Exploring the potential of quercetin in Alzheimer's Disease: Pharmacodynamics, Pharmacokinetics, and Nanodelivery systems.

Alzheimer's disease (AD) is a primary cause of dementia that affects millions of people worldwide and its prevalence is likely to increase largely in the coming decades. Multiple complex pathways, such as oxidative stress, tau and amyloid-beta (Aß) pathology, and cholinergic dysfunction, are involved in the pathogenesis of Alzheimer's disease. The conventional treatments provide only symptomatic relief and not a complete cure for the disease. On the other hand, recent studies have looked into the possibility of flavonoids as an effective therapeutic strategy for treating AD. Quercetin, a well-known flavonol, has been extensively studied for AD treatment. Therefore, this review mainly focuses on the pharmacokinetics properties of quercetin and its modes of action, such as antioxidant, anti-inflammatory, anti-amyloidogenic, and neuroprotective properties, which are beneficial in treating AD. It also highlights the nano delivery systems of quercetin, including liposomes, nanostructures lipid carriers, solid lipid nanoparticles, nanoemulsions, microemulsions, self-emulsifying drug delivery systems, and nanoparticles reported for AD treatment. The remarkable potential of quercetin nanocarriers has been reflected in enhancing its bioavailability and therapeutic efficacy. Therefore, clinical studies must be conducted to explore it as a therapeutic strategy for Alzheimer's disease.

Diabetes and its Complications: Role of Luteolin, A Wonder Chemical from the Natural Source.

Flavonoids have been reported to be vital in treating various chronic disorders. Luteolin (3',4',5,7-tetrahydroxyflavone) is a flavonoid present in a variety of plant sources such as celery, green pepper, olive oil, peppermint, thyme, rosemary, oregano, etc. It has been reported to have various pharmacological activities such as antioxidant, anti-inflammatory, anticancer, antidiabetic, anti-Alzheimer, antimicrobial, etc. Many scientific studies have been carried out on luteolin for its possible effects on diabetes and its associated complications. The present review focuses on the role of luteolin in diabetes mellitus and the associated complications. The antidiabetic impact of luteolin is linked with the increased expression of PPARγ and GLUT. Various in vitro and in vivo studies have been performed to explore the effects of luteolin on diabetic complications, and it has shown a significant impact in the management of the same.

Phloretin: a comprehensive review of its potential against diabetes and associated complications.

OBJECTIVES: Phloretin is ubiquitous in apples (Malus domestica) and other fruits and has potential antidiabetic properties. Considering the preclinical potential of phloretin, its transition to clinical observations has unintentionally been neglected, particularly within the diabetic population. Furthermore, a comprehensive understanding of its pharmacokinetics remains elusive. This review seeks to offer valuable insights into phloretin's physical properties, pharmacokinetics, and pharmacodynamics, aiming to unveil opportunities for additional research on its therapeutic potential in the context of diabetes. KEY FINDINGS: All pharmacokinetic reports of phloretin confirm that the utilization of phloretin gets enhanced during diabetic conditions. Phloretin targets pathomechanisms such as glucose transporter 4 (GLUT4) and peroxisome proliferator's activity-activated receptor-γ (PPAR-γ) to decrease insulin resistance in diabetic conditions. Moreover, phloretin targets inflammatory, oxidative, and apoptotic signaling to minimize the progression of diabetes-associated macro- and microvascular complications. SUMMARY: The pleiotropic antidiabetic action of phloretin is mainly dependent on its pharmacokinetics. Nevertheless, further investigation into the altered pharmacokinetics of phloretin during diabetic conditions is essential. Additionally, the results derived from clinical studies utilized apples, apple extract, and supplements containing phloretin. Greater emphasis should be placed on future clinical studies to assess the potential of phloretin as a standalone compound.

Mitigation of cisplatin-induced nephrotoxicity by chelidonic acid in Wistar rats.

INTRODUCTION: Cisplatin, an anti-cancer drug is used to treat a wide range of solid tumors. Nevertheless, nephrotoxicity is the major adverse effect that restricts its clinical application. The present study focuses on the effect of chelidonic acid in cisplatin-induced nephrotoxicity. METHODS: Wistar rats were injected with cisplatin (5 mg/kg, intraperitoneally (i.p.), once in a week for 4 weeks) and chelidonic acid (10, 20, and 40 mg/kg, per oral (p.o.) for 4 weeks). Body weight, urine, biochemical, and oxidative stress parameters were performed to evaluate the effect of chelidonic acid in cisplatin-induced nephrotoxicity in rats. Pro-inflammatory cytokines and nuclear factor erythroid 2-related factor 2 (Nrf2) concentrations were determined. Expression of phospho-AMP activated protein kinase (phospho-AMP) and hypoxia-inducible factor 1-alpha (HIF-1α) was studied with western blot. Haematoxylin and eosin, periodic acid-Schiff, and Masson's trichrome staining were used to study kidney tissues. RESULTS: Relative kidney weight and urine output were significantly increased in cisplatin-administered rats. Whereas, albumin, and creatinine concentration were decreased, and treatment with chelidonic acid reverses these deleterious effects of cisplatin significantly. Kidney functions were improved by chelidonic acid treatment with a reduction in tumor necrosis factor-alpha (TNF-α), Interleukin-6 (IL-6), and transforming growth factor-beta (TGF-ß1) concentration. The oxidative stress was decreased as compared to the cisplatin group. Furthermore, Nrf2 was significantly increased by chelidonic acid treatment. Chelidonic acid treatment significantly increased the expression of phospho-AMPK and HIF-1α in kidney tissue. Histopathological studies revealed that chelidonic acid reduced kidney damage. CONCLUSION: The findings showed that chelidonic acid increases phospho-AMPK and HIF-1α in the kidney tissue and significantly lowers the inflammatory cytokines, thus it is an effective molecule for providing protection against cisplatin-induced nephrotoxicity.

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

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

Effects of Acute and Repeated Dose Toxicity Profiling of Chelidonic Acid in Rats: in Silico and in Vivo Evidence.

Chelidonic acid is a phytoconstituent found in rhizomes of the perennial plant celandine. The current study aims to evaluate the acute and repeated dose oral toxicity study of chelidonic acid as per the OECD guidelines 425 and 407. The pharmacokinetic and toxicity profile of chelidonic acid was predicted using online servers and tools. A single dose of chelidonic acid (2000 mg/kg) was administered to female Wistar rats in an acute toxicity study, and the animals were monitored for 14 days. We studied the toxicity profile of chelidonic acid at 10, 20, and 40 mg/kg doses in Wistar rats for repeated dose toxicity (28 days). Clinical biochemistry, haematological, and urine parameters were estimated. A gross necropsy and histopathology were performed. A single oral dose of chelidonic acid (2000 mg/kg) showed no signs of toxicity or mortality. The Administration of chelidonic acid showed no significant alterations in haematological, biochemical, and urine parameters. The histopathology showed normal structure and architecture in all the vital organs. A gross necropsy of vital organs showed no signs of toxicity. The chelidonic acid was found to be safe at all selected dose levels in the acute and repeated dose toxicity study in rats.

Stem cells as a regenerative medicine approach in treatment of microvascular diabetic complications.

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by high blood glucose and is associated with high morbidity and mortality among the diabetic population. Uncontrolled chronic hyperglycaemia causes increased formation and accumulation of different oxidative and nitrosative stress markers, resulting in microvascular and macrovascular complications, which might seriously affect the quality of a patient's life. Conventional treatment strategies are confined to controlling blood glucose by regulating the insulin level and are not involved in attenuating the life-threatening complications of diabetes mellitus. Thus, there is an unmet need to develop a viable treatment strategy that could target the multi-etiological factors involved in the pathogenesis of diabetic complications. Stem cell therapy, a regenerative medicine approach, has been investigated in diabetic complications owing to their unique characteristic features of self-renewal, multilineage differentiation and regeneration potential. The present review is focused on potential therapeutic applications of stem cells in the treatment of microvascular diabetic complications such as nephropathy, retinopathy, and polyneuropathy.

Treatment with Terminalia chebula Extract Reduces Insulin Resistance, Hyperglycemia and Improves SIRT1 Expression in Type 2 Diabetic Rats.

BACKGROUND: Terminalia chebula Retz., Family Combretaceae (T. chebula) is one of the important plants mentioned in Ayurveda, a traditional system of medicine. The present work was designed to study the effect of the aqueous extract of T. chebula fruits in type 2 diabetic rats. METHODS: The aqueous extract of the fruits was prepared by the double maceration technique. The extract was subjected to HPTLC analysis, which showed the presence of ellagic acid and gallic acid. Type 2 diabetes was induced in rats with a low dose of Streptozotocin (35 mg/kg) after administering a high-fat diet for fourteen days. Diabetic animals were treated with 500 and 1000 mg/kg of aqueous extract of T. chebula fruits for six weeks. RESULTS: Diabetic rats showed a significantly (511.7 ± 17.6) (p < 0.001) high plasma glucose level compared to the normal group (106 ± 3.358). The T. chebula treatment group showed a significant (p < 0.001) reduction in plasma glucose at 500 mg/kg (394.3 ± 10.35) and 1000 mg/kg (368.6 ± 30.08) doses when compared with the diabetic control group. Treatment with aqueous extract significantly reduced lipid parameters in diabetic animals when compared to the animals in the diabetic control group. Treatment with extract at a dose of 500 mg/kg and 1000 mg/kg showed a significant reduction in AST (p < 0.01, p < 0.001) when compared with diabetic control rats. Treatment with extract significantly reduced ALT at 500 mg/kg (p < 0.05) and 1000 mg/kg (p < 0.001) doses when compared with diabetic control rats. The extract treatment improved insulin sensitivity and insulin sensitivity index (ISI) and significantly decreased HOMR-IR. Treatment with T. chebula aqueous extract at 1000 mg/kg significantly increased the level of GSH (p < 0.05) when compared to diabetic control rats. T. chebula treatment at 1000 mg/kg significantly increased levels of CAT (p < 0.01). Histopathology of pancreatic tissue revealed that the extract has a protective effect against the damage caused by hyperglycemia. Immunohistochemistry of pancreatic tissue showed increased expression of SIRT1 in diabetic animals treated with the extract. CONCLUSIONS: The results of the present study indicate that the extract of T. chebula has significant effects in the management of type 2 diabetes.

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

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

Effects of baicalein with memantine on aluminium chloride-induced neurotoxicity in Wistar rats.

Alzheimer's disease is a progressive neurodegenerative condition. It is one of the most common 28 forms of dementia accounting for 60-80% of people suffering from dementia. There are very few medications that are approved for the treatment of Alzheimer's disease. Baicalein, belonging to the flavone subclass of flavonoids, has been reported to have a neuroprotective effect by reducing oxidative stress and neuroinflammation, inhibiting the AChE enzyme, and reducing amyloid protein aggregation and toxicity. Memantine is one of the most important drugs used for treating Alzheimer's disease. The purpose of this work was to study the effect of baicalein with memantine on aluminum chloride-induced neurotoxicity in Wistar rats. Aluminum chloride (100 mg/kg p.o.) was administered for 42 days in male Wistar rats to induce neurotoxicity. Baicalein alone (10 mg/kg) and a combination of baicalein (5 mg/kg and 10 mg/kg) with memantine (20 mg/kg) were administered for 42 days. Treatment of baicalein with memantine showed significant improvement in behavioral parameters. The combination reduced oxidative stress and the formation of ß-Amyloid plaques and increased brain-derived neurotrophic factor (BDNF) expression. Based on findings, it can be concluded that treatment with baicalein and memantine may slow the progression of neurodegeneration in rats.

The Combination of Baicalein and Memantine Reduces Oxidative Stress and Protects against ß-amyloid-Induced Alzheimer's Disease in Rat Model.

Alzheimer's disease (AD) is a neuronal condition causing progressive loss of memory and cognitive dysfunction particularly in elders. An upsurge in the global old age population has led to a proportionate increase in the prevalence of AD. The current treatments for AD are symptomatic and have debilitating side effects. A literature review and current research have directed scientists to explore natural products with better safety and efficacy profiles as new treatment options for AD. Baicalein, belonging to the flavone subclass of flavonoids, has been reported for its anti-oxidant, anti-inflammatory, AChE enzyme inhibitory activity and anti-amyloid protein aggregation activity, which collectively demonstrates its benefits as a neuroprotective agent. Presently, memantine, a NMDAR antagonist, is one of the important drugs used for treatment of Alzheimer's disease. The current study aims to investigate the effect of baicalein in combination with memantine in ß-amyloid-induced AD in albino Wistar rats. Baicalein (10 mg/kg) alone, 5 mg/kg and 10 mg/kg in combination with memantine (20 mg/kg) was administered for 21 days. Treatment with baicalein in combination with memantine showed significant improvement in behavioural studies. The combination treatment decreased oxidative stress, ß-amyloid plaque formation and increased the expression of brain-derived neurotrophic factor (BDNF) in the brain. From the results, it can be concluded that treatment with baicalein and memantine could be beneficial for reducing the progression of neurodegeneration in rats. Baicalein has an additive effect in combination with memantine, making it a potential option for the treatment of AD.

Efficacy of collagenase Clostridium histolyticum in men with congenital penile curvature.

BACKGROUND: Collagenase Clostridium histolyticum (CCH) has been proven effective in multiple subpopulations of PD men; however, no studies have evaluated its role with congenital penile curvature (CPC). AIM: To evaluate the safety and efficacy of CCH in men with CPC. METHODS: A prospective registry was queried of men undergoing CCH injections at our institution. Beginning in 2016, CCH was administered to CPC men using a similar protocol to PD. A comparative analysis was performed between cohorts to evaluate the safety and efficacy of therapy. OUTCOMES: Objective measures included penile length and curvature, while subjective outcomes included standardized (International Index of Erectile Function and Peyronie's Disease Questionnaire) and non-standardized assessments. Curvature outcomes were categorized as follows: 1 - included all men, with the most recent assessment considered final, and 2 - only men who had completed eight CCH injections or stopped early due to satisfaction. RESULTS: From 2014 to Oct 2021, a total of 453 men (408 PD, 45 CPC) underwent one or more CCH injections. In comparing cohorts, CPC men were younger (33 vs 58 years, p<0.0001), had lesser baseline curvatures (52.5 vs 65°, p<0.01), more ventral curves (25.7 vs 9.2%, p<0.01), and longer penile lengths (12.5 vs 12.0 cm, p=0.04). Following treatment, both cohorts experienced similar curvature improvements. Specifically, PD men experienced 20-25° or 33-35% improvements depending on definition compared to 25-30° or 40-50% in CPC men (all p-values >0.05). CPC and PD men also demonstrated similar changes on standardized questionnaires, with the exception of the Psychological and Physical subdomain, which was more improved in CPC men (-11 vs -4, p<0.01). Baseline curvature was positively correlated with greater absolute (degree) and relative (percent) improvements. Adverse events were similar between groups after controlling for confounders. CLINICAL IMPLICATIONS: CCH may be safely and effectively administered in men with CPC. These data provide the first evidence for the efficacy of a non-surgical therapeutic option in this cohort. STRENGTHS AND LIMITATIONS: Strengths - large, prospective series with standardized assessments; Limitations - non-randomized study, short-term follow-up, and lack of standardized method to differentiate CPC from PD. CONCLUSIONS: CCH may be safely and effectively administered to men with CPC, with similar success rates compared to PD. Increasing curvature was associated with greater absolute (degree) and relative (percent) improvements, supporting the role for CCH in men with mild, moderate, or severe curvatures. External validation is warranted prior to routine implementation.

Neuroprotective Effect of Quercetin and Memantine against AlCl3-Induced Neurotoxicity in Albino Wistar Rats.

Recent evidences indicate that there is a substantial increase in worldwide cases of dementia. Alzheimer's disease is the leading cause of dementia and may contribute to 60-70% of cases. Quercetin is a unique bioflavonoid that has numerous therapeutic benefits such as anti-allergy, anti-ulcer, anti-inflammatory, anti-hypertensive, anti-cancer, immuno-modulatory, anti-infective, antioxidant, acetylcholinesterase inhibitory activity, neuroprotective effects, etc. In the present study, we evaluated the neuroprotective effect of orally administered quercetin with memantine in albino Wistar rats after inducing neurotoxicity through AlCl3 (100 mg/kg, p.o.). Chronic administration of AlCl3 resulted in poor retention of memory and significant oxidative damage. Various behavioral parameters, such as locomotor activity, Morris water maze, elevated plus maze, and passive avoidance test, were assessed on days 21 and 42 of the study. The animals were euthanatized following the completion of the last behavioral assessment. Various oxidative stress parameters were assessed to know the extent of oxidative damage to brain tissue. Quercetin with memantine has shown significant improvement in behavioral studies, inhibition of AChE activity, and reduction in oxidative stress parameters. Histopathological studies assessed for cortex and hippocampus using hematoxylin and eosin (H&E), and Congo red stain demonstrated a reduction in amyloid-ß plaque formation after treatment of quercetin with memantine. Immunohistochemistry showed that quercetin with memantine treatment also improved the expression of brain-derived neurotrophic factor (BDNF) and inhibited amyloid-ß plaque formation. The present study results demonstrated protective effects of treatment of quercetin with memantine in the neurotoxicity linked to aluminum chloride in albino Wistar rats.

Biomarkers in diabetic neuropathy.

CONTEXT: The prevalence of diabetic neuropathy is drastically increasing in the world. To halt the progression of diabetic neuropathy, there is an unmet need to have potential biomarkers for the diagnosis and new drug discovery. OBJECTIVE: To study various biomarkers involved in the pathogenesis of diabetic neuropathy. METHODS: The literature was searched with the help of various scientific databases and resources like PubMed, ProQuest, Scopus, and Google scholar from the year 1976 to 2020. RESULTS: Biomarkers of diabetic neuropathy are categorised as inflammatory biomarkers such as MCP-1, VEGF, TRPV1, NF-κB; oxidative biomarkers such as adiponectin, NFE2L2; enzyme biomarkers like NADPH, ceruloplasmin, HO-1, DPP-4, PARP α; miscellaneous biomarkers such as SIRT1, caveolin 1, MALAT1, and microRNA. All biomarkers have a significant role in the pathogenesis of diabetic neuropathy. CONCLUSION: These biomarkers have a potential role in the progression of diabetic neuropathy and can be considered as potential targets for new drug discovery.

Endoplasmic Reticulum Stress and Renin-Angiotensin System Crosstalk in Endothelial Dysfunction.

BACKGROUND: Vascular endothelial dysfunction (VED) significantly results in catastrophic cardiovascular diseases with multiple aetiologies. Variations in vasoactive peptides, including angiotensin II and endothelin 1, and metabolic perturbations like hyperglycaemia, altered insulin signalling, and homocysteine levels result in pathogenic signalling cascades, which ultimately lead to VED. Endoplasmic reticulum (ER) stress reduces nitric oxide availability, causes aberrant angiogenesis, and enhances oxidative stress pathways, consequently promoting endothelial dysfunction. Moreover, the renin-angiotensin system (RAS) has widely been acknowledged to impact angiogenesis, endothelial repair and inflammation. Interestingly, experimental studies at the preclinical level indicate a possible pathological link between the two pathways in the development of VED. Furthermore, pharmacological modulation of ER stress ameliorates angiotensin-II mediated VED as well as RAS intervention either through inhibition of the pressor arm or enhancement of the depressor arm of RAS, mitigating ER stress-induced endothelial dysfunction and thus emphasizing a vital crosstalk. CONCLUSION: Deciphering the pathway overlap between RAS and ER stress may open potential therapeutic avenues to combat endothelial dysfunction and associated diseases. Several studies suggest that alteration in a component of RAS may induce ER stress or induction of ER stress may modulate the RAS components. In this review, we intend to elaborate on the crosstalk of ER stress and RAS in the pathophysiology of VED.

Nanoformulations of flavonoids for diabetes and microvascular diabetic complications.

Diabetes is a chronic metabolic disease characterized by an excess of glucose in the blood. If the constant sugar level is not managed correctly in diabetic patients, it may lead to microvascular complications such as diabetic retinopathy, neuropathy, and nephropathy. There are several synthetic drugs for the management of diabetes; however, these drugs produce immense adverse effects in long-term use. Flavonoids are naturally occurring substances categorized in various classes. They are known for their diverse pharmacological actions, and one of them is prominent antihyperglycemic action and their activities in diabetic complications. In the last few decades, many research studies emphasized the potential of flavonoids in diabetes management. Nevertheless, most flavonoids are insoluble in water and cannot produce desired therapeutic action when administered in conventional dosage forms. To overcome this issue, flavonoids were formulated into different nanoformulations to enhance solubility, absorption, and therapeutic efficacy. This review article focuses on flavonoid nanoformulations and in vitro and in vivo studies reported to overcome diabetes mellitus and its complications.

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

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

Effect of Costus pictus per se and in combination with Metformin and Enalapril in streptozotocin induced diabetic nephropathy in rats.

Aim: The present study was designed to investigate the effect of methanolic extract of Costus pictus (MECP) per se and in combination with drugs (Metformin and Enalapril) used in clinical practice in streptozotocin (STZ) induced diabetic nephropathy (DN) in rats. Methods: Diabetes was induced in male Wistar rats by a single injection of STZ (50 mg/kg i.p.). After 28 days diabetic rats were divided into six groups. Two groups were treated with MECP (200 mg/kg p.o.), MECP (400 mg/kg p.o.) respectively; one group was treated with metformin (225 mg/kg), enalapril (3.2 mg/kg) combination; and two groups were treated with a combination of metformin, enalapril and MECP (200 mg/kg) and combination of metformin, enalapril and MECP (400 mg/kg) respectively. One group was kept as diabetic control. At the end of the study, body weight, kidney weight, and kidney hypertrophy index were evaluated. Biochemical and antioxidant parameters were evaluated. TGF-ß levels in serum were estimated. Histopathology of the kidney was also studied. Results: The combination therapy showed a significant increase in the body weight, lowered blood glucose levels and ameliorated kidney hypertrophy index in STZ induced diabetic nephropathy in rats. It also normalized the altered levels of serum and urine parameters. Histopathological evaluation revealed that combination therapy reduced the vacuolar degeneration of tubules. Conclusions: The results indicate that combination therapy of metformin, enalapril, and MECP has beneficial effects in management of diabetic nephropathy.

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

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