Repurposing of Drugs for Cardiometabolic Disorders: An Out and Out Cumulation.

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.

An inquest into regulatory mechanism of caveolin by ischemic preconditioning against orchidectomy-challenged rat heart.

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.

From Hypertension to Beyond: Unraveling the Diverse Mechanisms of Olmesartan in Disease Modulation.

Olmesartan, originally known for its antihypertensive properties, exhibits promising potential in addressing inflammation-mediated diseases. As an angiotensin II receptor blocker (ARB), Olmesartan influences pivotal pathways, including reactive oxygen species, cytokines, NF-κB, TNF-α, and MAPK. This suggests a viable opportunity for repurposing the drug in conditions such as ulcerative colitis, neuropathy, nephropathy, and cancer, as supported by multiple preclinical studies. Ongoing clinical trials, particularly in cardiomyopathy and nephropathy, suggest a broader therapeutic scope for Olmesartan. Repurposing efforts would entail comprehensive investigations using disease-specific preclinical models and dedicated clinical studies. The drug's established safety profile, wide availability, and well-understood ARB mechanism of action offer distinct advantages that could facilitate a streamlined repurposing process. In summary, Olmesartan's versatile impact on inflammation-related pathways positions it as a promising candidate for repurposing across various diseases. Ongoing clinical trials and the drug's favorable attributes enhance its appeal for further exploration and potential application in diverse medical contexts.

Empagliflozin-A Sodium Glucose Co-transporter-2 Inhibitor: Overview of Its Chemistry, Pharmacology, and Toxicology.

BACKGROUND: Empagliflozin is a sodium glucose co-transporter-2 (SGLT2) inhibitor that has gained significant attention in the treatment of type 2 diabetes mellitus. Understanding its chemistry, pharmacology, and toxicology is crucial for the safe and effective use of this medication. OBJECTIVE: This review aims to provide a comprehensive overview of the chemistry, pharmacology, and toxicology of empagliflozin, synthesizing the available literature to present a concise summary of its properties and implications for clinical practice. METHODS: A systematic search of relevant databases was conducted to identify studies and articles related to the chemistry, pharmacology, and toxicology of empagliflozin. Data from preclinical and clinical studies, as well as post-marketing surveillance reports, were reviewed to provide a comprehensive understanding of the topic. RESULTS: Empagliflozin is a selective SGLT2 inhibitor that works by constraining glucose reabsorption in the kidneys, causing increased urinary glucose elimination. Its unique mechanism of action provides glycemic control, weight reduction, and blood pressure reduction. The drug's chemistry is characterized by its chemical structure, solubility, and stability. Pharmacologically, empagliflozin exhibits favorable pharmacokinetic properties with rapid absorption, extensive protein binding, and renal elimination. Clinical studies have demonstrated its efficacy in improving glycemic control, reducing cardiovascular risks, and preserving renal function. However, adverse effects, for instance, urinary tract infections, genital infections, and diabetic ketoacidosis have been reported. Toxicological studies indicate low potential for organ toxicity, mutagenicity, or carcinogenicity. CONCLUSION: Empagliflozin is a promising SGLT2 inhibitor that offers an innovative approach to the treatment of type 2 diabetes mellitus. Its unique action mechanism and favorable pharmacokinetic profile contribute to its efficacy in improving glycemic control and reducing cardiovascular risks. While the drug's safety profile is generally favorable, clinicians should be aware of potential adverse effects and monitor patients closely. More study is required to determine the longterm safety and explore potential benefits in other patient populations. Overall, empagliflozin represents a valuable addition to the armamentarium of antidiabetic medications, offering significant benefits to patients suffering from type 2 diabetes mellitus. This study covers all aspects of empagliflozin, including its history, chemistry, pharmacology, and various clinical studies, case reports, and case series.

Encyclopaedic Review of Glipizide Pre-clinical and Clinical Status.

Glipizide is an oral glucose-lowering medication that is beneficial for the treatment of type 2 diabetes. This study compiles exhaustively all accessible information on glipizide, from preclinical to clinical studies. Glipizide may be used in concert with TRAIL to treat cancer cells; in vitro studies have shown that it suppresses angiogenesis and vasculogenesis while shielding cells from glycation-induced damage. Anticonvulsant effects and modifications in the pharmacokinetics of other medications, such as Divalproex Sodium, were seen in glipizide in vivo experiments. Propranolol amplifies glipizide's hypoglycemic effect briefly in normal animals but consistently enhances it in diabetic ones. In the treatment of cancer and neurodegenerative poly(Q) illnesses, glipizide has demonstrated to offer potential therapeutic advantages. It is ineffective in preventing DENA-induced liver cancer and may cause DNA damage over time. The way glipizide interacts with genetic variants may increase the risk of hypoglycemia. Combining Syzygium cumini and ARBE to glipizide may enhance glycemic and lipid control in type 2 diabetes. Individuals with coronary artery disease who take glipizide or glyburide have an increased risk of death. The risk of muscular responses and acute pancreatitis is minimal when glipizide and dulaglutide are combined. In conclusion, glipizide has shown promising therapeutic efficacy across a variety of disorders.

Development and evaluation of Resveratrol-loaded liposomes in hydrogel-based wound dressing for diabetic foot ulcer.

Diabetic foot wounds (DFUs) are counted as one of the most common microvascular complications associated with poorly controlled and chronic diabetes mellitus. It confers a serious challenge to clinical practice, surmounting hyperglycemia-induced disturbance in angiogenesis and endothelial dysfunction, with limited fruitful intervention to control the manifestations of DFUs. Resveratrol (RV) can improve endothelial function and has strong pro-angiogenic properties for the treatment of diabetic foot wounds. The present study aims to design an RV-loaded liposome-in-hydrogel system to effectively heal diabetic foot ulcers. A thin-film hydration method was used to prepare RV-loaded liposomes. Liposomal vesicles were assessed, for various characteristics such as particle size, zeta potential, and entrapment efficiency. The best-prepared liposomal vesicle was then incorporated into 1% carbopol 940 gel to develop a hydrogel system. The RV-loaded liposomal gel showed improved skin penetration. To assess the efficacy of the developed formulation, a diabetic foot ulcer animal model was used. The topical application of the developed formulation significantly reduced blood glucose and increased glycosaminoglycans (GAGs) to improve ulcer healing as well as wound closure on day 9. Faster re-epithelization, proliferation of fibroblast, formation of collagen, and reduced inflammatory cell infiltration at the wound site were also noted. Results indicate that RV-loaded liposomes in hydrogel-based wound dressing significantly accelerate wound healing in diabetic foot ulcers by restoring the altered wound healing process in diabetics.

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 ß-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.

Clinical Manifestation of AGE-RAGE Axis in Neurodegenerative and Cognitive Impairment Disorders.

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.

Emerging Nanotechnology for the Treatment of Alzheimer's Disease.

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 ß-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.

Leveraging Potential of Nanotherapeutics in Management of Diabetic Foot Ulcer.

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.

Repercussion of cAMP and EPAC in Memory and Signaling.

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.

Meticulous parade on naringin respecting its pharmacological activities and novel formulations.

Objective: 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. Materials and Methods: 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. Results: 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. Conclusion: The results of this exploration provides biological actions of bioflavonoid (naringin), predominantly on pharmacological and novel dosage forms of naringin.

Effectual Endeavors of Silk Protein Sericin against Isoproterenol Induced Cardiac Toxicity and Hypertrophy in Wistar Rats.

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.

An in-Depth Analysis of Ovarian Cancer: Pathogenesis and Clinical Manifestation.

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.

Aftermath of AGE-RAGE Cascade in the pathophysiology of cardiovascular ailments.

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.

A dossier on COVID-19 chronicle.

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 of Gala and Fuji apple juice against isoprenaline-induced cardiotoxicity in rats.

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.

Dig & Delve into Protein Based Nanoformulations.

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.

Diligent profiling of preclinical safety of the silk protein sericin.

BACKGROUND: Sericin is a widely used protein in the pharmaceutical industry derived from the silkworm, Bombyx mori, and used for the treatment of various diseases and pathological conditions. It is the main ingredient of the Unani preparation khameera abresham. The study was conducted to evaluate the preclinical toxicity of the silk protein sericin in mice. METHODS: In the acute toxicity study, sericin was administered once orally to different groups of animals at doses of 500, 1000, and 2000 mg/kg. Animals were observed for 14 days. In the sub-acute toxicity study, sericin was administered in mice for 4 weeks in the toxic group at doses of 500, 1000, and 2000 mg/kg, while in the recovery group it was administered for 4 weeks at doses of 500 and 2000 mg/kg followed by 2 weeks of distilled water administration. RESULTS: In the acute toxicity study, the observed parameters showed no significant difference, and no mortality was reported. In the sub-acute toxicity study, there were no toxicological effects in any of the estimated parameters, while histopathological analysis showed inflammation in vital organs at the dose of 2000 mg/kg. CONCLUSIONS: Results of our acute toxicity study suggest that sericin is safe at all administered doses, while the sub-acute study suggests that the NOAEL (no-observed-adverse-effect level) of sericin is below 2000 mg/kg, at which it can be considered safe.

Herbal Remedies: A Boon for Diabetic Neuropathy.

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.