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Cardiometabolic disorders (CMD) is a constellation of metabolic predisposing factors for atherosclerosis such as insulin resistance (IR) or diabetes mellitus (DM), systemic hypertension, central obesity, and dyslipidemia. Cardiometabolic diseases (CMDs) continue to be the leading cause of mortality in both developed and developing nations, accounting for over 32% of all fatalities globally each year. Furthermore, dyslipidemia, angina, arrhythmia, heart failure, myocardial infarction (MI), and diabetes mellitus are the major causes of death, accounting for an estimated 19 million deaths in 2012. CVDs will kill more than 23 million individuals each year by 2030. Nonetheless, new drug development (NDD) in CMDs has been increasingly difficult in recent decades due to increased costs and a lower success rate. Drug repositioning in CMDs looks promising in this scenario for launching current medicines for new therapeutic indications. Repositioning is an ancient method that dates back to the 1960s and is mostly based on coincidental findings during medication trials. One significant advantage of repositioning is that the drug’s safety profile is well known, lowering the odds of failure owing to undesirable toxic effects. Furthermore, repositioning takes less time and money than NDD. Given these facts, pharmaceutical corporations are becoming more interested in medication repositioning. In this follow-up, we discussed the notion of repositioning and provided some examples of repositioned medications in cardiometabolic disorders.

Abstract: Nanotechnology is a great choice for medical research, and the green synthesis approach is a novel and better way to synthesize nanoparticles. Biological sources are cost-effective, environmentally friendly, and allow large-scale production of nanoparticles. Naturally obtained 3 β-hydroxy-urs-12-en-28-oic acids reported for neuroprotective and dendritic structure are reported as solubility enhancers. Plants are free from toxic substances and act as natural capping agents. In this review, the pharmacological properties of ursolic acid (UA) and the structural properties of the dendritic structure are discussed. UA acid appears to have negligible toxicity and immunogenicity, as well as favorable biodistribution, according to the current study, and the dendritic structure improves drug solubility, prevents drug degradation, increases circulation time, and potentially targets by using different pathways with different routes of administration. Nanotechnology is a field in which materials are synthesized at the nanoscale. Nanotechnology could be the next frontier of humankind's technological advancement. Richard Feynman first used the term ‘Nanotechnology’ in his lecture, “There is Plenty of Room at the Bottom,” on 29th December, 1959, and since then, interest has increased in the research on nanoparticles. Nanotechnology is capable of helping humanity by solving major challenges, particularly in neurological disorders like Alzheimer's disease (AD), the most prevalent type, which may account for 60–70% of cases. Other significant forms of dementia include vascular dementia, dementia with Lewy bodies (abnormal protein aggregates that form inside nerve cells), and a number of illnesses that exacerbate frontotemporal dementia. Dementia is an acquired loss of cognition in several cognitive domains that are severe enough to interfere with social or professional functioning. However, dementia frequently co-occurs with other neuropathologies, typically AD with cerebrovascular dysfunction. Clinical presentations show that neurodegenerative diseases are often incurable because patients permanently lose some neurons. A growing body of research suggests that they also advance our knowledge of the processes that are probably crucial for maintaining the health and functionality of the brain. Serious neurological impairment and neuronal death are the main features of neurodegenerative illnesses, which are also extremely crippling ailments. The most prevalent neurodegenerative disorders cause cognitive impairment and dementia, and as average life expectancy rises globally, their effects become more noticeable.

The receptor of Advanced Glycation Endproducts (RAGE) and Advanced Glycation Endproducts (AGE) have multiple functions in our body and their restraint are being observed in neurodegenerative and memory impairment disorders. The review of different pathways allows an understanding of the probable mechanism of neurodegeneration and memory impairment involving RAGE and AGE. Commonly we observe AGE accumulation in neural cells and tissues but the extent of accumulation increases with the presence of memory impairment disorder. The presence of AGEs can also be seen in morbid accumulation, pathological structures in the form of amyloid clots, and nervous fibrillary tangles in Alzheimer’s Disease (AD) and memory impairment disease.Many neuropathological and biochemical aspects of AD are explained by AGEs, including widespread protein crosslinking, glial activation of oxidative stress, and neuronal cell death. Oxidative stress is due to different reasons and glycation end products set in motion and form or define various actions which are normally due to AGE changes in a pathogenic cascade. By regulating the transit of ß-amyloid in and out of the brain or altering inflammatory pathways, AGE and it’s ensnare receptor such as soluble RAGE may function as blockage or shield AD development. RAGE activates the transcription-controlling factor Necrosis Factor (NF-κB) and increases the protraction of cytokines, like a higher number of Tumor Necrosis Factor (TNF-α) and Interleukin (IL-I) by inducing several signal transduction cascades. Furthermore, binding to RAGE can pro-activate reactive oxygen species (ROS), which is popularly known to cause neuronal death.

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 < 0.01 in comparison with the TCG (Toxic Control Group). Levels of antioxidants in the plasma and the cardiac tissue were also established to be within range of the treated groups in comparison to TCG. Mitochondrial enzymes in cardiac tissue were found to be elevated in treated groups. Lysosomal hydrolases accomplish a significant role in counteracting the inflammatory pathogenesis followed by disease infliction, as perceived in the TCG group. These enzyme levels in the cardiac tissue were significantly improved after treatment with the nanoformulation. Total collagen content in the cardiac tissue of the NTG, SSG, and CSG groups was established to be highly statistically significant at p < 0.001 as well as statistically significant at p < 0.01, respectively. Hence, the outcomes of this study suggest that the developed nanoparticle formulation is effective against doxorubicin-induced cardiotoxicity.

Ovarian cancer is characterized by the establishment of tolerance, the recurrence of disease, as well as a poor prognosis. Gene signatures in ovarian cancer cells enable cancer medicine research, therapy, prevention, & management problematic. Notwithstanding advances in tumor puncture surgery, novel combinations regimens, and abdominal radiation, which can provide outstanding reaction times, the bulk of gynecological tumor patients suffer from side effects & relapse. As a consequence, more therapy alternatives for individuals with ovarian cancer must always be studied to minimize side effects and improve progression-free and total response rates. The development of cancer medications is presently undergoing a renaissance in the quest for descriptive and prognostic ovarian cancer biomarkers. Nevertheless, abnormalities in the BRCA2 or BRCA1 genes, a variety of hereditary predispositions, unexplained onset and progression, molecular tumor diversity, and illness staging can all compromise the responsiveness and accuracy of such indicators. As a result, current ovarian cancer treatments must be supplemented with broad-spectrum & customized targeted therapeutic approaches. The objective of this review is to highlight recent contributions to the knowledge of the interrelations between selected ovarian tumor markers, various perception signs, and biochemical and molecular signaling processes, as well as one’s interpretation of much more targeted and effective treatment interventions.

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.

Abstract: Ursolic acid (UA) has been utilized to improve memory-related cognitive processes and intellectual functions. This study aims to examine the ethnobotanical uses, phytochemical composition, toxicity, and central nervous system activities of UA. It promotes learning and memory and has biological effects against Alzheimer's disease, Parkinson's disease, and cognitive impairment, according to pharmacological investigations. UA did not cause any death, abnormal body weight, or pathological diseases at any of the test doses. Furthermore, no behavioral, neurotoxin, coagulation, haematological, or clinical chemistry changes were seen as a result of UA treatment. UA is also used as a cosmeceutical product to improve skin functions. This article examines all knowledge that has become available at this time for revealing the chemistry of the current has been extensively investigated based on the data, resulting in UA derivatives with improved potency, bioavailability, and stability being used to treat a number of non-communicable diseases. The pharmacological activity of UA has been exploited to improve learning and memory and treat depression, emotional stress, fatigue, anxiety, insomnia, Alzheimer’s disease, Parkinson’s disease, epilepsy, and schizophrenia. The effects of UA on the central nervous system detailed in this review. The majority of UA studies have been preclinical evaluations of cellular mechanisms in the central nervous system, and more translational clinical research is needed to assess the drug's safety and efficacy, as well as its favorable, biodistribution, which could be targeted using different pathways and administration routes. Several in vitro and in vivo studies have investigated the pharmacological properties of UA reporting neuroprotective effects and improvements in cognitive function. These effects are attributed to its antioxidant, antiapoptotic, and anti-inflammatory actions.

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 < 0.001 and **** p < 0.0001) prevented the symptoms of cardiomyopathy in subsequent groups when compared to disease control group.

The silkworm cocoon has been used in the treatment of various ailments in different Asian countries. This research was designed to evaluate the effect of sericin on myocardial necrosis and hypertrophy in isoproterenol-challenged rats. The rats were administered with sericin (500 and 1000 mg/kg, p.o.) for 28 days, followed by administration of isoprenaline (85 mg/kg, s.c.) on the 29th and 30th days. The cardioprotective activity was assessed by various physical, enzymatic, and histopathological parameters along with apoptotic marker expression. The cardioprotective effect showed that pre-treatment of rats with sericin significantly increased the non-enzymatic antioxidants marker in serum and heart tissue (glutathione, vitamin E, and vitamin C). The results were the same in enzymatic antioxidant marker, mitochondrial enzymes, and protein. The grading of heart, heart/body weight ratio, gross morphology, cardiac markers, oxidative stress markers in serum and heart tissue, glucose, serum lipid profiling and Lysosomal hydrolases, heart apoptotic markers such as MHC expression by western blot, apoptosis by flow cytometry, total myocardial collagen content, fibrosis estimation, myocyte size were significantly decreased when compared with isoproterenol (ISG) group however histopathological studies showed normal architecture of heart in both control and treated rats. The pharmacological study reflects that sericin on both doses i.e., 500 mg/kg and 1000 mg/kg have potent cardioprotective action against the experimental model which was confirmed by various physical, biochemical, and histopathological parameters evaluated further research is required to examine the molecular mechanism of cardioprotective effect of sericin.

Areca catechu is an important ancient drug commonly known as Supari in ayurvedic system of medicine. A lot of research work has been done on Areca catechu regarding various cardiovascular disorders such as Hypertension, Arrhythmia but no work has been done to find out its cardioprotective activity. Experimental procedures done on Wistar Albino rats as Normal control group (NC) received 0.5ml of normal saline throughout the study and served as control. Isoprenaline group (ISO) received 0.5ml of normal saline throughout the experimental phase and received Isoprenaline (85mg/kg, s.c.) on 14th and 15th day at a time lapse of 24 hours. Standard group (STD) received Metoprolol (pure) (10mg/kg/day, p.o.) for 13 days and received Isoprenaline (85mg/kg, s.c.) on 14th and 15th day. Test group received Areca catechu extract (100mg/kg/day, p.o.) and (200 mg/kg/day, p.o.) respectively for 13 days and Isoprenaline (85mg/kg, s.c.) on 14th and 15th day. On 16thday animals were sacrificed. The level of marker enzyme in serum as AST, ALT, CK, LDH, Troponin-I have shown significant decrease (P

Arecacatechu, commonly known as supari, consists of dried ripe nuts that came under Arecaceae family, which is cultivated in the tropical region of India and Southeast Asia. It is a prevalent traditional herbal medicine that is chewed to separate collected fluid in the alimentary canal and for killing worms. Areca catechu seed contains alkaloids (arecoline, arecaine, arecaidine, guvacoline, guvacine, and choline), tannin, gallic acid, gum, and various minerals such as copper, calcium, phosphorus, and iron. The chemical constituents of this plant have been used as antidiabetic, stomatitis, bleeding gums, gingivitis, conjunctivitis, glaucoma, leucorrhoea, urinary disorders, anorexia, diarrhea, blood pressure regulating activity, antiulcerogenic, antioxidant activity, anticonvulsant activity, central nervous system stimulant activity, antifertility, oxytocic activity, antiviral activity, anthelmintic, and foul breath. It showed a dose‐dependent toxicity profile, and various research has been done regarding its safety analysis and it would be considered safe when administered in the prescribed dose. The purpose of the present paper is to make available an up‐to‐date review on the ethnic, traditional description, morphology, phytochemistry, and the pharmacological and toxicological profile of this plant. Furthermore, the possible advances, trends, and a perspective for forthcoming research of this plant have also conversed.

Objectives Comparative evaluation of cardioprotective activity of Gala and Fuji apple juice against isoprenaline induced cardiotoxicity in rats. Methods Rats (125–150 g) were orally administered Gala (GA) and Fuji (FA) apple juice (3 mL/day, per oral) for 13 days. Myocardial injury was inducted on 14th and 15th day by the administration of Isoprenaline (85 mg/kg/day, subcutaneous). Results In treated group i.e. GA and FA, aspartate aminotransferase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), creatine kinase (CK), Troponin-I level and malondialdehyde (MDA) content was reduced while glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) level was significantly increased. Marked reduction in cholesterol, triglyceride, phospholipids, low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) was observed while high-density lipoprotein (HDL) level increased significantly. In tissue and serum total serum protein (TSP) level, Albumin, Globulin and A/G ratio increased very significantly in the treated group while the level of white blood corpuscles (WBC), haemoglobin (Hb), erythrocyte sedimentation rate (ESR), total fibrinogen (TF), bleeding time (BT), c-reactive protein (C-rP), red blood corpuscles (RBC), clotting time (CT) and prothrombin time (PT) showed a significant rise in the level. The level of Sialic acid, hexose, fucose and hexosamine was highly significantly increased, there was an increase in the level of K+ and glycogen while a significant reduction in electrolyte and glucose level was observed when all these parameters were compared to Isoprenaline (ISO) group. The above findings were supported by histopathological examination of hearts. Cardioprotective activity was compared with standard drug, metoprolol. On comparative analysis of both juices, GA juices have found more effective when compared to FA juice. Conclusions The study was concluded that Gala and Fuji apple possessed significant prophylactic and protective effects against Isoprenaline-induced cardiotoxicity in rats through maintaining inhibiting lipid peroxidation, endogenous antioxidant enzyme activities and cytokine levels.

High risks of cardiovascular diseases in women are associated with low estrogen levels. Ischemic preconditioning (IPC) exhibits protection in the heart by Glycogen synthase kinase-3β (GSK-3β) phosphorylation that inhibits the mPTP opening, and this protective action of IPC is attenuated by estrogen deficiency. An experiment was performed on female Wistar rats with/without ovariectomy (OVX). Isolated rat heart was attached with perfusion assembly. Infract size, coronary flow, LDH, CKMB and histopathology were estimated. Sham control group decreased the LDH, CKMB and infract size in normal rat heart. The IPC mediated protection of heart was attenuated in OVX rat heart. Inhibition of GSK-3β is found to enhance the threshold of mPTP opening during reperfusion. The treatment with atractyloside stuck significantly the protection of heart of IPC in normal and OVX rat heart. These observations show that downregulation of GSK-3β through an impaired opening of mPTP during reperfusion and GSK-3β might be potential adjuvant to IPC against cardiac injury in OVX challenged rats.

Herbal medicine is the core nucleus of holistic medicine which is gaining rapid popularity all over the world and gradually incorporating and integrating its position in the mainstream health care systems. Herbal medicines include plant and their parts that contain active ingredients alone or in combination to increase the efficacy, prevention and treatment of the disease. Analogous to conventional medicines herbal medicines are employed for various illness like cold, inflammation, diabetes, malaria, tuberculosis, cancer and so on. Indian traditional medicines or medicinal plants are indispensable source of new drugs. Foeniculum vulgare also known as Fennel, a member of Apiaceae family is used for various health benefits such as, it helps to regulate blood pressure, reduce water retention, improve eyesight and helps in reducing acne, constipation, arthritis, cough, gingival wound etc. Solanum nigrum also known as Makoh, a member of Solanaceae family is used in diverse medical conditions such as used to treat fever and to alleviate pain, used in treating the mouth ulcers, good herbal remedy for asthma, is the main ingredient in various medicines prepared to treat various liver disorders, helps in treating UTI and has excellent hepatoprotective and anti-inflammatory activity. Cichorium intybus also known as Kasni, a member of Asteracece family is used in inflammation, hepatomegaly, digestive ailments, malaria, gout, sedative. It is a remedy for high blood pressure, constipation, liver disorders, gallbladder disorders, skin inflammation, loss of appetite, heart failure and cancer. These drugs provide a noteworthy basis in pharmaceutical biology for the development and formulation of new drugs for future clinical uses.

Acute and subacute toxicity screening of novel entrants in the stream of polyherbal formulations opens new doors towards the scientific approach of establishing them in the clinical market. Toxicity profiling asserts the humongous pharmacological potential that the natural herbs hold and establishes their safety profile. To exemplify this statement, this study further deals with acute and subacute toxicity studies of an olive oil-based polyherbal combination (PHC). This combination has been developed with the view that it proves to be clinically effective in diabetic cardiomyopathy and neuropathy. However, until now, the acute and subacute toxicity studies have been done on the developed PHC, and experimentally effective dose combinations have been identified. The follow-up part of this research includes the screening of the PHC against specific in vivo screening models in its initial stages. This research paper strictly summarises the acute and subacute profile of the salubrious polyherbal combination. Three herbs with strong literature background were selected: Tinospora cordifolia, Withania somnifera and Boerrhavia diffusa; and their crude extracts were prepared. The reported ED50 values of each of these plants were selected and mixed in 5 different combinations and subjected to Acute Toxicity studies. It was followed by the 28-days subacute toxicity screening of 9 different combinations that were elucidated from the acute toxicity study results. The findings were supported with recovery group studies to conform to any late toxicity symptoms of the polyherbal combination. The findings of this study helped in reaching some pathbreaking conclusions on the polyherbal combination designed.

Diabetic foot ulcers (DFUs) are the most common complications associated with diabetes mellitus. DFUs are displayed as open sores or wounds located on the bottom of the foot as a secondary complication of diabetes mellitus (DM). DFUs are associated with significant morbidity and mortality and can subsequently lead to hospitalization and lower limb amputation if not recognized and treated on time. An immense challenge to conventional treatments is caused by the chronic nature of diabetic foot syndrome and it has led to the emergence of nanotechnology-based therapeutics. The greatest advantages of these nanotherapeutics are their unique biological, chemical, and physical properties. The present review highlights the augmentation of bacterial infections relating to delayed healing of DFUs and the potential of nanotherapeutics such as polymeric nanoparticles, metallic nanoparticles, siRNA-based nanoparticles, lipid nanoparticles, and nanofibers in accelerating wound healing in diabetic foot ulcers.

It is well recognized that cyclic adenosine monophosphate (cAMP) signaling within neurons plays a key role in the foundation of long-term memories. Memory storage is the process that demands the movement of signals, neural plasticity, and the molecules which can transfer the signals from the sensory neuron to the dorsal root ganglion (DRG) neurons and later into the temporal region of the brain. The discovery of cAMP in 1958 as the second messenger also had a role in memory formation and other neural aspects. Further, in 1998 the scientists found that cAMP does not just activate protein kinase A (PKA) but also exchange protein directly activated by cAMP (Epac) which has an active role to play in hyperalgesia, memory, and signaling. The cAMP has three targets, hyperpolarization-activated cyclic nucleotide modulated (HCN) channels, protein kinase A (PKA), and exchange protein activated by cAMP (Epac). Different research has exposed that both PKA and HCN channels are significant for long-term memory creation. Epac is a cAMP-dependent guanine nucleotide exchange factor for the small G proteins including Rap1. However, slight information is there about the role of Epac in this process. The effects of cAMP are predominantly imparted by activating protein kinase A (PKA) and the more newly discovered exchange proteins are directly activated by cAMP 1 and 2 (EPAC1 and EPAC2). This review provides an insight regarding the function and role of both of these secondary messengers in memory and nerve signaling.

Amidst several pathophysiological cascades, Advanced Glycation End products (AGEs) have been identified as a pivotal aetiology behind the pathogenesis and progression of cardiovascular disorders, by inducing oxidative stress and inflammation of myocardial and vascular tissues. Non-enzymatic glycation of reducing sugars with amino acids in proteins, lipids, and nucleic acids produce AGEs, which are a diverse set of compounds. Although AGEs are mostly generated endogenously, current research suggests that nutrition is a major exogenous source of AGEs. Extracellular and intracellular structure and function are affected by the presence and accumulation of AGEs in several cardiac cell types. AGEs give rise to several microvascular and macrovascular problems by establishing cross-links between molecules in the extracellular matrix's basement membrane as well as interacting with receptors for advanced glycation end products (RAGE). The transcription factor nuclear factor kappa B and its RAGE target genes are upregulated when RAGE is activated by AGEs. Engagement increases oxidative stress and triggers inflammatory and fibrotic responses, all of which contribute to the onset and progression of life-threatening cardiovascular diseases. This article discusses the probable targets of glycation in cardiac cells, as well as the underlying mechanisms that lead to heart failure.

Medicinal plants having antioxidant potential possess numerous constituents which are responsible for different beneficial effects and are used as an alternative resource of medicine to lessen diseases linked with oxidative stress. Flavonoids are identified in the plants since ages and display wide spectrum of biological actions that might be able to stimulate the steps which are disturbed in different diseases. Flavonoids are significant natural compounds with various biologic properties, among which the most common is the anti-oxidant potential. Citrus flavonoids establish an important stream of flavonoids. Naringin, very common flavonoids present in the diet, belongs to the family of flavanone. It is the principal constituent of citrus family that contains flavonoids for example tomatoes, grapefruits and oranges.In this article, we reviewed naringin with respect to sources, chemical property, pharmacokinetics, pharmacological activity, and novel formulations. The literature survey has been done by searching different databases such as Psyc INFO, Science Direct, PubMed, EMBASE, Google, Google Scholar, Medline.Naringin is known to behave as an antioxidant and possess anti-inflammatory, anti-apoptotic, anti-atherosclerotic, neuroprotective, anti-psychotic, anti-asthmatic, anti-diabetic, hepatoprotective, anti-tussive, cardioprotective, and anti-obesity activity. Further clinical studies using large sample sizes remain essential to obtain the appropriate dose and form of naringin for averting diseases. Furthermore, the therapeutic approach of these bioflavonoids is significantly inappropriate due to the lack of clinical evidence. Different plants must be explored further to find these bioflavonoids in them.The results of this exploration provides biological actions of bioflavonoid (naringin), predominantly on pharmacological and novel dosage forms of naringin.

The dissemination of the 2019 novel coronavirus (2019-nCoV) is presenting the planet with a new health emergency response or threat to health. The virus emerged in bats and was disseminated to humans in December 2019 via still unknown intermediate species in Wuhan, China. It is disseminated by inhalation or breaks out with infected droplets and the incubation period is between 2 and 14 days. The symptoms usually include high body temperature, cough, sore throat, dyspnea, low energy or tiredness, and weakness. The condition is moderate in most people; but in the elderly and those with comorbidities, it advances to pneumonia, acute respiratory distress syndrome (ARDS), and multiple organ failure. Popular research work includes normal/low WBC with upraised C-reactive protein (CRP). Treatment is generally supportive and requires home seclusion of suspected persons and rigorous infection control methods at hospitals. The Covid-19 has lower fatality than SARS and MERS. Among the proposed therapeutic regimen, hydroxychloroquine, chloroquine, remdisevir, azithromycin, toclizumab, and cromostat mesylate have shown promising results, and the limited benefit was seen with lopinavir–ritonavir treatment in hospitalized adult patients with severe COVID-19. Early development of the SARS-CoV-2 vaccine started based on the full-length genome analysis of severe acute respiratory syndrome coronavirus. Several subunit vaccines, peptides, nucleic acids, plant-derived, and recombinant vaccines are under pipeline. Research work, development of new medicines and vaccines, and efforts to reduce disease morbidity and mortality must be encouraged to improve our position in the fight against this disease and to protect human life.

Comparative evaluation of cardioprotective activity ofRats (125-150 g) were orally administeredIn treated group i.e. GA and FA, aspartate aminotransferase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), creatine kinase (CK), Troponin-I level and malondialdehyde (MDA) content was reduced while glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) level was significantly increased. Marked reduction in cholesterol, triglyceride, phospholipids, low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) was observed while high-density lipoprotein (HDL) level increased significantly. In tissue and serum total serum protein (TSP) level, Albumin, Globulin and A/G ratio increased very significantly in the treated group while the level of white blood corpuscles (WBC), haemoglobin (Hb), erythrocyte sedimentation rate (ESR), total fibrinogen (TF), bleeding time (BT), c-reactive protein (C-rP), red blood corpuscles (RBC), clotting time (CT) and prothrombin time (PT) showed a significant rise in the level. The level of Sialic acid, hexose, fucose and hexosamine was highly significantly increased, there was an increase in the level of KThe study was concluded that

Lower level of testosterone in men is related to major risks of cardiovascular diseases. This risk may increase due to the opening of mitochondrial permeability transition pore (mPTP). The mPTP is also regulated by ischemic preconditioning (IPC) and a membrane protein known as caveolin. The cardioprotective effect of IPC is the most effective methodologies used in testosterone deficiency. Daidzein (DDZ) a caveolin inhibitor shows cardioprotective action. The experiment has been designed to evaluate the pretreated DDZ effect in IPC-mediated cardioprotective action in orchidectomy (OCZ)-challenged rat heart. The experiment was designed on male Wistar rats with/without OCZ. The level of testosterone is decreased by OCZ which reduces general body growth. Isolated heart from normal and OCZ rat was tied up on Langendorff’s perfused apparatus and followed by ischemic reperfusion (IR) and IPC cycle. To investigate the cardioprotective effect of DDZ in heart with testosterone deficiency, a total of nine groups, each consisting of six rats (n = 6) were as follows: Sham, IR, IPC, IPC + OCZ, IPC + DDZ, IPC + OCZ + DDZ, IPC + sodium nitrite, IPC + OCZ + sodium nitrite, IPC + OCZ + DDZ + sodium nitrite. Hemodynamic parameters, cellular injury (infarct size, LDH, CKMB and cardiac troponin-T), oxidative stress, mitochondrial function, integrity and immunoblot analysis were assessed for each group. The experimental data showed that DDZ potentiated IPC-mediated increase in the heart rate, left ventricular diastolic pressure, coronary flow; + dp/dtmax, and − dp/dtmax. The pretreated DDZ decreases the action of LDH and CKMB, myocyte size, cardiac collagen content, infarct size and ventricular fibrillation and attenuation in oxidative stress and mitochondrial dysfunction in OCZ-challenged rat heart in all sets of experiments. Sodium nitrite, a producer of nitric oxide (NO), enhanced potentiating effects of DDZ on IPC-mediated cardioprotection in OCZ-challenged rats. These observations show that the downregulation of caveolin through impaired opening of mPTP during reperfusion and caveolin might be a potential adjuvant to IPC against cardiac injury in OCZ-challenged rats.

Past few decades have emerged as the era of nanotechnology worldwide leading to an extensive research in pharmaceutical science as well as other fields. Nanoformulations have shown a promising future in therapeutics and theronostics. Protein based nanoformulations attracting attention in research as it can be used as therapeutics as well as carrier. Carrier based protein nanoformulatios are capable of accommodating range of therapeutics such as dyes, drugs, contrast agents and inorganic nanoclusters makings its application vast. The nano size of formulation enables it to reach the desired places by some modification. This paper reviewed the various protein based nanoformulation. Human serum albumin, Bovine serum albumin, soy protein isolate, phycocyanin, casein, bromelein, collagen and sericin based nanoformulations are briefly discussed. Various limitations of these proteins can be diminished by developing it in nano form and emerged as promising candidate as carrier as well as therapeutics in drug delivery advancements.

Background: Khamira Abresham Hakim Arshadwala (KAHAW), a distinguished, traditional Unani formulation comprising constituents of herbal, animal, and mineral origin, holds salubrious cardioprotective potential and has been used for cardiac ailments in the Unani system for ages. KAHAW is a ‘sugar-based’ preparation, which hinders its ‘claim to fame’ amongst cardiac patients with diabetes. Hence, it is fascinating to develop a novel nanoformulation of the traditional one and screen its efficacy experimentally on the male Wistar rats (4-week-old) (150-180gm). The objective was to revolutionize this historic gem of a formulation and enhance its therapeutic efficacy, a novel nanoformulation of KAHAW was developed, and its cardioprotective potential screened against isoprenaline (ISO) induced cardiotoxicity in rodents. The results were analyzed with the traditional formulations and two clinically used drugs, Ramipril and Carvedilol. Methods: Various parameters viz; Physical, Enzymatic, Non-enzymatic, and cardiac-specific biomarkers like α/β-MHC expression (Western Blot), Flow cytometry, Cardiac collagen content, and Mitochondrial enzyme assay were assessed on plasma, blood, and tissue samples followed by histomorphological investigations. Results: The effect of nanoformulation showed highly significant results (***p Conclusions: The research reiterates that the novel nanoformulation offers improved efficacy at a reduced dose against ISO-induced experimental models of myocardial necrosis.

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, Sphingolipids

Diabetic neuropathy is a chronic complication of diabetes mellitus affecting about 50% of patients. Its symptoms include decreased motility and severe pain in peripheral parts. The pathogenesis involved is an abnormality in blood vessels that supply the peripheral nerves, metabolic disorders such as myo-inositol depletion, and increased nonenzymatic glycation. Moreover, oxidative stress in neurons results in activation of multiple biochemical pathways, which results in the generation of free radicals. Apart from available marketed formulations, extensive research is being carried out on herbal-based natural products to control hyperglycemia and its associated complications. This review is focused to provide a summary on diabetic neuropathy covering its etiology, types, and existing work on herbal-based therapies, which include pure compounds isolated from plant materials, plant extracts, and Ayurvedic preparations.

The aim of this study is to explore the effect of Tinospora cordifolia (Guduchi) on cardiotoxicity in streptozotocin induced diabetic rats. All animals were divided into 8 groups of 5 animals each, fed with High fat diet (HFD) except the ones in Sham, NPD and NPD-C-I groups. Food and water intake were monitored daily at the same time during the experimental period. The Food Efficiency Ratio (FER) was calculated during the experiment period. All the animals were pretreated as per the treatment protocol. Streptozotocin; STZ (50mg/ Kg) was administered subcutaneously to induce the diabetes which was confirmed in all the administered groups by testing blood glucose level after 48 hours. Cardiotoxicity was induced by administering isoprenaline (85mg/Kg). Troponin was checked after 4-5 hours of second isoprenaline injection to confirm cardiac damage. At the end of the study the animals were weighed and then sacrificed with high dose of Diethyl ether. Blood samples were collected from retro-orbital plexus and were used for biochemical estimations. The hearts were excised immediately and were weighed. Photomicrographs were taken for gross examination rest of the hearts were kept in 10% Formalin solution for histopathological studies. Pretreatment with Tinospora cordifolia (200 mg/kg ) showed very significant improvement against Streptozotocin induced diabetes (p< 0.01) as blood glucose level were found to be decreased when compared to the untreated D-HFD group. The Food efficiency ratio (FER) was found to be significantly increased when compared to D-HFD (p

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.