EFFECT OF TERMINALIA CHEBULA (HARAD) FRUIT EXTRACT ON CARDIOTOXICITY IN STREPTOZOTOCIN INDUCED DIABETIC RATS

Objective: The aim of the study was to explore the protective activity of Terminalia chebula fruit extract on cardiotoxicity in streptozotocin (STZ) induced diabetic rats.Methods: The animals were divided into eight groups of five each and were fed with high fat diet (HFD) except sham control, diabetic control and isoproterenol control. Diabetes was induced by administering single intraperitoneal (i. p.) injection of STZ (0.05 g/kg) in all groups except sham and isoproterenol control and was confirmed by testing blood glucose level after 48 h. Rats were pretreated with ethanolic extract of Terminalia chebula (0.25& 0.5 g/kg/d; per oral (p. o.)), pioglitazone (0.01 g/kg/d), carvedilol (0.002 g/kg/d) and normal saline throughout the study period (14 days). Cardiotoxicity was induced by the administrating two subcutaneous (s. c) injection of isoproterenol (ISO) (0.085 g/kg) at an interval of 24 h. Troponin was checked to confirm cardiotoxicity. The evaluation parameters include initial and final blood glucose level, change in body weight, food efficiency ratio (FER), heart weight-body weight ratio, biochemical estimations and histopathological studies.Results: Pretreatment with Terminalia chebula produced significant (p<0.01) decrease in blood glucose level and heart weight-body weight ratio. It significantly decrease the elevated activity of the cardiac marker enzymes, alanine transaminase (ALT), lactate dehydrogenase (LDH), creatinine kinase (CK-MB) (p<0.01), similar to the standard drug carvedilol in isoproterenol injected rats. Pretreatment with Terminalia chebula showed absence of troponin and lesser degree of necrosis, edema, and myofibrillar degeneration.Conclusion: Terminalia chebula has significant cardioprotective action against cardiotoxicity in STZ induced diabetic rats, which is comparable with standard drugs i.e., pioglitazone and carvedilol.Â

A COMPREHENSIVE STUDY ON LITERATURE EVIDENCE, CLINICAL STUDIES AND PRACTICES OF HERBAL DRUGS FOR DIABETIC NEUROPATHY AND CARDIOMYOPATHY

  Diabetes mellitus is a worldwide epidemic disease that eventually advances to a chronic stage and affects different vital organs by intensifying the underlying pathological factors, and through the remodeling of the tissues by the generation of reactive oxygen species leading to the development of respective organ failure. Two such complications are painful neuropathy and cardiomyopathy; both of which are common and progressive complications of diabetes. The symptoms of peripheral neuropathy include tingling, burning, lancinating pain, hyperesthesia, and allodynia. The course of the disease progression may vary from intermittent, mild symptoms to severe chronic, and daily pain; which culminates into poor quality of life. Another complication of diabetes mellitus, diabetic cardiomyopathy, is defined as a ventricular dysfunction disorder that occurs in diabetic patients. The development of the disease is characterized by a hidden subclinical period, during which cellular, structural changes and abnormalities lead to diastolic dysfunction, followed by systolic dysfunction, and terminating into heart failure. Left ventricular hypertrophy, metabolic abnormalities, extracellular matrix changes, small vessel disease, cardiac autonomic neuropathy, insulin resistance, oxidative stress, and apoptosis are the most important pathological advancements that lead to diabetic cardiomyopathy. Various pharmaceutical agents from different pharmacological categories have been proposed for the symptomatic treatment of painful diabetic neuropathy; however, it is a herculean task to select a drug due to the wide range of choices and lack of consistent guidelines for treatment. Similarly, treatment of cardiomyopathy is based on the general therapeutic rules of management of heart failure and no specifications have yet been addressed for this condition. Therefore, more studies are required to improve our knowledge of these complex syndromes. From this perspective, this review is designed to delineate a general overview of neuropathy and cardiomyopathy, referring to the conventional therapies in use and possible unconventional, natural, herbal, and safe treatments for both the above-mentioned complications of diabetes

A Clinical Insight into Gestational Diabetes

Pregnancy is a diabetogenic state manifested by insulin resistance and hyperglycaemia. The age group at risk of getting gestational diabetes is between 20 and 39 years in 96.8% of cases. Gestational diabetes is the development of symptoms and signs of diabetes mellitus during pregnancy and the glucose level reverting to normal during puerperium. Depending on the type of population and the diagnostic criteria used, gestational diabetes is said to complicate 1–16% of all pregnancies. Many researchers in American, European and Asian surveys have reported 3–6% of prevalence. Compared with white European women, the prevalence rate for GD is increased approximately elevenfold in women from the Indian subcontinent, eightfold in South East Asia, sixfold and threefold in Arab and black Afro-Caribbean women, respectively. Such figures draw a potent clinical interest towards gestational diabetes (GD), and this chapter attempts to highlight some major aspects of GD in respect to both the mother and the foetus or the newborn specially emphasizing on its management as per the World Health Organization (WHO) and International Federation of Gynaecology and Obstetrics (FIGO)

EFFECT OF ETHANOLIC EXTRACT OF GLYCYRIZZA GLABRA AGAINST STEREPTOZOTOCIN AND HIGH FAT DIET INDUCED DIABETES AND HYPERLIPIDEMIA

Objective: To study the effect of ethanolic extract of Glycyrrhiza glabra against streptozotocin and high-fat-diet-induced diabetes and hyperlipidemia.Methods: The present study was conducted on a 14 d model in which Glycyrrhiza glabra extract was given to Streptozotocin (STZ; 50 mg/kg; i. p.) induced diabetic rats fed with high fat diet (HFD), and its protective effect has been studied. The antihyperlipidemic and antihyperglycemic effects have been evaluated on the basis of physical, biochemical as well as histomorphological parameters.Results: The Glycyrrhiza glabra extract pre-treated group showed a significant decrease in biochemical parameters like Total cholesterol (TC), Triglyceride (TG), High-density lipoprotein (HDL), Lactate dehydrogenase(LDH), Alanine transaminase (ALT) compared with D-HFD group (p<0.01). The pre-treated groups also showed significant protection in physical parameters as compared to D-HFD group (p<0.01) which was also confirmed by histopathological studies. All these results were compared and found to be similar with two standard drugs metformin (500 mg/kg) and atorvastatin (10 mg/Kg).Conclusion: This study concluded that alcoholic extract of Glycyrrhiza glabra (500 mg/kg) has significant antidiabetic and antihyperlipidemic potential against streptozotocin and high-fat diet induced diabetic hyperlipidemic rats comparable to the clinically used drugs.Keywords: Atherosclerosis, Diabetic hyperlipidemia, Diabetes mellitus, Hyperlipidemia, Lipid profile, Streptozotoci

A conglomeration of preclinical models related to myocardial infarction

Cardiovascular diseases are the main source of death and morbidity in developed and developing nations. Animal models are required to propel our understanding of the pathogenesis, increase our knowledge, disease progress, and mechanism behind cardiovascular disorder, providing new approaches focused to improve the diagnostic and the treatment of these pathological conditions and additionally to test various therapeutic ways to deal with tissue regeneration and re-establish heart working following damage. A perfect model framework ought to be reasonable, effectively controlled, reproducible, and physiologically illustrative of human disease, show cardinal signs and pathology that resembles after the human ailment and ethically stable. The decision of selection of animal model should be considered precisely since it influences exploratory results and whether results of the research can be sensibly matched with the human. In this way, no specific technique splendidly reproduces the human disease, and relying upon the model, extra cost burden, resources, infrastructure and the necessity for technical hands, should also be kept under consideration. Here we have discussed and compiled various methods of inducing myocardial infarction in animals, basically by surgery, chemicals and through genetic modification, this may benefit the researchers in getting a complied data regarding various methods through which they can induce myocardial infarction in animals

Lipids: An insight into the neurodegenerative disorders

Summary: Brain development is a sequential anatomical process characterised by specific well-defined stages of growth and maturation. One of the fundamental and necessary events in the normal development of the central nervous system in vertebrates is the formation of a myelin sheath. This process is influenced by dietary lipids. A number of researches have indicated that the administration of a diet, deficient in essential fatty acids during development causes hypomyelination in the brain. Brain lipids determine the localization and function of proteins in the cell membrane and in doing so regulate synaptic signalling in neurons. Lipids may also function as transmitters and relay signals from the membrane to intracellular compartments or to other cells. Several experimental studies have suggested a crucial role of n-3 polyunsaturated fatty acids in membrane formation, as well as clinical role of glycerolipids, glycerophospholipids, and sphingolipids in the attenuation of depression- and anxiety-related behaviours. Hence it can be assumed that polyunsaturated fatty acids may also offer new treatment options (for example, targeted dietary supplementation or pharmacological interference with lipid-regulating enzymes). These lipids could be exploited for improved prevention and treatment. A very interesting and emerging approach in this direction is through ‘Lipidomics’ which is a relatively recent research field that has been driven by rapid advances in technologies such as mass spectrometry (MS), nuclear magnetic resonance (NMR) spectroscopy, fluorescence spectroscopy, dual polarisation interferometry and computational methods, coupled with the recognition of the role of lipids in many metabolic diseases such as obesity, atherosclerosis, stroke, hypertension and diabetes. Keywords: Glycerolipids, Glycolipids, Polyunsaturated fatty acids, Neurodegenerative disorders, Sphingolipid

PREPARATION, CHARACTERIZATION AND SAFETY ASSESSMENT OF COMBINATORIAL NANOPARTICLES OF CARVEDILOL AND SERICIN

Objective: The objective of the study is to prepare and evaluate the safety assessment of novel combinatorial Nanoparticle formulation. Methods: Chitosan nanoparticles were prepared by the ionic gelation method with slight modification. Drug-drug interaction was evaluated by Fourier Transform Infra-Red Spectroscopy. Size, Polydispersity Index, Zeta potential, Transmission Electron Microscopy Characterizations were performed as per standard procedures. Acute and subacute toxicity assessments were done by the standard protocol of OECD guideline number 425 and 407, respectively. Results: Size and zeta-potential were found to be 186.7 nm and-12.0mV, respectively. TEM analysis showed uniform, smooth, and spherical-sized particles. FTIR analysis of carvedilol, sericin, and physical mixture showed no interaction between them. The safety evaluation of prepared nanoparticle which was found to be safe at a dose of up to 1000 mg/kg body weight in single-dose acute toxicity and multiple-dose subacute toxicity study. Biochemical estimations were statistically evaluated and no significant differences were found that the mean P-value is greater than 0.05 and Histopathological examination has shown no marked disparity when compared to the normal control group. Conclusion: It can be concluded that the prepared Nanoparticles are safe in rodents and can be preceded for further evaluation for its preclinical cardioprotective potential

Fabrication of Nanoformulation Containing Carvedilol and Silk Protein Sericin against Doxorubicin Induced Cardiac Damage in Rats

Nanotechnology has emerged as an inspiring tool for the effective delivery of drugs to help treat Coronary heart disease (CHD) which represents the most prevalent reason for mortality and morbidity globally. The current study focuses on the assessment of the cardioprotective prospective ofanovel combination nanoformulation of sericin and carvedilol. Sericin is a silk protein obtained from Bombyx mori cocoon and carvedilol is a synthetic nonselective β-blocker. In this present study, preparation of chitosan nanoparticles was performed via ionic gelation method and were evaluated for cardioprotective activity in doxorubicin (Dox)-induced cardiotoxicity. Serum biochemical markers of myocardial damage play a substantial role in the analysis of cardiovascular ailments and their increased levels have been observed to be significantly decreased in treatment groups. Treatment groups showed a decline in the positivity frequency of the Troponin T test as well. The NTG (Nanoparticle Treated Group), CSG (Carvedilol Standard Group), and SSG (Sericin Standard Group) were revealed to have reduced lipid peroxide levels (Plasma and heart tissue) highly significantly at a level of p p p < 0.01, respectively. Hence, the outcomes of this study suggest that the developed nanoparticle formulation is effective against doxorubicin-induced cardiotoxicity

Augmentation and Evaluation of an Olive Oil Based Polyherbal Combination against Diabetic Cardiomyopathy in Experimental Model of Rodents

Diabetes mellitus is a metabolic disorder that is prima facie a cause for numerous macro and micro vascular complications. A common macroscopic complication associated with diabetes is cardiomyopathy. Cardiomyopathy refers to diseases of the heart muscle, where the heart muscle becomes enlarged, thick, or rigid. As cardiomyopathy worsens, the heart becomes weaker and is unable to conduct the right amount of blood through the body and maintain a normal electrical rhythm. This can lead to heart failure or arrhythmias. Chronic diabetes is one of the instigating factors behind the etiology of this cardiac complication. Type-II diabetes is associated with impaired glucose metabolism that increases the dependence of a diabetic heart on fatty acid oxidation to meet its functional demands, resulting in mitochondrial uncoupling, glucotoxicity, lipotoxicity and initially subclinical cardiac dysfunction that finally gives way to heart failure. The increasing diabetic population with cardiac disorders and the ironically decreasing trend in newer medications to counter this complication leave us at a crossroads for pharmacological management of diabetic cardiomyopathy. Keeping this in view, the present study proclaims a newly developed polyherbal combination (PHC) with three herbs, namely Tinospora cordifolia, Withania somnifera and Boerhavia diffusa based in olive oil and administered in fixed dose (PHC-6 and PHC-10) to screen its cardioprotective potential against a well-established experimental model for diabetic cardiomyopathy. The three herbs mentioned have been known through the traditional literature for their antidiabetic and cardioprotective roles, hence they became the obvious choice. The study follows an experimental model proposed by Reed et al., where the capacity of the β-cell is unobtrusively impeded without totally compromising insulin release, bringing about a moderate disability in glucose resilience. Various sophisticated parameters, namely intraventricular septum thickness of hearts, Western blot of α/β- MHC monoclonal antibody (Ab), cardiac pyruvate dehydrogenase (PDH) activity, medium chain acyl coenzyme A dehydrogenase (MCAD) enzyme, etc. showed promising results where treatment with PHC (PHC-6 and PHC-10) significantly (*** p p < 0.0001) prevented the symptoms of cardiomyopathy in subsequent groups when compared to disease control group