Oral Glucose Tolerance Test (OGTT) Evidence for the Postprandial Anti-Hyperglycemic Property of Salacca zalacca (Gaertn.) Voss Seed Extract.

Salak seed extract (Salacca zalacca) is known for its high antioxidant content and low caffeine levels, making it a promising candidate for the development of value-added health products. However, there is a lack of scientific evidence for its anti-hyperglycemic effects. To address this, we investigated the in vitro and in vivo anti-hyperglycemic and antioxidant effects of salak seed extract. The HPLC chromatogram of salak seed extract shows a prominent peak that corresponds to chlorogenic acid. In vitro studies revealed that salak seeds inhibited α-glucosidase activity and glucose uptake in Caco-2 cells in a concentration-dependent manner, while also exhibiting antioxidant properties. The extract exhibits a non-competitive inhibition on α-glucosidase activity, with an IC50 and Ki of 16.28 ± 7.22 and 24.81 µg/mL, respectively. In vivo studies utilizing streptozotocin-nicotinamide-induced diabetic mice showed that the extract significantly reduced fasting blood glucose (FBG) levels in the oral glucose tolerance test. Continuous administration of the salak seed extract resulted in lower FBG levels by 13.8% as compared with untreated diabetic mice, although this change was not statistically significant. The estimated LD50 value of salak seed extract exceeds 2000 mg/kg, and no toxicity symptoms have been detected. Our research supports that salak seed extract has the potential to serve as a functional food or supplement that may be beneficial in reducing postprandial hyperglycemia among people with type 2 diabetes. This effect was explained by the salak's inhibitory mechanisms of glucose absorption due to inhibition of both α-glucosidase activity and intestinal glucose uptake, coupled with its antioxidant effects.

Residential radon exposure in Astana and Aqsu, Kazakhstan.

A pilot study was carried out to measure indoor radon concentrations in a uranium mining area of northern Kazakhstan. A total of 80 places at kindergartens, elementary schools, and dwellings were selected in Aqsu village and Astana city as the uranium mining area and background area for comparison, respectively. In Astana and Aqsu, the 3-month radon concentrations from late summer to autumn in 2022 were measured using the RADUET passive radon detectors. Radon concentrations ranged from 4 to >2000 Bq m-3(mean ± standard deviation: 290 ± 173 Bq m-3) throughout the study areas. The concentrations were higher in Aqsu, and 70% of the dwellings there exceeded 300 Bq m-3, whereas only 5% of them exceeded 300 Bq m-3in Astana. Accordingly, the new dose conversion factor for radon recommended by International Commission on Radiological Protection Publication 137 was applied to calculate the annual effective dose. The annual effective dose from the inhalation of radon was estimated to be 3.6 ± 4.6 mSv y-1for Astana and 23.7 ± 15.6 mSv y-1, for Aqsu, which are both higher than the world average value of 2.5 mSv y-1.

Antihyperglycemic effects of Lysiphyllum strychnifolium leaf extract in vitro and in vivo.

CONTEXT: Lysiphyllum strychnifolium (Craib) A. Schmitz (LS) (Fabaceae) has traditionally been used to treat diabetes mellitus. OBJECTIVE: This study demonstrates the antidiabetic and antioxidant effects of aqueous extract of LS leaves in vivo and in vitro. MATERIALS AND METHODS: The effects of aqueous LS leaf extract on glucose uptake, sodium-dependent glucose cotransporter 1 (SGLT1) and glucose transporter 2 (GLUT2) mRNA expression in Caco-2 cells, α-glucosidase, and lipid peroxidation were evaluated in vitro. The antidiabetic effects were evaluated using an oral glucose tolerance test (OGTT) and a 28-day consecutive administration to streptozotocin (STZ)-nicotinamide (NA)-induced type 2 diabetic mice. RESULTS: The extract significantly inhibited glucose uptake (IC50: 236.2 ± 36.05 µg/mL) and downregulated SGLT1 and GLUT2 mRNA expression by approximately 90% in Caco-2 cells. Furthermore, it non-competitively inhibited α-glucosidase in a concentration-dependent manner with the IC50 and Ki of 6.52 ± 0.42 and 1.32 µg/mL, respectively. The extract at 1000 mg/kg significantly reduced fasting blood glucose levels in both the OGTT and 28-day consecutive administration models as compared with untreated STZ-NA-induced diabetic mice (p < 0.05). Significant improvements of serum insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and GLUT4 levels were observed. Furthermore, the extract markedly decreased oxidative stress markers by 37-53% reduction of superoxide dismutase 1 (SOD1) in muscle and malondialdehyde (MDA) in muscle and pancreas, which correlated with the reduction of MDA production in vitro (IC50: 24.80 ± 7.24 µg/mL). CONCLUSION: The LS extract has potent antihyperglycemic activity to be used as alternative medicine to treat diabetes mellitus.

Evaluation of in vitro transdermal permeation, mass spectrometric imaging, and in vivo analgesic effects of pregabalin using a pluronic lecithin organogel formulation in mice.

In clinical practice, pregabalin is orally administered for neuropathic pain, but causes severe central nervous system side effects, such as dizziness, which results in dose limitation or discontinuation. To reduce the central side effects of pregabalin, we developed four pregabalin preparations for transdermal application: 0.4% aqueous solution, pluronic lecithin organogel (PLO gel), hydrophilic cream, and lipophilic cream. Transdermal permeabilities of pregabalin among the four formulations were compared in vitro using hairless mouse skin. The longitudinal distribution of pregabalin within the skin was analyzed using mass spectrometric (MS) imaging. Furthermore, the in vivo analgesic effects of the formulations were evaluated using the von Frey filament test in a mouse model of diabetic neuropathy (DN). The PLO gel showed the highest permeability of pregabalin, followed by the aqueous solution, and no permeation was observed in the two cream formulations. The MS imaging analysis showed that pregabalin was distributed up to the dermis in the PLO gel 1 h after application, while the aqueous solution was distributed near the epidermis. A significant analgesic effect (p < .05) was observed 1.5 h after PLO gel application in the DN model mice, but the aqueous solution had no effect. This study indicated for the first time that pregabalin penetrated beyond the skin epidermis up to the dermis, from the PLO gel formulation, and that the application of this formulation exhibited an in vivo analgesic effect in the mouse model of DN.

Antidiabetic effects of Maclura cochinchinensis (Lour.) corner heartwood extract.

BACKGROUND AND AIM: Maclura cochinchinensis (MC) (Lour.) heartwood extract have been used traditionally to treat diabetes in Thailand, but their mechanism of action has not been elucidated. EXPERIMENTAL PROCEDURE: This study investigated the effects of an aqueous heartwood extract of MC on α-glucosidase and α-amylase activities. Moreover, its antidiabetic effect was evaluated using an oral glucose tolerance test (OGTT) and a 28-day administration to streptozotocin (STZ)-nicotinamide (NA)-induced type 2 diabetic mice. RESULTS: In both OGTT and the daily oral administration for 28 days in STZ-NA-induced type 2 diabetic mice models, the extract (1,000 mg/kg) significantly decreased fasting blood glucose. This hypoglycemic effect was explained by increased insulin levels and α-glucosidase inhibition (IC50:1.53 ±â€¯0.03 µg/mL). CONCLUSION: This first study on the hypoglycemic activity of MC heartwood extract indicates that it could be a potential natural remedy for type 2 diabetes.

Effects of Capsinoids on Daily Physical Activity, Body Composition and Cold Hypersensitivity in Middle-Aged and Older Adults: A Randomized Study.

Sedentary/inactive lifestyle leads middle-aged and older adults to metabolic syndrome and frailty. Capsinoids from nonpungent chili pepper cultivar have been reported to reduce body fat mass, promote metabolism, and improve unidentified complaints of chills. Additionally, they have an anti-inflammation effect; therefore, we hypothesized that continuous oral ingestion of capsinoids alleviates age-related inflammation in the brain and improves the physical activity (PA) in middle-aged and older adults. In our double-blind human study, 69 participants (17 male, 52 female; mean age: 74.1 ± 7.7 years; range: 52-87 years) were administered either 9 mg of capsinoids which were extracted from pepper fruit variety CH-19 Sweet (Capsicum anuum L.) (CP group), or a placebo (PL group) daily over a 3 month period. In an animal study, PA and inflammation-related mRNA expression in the brain were examined in 5-week (young) and 53-week (old) aged mice fed a diet with or without 0.3% dihydrocapsiate, a type of capsinoids, for 12 weeks. In a human study, capsinoids intake did not increase the amount of light-to-moderate PA less than 6.0 metabolic equivalents (METs) (CP: 103.0 ± 28.2 at baseline to 108.2 ± 28.3 at 12 weeks; PL: 104.6 ± 19.8 at baseline to 115.2 ± 23.6 at 12 weeks, METs × hour/week); however, in participants exhibiting an inactive lifestyle, it showed significant increase (CP: 84.5 ± 17.2 at baseline to 99.2 ± 24.9 at 12 weeks; PL: 99.7 ± 23.3 at baseline to 103.8 ± 21.9 at 12 weeks). The energy expenditure in physical activity also improved in the inactive CP group (CP: 481.2 ± 96.3 at baseline to 562.5 ± 145.5 at 12 weeks; PL: 536.8 ± 112.2 at baseline to 598.6 ± 127.6 at 12 weeks; kcal/day). In all participants, CP showed reduced waist circumference, percent body fat, and visceral fat volume; in addition, chills were eased in subjects aged 80 years and older. The older mice fed capsinoids showed increased locomotion activity, decreased inflammation, and oxidative stress in the brain. The results suggest that the continuous oral ingestion of capsinoids gains PA through anti-inflammation effect in the brain as well as reduces fat accumulation and chills in inactive and older humans.

Effects of exercise therapy on painful temporomandibular disorders.

Temporomandibular disorders (TMD) are common chronic musculoskeletal pain conditions among orofacial pain. Painful TMD condition such as myalgia and arthralgia can be managed by exercise therapy. However, as it is hard to access actual effect of each modality that is included in an exercise therapy programme due to multiple choice of the management modality, their efficacy remains controversial. Therefore, this review focused on the effects of exercise therapy for the management of painful TMD. The aims of this review were to summarise the effects of exercise therapy for major symptoms of painful TMD and to establish a guideline for the management of painful TMD, resulting in higher quality and reliability of dental treatment. In this review, exercise modalities are clearly defined as follows: mobilisation exercise, muscle strengthening exercise (resistance training), coordination exercise and postural exercise. Furthermore, pain intensity and range of movements were focused as outcome parameters in this review. Mobilisation exercise including manual therapy, passive jaw mobilisation with oral appliances and voluntary jaw exercise appeared to be a promising option for painful TMD conditions such as myalgia and arthralgia. This review addressed not only the effects of exercise therapy on various clinical conditions of painful TMD shown in the past, but also an urgent need for consensus among dentists and clinicians in terms of the management of each condition, as well as terminology.

Pharmacological effects of Chatuphalatika in hyperuricemia of gout.

CONTEXT: Chatuphalatika (CTPT), is a Thai herbal formulation mixture of Phyllanthus emblica Linn. (Euphorbiaceae), Terminalia belerica Linn. (Combretaceae), T. chebula and the fruit of T. arjuna (Roxb.) Wight & Arn. CTPT is considered to exert anti-inflammatory and antihyperuricemic effects, but there have been no reports to demonstrate these pharmacological effects in a quantitative manner. OBJECTIVES: To investigate the antioxidative, anti-inflammatory and antihyperuricemic effects of CTPT. MATERIALS AND METHODS: Antioxidant activities of CTPT extracts were measured in vitro by DPPH, ABTS and FRAP assays, and anti-inflammatory effect by measuring inflammatory mediator production induced by lipopolysaccharide (LPS) in RAW264.7 macrophages. The mechanism of the hypouricemic effect was investigated using oxonate-induced hyperuricemic ddY mice treated with oral administrations of CTPT at 250, 500 and 1000 mg/kg. RESULTS: Antioxidant activities of CTPT measured by ABTS and FRAP assays were 1.35 g TEAC/g extract and 10.3 mmol/100 g extract, respectively. IC50 for the inhibition of DPPH radical was 13.8 µg/mL. CTPT (10 µg/mL) significantly downregulated the mRNA expression of TNF-α and iNOS in RAW 264.7 cells. Lineweaver-Burk analysis of the enzyme kinetics showed that CTPT inhibited xanthine oxidase (XOD) activity in a noncompetitive manner with the Ki of 576.9 µg/mL. Oral administration of CTPT (1000 mg/kg) significantly suppressed uric acid production by inhibiting hepatic XOD activity, and decreased plasma uric acid levels in hyperuricemic mice by approximately 40% (p < 0.05). CONCLUSIONS: This study demonstrated for the first time the antioxidative, anti-inflammatory and antihyperuricemic effects of CTPT in vivo and in vitro, suggesting a possibility of using CTPT for the treatment of hyperuricemia in gout.

Hypoglycemic and Antioxidant Activities of the Water Extract of Aquilaria crassna Leaves in Streptozotocin-Nicotinamide-Induced Type-2 Diabetic Mice.

Antidiabetic effect of the water extract of Aquilaria crassna (A. crassna) leaves was recently claimed by some diabetic patients in Thailand, whereas its experimental evidence has not been published yet. The present study was therefore conducted to investigate pharmacological activities of the water extract of A. crassna leaves, focusing on its antioxidative and hypoglycemic effects in vitro and in vivo using streptozotocin (STZ)-nicotinamide (NA)-induced type 2 diabetic (DM) mice. An antioxidant activity of the herb extract was confirmed using a 2,2-diphenyl-1-picrylhydrazyl hydrate (DPPH) radical scavenging assay, and its IC50 on DPPH inhibition was determined to be 34.6 µg/mL. The extract also inhibited α-glucosidase in a concentration-dependent manner with the IC50 of 36.3 µg/mL. An enzyme-kinetic analysis using a Lineweaver-Burk plot indicated that the inhibition of α-glucosidase by the herb extract is an uncompetitive type with the inhibition constant (K(i)) of 39.8 µg/mL. An intragastric pretreatment of 1,000 mg/kg A. crassna in STZ-NA-induced type-2 DM significantly lowered the blood glucose at 30 and 60 min after an oral loading of 2 g/kg glucose (p < 0.05 and p < 0.01, respectively), as compared with the untreated-diabetic control. After 4 weeks-daily administration of 500 and 1,000 mg/kg A. crassna extract, the blood glucose levels were significantly reduced by about 66% and 86%, respectively, as compared with the untreated-diabetic control (p < 0.01). However, the expression of GLUT4 in skeletal muscle, detected by ELISA, was not significantly changed with the herb extract. In conclusion, our findings are the first to clearly demonstrate the hypoglycemic effects of A. crassna and to propose the α-glucosidase inhibition as an antidiabetic mechanism of the herb activity.

Neuroanatomic pathway associated with attentional deficits after stroke.

We used magnetic resonance imaging (MRI) and the statistical parametric mapping (SPM) image analysis technique to localize lesions in post-stroke patients with attention deficits. SPM can be used to combine image data from multiple participants and correlate these images with other data sets. Magnetic resonance imaging acquisitions were obtained from 115 post-stroke patients, who were systemically assessed for attention deficits using a standardized test (the Clinical Assessment for Attention; CAT) that probes various domains of attention. We created an SPM that displayed an association between lesion location and attention deficit severity. The overlay plots were localized to the right hemisphere during a visual cancellation test, and were localized to the left hemisphere during other attention tests. Cortical lesion varied across specific test domain, whereas lesions from the thalamus to the basal ganglia on the dominant side were associated with performance across all attention tests/domains. Our findings are suggestive of a large-scale multimodal attentional network associated with the thalamus/basal ganglia.

Effects of novel capsinoid treatment on fatness and energy metabolism in humans: possible pharmacogenetic implications.

BACKGROUND: Capsinoids from the Capsicum genus of plants are nonpungent capsaicin-related substances with effects on metabolism and body weight in animals. OBJECTIVES: Our objectives were to explore the safety and efficacy of capsinoids taken orally (6 mg/d) for weight loss, fat loss, and change in metabolism and to examine whether candidate genes are predictors of capsinoid response. DESIGN: This was a 12-wk, placebo-controlled, double-blind, randomized study. Eligibility criteria included a body mass index (BMI; in kg/m(2)) of 25-35. Body weight was measured, and dual-energy X-ray absorptiometry, indirect calorimetry (men only), and genotyping were conducted. RESULTS: Forty women and 40 men with a mean (+/- SD) age of 42 +/- 8 y and BMI of 30.4 +/- 2.4 were randomly assigned to a capsinoid or placebo group. Capsinoids were well tolerated. Mean (+/- SD) weight change was 0.9 +/- 3.1 and 0.5 +/- 2.4 kg in the capsinoid and placebo groups, respectively (P = 0.86). There was no significant group difference in total change in adiposity, but abdominal adiposity decreased more (P = 0.049) in the capsinoid group (-1.11 +/- 1.83%) than in the placebo group (-0.18 +/- 1.94%), and this change correlated with the change in body weight (r = 0.46, P < 0.0001). Changes in resting energy expenditure did not differ significantly between groups, but fat oxidation was higher at the end of the study in the capsinoid group (least-squares mean difference: 21.0 mg/min; P = 0.06). Of 13 genetic variants tested, TRPV1 Val585Ile and UCP2 -866 G/A correlated significantly with change in abdominal adiposity. CONCLUSIONS: Treatment with 6 mg/d capsinoids orally appeared to be safe and was associated with abdominal fat loss. Capsinoid ingestion was associated with an increase in fat oxidation that was nearly significant. We identified 2 common genetic variants that may be predictors of therapeutic response.

Hypocholesterolemic and antioxidant effects of aqueous extracts from the dried calyx of Hibiscus sabdariffa L. in hypercholesterolemic rats.

The present study was designed to investigate the hypolipidemic effects and antioxidant effects of Hibiscus sabdariffa L. (roselle) with regard to protection of LDL oxidation in vivo and ex vivo in rats made hypercholesterolemic by continuous cholesterol feeding. Administering the dried calyx extracts of roselle at doses of 500 and 1,000 mg/kg together with continuous cholesterol feeding to hypercholesterolemic rats for 6 weeks significantly decreased serum cholesterol level by 22% and 26%, respectively (p<0.001); serum triglycerides level by 33% and 28%, respectively (p<0.05); serum LDL level by 22% and 32%, respectively (p<0.05). However, serum HDL level was not affected. LDL was extracted from plasma of the hypercholesterolemic rats and the effects of the dried calyx extracts of roselle on the oxidation of LDL in vivo and ex vivo were examined. Six-week treatment with 250, 500 and 1,000 mg/kg of the extracts significantly decreased thiobarbituric acid reactive substances (TBARs) formation (p<0.05) while the formation of conjugated dienes during the oxidation of LDL induced by CuSO(4) was reduced, but not significantly different. These lines of evidence suggest that the aqueous extracts from the dried calyx of roselle possess both antioxidant effects against LDL oxidation and hypolipidemic effects in vivo. However, its mechanism(s) of action remains to be elucidated.

Antioxidant effects of aqueous extracts from dried calyx of Hibiscus sabdariffa Linn. (Roselle) in vitro using rat low-density lipoprotein (LDL).

The present study quantitatively investigated the antioxidant effects of the aqueous extracts from dried calyx of Hibiscus sabdariffa LINN. (roselle) in vitro using rat low-density lipoprotein (LDL). Formations of the conjugated dienes and thiobarbituric acid reactive substances (TBARs) were monitored as markers of the early and later stages of the oxidation of LDL, respectively. Thus, we demonstrated that the dried calyx extracts of roselle exhibits strong antioxidant activity in Cu(2+)-mediated oxidation of LDL (p<0.05) in vitro. The inhibitory effect of the extracts on LDL oxidation was dose-dependent at concentrations ranging from 0.1 to 5 mg/ml. Moreover, 5 mg/ml of roselle inhibited TBARs-formation with greater potency than 100 microM of vitamin E. In conclusion, this study provides a quantitative insight into the potent antioxidant effect of roselle in vitro.