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Pada penelitian awal didapatkan diet restriksi vitamin B12 menyebabkan hiperhomosisteinemia dan resistensi insulin, yang ditandai oleh hiperglikemia dan meningkatnya nilai Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Dengan menggunakan sampel jaringan biologik tersimpan, hati tikus Spraque-Dawley dari penelitian tersebut, penelitian lanjutan ini bertujuan mengetahui penyebab hiperglikemia, dalam hubungannya dengan proses glukoneogenesis, dengan melihat ekspresi forkhead box protein-O1 (FoxO1) dan gen glukosa 6 fosfatase (G6Pc). Adapun sampel terdiri dari 4 kelompok: kelompok kontrol dan tiga kelompok dengan diet restriksi vitamin B12 masing-masing selama 4, 8, dan 12 minggu. Ekspresi FoxO1 diperiksa dengan metode kuantitatif Western-Blot, sedangkan gen G6Pc diperiksa dengan metode real-time Polymerase Chain Reaction (rt-PCR). Hasil yang diperoleh, tidak terdapat perbedaan bermakna ekspresi FoxO1 (P > 0,05) dan gen G6Pc (P > 0,05) antara kelompok tikus kontrol dan kelompok diet restriksi vitamin B12. Hal ini menunjukkan, hiperglikemia pada diet restriksi vitamin B12 tidak terkait dengan glukoneogenesis. Pada kondisi resistensi insulin, insulin masih dapat meneruskan efek metaboliknya melalui jalur lain, seperti melalui reseptor yang memiliki kemiripan struktur dan fungsi dengan reseptor insu lin. Penyebab-penyebab lain terjadinya hiperglikemia seperti gangguan utilisasi glukosa oleh sel dan gangguan proses glikogenesis perlu diteliti lebih lanjut.

Objective: Memory is an essential function of cognition in humans, but an age- and disease-related deterioration of this function is common. The currently known treatments have high failure rates, and thus, the slowing down of memory degeneration at an early age is the preferred preventive approach. Exercise, specifically aerobic exercise, has been proven to enhance memory via various pathways, such as neurogenesis, angiogenesis, and growth factor expression. The aim of this study is to assess the effect of aerobic exercise on short-term and long-term memory function in rats. Methods: Twenty-four male Wistar rats aged 7 mo were randomly distributed into four groups: Control, short-term memory (C-S); Control, long-term memory (C-L); Aerobic, short-term memory (A-S); and Aerobic, long-term memory (A-L). The aerobic groups received exercise treatment for 30 min each five times per week, at a treadmill speed of 20 m/min. The treatment duration was 8 w. Short-term memory was assessed using the forced alteration Y-maze test, and long-term memory was assessed using the object location task. Results: The findings showed that rats placed under the aerobic exercise regimen had significantly better long-term memory function at the end of 8 w (p = 0.006), while no significant difference was observed in short-term memory function between the aerobic exercise group and the control group. Conclusion: The present study shows that aerobic exercise is beneficial in improving long-term memory function in rats.

Memory is an important cognitive function in humans. Exercise and environmental enrichment (EE) exposure have positive effects on memory function via improved neurogenesis through expression of growth factors such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). Exercise and environmental enrichment have independently been shown to increase BDNF and NGF, but the effect of the combination of these treatments has not been widely studied. This experimental study aims to analyse the effect of aerobic exercise, EE exposure, and combination of aerobic exercise and EE exposure on memory function. This study used twenty 7-month old male Wistar rats that were given treatment for 8 weeks. Memory function was tested using forced alternation Y-maze. Hippocampal expression of BDNF and NGF were also assessed. The results showed the combination group has highest performance in memory function test and also the highest level of hippocampal BDNF and NGF (P

Mitochondria are integrative hubs central to cellular adaptive pathways. Such pathways are critical in highly differentiated post-mitotic neurons, the plasticity of which sustains brain function. Consequently, defects in mitochondrial dynamics and quality control appear instrumental in neurodegenerative diseases and may also participate in cognitive impairments. To directly test this hypothesis, we analyzed cognitive performances in a mouse mitochondria-based disease model, due to haploinsufficiency in the mitochondrial optic-atrophy-type-1 (OPA1) protein. While in Dominant Optic Atrophy (DOA) models, the known main symptoms are late onset visual deficits, we discovered early impairments in hippocampus-dependent spatial memory attributable to defects in adult neurogenesis. Moreover, less connected hippocampal adult-born neurons showed a decrease in mitochondrial content. Remarkably, modulating mitochondrial function through voluntary exercise or pharmacological treatment restored spatial memory.Altogether, our study identifies a crucial role for OPA1-dependent mitochondrial functions in adult neurogenesis, and thus in hippocampal-dependent cognitive functions. More generally, our findings show that adult neurogenesis is highly sensitive to mild mitochondrial defects, generating impairments in spatial memory that can be detected at an early stage and counterbalanced by physical exercise and pharmacological targeting of mitochondrial dynamics. Thus, early amplification of mitochondrial function appears beneficial for late-onset neurodegenerative diseases.

BACKGROUND: Memory declines with the progression of age through the neurodegeneration process. Aerobic exercise and environmental enrichment can delay neurodegeneration by improving neuroplasticity via expression of insulin like growth factor 1 (IGF-1), fibroblast growth factor 2 (FGF-2) and other proteins. Combination treatment of aerobic exercise and continuous environmental enrichment and their effect on the expression of IGF-1 and FGF-2 which were expected to improve memory function has not been studied previously. Thus, this study aimed to observe it. METHODS: This is an experimental research using 24 male Wistar rats (Rattus norvegicus, 300-400 g, age 7-8 months) divided randomly into 4 groups: control (C), aerobic exercise (A), continuous (EE), and combination of aerobic exercise and continuous environmental enrichment (A-EE). At the end of an 8-week treatment, rats were sacrificed, and an enzyme-linked immunosorbent assay (ELISA) examination was performed to assess hippocampal IGF-1 and FGF-2 levels. RESULTS: In the 8th week, A-EE group showed the best improvement in rats’ spatial memory (47.84±10.6 %) followed by EE group (45.03±4.1 %), A group (38.61±3.8 %), and C group (22.76±7.12 %). However, A-EE group’s hippocampal IGF-1 (16.21±7.56 ng/mg protein) and FGF-2 (1.29±0.57 ng/mg protein) expression were not higher than other groups. CONCLUSION: Improvement in memory function in the combination group is a result of induction of various growth factors’ expression in the hippocampus, including IGF-1 and FGF-2, but the primary pathway of memory function improvement may be from other growth factors. KEYWORDS: spatial memory, aerobic exercise, environmental enrichment, hippocampus, IGF-1, FGF-2

Objective: Studies have shown that prolonged physical exercise increases ventricular wall mass. Physiologically, this increase is followed by an increase of mitochondrial biogenesis. However, increases of ventricular mass in some cardiovascular diseases are not followed by an increase of PPARγ coactivator-1α (PGC-1α), a marker of mitochondrial biogenesis. No data regarding cardiac PGC-1α during an excessive physical exercise program that causes pathological conditions (overtraining) are available. Thus, we aimed to determine the effect of overtraining on cardiac hypertrophy index and PGC-1α level. Furthermore, we aimed to elucidate the cardio protective effect of Hibiscus sabdariffa Linn. (HSL) administration on these cardiac parameters. Methods: Twenty-five male adult Wistar rats aged 8–10 w were randomly divided into five groups: control (C), control-HSL (C-HSL), aerobic training (A), overtraining (OT), and overtraining-HSL (OT-HSL). Treatments were conducted five times a week, for 11 w. Differences in heart mass were determined by measuring ratios of ventricular weight to body weight (hypertrophy index). PGC-1α levels were measured using an ELISA method. Results: We found that overtraining increased ventricular wall mass; however, it did not increase cardiac PGC-1α levels, whereas mild-aerobic exercise robustly increased cardiac levels of PGC-1α. Furthermore, administration of a methanol extract of HSL did not show any significant effect on cardiac mass or PGC-1α level. Conclusion: Thus, our study showed that ventricular hypertrophy elicited by overtraining conditions was not followed by an increase in cardiac PGC-1α, and administration of H. sabdariffa extract did not ameliorate this condition.

Objective: This study aims to determine the effect of Hibiscus sabdariffa Linn. (HSL) administration on the interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) levels in rat heart. Overtraining was proven to increase the IL-6 and TNF-α levels in the blood, and HSL had anti-inflammatory and anti-oxidant properties. However, no studies have been conducted on the effect of methanolic extract of HSL administration on the IL-6 and TNF-α levels in overtrained rat heart. Methods: This study used 25 male adult Wistar rats aged 8–10 w and weighing 200–250 g. The rats were randomly divided into five groups: control (C), control H. sabdariffa Linn (C+HSL), overtraining (OT), overtraining H. sabdariffa Linn (OT+HSL), and aerobic (A). Treatment was given 5 times a week for 11 w. At the end of the study, the IL-6 and TNF-α levels were measured using a standard ELISA kit. Results: IL-6 and TNF-α levels in the heart were the highest in the overtraining group. The group that received HSL administration showed the lowest TNF-α and IL-6 levels. Conclusion: HSL could be a used to protect the heart from an inflammatory state, particularly in an overtraining condition.

Adult hippocampal neurogenesis is strongly impaired in Alzheimer's disease (AD). In several mouse models of AD, it was shown that adult-born neurons exhibit reduced survival and altered synaptic integration due to a severe lack of dendritic spines. In the present work, using the APPxPS1 mouse model of AD, we reveal that this reduced number of spines is concomitant of a marked deficit in their neuronal mitochondrial content. Remarkably, we show that targeting the overexpression of the pro-neural transcription factor Neurod1 into APPxPS1 adult-born neurons restores not only their dendritic spine density, but also their mitochondrial content and the proportion of spines associated with mitochondria. Using primary neurons, a bona fide model of neuronal maturation, we identified that increases of mitochondrial respiration accompany the stimulating effect of Neurod1 overexpression on dendritic growth and spine formation. Reciprocally, pharmacologically impairing mitochondria prevented Neurod1-dependent trophic effects. Thus, since overexpression of Neurod1 into new neurons of APPxPS1 mice rescues spatial memory, our present data suggest that manipulating the mitochondrial system of adult-born hippocampal neurons provides neuronal plasticity to the AD brain. These findings open new avenues for far-reaching therapeutic implications towards neurodegenerative diseases associated with cognitive impairment.

Accumulation of overtraining/OT volume, in the long run can lead to decreased performance called overtraining syndrome (OTS). Oxidative stress, an imbalance state of endogenous antioxidants and free radicals, is closely related to pathophysiology of OTS and in the long run can cause cardiovascular disorders. Some research shows that oxidative stress can be inhibited through antioxidants supplementation. Hibiscus Sabdariffa Linn. (H. sabdariffa) is a plant that contains high antioxidants. This study aims to explore the effect of OT on oxidative stress level in rat’s cardiac tissue and the effect of H. Sabdariffa supplementation to the level of oxidative stress in OT rats. The study was an experimental study using 25 adult Wistar rats, 8–10 weeks, 290–390 gr, randomized into five groups: Control (C), Control+Hibiscus (C-Hib), Aerobic Exercise (A), Overtraining (OT) and Overtraining + Hibiscus (OT-Hib). Dosage of H. sabdariffa given: 500 mg / kg / day. Aerobic physical exercise was given 2 x/wk, 10 min, 12 m/min, lasted for 11 wks. Overtraining protocols was given 5x/wk with increasing frequency and decreasing recovery time between sessions for 11 wks. Calculated levels of MDA, SOD and GSH using spectrophotometry and Nox2 using ELISA at the end of Week 11. The result showed that overtraining induces an oxidative stress condition in the rat’s cardiac tissue characterized by higher MDA levels than aerobic and control rats, and lower GSH levels than aerobic rats. The administration of H. sabdariffa may induce oxidative stress reduction in overtraining rat’s cardiac tissue, characterized by lower MDA levels and higher GSH levels in overtraining rats given H. sabdariffa compared to overtraining rats.

International audience; Generation of new neurons is a tightly regulated process that involves several intrinsic and extrinsic factors. Among them, a metabolic switch from glycolysis to oxidative phosphorylation, together with mitochondrial remodeling, has emerged as crucial actors of neurogenesis. However, although accumulating data raise the importance of mitochondrial morphology and function in neural stem cell proliferation and differentiation during development, information regarding the contribution of mitochondria to adult neurogenesis processes remains limited. In the present review, we discuss recent evidence covering the importance of mitochondrial morphology, function, and energy metabolism in the regulation of neuronal development and adult neurogenesis, and their impact on memory processes.

Latar belakang: Dislipidemia dan stres oksidatif memiliki peran penting sebagai penyebab resistensi insulin. Salah satu herba yang memiliki efek antioksidan kuat dan dapat memperbaiki dislipidemia adalah Hibiscus sabdariffa Linn. Penelitian ini bertujuan mengetahui efek ekstrak Hibiscus sabdariffa Linn. terhadap kadar glukosa darah puasa, kadar insulin darah puasa dan indeks resistensi insulin (HOMA-IR) pada tikus yang diberi diet tinggi fruktosa. Metode: Penelitian eksperimental in vivo ini dilakukan pada 25 tikus Sprague-Dowley yang diberi diet tinggi fruktosa (10% ad libitum) bersamaan dengan pemberian ekstrak Hibiscus sabdariffa Linn. pada dosis 100, 200 dan 400 mg/kgBB/hari selama 5 minggu. Pada akhir penelitian dilakukan pengukuran kadar glukosa darah puasa, kadar insulin puasa, dan indeks resistensi insulin (HOMA-IR). Hasil: Kadar glukosa darah puasa, kadar insulin darah puasa, dan HOMA-IR pada kelompok tikus yang diberi diet tinggi fruktosa bersamaan dengan Hibiscus sabdariffa Linn. pada dosis 100 mg/kgBB/hari tidak berbeda bermakna dibandingkan kelompok tikus yang hanya diberikan diet tinggi fruktosa sedangkan pada dosis 400 mg/kgBB/hari lebih rendah secara bermakna dibandingkan pada kelompok tikus yang hanya diberi diet tinggi fruktosa (masing-masing 4,84 mmol/L vs 6,11 mmol/L, 0,07 µU/L vs 0,3 µU/L, dan 0,02 vs 0,08). Kesimpulan: Hibiscus sabdariffa Linn. dapat mencegah terjadinya resistensi insulin yang diinduksi diet tinggi fruktosa pada tikus.

Background: Excessive physical exercises (overtraining) can increase the production of reactive oxygen species (ROS). One of the indicators of overtraining syndrome is a decrease in insulin-like growth factor binding protein 3 (IGFBP-3). Administration of Hibiscus sabdariffa Linn., a powerful antioxidant, is expected to boost endogenous antioxidants, and thus prevents overtraining. The aim of this study is to determine the effect of H. sabdariffa on IGFBP-3 levels in rats under ”overtraining physical excersice”. Methods: This experimental study was conducted on 30 male rats ( Rattus norvegicus 200-250 grams), randomly allocated into 5 groups: 1) control group (C); 2) control with H. sabdariffa (C-Hib); 3) mild aerobic exercise (A-Ex); 4) overtraining exercise (OT); 5) overtraining exercise with H. Sabdariffa (OT-Hib). H. sabdariffa (400 mg/kg/d, 11 weeks) were administered orally via syringe cannula. IGFBP-3 was measured by using ELISA (Cusa bio kit) and data were analyzed with ANOVA test. Results: Plasma level of IGFBP-3 in the C and OT groups were 17.4 ± 10 mIU/L, the lowest in OT groups (10.7 ± 9.9 mIU/L) and the OT-Hib group had the highest level (31.5 ± 6.2 mIU/L). There was significant difference of the level IGFBP-3 in OT groups with A-Ex groups (10.7 ± 9.9 vs 23.5 ± 9.7 mIU/L; p < 0,05). The significant difference was also observed in the level of IGFBP 3 between C groups and the OT-Hib groups (17.4 ± 10 vs 31.5 ± 6.2; p < 0.05). Conclusion: Administration of H. sabdariffa can prevent the decrease of IGFBP-3 levels in overtraining rats, indicating its role in preventing overtraining syndrome.

Background: Excessive physical exercises (overtraining) can increase the production of reactive oxygen species (ROS). One of the indicators of overtraining syndrome is a decrease in insulin-like growth factor binding protein 3 (IGFBP-3). Administration of Hibiscus sabdariffa Linn., a powerful antioxidant, is expected to boost endogenous antioxidants, and thus prevents overtraining. The aim of this study is to determine the effect of H. sabdariffa on IGFBP-3 levels in rats under ”overtraining physical excersice”.Methods: This experimental study was conducted on 30 male rats (Rattus norvegicus 200-250 grams), randomly allocated into 5 groups: 1) control group (C); 2) control with H. sabdariffa (C-Hib); 3) mild aerobic exercise (A-Ex); 4) overtraining exercise (OT); 5) overtraining exercise with H. Sabdariffa (OT-Hib). H. sabdariffa (400 mg/kg/d, 11 weeks) were administered orally via syringe cannula. IGFBP-3 was measured by using ELISA (Cusa bio kit) and data were analyzed with ANOVA test.Results: Plasma level of IGFBP-3 in the C and OT groups were 17.4 ± 10 mIU/L, the lowest in OT groups (10.7 ± 9.9 mIU/L) and the OT-Hib group had the highest level (31.5 ± 6.2 mIU/L). There was significant difference of the level IGFBP-3 in OT groups with A-Ex groups (10.7 ± 9.9 vs 23.5 ± 9.7 mIU/L; p < 0,05). The significant difference was also observed in the level of IGFBP 3 between C groups and the OT-Hib groups (17.4 ± 10 vs 31.5 ± 6.2; p < 0.05).Conclusion: Administration of H. sabdariffa can prevent the decrease of IGFBP-3 levels in overtraining rats, indicating its role in preventing overtraining syndrome.

Background: Dyslipidemia and stress oxidative play an important role as the cause of insulin resistance. One herb that has potent antioxidant effect and may improve dyslipidemia is Hibiscus sabdariffa Linn. The aim of this study was to evaluate the effect of Hibiscus sabdariffa Linn. extract on fasting blood glucose level, fasting blood insulin level, and insulin resistance index (HOMA-IR) in high-fructose fed rat.Methods: This was an experimental study in 25 Sprague-Dawley rats which were administered with a high-fructose diet (10% ad libitum) and Hibiscus sabdariffa Linn. extract at a dose of 100, 200, and 400 mg/kgBW/d simultaneously for 5 weeks. At the end of study, fasting blood glucose level, fasting blood insulin level and insulin resistance index (HOMA-IR) were measured.Results: Fasting blood glucose, blood insulin, and HOMA-IR level of rats given high-fructose diet with Hibiscus sabdariffa Linn. at dose 100 mg/kgBW/d were not significantly different than the group of rats given only high-fructose fed. While at the dose of 400 mg/kgBW/d, they were significantly lower than the group given only high-fructose fed (4.84 mmol/L vs 6.11 mmol/L, 0.07 µU/L vs 0.3 µU/L, and 0.02 vs 0.08 respectively).Conclusion: Oral administration of Hibiscus sabdariffa Linn. could prevent the development of insulin resistance induced by high-fructose diet in the rat.

Background: Phospholipase A2 (PLA2) is involved in inflammation and cell death following stroke, and inhibition of its activity may promote neuroregeneration. This study aimed to observe the influence of Acalypha indica Linn root extract towards relative cell viability and PLA2 enzyme level in post-hypoxic hippocampal tissue culture.Methods: Experimental in vitro study using 24 primary neuronal cell cultures obtained from Sprague Dawley rat exposed to hypoxia with 5% O2 / 5% CO2 / N2 balanced gas for 24 hours. Post-hypoxia, Acalypha indica Linn root extract was added at doses of 10, 15, and 20 mg/mL to three treatment groups. No treatment was given to the control group. Each group consists of six samples. After 72 hours of incubation, relative cell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) examination, and phospholipase A2 enzyme level was determined using ELISA.Results: PLA2 enzyme level of rat hippocampal tissue culture treated with Acalypha indica Linn root extract at 10, 15, and 20 mg/mL were significantly lower than that of control (5.55 ng/mL, 6.85 ng/mL, and 7.42 ng/mL vs 7.96 ng/mL, p < 0.05).Conclusion: Acalypha indica Linn root extract increases the relative cell viability and decreases the PLA2 enzyme level of post-hypoxic mouse hippocampal tissue with the optimal dose of the extract at 10 mg/mL. (Med J Indones. 2013;22:136-40 doi: 10.13181/mji.v22i3.581)Keywords: Acalypha indica Linn, cell viability, hypoxia, neurogenesis, phospholipase A2

Background: Phospholipase A2 (PLA2) is involved in inflammation and cell death following stroke, and inhibition of its activity may promote neuroregeneration. This study aimed to observe the influence of Acalypha indica Linn root extract towards relative cell viability and PLA2 enzyme level in post-hypoxic hippocampal tissue culture. Methods: Experimental in vitro study using 24 primary neuronal cell cultures obtained from Sprague Dawley rat exposed to hypoxia with 5% O2 / 5% CO2 / N2 balanced gas for 24 hours. Post-hypoxia, Acalypha indica Linn root extract was added at doses of 10, 15, and 20 mg/mL to three treatment groups. No treatment was given to the control group. Each group consists of six samples. After 72 hours of incubation, relative cell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) examination, and phospholipase A2 enzyme level was determined using ELISA. Results: PLA2 enzyme level of rat hippocampal tissue culture treated with Acalypha indica Linn root extract at 10, 15, and 20 mg/mL were significantly lower than that of control (5.55 ng/mL, 6.85 ng/mL, and 7.42 ng/mL vs. 7.96 ng/mL, p < 0.05). Conclusion: Acalypha indica Linn root extract increases the relative cell viability and decreases the PLA2 enzyme level of post-hypoxic mouse hippocampal tissue with the optimal dose of the extract at 10 mg/mL. (Med J Indones. 2013;22:136-40 doi:10.13181/mji.v22i3.581)