Inflammation and Oxidative Stress in an Obese State and the Protective Effects of Gallic Acid

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Insulin 1 endocrinologydiseasesdrugs
Troglitazone 1 endocrinologydiseasesdrugs
acarbose 1 endocrinologydiseasesdrugs
hypertriglyceridemia 1 endocrinologydiseases
metabolic syndrome 4 endocrinologydiseases
obesity 69 endocrinologydiseases
pioglitazone 1 endocrinologydiseasesdrugs
simvastatin 1 endocrinologydiseasesdrugs
hyperglycemia 4 endocrinologydiseases
hyperlipidemia 1 endocrinologydiseases
metformin 1 endocrinologydiseasesdrugs

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Insulin 9437 oxidative stress are discussed to highlight the anti-obesity potential of gallic acid.2. Inflammation and Insulin Resistance in Adipose TissueGenerally, it is well accepted that adipose tissue expansion in an obese
Troglitazone 52799 2016 [[16]]3T3-L1 adipocytes were treated with gallic acid at 10–30 µM during differentiation period Troglitazone was used at 10 μM, while Terminalia bellirica hot water extract was used at 0.1, 1.0 and 10 during
acarbose 67160 α-glucosidase inhibitory assays for Limonium spp (Plumbaginaceae) rich in epigallocatechinsCompared with acarbose , aqueous extracts of L. contortirameum and L. virgatumAll extract showed inhibitory activity on pancreatic
metformin 19835 preventing these diseases [[72],[73],[74],[75]]. In addition to well-established antidiabetic drugs such as metformin and insulin, literature on the anti-inflammatory and antioxidant effects of some other agents like salsalate,
pioglitazone 30331 (HMG-CoA) reductase [[108]]. However, although data on its comparison with a known antidiabetic agent, pioglitazone [[20]], there is very limited literature that compares the beneficial effects of gallic acid with widely
simvastatin 66441 weight, while silymarin was used at 100 mg/kg body weight for 6 weeksThe extract performed comparable to simvastatin and silymarin in reducing body weight, body lipid accumulation, and activities of fatty acid synthase,
Select Disease Character Offset Disease Term Instance
hyperglycemia 13628 with inflammation in obese people living with T2D [[49]]. On the other side, it has been found that hyperglycemia induces the production of TNF-α through the down-regulation of monocyte cell surface CD33, a transmembrane
hyperglycemia 25681 mice [[95]], a mouse model known to be susceptible to obese characteristics, including cholesterol, hyperglycemia and hypertriglyceridemia in response to obesogenic diet [[95]]. Besides the use of cultured 3T3-L1 adipocytes
hyperglycemia 39477 extracts at 7 and 14 mg gallic acid equivalent for 8 weeks protected against dyslipidemia, fasting hyperglycemia , and further attenuated both hepatic gluconeogenesis and inflammation as observed by the expression
hyperglycemia 68233 equivalent (GAE)/kg body weight for 8 weeksNone The extract protected against dyslipidemia, fasting hyperglycemia , and attenuated both hepatic gluconeogenesis and inflammation as observed by the expression of tumor
hyperlipidemia 61081 in diet for 8 weeksNoneThe extract displayed preventive effect on obesity, insulin resistance, and hyperlipidemia . It suppressed absorption of triacylglycerol in an olive oil loading test (in vivo test)In vitro pancreatic
hypertriglyceridemia 25699 mouse model known to be susceptible to obese characteristics, including cholesterol, hyperglycemia and hypertriglyceridemia in response to obesogenic diet [[95]]. Besides the use of cultured 3T3-L1 adipocytes [[21],[96],[97]],
metabolic syndrome 8837 for primary findings. Medical subject heading (MeSH) terms such as gallic acid and its derivatives, metabolic syndrome , obesity, inflammation, oxidative stress, and apoptosis, including corresponding synonyms and associated
metabolic syndrome 43427 lowering drugs and other obesity therapies, is still necessary.11. Concluding RemarksObesity and the metabolic syndrome are of significant scientific and clinical interest, due to their contribution in the rapid rise of
metabolic syndrome 44129 a few therapies are available to improve the lives of obese patients at high risk of developing the metabolic syndrome . To date, some natural products, including gallic acid have been shown to ameliorate complications associated
metabolic syndrome 44267 natural products, including gallic acid have been shown to ameliorate complications associated with the metabolic syndrome . This may be through mechanisms involving the reduction of excessive body fat, or ameliorating inflammation
obesity 1985 Of interest is gallic acid, a trihydroxybenzoic acid that has progressively demonstrated robust anti- obesity capabilities in various experimental models. In addition to reducing excessive lipid storage in obese
obesity 2560 its therapeutic potential and improvement of human health, available evidence reporting on the anti- obesity properties of gallic acid and its derivatives will be discussed, with emphases on its modulatory effect
obesity 2975 these individuals are classified as obese [[1]]. The rising trend in the incidence of overweight and obesity is not only limited to developed countries as factors such as urbanization and unhealthy lifestyle,
obesity 3417 translate to complications and adverse effects on infant health, as previously hypothesized [[2]]. Visceral obesity is associated with the development of chronic metabolic diseases including insulin resistance, type
obesity 3599 insulin resistance, type 2 diabetes (T2D), and cardiovascular disease [[3]]. The mechanism linking obesity to these comorbidities has not been fully elucidated. However, a growing body of knowledge suggests
obesity 3940 within an adipose tissue (Figure 1). Adipose tissue inflammation plays a crucial role in promulgating obesity -related metabolic complications including the development of insulin resistance [[4],[5]]. An imbalance
obesity 4277 [[6]].Adipose tissue is regarded as an endocrine organ that plays a pivotal role in the development of obesity . As excessive fat accumulation in the adipose tissue is associated with weight gain [[6]]. Over the
obesity 5658 or intracellular control of these factors has been an ideal therapeutic target aimed at preventing obesity or ameliorating its associated complications.The use of natural products as therapeutic agents in preventing
obesity 6703 experimental data evaluating the ameliorative effects of gallic acid on metabolic diseases, including obesity [[17],[18],[19],[20],[21],[22]]. Furthermore, several reviews focusing on the therapeutic potential
obesity 8031 therapeutic potential of gallic acid and its derivatives, none have appraised literature on the anti- obesity properties of this phenolic acid. The current review systematically extracted the available primary
obesity 8215 extracted the available primary findings and critically assessed these studies to better inform on the anti- obesity properties of gallic acid by modifying an already published protocol [[29]]. For data extraction, a
obesity 8373 published protocol [[29]]. For data extraction, a search on the association between gallic acid and obesity was conducted using major search engines and databases such as PubMed/Medline, EMBASE, Cochrane Library
obesity 8857 findings. Medical subject heading (MeSH) terms such as gallic acid and its derivatives, metabolic syndrome, obesity , inflammation, oxidative stress, and apoptosis, including corresponding synonyms and associated terms
obesity 9384 effects of enhanced pro-inflammatory response and oxidative stress are discussed to highlight the anti- obesity potential of gallic acid.2. Inflammation and Insulin Resistance in Adipose TissueGenerally, it is well
obesity 10654 angiogenesis and vasculatures in adipose tissue has been proposed to be a viable mechanism to reverse obesity associated complications [[34]]. However, uncontrolled adipose tissue expansion in an obese state is
obesity 11413 earliest pro-inflammatory cytokines identified and its abnormally elevated levels are associated with obesity , insulin resistance and T2D. For example, knockout of TNF-α in diet-induced obese or leptin deficient
obesity 11736 human subjects and leptin resistant mice where elevated lipids or TNF-α have been associated with obesity , insulin resistance and cardiovascular complications [[39],[40],[41]], suggesting that adipose tissue
obesity 11863 and cardiovascular complications [[39],[40],[41]], suggesting that adipose tissue inflammation and obesity are implicated in the development of T2D.Macrophage infiltration into the adipose tissue can also initiate
obesity 12486 hypoxia and adipocyte cell death [[38]]. The order of immune cell recruitment remains unclear however in obesity , macrophages represent more than half of leukocyte population present in visceral and subcutaneous adipose
obesity 12807 visceral white adipose tissue and increased body mass index [[44]]. In animal models of diet induced obesity , macrophages constitute around 50% of all adipose tissue cells [[30]], whereas in lean mice and humans,
obesity 15866 to driving an enhanced pro-inflammatory response, adipose tissue expansion during the progression of obesity can result in excess production of toxic radical species that can cause generation of oxidative stress.
obesity 16815 by oxidizing cellular constituents such as proteins, lipids and DNA [[62],[63]]. In adipose tissue, obesity can induce oxidative stress mainly via catalytic activity of nicotinamide adenine dinucleotide phosphate
obesity 18000 development of insulin resistance in adipose tissue. High levels of FFAs and glucose, which are abundant in obesity seem to contribute to NOX activation and ROS production (Figure 2). In cultured 3T3-L1 adipocytes, high
obesity 18623 studies have shown that mitochondrial-derived ROS production is associated with the late stages of obesity as compared to NOX-derived ROS production, which is associated with the early stages of obesity [[64]].
obesity 18719 of obesity as compared to NOX-derived ROS production, which is associated with the early stages of obesity [[64]]. In a morbidly obese state, adipocytes utilize FFAs derived from triglyceride stores via excessive
obesity 24884 Effects of Gallic AcidCurrently, various experimental models are being explored to investigate the anti- obesity properties of pharmacological compounds, including natural products and plant-derived extracts [[94]].
obesity 25018 pharmacological compounds, including natural products and plant-derived extracts [[94]]. Pre-clinical models of obesity are presently divided into different categories, the major ones being based on genetic mutations or
obesity 25559 the use of fat pads from high fat diet (HFD) fed rats and mice. The only reported transgenic model of obesity used were ddY mice [[95]], a mouse model known to be susceptible to obese characteristics, including
obesity 25875 of cultured 3T3-L1 adipocytes [[21],[96],[97]], other models that were widely used to test the anti- obesity properties of gallic acid were in vitro experiments that inhibit various enzymes involved in fat breakdown
obesity 26569 against complications such as hemoptysis as early as the 1800s [[140]], studies reporting on its anti- obesity properties started emerging about three decades ago [[113]]. A search with the terms “gallic acid
obesity 26833 articles; however, only 60 studies were specific to gallic acid and its ameliorative effects against obesity associated complications. Data reporting on the ameliorative effect of gallic acid or its derivative
obesity 27486 models discussed above, gallic acid has demonstrated an increased potential to ameliorate a number obesity associated complications, as summarized in Table 1. Concise evidence shows that gallic acid presents
obesity 28791 celastrol and resveratrol have been shown to control glucose and lipid metabolism and thereby ameliorate obesity associated complications, including inflammation and oxidative stress through mostly modulating mechanisms
obesity 29499 involved in adipogenesis and proliferation may be another mechanism by which gallic acid attenuates obesity associated complications [[16],[21]]. For instance, through upregulation of peroxisome proliferator-activated
obesity 30459 is very limited literature that compares the beneficial effects of gallic acid with widely used anti- obesity or antidiabetic drugs.7. Evidence on the Anti-Obesity Effects of Gallic Acid Derived CompoundsTable
obesity 30652 CompoundsTable 2 summarizes some of the well-investigated derivatives of gallic acid for their anti- obesity properties, including 6-deoxytetra-O-galloyl-α-d-glucopyranose, tetra-O-galloyl-α-d-xylopyranose,
obesity 33122 the beneficial effects of tea and fruits containing gallic acid or its derivative compounds against obesity associated complications. Besides tea (Camellia sinensis), fruits that have been shown to contain high
obesity 34059 presented in Table 3, tea appears to be the leading gallic acid-rich product that is explored for its anti- obesity properties. This may be due to the fact that tea is among the world’s most consumed beverage and is
obesity 34874 Consistently, evidence on this review showed that black and Pu-erh teas have great potential in ameliorating obesity associated complications by mainly reducing visceral fat deposition and lowering hepatic triglyceride
obesity 35284 and malic enzyme, are proposed to be the mechanisms involved in the beneficial effects of tea against obesity linked complications. Thus, suggesting that additional studies are required to explore molecular mechanisms
obesity 35467 to explore molecular mechanisms involved in the beneficial effect of gallic acid-rich teas against obesity associated complications, especially targeting its role in adipogenesis, insulin signaling, inflammation,
obesity 35733 evidence on the therapeutic potential of fruits rich in gallic acid or its derivatives in preventing obesity has also emerged. Fruits of interest include avocado, blackcurrant, grapes, guava, mango, mulberry,
obesity 37909 insulin receptor substrate 1 (IRS1), interleukin 6 (IL-6) and other proteins involved in diabetes and obesity associated complications [[132]]. Last but not least, pomegranate (Punica granatum) extracts, using
obesity 38268 presented in this review support the beneficial effects of fruits-rich in gallic acid on ameliorating obesity associated complications [[11],[120],[123],[124],[128],[129],[130],[131],[132],[133],[134]]. However,
obesity 38582 demonstrating limitation in unravelling molecular mechanisms by which these fruits can protect against obesity linked anomalies.9. Anti-Obesity Properties of other Plants Rich in Gallic AcidBesides wine-making products,
obesity 39085 various experimental models these plant extracts display a broad spectrum of ameliorative effects against obesity associated complications. For example, the use of herbal mixture extract rich in gallic acid at 790
obesity 39350 defective antioxidant stability, and insulin resistance in HFD fed rats [[119]]. In a similar model of obesity , the use of cagaita extracts at 7 and 14 mg gallic acid equivalent for 8 weeks protected against dyslipidemia,
obesity 41170 that the presence of gallic acid in some plants may enhance their therapeutic effects in preventing obesity associated complications.10. Human Studies Reporting on the Therapeutic Potential of Gallic Acid against
obesity 41733 the acknowledged draw backs identified in clinical evaluation of herbal medicine for the treatment of obesity [[155],[156],[157]]. Two of the six clinical studies on the anti-obesity properties of gallic acid included
obesity 41806 medicine for the treatment of obesity [[155],[156],[157]]. Two of the six clinical studies on the anti- obesity properties of gallic acid included in the current review showed that this phenolic acid or its derivatives
obesity 42184 that although strong evidence linking consumption of natural supplements with effective management of obesity is insufficient, most natural compounds have been specifically credited for attenuating metabolic complications
obesity 42543 clinical studies supported the beneficial effect of gallic acid and its derivatives in ameliorating some obesity associated complications [[144],[143]]. These studies showed that in addition to improving the quality
obesity 43182 and larger cohorts is required to fully elucidate the therapeutic potential of gallic acid to combat obesity and associated complications in human subjects. Furthermore, a comparison of its effects with other
obesity 43351 a comparison of its effects with other available treatments, such as lipid lowering drugs and other obesity therapies, is still necessary.11. Concluding RemarksObesity and the metabolic syndrome are of significant
obesity 43777 and oxidative stress are understood to be some of the major causal factors implicated in worsening of obesity associated perturbations. Thus, in addition to reducing raised blood glucose or lipid levels, amelioration
obesity 44574 summarized in this review support the beneficial effects of gallic acid or its derivatives in preventing obesity -associated complications. Although demonstrated to partially interfere with allergic disorders by acting
obesity 45262 this review include limited to no studies assessing the ameliorative effects of gallic acid against obesity -associated complications in human subjects to confirm its therapeutic potential. This can be further
obesity 45674 sedentary lifestyle and genetic susceptibility are the leading factors associated with the development of obesity . In addition to dysfunctional angiogenesis, an obese state is characterized by an abnormal inflammatory
obesity 46920 gallate, methyl gallate, propyl gallate, theaflavin-3-gallate that are increasingly studied for their anti- obesity properties.Figure 4In addition to tea, avocado, blackcurrant, grapes, guava, mango, mulberry and pomegranate
obesity 47151 plants rich in gallic acid or its derivative compounds that are increasingly investigated for their anti- obesity properties. The following websites were used for the extraction of images: Tea, https://www.coffeebean.com/cafe-menu/tea;
obesity 47898 https://www.organicfacts.net/health-benefits/fruit/health-benefits-of-pomegranate.html.nutrients-11-00023-t001_Table 1Table 1Overview of studies reporting on the ameliorative effect of gallic acid against obesity -associated complications.Author, YearExperimental Model, Dose Used, and Intervention PeriodComparative/Combination
obesity 53538 2Overview of studies reporting on the ameliorative effect of gallic acid derived compounds against obesity -associated complications.Author, YearExperimental Model, Dose Used, and Intervention PeriodComparative/Combination
obesity 57715 3Overview of studies reporting on the ameliorative effect of tea and fruits-rich in gallic acid against obesity -associated complications.Author, YearExperimental Model, Dose Used, and Intervention PeriodComparative/Combination
obesity 59603 docking screening of traditional Chinese medicine, rich in gallic acid, for inhibition of fat mass and obesity -associated protein activity(S)-tryptophan-betaxanthin, 3-methoxytyramine-betaxanthin, 4-O-methylgallic
obesity 59987 3-methoxytyramine-betaxanthin and 4-O-methylgallic acid were among the leading compounds shown to inhibit fat mass and obesity -associated protein activityKoh et al., 2011 [[122]]High fat diet fed male Sprague Dawley rats treated
obesity 61048 gallic acid, at 1% and 3% supplemented in diet for 8 weeksNoneThe extract displayed preventive effect on obesity , insulin resistance, and hyperlipidemia. It suppressed absorption of triacylglycerol in an olive oil
obesity 65183 insulin receptor substrate 1 (IRS1), interleukin 6 (IL-6) and other proteins involved in diabetes and obesity associated complicationsSandoval-Gallegos et al., 2018 [[133]]High fat diet fed male Wistar rats treated
obesity 65963 4Overview of studies reporting on the ameliorative effects of other gallic acid-rich plants against obesity -associated complications.Author, YearExperimental Model, Dose Used, and Intervention PeriodComparative/Combination
obesity 68553 5Human studies reporting on the therapeutic potential of gallic acid or gallic acid rich plants against obesity -associated complications.Author, Year.Experimental Model, Dose Used, And Intervention PeriodComparative/Combination

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