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Alzheimer's disease (AD) is a widespread neurodegenerative disorder characterized by progressive memory and cognitive decline, posing a formidable public health challenge. This review explores the intricate interplay between two pivotal players in AD pathogenesis: ß-amyloid (Aß) and tau protein. While the amyloid cascade theory has long dominated AD research, recent developments have ignited debates about its centrality. Aß plaques and tau NFTs are hallmark pathologies in AD. Aducanumab and lecanemab, monoclonal antibodies targeting Aß, have been approved, albeit amidst controversy, raising questions about the therapeutic efficacy of Aß-focused interventions. On the other hand, tau, specifically its hyperphosphorylation, disrupts microtubule stability and contributes to neuronal dysfunction. Various post-translational modifications of tau drive its aggregation into NFTs. Emerging treatments targeting tau, such as GSK-3ß and CDK5 inhibitors, have shown promise in preclinical and clinical studies. Restoring the equilibrium between protein kinases and phosphatases, notably protein phosphatase-2A (PP2A), is a promising avenue for AD therapy, as tau is primarily regulated by its phosphorylation state. Activation of tau-specific phosphatases offers potential for mitigating tau pathology. The evolving landscape of AD drug development emphasizes tau-centric therapies and reevaluation of the amyloid cascade hypothesis. Additionally, exploring the role of neuroinflammation and its interaction with tau pathology present promising research directions.
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Enfermedad de Alzheimer , Proteínas tau , Humanos , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/terapia , Proteínas tau/metabolismo , Fosforilación , Animales , Péptidos beta-Amiloides/metabolismoRESUMEN
The immune system is one of the essential defense mechanisms. Immune system inadequacy increases the risk of infections and cancer diseases, whereas over-activation of the immune system causes allergies or autoimmune disorders. Immunomodulators have been used in the treatment of immune-related diseases. There is growing interest in using herbal medicines as multicomponent agents to modulate the complex immune system in immune-related diseases. Many therapeutic phytochemicals showed immunomodulatory effects by various mechanisms. This mechanism includes stimulation of lymphoid cell, phagocytosis, macrophage, and cellular immune function enhancement. In addition increased antigen-specific immunoglobulin production, total white cell count, and inhibition of TNF-α, IFN-γ, NF-kB, IL-2, IL-6, IL-1ß, and other cytokines that influenced the immune system. This review aims to overview, widely investigated plant-derived phytoconstituents by targeting cells to modulate cellular and humoral immunity in in vivo and in vitro. However, further high-quality research is needed to confirm the clinical efficacy of plant-based immunomodulators.
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Citocinas , Factores Inmunológicos , Factores Inmunológicos/farmacología , Adyuvantes Inmunológicos/farmacología , Inmunidad Humoral , Sistema InmunológicoRESUMEN
Nuclear factor kappa B cells (NF-κB) activation causes induction of the noncanonical IκB kinases (I-kappa-B kinase epsilon (IKKε) and TANK-binding kinase 1 (TBK1) in liver and fat after high fat diet which followed activating of cascade of counter-inflammation that conserves energy storage. Chrysin (5,7-dihydroxyflavone), a natural flavonoid, present in many plants, honey and propolis, used conventionally to treat numerous ailments. The present study was aimed to identify the protective role of chrysin on the glucose lowering and insulin sensitivity in diet induced obese (DIO) mice by regulating IKKε/TBK1. Chrysin administered therapeutically (60, 100, 200 mg/kg body weight) and preventive mode (200 mg/kg body weight) for 4 and 10 weeks respectively to DIO mice. At last fasting blood glucose, oral glucose tolerance test, serum lipid profile, as well as the expression level of IKKε/TBK1 and triglyceride in the liver tissue were assessed. DIO mice showed impaired glucose tolerance, reduced weight gain, elevated hepatic IKKε/TBK1 expression, fatty acid infiltration triglyceride and increased in plasma insulin and glucose. Chrysin in both therapeutic and preventive mode normalized the altered levels of the same. Overall chrysin improves glycemic control and insulin sensitivity through regulating expression of IKKε/TBK1 in liver of DIO mice.
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Quinasa I-kappa B , Resistencia a la Insulina , Animales , Dieta Alta en Grasa/efectos adversos , Flavonoides/farmacología , Quinasa I-kappa B/metabolismo , Hígado/metabolismo , Ratones , Ratones Obesos , Proteínas Quinasas/metabolismo , Proteínas Serina-Treonina QuinasasRESUMEN
Prostate cancer is the second most common malignancy in the human reproductive system. Eupalitin is one of the O-methylated flavonol-exhibited enhanced cancer chemopreventive agents. The current study highlights the structural determination of eupalitin and aims to explore the antitumor activity of eupalitin in human prostate cancer cell (PC3) and its underlying mechanism. Eupalitin structure was determined by using FTIR, (1)H NMR, and (13)C NMR. PC3 cells were treated with increasing concentrations of eupalitin, followed by analysis of the cell viability with an MTT assay. The results demonstrated that eupalitin markedly inhibited the proliferation of PC3 cells in a concentration-dependent manner. The results from fluorescent microscopic analysis of nuclear condensation and intracellular ROS generation determined that eupalitin significantly induced ROS level lead to nuclear apoptosis. Cell cycle analysis revealed that eupalitin-induced cell cycle progression as a percentage of cells in G0/G1 phase decreased whereas S phase increased. Caspase-3 immunofluorescence analysis confirms the efficacy of eupalitin-inducing apoptotic pathway and cell death. Thus, our study is helpful in understanding the mechanism underlying these effects in prostate cancer and it may provide novel molecular targets for prostate cancer therapy.
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Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Flavonoides/farmacología , Neoplasias de la Próstata/tratamiento farmacológico , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Fase G1/efectos de los fármacos , Humanos , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Fase S/efectos de los fármacosRESUMEN
Diabetes is a chronic condition that has an impact on a huge part of the world. Both animals and humans have been demonstrated to benefit from natural goods, and organisms (animals, or microbes). In 2021, approximately 537 million adults (20-79 years) are living with diabetes, making it the one of the biggest cause of death worldwide. Various phytoconstituent preserved ß- cells activity helps to prevent the formation of diabetes problems. As a result, ß-cells mass and function are key pharmaceutical targets. The purpose of this review is to provide an overview of flavonoids' effects on pancreatic ß-cells. Flavonoids have been demonstrated to improve insulin release in cell lines of isolated pancreatic islets and diabetic animal models. Flavonoids are thought to protect ß-cells by inhibiting nuclear factor-κB (NF-κB) signaling, activating the phosphatidylinositol 3-kinase (PI3K) pathway, inhibiting nitric oxide production, and lowering reactive oxygen species levels. Flavonoids boost ß-cells secretory capacity by improving mitochondrial bioenergetic function and increasing insulin secretion pathways. Some of the bioactive phytoconstituents such as S-methyl cysteine sulfoxides stimulate insulin synthesis in the body and increase pancreatic output. The berberine increased insulin secretion in the HIT-T15 and Insulinoma 6 (MIN6) mouse cell line. Epigallocatechin-3-Gallate protects against toxicity accrued by cytokines, reactive oxygen species (ROS), and hyperglycemia. Quercetin has been proven to boost insulin production by Insulinoma 1 (INS-1) cells and also protect cell apoptosis. Overall flavonoids have beneficial effects on ß-cells by prevented their malfunctioning or degradation and improving synthesis or release of insulin from ß-cells.
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Diabetes Mellitus , Células Secretoras de Insulina , Insulinoma , Neoplasias Pancreáticas , Ratones , Animales , Humanos , Insulina/metabolismo , Flavonoides/farmacología , Flavonoides/uso terapéutico , Flavonoides/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Células Secretoras de Insulina/metabolismo , FN-kappa B , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/metabolismo , ApoptosisRESUMEN
Curcumin is a naturally occurring polyphenolic compound extracted from the rhizomes of Curcuma longa, commonly known as turmeric. It has been used for centuries in traditional medicine and is gaining increasing attention in modern medicine owing to its potential therapeutic benefits. Psoriasis is a chronic inflammatory disease characterized by red scaly patches on the skin. Curcumin has been found to be effective in treating psoriasis by inhibiting the activity of various enzymes and proteins involved in the inflammation and proliferation of psoriatic skin cells. Nanogel preparation of curcumin has been found to be a promising approach for the delivery of compounds to treat psoriasis. Nanogels are composed of biocompatible and biodegradable crosslinked hydrogels. The nanogel formulation of curcumin increases its solubility, stability, and bioavailability, indicating that a lower dose is needed to achieve the same therapeutic effect. This review article suggests that the nanogel preparation of curcumin can be a better alternative for psoriasis treatment as it increases the bioavailability and stability of curcumin and also reduces the required dosage. This study suggests that curcumin nanogel preparations are promising alternatives to traditional psoriasis treatments and could potentially be used as a more effective and safe treatment option. This article highlights the need for further research to fully understand the potential of curcumin nanogel preparations for psoriasis treatment in humans.
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The field of dementia research has witnessed significant developments in our understanding of neurodegenerative disorders, with a particular focus on Alzheimer's disease (AD) and Frontotemporal Dementia (FTD). Dementia, a collection of symptoms arising from the degeneration of brain cells, presents a significant healthcare challenge, especially as its prevalence escalates with age. This abstract delves into the complexities of these disorders, the role of biomarkers in their diagnosis and monitoring, as well as emerging neurophysiological insights. In the context of AD, anti-amyloid therapy has gained prominence, aiming to reduce the accumulation of amyloid-beta (Aß) plaques in the brain, a hallmark of the disease. Notably, Leqembi recently received full FDA approval, marking a significant breakthrough in AD treatment. Additionally, ongoing phase 3 clinical trials are investigating novel therapies, including Masitinib and NE3107, focusing on cognitive and functional improvements in AD patients. In the realm of FTD, research has unveiled distinct neuropathological features, including the involvement of proteins like TDP-43 and progranulin, providing valuable insights into the diagnosis and management of this heterogeneous condition. Biomarkers, including neurofilaments and various tau fragments, have shown promise in enhancing diagnostic accuracy. Neurophysiological techniques, such as transcranial magnetic stimulation (TMS), have contributed to our understanding of AD and FTD. TMS has uncovered unique neurophysiological signatures, highlighting impaired plasticity, hyperexcitability, and altered connectivity in AD, while FTD displays differences in neurotransmitter systems, particularly GABAergic and glutamatergic circuits. Lastly, ongoing clinical trials in anti-amyloid therapy for AD, such as Simufilam, Solanezumab, Gantenerumab, and Remternetug, offer hope for individuals affected by this devastating disease, with the potential to alter the course of cognitive decline. These advancements collectively illuminate the evolving landscape of dementia research and the pursuit of effective treatments for these challenging conditions.
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Enfermedad de Alzheimer , Demencia Frontotemporal , Humanos , Demencia Frontotemporal/psicología , Proteínas tau , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides , BiomarcadoresRESUMEN
Every year, the World Health Organization reports 500,000 new cases of drug-resistant tuberculosis (TB), which poses a serious global danger. The increased number of XDR-TB and MDR-TB cases reported worldwide necessitates the use of new therapeutic approaches. The main issues with the antitubercular medications now in use for the treatment of multidrug-resistant tuberculosis are their poor side effect profile, reduced efficacy, and antimicrobial resistance. One possible remedy for these problems is bedaquiline. The need for better treatment strategies is highlighted by the strong minimum inhibitory concentrations that bedaquiline (BDQ), a novel anti-TB medicine, exhibits against both drug-resistant and drug-susceptible TB. Bedaquiline may be able to help with these problems. Bedaquiline is a medication that is first in its class and has a distinct and particular mode of action. Bedaquiline is an ATP synthase inhibitor that is specifically directed against Mycobacterium tuberculosis and some nontuberculous mycobacteria. It is metabolized by CYP3A4. Bedaquiline preclinical investigations revealed intralesional drug biodistribution. The precise intralesional and multi-compartment pharmacokinetics of bedaquiline were obtained using PET bioimaging and high-resolution autoradiography investigations. Reduced CFU counts were observed in another investigation after a 12-week course of therapy. Meta-analyses and systematic reviews of phase II trials on bedaquiline's efficacy in treating drug-resistant tuberculosis in patients reported higher rates of cure, better culture conversion, and lower death rates when taken in conjunction with a background regimen. Here is a thorough medication profile for bedaquiline to aid medical professionals in treating individuals with tuberculosis.
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Antituberculosos , Diarilquinolinas , Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Tuberculosis Pulmonar , Diarilquinolinas/uso terapéutico , Diarilquinolinas/farmacocinética , Humanos , Antituberculosos/uso terapéutico , Antituberculosos/farmacocinética , Antituberculosos/farmacología , Antituberculosos/administración & dosificación , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/microbiología , Mycobacterium tuberculosis/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , AnimalesRESUMEN
Oral disintegrating tablets (ODT) offer an attractive choice for Gastroesophageal Reflux Disease (GERD) patients suffering from dysphagia. In chronic condition, GERD patient suffers from severe erosive esophagitis. Thus patients feel difficulty and pain during swallowing, which results in patient in-compliance toward medication of tablets or capsules- especially in geriatrics and pediatric patients. These symptoms of GERD patients have attracted the formulation scientists in improving the formulation methodology for such patients. Orally disintegrating tablets could increase the therapeutic impact and drug compliance in these patients. The aim of this compilation is to provide a more convenient way to develop an oral disintegrating drug delivery system of proton pump inhibitors in patients suffering from odynophagia, associated with chronic Gastroesophageal Reflux Disease (GERD). Oral disintegrating tablets (ODT), when placed on the tongue, can quickly disintegrate and release the medicament. It later dissolves or disperses in saliva without any additional water. The saliva containing drug can easily be swallowed and descends into the stomach leading to maximum absorption from the mouth, throat, and upper esophagus. The patient compliance and bio-availability of Oral disintegrating tablets (ODT) are high compared to other conventional tablets.
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Trastornos de Deglución , Reflujo Gastroesofágico , Humanos , Niño , Inhibidores de la Bomba de Protones/uso terapéutico , Reflujo Gastroesofágico/tratamiento farmacológico , Comprimidos/uso terapéutico , Cumplimiento de la MedicaciónRESUMEN
BACKGROUND: Medicinal plants have been found beneficial in the control and therapy of many ailments as they contain bioactive compounds, and many of them are used as precursors in the biosynthesis of natural medicines. Diuretics are used as a primary treatment in patients with edema associated with liver cirrhosis and kidney diseases, hyperkalemia, hypertension, heart failure, or renal failure. Furthermore, they are also used to increase the excretion of sodium and reduce blood volume. Due to various adverse events associated with synthetic diuretics, there is a need to investigate alternate plant-based bioactive components that have effective diuretic activity with minimal side effects. OBJECTIVE: This review compiled the reported bioactive compounds from different plant sources along with their mechanisms of diuretic activity. METHODS: Different sources were used to collect information regarding herbal plants with therapeutic value as diuretics. These included published peer-reviewed journal articles, scholarly articles from StatPearls, and search engines like Google Scholar, PubMed, Scopus, Springer, ScienceDirect, Wiley, etc. Results: In this review, it was found that flavonoids like rutin, acacetin, naringenin, etc. showed significant diuretic activity in experimental models by various mechanisms, but mostly by blocking the sodium-potassium-chloride co-transporter, while some bioactive compounds showed diuretic actions via other mechanisms as well. CONCLUSION: Research on clinical trials of these isolated bioactive compounds needs to be further conducted. Thus, this review provides an understanding of the potential diuretic bioactive compounds of plants for further research and pharmaceutical applications.
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Hipertensión , Enfermedades Renales , Humanos , Diuréticos/efectos adversos , Diuresis , Hipertensión/diagnóstico , Hipertensión/tratamiento farmacológico , Hipertensión/inducido químicamente , Sodio/uso terapéuticoRESUMEN
Cardiac dysfunction such as cirrhotic cardiomyopathy is more common in liver cirrhosis related disorders including primary biliary cholangitis or biliary cirrhosis and primary sclerosing cholangitis. Bile duct ligation (BDL) is an effective model of biliary cholestasis, producing oxidative damage and fibrosis. This research was designed to evaluate the effect of Lupeol and Naringin and its combination on bile duct ligation induced cardiac injury in rats. For pharmacological evaluation, rats were randomly divided into seven groups; intrahepatic cholestasis induced by ligation of the bile duct might lead to cirrhotic cardiomyopathy. The results were analyzed by physical, biochemical and histological examination. The Lupeol (100 mg/kg, p.o.), Naringin (100 mg/kg, p.o.) and its combination (100 mg/kg each) treated group significantly improved physical infarct size, biochemical (Nitrite, SOD, CAT, and GSH) and histological (heart tissue- mitochondrial function/integrity and fibrosis) alterations occurs due to BDL-ligation. This study was concluded that oral administration of Lupeol, Naringin, and its combination has a curative potential against BDL-induced cardiac injury in rats by reducing oxidative stress and inflammatory reactions, resulting in reduced heart necrosis/myocardial infarction and increased myocardial activity. It also inhibits cardiac damage in the rat heart, these effects may be linked to the NO level (eNOS) is increased and the inactivation of the NF-kB-p65 expression pathways.This study also provides new insights into the development of lupeol and Naringin combination that can be used as supportive therapy for cardiovascular diseases.
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Hepatopatías , FN-kappa B , Animales , Ratas , Conductos Biliares/cirugía , Conductos Biliares/metabolismo , Conductos Biliares/patología , Fibrosis , Ligadura , Hígado/metabolismo , Cirrosis Hepática/metabolismo , FN-kappa B/metabolismo , FN-kappa B/farmacología , Nitritos , Estrés OxidativoRESUMEN
Uterine fibroids (UFs), leiomyomas or myomas, are a type of malignancy that affects the smooth muscle of the uterus, and it is most commonly detected in women of reproductive age. Uterine fibroids are benign monoclonal growths that emerge from uterine smooth muscle cells (myometrium) as well as fibroblasts. Uterine fibroid symptoms include abnormal menstrual bleeding leading to anaemia, tiredness, chronic vaginal discharge, and pain during periods. Other symptoms include protrusion of the abdomen, pain during intercourse, dysfunctions of bladder/bowel leading to urinary incontinence/retention, pain, and constipation. It is also associated with reproductive issues like impaired fertility, conceiving complications, and adverse obstetric outcomes. It is the leading cause of gynaecological hospitalisation in the American subcontinent and a common reason for the hysterectomy. Twenty-five percent of the reproductive women experience the symptoms of uterine fibroids, and among them, around 25% require hospitalization due to the severity of the disease. The frequency of the disease remains underestimated as many women stay asymptomatic and symptoms appear gradually; therefore, the condition remains undiagnosed. The exact frequency of uterine fibroids varies depending on the diagnosis, and the population investigated; nonetheless, the incidence of uterine fibroids in reproductive women ranges from 5.4 percent to 77 percent. The uterine fibroid treatment included painkillers, supplementation with iron, vitamin D3, birth control, hormone therapy, gonadotropin-releasing hormone (GnRH) agonists, drugs modulating the estrogen receptors, and surgical removal of the fibroids. However, more research needed at the level of gene to get a keen insight and treat the disease efficiently.
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Leiomioma , Neoplasias Uterinas , Embarazo , Femenino , Humanos , Neoplasias Uterinas/terapia , Neoplasias Uterinas/tratamiento farmacológico , Leiomioma/terapia , Leiomioma/tratamiento farmacológico , Útero , Histerectomía , DolorRESUMEN
Diabetic neuropathy (DN) is a common and debilitating complication of diabetes mellitus that affects the peripheral nerves and causes pain, numbness, and impaired function. The pathogenesis of DN involves multiple molecular mechanisms, such as oxidative stress, inflammation, and pathways of advanced glycation end products, polyol, hexosamine, and protein kinase C. Phytochemicals are natural compounds derived from plants that have various biological activities and therapeutic potential. Flavonoids, terpenes, alkaloids, stilbenes, and tannins are some of the phytochemicals that have been identified as having protective potential for diabetic neuropathy. These compounds can modulate various cellular pathways involved in the development and progression of neuropathy, including reducing oxidative stress and inflammation and promoting nerve growth and repair. In this review, the current evidence on the effects of phytochemicals on DN by focusing on five major classes, flavonoids, terpenes, alkaloids, stilbenes, and tannins, are summarized. This compilation also discusses the possible molecular targets of numerous pathways of DN that these phytochemicals modulate. These phytochemicals may offer a promising alternative or complementary approach to conventional drugs for DN management by modulating multiple pathological pathways and restoring nerve function.
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Colorectal cancer (CRC) is the second most common cause of cancer related deaths in the United States. However, more than half of all incidence and mortality are caused by risk factors such as smoking, unhealthy diet, excessive alcohol consumption, inactivity, and excess weight, and thus can be protected. CRC morbidity and mortality can also be reduced by proper screening and monitoring. Over the last few years the amalgamation of nanotechnology with healthcare system has brought about the potential to administer the delivery of certain therapeutic drugs to cancer cells without affecting normal tissues. Recent strategies combine the diagnostic and therapeutic approaches to improve the overall performance of cancer nanomedicines. Targeted cancer nanotherapeutics provides many more opportunities for the selective detection of toxic chemicals within cancer cells. The distinctive features of nanoparticles, such as their small size, large surface to volume ratio, and the ability of nanoparticles to achieve several interactions of ligands at surface, offer great benefits of nanomedicines to treat various types of cancers. This review highlights the molecular mechanisms of colorectal carcinogenesis and discusses various key concepts in the development of nanotherapeutics targeted for CRC treatment.
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Neoplasias Colorrectales , Nanopartículas , Humanos , Sistemas de Liberación de Medicamentos , Nanomedicina , Nanopartículas/química , Nanotecnología , Neoplasias Colorrectales/tratamiento farmacológicoRESUMEN
Insulin resistance (IR) is a condition in which target cells become insensitive to normal insulin concentrations in order to deliver glucose. The goal of this study was to see if solasodine combined with coenzyme Q10 could help rats with insulin resistance caused by a high-fat diet (HFD) by regulating the expression of IRS-I and PPAR-γ proteins.One of the six groups (n=6) got a conventional diet for 16 weeks as a control (normal), the HFD was given to the other five groups for 16 weeks, which further classified as-one group as HFD control while others treated with pioglitazone (10 mg/kg), coenzyme Q10 (50 mg/kg), solasodine (50 mg/kg) and combination of solasodine and coenzyme Q10i.e. SDQ10 (total 50 mg/kg) for the last 4 weeks orally once daily. Blood and tissue samples were collected by the end of study period for the biochemical and histological studies. As a result, HFD fed rats exhibited a significant increase in food and energy intake, body mass index, kidney and pancreas weight, fasting glucose, glycosylated haemoglobin, insulin level, liver enzyme ALT and AST and decrease antioxidant activity of superoxide dismutase and catalase. HFD received animals also produced a lower level of p-IRS1 and PPAR-y protein expression in western blot analysis. SDQ10 in combination successfully restored the above-mentioned complexity of insulin resistance caused by aHFD. Besides, increasesthe antioxidant activity of superoxide dismutase and catalase and normalized the architecture of kidney, pancreas and adipose tissue as well astreatment with SDQ10 raised the level of p-IRS1 and PPAR-y protein in liver tissue. As a result, supplementing with solasodine and coenzyme Q10 reversed the effect of the HFD on p-IRS1 and PPAR-y protein in liver tissue while also alleviating insulin resistance symptoms.
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Resistencia a la Insulina , Insulinas , Alcaloides Solanáceos , Ubiquinona , Animales , Antioxidantes/farmacología , Glucemia , Catalasa/metabolismo , Dieta Alta en Grasa/efectos adversos , Insulina/metabolismo , Proteínas Sustrato del Receptor de Insulina , Insulinas/metabolismo , Insulinas/farmacología , Hígado/metabolismo , PPAR gamma/metabolismo , Ratas , Alcaloides Solanáceos/farmacología , Superóxido Dismutasa/metabolismo , Ubiquinona/análogos & derivados , Ubiquinona/farmacologíaRESUMEN
The ethanolic extracts of Spondias mangifera fruit (SMFE) were evaluated for aphrodisiac activity. The in-vitro phosphodiesterase-5 (PDE-5) inhibition was assessed based on in-silico molecular docking and simulation studies. In addition, the in-vivo sexual behavior was analyzed in the form of mount (MF, ML), intromission (IF, IL), and ejaculation (EF, EL) frequencies and latencies to validate the in-vitro results. Some biochemical parameters, including PDE-5, nitric oxide, and testosterone, were also observed. The above extract constituted ß-amyrin, ß-sitosterol, and oleanolic acid and showed tremendous binding with phosphodiesterase-5 and sildenafil. Both the sildenafil and ethanolic extracts (200 and 400 mg/kg/d bodyweight) significantly (p < 0.1, p < 0.05) increased MF, IF, and EF, respectively. In contrast, ML and IL significantly (p < 0.1) decreased, and EL significantly (p < 0.1) increased compared with a normal group of animals. The ethanolic extracts (200 and 400 mg/kg/d bodyweight) and sildenafil further significantly (p < 0.05, p < 0.1) diminished PDE-5 activity significantly (p < 0.05, p < 0.1) and enhanced nitric oxide and testosterone levels, as compared with normal rodents. Therefore, the S. mangifera ethanolic extract might be a valuable alternate aphrodisiac for erectile dysfunction.
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Obesity, type 2 diabetes, and cardiovascular illnesses have known risk factors in the pathophysiology of an unhealthy diet. Obesity now affects almost a third of the world's population and is widely seen as a side effect of the Industrial Revolution. The current study aimed to determine natural phytoconstituents that have a significant role in the management of obesity. In this view, we have selected the plant Boerhavia diffusa which has different pharmacological actions and is traditionally used to treat sickness caused by lifestyle modification. The methanolic extract of the plant material was prepared and then further fractionated by means of solvents (n-hexane, chloroform, n-butanol, and water). The absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis was done by taking the active constituent of the plant (Punarnavine, Boeravinone B, and Eupalitin). The molecular docking analysis of these compounds is also performed by targeting the cannabinoid receptor (CR). Structural analysis of the best complex was done using the Discovery Studio visualizer tool. High-performance thin-layer chromatography (HPTLC) analysis was done by using a solvent system (chloroform and methanol in a ratio of 8:2). The in vivo study was done on the Sprague-Dawley (SD) rats treated with a high-fat diet to induce obesity and different parameters such as body weight, behavioral activity, organ fat pad weight, lipid profile, and liver biomarkers (AST, ALT, BUN, and creatinine) were estimated. The result of the study suggested that the phytoconstituents of B. diffusa upon molecular docking revealed the possible binding mechanisms with the CR and thus show potent anti-obesity action.
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AIM OF THE STUDY: The role of pterostilbene against induced neurobehavioral alterations in global cerebral ischemia-reperfusion and oxidative damage was studied. MATERIALS AND METHODS: Male SD rats (180-200 g) were exposed for 30 min to bilateral carotid artery occlusion accompanied by 60 min reperfusion to cause cerebral injury. Pretreatment with pterostilbene (200 and 400 mg/kg, orally) was given to the animals for ten days followed by ischemia-reperfusion injury. Various behavioral tests (locomotor activity, neurological score, transfer latency, hanging wire test) were studied. The brain tissues of animals were used for both the biochemical parameters (lipid peroxidation, reduced glutathione, superoxide dismutase, catalase activity) and histopathological study. RESULT: The pterostilbene as given orally significantly improved neurobehavioral alterations compared to control ischemia-reperfusion. Treatment with pterostilbene (200, and 400 mg/kg, orally) also significantly attenuated oxidative damage as indicated by reduced lipid peroxidation, nitrite concentration, restored reduced glutathione, and catalase activity as compared to control (ischemia-reperfusion) animals. Overall, pterostilbene treated animals showed non significant histological alteration as compared to ischemia-reperfusion control. CONCLUSION: This work suggests the beneficial effect of pterostilbene and its therapeutic potential against reperfusion-induced ischemia and associated behavioral changes in rats due to the stabilization of DNA damage with significant free radical scavenging properties.
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N-acetylcysteine (NAC) is considered as the body's major antioxidant molecules with diverse biological properties. In this review, the pharmacokinetics, safety and efficacy report on both the preclinical and clinical summary of NAC is discussed. Both in vitro and in vivo preclinical studies along with the clinical data have shown that NAC has enormous biological properties. NAC is used in the treatment of acetaminophen poisoning, diabetic nephropathy, Alzheimer's disease, schizophrenia, and ulcerative colitis, etc. Numerous analytical techniques, for instance, UPLC, LC-MS, HPLC, RP-IPC are primarily employed for the estimation of NAC in different single and fixed-dose combinations. The molecular docking studies on NAC demonstrate the binding within Sudlow's site-I hydrogen bonds and formation of NAC and BSA complexes. Various hydrophobic and hydrophilic amino acids generally exist in making contact with NAC as NAC-BSA complexes. Docking studies of NAC with the active site of the urease exposed an O-coordinated bond through nickel 3002 and a hydrogen bond through His-138. NAC and its analogs also made the allosteric pockets that helped to describe almost all favorable pose for the chaperone in a complex through the protein. Thus, we intended to highlight the several health benefits of this antioxidant compound and applications in pharmaceutical product development.
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Acetilcisteína , Antioxidantes , Acetilcisteína/metabolismo , Acetilcisteína/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Cromatografía Líquida de Alta Presión , Composición de Medicamentos , Simulación del Acoplamiento MolecularRESUMEN
BACKGROUND: Stroke is one of the causes of death and disability globally. Brain attack is because of the acute presentation of stroke, which highlights the requirement for decisive action to treat it. OBJECTIVE: The mechanism and in-vivo experimental models of stroke with various neuroprotective agents are highlighted in this review. METHOD: The damaging mechanisms may proceed by rapid, nonspecific cell lysis (necrosis) or by the active form of cell death (apoptosis or necroptosis), depending upon the duration and severity and of the ischemic insult. RESULTS: Identification of injury mediators and pathways in a variety of experimental animal models of global cerebral ischemia has directed to explore the target-specific cytoprotective strategies, which are critical to clinical brain injury outcomes. CONCLUSION: The injury mechanism, available encouraging medicaments thereof, and outcomes of natural and modern medicines for ischemia have been summarized. In spite of available therapeutic agents (thrombolytics, calcium channel blockers, NMDA receptor antagonists and antioxidants), there is a need for an ideal drug for strokes.