Ankit Laddha - Academia.edu (original) (raw)

Papers by Ankit Laddha

Pharmacognosy Magazine, 2020

Context: Tinospora cordifolia (Willd.) Miers is an antidiabetic herb globally marketed as a singl... more Context: Tinospora cordifolia (Willd.) Miers is an antidiabetic herb globally marketed as a single or polyherbal formulation. The pharmacological activities of T. cordifolia suggest its potential to be co-administered with commonly prescribed oral hypoglycemic drugs in the therapeutic management of diabetes mellitus. Aims: The aim of this study was to evaluate the potential pharmacokinetic (PK) and pharmacodynamic (PD) interactions of the aqueous extract of T. cordifolia (TCE) with metformin (MET), sitagliptin (SITA), and glibenclamide (GLI) in streptozotocin (STZ)-induced diabetes in rats. Settings and Design: The aqueous TCE (400 mg/kg, p.o.) was co-administered with MET (90 mg/kg, p. o.), SITA (10 mg/kg, p. o.), and GLI (1 mg/kg, p. o.) for 28 days in STZ-induced diabetes in rats. Materials and Methods: The PK parameters of the three drugs were calculated using Phoenix WinNonlin®, and PD activity was determined by estimating fasting blood glucose, liver and kidney function tests, and lipid parameters. Further, histopathological examination of pancreatic cells and estimation of pancreatic antioxidant enzymes was carried out. Statistical Analysis Used: The pharmacokinetic parameters were estimated using pharmacokinetic program WinNonlin® version 3.0 (Pharmasight corporation, Mountain view, CA). The pharmacodynamic parameters were analysed using Graph Pad prism Version 6.00 applying one-way ANOVA followed by the Tukey–Kramer post test. Results: No significant PK interaction was observed between TCE and the three oral hypoglycemics. However, a significant improvement was observed in glycemic control and the conditions associated with diabetes mellitus. In addition, no incidences of hypoglycemia were observed. Conclusion: The co-administration of TCE with MET, SITA, and GLI helped in better management of diabetes and associated comorbidities than their individual administrations. There were no significant PK interactions observed. Our findings provide insights into the safety and efficacy of the combination therapy of TCE with MET, SITA, and GLI in the management of diabetes and associated conditions.

Journal of Traditional and Complementary Medicine, Oct 1, 2019

Eugenia jambolana (EJ) is an Indian traditional herb widely used for the treatment of diabetes me... more Eugenia jambolana (EJ) is an Indian traditional herb widely used for the treatment of diabetes mellitus. This herb is globally marketed as single or multi herb formulations. Many diabetes patients consume EJ extract oral hypoglycemic drugs together. This calls for a need to assess risks versus benefit of this coadministration. In present investigation, pharmacodynamic and pharmacokinetic interactions of aqueous extract of EJ seeds at the dose of 400 mg/kg are studied with 10 mg/kg of oral hypoglycaemic drug sitagliptin (SITA) by co-administrating them for 28 days in streptozotocin (STZ) induced diabetic rats. The pharmacokinetic parameters of SITA were determined using HPLC-ESI-MS/MS and it was found that the combination treatment reduces the systemic exposure of SITA by showing 38.70% reduction in concentration maximum (Cmax) and 22.40% reduction in area under curve (AUC). Despite low levels of SITA, the combination demonstrated a significant reduction in blood glucose level when compared with individual drug and individual extract administered groups during pharmacodynamic study. In addition, the liver function, the kidney function and the lipid parameters were found to be significantly improved and beneficial effects were found with respect to food intake and water intake and urine output in case of combination treatment groups when compared with individual treatment groups. Histopathological examination of pancreatic tissue suggests its significant recovery of having normal acinus with better cell protection in combination treatment. In conclusion, the combination treatment demonstrated reduced systemic exposure of SITA without compromising on its antihyperglycemic activity and improvement in conditions associated with diabetes.

Trends in Pharmacological Sciences, Jul 1, 2022

South African Journal of Botany, Aug 1, 2020

Hyperglycemia, hyperlipidemia, and oxidative stress are an important pathological conditions in d... more Hyperglycemia, hyperlipidemia, and oxidative stress are an important pathological conditions in diabetes which are linked with the progression of diabetic cardiomyopathy. Cardiomyopathy is considered as one of the major cause of mortality in diabetic patients. The present study focuses on the effect of Bauhinia variegata Linn leaves in the management of diabetic cardiomyopathy. Alcoholic extract of Bauhinia variegata Linn leaves (AlcE) was prepared and standardized using liquid chromatography-mass spectroscopy (LC-MS) analysis. Male Sprague Dawley rats received a single intraperitoneal injection of streptozotocin (55 mg/kg) for induction of diabetes. After 6 weeks of diabetes induction, animals were treated with AlcE at the dose of 250, 500 and 1000 mg/kg by oral route for next 28 days. Diabetic control animals showed a significant increased level of blood glucose (P<0.001) when compared with normal control. Treatment with AlcE at dose 500 and 1000 mg/ kg significantly reduced the elevated blood glucose (521.0 § 8.40 and 459.3 § 49.42, respectively) after 28 days of treatment (p<0.05 and p<0.001). Diabetic control group also showed significant increased level of cardiac marker enzyme-like aspartate transaminase (299.7 § 17.0), lactate dehydrogenase (1235 §40.39), creatinine kinase-MB (1081 §42.49) in plasma. Treatment with AlcE at dose 1000 mg/kg significantly reduced the elevated level of aspartate transaminase (194.4 § 12.27), lactate dehydrogenase (872.3 § 28.58) and creatinine kinase-MB (735.5 § 38.35) (p<0.001, p<0.001 and p<0.001, respectively). Elevated lipid markers like total cholesterol and triglyceride were found to be significantly attenuated after AlcE treatment at dose 1000 mg/kg (p<0.001 and p<0.05, respectively). AlcE treatment also significantly prevented the loss of antioxidant enzymes like superoxide dismutase, catalase and glutathione and reduced formation of lipid malondialdehyde in cardiac tissue (p<0.01, p<0.00, p<0.001 and P<0.001). Restoration of altered electrocardiogram pattern and hemodynamic parameters were also observed after AlcE treatment. Histopathological findings indicated that AlcE treatment prevented cardiac tissue from necrotic damage and collagen deposition. Form the results, it can be concluded that Bauhinia variegata extract is having significant effect in the management of diabetic cardiomyopathy.

Pharmacological Research, Jun 1, 2021

Diabetes is a chronic metabolic disorder with a high rate of morbidity and mortality. Insufficien... more 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 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-kβ), tissue growth factor-beta (TGF-β), 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.

Phytomedicine, Mar 1, 2019

The present review was designed to compile the data of tannins and their beneficial effects in th... more 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 researchers to find some leads for the development of new cost effective therapy using dietary source for the management of diabetic complications.

Drug and Chemical Toxicology, Oct 15, 2020

Abstract Daidzein is a naturally occurring compound belonging to the class isoflavones and found ... more Abstract 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.

Life Sciences, 2021

For José Nuno Oliveira, on his 60th birthday A classical result in algebraic specification states... more For José Nuno Oliveira, on his 60th birthday A classical result in algebraic specification states that a total function defined on an initial algebra is a homomorphism if and only if the kernel of that function is a congruence. We expand on the discussion of that result from an earlier paper: extending it from total to partial functions, simplifying the proofs using relational calculus, and generalising the setting to regular categories.

European Journal of Pharmacology, Aug 1, 2020

The human body has a mechanism for balancing the generation and neutralization of reactive oxygen... more 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-β, TNF-α, NF-kβ, 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.

Journal of diabetes and metabolic disorders, Jun 3, 2022

The FASEB Journal, Apr 1, 2020

Diabetic nephropathy is one of the major complications of diabetes which is responsible for 40% o... more Diabetic nephropathy is one of the major complications of diabetes which is responsible for 40% of death among diabetes population. In persistent hyperglycaemia, nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) causes overproduction of reactive oxygen species in podocytes, endothelial cells and mesangial cells in glomeruli. It plays a key role in progression of diabetic nephropathy. Many natural products are widely been studied in management diabetic nephropathy. Daidzein is an isoflavone present in leguminous plants and has been reported for anti‐oxidant, anti‐inflammatory and anti‐apoptotic activity. Present study was designed to observe effect of daidzein in experimental model of diabetic nephropathy in rats. Streptozotocin was used for induction of diabetes in male Sprague Dawley rats at dose of 55 mg/kg, intraperitoneally. After 28 days of diabetic induction, animals were treated with daidzein at dose of 25, 50 and 100 mg/kg, orally for next 28 days. Biochemical parameters and urine parameters were assessed at the end of study. Kidney function parameters like glomerular filtration rate, creatinine clearance, urea clearance and oxidative stress marker in kidney tissue were evaluated. Histopathology of kidney tissue was studied using haematoxylin‐eosin staining. Diabetic animal showed significant increase in plasma biochemical parameters like creatinine and blood urea nitrogen (p<0.001). Treatment with daidzein at high dose (100 mg/kg) for 28 days showed significant reduction in elevated levels of creatinine and blood urea nitrogen (p<0.01 and p<0.001). Reduced level of total protein and albumin in diabetic animals was also significantly increased after daidzein treatment at high dose (p<0.01 and p<0.05). Urine creatinine and urine urea were significantly improved in daidzein treated animals as compared to diabetic control animals (p<0.01 and p<0.05). Kidney function parameters like urea clearance, creatinine clearance and glomerular filtration rate were significantly (p<0.001) reduced in diabetic control animals. Treatment with diadzein for 28 days significantly improved kidney function. Loss of anti‐oxidant enzymes like glutathione, catalase and superoxide dismutase was prevented and generation of malondialdehyde was inhibited in kidney tissue of diabetic animals treated with daidzein. Daidzein treatment also ameliorates histological changes in diabetic rats. From results, it can be concluded that daidzein attenuates progression of diabetic nephropathy and can be a considered as effective management option for diabetic nephropathy.

Life Sciences, Nov 1, 2021

AIM Present study focuses on the effect of daidzein in an experimental model of diabetic cardiomy... more 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 daidzein treated animals. Daidzein treatment maintained oxidative defense mechanism and prevented cardiac tissue from necrosis and fibrosis. SIGNIFICANCE From all the results, it can be concluded that daidzein mitigates the progression of diabetic cardiomyopathy by inhibiting NOX-4 induced oxidative stress in cardiac tissue.

Respiratory Medicine, Sep 1, 2019

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

The FASEB Journal, Apr 1, 2019

Phytotherapy Research, Apr 28, 2023

Naunyn-Schmiedeberg's Archives of Pharmacology

Journal of Diabetes & Metabolic Disorders, 2022

Purpose Ayurvedic system, a traditional medicinal system has mentioned a preparation Bruhat Vata ... more 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.