Deciphering Acetaminophen-Induced Hepatotoxicity: The Crucial Role of Transcription Factors like Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) as Genetic Determinants of Susceptibility to Drug-Induced Liver Injury.

Acetaminophen (APAP) is the most used non-prescription drug throughout the world. At therapeutic doses, APAP has potent analgesic and antipyretic effects. The efficacy and safety of APAP are influenced by multi-factorial processes that are dependent upon dosing, namely frequency and total dose. APAP poisoning by repeated ingestion of supratherapeutic doses, depletes glutathione (GSH) stores in liver and other organs capable of metabolic bioactivation, leading to hepatocellular death due to exhausted antioxidant defenses. Numerous genes, encompassing transcription factors and signaling pathways, have been identified as playing pivotal roles in APAP toxicity, with the liver being the primary organ studied due to its central role in APAP metabolism and injury. Nuclear factor erythroid 2-related factor 2 (Nrf2) and its array of downstream responsive genes are crucial in counteracting acetaminophen APAP toxicity. Nrf2, along with its negative regulator Kelch-like ECH-associated protein 1 (Keap1), plays a vital role in regulating intracellular redox homeostasis. This regulation is significant in modulating the oxidative stress, inflammation, and hepatocellular death induced by APAP. In this review, we provide an updated overview of the mechanisms through which Nrf2 activation and signaling critically influence the threshold for developing APAP toxicity. We also describe how genetically modified rodent models for Nrf2 and related genes have been pivotal in underscoring the significance of this antioxidant response pathway. While Nrf2 is a primary focus, the article comprehensively explores other genetic factors and related pathways that contribute to APAP toxicity, thereby providing a holistic understanding of the genetic landscape influencing susceptibility to this condition. Significance Statement This review scrutinizes the genetic elements and signaling pathways underlying acetaminophen (APAP)-induced liver toxicity, with a focus on the crucial protective role of the transcription factor NRF2. This review also delves into the genetic intricacies influencing APAP safety and potential liver harm and it emphasizes the need for deeper insight into the molecular mechanisms of hepatotoxicity, especially the interplay of NRF2 with other pathways.

Impact of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) on the expression and function of hepatobiliary transporters: A comprehensive mechanistic review.

The liver plays a central role in the biotransformation and disposition of endogenous molecules and xenobiotics. In addition to drug-metabolizing enzymes, transporter proteins are key determinants of drug hepatic clearance. Hepatic transporters are transmembrane proteins that facilitate the movement of chemicals between sinusoidal blood and hepatocytes. Other drug transporters translocate molecules from hepatocytes into bile canaliculi for biliary excretion. The formers are known as basolateral, while the latter are known as canalicular transporters. Also, these transporters are classified into two super-families, the solute carrier transporter (SLC) and the adenosine triphosphate (ATP)-binding cassette (ABC) transporter. The expression and function of transporters involve complex regulatory mechanisms, which are contributing factors to interindividual variability in drug pharmacokinetics and disposition. A considerable number of liver diseases are known to alter the expression and function of drug transporters. Among them, non-alcoholic fatty liver disease (NAFLD) is a chronic condition with a rapidly increasing incidence worldwide. NAFLD, recently reclassified as metabolic dysfunction-associated steatotic liver disease (MASLD), is a disease continuum that includes steatosis with or without mild inflammation (NASH), and potentially neuroinflammatory pathology. NASH is additionally characterized by the presence of hepatocellular injury. During NAFLD and NASH, drug transporters exhibit altered expression and function, leading to altered drug pharmacokinetics and pharmacodynamics, thus increasing the risk of adverse drug reactions. The purpose of the present review is to provide comprehensive mechanistic information on the expression and function of hepatic transporters under fatty liver conditions and hence, the impact on the pharmacokinetic profiles of certain drugs from the available pre-clinical and clinical literature.

SP-Max-A herbomineral formulation attenuates busulfan-induced oligospermia in mice by preventing loss of reproductive hormones.

SP-Max herbal capsule formulation contains Withania somnifera, Asparagus recemosus, Mucuna pruriens, Chlorophytum arundinaceum, Ipomoea digitata, and Dioscorea bulbifera which are reported in the 'Ayurveda', an Indian Traditional System of medicine as aphrodisiacs. The present study focused on the effect of herbomineral formulation, SP-Max in the treatment of oligospermia. Oligospermia was induced in male Swiss Albino mice by a single intraperitoneal injection of busulfan at a dose of 45 mg/kg. SP-Max herbomineral formulation was given at various doses of 130, 270, and 390 mg/kg for 45 days. Treatment with SP-Max herbomineral formulation at 130, 270 and 390 mg/kg doses significantly improved the sperm count, sperm motility and viability (p < 0.001). SP-Max treatment at a dose of 390 mg/kg significantly prevented the loss of anti-oxidant enzymes in testicular cells. SP-Max prevented the reduction in the level of testosterone, luteinizing hormone, and follicle-stimulating hormone. Histological findings showed that SP-Max treatment prevented degeneration of spermatid, interstitial cells, and Sertoli cells of the testes and also improved epididymal sperm count. High dose of SP-Max treatment i.e 390 mg/kg found to be more effective. Results showed that SP-Max herbomineral formulation is an effective treatment option for oligospermia by decreasing free radical damage to the testes and improving the levels of reproductive hormones.

Pharmacokinetics, pharmacodynamics, toxicity, and formulations of daidzein: An important isoflavone.

Daidzein, 7-hydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one is a naturally occurring compound present in leguminous plants, especially in soybeans. Chemically it belongs to the isoflavone class and possesses high nutritive value. Daidzein acts on estrogen receptor and is non-steroidal in nature hence it can also be called as non-steroidal phytoestrogenic compound. Daidzein has been studied by many researchers for its pharmacological activities. Daidzein metabolites were also studied in detail for their health benefits. Researchers have developed novel formulations of daidzein in the past few years to improve its aqueous solubility and bioavailability. Self-emulsified daidzein, poly(lactic-co-glycolic) acid daidzein nanoparticles, nanoemulsion, nanoemulsion gel, and co-crystals are a few of them. The present review provides detailed information on the chemistry, drug development aspects, pharmacokinetics, and pharmacodynamics of daidzein. A literature search was performed using various datasets like PubMed, EBSCO, ProQuest Scopus, and selected websites including the National Institutes of Health and the World Health Organization. Daidzein has a wide range of pharmacodynamic properties in the treatment of cancer, neurodegenerative disorders, cardiac disorders, diabetes and its complication, osteoporosis, and skin disorders. The pharmacokinetic, pharmacodynamics, and drug development aspects of daidzein will help researchers to design further research work on daidzein in the future.

Correction to: Cardioprotective effect of Hrudroga Chintamani Rasa in isoproterenol induced cardiotoxicity in male Sprague Dawley rats.

[This corrects the article DOI: 10.1007/s40200-022-01012-4.].

Cardioprotective effect of Hrudroga Chintamani Rasa in isoproterenol induced cardiotoxicity in male Sprague Dawley rats.

Purpose: Ayurvedic system, a traditional medicinal system has mentioned a preparation Bruhat Vata Chintamani Rasa (Suvarnayukta) for management of heart diseases. Hrudroga Chintamani Rasa (HCR) is a formulation containing Bruhat Vata Chintamani Rasa and a few additional ingredients having beneficial effects in heart diseases. The present study was designed to investigate the cardioprotective activity of the Hrudroga Chintamani Rasa in isoproterenol (ISO)-induced myocardial infarction in rats. Methods: Male Sprague Dawley rats were treated with HCR at a dose of 56.16 and 112.32 mg/kg for 30 days. Animals received ISO (85 mg/kg. s.c.) on 28th and 29th day at an interval of 24 h. Result: Disease control animals treated with HCR at a dose of 56.16 mg/kg and 112.32 mg/kg to rats showed a significant reduction in elevated levels of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and creatine phosphokinase MB (CK-MB), and prevented loss of depleted antioxidant enzymes from the cardiac tissue. ISO-altered electrocardiogram pattern and haemodynamic parameters were also brought about to normal by treatment with HCR. HCR treatment also improved the levels of 5' adenosine monophosphate-activated protein kinase (AMPK) and Silent information regulator 1 (SIRT1) which have potent role in antioxidant defence mechanism. Histopathological findings also showed HCR treatment prevented cardiac tissue from damage. Conclusion: HCR treatment showed a significant cardioprotective effect in ISO-induced cardiotoxicity in rats probably because of the potent antioxidant activity. Supplementary information: The online version contains supplementary material available at 10.1007/s40200-022-01012-4.

Daidzein attenuates urinary bladder dysfunction in streptozotocin-induced diabetes in rats by NOX-4 and RAC-1 inhibition.

Reactive oxygen species via NADPH oxidase (NOX) activation are involved in the pathogenesis of many disease conditions such as diabetes and its complications. In the present study, we have examined the effect of daidzein in the management of diabetic cystopathy. Diabetes was induced in male Sprague Dawley rats via intraperitoneal injection of streptozotocin (STZ) at a dose of 55 mg/kg. After 6 weeks of diabetes induction, animals were treated with daidzein orally at a dose of 25, 50, and 100 mg/kg for 4 weeks. Diabetic animals showed increase (p < 0.001) in bladder capacity (4.32 ± 0.43 mL) and residual volume (2.53 ± 0.19 mL) when compared with normal control animals (2.10 ± 0.40 mL and 0.51 ± 0.12 mL res). Treatment with daidzein at dose of 50 and 100 mg/kg significantly reduced the elevated bladder capacity (2.91 ± 0.11 mL, p < 0.01 and 2.65 ± 1.13 mL, p < 0.001) and residual volume (1.40 ± 0.15 mL, p < 0.001 and 1.15 ± 0.05 mL, p < 0.001). Daidzein-treated animals also showed improvement in voiding efficiency. Elevated threshold and baseline pressure were also found to be reduced in diabetic animals after 4 weeks of daidzein treatment. Daidzein treatment also prevented the loss of antioxidant enzymes in the urinary bladder and also reduced the expression of NOX-4 and RAC-1 in the bladder. From the results, it can be concluded that daidzein showed a beneficial effect on urinary bladder dysfunction in diabetic animals.

In-vivo and in-silico toxicity studies of daidzein: an isoflavone from soy.

Daidzein is a naturally occurring compound belonging to the class isoflavones and found in soya beans and other legumes. Acute oral toxicity was performed as per OECD guideline (TG 423) with slight modifications. A repeated dose toxicity study was carried out as per OECD guideline (TG 407). In-silico toxicity such as AMES toxicity, carcinogenicity, mutagenicity, immunotoxicity, hepatotoxicity, skin irritation, reproductive effect, rat and mouse toxicity, LD50, hERG I, II inhibitor and minnow toxicity were predicted using online servers and tools. In an acute oral toxicity study, daidzein did not show any mortality in experimental animals. The No Observed Adverse Effect Level (NOAEL) of daidzein was found to be above 5000 mg/kg. 28 days treatment of diadzein at all doses did not show changes in hematology parameters, clinical biochemistry and kidney function parameters. Gross necropsy or histopathology of important organs showed no signs of toxicity. In-silico predicted parameters also demonstrated risks ranging from low to a nontoxic level. Thus, daidzein was found to be safe in acute and repeated oral dose toxicity studies at all selected doses. In-silico study also indicated that daidzein is safe.

Neuroprotective effect of Bauhinia variegata Linn. leaf extracts in streptozotocin induced diabetes in Sprague Dawley rats.

BACKGROUND: Bauhinia variegata, a ayurvedic medicinal plant reported for its valuable effects in various diseases. It has shown significant effects in type 1 and type 2 diabetes. OBJECTIVE: The present work was designed to study effects of aqueous and alcoholic extract (AE and AlcE) of Bauhinia variegata Linn. leaves in diabetic neuropathy. METHODS: Male Sprague Dawley rats become diabetic using intraperitoneal injection of streptozotocin (STZ) at 55 mg/kg dose. After 6 weeks, animals were divided and were treated with AE and AlcE at a dose of 250, 500, and 1000 mg/kg (p. o.) for the next four weeks. Various parameters such as glucose, thermal hyperagesia, mechanical allodynia, MNCV and oxidative stess were assessed at the end of the study. RESULTS: Diabetic animals showed a significant reduction in response time in tail immersion and hot plate test as compared to animals in normal control group. AE and AlcE at 250, 500, and 1000 mg/kg dose significantly increased response time in the tail immersion test. Whereas, AE and AlcE at doses 500 and 1000 mg/kg showed significant improvement and in response time in the hot plate test.AlcE at 250, 500 and 1000 mg/kg dose increased the nociceptive threshold significantly. AE at doses 500 and 1000 mg/kg showed significant improvement in the nociceptive threshold. The decrease in motor nerve conduction velocity was observed in diabetic control animals, which was significantly improved after AlcE treatment as compared to AE treatment. Treatment with AE and AlcE decreased the lipid peroxidation and increased the antioxidant enzyme activity significantly in the sciatic nerve. CONCLUSION: The results showed that Bauhinia variegata extracts may be considered as a effective option for management of diabetic neuropathy.

Daidzein mitigates myocardial injury in streptozotocin-induced diabetes in rats.

AIM: Present study focuses on the effect of daidzein in an experimental model of diabetic cardiomyopathy in rats. MATERIALS AND METHODS: Diabetes was induced in male Sprague Dawley rats by a single intraperitoneal injection of STZ at dose 55 mg/kg. Daidzein treatment was started after six weeks of diabetes induction. Animals received daidzein at a dose of 25, 50, and 100 mg/kg orally for the next four weeks. KEY FINDINGS: Diabetic control animals showed significant prolongation in QT interval, PR interval, and R wave amplitude as compared to normal control animals. Treatment with daidzein at dose 100 mg/kg significantly normalized the QT interval, PR interval, and R wave amplitude. A significant reduction in QRS duration was observed in diabetic animals. Treatment with daidzein significantly improved the QRS duration after treatment. Hemodynamic parameters like systolic pressure (SBP), diastolic pressure (DBP) and mean atrial pressure (MAP) were found to be significantly decreased in diabetic animals. Treatment with daidzein at dose 100 mg/kg significantly improved the SBP, DBP, and MAP. Daidzein treatment prevented the loss of cardiac marker enzyme from heart tissue and also increased the level of AMPK and SIRT1 in plasma. Protein expression of NOX-4 and RAC-1 was also found to be reduced in cardiac tissue of daidzein treated animals. Daidzein treatment improved oxidative defense mechanism and reduced cardiac tissue necrosis and fibrosis. SIGNIFICANCE: From the results, it can be concluded that daidzein mitigates the progression of diabetic cardiomyopathy by inhibiting NOX-4 induced oxidative stress in cardiac tissue.

Role of dietary modifications in the management of type 2 diabetic complications.

Diabetes is a chronic metabolic disorder with a high rate of morbidity and mortality. Insufficient insulin secretion and insulin action are two major causes for the development of diabetes, which is characterized by a persistent increase in blood glucose level. Diet and sedentary life style play pivotal role in development of vascular complications in type 2 diabetes. Dietary modification is associated with a reprogramming of nutrient intake, which are proven to be effective for the management of diabetes and associated complications. Dietary modifications modulate various molecular key players linked with the functions of nutrient signalling, regulation of autophagy, and energy metabolism. It activates silent mating type information regulation 2 homolog1 (SIRT1) and AMP-activated protein kinase (AMPK). AMPK mainly acts as an energy sensor and inhibits autophagy repressor Mammalian target of rapamycin (mTOR) under nutritional deprivation. Under calorie restriction (CR), SIRT1 gets activated directly or indirectly and plays a central role in autophagy via the regulation of protein acetylation. Dietary modification is also effective in controlling inflammation and apoptosis by decreasing the level of pro-inflammatory cytokines like nuclear factor kappa- beta (NF-kß), tissue growth factor-beta (TGF-ß), tissue necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). It also improves glucose homeostasis and insulin secretion through beta cell regeneration. This indicates calorie intake plays a crucial role in the pathogenesis of type 2 diabetes-associated complications. The present review, emphasizes the role of dietary modifications in diabetes and associated complications.

Pharmacology of apocynin: a natural acetophenone.

Apocynin is a naturally occurring acetophenone, found in the roots of Apocynum cannabinum and Picrorhiza kurroa. Various chemical and pharmaceutical modifications have been carried out to enhance the absorption and duration of action of apocynin, like, formulation of chitosan-based apocynin-loaded solid lipid nanoparticles, chitosan-oligosaccharide based nanoparticles, and biodegradable polyanhydride nanoparticles. Apocynin has been subjected to a wide range of experimental screening and has proved to be useful for amelioration of a variety of disorders, like diabetic complications, neurodegeneration, cardiovascular disorders, lung cancer, hepatocellular cancer, pancreatic cancer, and pheochromocytoma. Apocynin has been primarily reported as an NADPH oxidase (NOX) inhibitor and prevents translocation of its p47phox subunit to the plasma membrane, observed in neurodegeneration and hypertension. However, recent studies highlight its off-target effects that it is able to function as a scavenger of non-radical oxidant species, which is relevant for its activity against NOX 4 mediated production of hydrogen peroxide. Additionally, apocynin has shown inhibition of eNOS-dependent superoxide production in diabetic cardiomyopathy, reduction of NLRP3 activation and TGFß/Smad signaling in diabetic nephropathy, diminished VEGF expression and decreased retinal NF-κB activation in diabetic retinopathy, inhibition of P38/MAPK/Caspase3 pathway in pheochromocytoma, inhibition of AKT-GSK3ß and ERK1/2 pathways in pancreatic cancer, and decreased FAK/PI3K/Akt signaling in hepatocellular cancer. This review aims to discuss the pharmacokinetics and mechanisms of the pharmacological actions of apocynin.

Daidzein ameliorates diabetic retinopathy in experimental animals.

AIM: The present study was designed to check the effect of daidzein in the management of diabetic retinopathy. MAIN METHODS: Streptozotocin at dose 55 mg/kg was used for inducing diabetes in rats. After 28 days of diabetic induction, animals were treated with daidzein at dose 25, 50, and 100 mg/kg for the next 28 days. Electroretinography, estimation of plasma glucose, lactate dehydrogenase, aldose reductase, sorbitol dehydrogenase and oxidative stress parameters were performed at the end of the study. Histopathology of retina was carried out at the end of the study. KEY FINDINGS: Diabetic control animals showed a significant increase in levels of plasma glucose and plasma lactate dehydrogenase (p < 0.001). Treatment with daidzein at a dose of 50 and 100 mg/kg significantly reduced the elevated level of blood glucose (p < 0.01 and p < 0.01). Whereas, treatment with daidzein at a dose 100 mg/kg significantly reduced the elevated level of lactate dehydrogenase in plasma after 28 days of treatment (p < 0.01). Treatment with daidzein at a dose of 100 mg/kg significantly reduced the level of aldose reductase and sorbitol dehydrogenase (p < 0.01 and p < 0.001 respectively). Electroretinography revealed that daidzein treatment at a dose of 100 mg/kg significantly prevented the change in 'a' and 'b' wave amplitude and latency. Oxidative stress was also found to be significantly reduced after 28 days of daidzein treatment. Histopathological findings showed a reduction in retinal thickness after daidzein treatment. SIGNIFICANCE: Daidzein treatment protected retina from damage in hyperglycaemic conditions. Thus, Daidzein can be considered as an effective treatment option for diabetic retinopathy.

Development and Validation of HPLC Method for Determination of Sodium Copper Chlorophyllin - A Food Colorant and Its Application in Pharmacokinetic Study.

A simple, accurate, and precise bioanalytical method was developed and validated for the determination of pharmacokinetic parameters of sodium copper chlorophyllin, a USFDA approved food additive and colorant in rat plasma. The column used was Luna® C18 250×4.6 mm, 100 Å, having particle size 4.5 µm, and the mobile phase used was methanol (MeOH), and 10 mM ammonium acetate buffer in the ratio of 90 : 10, the flow rate was 1 ml/min, and the injection volume of 20 µL. The retention time of sodium copper chlorophyllin was obtained at 9 min. The method was found to be linear at the range of 0.50-8.00 µg mL-1 .

NADPH oxidase: A membrane-bound enzyme and its inhibitors in diabetic complications.

The human body has a mechanism for balancing the generation and neutralization of reactive oxygen species. The body is exposed to many agents that are responsible for the generation of reactive oxygen/nitrogen species, which leads to disruption of the balance between generation of these species and oxidative stress defence mechanisms. Diabetes is a chronic pathological condition associated with prolonged hyperglycaemia. Prolonged elevation of level of glucose in the blood leads to the generation of reactive oxygen species. This generation of reactive oxygen species is responsible for the development of diabetic vasculopathy, which includes micro- and macrovascular diabetic complications. Nicotinamide adenine dinucleotide phosphate oxidase (NOX) is a membrane-bound enzyme responsible for the development of reactive oxygen species in hyperglycaemia. Phosphorylation of the cytosolic components of NOX, such as p47phox, p67phox, and RAC-1, in hyperglycaemia is one of the important causes of conversion of oxygen to reactive oxygen. Overexpression of NOX in pathological conditions is associated with activation of aldose reductase, advanced glycation end products, protein kinase C and the hexosamine pathway. In addition, NOX also promotes the activation of inflammatory cytokines, such as TGF-ß, TNF-α, NF-kß, IL-6, and IL-18, the activation of endothelial growth factors, such as VEGF and FGF, hyperlipidaemia, and the deposition of collagen. Thus, overexpression of NOX is linked to the development of diabetic complications. The present review focuses on the role of NOX, its associated pathways, and various NOX inhibitors in the management and treatment of diabetic complications, such as diabetic nephropathy, retinopathy, neuropathy and cardiomyopathy.

VEGF and FGF-2: Promising targets for the treatment of respiratory disorders.

The endothelial cells play a crucial role in the progression of angiogenesis, which causes cell re-modulation, proliferation, adhesion, migration, invasion and survival. Angiogenic factors like cytokines, cell adhesion molecules, growth factors, vasoactive peptides, proteolytic enzymes (metalloproteinases) and plasminogen activators bind to their receptors on endothelial cells and activate the signal transduction pathways like epidermal growth factor receptor (EGFR phosphatidylinositol 3-kinase and (PI3K)/AKT/mammalian target of rapamycin (mTOR) which initiate the process of angiogenesis. Cytokines that stimulate angiogenesis include direct and indirect proangiogenic markers. The direct proangiogenic group of markers consists of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF-2) and hepatocyte growth factor (HGF) whereas the indirect proangiogenic markers include transforming growth factor-beta (TGF-ß), interleukin 6 (IL-6), interleukin 8 (IL-8) and platelet-derived growth factor (PDGF). VEGF and FGF-2 are the strongest activators of angiogenesis which stimulate migration and proliferation of endothelial cells in existing vessels to generate and stabilize new blood vessels. VEGF is released in hypoxic conditions as an effect of the hypoxia-inducible factor (HIF-1α) and causes re-modulation and inflammation of bronchi cell. Cell re-modulation and inflammation leads to the development of various lung disorders like pulmonary hypertension, chronic obstructive pulmonary disease, asthma, fibrosis and lung cancer. This indicates that there is a firm link between overexpression of VEGF and FGF-2 with lung disorders. Various natural and synthetic drugs are available for reducing the overexpression of VEGF and FGF-2 which can be helpful in treating lung disorders. Researchers are still searching for new angiogenic inhibitors which can be helpful in the treatment of lung disorders. The present review emphasizes on molecular mechanisms and new drug discovery focused on VEGF and FGF-2 inhibitors and their role as anti-angiogenetic agents in lung disorders.

Tannins and vascular complications of Diabetes: An update.

BACKGROUND: Diabetes mellitus is a chronic metabolic disorder associated with persistent increased level of glucose in the blood. According to a report by World Health Organisation (WHO), prevalence of diabetes among adults over 18 years of age had reached to 8.5% in year 2014 which was 4.7% in 1980s. The Prolong increased level of glucose in blood leads to development of microvascular (blindness, nephropathy and neuropathy) and macrovascular (cardiovascular and stroke) degenerative complications because of uncontrolled level of glucose in blood. This also leads to the progression of oxidative stress and affecting metabolic, genetic and haemodynamic system by activation of polyol pathway, protein kinase C pathway, hexosamine pathway and increases advanced glycation end products (AGEs) formation. Diabetes mellitus and its associated complications are one of the major leading causes of mortality worldwide. Various natural products like alkaloids, glycosides, flavonoids, terpenoids and polyphenols are reported for their activity in management of diabetes and its associated diabetic complications. Tannins are systematically studied by many researchers in past few decades for their effect in diabetes and its complications. AIM: The present review was designed to compile the data of tannins and their beneficial effects in the management of diabetic complications. METHOD: Literature search was performed using various dataset like pubmed, EBSCO, proQuest Scopus and selected websites including the National Institutes of Health (NIH) and the World Health Organization (WHO). RESULTS: Globally, more than 400 natural products have been investigated in diabetes and its complications. Tannins are the polyphenolic compounds present in many medicinal plants and various dietary sources like fruits, nuts, grains, spices and beverages. Various reports have shown that compounds like gallic acid, ellagic acid, catechin, epicatechin and procynidins from medicinal plants play major role in controlling progression of diabetes and its related complications by acting on molecular pathways and key targets involved in progression. Many chemists used above mentioned phyto-constituents as a pharmacophore for the developing new chemical entities having higher therapeutic benefits in management of diabetic complications. CONCLUSION: This review focuses on the role of various tannins in prevention and management of diabetic complications like diabetic nephropathy, diabetic neuropathy, diabetic retinopathy and diabetic cardiomyopathy. It will help researchers to find some leads for the development of new cost effective therapy using dietary source for the management of diabetic complications.