Harisun Yaakob

Potential anti-dengue medicinal plants: A review

Dengue fever causes mortality and morbidity around the world, specifically in the Tropics and subtropic regions, which has been of major concern to governments and the World Health Organization (WHO). As a consequence, the search for new anti-dengue agents from medicinal plants has assumed more urgency than in the past. Medicinal plants have been used widely to treat a variety of vector ailments such as malaria. The demand for plant-based medicines is growing as they are generally considered to be safer, non-toxic and less harmful than synthetic drugs. This article reviews potential anti-dengue activities from plants distributed around the world. Sixty-nine studies from 1997 to 2012 describe 31 different species from 24 families that are known for their anti-dengue activities. About ten phytochemicals have been isolated from 11 species, among which are compounds with the potential for development of dengue treatment. Crude extracts and essential oils obtained from 31 species showed a broad activity against Flavivirus. Current studies show that natural products represent a rich potential source of new anti-dengue compounds. Further ethnobotanical surveys and laboratory investigations are needed established the potential of identified species in contributing to dengue control.

Mitochondrial dysfunction as a central event for mechanisms underlying insulin resistance: the roles of long chain fatty acids

Insulin resistance is characterized by hyperglycaemia, dyslipidaemia and oxidative stress prior to the development of type 2 diabetes mellitus. To date, a number of mechanisms have been proposed to link these syndromes together, but it remains unclear what the unifying condition that triggered these events in the progression of this metabolic disease. There have been a steady accumulation of data in numerous experimental studies showing the strong correlations between mitochondrial dysfunction, oxidative stress and insulin resistance. In addition, a growing number of studies suggest that the raised plasma free fatty acid level induced insulin resistance with the significant alteration of oxidative metabolism in various target tissues such as skeletal muscle, liver and adipose tissue. In this review, we herein propose the idea of long chain fatty acid‐induced mitochondrial dysfunctions as one of the key events in the pathophysiological development of insulin resistance and type 2 diabetes. The accumulation of reactive oxygen species, lipotoxicity, inflammation‐induced endoplasmic reticulum stress and alterations of mitochondrial gene subset expressions are the most detrimental that lead to the developments of aberrant intracellular insulin signalling activity in a number of peripheral tissues, thereby leading to insulin resistance and type 2 diabetes. Copyright

Mitochondrial dysfunction as a central event for mechanisms underlying insulin resistance

Insulin resistance is characterized by hyperglycaemia, dyslipidaemia and oxidative stress prior to the development of type 2 diabetes mellitus. To date, a number of mechanisms have been proposed to link these syndromes together, but it remains unclear what the unifying condition that triggered these events in the progression of this metabolic disease. There have been a steady accumulation of data in numerous experimental studies showing the strong correlations between mitochondrial dysfunction, oxidative stress and insulin resistance. In addition, a growing number of studies suggest that the raised plasma free fatty acid level induced insulin resistance with the significant alteration of oxidative metabolism in various target tissues such as skeletal muscle, liver and adipose tissue. In this review, we herein propose the idea of long chain fatty acid‐induced mitochondrial dysfunctions as one of the key events in the pathophysiological development of insulin resistance and type 2 diabetes. The accumulation of reactive oxygen species, lipotoxicity, inflammation‐induced endoplasmic reticulum stress and alterations of mitochondrial gene subset expressions are the most detrimental that lead to the developments of aberrant intracellular insulin signalling activity in a number of peripheral tissues, thereby leading to insulin resistance and type 2 diabetes. Copyright

Optimization of ingredient and processing levels for the production of coconut yogurt using response surface methodology

In this study, response surface methodology (RSM) was employed to optimize the ingredient formulation and processing parameters of coconut milk yogurt production such as temperature, time, and amount of starter culture on the sensory evaluation responses. Besides, the physicochemical properties such as pH, titratable acidity, and viscosity of the yogurt were also analysed. The analyses show that the coconut yogurts have a pH from 4.01 to 5.79, acidity from 0.461 to 2.079 (%), and viscosity from 433 to 21,833 cp during the optimization process. From the analysis of variance, the R2 of all response variables is more than 0.73 that indicates that a high proportion of variability was explained by the model. Based on the response surface 3D plot of the sensory evaluation, the optimum acceptability of the coconut yogurt processing parameter are at temperature of 37oC, 8 h of the fermentation duration, and 3%(w/w) of the starter culture.

Amelioration of mitochondrial dysfunction-induced insulin resistance in differentiated 3T3-L1 adipocytes via inhibition of NF-κB pathways.

A growing body of evidence suggests that activation of nuclear factor kappa B (NF-κB) signaling pathways is among the inflammatory mechanism involved in the development of insulin resistance and chronic low-grade inflammation in adipose tissues derived from obese animal and human subjects. Nevertheless, little is known about the roles of NF-κB pathways in regulating mitochondrial function of the adipose tissues. In the present study, we sought to investigate the direct effects of celastrol (potent NF-κB inhibitor) upon mitochondrial dysfunction-induced insulin resistance in 3T3-L1 adipocytes. Celastrol ameliorates mitochondrial dysfunction by altering mitochondrial fusion and fission in adipocytes. The levels of oxidative DNA damage, protein carbonylation and lipid peroxidation were down-regulated. Further, the morphology and quantification of intracellular lipid droplets revealed the decrease of intracellular lipid accumulation with reduced lipolysis. Moreover, massive production of the pro-inflammatory mediators tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were markedly depleted. Insulin-stimulated glucose uptake activity was restored with the enhancement of insulin signaling pathways. This study signified that the treatments modulated towards knockdown of NF-κB transcription factor may counteract these metabolic insults exacerbated in our model of synergy between mitochondrial dysfunction and inflammation. These results demonstrate for the first time that NF-κB inhibition modulates mitochondrial dysfunction induced insulin resistance in 3T3-L1 adipocytes.

Cytotoxic effect of Annona muricata Linn leaves extract on Capan-1 cells -

Annona muricata Linn has been reported to contain valuable bioactive compounds known as Annonaceous acetogenins. These long chain fatty acids were widely discussed for its potential in promoting anticancer and anti-proliferative activity in various cancer cell lines. However, little study has been done on A. muricata effect in pancreatic cancer cells. In this study, the viability of Capan-1 after treatment with A. muricata extracts was determined by using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The results displayed that only hexane and commercialized extract inhibited cell proliferation in a concentration-dependent manner with IC25 varied ~7.8-8 μg/ml and ~0.9-1.0 μg/ml respectively. The data demonstrate that A. muricata hexane and commercialized extracts induced mild cytotoxicity in pancreatic cancer cells (Capan-1).

Celastrol protects against antimycin A-induced insulin resistance in human skeletal muscle cells

Mitochondrial dysfunction and inflammation are widely accepted as key hallmarks of obesity-induced skeletal muscle insulin resistance. The aim of the present study was to evaluate the functional roles of an anti-inflammatory compound, celastrol, in mitochondrial dysfunction and insulin resistance induced by antimycin A (AMA) in human skeletal muscle cells. We found that celastrol treatment improved insulin-stimulated glucose uptake activity of AMA-treated cells, apparently via PI3K/Akt pathways, with significant enhancement of mitochondrial activities. Furthermore, celastrol prevented increased levels of cellular oxidative damage where the production of several pro-inflammatory cytokines in cultures cells was greatly reduced. Celastrol significantly increased protein phosphorylation of insulin signaling cascades with amplified expression of AMPK protein and attenuated NF-κB and PKC θ activation in human skeletal muscle treated with AMA. The improvement of insulin signaling pathways by celastrol was also accompanied by augmented GLUT4 protein expression. Taken together, these results suggest that celastrol may be advocated for use as a potential therapeutic molecule to protect against mitochondrial dysfunction-induced insulin resistance in human skeletal muscle cells.

In Vitro Pro-apoptotic and Anti-migratory Effects of Ficus deltoidea L. Plant Extracts on the Human Prostate Cancer Cell Lines PC3

This study aims to evaluate the in vitro cytotoxic and anti-migratory effects of Ficus deltoidea L. on prostate cancer cells, identify the active compound/s and characterize their mechanism of actions. Two farmed varieties were studied, var. angustifolia (FD1) and var. deltoidea (FD2). Their crude methanolic extracts were partitioned into n-hexane (FD1h, FD2h) chloroform (FD1c, FD2c) and aqueous extracts (FD1a, FD2a). Antiproliferative fractions (IC50 < 30 μg/mL, SRB staining of PC3 cells) were further fractionated. Active compound/s were dereplicated using spectroscopic methods. In vitro mechanistic studies on PC3 and/or LNCaP cells included: annexin V-FITC staining, MMP depolarization measurements, activity of caspases 3 and 7, nuclear DNA fragmentation and cell cycle analysis, modulation of Bax, Bcl-2, Smac/Diablo, and Alox-5 mRNA gene expression by RT-PCR. Effects of cytotoxic fractions on 2D migration and 3D invasion were tested by exclusion assays and modified Boyden chamber, respectively. Their mechanisms of action on these tests were further studied by measuring the expression VEGF-A, CXCR4, and CXCL12 in PC3 cells by RT-PCR. FD1c and FD2c extracts induced cell death (P < 0.05) via apoptosis as evidenced by nuclear DNA fragmentation. This was accompanied by an increase in MMP depolarization (P < 0.05), activation of caspases 3 and 7 (P < 0.05) in both PC3 and LNCaP cell lines. All active plant extracts up-regulated Bax and Smac/DIABLO, down-regulated Bcl-2 (P < 0.05). Both FD1c and FD2c were not cytotoxic against normal human fibroblast cells (HDFa) at the tested concentrations. Both plant extracts inhibited both migration and invasion of PC3 cells (P < 0.05). These effects were accompanied by down-regulation of both VEGF-A and CXCL-12 gene expressions (P < 0.001). LC–MS dereplication using taxonomy filters and molecular networking databases identified isovitexin in FD1c; and oleanolic acid, moretenol, betulin, lupenone, and lupeol in FD2c. In conclusion, FD1c and FD2c were able to overcome three main hallmarks of cancer in PC3 cells: (1) apoptosis by activating of the intrinsic pathway, (2) inhibition of both migration and invasion by modulating the CXCL12-CXCR4 axis, and (3) inhibiting angiogenesis by modulating VEGF-A expression. Moreover, isovitexin is here reported for the first time as an antiproliferative principle (IC50 = 43 μg/mL, SRB staining of PC3 cells).

Microwave-Assisted stabilisation and storage stability study of rice bran oil from different varieties

Rice bran is a by-product from milling process of paddy rice to produce refined rice, however until today, there was limited utilisation of rice bran even though rice bran has the ability and potential to become of the major supplementary sources that function as food agent substance. This is due to the instability of rice bran as it will become unstable due to the hydrolysis and oxidation process. The oxidation process, mainly due to the oil presence in the rice bran, releases substances that is unsuitable for consumption. Immediate extraction of the oil from the rice bran is needed as it will be hydrolysed into free fatty acids (FFA) and glycerol by the activity of lipase enzymes. The stabilisation of rice bran can be done by controlling the lipase activity. This process could indirectly prevent the rice bran from being oxidised. Studies have shown that the lipase enzymes in the rice bran can be inactivated depends on the temperature and duration of heat exposure (stabilisation) as well as the moisture content. In this study, the effect of microwave-assisted stabilisation of rice bran was investigated on the quality of rice bran oil (RBO) extracted. Different varieties of rice bran were used in this study which was from lowland, upland and Bario. Extraction of the rice bran was performed using soxtherm extractor and quality of RBO was determined by analysing its properties in terms of crude RBO yield, moisture content and free fatty acid content. Storage stability of the rice bran was evaluated until 40 d. The results demonstrated that the Bario rice bran showed decrease of oil yield from 0 - 40 d with a difference of 48.9 %, followed by the lowland rice bran by 48.7 %. The upland rice bran oil gives the higher different percentage of 64.2 % during the storage. An increase of moisture content was observed during the storage for all stabilised and unstabilised rice brans. Free fatty acid contents show increase amount in almost all types of rice bran range from 2.5 to 11.9 %.

Metabolomics - the complementary field in systems biology

Metabolomic studies on obesity and type 2 diabetes mellitus have led to a number of mechanistic insights into biomarker discovery and comprehension of disease progression at metabolic levels. This article reviews a series of metabolomic studies carried out in previous and recent years on obesity and type 2 diabetes, which have shown potential metabolic biomarkers for further evaluation of the diseases. Literature including journals and books from Web of Science, Pubmed and related databases reporting on the metabolomics in these particular disorders are reviewed. We herein discuss the potential of reported metabolic biomarkers for a novel understanding of disease processes. These biomarkers include fatty acids, TCA cycle intermediates, carbohydrates, amino acids, choline and bile acids. The biological activities and aetiological pathways of metabolites of interest in driving these intricate processes are explained. The data from various publications supported metabolomics as an effective strategy in the identification of novel biomarkers for obesity and type 2 diabetes. Accelerating interest in the perspective of metabolomics to complement other fields in systems biology towards the in-depth understanding of the molecular mechanisms underlying the diseases is also well appreciated. In conclusion, metabolomics can be used as one of the alternative approaches in biomarker discovery and the novel understanding of pathophysiological mechanisms in obesity and type 2 diabetes. It can be foreseen that there will be an increasing research interest to combine metabolomics with other omics platforms towards the establishment of detailed mechanistic evidence associated with the disease processes.