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Involvement of liver in diabetes mellitus: herbal remedies

Thent ZC, Das S

Clin Ter, 2014;165(4):223-30.
PMID: 25203338 DOI: 10.7417/CT.2014.1738

Liver disease is considered as one of the major complications in oxidative stress disorders like diabetes mellitus (DM). DM presents with deterioration in carbohydrate metabolism which is characterized with chronic hyperglycemia. The organ which involves in glucose or carbohydrate metabolism and is most likely to be affected is the liver. Deterioration in liver architecture and metabolism in DM, are considered as common findings. In the present review both biochemical and histological changes occurring in diabetic liver are conferred in detail. To counteract the oxidative stress disorders and its untoward complications, antioxidant or herbs have emerged as alternative medicine. The present review focuses on several herbs with antioxidant properties towards diabetic liver disease such as Liquorice, Pelargonium gravenolens, Momordica charantia, Propolis from bee hives, Dihar, Curcuma Longa, Tinospora cordifolia, Kangen-karyu, Parsley, Chard, Green tea Catechins and Piper sarmentosum (P.s). The herbs or the compounds present in herbs have potential to improve the liver metabolism and maintain the integrity of liver tissue in DM. The review also opens the door for effective use of herbal products for complications involved in the diabetic liver disease.
An insight into the harmful effects of soy protein: A review

Sukalingam K, Ganesan K, Das S, Thent ZC

Clin Ter, 2015;166(3):131-9.
PMID: 26152621 DOI: 10.7417/CT.2015.1843

Soy protein (SP) is a protein derived from soybean meal. SP is obtained from the removal of the outer shell of soybean and the fatty acid. The dietary supplementation of SP was was reported to have positive effects on human health. Therefore, the attention towards SP is increasing among the consumers, industrialist and researchers. However, the side effects and toxicity related to SP was not summarized, to date. This review summarized the toxic effects such as hormonal disturbances, carcinogenic and organotoxicity of SP based on the clinical and experimental studies. The review mainly focused on the effect of soy isoflavone-genistein on various organs. The main aim of the present review is to increase the public awareness on the harmful effect of SP on the various health aspects and draw the attention of the health care personnel and researchers.
Fulltext Protective effect of Momordica charantia fruit extract on hyperglycaemia-induced cardiac fibrosis

Abas R, Othman F, Thent ZC

Oxid Med Cell Longev, 2014;2014:429060.
PMID: 25371774 DOI: 10.1155/2014/429060

In diabetes mellitus, cardiac fibrosis is characterized by increase in the deposition of collagen fibers. The present study aimed to observe the effect of Momordica charantia (MC) fruit extract on hyperglycaemia-induced cardiac fibrosis. Diabetes was induced in the male Sprague-Dawley rats with a single intravenous injection of streptozotocin (STZ). Following 4 weeks of STZ induction, the rats were subdivided (n = 6) into control group (Ctrl), control group treated with MC (Ctrl-MC), diabetic untreated group (DM-Ctrl), diabetic group treated with MC (DM-MC), and diabetic group treated with 150 mg/kg of metformin (DM-Met). Administration of MC fruit extract (1.5 g/kg body weight) in diabetic rats for 28 days showed significant increase in the body weight and decrease in the fasting blood glucose level. Significant increase in cardiac tissues superoxide dismutase (SOD), glutathione contents (GSH), and catalase (CAT) was observed following MC treatment. Hydroxyproline content was significantly reduced and associated morphological damages reverted to normal. The decreased expression of type III and type IV collagens was observed under immunohistochemical staining. It is concluded that MC fruit extract possesses antihyperglycemic, antioxidative, and cardioprotective properties which may be beneficial in the treatment of diabetic cardiac fibrosis.
Fulltext Role of exercise in the management of diabetes mellitus: the global scenario

Thent ZC, Das S, Henry LJ

PLoS One, 2013;8(11):e80436.
PMID: 24236181 DOI: 10.1371/journal.pone.0080436

Background: Exercise training programs have emerged as a useful therapeutic regimen for the management of type 2 diabetes mellitus (T2DM). Majority of the Western studies highlighted the effective role of exercise in T2DM. Therefore, the main aim was to focus on the extent, type of exercise and its clinical significance in T2DM in order to educate the clinicians from developing countries, especially in Asians.

Methods: Pubmed, Science Direct, Scopus, ISI Web of Knowledge and Google scholar were searched using the terms "type 2 diabetes mellitus," "type 2 DM," "exercise," and/or "physical activity," and "type 2 diabetes mellitus with exercise." Only clinical or human studies published in English language between 2000 and 2012 were included. Certain criteria were assigned to achieve appropriate results.

Results: Twenty five studies met the selected criteria. The majority of the studies were randomized controlled trial study design (65%). Most of the aerobic exercise based studies showed a beneficial effect in T2DM. Resistance exercise also proved to have positive effect on T2DM patients. Minimal studies related to other types of exercises such as yoga classes, joba riding and endurance-type exercise were found. On the other hand, United States of America (USA) showed strong interest of exercise management towards T2DM.

Conclusion: Aerobic exercise is more common in clinical practice compared to resistance exercise in managing T2DM. Treatment of T2DM with exercise training showed promising role in USA. A large number of researches are mandatory in the developing countries for incorporating exercise in the effective management of T2DM.
The underlying mechanism of action for various medicinal properties of Piper betle (betel)

Haslan H, Suhaimi FH, Thent ZC, Das S

Clin Ter, 2015;166(5):208-14.
PMID: 26550811 DOI: 10.7417/CT.2015.1880

Piper betle (betel) plant belongs to the Piperaceae family. Piper. betle is widely known for its potent medicinal properties. Various active compounds are present in Piper. betle such as allylpyrocatechol, hydroxychavicol, piperbetol, ethylpiperbetol, piperol A, piperol B, chavibetol, and alkaloids which account for these beneficial medicinal properties. In the present narrative review, we looked into the various active compounds present in the Piper betle and attempted to understand their underlying mechanism of action. Proper understanding of the molecular biology involving the mechanism of action may help in better drug formulation and provide better therapeutic actions in the field of alternative and complementary medicine.
Muscle attachment to the condylar process of mandible: anatomical considerations

Thent ZC, Das S, Mahakkanukrauh P

Surg Radiol Anat, 2016 07;38(5):635.
PMID: 26875077 DOI: 10.1007/s00276-016-1641-x
Fulltext Fructose-Drinking Water Induced Nonalcoholic Fatty Liver Disease and Ultrastructural Alteration of Hepatocyte Mitochondria in Male Wistar Rat

Mamikutty N, Thent ZC, Haji Suhaimi F

Biomed Res Int, 2015;2015:895961.
PMID: 26273656 DOI: 10.1155/2015/895961

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the complications of the metabolic syndrome. It encompasses a wide range of disease spectrum from simple steatosis to liver cirrhosis. Structural alteration of hepatic mitochondria might be involved in the pathogenesis of NAFLD.
AIMS: In the present study, we used a newly established model of fructose-induced metabolic syndrome in male Wistar rats in order to investigate the ultrastructural changes in hepatic mitochondria that occur with fructose consumption and their association with NAFLD pathogenesis.
METHODS: The concentration of fructose-drinking water (FDW) used in this study was 20%. Six male Wistar rats were supplemented with FDW 20% for eight weeks. Body composition and metabolic parameters were measured before and after 8 weeks of FDW 20%. Histomorphology of the liver was evaluated and ultrastructural changes of mitochondria were assessed with transmission electron micrograph.
RESULTS: After 8 weeks of fructose consumption, the animals developed several features of the metabolic syndrome. Moreover, fructose consumption led to the development of macrovesicular hepatic steatosis and mitochondrial ultrastructural changes, such as increase in mitochondrial size, disruption of the cristae, and reduction of matrix density.
CONCLUSION: We conclude that in male Wistar rat 8-week consumption of FDW 20% leads to NAFLD likely via mitochondrial structural alteration.
Emerging Trends On Drug Delivery Strategy of Momordica charantia against Diabetes and its Complications

Thent ZC, Das S, Zaidun NH

Curr Drug Deliv, 2018;15(4):453-460.
PMID: 28545355 DOI: 10.2174/1567201814666170525122224

BACKGROUND: The incidence of diabetes mellitus has increased drastically over the past few decades. This oxidant-antioxidant imbalance resulting in complication of diabetes mellitus includes macro- and microvascular complications. Resistance to conventional treatment and patient compliance has paved the way to the usage of effective natural products and supplements. Momordica charantia (bitter gourd) is widely consumed in many parts of Malaysia as a vegetable. Momordica charantia (MC) is mainly used in the management of diabetes mellitus.
OBJECTIVE: The present review discusses the literature concerning the antidiabetic and antioxidant properties of MC focusing on the complication of diabetes mellitus along with its mode of delivery. We found that among the whole part of MC, its fruit extract has been widely studied, therapeutically. The evidence based analysis of the beneficiary effects of MC on the different organs involved in diabetes complication is also highlighted. This review elucidated an essential understanding of MC based drug delivery system in both clinical and experimental studies and appraised the great potential of the protein based MC extract against diabetes mellitus.
CONCLUSION: The review paper is believed to assist the researchers and medical personnel in treating diabetic associated complications.
Combating oxidative stress disorders with citrus flavonoid: Naringenin

Zaidun NH, Thent ZC, Latiff AA

Life Sci, 2018 Sep 01;208:111-122.
PMID: 30021118 DOI: 10.1016/j.lfs.2018.07.017

The incidence of diseases related to oxidative stress disorders have been increased dramatically. Alternatives medicine or the active compound extracted from the natural products received great attention among researches at the present era. Naringenin (NG), a common dietary flavanone, found in the citrus fruits such as oranges, bergamots, lemons and grapefruit. It is used in the several oxidative stress disorders as the nutraceutical value of the compound emerges. Functionally, the antioxidants effect of NG is primarily attributed by reducing the free radical like reactive oxygen species (ROS) and enhancing the antioxidants activity such as superoxide dismutase (SOD), catalase, glutathione (GSH) in chronic diseases such as cardiovascular, neurodegenerative, diabetes, pulmonary, cancer and nephropathy. The present review article summarised the antioxidant property of NG and its molecular mechanism towards such diseases. Pubmed, Science Direct, Scopus, Web of Science and Google scholar were searched using the terms 'naringenin', 'oxidative stress disorders', 'naringenin and cardiovascular diseases', 'naringenin and diabetes mellitus', 'naringenin and neurodegenerative diseases', 'naringenin and pulmonary diseases', 'naringenin and cancer' and 'naringenin and nephropathy'. There has been special attention on evaluating anti-oxidative effect of NG on neurodegenerative diseases. Although some mechanisms of action remain vague, the current review highlighted the potential use of NG as a oxidative stress reliever which can be used as next prophylaxis compound in the treatment of the various oxidative stress disorders.
Bisphenol A exposure disturbs the bone metabolism: An evolving interest towards an old culprit

Thent ZC, Froemming GRA, Muid S

Life Sci, 2018 Apr 01;198:1-7.
PMID: 29432759 DOI: 10.1016/j.lfs.2018.02.013

Bisphenol A (BPA) (2,2,-bis (hydroxyphenyl) propane), a well-known endocrine disruptor (ED), is the exogenous chemical that mimic the natural endogenous hormone like oestrogen. Due to its extensive exposure to humans, BPA is considered to be a major toxicological agent for general population. Environmental exposure of BPA results in adverse health outcomes including bone loss. BPA disturbs the bone health by decreasing the plasma calcium level and inhibiting the calcitonin secretion. BPA also stimulated differentiation and induced apoptosis in human osteoblasts and osteoclasts. However, little is known about the underlying mechanisms of the untoward effect of BPA against bone metabolism. The present review gives an overview on the possible mechanisms of BPA towards bone loss. The previous literature shows that BPA exerts its toxic effect on bone cells by binding to the oestrogen related receptor-gamma (ERγ), reducing the bone morphogenic protein-2 (BMP-2) and alkaline phosphatase (ALP) activities. BPA interrupts the bone metabolism via RANKL, apoptosis and Wnt/β-catenin signaling pathways. It is, however, still debated on the exact underlying mechanism of BPA against bone health. We summarised the molecular evidences with possible mechanisms of BPA, an old environmental culprit, in bone loss and enlightened the underlying understanding of adverse action of BPA in the society.
Fulltext Effect of Momordica charantia fruit extract on vascular complication in type 1 diabetic rats

Abas R, Othman F, Thent ZC

EXCLI J, 2015;14:179-89.
PMID: 26417358 DOI: 10.17179/excli2014-539

Diabetes mellitus is one of the risk factors in the development of vascular complications. Decreased nitric oxide (NO) production and increased lipid peroxidation in diabetes mellitus are the dominant exaggerating factors. Mormodica charantia (MC) was proven to be useful in improving diabetes mellitus and its complications. In the present study, a total of 40 male Sprague-Dawley rats were used. Diabetes was induced by a single dose (50 mg/kg) of streptozotocin (STZ), intramuscularly. Following 4 weeks of STZ induction, the animals were equally divided into five groups (n = 8); Control group (Ctrl), control group treated with MC (Ctrl-MC), diabetic untreated group (DM-Ctrl), diabetic group treated with MC (DM-MC) and diabetic group treated with metformin 150 g/kg (DM-Met). Oral administration of the MC fruit extract (1.5 g/kg) was continued for 28 days. DM-MC group showed a significant decrease (P < 0.05) in blood pressure, total cholesterol and triglyceride levels compared to the DM-Ctrl group. Aortic tissue NO level was significantly increased and malondialdehyde level was decreased in the DM-MC group. Immunohistochemical staining showed an increase in eNOS expression in the endothelial lining of the DM-MC group. Similarly, morphological deterioration of the aortic tissues was reverted to normal. In summary, treatment with the MC fruit extract exerted the significant vasculoprotective effect in the type 1 diabetic rat model.
Does Vitamin K Intake Influence High Phosphate Induced Vascular Pseudo-ossification: An Underappreciated Therapeutic Prospect in General Population?

Thent ZC, Froemming GRA, Muid SA

Curr Drug Targets, 2019;20(4):421-430.
PMID: 30378497 DOI: 10.2174/1389450119666181031124430

Increasing interest in vascular pseudo-ossification has alarmed the modern atherosclerotic society. High phosphate is one of the key factors in vascular pseudo ossification, also known as vascular calcification. The active process of deposition of the phosphate crystals in vascular tissues results in arterial stiffness. High phosphate condition is mainly observed in chronic kidney disease patients. However, prolonged exposure with high phosphate enriched foods such as canned drinks, dietary foods, etc. can be considered as modifiable risk factors for vascular complication in a population regardless of chronic kidney disease. High intake of vitamin K regulates the vascular calcification by exerting its anti-calcification effect. The changes in serum phosphate and vitamin K levels in a normal individual with high phosphate intake are not well investigated. This review summarised the underlying mechanisms of high phosphate induced vascular pseudo ossification such as vascular transdifferentiation, vascular apoptosis and phosphate uptake by sodium-dependent co-transporters. Pubmed, Science Direct, Scopus, ISI Web of Knowledge and Google Scholar were searched using the terms 'vitamin K', 'vascular calcification, 'phosphate', 'transdifferentiation' and 'vascular pseudoossification'. Vitamin K certainly activates the matrix GIA protein and inhibits vascular transition and apoptosis in vascular pseudo-ossification. The present view highlighted the possible therapeutic linkage between vitamin K and the disease. Understanding the role of vitamin K will be considered as potent prophylaxis agent against the vascular disease in near future.
Fulltext Histological changes in the heart and the proximal aorta in experimental diabetic rats fed with Piper sarmentsoum

Thent ZC, Lin TS, Das S, Zakaria Z

Afr J Tradit Complement Altern Med, 2012;9(3):396-404.
PMID: 23983373

Cardiovascular complications are one of the major causes of death in diabetes mellitus. Piper sarmentosum (P.s) is an herb that possesses antihyperglycaemic effects. The main aim of the study was to observe the histological changes in the heart and the proximal aorta of streptozotocin-induced diabetic rats following P.s administration. Twenty-four male Sprague-Dawley rats (n=24) were equally randomized into four groups: control group supplemented with normal saline (C); control group supplemented with P.s (CTx) ; diabetic group supplemented with normal saline (D) and, diabetic group supplemented with P.s (DTx). Diabetes was induced by STZ (50mg/kg body weight) intramuscularly. P.s extract (0.125g/kg) was administered orally for 28 days, following four weeks of STZ induction. The cardiac and aortic tissues were collected and processed under different stains: Haematoxylin and Eosin (H & E), Verhoeff-Van Gieson (VVG), Masson's Trichome (MT) and Periodic Acid- Schiff (PAS). There were abnormal cardiomyocytes nuclei, disarray of myofibres and increase in connective tissue deposits in cardiac tissues of the diabetic untreated group. The thickness of tunica media and ratio of tunica intima to media were found to be significantly increased in the aorta of diabetic untreated group (P < 0.05) compared to the control group. There were degenerative changes in the proximal aorta in diabetic untreated groups. All the histological damages of cardiac and aortic tissues were found to be lesser in the diabetic treated groups. Supplementation with P.s extract prevented the oxidative damage arising from diabetes mellitus, and reduced its complications.
Fulltext Effect of Piper sarmentosum Extract on the Cardiovascular System of Diabetic Sprague-Dawley Rats: Electron Microscopic Study

Thent ZC, Seong Lin T, Das S, Zakaria Z

Evid Based Complement Alternat Med, 2012;2012:628750.
PMID: 23304208 DOI: 10.1155/2012/628750

Although Piper sarmentosum (PS) is known to possess the antidiabetic properties, its efficacy towards diabetic cardiovascular tissues is still obscured. The present study aimed to observe the electron microscopic changes on the cardiac tissue and proximal aorta of experimental rats treated with PS extract. Thirty-two male Sprague-Dawley rats were divided into four groups: untreated control group (C), PS-treated control group (CTx), untreated diabetic group (D), and PS-treated diabetic group (DTx). Intramuscular injection of streptozotocin (STZ, 50 mg/kg body weight) was given to induce diabetes. Following 28 days of diabetes induction, PS extract (0.125 g/kg body weight) was administered orally for 28 days. Body weight, fasting blood glucose, and urine glucose levels were measured at 4-week interval. At the end of the study, cardiac tissues and the aorta were viewed under transmission electron microscope (TEM). DTx group showed increase in body weight and decrease in fasting blood glucose and urine glucose level compared to the D group. Under TEM study, DTx group showed lesser ultrastructural degenerative changes in the cardiac tissues and the proximal aorta compared to the D group. The results indicate that PS restores ultrastructural integrity in the diabetic cardiovascular tissues.
Fulltext The establishment of metabolic syndrome model by induction of fructose drinking water in male Wistar rats

Mamikutty N, Thent ZC, Sapri SR, Sahruddin NN, Mohd Yusof MR, Haji Suhaimi F

Biomed Res Int, 2014;2014:263897.
PMID: 25045660 DOI: 10.1155/2014/263897

Metabolic syndrome can be caused by modification of diet by means of consumption of high carbohydrate and high fat diet such as fructose.
The Molecular Concept of Atheromatous Plaques

Thent ZC, Chakraborty C, Mahakkanukrauh P, Nik Ritza Kosai Nik Mahmood N, Rajan R, Das S

Curr Drug Targets, 2017;18(11):1250-1258.
PMID: 27138760 DOI: 10.2174/1389450117666160502151600

BACKGROUND: Recently, there are scientific attempts to discover new drugs in the biotechnology industry in order to treat various diseases including atherosclerosis.
OBJECTIVE: The main objective of the present review was to highlight the cellular, molecular biology and inflammatory process related to the atheromatous plaques.
METHODS: A thorough literature search of Pubmed, Google and Scopus databases was done.
RESULTS: Atherosclerosis is considered to be a leading cause of death throughout the world. Atherosclerosis involves oxidative damage to the cells with production of reactive oxygen species (ROS). Development of atheromatous plaques in the arterial wall is a common feature. Specific inflammatory markers pertaining to the arterial wall in atherosclerosis may be useful for both diagnosis and treatment. These include Nitric oxide (NO), cytokines, macrophage inhibiting factor (MIF), leucocytes and Pselectin. Modern therapeutic paradigms involving endothelial progenitor cells therapy, angiotensin II type-2 (AT<sub>2</sub>R) and ATP-activated purinergic receptor therapy are notable to mention.
CONCLUSION: Future drugs may be designed aiming three signalling mechanisms of AT<sub>2</sub>R which are (a) activation of protein phosphatases resulting in protein dephosphorylation (b) activation of bradykinin/nitric oxide/cyclic guanosine 3',5'-monophosphate pathway by vasodilation and (c) stimulation of phospholipase A(2) and release of arachidonic acid. Drugs may also be designed to act on ATP-activated purinergic receptor channel type P2X7 molecules which acts on cardiovascular system.
Fulltext Phytoestrogens by inhibiting the non-classical oestrogen receptor, overcome the adverse effect of bisphenol A on hFOB 1.19 cells

Thent ZC, Froemming GRA, Ismail ABM, Fuad SBSA, Muid S

Iran J Basic Med Sci, 2020 Sep;23(9):1155-1163.
PMID: 32963737 DOI: 10.22038/ijbms.2020.45296.10545

Objectives: Since bisphenol A (BPA) induces bone loss and phytoestrogens enhance the osteoblastogenesis by binding to the non-classical and classical oestrogen receptors, respectively, the present study was aimed to observe the osteoprotective effect of phytoestrogens on BPA-induced osteoblasts in hFOB 1.19 cells.
Materials and Methods: All groups of hFOB 1.19 cells were induced with 12.5 μg/ml of BPA except the control (Ctrl) group. Meanwhile, treated groups received phytoestrogens; Daidzein (Dz), Genistein (Gt), Equol (Eq) and 17β-oestradiol (Est) in different concentrations for 24 hr duration.
Results: We found that the protein expression of non-classical oestrogen-related receptor (ERRG) was highly expressed in BPA group, whereas classical oestrogen receptor alpha (ERα) and oestrogen receptor beta (ERβ) were relatively increased with phytoestrogens treatment under BPA exposure. The dense actin cytoskeletal filaments were also observed. qRT-PCR showed up-regulation of mitogen-activated protein kinase 3 (MAPK3) and G protein-coupled receptor 30 (GPR30) expressions; significant down-regulation of ERRG and up-regulation of ERα and ERβ were observed in phytoestrogens-treated cells, which was supported by the increased expressions of oestrogen receptor 1 (ESR1) and oestrogen receptor 2 (ESR2).
Conclusion: Phytoestrogens improved the deteriorative effect of BPA via down-regulation of ERRG in hFOB 1.19 cells. This study showed that the efficacy of consumption of phytoestrogens in rendering them as potential therapeutic strategy in combating the adverse bone effects of BPA.
Employing different types of phytoestrogens improve bone mineralization in bisphenol A stimulated osteoblast

Thent ZC, Froemming GRA, Ismail ABM, Fuad SBSA, Muid S

Life Sci, 2018 Oct 01;210:214-223.
PMID: 30145154 DOI: 10.1016/j.lfs.2018.08.057

AIMS: Phytoestrogens and xenoestrogens act as agonists/antagonists in bone formation and differentiation. Strong bones are depending of the ability of osteoblasts to form new tissue and to mineralize the newly formed tissue. Dysfunctional or loss of mineralization leads to weak bone and increased fracture risk. In this study, we reported the effect of different types of phytoestrogens (daidzein, genistein and equol) on mineralization in hFOB 1.19 cells stimulated with bisphenol A (BPA).
MAIN METHODS: Cell mineralization capacity of phytoestrogens was investigated by evaluating calcium, phosphate content and alkaline phosphatase activity. Bone related markers, osteocalcin and osteonectin, responsible in maintaining mineralization were also measured.
KEY FINDINGS: BPA is significantly interfering with bone mineralization in hFOB 1.19 cells. However, the enhanced mineralization efficacy of daidzein and genistein (particularly at a dose of 5 and 40 μg/mL, respectively) was evidenced by increasing calcium and phosphate content, higher ALP activity, compared to the untreated BPA group. The quantitative analyses were confirmed through morphological findings. Osteocalcin and osteonectin levels were increased in phytoestrogens-treated cells. These findings revealed the potential effect of phytoestrogens in reverting the demineralization process due to BPA exposure in hFOB 1.19 cells.
SIGNIFICANCE: We found that osteoblast differentiation and mineralization were maintained following treatment with phytoestrogens under BPA exposure.
Is Metformin a Therapeutic Paradigm for Colorectal Cancer: Insight into the Molecular Pathway?

Thent ZC, Zaidun NH, Azmi MF, Senin MI, Haslan H, Salehuddin R

Curr Drug Targets, 2017;18(6):734-750.
PMID: 27919208 DOI: 10.2174/1389450118666161205125548

Colorectal cancer (CRC) remains one of the major leading causes of cancer related morbidity and mortality. Apart from the conventional anti-neoplastic agents, metformin, a biguanide anti-diabetic agent, has recently found to have anti-cancer property. Several studies observed the effect of metformin towards its anti-cancer effect on colon or colorectal cancer in diabetic patients. However, only a few studies showed its effect on colorectal cancer in relation to the non-diabetic status. The present review aimed to highlight the insight into the molecular pathway of metformin towards colorectal cancer in the absence of diabetes mellitus. In CRC-independent of diabetes mellitus, highly deregulation of PI3K/AKT pathway is found which activates the downstream mammalian target of rapamycin (mTOR). Metformin inhibits cancer growth in colon by suppressing the colonic epithelial proliferation by inhibiting the mTOR pathway. Metformin exerts its anti-neoplastic effects by acting on tumour suppressor pathway via activating the adenosine monophosphate.activated protein kinase (AMPK) signaling pathway. Metformin interrupts the glucose metabolism by activating the AMPK. Metformin reduces tumour cell growth and metastasis by activating the p53 tumour suppressor gene. In addition to its therapeutic benefits, metformin is easily accessible, cost effective with better tolerance to the patients compared to the chemotherapeutic agents. This review summarised modern findings on the therapeutic applications of metformin on the colorectal cancer with no evidences of diabetes mellitus.
Fulltext Zika virus infection and its emerging trends in Southeast Asia

Salehuddin AR, Haslan H, Mamikutty N, Zaidun NH, Azmi MF, Senin MM, et al.

Asian Pac J Trop Med, 2017 Mar;10(3):211-219.
PMID: 28442104 DOI: 10.1016/j.apjtm.2017.03.002

Zika virus is a mosquito-borne flavivirus that represents a public health emergency at the ongoing epidemic. Previously, this rare virus was limited to sporadic cases in Africa and Asia until its emergence in Brazil, South America in 2015, where it rapidly spread throughout the world. Recently, a high number of cases were reported in Singapore and other Southeast Asia countries. A combination of factors explains the current Zika virus outbreak although it is highly likely that the changes in the climate and high frequency of travelling contribute to the spread of Aedes vector carrying the Zika virus mainly to the tropical climate countries such as the Southeast Asia. The Zika virus is known to cause mild clinical symptoms similar to those of dengue and chikungunya and transmitted by different species of Aedes mosquitoes. However, neurological complications such as Guillain-Barré syndrome in adults, and congenital anomalies, including microcephaly in babies born to infected mothers, raised a serious concern. Currently, there is no specific antiviral treatment or vaccine available for Zika virus infection. Therefore, international public health response is primarily focused on preventing infection, particularly in pregnant women, and on providing up-to-date recommendations to reduce the risk of non-vector transmission of Zika virus.

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