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Cardioprotective effects of gallic acid in diabetes-induced myocardial dysfunction in rats

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Normalization of hyperglycemia, hyperlipidemia, and oxidative stress is an important objective in preventing diabetes-induced cardiac dysfunction. This study was undertaken to examine the effects of gallic acid in myocardial dysfunctions associated with type-1 diabetes. Diabetes was induced by single intravenous injection of streptozotocin (STZ, 50 mg/kg i.v.). Gallic acid was administered daily at three different doses (100, 50, and 25 mg/kg p.o.) for 8 weeks at the end of which blood samples were collected and analyzed for various biochemical parameters. Injection of STZ produced significant loss of body weight (BW), polyphagia, polydypsia, hyperglycemia, hypoinsulinemia, hyperlipidemia, hypertension, bradycardia, and myocardial functional alterations. Treatment with gallic acid significantly lowered fasting glucose, the AUC(glucose) level in a dose-dependent manner; however, the insulin level was not increased significantly at same the dose and prevented loss of BW, polyphagia, and polydypsia in diabetic rats. It also prevented STZ-induced hyperlipidemia, hypertension, bradycardia, structural alterations in cardiac tissue such as increase in force of contraction, left ventricular weight to body weight ratio, collagen content, protein content, serum lactate dehydrogenase, and creatinine kinase levels in a dose-dependent manner. Further, treatment also produced reduction in lipid peroxidation and increase in antioxidant parameters in heart of diabetic rats. The results of this study suggest that gallic acid to be beneficial for the treatment of myocardial damage associated with type-1 diabetes.
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... Oxidative stress contributes to increase protein, lipid, and carbohydrate metabolisms, which links with increased free radical release accompanied by a decrease in antioxidants, leading to diabetes [5]. The rate of hyperglycemia and hyperlipidemia has been extensively documented and is implicated in the pathogenesis of various cardiovascular complications, including cardiomyopathy [1,6]. ...
... Nutraceutical therapies for diabetes mellitus have established growing consideration during topical times, and various antioxidants, nutritional approaches, and medicinal plants have been anticipated for the management of metabolic disorders in diabetic patients [6]. A. conyzoides belongs to the Asteraceae family. ...
... Several antidiabetic plants have revealed an ameliorative effect on the cardiovascular system [1,6]. The leaves of A. conyzoides were a potential source of antidiabetic agents [26]. ...
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Diabetes mellitus has developed into one of the debilitating diseases disturbing the health of many people living with cardiovascular diseases in modern times. The root of Ageratum conyzoides was investigated for its effects on alloxan-induced diabetic Wistar rats’ cardiac tissues. Thirty-two (32) Wistar rats weighing between 180 and 190 g were randomly divided into four groups. The animals in groups B-D were induced with a single dose of 150 mg/kg body weight of alloxan (ALX) intraperitoneally. They were confirmed hyperglycemic after 72 hours of induction and then sustained in hyperglycemic condition for 2 weeks. Animals in groups C and D received AC intervention, as stated above, for four weeks. The body weight of the experimental animals and blood collection for glucose estimation were taken weekly for six weeks using appropriate instruments. Biochemical assays for lipid profile, antioxidant enzymatic, and nonenzymatic markers were carried out. Histopathological changes in the cardiac tissues were also studied. Administration of 150 mg/kg of ALX to experimental rats induced diabetes and significantly reduced the body weights, significantly () increased the glucose level, triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL) levels, and decreased the levels of high-density lipoprotein (HDL) and antioxidant enzymatic markers such as catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) while the antioxidant nonenzymatic marker such as malondialdehyde (MDA) level was significantly increased. By contrast, rats given the ethanolic extract root of A. conyzoides had significantly () increased the body weight gain, whereas the glucose levels significantly () improved in treated diabetic rats. This extract also improved the cardiovascular system of the diabetic rats by significantly decreasing TG and LDL levels, significantly () increasing the HDL level, significantly reducing the cardiac contents of CAT, SOD, and GPx, and significantly () decreasing MDA. Ethanolic extract root of A. conyzoides exhibited antihyperglycemic and antihyperlipidemic activities and mitigates damage to the heart from the ALX-induced myocardial toxicity associated with type-1 diabetes. 1. Background Diabetes mellitus (DM) is a persistent metabolic disorder associated with carbohydrate, lipid, and protein metabolisms that contribute to several kinds of complications, including diabetic cardiomyopathy [1]. Diabetic cardiomyopathy is one of the significant complications of diabetes mellitus. Diabetic cardiomyopathy is the most imperative basis of death in 65% of patients with diabetes [1]. Hyperglycemia and hyperlipidemia are the most critical risk factors for cardiovascular disorders [1]. The group of lipid abnormalities was coupled with diabetes with the occurrence of a high concentration of triglycerides (TGs), low concentration of high-density lipoprotein (HDL), and small dense low-density lipoprotein (LDL), and plasma cholesterol levels is generally expected [2]. Persistent hyperglycemia in the course of DM contributes to diabetic complications characterized by overproduction of reactive oxygen species (ROS) and buildup of lipid peroxidation by-products [3]. Experimental diabetes induced by alloxan (ALX) selectively disrupts the pancreas β cells, which are known to be one of the weakest structures to oxidative stress by generating excess reactive oxygen species and produces heart lesions that are similar to human diabetic cardiomyopathy [4]. Oxidative stress contributes to increase protein, lipid, and carbohydrate metabolisms, which links with increased free radical release accompanied by a decrease in antioxidants, leading to diabetes [5]. The rate of hyperglycemia and hyperlipidemia has been extensively documented and is implicated in the pathogenesis of various cardiovascular complications, including cardiomyopathy [1, 6]. Nutraceutical therapies for diabetes mellitus have established growing consideration during topical times, and various antioxidants, nutritional approaches, and medicinal plants have been anticipated for the management of metabolic disorders in diabetic patients [6]. A. conyzoides belongs to the Asteraceae family. It is an annual herbaceous plant that is widely circulated tropically and commonly used in Southern Nigeria. It is a scrub with a broad crown, fissured bark, and scented white flowers [7]. The plant is commonly found in West Africa and abundant, particularly in the Southern part of Nigeria. It is located in the savannah regions and swampy areas of Nigeria. It is generally called goat weed in English, Imi Esu in Yoruba, Igwulube in Igbo, Alkama Tuturuwa in Hausa, Otiti in Efik, and Nnyano in Ibibio. The leaves and roots of A. conyzoides (AC) are used in India and Brazil to treat fever and gastrointestinal diseases such as diarrhea, dysentery, rheumatism, ovarian inflammation, and intestinal colic with flatulence [8, 9]. In Cameroon and Congo, the leaves of AC are also used traditionally to treat fever, rheumatism, headache, and colic [10, 11]. In Central Africa, it is used traditionally to treat pneumonia; it is also used as an insecticide and nematicide [12]. The leaves are also used in dressing wounds and burns, and it has been shown to exhibit antibacterial activity [12, 13]. In reunion, the whole plant is used as an antidysenteric activity [14]. The whole plant has been used to treat colic, colds, rheumatism, spasms, and diarrhea, and it is also used as a tonic [15]. In Nigeria, the leaves and roots are useful in treating boils, leprosy, skin diseases, eye pains, and inflammation [16]. It has been shown to possess antidysenteric [17], analgesic [18], fertility, antispasmodic, and muscle relaxation properties [19, 20]. It has also been shown to possess anti-inflammatory and antipyretic properties [21]. The leaves and roots are also useful in treating hepatitis, breast myiasis sores, and arthritis [21, 22]. It has been reported to exhibit radioprotective, cardioprotective, and hepatoprotective properties [23–25]. Phytochemical screenings have shown that A. conyzoides extract root contains various phytochemical constituents, including flavonoids, saponins, tannins, terpenoids, alkaloids, and cardiac glycosides and does not contain anthracene derivatives [14, 17, 25]. Several antidiabetic plants have revealed an ameliorative effect on the cardiovascular system [1, 6]. The leaves of A. conyzoides were a potential source of antidiabetic agents [26]. Despite extensive natural use of A. conyzoides in traditional medicine for DM and other diverse ailments, its cardioprotective effects on the persistent metabolic disorder have not been scientifically validated. Therefore, the present study was designed to investigate the cardioprotective effects of ethanolic extract root of A. conyzoides on cardiac damage in the metabolic disorder of ALX-induced rats. 2. Materials and Methods 2.1. Sources of Chemicals, Reagents, and Kits Alloxan (ALX) was purchased from a Sigma company representative in Nigeria, Glucometer kits were also purchased from the Fine test representative in Lagos, Nigeria (Fine-test®, Infopia Diagnostics). All other chemicals and reagents used in this study were of analytical grade. 2.2. Plant Material The roots of A. conyzoides were collected from farmland in Ijebu-Ilugun, Ogun State, Nigeria, in the month of April 2016. The plant sample was identified and authenticated in the Forestry Research Institute of Nigeria (FRIN), Ibadan, Nigeria. The voucher specimen was deposited in the herbarium with a voucher number (FHI: 111925). 2.2.1. Preparation and Extraction of the Plant Material The roots of A. conyzoides were washed, cut into small pieces, sun-dried at room temperature for seven days, and crushed to a coarse powder with the electric marker. The powder (2500 g) was extracted with 96% absolute alcohol in 3 cycles using a soxhlet extractor. The crude extract was filtered with filter paper (Whatman No. 4). The filtrate was dried by a rotary vacuum evaporator at 30°C to obtain 387.2 g dry residue, a viscous brownish-coloured extract. It was stored in an airtight bottle kept in a refrigerator at 4°C till used. The extracted root was then reconstituted in distilled water at a suitable concentration for the experiment. Ojewale et al. [25] stated in their work that the LD50 of A. conyzoides was 5000 mg/kg body weight administered intraperitoneally; hence, the dosage used equivalent to 1/10th dose (500 mg/kg body weight) was selected as the highest extract dose. The dose used was consistent with the previous investigation on the plant [25]. 2.3. Experimental Animals Thirty-two (32) healthy Wistar rats weighing between 180 and 190 g of either sex were obtained from the Laboratory Animal Center of College of Medicine, University of Lagos, Idi-Araba, Lagos, Nigeria. The rats were housed in clean, sharp cages and kept in a spacious room under room temperature at the Animal House of Faculty of Basic Medical Sciences, Obafemi Awolowo College of Health Sciences, Olabisi Onabanjo University, Ikenne, Ogun, Nigeria. They were fed with standard animal pellets obtained from Pfizer Feeds Plc., Nigeria, and had access to water ad libitum. They were allowed to acclimatize for 14 days to the laboratory conditions before the experiment. The principles governing the use of laboratory animals as laid out by the Obafemi Awolowo College of Health Sciences, Olabisi Onabanjo University Research Ethical Committee were approved with the ethical number 06-08-2017-18, and the use and care of the animals and the experimental protocol were in strict conformity with the Institute of Laboratory Animal Research (ILAR) guidelines [27]. 2.4. Induction of Experimental Diabetes ALX was prepared in fresh normal saline. Diabetes was induced by intraperitoneal (ip) injection of alloxan monohydrate (150 mg/kg bwt) in a volume of 3 mL [28]. After 72 h, blood was withdrawn for blood glucose estimation monitored with a glucometer (Fine-test®, Infopia Diagnostics). The animals with ≥250 mg/dl blood glucose levels were considered diabetic and included in the experiment [29]. The diabetic animals were randomly distributed into three groups of eight animals each while the last group, the positive control, had eight normal rats (Table 1). Groups Treatment A Normal control group administered with normal saline for 6 weeks. B Diabetic untreated group was induced with 150 mg/kg bwt of alloxan and was given normal saline for 6 weeks. C Diabetic untreated rats for 2 weeks; diabetic rats were then administrated with the 250 mg/kg bodyweight of A. conyzoides for 4 weeks. D Diabetic untreated rats for 2 weeks; diabetic rats were then administrated with the 500 mg/kg bodyweight of A. conyzoides for 4 weeks.
... The concentrations of metformin and GA used in this study are 40 mg/ml and 20 mg/mL, respectively. Choice of doses for metformin and GA used in this study was based on findings from literature [28,29]. Treatment doses used in this study Means of extrapolating these doses to humans can be obtained from the work of Nair and Jacob [30]. ...
... Glucose-6-phosphatase on the other hand is a key regulator of gluconeogenesis pathway and also important in the pathophysiology of hyperglycemia [68]. Alteration of these glucose metabolizing enzymes portrayed by reduced glucokinase activity and elevated glucose-6-phosphatase activity has been reported in type 2 diabetic rats [29]. Such changes result in diminished liver glycogen and hyperglycemia [69]. ...
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Over time, diabetes patients usually need combination therapy involving two or more agents, including phytonutrients to attain therapeutic targets. The purpose of this research is to elucidate the combined effect of metformin and gallic acid (GA) on glucose metabolism, inflammation as well as oxidative and endoplasmic reticulum (ER) stresses in fructose-fed diabetic rats. Thirty-five rats of Wistar strain were arbitrarily distributed into five groups, each containing seven animals as follows: normal control, diabetic control, groups administered 100 mg/kg bw metformin only, 50 mg/kg bw gallic acid only and a combination of both. Experimental animals were made diabetic by single injection of 40 mg/kg streptozotocin (intraperitoneally) subsequent to 14 days administration of 10% fructose prior. Treatment of rats continued for 21 days following diabetes confirmation. Glucose and insulin levels as well as lipid profile were evaluated in the serum, while activities of catalase and superoxide dismutase were estimated in both liver and pancreas. In addition, levels of malondialdehyde, interleukin-6 and tumor necrosis factor-alpha, as well as expression of activating transcription factor-4 were evaluated in liver and pancreas of diabetic rats. Activities of glucose-6- phosphatase and glucokinase were also determined in liver of diabetic animals. Metformin only, GA only and combination of metformin and GA significantly improved antioxidant status and glucose homeostasis while inflammation and endoplasmic reticulum stress were significantly ameliorated in diabetic rats. Metformin/GA combination appeared to improve glucose metabolism by increasing insulin level and ameliorating the dysregulated activities of glucose metabolizing enzymes and ER stress better than either metformin only or GA only. It could be concluded that coadministration of metformin/GA produced a combined effect in ameliorating diabetes in Wistar rats and could be considered in treatment of diabetes.
... The consumption of these compounds has both harmful and beneficial effects on the nutrition of ruminants and monogastric animals, depending on their types and level of intake [6,7]. The HT has shown many health promoting properties like antioxidants, anti-diabetic, anti-obesity, improvement of serum lipids and the reduction of the CVD risk factors [8]. However, the HT also exerts anti-nutritional effects on nutrient feed intake and its digestibility which results in weight loss. ...
... However, the lack of experimental effect of HT was observed on the serum total protein which was in agreement with the previous study [18] and showed that HT had shown non toxic effects on protein metabolism. In this study the increased water intake was also observed in PCOS rats which were also observed in various previous research trials [8]; but the experimental effect of HT was observed to decrease the water intake in rats [42]. However, this effect might be due to the role of HT to maintain the water homeostasis which helped in the prevention of water loss from body [43]. ...
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Abstract Background Food intake and eating behavior are two important risk factors that lead to obesity and other associated metabolic and reproductive disorders like polycystic ovarian syndrome (PCOS). Most of the phytonutrients like hydrolysable tannin (HT) have the ability to reduce the nutrient intake that might be a suitable remedy for weight management of females in their reproductive age. Therefore, the present research is aimed to find out the effect of HT on nutrient intake, weekly body weight, blood glucose, serum lipids, minerals, immunoglobulins and satiety hormones in PCOS rats. Materials and methods A total of forty five adult healthy female rats of 56 days old, weighed 135 ± 5 g with two consecutive estrous cycles were selected. In order to induce PCOS in rats, the intramuscular injection of 4 mg/rat/kg Estradiol- Valerate was used. After induction, a Complete Randomized Design was used to divide the rats into five equal groups (n = 9) named as Pc0, Pc0.5, Pc1, Pc1.5 and Pc2. The groups of rats were offered different doses of HT i.e. 0, 0.5, 1, 1.5 and 2 % respectively per kg body weight in solution form through oral gavage once in a day for 60 days. Results After the intake of different levels of HT, the statistical results had shown a significant decrease (p
... Phenolic acids, which are naturally produced by numerous have a strong antioxidant and free radical scavenging ability, wi hibiting the enzymes that generate ROS [46]. Latest study has sho exacerbates the development of diabetes, while consuming an a creases it risk [47]. Gentisic acid did not demonstrate an orien specific receptor but it general ability as antioxidant and anti-in beneficial as a treatment complement for people with diabetes Glycogen phosphorylase is known to be one of the causes of hyperglycemia since it is responsible for the development of glucose. ...
... Phenolic acids, which are naturally produced by numerous plants, are assumed to have a strong antioxidant and free radical scavenging ability, with the mechanism of inhibiting the enzymes that generate ROS [46]. Latest study has shown that oxidative stress exacerbates the development of diabetes, while consuming an antioxidant-rich diet decreases it risk [47]. Gentisic acid did not demonstrate an oriented inhibition toward a specific receptor but it general ability as antioxidant and anti-inflammatory [9] could be beneficial as a treatment complement for people with diabetes; in contrast, amentoflavone with its spectacular affinities toward multiple receptors could serve as a specific inhibitor such as DPP4 or α-glucosidase inhibitors which are a class of antidiabetic commercialized drugs. ...
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Numerous scientific studies have confirmed the beneficial therapeutic effects of phenolic acids. Among them gentisic acid (GA), a phenolic acid extensively found in many fruit and vegetables has been associated with an enormous confirmed health benefit. The present study aims to evaluate the antidiabetic potential of gentisic acid and highlight its mechanisms of action following in silico and in vitro approaches. The in silico study was intended to predict the interaction of GA with eight different receptors highly involved in the management and complications of diabetes (dipeptidyl-peptidase 4 (DPP4), protein tyrosine phosphatase 1B (PTP1B), free fatty acid receptor 1 (FFAR1), aldose reductase (AldR), glycogen phosphorylase (GP), α-amylase, peroxisome proliferator-activated receptor gamma (PPAR-γ) and α-glucosidase), while the in vitro study studied the potential inhibitory effect of GA against α-amylase and α-glucosidase. The results indicate that GA interacted moderately with most of the receptors and had a moderate inhibitory activity during the in vitro tests. The study therefore encourages further in vivo studies to confirm the given results.
... Retinoblastoma (Rb) is a tumor suppressor that is a major regulator of the G1/S transition. Rb can be phosphorylated by cyclin/cyclin-dependent kinases (CDKs) and forms a complex transcription anti-senescence accelerated mice [56], anti-dementia [57], anti-diabetes [58,59] and neuroprotective effect [24,60]. ...
... Noticeably, the difference of the effect on cell-cycle associated protein expression between CHP-treated and CHL-treated groups might be due to the compositional differences of the two extracts, as shown by the GC-MS analysis. GC-MS analysis (Tables 4 and 6) revealed that phytochemical constituents of isooxypeucedanin, α-terpineol and umbelliferone were only found in CHP and exerted antidiabetic effect by normalizing blood glucose level and re-establishing insulin sensitivity [57,58,66]. The previous studies showed the effect of certain antidiabetic drugs on the cell-cycle through the decrease of cyclin D1 expression [118]. ...
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Citrus hystrix (CH) is a beneficial plant utilized in traditional folk medicine to relieve various health ailments. The antisenescent mechanisms of CH extracts were investigated using human neuroblastoma cells (SH-SY5Y). Phytochemical contents and antioxidant activities of CH extracts were analyzed using a gas chromatograph-mass spectrometer (GC-MS), 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) assay and 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) assay. Effects of CH extracts on high glucose-induced cytotoxicity, reactive oxygen species (ROS) generation, cell cycle arrest and cell cycle-associated proteins were assessed using a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium (MTT) assay, non-fluorescent 2', 7'-dichloro-dihydrofluorescein diacetate (H2DCFDA) assay, flow cytometer and Western blot. The extracts protected neuronal senescence by inhibiting ROS generation. CH extracts induced cell cycle progression by releasing senescent cells from the G1 phase arrest. As the Western blot confirmed, the mechanism involved in cell cycle progression was associated with the downregulation of cyclin D1, phospho-cell division cycle 2 (pcdc2) and phospho-Retinoblastoma (pRb) proteins. Furthermore, the Western blot showed that extracts increased Surtuin 1 (SIRT1) expression by increasing the phosphorylation of Glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Collectively, CH extracts could protect high glucose-induced human neuronal senescence by inducing cell cycle progression and up-regulation of SIRT1, thus leading to the improvement of the neuronal cell functions.
... Life style modi cation, balanced diet with richest source of bio-molecules (plant based) might be best weight loss treatment strategies for the obese patients [1,5]. Hydrolysable tannin (HT) is one of the plants bio-molecules and has shown many health promoting properties like anti-diabetic, anti-obesity, improvement of serum lipids and reduced the CVD risk factors [6,7]. The HT is a phenolic compound and exerts negative effects on nutrient feed intake and results in weight loss [8]. ...
... However, the lack of experimental effect of HT was observed on the serum total protein which was in agreement with the previous study [41] and showed that HT had shown non toxic effects on protein metabolism. In this study the increased water intake was also observed in PCOS rats which were also observed in various previous research trials [6]; but the experimental effect of HT was observed to decrease the water intake in rats [42]. However, this effect might be due to the role of HT to maintain the water homeostasis which helped in the prevention of water loss from body [43]. ...
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Background: Food intake and eating behavior are two important risk factors that lead to obesity and other metabolic and reproductive disorders like polycystic ovarian syndrome (PCOS). Most of the phytonutrients like hydrolysable tannin (HT) have the ability to reduce the nutrient intake that might be a suitable remedy for weight management of females in their reproductive age. Therefore, the present research is aimed to find out the effect of HT on nutrient intake, weekly body weight, weight gain, serum lipids, minerals, immunoglobulins and satiety hormones in PCOS rats. Methods: A total of forty five adult healthy female rats of 56 days old, weighed 135±5g with two consecutive estrous cycles were selected. In order to induce PCOS in rats, the intramuscular injection of 4mg/rat/kg Estradiol- Valerate was used. After induction, a Complete Randomized Design was used to divide the rats into five equal groups (n=9) named as Pc0, Pc0.5, Pc1, Pc1.5 and Pc2. The groups of rats were offered different doses of HT i.e. 0, 0.5, 1, 1.5 and 2% respectively per kg body weight in solution form through oral gavage once in a day for 60 days. Results: After the intake of different levels of HT, the statistical results had shown a significant decrease (p<0.05) in the weekly nutrient intake, body weight, water intake, weight gain, blood glucose in PCOS rats. A similar trend of decrease (p<0.05) was noticed in serum iron, IgM, IgG, leptin, ghrelin, cholesterol, low density lipoprotein and triglycerides while a significant improvement (p<0.05) was also observed in high density lipoprotein in the PCOS rats. However, a non-significant effect (p>0.05) was observed on serum protein and calcium levels. Conclusions: The study concluded that HT had a therapeutical potential to decrease the nutrient intake and its anti-nutritional property could be used as remedy for the management of body weight, hyperglycemia, dyslipidemia and cardiovascular risk factors of PCOS rats.
... Selain itu, keberadaan naringin juga dapat mengurangi ketidakstabilan kromosom pada penderita diabetes [17]. Senyawa lainnya yaitu hesperidin dilaporkan memiliki kemampuan anti-diabetes dengan cara menghambat kinerja enzim α-amilase dan α-glukosidase dalam saluran usus sekelompok tikus percobaan [18].Oleh karena itu kulit jeruk mempunyai potensi besar untuk dikembangkan sebagai agen anti-diabetes alami.Terlebih lagi, senyawa-senyawa dalam tersebut dapat mengembalikan kinerja organ tubuh yang berkurang atau mengalami perubahan fungsi organ [7], termasuk kelainan jantung sebagai efek samping diabetes juga telah dilaporkan [19]. Pengaruh varietas tanaman terhadap keberadaan senyawa fenolik telah dipelajari oleh Sarepoua [2] dan hasilnya menunjukkan bahwa varietas tanaman memberikan pengaruh terhadap metabolism sekunder tanaman sehingga mempengaruhi jumlah senyawa fenolik yang terdapat di dalam tanaman tersebut. ...
Article
Agricultural by-products such as corn silk and kaffir limepeels have not been utilized well. Since every part of a plant contains phenolicscompounds as a result of their secondary metabolism, it is possible that these two wastes can be used as a source of natural antioxidants. Therefore in this study, we investigated the phenolic content in corn silk and citrus peel and assess the ability of the extracts to reduce the conversion of starch to sugar in antidiabetic assessment. Research procedures include raw materialpreparation, extraction, activity assessment and loading the extract into the nanomaterialpores. The results showed that corn silk and kaffir lime peels have different total phenolic contents. Specifically for corn silk, it can be seen clearly that the plant varietycontribute to the amount of total phenolic content. Corn silk from P11 variety has the largest phenolic content up to 1.58 mg GAE/g. Therefore this materialexhibited the highest antioxidant activity against DPPH free radicals, but it has a relatively low for antidiabetic activity. For citrus, this study showed that peels of lemon, lime and kaffir lime exhibited different content of phenolicswith kaffir lime peels extract had the highest phenolics, up to 23.36 mg GAE/g, while the extract of lemon and lime peels were 7.94 and 9.71 mg GAE/g, respectively. In addition, extract of kaffir lime peels has the highest phenolics content compared to other parts such as leaves and juice. The use of different solvents provides different antidiabetic activity. The loading of kaffir lime peels extract into nanomaterial pores was successful, promising future application in the field of drug delivery. However, other studies are still required to improve the effectiveness of diabetes therapy using natural products.
... GA protects the brain by increasing antioxidant enzymes and decreasing inflammation 22,23 . Gallic acid can reduce the incidence of inflammation-related diseases, including cancer 24,25 , cardiovascular disease 26,27 , liver disease 28,29 , inflammation 30,31 , and neurodegenerative diseases. Gallic acid can inhibit the inflammatory process by eliminating superoxide anions, inhibiting the release and activity of myeloperoxidase (MPO), and possibly participating in the accumulation of active NADPH-oxidase 31 . ...
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Cadmium is a highly neurotoxic heavy metal that disrupts membranes and causes oxidative stress in the brain. The study aimed to investigate the neuroprotective effect of gallic acid on oxidative damage in the brains of Wistar rats exposed to cadmium chloride (CdCl2). Male Wistar rats were divided into four groups of five rats each. Group 1 was administered distilled water only throughout the study. Throughout the study, Group 2 received CdCl2 alone (5 mg/kg b.w./day), Group 3 received gallic acid (20 mg/kg b.w./day), and Group 4 received CdCl2 + gallic acid (20 mg/kg). Treatments were oral with distilled water as a vehicle. The study lasted 21 days. In the brain, the activities of cholinesterase and antioxidant enzymes were evaluated, as well as the levels of reduced glutathione, malondialdehyde, neurotransmitters, Na+/K+ ATPase, myeloperoxidase activity, nitric oxide, and interleukin-6. CdCl2-induced brain impairments in experimental animals and gallic acid prevents the following CdCl2-induced activities: inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), elevated neurotransmitters (serotonin and dopamine), decreased antioxidant enzymes (superoxide dismutase, catalase), decreased glutathione, Na+/K+ ATPases, and increased MDA and neuroinflammatory markers (myeloperoxidase (MPO), nitric oxide, and interleukin-6 in the brain of experimental rats exposed to CdCl2 (p < 0.05). Taken together, the neuroprotective effects of gallic acid on CdCl2-induced toxicity in the brains of rats suggest its potent antioxidant and neurotherapeutic properties.
... Gallic acid is reported to have hypoglycemic activity by activating pancreatic cells (Fatima et al., 2017). Others reported the antioxidant potential of gallic acid as an agent for protection against diabetes-induced diseases (Patel and Goyal, 2011). Variya et al. (2020) suggested its action is due to improved Glut4 translocation leading to improved glucose uptake in 3 T3-L1 cells and stimulation of adipogenesis and lipid accumulation in 3 T3-L1 adipocytes. ...
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IntroductionDiabetes mellitus is a chronic metabolic disorder that exhibited great expansion all over the world. It is becoming an epidemic disease adding a major burden to the health care system, particularly in developing countries.Methods The plant under investigation in the current study Phragmanthera austroarabica A. G. Mill and J. A. Nyberg is traditionally used in Saudi Arabia for the treatment of diabetes mellitus. The methanolic extract (200 mg/kg) of the plant and pure gallic acid (40 mg/kg), a major metabolite of the plant, as well as their silver nanoparticle formulae (AgNPs) were evaluated for their antidiabetic activity.Results and DiscussionThe results showed a decrease in body fat, obesity, an improvement in lipid profiles, normalization of hyperglycemia, insulin resistance, and hyperinsulinemia, and an improvement in liver tissue structure and function. However, the results obtained from AgNPs for both extract and the pure gallic acid were better in most measured parameters. Additionally, the activity of both the crude extract of the plant and its AgNPs were evaluated against a number of gram-positive, gram-negative bacteria and fungi. Although the activity of the crude extract ranged from moderate to weak or even non-active, the AgNPs of the plant extract clearly enhanced the antimicrobial activity. AgNPs of the extract demonstrated remarkable activity, especially against the Gram-negative pathogens Proteus vulgaris (MIC 2.5 μg/ml) and Pseudomonas aeruginosa (MIC 5 μg/ml). Furthermore, a promising antimicrobial activity was shown against the Gram-positive pathogen Streptococcus mutants (MIC 1.25 μg/ml).
... For instance, these strains may enhance colonic gallic acid and pyrogallol bioaccessibility by performing the first limiting transformation step of unabsorbed gallotannins (more than 60% 66,67 ). By increasing the bioaccessibility of these phenolic metabolites, TanA+ strains may enhance the anti-obesity 68,69 , antidiabetic 69 , cardioprotective 70,71 , and neuroprotective effects 72,73 of gallotannins. ...
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Extracellular tannase Lactiplantibacillus plantarum-producing strains (TanA+) release bioactive metabolites from dietary tannins. However, there is a paucity of knowledge of TanA+ strains and their hydrolyzing capacities. This study aimed to shed light on the metabolic and genomic features of TanA+ L. plantarum strains and to develop a screening technique. The established spectrophotometric was validated by UPLC-UV-QToF. Eight of 115 screened strains harbored the tanA gene, and six presented TanA activity (PROBI S126, PROBI S204, RKG 1-473, RKG 1-500, RKG 2-219, and RKG 2-690). When cultured with tannic acid (a gallotannin), TanA+ strains released 3.2−11 times more gallic acid than a lacking strain (WCFS1) (p < 0.05). TanA+ strains with gallate decarboxylase (n = 5) transformed this latter metabolite, producing 2.2–4.8 times more pyrogallol than the TanA lacking strain (p < 0.05). However, TanA+ strains could not transform punicalagin (an ellagitannin). Genomic analysis revealed high similarity between TanA+ strains, as only two variable regions of phage and polysaccharide synthesis were distinguished. A phylogenetic analysis of 149 additional genome sequences showed that tanA harboring strains form a cluster and present two bacteriocin coding sequences profile. In conclusion, TanA+ L. plantarum strains are closely related and possess the ability to resist and transform gallotannins. TanA can be screened by the method proposed herein.
... The -OH extracts of Jamun seeds have flavonoids, steroids, alkaloids, glycosides, saponins, triterpenoids, and tannins with potential anti-diabetic, antispasmodic, and anti-bacterial activity (Kamal, 2014). Gallic acid (@250 mg/kg) has maximal antioxidant activity, and continuous consumption for 21 days can lower blood glucose levels, and lipid peroxidation in brain tissues and improve the activity of antioxidant stimulating enzymes in the brain in diabetic rodents (Patel and Goyal, 2011). Histopathology of the brain documents the defensive impacts of gallic acid against brain dysfunction (Mainzen Prince et al., 2011). ...
Article
Jamun is a valuable therapeutic plant in India and is also referred to as “Black Jamun” while, all the plant parts, i.e., leaves, bark, fruit, roots, and seeds, have therapeutic applications. The fruits are perishable seasonal berries containing the pulp and are processed into several value-added products like health drinks, juices, squashes, jellies, and wine leaving behind kernels as a significant waste. The kernels are not only rich in carbohydrates, protein, minerals, and crude fibers but also contain a substantial variety of biogenic phytochemicals with versatile applications in both the food and nonfood industries. The enormous functional properties of these bioactive compounds get well-reported while the plant parts are used to produce a variety of traditional medicines with antioxidants, anti-diabetic, anti-pyretic, nephroprotective, and anti-diarrheal activities. Amongst all, the anti-diabetic properties are the most promising and explored as the seeds contain jambosin, alkaloid, and anti-mellin or jambolin glycosides, which impede the diastatic starch to sugar conversion. The plant has a long history of therapeutic applications with limited documented evidence to support its use. Health-conscious people often seek healthy diets loaded with natural substances with the highest functional properties, which has resulted in increased consumption of Jamun fruits in the recent past. Thus, there is a need to evolve, establish and document the traditional medicinal use of the Jamun with strong scientific rationales to outspread its consumption further. Therefore, the present era demands scientific intervention to explore this plant for its utilization in the food and pharmacy industry.
... officinalis also demonstrated significant hypoglycemic and hypolipidemic activity [26]. Freeze-dried aqueous extract of E. officinalis fruit, atthe dose of 1.25 g/kg, showed significant reduction in serum glucose and triglyceride levels with improved glutathione in STZ-induced diabetic male Long-Evans rats [27]. Mandarika with Ca+2 ion and affects protein glycation and starch digestion. ...
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Emblica officinalis or Phyllanthus emblica Linn, commonly known as Indian gooseberry or Amla, is perhaps the most important medicinal plant in the Indian traditional system of medicine, the Ayurveda. Several parts of the plant are used to treat a variety of diseases, but the most important is the fruit. Many ailments are treated by the fruit which is used either alone or in combination with other plants. These include common cold and fever; as a diuretic, laxative, liver tonic, refrigerant, stomachic, restorative, alterative, antipyretic, anti-inflammatory, hair tonic; to prevent peptic ulcer and dyspepsia, and as a digestive..This review summarizes the results related to these properties and also emphasizes the aspects that warrant future research establishing its activity and utility as a cancer preventive and therapeutic drug in humansneuroprotective properties as demonstrated in numerous preclinical studies.
... This phenolic compound (3,4,5-trihydroxybenzoic acid) possess a strong antioxidant capacity which can be used as a protective agent against the oxidative damage caused by a wide range of pathologies like cancer, cardiovascular, liver and neurodegenerative diseases, and inflammation [126][127][128][129][130][131][132][133][134][135][136][137]. Li et al., [18] identified the gallic acid (31.76 mg/100g dry extracts) as one of the main components present in pineapple peel. ...
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Pineapple processing industry generates large amounts of by-products (peel, core and crown) with a negative environmental impact. The elimination of these implies high costs for food industries, being their main destination animal feed or composting, thus wasting their great potential value attributed to the rich content of bioactive compounds. In this review, we have focused on the description of the bioactive compounds present in pineapple by-products and on the environment-friendly extraction methodologies used to obtain them (ultrasound-assisted extraction, microwave-assisted extraction, submerged and solid-state fermentation), as well as applications of these compounds in different areas. The use of these by-products is a great alternative to mitigate current environmental problems; in addition, green extraction technologies have the advantage of using few solvents, have shorter extraction times and good yields, so they are suitable for obtaining bioactive compounds (gallic acid, catechin, epicatechin, ferulic acid, among others) present in these by-products, which have a high antioxidant, anti-inflammatory, antifungal, anticancer activity and have very relevant applications. This review article demonstrates the great potential of the bioactive compounds present in the pineapple waste that might be used on drugs or foods for treatment of diseases or improvement of the people health. Graphical abstract
... In addition to its broad-spectrum industrial applications, GA also exhibits a promising pharmaceutical potent against cardiovascular diseases. For example, in a rat model of streptozotocin-induced diabetes, GA effectively prevents cardiac remodeling and dysfunction by improving glucose/lipid metabolism and reducing oxidative stress [6]; furthermore, in mouse models of cardiac remodeling and failure induced either by isoproterenol or pressure overload, GA has been demonstrated to attenuate cardiac hypertrophy and fibrosis through multiple signaling pathways [7][8][9]. However, whether GA could produce beneficial effects on maintaining cardiometabolic homeostasis and preventing ASCVD are still not defined. ...
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Diets rich in polyphenols are known to be beneficial for cardiovascular health. Gallic acid (GA) is a plant-derived triphenolic chemical with multiple cardio-protective properties, such as antiobesity, anti-inflammation, and antioxidation. However, whether GA could protect against atherosclerotic cardiovascular diseases is still not defined. Here, we investigated the effects of low-dose GA administration on diet-induced metabolic disorders and atherosclerosis in the atherosclerosis-prone apolipoprotein E (Apoe) knockout mice fed on a high-fat Western-type diet (WTD) for 8 weeks. Our data showed that GA administration by oral gavage at a daily dosage of 20 mg/kg body weight did not significantly ameliorate WTD-induced hyperlipidemia, hepatosteatosis, adipogenesis, or insulin resistance; furthermore, GA administration did not significantly ameliorate WTD-induced atherosclerosis. In conclusion, our data demonstrate that low-dose GA administration does not elicit significant health effect on diet-induced metabolic disorders or atherosclerosis in the Apoe knockout mice. Whether GA could be beneficial for atherosclerotic cardiovascular diseases therefore needs further exploration.
... Several research groups have consistently reported that during fermentation, the levels of catechins epigallocatechin-3-gallate, epigallocatechin, epicatechin-3-gallate, and quinic acid were significantly decreased, but the overall content of gallic acid was elevated [2,55,56]. Gallic acid has been considered one of main active constituents in Pu-erh tea that may explain some of its effect in terms of anti-obesity, hyperglycemia, hyperlipidemia, among others [12,47,[57][58][59][60][61]. Here, we found largely consistent results with the earlier reports, providing evidence of how Pu-erh tea can decrease fat storage in C. elegans (Fig. 1A and 1B). ...
... Gallic acid (GA), a polyphenol compound that exists widely in nature (Kosuru et al. 2018), has been shown to impart a variety of effects, i.e., antidepressant, anti-Parkinson's disease, antidiabetic, antimalaria, and antiviral (Kratz et al. 2008;Patel and Goyal 2011). GA has also been reported to help to alleviate acetaminophen-induced liver injury in mice, reduce liver ischemia-re-perfusion as well as CCl 4 -induced acute liver injury in rats, and suppress sodium fluoride-induced oxidative stress in the kidneys of rats (Kanai and Okano 1998;Nabavi et al. 2013). ...
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Microglia, the main immune effector cells in the central nervous system, play a dual role in the function/structure of the blood–brain barrier (BBB) and brain health. During and soon after a cerebral ischemic injury, microglia produce neurotrophic factors and neurotoxins that can impact on the injury itself and pathology progression. At the same time, microglia undergo polarization to M1 or M2 pro- vs. anti-inflammatory subtypes that also help drive the outcome of the injury process. Thus, agents that can mitigate cerebral ischemic injury progression, promote protective functions of microglia, and help maintain BBB and overall brain health/host neurologic function after a cerebral ischemic event would be of great use in clinical settings. Protective effects from gallic acid (GA) in cerebral ischemia/re-perfusion-induced injury to the BBB and other sites in the brain have not yet been assessed. To address this, a middle cerebral artery occlusion (MCAO) method was used to establish an experimental ischemic stroke model in mice. Mice were placed in sham operation (Sham), model (MCAO), MCAO + GA (50 mg/kg), MCAO + GA (100 mg/kg), or MCAO + GA (150 mg/kg) groups. At various times post-stroke, cerebral infarct volume and host neurological function were evaluated. In addition, qRT-PCR, Western blotting, and ELISA were used to evaluate the expression and tissue content of microglia-related factors. The results showed GA treatment protected the integrity of the BBB, significantly reduced brain edema, and helped lead to improved neurological function scores in the MCAO mice. Whether these changes were due to that GA attenuated cerebral ischemia/re-perfusion-induced activation of microglial cells overall, in part, by inhibiting their polarization to the M1 subtype, is uncertain. Taking these outcomes together, for now it is reasonable to suggest that use of GA either as a prophylactic or immediately in the event of a cerebral ischemic event/stroke could help to promote neuronal survival and allow for a more likely of host neurological function over time.
... The highest content of chlorogenic acid was determined for HB1, with mulberry leaves as the only ingredient (Table 3). Six out of the seven studied HBs contained gallic acid, whose antidiabetic potential has been supported by various studies [30,31]. The highest content of this phenolic compound was observed in the herbal infusions containing mulberry leaves (HB1, HB5, HB6), which is consistent with previous literature data [32]. ...
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Herbal infusions are an underestimated and easy to intake a source of biologically active natural compounds (polyphenols), which, in the dissolved form, are more easily absorbed. Therefore, this study aimed to assess the potential of herbal infusions as a functional food to reduce postprandial hyperglycemia (inhibition of α-amylase and α-glucosidase) and to reduce the effects of increased blood glucose level (antioxidant effect-DPPH, CUPRAC, and Fe2+ chelating assays, as well as anti-inflammatory activity-inhibition of collagenase). We showed that polyphenols are present in the examined aqueous herbal infusions (including chlorogenic and gallic acids). Subsequently, our research has shown that herbal infusions containing cinnamon bark, mulberry leaves, and blackberry fruits most strongly inhibit glucose release from complex carbohydrates, and that all herbal infusions can, to different degrees, reduce the effects of elevated blood sugar. In conclusion, infusions prepared from herbal blends could be recommended to prevent type II diabetes.
... These obtained results are in agreement with previous studies indicating that arsenic compounds reduce antioxidant defenses and induces oxidative stress. The cardio-protective effect of A. sativum has been reported in previous studies indicating reduced functional and structural changes in cardiac tissue accompanied by the increased activity of antioxidant enzymes and the reduced level of lipid peroxidation in the heart tissue (Patel and Goyal, 2011). The treatment also reduced the serum level of cardiac biomarkers CK and CK-MB. ...
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Background: Arsenic present in underground water affects the overall health. The therapeutic effects of Allium sativum was investigated for ameliorating the toxic effects of arsenic exposed ducks. Even though, heavy metals especially arsenic toxicity and ameliorative effects of Allium sativum has been largely studied, yet the histopathological cardiac lesion grading and its correlation with oxidative stress and biochemical parameters is scarce. This study is aimed at evaluating cardiotoxic lesions due to arsenic and ameliorative effects of Allium sativum in accordance with histopathological grading with respect to oxidative and biochemical parameters. Methods: In the present study, 105 birds were randomly distributed in 5 groups. GRP II was given arsenic @ 30 ppm whereas GRP III, IV, V were given Allium sativum @ 0.5 gm/ kg feed, 1 gm/kg feed and 2 gm/kg feed respectively along with arsenic to study the ameliorative effects. At the end of 42 days, 6 birds from each group were slaughtered after blood collection and the extend of arsenic toxicity with Allium sativum effects were studied as biochemical and oxidative parameters with histopathological grading of lesions. The extent of lesions was graded as mild (+), moderate (++) and severe (+++). Result: Grossly, heart revealed dilatation and thickening of ventricular wall in GRP II along with congestion in coronary vessels. In GRP V, grossly heart revealed no congestion and comparatively reduced enlargement. Whereas microscopically, myocardial and epicardial oedema, disruption of muscle fiber and hemorrhage was observed. Along with this, there was increase in cardiac biomarkers - Total serum creatinine kinase (CK), creatine kinase-MB (CK-MB) levels and tissue oxidative parameters (LPO), with decrease in GSH, CAT, total antioxidant and SOD levels in GRP II which was comparably restored in GRP V.
... According to Kang et al., gallic acid showed therapeutical effect on cardiovascular disease owing to the potent vasorelaxant and antihypertensive effect (Kang et al., 2015). Patel et al. suggest gallic acid as a favorable molecule for the treatment of myocardial damage (Patel & Goyal, 2011). In addition, gallic acid is widely distributed in various medicinal plants such as Carthamus tinctorius L, one of the main representative medicines promoting blood circulation and removing blood stasis. ...
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Objective This study was devoted to identifying natural thrombin inhibitors from traditional Chinese medicine (TCM) and evaluating its biological activity in vitro and binding characteristics. Methods A combination strategy containing molecular docking, thrombin inhibition assay, surface plasmon resonance (SPR) and molecular dynamics simulation were applied to verify the study result. Results Gallic acid was confirmed as a direct thrombin inhibitor with IC50 of 9.07 μmol/L and showed a significant inhibitory effect on thrombin induced platelet aggregation. SPR-based binding studies demonstrated that gallic acid interacted with thrombin with a KD value of 8.29 μmol/L. Molecular dynamics and binding free energy analysis revealed that thrombin-gallic acid system attained equilibrium rapidly with very low fluctuations, the calculated binding free energies was −14.61 kcal/mol. Ala230, Glu232, Ser235, Gly258 and Gly260 were the main amino acid residues responsible for thrombin inhibition by gallic acid, providing a mechanistic basis for further optimization. Conclusion This study proved that gallic acid is a direct thrombin inhibitor with platelet aggregation inhibitory effect, which could provide a basis for the follow-up research and development for novel thrombin inhibitors.
... The period of the study protocol was following that of Patel & Goyal [17] who demonstrated that 8 weeks of experimentally induced type-2 DM could produce diabetic cardiomyopathy in rats. ...
... Gallic acid and ellagic acid are major phytochemicals belonging to the class of tannins present in the Triphala churna. Reports have confirmed the beneficial role of gallic acid in the management of diabetes and diabetic complications such as diabetic nephropathy and cardiomyopathy, neuropathy due to its potent antioxidant, anti-inflamamtory TGF-β inhibitory activity and by increasing insulin sensitivity (Abdel-Moneim et al., 2017;Garud and Kulkarni, 2018;Patel and Goyal, 2011;Raafat and Samy, 2014). Ellagic acid has also shown beneficial effects in the management of diabetes and its associated complications via its anti-oxidant, anti-glycative action and via regulation of inflammatory signalling (Ahad et al., 2014;Chao et al., 2010;D'souza et al., 2014;Zhou et al., 2019). ...
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Neuropathy is a common complication of diabetes affecting a large number of people worldwide. Triphala churna is a formulation mentioned in Ayurveda-a traditional system of medicine. It is a simple powder formulation consisting of powders of three fruits, Emblica officinalis L., Terminalia bellirica (Gaertn.) Roxb. and Terminalia chebula Retz. Individual components of Triphala churna have anti-diabetic and antioxidant activities. Hence, this study was designed to evaluate the effect of Triphala churna on diabetic neuropathy. Diabetes was induced with streptozotocin (STZ, 55 mg/kg, i. p.) in rats. Animals were grouped and treated orally with Triphala churna at a dose of 250, 500, and 1,000 mg/kg after 6 weeks of diabetes induction for the next 4 weeks. At the end of study, parameters such as body weight, plasma glucose level, motor nerve conduction velocity were determined. The effect of Triphala churna on thermal hyperalgesia, mechanical hyperalgesia, and mechanical allodynia was also determined at the end of study. The plasma cytokine levels like TGF-β1, TNF-α, and IL-1β were determined by ELISA assay. Histopathology study of the sciatic nerve was studied. Western blotting was performed to study the expression of neuronal growth factor.Treatment with Triphala churna showed a significant reduction in plasma glucose and a significant rise in body weight. Triphala treatment significantly increased the motor nerve conduction velocity and decreased the thermal and mechanical hyperalgesia, as well as mechanical allodynia. The treatment significantly inhibited levels of circulatory cytokines like TGF-β1, TNF-α, and IL-1β. Histopathology study confirmed the neuroprotective effect of Triphala churna. The expression of NGF was significantly increased in sciatic nerves after treatment with Triphala churna. From the results, it can be concluded that Triphala churna delays the progression of neuropathy in diabetic rats.
... There are reports that various biologically active compounds in PE fruit includes the flavonoids, mainly C-glycosylflavones schaftoside, isoschaftoside, isoorientin, orientin, isovitexin, luteolin-6-Cchinovoside, and luteolin-6-C-fucoside have been identified [24]. Among the different bioactives, gallic acid (Fig. 4d), a powerful antioxidant reveals significant cardioprotective activity with various experimental models [25]. Catechol, another well-known phenolic compound (Fig. 4b), as well as cinnamic acid (Fig. 4c), are reported to have excellent antioxidant activity and can also exhibit cardioprotective activities [26,27]. ...
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The common reason for mortality globally is myocardial infarction. The study aimed to evaluate Passiflora edulis (PE) fruit juice potential in the experimental isoproterenol (ISO) treated rat model to manage myocardial injury. ISO (20 mg/100 g body weight) treated rats showed a significant increment in serum marker enzymes lactate dehydrogenase (LDH) and creatinine kinase (CK), serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), serum alkaline phosphatase (ALP) and serum acid phosphatase (ACP) activity. Besides, phosphorus and calcium, serum cholesterol, and triglyceride levels (TG) were high in ISO groups. A significant decline in antioxidant activity and histopathological alteration was observed in ISO treated groups. PE juice pre-treatment (2 ml/kg) for 28 days and ISO treatment on the 29th and 30th days showed a protective effect on distorted biochemical and histopathologic parameters compared with reference drug metoprolol. These findings indicate the cardioprotective effect of PE juice on ISO-induced myocardial infracted rats.
... -TIDM: Diabetes was induced by a single intraperitoneal (IP) injection of STZ (50 mg/kg), which was dissolved in freshly prepared 0.1M citrate buffer (pH 4.5) (Patel and Goyal, 2011). We supplied a 5% glucose solution orally to the rats to prevent hypoglycemia during the first 24 h following the streptozocin (STZ) (Sigma-Aldrich, St. Louis, MO) administration (Patel et al., 2013). ...
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Diabetes mellitus (DM) is a multisystem endocrine disorder affecting the brain. Mesenchymal stem cells (MSCs) pretreated with Melatonin have been shown to increase the potency of MSCs. This work aimed to compare Melatonin, stem cells, and stem cells pretreated with Melatonin on the cognitive functions and markers of synaptic plasticity in an animal model of type I diabetes mellitus (TIDM). Thirty-six rats represented the animal model; six rats for isolation of MSCs and 30 rats were divided into five groups: control, TIDM, TIDM + Melatonin, TIDM + Stem cells, and TIDM + Stem ex vivo Melatonin. Functional assessment was performed with Y-maze, forced swimming test and novel object recognition. Histological and biochemical evaluation of hippocampal Neuroligin 1, Sortilin, Brain-Derived Neurotrophic Factor (BDNF), inducible nitric oxide synthase (iNOS), toll-like receptor 2 (TLR2), Tumor necrosis factor-alpha (TNF-α), and Growth Associated Protein 43 (GAP43). The TIDM group showed a significant decrease of hippocampal Neuroligin, Sortilin, and BDNF and a significant increase in iNOS, TNF-α, TLR2, and GAP43. Melatonin or stem cells groups showed improvement compared to the diabetic group but not compared to the control group. TIDM + Stem ex vivo Melatonin group showed a significant improvement, and some values were restored to normal. Ex vivo melatonin-treated stem cells had improved spatial working and object recognition memory and depression, with positive effects on glucose homeostasis, inflammatory markers levels and synaptic plasticity markers expression.
... The role of S. cumini seeds on HGinduced cardiac stress is not known so far; therefore, in the present study, methanol extract of S. cumini seeds was used to examine its effect on HG-induced cardiomyocytes. The effect was also examined with a purified form of a known constituent of S. cumini seed extract, gallic acid, a well-known cardioprotectant in diabetes-induced myocardial dysfunction and also an antioxidant [43]. We found S. cumini MSE to be enriched with polyphenols and had the potential to suppress HG-induced gelatinase-B activity in H9C2 cells which was comparatively better than that of gallic acid. ...
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Black berry (Syzygium cumini) fruit is useful in curing diabetic complications; however, its role in diabetes-induced cardiomyopathy is not yet known. In this study, we investigated the regulation of gelatinase-B (MMP-9) by S. cumini methanol seed extract (MSE) in diabetic cardiomyopathy using real-time PCR, RT-PCR, immunocytochemistry, gel diffusion assay, and substrate zymography. The regulatory effects of MSE on NF-κB, TNF-α, and IL-6 were also examined. Identification and estimation of polyphenol constituents present in S. cumini extract were carried out using reverse-phase HPLC. Further, in silico docking studies of identified polyphenols with gelatinase-B were performed to elucidate molecular level interaction in the active site of gelatinase-B. Docking studies showed strong interaction of S. cumini polyphenols with gelatinase-B. Our findings indicate that MSE significantly suppresses gelatinase-B expression and activity in high-glucose- (HG-) stimulated cardiomyopathy. Further, HG-induced activation of NF-κB, TNF-α, and IL-6 was also remarkably reduced by MSE. Our results suggest that S. cumini MSE may be useful as an effective functional food and dietary supplement to regulate HG-induced cardiac stress through gelatinase.
... GA has been reported to facilitate favorable biological activities, including radical scavenging, oxidation inhibition (Hsu and Yen, 2007), inflammation alleviation (Hsiang et al., 2013), obesity reduction (Hsu and Yen, 2007;Oi et al., 2012), and tumor suppression (Subramanian et al., 2015). Moreover, GA functions to alleviate metabolic diseases, including NAFLD (Chao et al., 2014) and diabetes, by upregulating the peroxisome proliferation-activated receptor (PPAR) in the liver, muscles, and adipose tissue, thereby reducing blood glucose (Gandhi et al., 2014), hepatic lipid peroxidation (Punithavathi et al., 2011b), diabetes induced myocardial dysfunction (Patel and Goyal, 2011), and diabetic nephropathy (Ahad et al., 2015) while enhancing pancreatic antioxidase activity (Punithavathi et al., 2011a). Additionally, studies have reported that GA inhibits the activities of glycogen phosphorylase (Kyriakis et al., 2015) and α-glucosidase (Benalla et al., 2010). ...
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Gallic acid (GA) is a simple polyphenol found in food and traditional Chinese medicine. Here, we determined the effects of GA administration in a combined mouse model of high-fat diet (HFD)-induced obesity and low-dose streptozotocin (STZ)-induced hyperglycemia, which mimics the concurrent non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes pathological condition. By combining the results of physiological assessments, pathological examinations, metabolomic studies of blood, urine, liver, and muscle, and measurements of gene expression, we attempted to elucidate the efficacy of GA and the underlying mechanism of action of GA in hyperglycemic and dyslipidemic mice. HFD and STZ induced severe diabetes, NAFLD, and other metabolic disorders in mice. However, the results of liver histopathology and serum biochemical examinations indicated that daily GA treatment alleviated the high blood glucose levels in the mice and decelerated the progression of NAFLD. In addition, our results show that the hepatoprotective effect of GA in diabetic mice occurs in part through a partially preventing disordered metabolic pathway related to glucose, lipids, amino acids, purines, and pyrimidines. Specifically, the mechanism responsible for alleviation of lipid accumulation is related to the upregulation of β-oxidation and ketogenesis. These findings indicate that GA alleviates metabolic diseases through novel mechanisms.
... The phenolic compounds have a high antioxidant capacity and a cardioprotective effect (Patel & Goyal, 2011;Stefanello et al., 2016). The maintenance of vascular integrity, anti-inflammatory effects, reduced platelet aggregation with the use of guabirobeira were also shown in other studies in vivo and in vitro (Klafke et al, 2012(Klafke et al, , 2016. ...
Article
Campomanesia xanthocarpa produces an edible yellow-orange fruit, known as “guabiroba”, with an acid and sweet flavor, consumed fresh or after processing as jelly, ice cream, liquor or tea. Leaf infusions are used in folk medicine to treat rheumatic, urinary and inflammatory diseases, obesity and hypercholesterolemia. This literature review was conceived to approach the potential of compounds present in the fruits, seeds and leaves of C. xanthocarpa in the prevention and treatment of diseases. The fruit is a good source of carbohydrates and fibers, in addition to having good concentrations of vitamin C, vitamin A and potassium; it also contains carotenoids and flavonoids. The seeds are high in terpenoids and essential fatty acids and the leaves contains phenolic acids and flavonoids. Fruits, seeds and leaves have high antioxidant potential in vitro and the powdered leaves can reduce plasma oxidative stress in humans. The biological effects of the C. xanthocarpa consist of antiulcerogenic, anti-inflammatory, anti-obesity, hypoglycemic, and hypolipidemic activities in addition to promising effects such as anticarcinogenic, photoprotection and analgesic. In conclusion, C. xanthocarpa has a potential to be used by the food and pharmaceutical industries.
... It acts as an anticancer agent against various types of human malignancies such as lung, breast, glioblastoma, prostate, colon, and pancreatic cancers (Muhammad et al., 2019). Gallic acid has been reported to possess antidepressant (Chhillar and Dhingra, 2013), antiparkinson (Chen, 2004), anti diabetic (Prasad et al., 2010), anti malarial (Griffith et al., 2002), diuretic (Ramya et al., 2014) and cardioprotective properties (Patel and Goyal, 2011). ...
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Scientific finding on phenolic content and anti-oxidant properties of Curcuma caesia and Chenopodium album can be useful and interesting as this work may lead to finding new sources for natural anti-oxidants, functional food, pharmaceuticals, and nutraceuticals. A total of seven different types of extracts were investigated for phenolic content of Curcuma caesia and Chenopodium album. Antioxidant activity for both the plant species was also evaluated as these plant species are traditionally used for ethno medicine practices. Antioxidant activity was determined by DPPH and phenolic content was determined by Folin Ciocalteu method. Phenolic content was found to be higher in Curcuma ceasia for all types of extracts investigated. Total phenolics content was found to be a maximum of 80% in crude methanol extract for both C. album (2585.0 µg/g gallic acid equivalent) and C. caesia (6672.4 μg/g gallic acid equivalent). A good correlation has
... In fact, potent antioxidants gallic acid also prevented the lipid peroxidation and inflammation in heart of ISO administered rats. This result is also supported by previous report suggests cardioprotective role of gallic acid in ISO administered rats (Priscilla and Prince, 2009) and streptozotocine induced diabetic rats (Patel and Goyal, 2011). ...
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Background Beet root (Beta vulgaris) subsp. vulgaris (conditiva) has been reported to possess many benefits and medicinal properties. However, the protective effect of beet root against isoproterenol (ISO) induced myocardial damage have not been clarified fully yet. The aim of the present study was to investigate the effects of beet root on oxidative stress, fibrosis, and myocardial damage in isoproterenol induced rats. Methods Male Long Evans rats were divided into five groups: control, ISO, control + beet root, ISO + beet root and ISO + gallic acid (standard). Rats were administered with ISO Subcutaneously (50 mg /kg) twice a week and were supplemented with freshly prepared crashed beet root (2.5 % wt/wt of diet) with powdered chaw food. At the end of the study, all rats were sacrificed for blood and organ sample collection to evaluate biochemical parameters and oxidative stress markers. Histopathological examinations were also conducted to assess inflammatory cell infiltration and fibrosis in heart and kidneys. Results Our investigation revealed that ISO administration markedly increased left ventricular wet weight of rats compared to control rats. The levels of oxidative stress markers were also significantly increased while the level of cellular antioxidants, catalase activity in ISO induced rats decreased. Beet root supplementation and gallic acid treatment to ISO administered rats prevented the rises of lipid peroxidation products MDA, nitric oxide and advanced protein oxidation product. Moreover, elevated activities of AST, ALT, and ALP enzymes in ISO administered rats were also lowered by both gallic acid and beet root supplementation. ISO induced rats also showed massive inflammatory cells infiltration and fibrosis in heart and kidneys compared to control rats. Furthermore, gallic acid and beet root supplementation prevented the inflammatory cells infiltration and fibrosis in ISO administered rats. Conclusion In conclusion, these results suggested that beet root supplementation is capable of protecting heart in ISO administered myocardial infarction in rats probably by preventing oxidative stress, inflammation, and fibrosis. Further research is warranted to examine molecular mechanism of cardioprotective effect of beet root powder.
... In fact, potent antioxidants gallic acid also prevented the lipid peroxidation and inflammation in heart of ISO administered rats. This result is also supported by previous report suggests cardioprotective role of gallic acid in ISO administered rats (Priscilla and Prince, 2009) and streptozotocine induced diabetic rats (Patel and Goyal, 2011). ...
Thesis
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Background Beet root (Beta vulgaris) subsp. vulgaris (conditiva) has been reported to possess many benefits and medicinal properties. However, the protective effect of beet root against isoproterenol (ISO) induced myocardial damage have not been clarified fully yet. The aim of the present study was to investigate the effects of beet root on oxidative stress, fibrosis, and myocardial damage in isoproterenol induced rats. Methods Male Long Evans rats were divided into five groups: control, ISO, control + beet root, ISO + beet root and ISO + gallic acid (standard). Rats were administered with ISO Subcutaneously (50 mg /kg) twice a week and were supplemented with freshly prepared crashed beet root (2.5 % wt/wt of diet) with powdered chaw food. At the end of the study, all rats were sacrificed for blood and organ sample collection to evaluate biochemical parameters and oxidative stress markers. Histopathological examinations were also conducted to assess inflammatory cell infiltration and fibrosis in heart and kidneys. Results Our investigation revealed that ISO administration markedly increased left ventricular wet weight of rats compared to control rats. The levels of oxidative stress markers were also significantly increased while the level of cellular antioxidants, catalase activity in ISO induced rats decreased. Beet root supplementation and gallic acid treatment to ISO administered rats prevented the rises of lipid peroxidation products MDA, nitric oxide and advanced protein oxidation product. Moreover, elevated activities of AST, ALT, and ALP enzymes in ISO administered rats were also lowered by both gallic acid and beet root supplementation. ISO induced rats also showed massive inflammatory cells infiltration and fibrosis in heart and kidneys compared to control rats. Furthermore, gallic acid and beet root supplementation prevented the inflammatory cells infiltration and fibrosis in ISO administered rats. Conclusion In conclusion, these results suggested that beet root supplementation is capable of protecting heart in ISO administered myocardial infarction in rats probably by preventing oxidative stress, inflammation, and fibrosis. Further research is warranted to examine molecular mechanism of cardioprotective effect of beet root powder.
... Considering the association between oxidation of LDL particles and risk of heart diseases and that resveratrol can be detected in human LDL particles after wine consumption [69], we can assume that resveratrol might prevent diseases which is consistent with its ability to reduce lipid peroxidation. Consistently, gallic acid and curcumin produced similar effects, in vivo [77,86]. Mechanisms involved in gallic acid pharmacological effects were recently reviewed [87]. ...
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Glyoxal (GO), a by-product of glucose auto-oxidation, is involved in the glycation of proteins/ lipids and formation of advanced glycation (AGE) and lipoxidation (ALE) end products. AGE/ALE were shown to contribute to diabetic complications development/progression such as nephropathy. Diabetic nephropathy progression has an oxidative nature. Given the antioxidant effects of polyphenols, potential protective effects of resveratrol, curcumin and gallic acid, in rat renal cells treated with GO, were evaluated in the present work. According to our results, incubation of GO with the cells reduced their viability and led to membrane lysis, reactive oxygen species (ROS) formation, lipid peroxidation, mitochondrial membrane potential collapse, and lysosomal membrane leakage. These findings were prevented by pre-treatment with resveratrol, curcumin and gallic acid. Mitochondrial and lysosomal toxic interactions appear to worsen oxidative stress/cytotoxicity produced by GO. Resveratrol, curcumin and gallic acid inhibited ROS formation and attenuated GO-induced renal cell death.
... Another possible reason of the decreased glucose level might be the decline in the glucose absorption from intestine 46 due to the decrease in the digestibility of carbohydrates which was also observed in the present trial. As reported previously 44,47 in different research trials that poor digestibility of the carbohydrate might be due to the formation of complexes of tannin with starch digestive enzymes which further inhibited the process of digestion; while no change in insulin level was observed in the present trial due to the extra pancreatic effect of tannin which was independent of insulin 46 or the HT had insulin like activity that maintained the antioxidant environment of the pancreatic β-cells 48 . Another statistical finding of present trial was the decreased levels of serum LDL, cholesterol and triglycerides and increased level of serum HDL which was also reported previously 47 . ...
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The present work aimed to find out the effect of different levels of hydrolysable tannin (HT) on serum hormonal profile, biochemical indices, lipid profile, apparent digestibility of nutrients and body weight gain in healthy female rats. Forty five adult healthy female rats of 8 weeks old were randomly divided into five equal groups. Different doses of HT 0, 0.5, 1, 1.5 and 2% were administered daily to each rats group on the body weight basis for 6 weeks. The results had shown the reduction trend (p < 0.05) in the blood glucose, serum cholesterol, low density lipoprotein, testosterone, prolactin, ghrelin, total oxidative stress and serum iron levels; while an improvement (p < 0.05) was seen in serum follicle stimulating hormone, progesterone, luteinizing hormone, high density lipoprotein, IgM and total antioxidant capacity. However, no effect (p > 0.05) was noticed in serum IgG, protein, estrogen and calcium levels. A significant reduction (p < 0.05) was seen in the apparent nutrient digestibility and body weight gain. The results had shown improvement in the feed conversion ratio (p < 0.05) but non-significant decrease (p > 0.05) in the feed intake. The findings showed that HT had healthy effects on the serum biochemical indices and reproductive hormonal profile but had a negative impact on the nutrient digestibility. Thus, the study concluded that HT could be used as an herbal medicine for the treatment of leading metabolic and infertility diseases like obesity and polycystic ovarian syndrome in females.
... The cardioprotective effect of amla fruit has been demonstrated in several studies ( Table 2). It has also been reported that it prevents the myocardial depletion of creatine kinase-MB (CK-MB), a marker of cardiac damage, and improves hemodynamic parameters, further showing its cardioprotective effects (Patel and Goyal, 2011;Ojha et al., 2012). Emblicanin-A and B, two small-sized hydrolysable gallotanins, have exhibited a protective effect in ischemia-reperfusion (I/R)-induced cardiac damage in rats. ...
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A new coronavirus causing severe acute respiratory syndrome (SARS-CoV-2) has emerged and with it, a global investigation of new antiviral treatments and supportive care for organ failure due to this life-threatening viral infection. Traditional Persian Medicine (TPM) is one of the most ancient medical doctrines mostly known with the manuscripts of Avicenna and Rhazes. In this paper, we first introduce a series of medicinal plants that would potentially be beneficial in treating SARS-CoV-2 infection according to TPM textbooks. Then, we review medicinal plants based on the pharmacological studies obtained from electronic databases and discuss their mechanism of action in SARS-CoV-2 infection. There are several medicinal plants in TPM with cardiotonic, kidney tonic, and pulmonary tonic activities, protecting the lung, heart, and kidney, the three main vulnerable organs in SARS-CoV-2 infection. Some medicinal plants can prevent "humor infection", a situation described in TPM which has similar features to SARS-CoV-2 infection. Pharmacological evaluations are in line with the therapeutic activities of several plants mentioned in TPM, mostly through antiviral, cytoprotective, anti-inflammatory, antioxidant, and anti-apoptotic mechanisms. Amongst the primarily-introduced medicinal plants from TPM, rhubarb, licorice, garlic, saffron, galangal, and clove are the most studied plants and represent candidates for clinical studies. The antiviral compounds isolated from these plants provide novel molecular structures to design new semisynthetic antiviral agents. Future clinical studies in healthy volunteers as well as patients suffering from pulmonary infections are necessary to confirm the safety and efficacy of these plants as complementary and integrative interventions in SARS-CoV-2 infection.
... Normalization of hyperglycemia, hyperlipidemia, and oxidative stress is crucial in the prevention of diabetesinduced cardiac dysfunction. Oral ingestion of gallic acid (tannin present in Emblica fruit) at 25À100 mg/kg or Emblica fruit juice has been noted to have cardioprotective effects in diabetic rats in a dose-dependent manner (Patel and Goyal, 2011); this was attributable to the antioxidative effects of the polyphenols present, independent of blood sugar reduction. ...
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Indian gooseberries (Emblica officinalis) traditionally have been used in Indian medicine (Ayurveda) for enhancing general vitality and cognition, to relieve anxiety, and promote longevity. Although there is very limited human evidence, it appears to be promising for the management of blood glucose and lowering of blood cholesterol in diabetics. The antioxidant properties of Emblica also contribute to the alleviation of secondary complications in diabetes. In animal models, these fruits appear to be able to reduce cholesterol and triglycerides, thus contributing to cardiovascular health. Most of these actions are attributed to its antioxidant properties, which are partially derived from high ascorbic acid content but also from a large amount of phenolic tannin compounds. Hair growth-promoting effect and longevity-promoting effect in this fruit are interesting and appear to be more effective than other nutraceutical options. Emblica fruit has been endowed with immune-modulating properties. Emblica fruit has a significant ulcer protective and healing effect. Emblica fruit scientifically qualifies to be a constituent of many hepatoprotective formulations. Much information from both in vitro and in vivo studies indicates that Emblica fruit possesses potent anticancer properties. Scientific evidence thus far documented suggest that these berries possess a wide spectrum of potential health benefits. While there is a need for further research, these fruits potentially may contribute to general well-being and longevity as suggested by their use in traditional medicine.
... Gallic acid also reduced triglyceride, total cholesterol, urea, uric acid, low-density lipoprotein (LDL) cholesterol, and creatinine and significantly increased insulin level in blood and glucose tolerance. Gallic acid benefits in both the ways in diabetes by working as an anti-oxidant, which reduced the oxidative damage in β-cells and improve blood glucose and lipid level in patients having greater cardiac risk (Patel & Goyal, 2011). ...
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Diabetes is a disease of serious concern faced by the health care industry today. Primary diabetes mellitus and its complications are still costly to manage with modern drugs. Extensive research on the screening of anti-diabetic agents in past decades established natural products as one of the major potential sources of drug discovery. However, only a few drugs of plant origin have been scientifically validated. Therefore, the development of new anti-diabetic drugs is of great demand. Hence, natural products could be explored as potential anti-diabetic drugs. Natural plants derived extracts and molecules like berberine, ginsenosides, curcumin, stevioside, gingerols, capsaicin, catechins, simple phenolic compounds, anthocyanins, resveratrol, genistein and hesperidin obtained from different species are used for curing diabetes and found to possess different action mechanisms. In this review, the importance of medicinal plants and their active constituents for anti-diabetic agents are described. The present study also emphasized the importance of diabetes control, reduction in its complications and use of the anti-diabetic agents. The detailed action mechanism of these extracts/compounds for their activities are also described. However, the anti-diabetic drugs from plant origin require scientific validation through animal and clinical studies to exploit in terms of modern commercial medicines.
... Muchuweti et al. [28] reported a 6.7 µg/g DM gallotannin level in ripe fruit pulp. Gallotannins are known to have bioactivity such as anticancer, antioxidant, anti-inflammatory, anti-hyperglycaemic, lipid-lowering and antimicrobial action [40]. The presence of these polyphenols in the fruit pulp plays an important technological role of being determinants of antioxidant activity. ...
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Consumption of Uapaca kirkiana indigenous fruit by the local populace is growing in popularity because of the acclaimed health and functional benefits. The aim of the study was to determine the bioactive compounds and functional properties of the U. kirkiana fruit. Besides the fruit’s pulp yield, the bioactive phytochemical constituent, physicochemical properties and functional characteristics of the pulp were analysed. The sugar, starch, minerals, and ascorbic acid constituents of the fruit pulp were, respectively determined using the following instruments: brix refractometer, megazyme kit, inductive coupled plasma-optical emission spectrometer and 2,6-dichlorophenolindophenol (DCPIP) titration test. The total phenolic content (TPC), tannin, and flavonoid contents were evaluated using Folin Ciocalteau test, tannin binding test and vanillin test, respectively. The average weight of the U. kirkiana fruits harvested from three regions having different climatic conditions ranged from 23.56 to 34.20 g per fruit. The mean pulp weight was from 12.15 g/100 g to 15.09 g/100 g per fruit. The biochemical and functional parameters obtained include total titratable acid (0.3 - 0.48 g/kg), antioxidant activity (34.96 - 36.68%), vitamin C (15.74 - 16.63 mg/100 g), dry matter content (28.81 - 29.38%), pH (4.3 - 4.6) and sugar content (20.29 - 21.87 g/100 g). Fructose was the dominant sugar (10.12-11.0 g/100 g). Preliminary phytochemical screening of the pulp indicated the presence of tannins, flavonoids, amino acids and carbohydrate content. Total phenolic content ranged from 67.0 to 82.5 μg GAE/g. The essential elements constituent evaluation of the pulp revealed that Fe content was 11.3 - 12.2 mg/100 g, K (383.07 - 439.8 mg/100 g), Mg (28.7 - 35.1 mg/100 g), Ca (16.4 - 17.3 mg/100 g), P (13.4 - 15.1 mg/100 g), Na (9.08 - 9.78 mg/100 g), Cu (0.8 - 0.94 mg/100 g) and Zn (0.87 - 0.94 mg/100 g). This study, besides establishing U. kirkiana fruit as a good source of micronutrients (Fe, Cu, Zn), reveals that the fruit is also an excellent source of phenolic compounds, vitamin C and sugars, hence use as a dietary supplement may combat some nutritional deficiencies. We, therefore, recommend U. kirkiana fruits to be used to produce nutritive functional foods with health benefits such as probiotic jams and as an additive.
... Muchuweti et al. [28] reported a 6.7 µg/g DM gallotannin level in ripe fruit pulp. Gallotannins are known to have bioactivity such as anticancer, antioxidant, anti-inflammatory, anti-hyperglycaemic, lipid-lowering and antimicrobial action [40]. The presence of these polyphenols in the fruit pulp plays an important technological role of being determinants of antioxidant activity. ...
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Consumption of Uapaca kirkiana indigenous fruit by the local populace is growing in popularity because of the acclaimed health and functional benefits. The aim of the study was to determine the bioactive compounds and functional properties of the U. kirkiana fruit. Besides the fruit’s pulp yield, the bioactive phytochemical constituent, physicochemical properties and functional characteristics of the pulp were analysed. The sugar, starch, minerals, and ascorbic acid constituents of the fruit pulp were, respectively determined using the following instruments: brix refractometer, megazyme kit, inductive coupled plasma-optical emission spectrometer and 2,6-dichlorophenolindophenol (DCPIP) titration test. The total phenolic content (TPC), tannin, and flavonoid contents were evaluated using Folin Ciocalteau test, tannin binding test and vanillin test, respectively. The average weight of the U. kirkiana fruits harvested from three regions having different climatic conditions ranged from 23.56 to 34.20 g per fruit. The mean pulp weight was from 12.15 g/100 g to 15.09 g/100 g per fruit. The biochemical and functional parameters obtained include total titratable acid (0.3 - 0.48 g/kg), antioxidant activity (34.96 - 36.68%), vitamin C (15.74 - 16.63 mg/100 g), dry matter content (28.81 - 29.38%), pH (4.3 - 4.6) and sugar content (20.29 - 21.87 g/100 g). Fructose was the dominant sugar (10.12-11.0 g/100 g). Preliminary phytochemical screening of the pulp indicated the presence of tannins, flavonoids, amino acids and carbohydrate content. Total phenolic content ranged from 67.0 to 82.5 µg GAE/g. The essential elements constituent evaluation of the pulp revealed that Fe content was 11.3 - 12.2 mg/100 g, K (383.07 - 439.8 mg/100 g), Mg (28.7 - 35.1 mg/100 g), Ca (16.4 - 17.3 mg/100 g), P (13.4 - 15.1 mg/100 g), Na (9.08 - 9.78 mg/100 g), Cu (0.8 - 0.94 mg/100 g) and Zn (0.87 - 0.94 mg/100 g). This study, besides establishing U. kirkiana fruit as a good source of micronutrients (Fe, Cu, Zn), reveals that the fruit is also an excellent source of phenolic compounds, vitamin C and sugars, hence use as a dietary supplement may combat some nutritional deficiencies. We, therefore, recommend U. kirkiana fruits to be used to produce nutritive functional foods with health benefits such as probiotic jams and as an additive.
Chapter
By 2030, diabetes will be the 7th leading cause of premature mortality worldwide, according to the World Health Organisation. The application of nanotechnology in medicine holds many possible advantages and over the past few decades, there has been huge progress in its utilisation. Nanotechnology is widely applied for cancer treatment and other diseases but, the use of it for diabetes treatment is now starting to flourish. This book presents the latest developments of nanomedicine for the treatment of different facets of diabetes and related disorders. With a multidisciplinary approach, chapters focus on previously overlooked topics in glucose sensing, insulin delivery and secretion, bioimaging and transplantation of islets. This book is suitable for researchers of nanomedicine, nanotechnology and diabetes looking into the emergence of new approaches for the treatment of this life-threatening disease.
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Pomegranate (Punica granatum L.) is a fruit rich in bioactive compounds with various biological properties that help maintain good health. In particular, the polyphenolic compounds punicalagin, ellagic acid, urolithins and gallic acid are among the main molecules with antioxidant potential identified in this fruit; that is, these compounds have the ability to prevent cellular alterations caused by oxidative stress and/or induce the body's own antioxidant response to protect cells. As a result, numerous scientific studies have emerged in the last decade, focused on recognizing the pharmacological properties of these molecules, to prevent the development and progression of diseases in which oxidative stress plays a fundamental role. The objectives of this review are: 1) to point out the importance of antioxidants obtained from the diet and in particular those obtained from pomegranate, 2) to highlight the beneficial effects of ellagitannins, ellagic acid, urolithins and gallic acid against various pathologies, and 3) recognize that despite their potential as therapeutic agents, further research in humans is required to promote their use in the clinic.
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Background: Diabetes is one of the most challenging health problems in 21st century. It is a group of endocrine-metabolic disorder characterized by high glucose level (hyperglycemia) due to insufficient insulin secretion/action or both. It causes multi-organ failure viz hepatorenal damage, adult-onset blindness, lower-limb amputations, heart diseases and stroke, high blood pressure and nerve damage. Moreover, diabetic patients are having higher risk of cardiovascular complications including atherosclerosis, hypertension, lipoprotein abnormalities and cerebrovascular disease. Study design: Considering the potencies of currently available drugs for the treatment of diabetes and associated complications, present study was focussed to explore the role of plant bioactive components as alternative and easily accessible therapeutic remedies. Hypothesis/Purpose: This study the pooled status of diabetes, available treatments, attitude and traditional herbal polyphenols regarding diabetes. Results: This study was aimed to summarize the natural polyphenols having anti-diabetic, anti-inflammatory, anti-apoptotic and anti-cancerous activities. Polyphenols can decrease other metabolic diseases such as insulin resistance, hyperglycemia, hyperlipidemic, and obesity and Type-2 diabetes. Conclusion: Polyphenols are promising alternatives that can decrease the severity of diabetes and promote the other protective roles by decreasing the adverse effects of diabetes on other metabolic organs and their functions.
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Background: Mitochondria are the main target organelles through which drugs and chemicals exert their toxic effect on cardiomyocytes. The mitochondria-related mechanisms of celecoxib-induced cardiotoxicity have been extensively studied. Accumulated evidence shows natural molecules targeting mitochondria have proven to be effective in preventing cardiotoxicity. Purpose: In the present study, we examined the ameliorative effect of gallic acid (GA) against celecoxib-induced cellular and mitochondrial toxicity in isolated cardiomyocytes and mitochondria. Research design: The isolated cardiomyocytes and mitochondria were divided into various group, namely, control, celecoxib, celecoxib + GA (10, 50, and 100 µM). Several cellular and mitochondrial parameters such as cell viability, lipid peroxidation, succinate dehydrogenase (SDH) activity, reactive oxygen species (ROS) formation, mitochondrial membrane potential (MMP) collapse, and mitochondrial swelling were assessed in isolated cardiomyocytes and mitochondria. Results: Our results showed that administration of celecoxib (16 µg/ml) induced cytotoxicity and mitochondrial dysfunction at 6 h and 1 h, respectively, which is associated with lipid peroxidation intact cardiomyocytes, mitochondrial ROS formation, MMP collapse, and mitochondrial swelling. The cardiomyocytes and mitochondria treated with celecoxib + GA (10, 50, and 100 µM) significantly and dose-dependently restore the altered levels of cellular and mitochondrial parameters. Conclusions: We concluded that GA through antioxidant potential and inhibition of mitochondrial permeability transition (MPT) pore exerted ameliorative role in celecoxib-induced toxicity in isolated cardiomyocytes and mitochondria. The data of the current study suggested that GA supplementation may reduce celecoxib-induced cellular and mitochondrial toxicity during exposure and may provide a potential prophylactic and defensive candidate for coxibs-induced mitochondrial dysfunction, oxidative stress, and cardiotoxicity.
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Background and Objective Many natural bioactive chemicals have been shown to have functional activity, suggesting that they could be useful in the treatment and management of a wide range of chronic conditions. Flavonoids, which include gallic acid (GA), are the most abundant polyphenols found in nature. Skeletal muscle relaxants are drugs that reduce undesired spasms while maintaining awareness and reflexes unaffected. The purpose of this investigation was to determine if GA has any skeletal muscle relaxant properties in experimental animal models. Materials and Methods: The muscle relaxant activity of three dosages of GA (5, 10, and 20 mg/kg) was compared to that of normal diazepam (5 mg/kg) utilizing climbing, chimney, and modified Kondziela's inverted tests. An analysis of variance (ANOVA) and a post-ANOVA Tukey multiple comparisons test were used to assess the data. Results: Animals given 10 and 20 mg/kg of GA had a great deal of trouble climbing up the chain, presumably because their muscles were relaxed. Similarly, rats given a high dose of GA (20 mg/kg) had a significantly (P<0.05)longer response time in the chimney test, indicating a lack of attention and slowed muscle tone, resulting in problems with motor coordination. In inverted testing, animals given a high dose of GA had a significantly (P<0.01)reduced holding capacity on the mesh for a longer period of time. A decrease in holding time is caused by a decrease in muscular contraction. The low dose of GA, on the other hand, failed to show muscle relaxant effect in any of the three models. Conclusions: As a conclusion, our data show that GA has a dose-dependent skeletal muscle relaxant effect when administered orally to mice.
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Acalypha indica is a significant medicinal plant. The purpose of this review is to bring traditional usage, phytochemistry, and scientific applications of A.indica up to date. Microbial infections, fertility, stomach ulcers, snake bites, pains, wounds, liver/kidney problems, and rheumatism have all been traditionally treated with A.indica paste, decoction, sap, and synergy with other plants/plant products, which have all been scientifically proven through in vitro and in vivo experiments. Regardless of traditional knowledge, this plant extracts have been scientifically proven to help against cancer, inflammation, cardiac damage, diabetes, TB, and malaria. Phytochemical investigation revealed that A.indica has phenols, flavonoids, tannins, coumarins, alkaloids and their glycosides, saponins, volatiles and fatty acids. In summary, the presence of phytoconstituents is responsible for the A.indica traditional and pharmacological qualities. Further, conformational clinical trails in humans are necessary to ascertain the extracts efficacy. Extensive future studies are to be conducted to reveal the mechanism of action, pharmacokinetic properties and active phythochemicals of A.indica extracts.
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Background: Diabetes mellitus is a disease that has reached a dangerous point. Today, nearly 500 million men and women around the world live with diabetes. Gallic acid (Gal) affects diabetes. Objective: To evaluate the effects of Gal and metformin (met) on the levels of glucose, insulin, testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sperm count, antioxidant status, and histological changes in the testes of diabetic mice induced by methylglyoxal (MGO). Materials and methods: In this experimental study, 50 male adult NMRI mice, weighting 25-30 gr, aged 3-4 months were randomly divided into five equal groups (n = 10/each). (i) Control (vehicle, normal saline), (ii) MGO (600 mg/kg/d) orally for 28 days, (iii) Gal (50 mg/kg/d), (iv) MGO+Gal, and (v) MGO+met (200 mg/kg/d). Gal and met were administered orally for 21 consecutive days after the induction of diabetes. Blood samples were taken at 24 hr after the latest doses of treatment. Histological assessment of the testis was done, and the epididymis sperm count was obtained. Antioxidant indices, glucose, insulin, LH, FSH, and testosterone levels were measured. Results: In the MGO group compared to the control group, insulin, glucose (p = 0.001), LH (p = 0.04) and malondialdehyde (p = 0.001) were increased. However, the level of testosterone (p = 0.001), seminiferous tubule diameters, epithelial height, sperm count, superoxide dismutase activity (p = 0.02), and testis volume (p = 0.01) were decreased. The results indicated that Gal and met ameliorated the MGO effects. Conclusion: These findings suggested that the animals receiving MGO became diabetic. According to the results, Gal and met can effectively prevent MGO-induced diabetes. The effect of Gal was equivalent and sometimes better than metformin.
Chapter
Vegetables are used as an important source of food, and also generates a huge amount of waste annually during various stages of the agricultural process or in the food industries. If vegetable waste is not processed properly it can lead to contamination of the environment, which has led to the search for a green effect. Vegetable wastes or their byproducts contain a large number of primary (carbohydrates, proteins, lipids, vitamins, etc.) and secondary metabolites (flavonoids, polyphenols, carotenoids, etc.) with potential therapeutic efficacy such as antioxidant, antiinflammatory, anticancer, and cardioprotective activities. Valorization of vegetable byproducts through various processes makes them a potential source of nutraceuticals, food ingredients, functional foods, food additives, and cosmetic products, along with enabling a reduction in environmental contamination. Since most of medicinal plants were also cultivated for production of these bioactives, valorization of vegetable wastes and byproducts serves as an alternate and cheaper source for their procurement, along with the protection of endangered plant species. This chapter enumerates the important vegetable wastes and byproducts with potentially important bioactives and their valorization. It also focuses on the applications of various vegetable byproducts in food industries and the healthcare sector, vegetable preservation methods and extraction and isolation, as well as the sustainability of vegetable wastes.
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Vascular calcification (VC), which is closely associated with significant mortality in cardiovascular disease, chronic kidney disease (CKD), and/or diabetes mellitus, is characterized by abnormal deposits of hydroxyapatite minerals in the arterial wall. The impact of oxidative stress (OS) on the onset and progression of VC has not been well described. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, xanthine oxidases, myeloperoxidase (MPO), nitric oxide synthases (NOSs), superoxide dismutase (SOD) and paraoxonases (PONs) are relevant factors that influence the production of reactive oxygen species (ROS). Furthermore, excess ROS-induced OS has emerged as a critical mediator promoting VC through several mechanisms, including phosphate balance, differentiation of vascular smooth muscle cells (VSMCs), inflammation, DNA damage, and extracellular matrix remodeling. Because OS is a significant regulator of VC, antioxidants may be considered as novel treatment options.
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Diabetes mellitus (DM) is a worldwide health problem. The Micro- and macro-vascular complications are the major causes of morbidity and mortality of DM. Molecular regulation of mitochondrial fission/fusion cycles is being studied, but the results were not conclusive. The aim of this study is to investigate the possible functional role of lncRNA H19 and its relation to mitofusin-2 (Mfn-2) gene expression in diabetic rats with cardiac and renal complications. Streptozotocin-induced diabetic male, albino rats and a matched control group were investigated. Cardiac weights, blood pressure and ECG were recorded. Biochemical evaluation of cardiac and renal functions was performed. Molecular determination of lncRNA H19 and Mfn-2 gene expression and histological examination by light and electron microscopy for cardiac and renal tissues were performed. Diabetic rats showed a significant increase of left ventricle weight/whole body weight ratio, R wave voltage, and a significant decrease of blood pressure, heart rate, and P wave voltage. At the molecular level, lncRNA H19 and Mfn-2 mRNA showed altered expression with a statistically significant downregulation of Mfn-2 mRNA expression in renal tissues. In conclusion, the changes in lncRNA H19 and Mfn-2 mRNA expression may help better understanding of the pathogenesis of cardiac and renal dysfunctions associated with type 1 DM.
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After spinal cord injury (SCI), blood-spinal cord barrier (BSCB) disruption results in secondary injury including apoptotic cell death of neurons and oligodendrocytes, thereby leads to permanent neurological deficits. Recently, we reported that the histone H3K27me3 demethylase Jmjd3 plays a role in regulating BSCB integrity after SCI. Here, we investigated whether gallic acid (GA), a natural phenolic compound that is known to be anti-inflammatory, regulates Jmjd3 expression and activation, thereby attenuates BSCB disruption following the inflammatory response and improves functional recovery after SCI. Rats were contused at T9 and treated with GA (50 mg/kg) via intraperitoneal injection immediately, 6 h and 12 h after SCI, and further treated for 7 d with the same dose once a day. To elucidate the underlying mechanism, we evaluated Jmjd3 activity and expression, and assessed BSCB permeability by Evans blue assay after SCI. GA significantly inhibited Jmjd3 expression and activation after injury both in vitro and in vivo. GA also attenuated the expression and activation of matrix metalloprotease-9, which is well known to disrupt the BSCB after SCI. Consistent with these findings, GA attenuated BSCB disruption and reduced the infiltration of neutrophils and macrophages compared with the vehicle control. Finally, GA significantly alleviated apoptotic cell death of neurons and oligodendrocytes and improved behavior functions. Based on these data, we propose that GA can exert a neuroprotective effect by inhibiting Jmjd3 activity and expression followed the downregulation of matrix metalloprotease-9, eventually attenuating BSCB disruption after SCI.
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Ethnopharmacology relevance Nowadays, there is an increase in global tendency to use medicinal plants as preventive and therapeutic agents to manage diabetes and its long-term complications such as cardiovascular disorders owing to their availability and valuable traditional background. Aim of study This review aims to introduce common medicinal plants, which have been demonstrated to have cardioprotective effects on diabetes and their mechanisms of action. Materials and methods Online literature databases, including Web of Sciences, PubMed, Science Direct, Scopus and Google Scholar were searched without date limitation by May 2020. The following keywords (natural products or medicinal plants or herbal medicine or herb or extract) and (diabetes or antidiabetic or hyperglycemic) and (cardiomyopathy or heart or cardioprotective or cardiac or cardio) were used, and after excluding non-relevant articles, 81 original English articles were selected. Results The surveyed medicinal plants induced cardioprotective effects mostly through increasing antioxidant effects leading to attenuating ROS production as well as by inhibiting inflammatory signaling pathways and related cytokines. Moreover, they ameliorated the Na+/K+ ATPase pump, the L-type Ca2⁺ channel current, and the intracellular ATP. They also reduced cardiac remodeling and myocardial cell apoptosis through degradation of caspase-3, Bax, P53 protein, enhancement of Bcl-2 protein expression as well as downregulation of TGFβ1 and TNFα expression. In addition, the extracts improved cardiac function through increasing EF% and FS% as well as restoring hemodynamic parameters. Conclusions The reviewed medicinal plants demonstrated cardioprotective manifestations in diabetes through intervention with mechanisms involved in the diabetic heart to restore cardiovascular complications.
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The traditional system of medicine has shown much better improvement, less side effect, and less expensive as compared to modern synthetic drugs in the treatment of diabetes mellitus. Medicinal plants and phytochemicals have much importance in the present scenario in developing countries where resources are limited. The effectiveness and activity of a phytochemical depend upon its binding ability with the target molecules. Identification of the target molecule, its mechanism, and interaction with the specific phytochemical drug, can be proved to be an efficient therapeutic against diabetes. This review addressed different classes of molecules and enzymes involved in the pathogenesis of diabetes mellitus, antidiabetic activities of different classes of phytochemicals, its activity on antidiabetic drug targets, as well as possibilities of herbal drug development for diabetes in context with targeted therapy.
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It has been established that diabetes results in a cardiomyopathy, and increasing evidence suggests that an altered substrate supply and utilization by cardiac myocytes could be the primary injury in the pathogenesis of this specific heart muscle disease. For example, in diabetes, glucose utilization is insignificant, and energy production is shifted almost exclusively towards beta-oxidation of free fatty acids (FFA). FFA's are supplied to cardiac cells from two sources: lipolysis of endogenous cardiac triglyceride (TG) stores, or from exogenous sources in the blood (as free acid bound to albumin or as TG in lipoproteins). The approximate contribution of FFA from exogenous or endogenous sources towards beta-oxidation in the diabetic heart is unknown. In an insulin-deficient state, adipose tissue lipolysis is enhanced, resulting in an elevated circulating FFA. In addition, hydrolysis of the augmented myocardial TG stores could also lead to high tissue FFA. Whatever the source of FFA, their increased utilization may have deleterious effects on myocardial function and includes the abnormally high oxygen requirement during FFA metabolism, the intracellular accumulation of potentially toxic intermediates of FFA, a FFA-induced inhibition of glucose oxidation, and severe morphological changes. Therapies that target these metabolic aberrations in the heart during the early stages of diabetes could potentially delay or impede the progression of more permanent sequelae that could ensue from otherwise uncontrolled derangements in cardiac metabolism.
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The effects of hydralazine on blood lipids, systolic pressure and cardiac performance were assessed in male Wistar rats, 6 weeks after they were made diabetic with streptozotocin (STZ). STZ-induced diabetes results in a loss of body weight, hyperglycemia and hypoinsulinemia. These effects are not altered after hydralazine treatment. STZ-diabetes also produced a significant bradycardia, elevation of blood pressure, hyperlipidemia and decreases in the levels of triiodothyronine and thyroxine. Hydralazine treatment successfully prevented all these alterations. In addition, cardiac performance was depressed in the untreated diabetic animals, but the cardiac performance of the hydralazine-treated diabetic animals showed a definite improvement. Thus, hydralazine controlled the high serum lipids and blood pressure and improved cardiac performance in STZ diabetic rats.
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Isolated perfused hearts from diabetic rats exhibit a decreased responsiveness to increasing work loads. However, the precise time point at which functional alterations occur is not clearly established. Previous observations in our laboratory have suggested that the alterations in myocardial function are not apparent at 30 days whereas they are clearly seen 100 days after streptozotocin-induced diabetes. We studied the cardiac function of 6-week diabetic rats using the isolated perfused heart preparation. The 6-week time period was found to be sufficient to cause depression of myocardial function in these animals. We also studied the effect of insulin treatment on myocardial performance of diabetic rats. Insulin treatment was initiated 3 days and 6 weeks after injection of streptozotocin (STZ). The treatment was continued for 6 and 4 weeks in the respective groups. Hearts from 6-week diabetic animals exhibited a depressed left ventricular developed pressure (LVDP) and positive and negative dP/dt at higher filling pressures when compared with 6-week control animals. However, the depression was not seen in the 6-week insulin-treated diabetic animals. Ten-week diabetic rat hearts also showed a depression of LVDP and positive and negative dP/dt when compared with 10-week controls. The group of animals that had been diabetic for 6 weeks and then treated for 4 weeks with insulin exhibited a reversal of the depressed myocardial function. These results demonstrate that depression of myocardial performance, which is evident 6 weeks after diabetes is induced, can be prevented if insulin treatment is initiated as the disease is induced. Further, insulin treatment is capable of reversing the abnormalities after they have occurred.
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Tannins occur naturally in relatively abundant amounts in fruits, herbal medicines and common beverages. Thus an understanding of how these polyphenols affect peptide hormone action is of importance. We report here that tannic acid (a hydrolysable tannin) inhibits insulin-stimulated lipogenesis in rat adipose tissue in vitro, with an IC50 estimated to be about 350 microM. However, its monomer, gallic acid, did not show a similar inhibitory effect at concentrations up to 1 mM. The inhibition by tannic acid was less evident with higher concentrations of bovine serum albumin in the incubation buffer. This was attributed to the formation of a tannin-protein complex between bovine serum albumin and tannic acid. In a binding assay, it was observed that the specific binding of insulin to its receptor was not inhibited by tannic acid in the concentration range 0-200 microM. However, insulin-stimulated autophosphorylation of the insulin receptor, and receptor-associated tyrosine kinase phosphorylation of RR-SRC peptide, were inhibited by tannic acid at concentrations as low as 25 microM. Our data do not support the current speculation that tannins affect the activity of peptide hormones by binding to them. Therefore, our finding opens up a new perspective in the understanding of the mode of action of tannins on such hormones.
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To investigate anaerobic glycolysis and glucose oxidation in the diabetic heart, we studied the effects of anoxia and low exogenous free fatty acid (FFA) on myocardial adenosine triphosphate (ATP) content in the isolated perfused heart from streptozotocin-diabetic rats. The perfusate consisted of Krebs-Ringer buffer (pH 7.4) containing 5 mM glucose and 0.30 mM or 0.05 mM FFA, equilibrated with 95% O2 + 5% CO2 or 95% N2 + 5% CO2 gas. Under aerobic conditions, glucose uptake, lactate production and glucose oxidation by the diabetic heart were reduced by 68, 57 and 53% of the control, respectively, and FFA oxidation by the diabetic heart was increased by 67% of the control. Under anoxic conditions, the increments in glucose uptake and lactate production by the diabetic heart were much smaller than those by the control (2.6 and 9.5 mumol/g/30 min vs. 11.4 and 40 mumol/g/30 min, respectively). The ATP content in the diabetic myocardium was decreased more rapidly in the anoxic perfusion than that in the control. In the aerobic perfusion, the ATP content in the control myocardium was maintained for 60 min at low FFA (0.05 mM) in the perfusate. The ATP content in the diabetic myocardium was reduced after 40 min at low FFA but was well maintained for 60 min by the addition of 0.30 mM FFA. Thus the ATP content in aerobic diabetic myocardium was not well maintained when exogenous FFA supply was depleted. These results suggest that diabetic hearts have a primary defect in the stimulation of glycolysis and glucose oxidation, which does not result from increased FFA utilization.