Manilkara zapota (L.) P. Royen (Family: Sapotaceae), commonly called as sapodilla, has been applied as traditional folk medicine for diarrhea and pulmonary infections. Conventional therapy in colorectal cancer is not likely effective due to undesirable outcomes. The anti-colon cancer properties of Manilkara zapota leaf water extract have yet to be investigated thus far. Therefore, our present study aimed to evaluate the ability to induce apoptosis and the underlying mechanisms of Manilkara zapota leaf water extract against human colorectal cancer (HT-29) cells. The cytotoxicity of Manilkara zapota leaf water extract was screened in different cancer cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) analyses. The morphological changes in HT-29 cell lines after exposure to Manilkara zapota leaf water extract were viewed under fluorescence and inverted light microscope. The apoptotic cell was measured by Annexin V-propidium iodide staining. The caspase-3 and -8 activities were assessed by colorimetric assay. Overall analyses revealed that treatment with Manilkara zapota leaf water extract for 72 h can inhibit the viability of HT-29 cells. Incubation with Manilkara zapota leaf water extract for 24, 48, and 72 h significantly increased (p < 0.05) the total apoptotic cells compared to the control. Treatment with 21, 42, and 84 μg/mL of Manilkara zapota leaf water extract for 72 h triggered both caspase-3 and -8 activities in a concentration-dependent pattern. We also found that the catalase level in the two treatment groups (21 and 42 μg/mL) was significantly elevated after 24 h incubation. Incubation with Manilkara zapota leaf water extract for 72 h triggered the transcriptional elevation of the adenomatous polyposis coli (APC), glycogen synthase kinase 3β (GSK3β), AXIN1, and casein kinase 1 (CK1). The β-catenin mRNA levels were reduced accordingly when the concentration of the Manilkara zapota leaf water extract was increased. Our results suggested that Manilkara zapota leaf water extract offer great potential against colorectal cancer through modulation of Wnt/β-catenin signaling pathway, caspase-dependent pathway, and antioxidant enzyme.
Prostate cancer has become the second leading cancer in men worldwide. Androgen plays an important role in normal functioning, development, and differentiation of the prostate, and thus is considered to be the most powerful candidate that mediates reactive oxygen species (ROS) balance in the prostate. The elevation of ROS has been associated with the progression and development of this disease. Conventional therapy has shown a high cure rate in patients with localized prostate cancer. Despite the patients respond favorably initially, this therapy fails to response in the advanced stage of the diseases even in the absence of androgens. Indeed, the onset and progression of prostate cancer could be prevented by changing dietary habits. Much information indicates that oxidative stress and prostate cancer can be modulated by dietary components rich in antioxidants. While there is substantial evidence to suggest an association between prostate cancer risk and ROS-mediated oxidative stress; therefore, the interactions and mechanisms of this phenomenon are worth to discuss further. This review aimed to discuss the mechanisms of action of oxidative stress involved in the progression of prostate cancer. We also highlighted how some of the vital dietary components dampen or exacerbate inflammation, oxidative stress, and prostate cancer. Overall, the reported information would provide a useful approach to the prevention of prostate cancer.
Cancer is a significant global health concern affecting men and women worldwide. Although current chemopreventive drugs could inhibit the growth of cancer cells, they exert many adverse side effects. Dietary factor plays a crucial role in the management of cancers and has drawn the attention of researchers to be used as an option to combat this disease. Both in vitro and in vivo studies showed that rice and its by-products display encouraging results in the prevention of this disease. The mechanism of anticancer effect is suggested partly through potentiation of bioactive compounds like vitamin E, phytic acid, γ-aminobutyric acid (GABA), γ-oryzanol, and phenolics. Nevertheless, the bioactivity of rice and its by-products is still incompletely understood. In this review, we present the findings from a preclinical study both in in vitro and in animal experiments on the promising role of rice by-products with focus on cancer prevention.
Cognitive dysfunction is linked to chronic low-grade inflammatory stress that contributes to cell-mediated immunity in creating an oxidative environment. Food is a vitally important energy source; it affects brain function and provides direct energy. Several studies have indicated that high-fat consumption causes overproduction of circulating free fatty acids and systemic inflammation. Immune cells, free fatty acids, and circulating cytokines reach the hypothalamus and initiate local inflammation through processes such as microglial proliferation. Therefore, the role of high-fat diet (HFD) in promoting oxidative stress and neurodegeneration is worthy of further discussion. Of particular interest in this article, we highlight the associations and molecular mechanisms of HFD in the modulation of inflammation and cognitive deficits. Taken together, a better understanding of the role of oxidative stress in cognitive impairment following HFD consumption would provide a useful approach for the prevention of cognitive dysfunction.
Despite an increase in life expectancy that indicates positive human development, a new challenge is arising. Aging is positively associated with biological and cognitive degeneration, for instance cognitive decline, psychological impairment, and physical frailty. The elderly population is prone to oxidative stress due to the inefficiency of their endogenous antioxidant systems. As many studies showed an inverse relationship between carotenoids and age-related diseases (ARD) by reducing oxidative stress through interrupting the propagation of free radicals, carotenoid has been foreseen as a potential intervention for age-associated pathologies. Therefore, the role of carotenoids that counteract oxidative stress and promote healthy aging is worthy of further discussion. In this review, we discussed the underlying mechanisms of carotenoids involved in the prevention of ARD. Collectively, understanding the role of carotenoids in ARD would provide insights into a potential intervention that may affect the aging process, and subsequently promote healthy longevity.
Many chemotherapeutic drugs have been used for the treatment of cancer, for instance, doxorubicin, irinotecan, 5-fluorouracil, cisplatin, and paclitaxel. However, the effectiveness of chemotherapy is limited in cancer therapy due to drug resistance, therapeutic selectivity, and undesirable side effects. The combination of therapies with natural compounds is likely to increase the effectiveness of drug treatment as well as reduce the adverse outcomes. Curcumin, a polyphenolic isolated from Curcuma longa, belongs to the rhizome of Zingiberaceae plants. Studies from in vitro and in vivo revealed that curcumin exerts many pharmacological activities with less toxic effects. The biological mechanisms underlying the anticancer activity of co-treatment curcumin and chemotherapy are complex and worth to discuss further. Therefore, this review aimed to address the molecular mechanisms of combined curcumin and chemotherapy in the treatment of cancer. The anticancer activity of combined nanoformulation of curcumin and chemotherapy was also discussed in this study. Taken together, a better understanding of the implication and underlying mechanisms of action of combined curcumin and chemotherapy may provide a useful approach to combat cancer diseases.
This study is carried out to determine the potential of phytic acid extracted from rice bran in the suppression of colon carcinogenesis induced by azoxymethane (AOM) in rats. Seventy-two male Sprague-Dawley rats were divided into 6 groups with 12 rats in each group. The intended rats for cancer treatment received two intraperitoneal injections of AOM in saline (15mg/kg bodyweight) over a 2-week period. The treatments of phytic acid were given in two concentrations: 0.2% (w/v) and 0.5% (w/v) during the post-initiation phase of carcinogenesis phase via drinking water. The colons of the animals were analyzed for detection and quantification of aberrant crypt foci (ACF) after 8 weeks of treatment. The finding showed treatment with 0.2% (w/v) extract phytic acid (EPA) gave the greatest reduction in the formation of ACF. In addition, phytic acid significantly suppressed the number of ACF in the distal, middle and proximal colon as compared to AOM alone (p<0.05). For the histological classification of ACF, treatment with 0.5% (w/v) commercial phytic acid (CPA) had the highest percentage (71%) of non-dysplastic ACF followed by treatment with 0.2% (w/v) EPA (61%). Administration of phytic acid also reduced the incidence and multiplicity of total tumors even though there were no significant differences between groups. In conclusion, this study found the potential value of phytic acid extracted from rice bran in reducing colon cancer risk in rats.
The inhibitory effect of phytate on the bioavailability of iron, zinc and calcium was determined by measuring their molar ratios. A total of 29 food samples consisting of 12 rice and rice products, 5 wheat and wheat products, 5 grains and cereal based products and 7 different popular varieties of cooked rice and rice products were selected. The phytate content was analysed using anion-exchange chromatography whereas mineral contents were analysed using atomic absorption spectrophotometry(AAS). One-way ANOVA test was used to statistically analyse the mean difference between the phytate and mineral contents between the food group samples. In general, results show that cooked products have lower content of phytate and minerals as compared to raw products. This could be due to the influence of the cooking method on phytate and mineral content in the food. Based on one-way ANOVA test, there were no significant difference in phytate and zinc content between four food groups (p >0.05). Significant differences were found only in iron and calcium content (p <0.05). Of the 29 food samples, 25 food samples had a phytate/iron molar ratio > 1, 5 food samples had a phytate/zinc molar ratio > 15 and 23 food samples had a phytate/calcium molar ratio of 0.24. These results show that although many of the food samples analysed had high mineral content, the high phytate content may impair the bioavailability of the mineral in the body.
Magnetic iron oxide nanoparticles are among the most useful metal nanoparticles in biomedical applications. A previous study had confirmed that phytic acid-chitosan-iron oxide nanocomposite (Phy-CS-MNP) exhibited antiproliferative activity towards human colorectal cancer (HT-29) cells. Hence, in this work, we explored the in vitro cytotoxicity activity and mechanistic action of Phy-CS-MNP nanocomposite in modulating gene and protein expression profiles in HT-29 cell lines. Cell cycle arrest and apoptosis were evaluated by NovoCyte Flow Cytometer. The mRNA changes (cyclin-dependent kinase 4 (Cdk4), vascular endothelial growth factor A (VEGFA), c-Jun N-terminal kinase 1 (JNK1), inducible nitric oxide synthase (iNOS), and matrix metallopeptidase 9 (MMP9)) and protein expression (nuclear factor-kappa B (NF-κB) and cytochrome c) were assessed by quantitative real-time polymerase chain reaction (PCR) and western blotting, respectively. The data from our study demonstrated that treatment with Phy-CS-MNP nanocomposite triggered apoptosis and G₀/G₁ cell cycle arrest. The transcriptional activity of JNK1 and iNOS was upregulated after treatment with 90 μg/mL Phy-CS-MNP nanocomposite. Our results suggested that Phy-CS-MNP nanocomposite induced apoptosis and cell cycle arrest via an intrinsic mitochondrial pathway through modulation of Bax and Bcl-2 and the release of cytochrome c from the mitochondria into the cytosol.
Rice (Oryza sativa L.) is a principal food for more than half of the world's people. Rice is predominantly consumed as white rice, a refined grain that is produced during the rice milling process which removes the bran and germ and leaves the starchy endosperm. Rice bran is a by-product produced from the rice milling process, which contains many bioactive compounds, for instance, phenolic compounds, tocotrienols, tocopherols, and γ-oryzanol. These bioactive compounds are thought to protect against cancer, vascular disease, and type 2 diabetes. Extraction of rice bran oil also generates various by-products including rice bran wax, defatted rice bran, filtered cake, and rice acid oil, and some of them exert bioactive substances that could be utilized as functional food ingredients. However, rice bran is often utilized as animal feed or discarded as waste. Therefore, this review aimed to discuss the role of rice bran in metabolic ailments. The bioactive constituents and food product application of rice bran were also highlighted in this study. Collectively, a better understanding of the underlying molecular mechanism and the role of these bioactive compounds exerted in the rice bran would provide a useful approach for the food industry and prevent metabolic ailments.
Manilkara zapota (L.) P. Royen, called sapodilla, or locally known as ciku, belongs to the family Sapotaceae. We found that Manilkara zapota leaf water extract has cytotoxic effect against human hepatocellular carcinoma (HepG2) cell line in our earlier study. Therefore, this study aimed to explore the anticancer properties of Manilkara zapota leaf water extract in HepG2 cells. We also aimed to unravel yet undiscovered mechanisms and identified several expressed genes whose functions in cytotoxicity activity of Manilkara zapota leaf water extract in HepG2 cells have not been well-studied. The apoptosis and intracellular reactive oxygen species (ROS) activities were analyzed using Annexin V-propidium iodide staining and dichlorodihydrofluorescein diacetate, respectively, by NovoCyte Flow Cytometer. Bax and Bcl-2 expression were assessed using Enzyme-Linked Immunosorbent Assay. The associated molecular pathways were evaluated by quantitative real-time PCR. Overall analyses revealed that Manilkara zapota leaf water extract can increase percentage of early apoptotic cells, induce the formation of ROS, upregulate c-Jun N-terminal kinase 1 (JNK1) and inducible nitric oxide synthase (iNOS), and reduce Akt1 and vascular endothelial growth factor A (VEGFA) transcriptional activities. Our data suggest that Manilkara zapota leaf water extract can suppress the growth of HepG2 cells via modulation of ERK1/2/Akt1/JNK1 transcriptional expression.
Manilkara zapota (L.) P. Royen (family: Sapotaceae) is commonly called sapodilla, or locally known as ciku. The detailed mechanisms underlying Manilkara zapota leaf methanol extract against HeLa human cervical cancer cells have yet to be investigated. Therefore, our present study is designed to investigate the ability to induce apoptosis and the underlying mechanisms of Manilkara zapota leaf methanol extract inducing cytotoxicity in HeLa cells. The apoptotic cell death was assessed using Annexin V-propidium iodide staining. Intracellular reactive oxygen species (ROS) and mitochondrial membrane potential activities were measured using dichlorodihydrofluorescein diacetate and MitoLite Orange, respectively, by NovoCyte Flow Cytometer. Bax and Bcl-2 expression were evaluated using Enzyme-Linked Immunosorbent Assay. Caspase-3 activity was determined using a colorimetric assay. The associated biological interaction pathways were evaluated using quantitative real-time PCR. Our data showed that HeLa cells were relatively more sensitive to Manilkara zapota leaf methanol extract than other cancer cell lines studied. Overall analyses revealed that Manilkara zapota leaf methanol extract can inhibit the viability of HeLa cells, induce mitochondrial ROS generation, and inhibit nuclear factor-kappa B (NF-κB) and epidermal growth factor receptor (EGFR) transcriptional activities. Our results suggested that Manilkara zapota leaf methanol extract might represent a potential anticervical cancer agent.
Gallic acid (GA) is a polyhydroxy phenolic compound that has been detected in various natural products, such as green tea, strawberries, grapes, bananas, and many other fruits. In inflammatory bowel disease, inflammation is promoted by oxidative stress. GA is a strong antioxidant; thus, we evaluated the cytoprotective and anti-inflammatory role of GA in a dextran sulfate sodium (DSS)-induced mouse colitis model. Experimental acute colitis was induced in male BALB/c mice by administering 2.5% DSS in the drinking water for 7 days. The disease activity index; colon weight/length ratio; histopathological analysis; mRNA expressions of IL-21 and IL-23; and protein expression of nuclear erythroid 2-related factor 2 (Nrf2) were compared between the control and experimental mice. The colonic content of malondialdehyde and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activity were examined as parameters of the redox state. We determined that GA significantly attenuated the disease activity index and colon shortening, and reduced the histopathological evidence of injury. GA also significantly (P<0.05) reduced the expressions of IL-21 and IL-23. Furthermore, GA activates/upregulates the expression of Nrf2 and its downstream targets, including UDP-GT and NQO1, in DSS-induced mice. The findings of this study demonstrate the protective effect of GA on experimental colitis, which is probably due to an antioxidant nature of GA.
Brewers' rice, which is known locally as temukut, is a mixture of broken rice, rice bran, and rice germ. Our present study was designed to identify the effect of brewers' rice on the attenuation of liver and kidney damage induced by azoxymethane (AOM). Alanine transaminase (ALT), alkaline phosphatase (ALP), aspartate transaminase (AST), creatinine, and urea were evaluated to understand potential hepatoprotective effects and the ability of brewers' rice to attenuate kidney pathology induced by AOM treatment. Liver and kidney tissues were evaluated by hematoxylin and eosin (H&E) staining. Overall analyses revealed that brewers' rice improved the levels of serum markers in a manner associated with better histopathological outcomes, which indicated that brewers' rice could enhance recovery from hepatocyte and kidney damage. Taken together, these results suggest that brewers' rice could be used in future applications to combat liver and kidney disease.
Brewers' rice, a mixture of broken rice, rice bran, and rice germ, is a rice by-product in the rice industry. The present study was designed to investigate the in vitro cytotoxicity of the water extract of brewers' rice (WBR) against colorectal cancer (HT-29) cells.
Phytic acid (PA) has been shown to have positive nutritional benefits. There are also claims that it is able to prevent cancer through its antioxidant capability. This study investigated antioxidant activity and cytotoxic effect of PA extracted from rice bran against selected cancer cell lines (i.e. ovarian, breast and liver cancer).
INTRODUCTION: There is a lack of information on the trans fatty acid (TFA) content in Malaysian foods. The objective of this study is to determine the TFA content of bakery products, snacks, dairy products, fast foods, cooking oils and semisolid fats, and breakfast cereals and Malaysian fast foods. This study also estimated the quantity of each isomer in the foods assayed.
METHODS: The trans fatty acid content of each food sample was assessed in duplicate by separating the fatty acid methyl esters (FAME) in a gas chromatography system equipped with HP-88 column (USA: split ratio 10: 1) for cis/trans separation. Five major TFA isomers, palmitoelaidic acid (16: 1t9), petroselaidic acid (18:1t6), elaidic acid (18:1t9), vaccenic acid (18: 1t11) and linoelaidic acid (18:2t9, 12), were measured using gas chromatography (GC) and the data were expressed in unit values of g/100 g lipid or g/100 g food.
RESULTS: The total TFA contents in the studied foods were < 0.001 g-8.77 g/100 g lipid or < 0.001 g-5.79 g/100 g foods. This value falls within the standard and international recommendation level for TFA. The measured range of specific TFA isomers were as follows: palmitoelaidic acid (< 0.001 g-0.26 g/100 g lipid), petroselaidic acid (< 0.001 g - 3.09 g/100 g lipid), elaidic acid (< 0.001 g-0.87 g/100 g lipid), vaccenic acid (< 0.001 g-0.41 g/100 g lipid) and linoelaidic acid (< 0.001 g-6.60 g/100 g lipid).
CONCLUSION: These data indicate that most of the tested foods have low TFA contents (< 1 g/100 g lipid).
There are different types of nutritionally mediated oxidative stress sources that trigger inflammation. Much information indicates that high intakes of macronutrients can promote oxidative stress and subsequently contribute to inflammation via nuclear factor-kappa B- (NF-κB-) mediated cell signaling pathways. Dietary carbohydrates, animal-based proteins, and fats are important to highlight here because they may contribute to the long-term consequences of nutritionally mediated inflammation. Oxidative stress is a central player of metabolic ailments associated with high-carbohydrate and animal-based protein diets and excessive fat consumption. Obesity has become an epidemic and represents the major risk factor for several chronic diseases, including diabetes, cardiovascular disease (CVD), and cancer. However, the molecular mechanisms of nutritionally mediated oxidative stress are complex and poorly understood. Therefore, this review aimed to explore how dietary choices exacerbate or dampen the oxidative stress and inflammation. We also discussed the implications of oxidative stress in the adipocyte and glucose metabolism and obesity-associated noncommunicable diseases (NCDs). Taken together, a better understanding of the role of oxidative stress in obesity and the development of obesity-related NCDs would provide a useful approach. This is because oxidative stress can be mediated by both extrinsic and intrinsic factors, hence providing a plausible means for the prevention of metabolic disorders.
Aging is the progressive loss of organ and tissue function over time. Growing older is positively linked to cognitive and biological degeneration such as physical frailty, psychological impairment, and cognitive decline. Oxidative stress is considered as an imbalance between pro- and antioxidant species, which results in molecular and cellular damage. Oxidative stress plays a crucial role in the development of age-related diseases. Emerging research evidence has suggested that antioxidant can control the autoxidation by interrupting the propagation of free radicals or by inhibiting the formation of free radicals and subsequently reduce oxidative stress, improve immune function, and increase healthy longevity. Indeed, oxidation damage is highly dependent on the inherited or acquired defects in enzymes involved in the redox-mediated signaling pathways. Therefore, the role of molecules with antioxidant activity that promote healthy aging and counteract oxidative stress is worth to discuss further. Of particular interest in this article, we highlighted the molecular mechanisms of antioxidants involved in the prevention of age-related diseases. Taken together, a better understanding of the role of antioxidants involved in redox modulation of inflammation would provide a useful approach for potential interventions, and subsequently promoting healthy longevity.
Brewers' rice is one of abundant agricultural waste products in the rice industry. The present study is designed to investigate the potential of brewers' rice to inhibit the development of aberrant crypt foci (ACF) in colon of azoxymethane (AOM)-treated rats. The effects on the attenuation of hepatic toxicity and kidney function enzymes were also evaluated. Male Sprague-Dawley rats were randomly divided into five groups: (G1) normal; (G2) AOM alone; and (G3), (G4), and (G5), which were AOM fed with 10%, 20%, and 40% (w/w) of brewers' rice, respectively. The rats in group 2-5 were injected intraperitoneally with AOM (15 mg/kg body weight) once weekly for two weeks. After 8 weeks of treatment,the total number of ACF/colon and the number of ACF in the distal and middle colon were significantly reduced in all treatment groups compared to G2 (p<0.05). Brewers' rice decreased the number of ACF with dysplastic morphology in a dose-dependent manner. Alkaline phosphatase (ALP) level in G5 was significantly lower compared to the G2 (p<0.05). In conclusion, this study found the potential value of brewers' rice in reducing the risk of cancer susceptibility in colon.