in hydrogen peroxide (H2O2)-induced senescence in SK-N-SH cells. Herein, we demonstrated that MH significantly increased cell viability and decreased both of apoptotic cells and ROS production in a dose-dependent manner comparing to aging group (P < 0.01) using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry, and ROS assay. Furthermore, the number of SA-ß-gal-positive cells was also reduced in MH treatment (P < 0.01) together with the promotion of Sirt-1 protein. Importantly, MH also promoted the synaptic plasticity by decreased acetylcholinesterase activity and increased synaptophysin expression in aging neurons comparing to aging group (P < 0.01). Hispidulin (the active ingredient in MH) was also revealed the similarly effects to MH. Therefore, we suggested that MH might be beneficially for neurodegenerative disease that caused by aging.

Phonophoresis of Phyllanthus amarus nanoparticle gel improves functional capacity in individuals with knee osteoarthritis: A randomized controlled trial.

OBJECTIVE: This study examined the effects of treatment with Phyllanthus amarus nanoparticle gel applied by phonophoresis (PP) and ultrasound therapy (UT) in patients with symptomatic knee osteoarthritis (OA) using a randomized, double-blind, controlled trial. METHODS: Patients with knee OA (n = 40; mean age ±â€¯SD, 64.30 ±â€¯9.71 years), who had visual analogue scale (VAS) scores for knee pain intensity of 68.00 ±â€¯9.58 (UT group) and 71.00 ±â€¯8.74 (PP group, respectively) before treatment, were randomly allocated into two groups. Both groups were treated with an ultrasound program in continuous mode, 1.0 W/cm2, 10 min per session, for 10 sessions. Nanoparticles of P. amarus were used in the PP group, whereas a nondrug coupling gel was used in the UT group. The 6-min walk test (6-MWT) was performed to evaluate functional capacity. The VAS and the 6-MWT were evaluated before and after 10 treatment sessions in both groups using a double-blind procedure. RESULTS: VAS and 6-MWT showed significant improvement after treatment in both groups (p < 0.05). The PP group showed more significant effects than the UT group, in terms of both reducing the VAS pain score (p < 0.05) and improving 6-MWT (p < 0.05). CONCLUSIONS: PP is suggested as an effective method for the treatment of symptomatic knee OA for reducing pain and improving functional capacity.

Simple artificial training device for respiratory muscle strength and lung volumes in healthy young male and female subjects: A pilot study.

OBJECTIVE: The aim of this study was to evaluate the efficiency of a simple artificial device for respiratory muscle strength training and lung volumes using either combined or non-combined exercise with elastic bands in healthy young participants. METHODS: Forty healthy young participants (20 male and 20 female) aged 19-24 years old were randomized into two main experiments with four sub-groups; (1) artificial device (n = 10) & standard device (n = 10) training, and (2) artificial device training combined with elastic band (EB) exercise (n = 10) & standard device training combined with EB (n = 10) exercise. Respiratory muscle strength with maximal peak inspiratory pressure (PImax), and lung volumes; tidal volume (TV), inspiratory reserve volume (IRV), expiratory reserve volume (ERV) and vital capacity (VC) were evaluated before and after training once daily for 3 weeks. Moreover, the peak dyspnea score and vital sign parameters were compared between the experimental groups after final training. RESULTS: All parameters had no statistical differences (p > 0.5) between the training devices alone and those combined with EB exercise prior to any experiments. Results from the first experiment showed that training with an artificial device increased all parameters (PImax, VC, IRV, ERV) significantly (p < 0.05), except for TV, when compared to pre training results, which were the same as those in the standard device training group. No statistical difference was shown between these groups after the training period had been performed. Furthermore, results of applying artificial device training combined with EB exercise showed a significant increase in all parameters, except for TV, and they were the same as the increased results in training with the standard device combined with EB exercise. There was no significant difference of data between these groups after the training period. Finally, the results of peak dyspnea score and all vital sign parameters from using the artificial device, with or without EB exercise, showed no statistical difference when compared to use of the standard device. CONCLUSION: This study proposed that a simple artificial device can be used to train the respiratory muscle with or without elastic band exercise in healthy young subjects.

Effects of a simple prototype respiratory muscle trainer on respiratory muscle strength, quality of life and dyspnea, and oxidative stress in COPD patients: a preliminary study.

BACKGROUND: The aim of this study was to evaluate the efficiency of a simple prototype device for training respiratory muscles in lung function, respiratory muscle strength, walking capacity, quality of life (QOL), dyspnea, and oxidative stress in patients with COPD. METHODS: Thirty COPD patients with moderate severity of the disease were randomized into three groups: control (n=10, 6 males and 4 females), standard training (n=10, 4 males and 6 females), and prototype device (n=10, 5 males and 5 females). Respiratory muscle strength (maximal inspiratory pressure [PImax] and maximal expiratory pressure [PEmax]), lung function (forced vital capacity [FVC], percentage of FVC, forced expiratory volume in 1 second [FEV1], percentage of FEV1 [FEV1%], and FEV1/FVC), 6-minute walking distance (6MWD), QOL, and oxidative stress markers (total antioxidant capacity [TAC]), glutathione (GSH), malondialdehyde (MDA), and nitric oxide (NO) were evaluated before and after 6 weeks of training. Moreover, dyspnea scores were assessed before; during week 2, 4, and 6 of training; and at rest after training. RESULTS: All parameters between the groups had no statistical difference before training, and no statistical change in the control group after week 6. FVC, FEV1/FVC, PImax, PEmax, QOL, MDA, and NO showed significant changes after 6 weeks of training with either the standard or prototype device, compared to pre-training. FEV1, FEV1%, 6MWD, TAC, and GSH data did not change statistically. Furthermore, the results of significant changes in all parameters were not statistically different between training groups using the standard and prototype device. The peak dyspnea scores increased significantly in week 4 and 6 when applying the standard or prototype device, and then lowered significantly at rest after 6 weeks of training, compared to pre-training. CONCLUSION: This study proposes that a simple prototype device can be used clinically in COPD patients as a standard device to train respiratory muscles, improving lung function and QOL, as well as involving MDA and NO levels.

Consumption of star fruit juice on pro-inflammatory markers and walking distance in the community dwelling elderly.

PURPOSE: This study aimed to evaluate the effect of star fruit juice supplementation on tumor necrosis factor-alpha (TNF-α), interleukin-23 (IL-23) and interleukin-2 (IL-2), nitric oxide (NO), and 6 min walking distance (6MWD) in a group of elderly individuals. METHODS: Twenty-nine individuals (20 males, 9 females) with a mean age of 72.4±8.3 years completed this study. A two-week control period was followed by four weeks of 100g fresh star fruit juice consumption twice per day after meals. RESULTS: Plasma TNF-α, IL-23, IL-2, NO and the 6MWD were evaluated twice during the control period (weeks 0 and 2) and once after the star fruit juice consumption (week 6). RESULTS: The results showed that all parameters in the blood did not change significantly during the control period. After 4 weeks of star fruit juice consumption, a significant reduction in NO, TNF-α and IL-23 was found; however, there was no change in IL-2. Moreover, the 6MWD increased significantly at week 6, when compared to that at week 0 and 2. Furthermore, the results also showed a significantly positive and negative correlation of NO and TNF-α to the 6MWD, but no correlation of IL-23 and IL-2. CONCLUSION: This preliminary study concluded that consumption of star fruit juice at 100g twice daily for one month can significantly depress the pro-inflammation cytokines: TNF-α, IL-23, and NO, while increasing walking distance. Low TNF-α and high NO also present a significant correlation to walking capacity in elderly individuals.

Neuroprotective effect of purple rice extract and its constituent against amyloid beta-induced neuronal cell death in SK-N-SH cells.

This study evaluated the protective effects of purple rice (Oryza sativa L.) extract (PRE) and its major constituent, cyanidin, and their underlying mechanisms against Aß 25-35-induced neuronal cell death in SK-N-SH cells. Aß 25-35-induced neuronal toxicity is characterized by decrease in cell viability, the release of lactate dehydrogenase (LDH), decrease superoxide dismutase (SOD) activity, increase in reactive oxygen species (ROS) production, morphological alteration, and activation of mitochondrial death pathway. Pretreatment with PRE and cyanidin significantly attenuated Aß 25-35-induced loss of cell viability, apoptosis, and increase in ROS and RNS production in a dose-dependent manner. In addition, PRE and cyanidin also helped to bring about the downregulation of the expression of Bax, cytochrome c, cleavage caspase-9, and cleavage caspase-3 proteins, and the upregulation of the Bcl-XL protein in cascade. Therefore, it is evident that PRE and its major constituent, cyanidin, were successful in protecting from the cytotoxic effect of Aß 25-35 through attenuation ROS and RNS production and modulation of mitochondrial death pathway in SK-N-SH cells. This result suggests that PRE and its major constituent, cyanidin, might be beneficial as potential therapeutic agents in preventing neurodegenerative diseases.

Morelloflavone, a biflavonoid inhibitor of migration-related kinases, ameliorates atherosclerosis in mice.

While macrophages take up modified LDL to form foam cells and multiply to develop fatty streaks, vascular smooth muscle cells (VSMC) migrate from the media to intima, secrete extracellular matrix, and increase the volume of atherosclerotic lesions. A medicinal plant Garcinia dulcis has been used in traditional Thai medicine for centuries to treat various chronic human diseases. Morelloflavone, a biflavonoid and an active ingredient of the plant, has been shown to inhibit VSMC migration through its inhibition of multiple migration-related kinases such as focal adhesion kinase, c-Src, ERK, and RhoA. However, the exact role of morelloflavone in atherosclerogenesis was unknown. We fed Ldlr(-/-)Apobec1(-/-) mice with either normal chow or chow containing 0.003% morelloflavone for 8 mo and assessed the extent of atherosclerosis by the en face and cross-sectional analyses. A cell composition analysis of atherosclerotic tissue was carried out using immunohistochemical staining. Oral morelloflavone therapy significantly reduced the atherosclerotic areas of the mouse aortas (a 26% reduction), without changing plasma lipid profiles or weights. Immunohistochemical analyses showed that morelloflavone reduced the number of VSMC in the atherosclerotic lesion while it did not change the density of macrophages in the lesion or the percentages of proliferating and apoptotic cells. Oral, low-dose, morelloflavone therapy retards atherosclerogenesis by limiting the migration of VSMC into the intima in the mouse model of human atherosclerosis. Upon further investigation, morelloflavone may be found to be a novel oral antiatherosclerotic agent and a viable addition to the conventional therapies such as statins in humans.

Morelloflavone from Garcinia dulcis as a novel biflavonoid inhibitor of HMG-CoA reductase.

Morelloflavone, a biflavonoid from Garcinia dulcis previously shown to have hypocholesterolemic activity, was examined for its effect on HMG-CoA reductase, the rate-limiting enzyme of the cholesterol biosynthetic pathway. By using the catalytic domain of house mouse HMG-CoA reductase, morelloflavone was found to inhibit the enzyme activity by competing with HMG-CoA whereas it was non-competitive towards NADPH. The inhibition constants (K(i)) with respect to HMG-CoA and NADPH were 80.87 ± 0.06 µm and 103 ± 0.07 µm, respectively. Both flavonoid subunits of this compound, naringenin and luteolin, equally competed with HMG-CoA with K(i) of 83.58 ± 4.37 µm and 83.59 ± 0.94 µm, respectively, and were also non-competitive with NADPH (K(i) of 182 ± 0.67 µm and 188 ± 0.14 µm, respectively). Due to these findings, we suggest that each subunit of morelloflavone would occupy the active site of the enzyme, thereby blocking access of its substrate. The present study thus demonstrates the ability of morelloflavone from G. dulcis to inhibit HMG-CoA reductase in vitro. As a result, this biflavonoid might serve as a new candidate for the future development of hypocholesterolemic agents.

Morelloflavone blocks injury-induced neointimal formation by inhibiting vascular smooth muscle cell migration.

BACKGROUND: In-stent restenosis, or renarrowing within a coronary stent, is the most ominous complication of percutaneous coronary intervention, caused by vascular smooth muscle cell (VSMC) migration into and proliferation in the intima. Although drug-eluting stents reduce restenosis, they delay the tissue healing of the injured arteries. No promising alternative anti-restenosis treatments are currently on the horizon. METHODS: In endothelium-denudated mouse carotid arteries, oral morelloflavone-an active ingredient of the Thai medicinal plant Garcinia dulcis-significantly decreased the degree of neointimal hyperplasia, without affecting neointimal cell cycle progression or apoptosis as evaluated by Ki-67 and TUNEL staining, respectively. At the cellular level, morelloflavone robustly inhibited VSMC migration as shown by both scratch wound and invasion assays. In addition, morelloflavone prevented VSMCs from forming lamellipodia, a VSMC migration apparatus. Mechanistically, the inhibition by morelloflavone of VSMC migration was through its negative regulatory effects on several migration-related kinases, including FAK, Src, ERK, and RhoA. Consistently with the animal data, morelloflavone did not affect VSMC cell cycle progression or induce apoptosis. RESULTS: These data suggest that morelloflavone blocks injury-induced neointimal hyperplasia via the inhibition of VSMC migration, without inducing apoptosis or cell cycle arrest. GENERAL SIGNIFICANCE: We propose morelloflavone to be a viable oral agent for the prevention of restenosis, without compromising effects on the integrity and healing of the injured arteries.