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1.
World J Diabetes ; 15(3): 572-574, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38591082

ABSTRACT

The Advanced Glycation End Products (AGE) binding with its receptor can increase reactive oxygen species (ROS) generation through specific signaling mediators. The effect of superoxide (O2-) and O2- mediated ROS and reactive nitrogen species depends on their concentration and location of formation. Nitric oxide (NO) has anti-inflammatory and anticoagulant properties and a vasodilation effect, but NO can be deactivated by reacting with O2-. This reaction between NO and O2- produces the potent oxidant ONOO-. Therefore, ONOO-'s regulatory role in AGEs in diabetic cardiovascular complications must considered as a regulator of cardiovascular complications in diabetes.

2.
J Environ Pathol Toxicol Oncol ; 43(3): 13-38, 2024.
Article in English | MEDLINE | ID: mdl-38608143

ABSTRACT

Around 2 million people are diagnosed with lung cancer annually, causing 20,000 deaths. Non-small cell carcinomas account for 80-85% of lung cancer cases. Over the last few decades, there has been an improved understanding of the chromosomal makeup of lung cancer. As a result, the clinical care and treatment of patients with advanced or metastatic non-small-cell lung cancer (NSCLC) have changed. This is possible due to advanced molecular techniques and chromosomal analysis, which have revealed persistent genetic abnormalities. Specific medications have increased the median survival time for NSCLC patients. Pulmonary pathology and oncology patients now receive personalized medication based on genetic abnormalities and other prognostic indicators. However, the diagnosis algorithms become complicated due to the various testing methods available. Consensus standards and recommendations have standardized NSCLC diagnostic testing. This article discusses the molecular genetic landscape of NSCLC and the latest therapy developments, focusing on clinically relevant changes using several schematic and tabular representations.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics
3.
J Pharm Pharmacol ; 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38546509

ABSTRACT

INTRODUCTION: The Bruguiera cylindrica L. is a mangrove plant that is typically found in coastal areas of Asia, including India. It has been known for its medicinal properties, which have been utilized for generations. For example, in Thailand, it has been used to treat wounds and diarrhoea, while in India, it has been effective in addressing diabetes, ulcers, and other health issues. This particular study sought to investigate the potential of B. cylindrica bark extract in reducing the symptoms of diabetes in rats. METHODS: In this study, we examined the potential of B. cylindrica bark extract as an inhibitor of α-amylase and α-glucosidase enzymes in vitro. We also evaluated the effects of the extract and Metformin on rats fed high-fat diets and measured their lipid profiles and biochemical parameters. Furthermore, we conducted a network pharmacology analysis to identify proteins and pathways involved in the amelioration of diabetes. RESULTS: Through metabolite profiling, we identified 58 compounds in B. cylindrica hydroalcoholic extract. These compounds include alkaloids, phenolics, flavonoids, and fatty acids. The extract was found to have a dose-dependent inhibition activity against α-amylase and α-glucosidase, with IC50 values similar to acarbose. In rats, oral administration of 200-400 mg/kg of B. cylindrica led to reduced blood glucose levels and normalized serum biochemical parameters. CONCLUSIONS: Bruguiera cylindrica bark may reduce blood sugar levels in rats with diabetes. The study found metabolites that interact with protein targets associated with different types of diabetes.

4.
J Gene Med ; 26(2): e3677, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38380785

ABSTRACT

Rett syndrome (RTT) is a rare but dreadful X-linked genetic disease that mainly affects young girls. It is a neurological disease that affects nerve cell development and function, resulting in severe motor and intellectual disabilities. To date, no cure is available for treating this disease. In 90% of the cases, RTT is caused by a mutation in methyl-CpG-binding protein 2 (MECP2), a transcription factor involved in the repression and activation of transcription. MECP2 is known to regulate several target genes and is involved in different physiological functions. Mouse models exhibit a broad range of phenotypes in recapitulating human RTT symptoms; however, understanding the disease mechanisms remains incomplete, and many potential RTT treatments developed in mouse models have not shown translational effectiveness in human trials. Recent data hint that the zebrafish model emulates similar disrupted neurological functions following mutation of the mecp2 gene. This suggests that zebrafish can be used to understand the onset and progression of RTT pathophysiology and develop a possible cure. In this review, we elaborate on the molecular basis of RTT pathophysiology in humans and model organisms, including rodents and zebrafish, focusing on the zebrafish model to understand the molecular pathophysiology and the development of therapeutic strategies for RTT. Finally, we propose a rational treatment strategy, including antisense oligonucleotides, small interfering RNA technology and induced pluripotent stem cell-derived cell therapy.


Subject(s)
Intellectual Disability , Rett Syndrome , Mice , Animals , Female , Humans , Rett Syndrome/genetics , Rett Syndrome/therapy , Zebrafish/genetics , Gene Expression Regulation , Mutation
5.
Article in English | MEDLINE | ID: mdl-38231052

ABSTRACT

BACKGROUND: As per the recommendation of the United States Food and Drug Administration, more research is needed to determine the antibody titer against COVID-19 vaccination. OBJECTIVE: The study aimed to understand the relationship between the antibody titer to the demographics, infection severity, and cycle threshold (CT) values of confirmed COVID-19 patients. METHODS: Initially, we obtained consent from 185 populations and included sixty RT-PCRpositive COVID-19 patients from Kamrup District in the Northeast State of Assam, India. The vaccination status was recorded and tested for the level of serum immunoglobulin (IgG). The CT values, gender, and clinical symptoms-based scoring (CSBS) correlated with their IgG value. RESULTS: Around 48% of participants gained an antibody titer more than the threshold value and showed CT values between 18-25. Moreover, the maximum distributed score above the average was found between the CT values 18-25. CONCLUSION: The IgG titer value differs significantly amongst the vaccinated population, which may depend upon their genetic and demographic variability.

7.
Article in English | MEDLINE | ID: mdl-37691221

ABSTRACT

BACKGROUND: The medicinal plants of the Cucurbitaceae family, such as Solena heterophylla Lour. fruits, have significant ethnobotanical value and are readily accessible in North East India. AIMS: We conducted a study on Solena heterophylla Lour. fruits to evaluate their anti-diabetic activity in vivo, standardize their HPTLC, and profile their metabolites using LC-QTOF-MS. We aimed to explore the molecular mechanism behind their effects on oxidative stress and glycosylated hemoglobin (HbA1c). METHODS: Firstly, the ethyl acetate fraction of Solena heterophylla Lour. fruits was standardized using Cucurbitacin B as a standard marker by conducting HPTLC evaluation. Next, we delved into analyzing metabolite profiling. In addition, the standardized fraction was utilized in an experimental study to investigate the molecular mechanism of action in an in vivo high-fat diet and a low dose of streptozotocin-induced diabetic model. RESULTS: We have reportedly identified 52 metabolites in the ethyl acetate fraction of Solena heterophylla (EASH). In the in vitro tests, it has been observed that this extract from plants possesses notable inhibitory properties against α-amylase and α-glucosidase. Solena heterophylla fruits with high levels of Cucurbitacin B (2.29% w/w) helped lower FBG levels in animals with EASH treatment. EASH treatment reduced HbA1c levels and normalized liver lipid peroxidation and antioxidant enzyme levels. SGOT, SGPT, and SALP serum enzyme levels also returned to normal. CONCLUSION: Based on the current evaluation, it was found that EASH exhibited encouraging hypoglycemic effects in diabetic rats induced by a low dose of STZ and high-fat diet, which warrants further investigation.


Subject(s)
Acetates , Cucurbitaceae , Diabetes Mellitus, Experimental , Triterpenes , Rats , Animals , Glycated Hemoglobin , Plant Extracts/adverse effects , Antioxidants/pharmacology , Oxidative Stress , Hypoglycemic Agents/adverse effects , Streptozocin/adverse effects , Plants, Edible , Blood Glucose
8.
Article in English | MEDLINE | ID: mdl-37937564

ABSTRACT

According to the World Health Organization (WHO), diabetes has been increasing steadily over the past few decades. In developing countries, it is the cause of increased morbidity and mortality. Diabetes and its complications are associated with education, occupation, and income across all levels of socioeconomic status. Factors, such as hyperglycemia, social ignorance, lack of proper health knowledge, and late access to medical care, can worsen diabetic complications. Amongst the complications, neuropathic pain and inflammation are considered the most common causes of morbidity for common populations. This review is focused on exploring protein kinase C (PKC)-mediated TGF-ß regulation in diabetic complications with particular emphasis on allodynia. The role of PKC-triggered TGF-ß in diabetic neuropathy is not well explored. This review will provide a better understanding of the PKC-mediated TGF-ß regulation in diabetic neuropathy with several schematic illustrations. Neuroinflammation and associated hyperalgesia and allodynia during microvascular complications in diabetes are scientifically illustrated in this review. It is hoped that this review will facilitate biomedical scientists to better understand the etiology and target drugs effectively to manage diabetes and diabetic neuropathy.

9.
Inflammopharmacology ; 31(6): 3367-3370, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37558921

ABSTRACT

There is a group of enzymes called monoamine oxidase(s) (MAOs) that help with the oxidation of amines found in both our diet and our bodies. Currently, monoamine oxidase inhibitors (MAO-Is) are utilized to manage conditions like depression, Parkinson's disease, and other psychiatric disorders. Rheumatoid arthritis (RA) is an auto-immune disease that has been linked to negative changes in mental health, such as depression. When depression co-occurs with RA, it can further worsen the outcome of the disease. Inhibiting monoamine oxidases could potentially treat RA by improving its pathological markers. Using existing pre-clinical and clinical data on safety and toxicity makes drug re-purposing advantageous. Hence, the pre-clinical validation of MAO-I's effectiveness in managing RA requires urgent regulatory intervention to commence clinical trials. Back in 1983, a clinical case report put forward the idea of repurposing MAO-I for RA treatment. Although MAO-I had been used for depression, it was observed to have a significant reduction in joint pain and stiffness. However, no significant clinical research has been conducted on this matter since then. In this commentary article, we provide a summary of the pre-clinical data that is currently available. The main focus of our discussion is on the significance of clinical trials for MAO-I, repurposing it for RA, and using it for the simultaneous management of depression and RA.


Subject(s)
Arthritis, Rheumatoid , Autoimmune Diseases , Parkinson Disease , Humans , Monoamine Oxidase Inhibitors/pharmacology , Monoamine Oxidase Inhibitors/therapeutic use , Monoamine Oxidase/therapeutic use , Parkinson Disease/drug therapy , Arthritis, Rheumatoid/drug therapy , Autoimmune Diseases/drug therapy
10.
Article in English | MEDLINE | ID: mdl-36788687

ABSTRACT

Programmed cell death protein 1 or Programmed death-1 (PD-1) and Programmed Cell Death Ligand 1 (PD-L1) research have tremendously been taken into great consideration in the field of cancer immune pharmacology. Cancer immunotherapy has been convoyed by a capable outcome over the past few years. PD-1 and PD-L1 play a pivotal role in attenuating immune involvement, modulating the activity of T-cells, and promoting different types of programmed cell death. Participation of antigen-specific T cells and regulatory T cells and their acute mutations during cancer cell invasion and migration may lead to challenges for three programmed cell death methods, namely, pyroptosis, apoptosis, and necroptosis called "PANoptosis". This review aimed to explore the correlation between the PD-1/PD-L1 pathway in "PANoptosis" using available recently published literature with several schematic representations. Hopefully, the review will facilitate the biomedical scientist targeting cancer immune pharmacological aspect for the management of Breast Adenocarcinoma shortly.

11.
Inflammopharmacology ; 31(3): 1305-1317, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36826724

ABSTRACT

OBJECTIVE: This study aims to investigate the anti-inflammatory mechanism of monoamine oxidase inhibitor (MAOI) in carrageenan (CARR) induced inflammation models to reprofile their use. We also aimed to explore the role of monoamine oxidase (MAO)-mediated H2O2-NF-κB-COX-2 pathway in acute inflammation. METHODS: In vitro anti-inflammatory activity and hydrogen peroxide (H2O2) scavenging activity were performed according to the established procedure. Inflammation was induced using CARR in BALB/c mice at the foot paw and peritoneal cavity. Hourly measurement of paw swelling was performed. The level of nitric oxide (NO), myeloperoxidase (MPO), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2) and nuclear factor κB (NF-κB) was determined using enzyme-linked immunosorbent assay (ELISA). Peritoneal fluid was collected to investigate total count, differential count of leukocytes, and capillary permeability. RESULTS: In vitro anti-inflammatory evaluations revealed the potential role of MAOI to inhibit heat-induced protein denaturation and human red cell membrane destabilization. H2O2 inhibition activity of MAOI also proved their powerful role as an H2O2 scavenger. Treatment with MAOI in CARR-induced mice significantly reduced paw edema, leukocyte extravasation, and total and differential leukocyte count. The result of ELISA showed MAOI effectively reduce the level of COX-2, PGE2 and NF-κB in inflamed tissue. CONCLUSIONS: In short, this study demonstrates that inhibition of H2O2 by MAOI alleviates CARR-induced paw edema possibly by inhibiting the H2O2-mediated NF-κB-COX-2 pathway. The present investigation identifies MAOI might reprofile for the treatment of acute inflammation also, the MAO enzyme may use as a novel therapeutic target to design and develop new class of anti-inflammatory agents.


Subject(s)
Hydrogen Peroxide , NF-kappa B , Mice , Humans , Animals , NF-kappa B/metabolism , Cyclooxygenase 2/metabolism , Hydrogen Peroxide/metabolism , Monoamine Oxidase Inhibitors/adverse effects , Signal Transduction , Carrageenan/pharmacology , Inflammation/metabolism , Anti-Inflammatory Agents/therapeutic use , Edema/metabolism , Monoamine Oxidase/metabolism , Monoamine Oxidase/pharmacology , Monoamine Oxidase/therapeutic use , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/metabolism
12.
Curr Drug Saf ; 18(2): 214-223, 2023.
Article in English | MEDLINE | ID: mdl-35570534

ABSTRACT

INTRODUCTION: Drymaria cordata (Linn.) Willd is a creeping herb belonging to the Caryophyllaceae family, widely used as a traditional medicine in Africa and North-east India for various ailments. Many therapeutic applications of D. cordata have been reported in various scientific studies, but the teratogenicity study of this herb has not been documented till now. METHODS: The present study aimed to assess the developmental toxic effect and median lethal concentration (LC50) of methanol extract of Drymaria cordata leaf (DCME) using zebrafish embryos. After spawning of male and female zebrafish, healthy zebrafish embryos were selected by microscopic screening and transferred into 96-well plate for the study. Embryos were exposed to DCME at concentrations ranging from 50-400 µg/ml in 2% DMSO from 24 hpf to 72 hpf. RESULTS: Developmental and morphological abnormalities were microscopically evaluated. Fifty percent lethal concentration (LC50) of DCME was determined by observation from 24 hpf to 72 hpf. The concentration-dependent toxic effects of DCME on developing embryos of zebrafish were found in the study in a time-dependent manner. CONCLUSION: At 72 hpf, the median lethal concentration (LC50) of DCME was found with visible developmental defects, such as heartbeat rate, less pigmentation, oedema, spinal curvature, immature yolk sac as well as reduced hatching rate and a slow growth. The median lethal dose was found to be 448 µg/ml at 72 hpf for zebra fish embryos, meriting further studies on toxicological profiling of the plants.


Subject(s)
Caryophyllaceae , Zebrafish , Animals , Embryo, Nonmammalian
13.
Curr Diabetes Rev ; 19(5): e130522204763, 2023.
Article in English | MEDLINE | ID: mdl-35570545

ABSTRACT

Alzheimer's disease (AD) is the most common type of dementia that affects the elderly around the world. Chronic type 2 diabetes (T2DM) has been proven to be closely related to neurodegeneration, especially AD. T2DM is characterized by the cell's failure to take up insulin as well as chronic hyperglycemia. In the central nervous system, insulin plays vital regulatory roles, while in chronic hyperglycemia, it leads to the formation and accumulation of advanced glycation end products (AGEs). Inflammation plays a crucial role in development of insulin resistance in AD and T2DM. The microtubule-related protein tau is involved in the pathogenesis of several neurological diseases known as tauopathies, and is found to be abnormally hyperphosphorylated in AD and accumulated in neurons. Chronic neuroinflammation causes the breakdown of the blood-brain barrier (BBB) observed in tauopathies. The development of pro-inflammatory signaling molecules, such as cytokines, chemokines from glial cells, neurons and endothelial cells, decides the structural integrity of BBB and immune cell migration into the brain. This review highlights the use of antidiabetic compounds as promising therapeutics for AD, and also describes several new pathological molecular mechanisms associated with diabetes that increase AD pathogenesis.


Subject(s)
Alzheimer Disease , Diabetes Mellitus, Type 2 , Hyperglycemia , Tauopathies , Humans , Aged , Alzheimer Disease/etiology , Alzheimer Disease/metabolism , Diabetes Mellitus, Type 2/complications , Endothelial Cells/metabolism , Tauopathies/complications , Tauopathies/metabolism , Tauopathies/pathology , tau Proteins/metabolism , Hyperglycemia/complications , Insulin
14.
Molecules ; 27(11)2022 May 30.
Article in English | MEDLINE | ID: mdl-35684442

ABSTRACT

Background: This study comparatively assessed seven indigenous traditional tea plants on several attributes that included antioxidant, nutritional, caffeine contents, and cyclooxygenase activity. Methodology: Nutritional content of all tea plants were determined for energy, fat, carbohydrates, total sugars, dietary fiber and amino acids. Antioxidant potential and the antioxidant potentiating secondary metabolites were also measured and compared. Further, we investigated the tea plants for any role they would have on cyclooxygenase (COX) activity on cobalt chloride (CoCl2) induced human glioma cell lines (U87MG). Results: The tea plants were found non-cytotoxic at concentrations tested against the human Chang liver and HeK 293 kidney cells and were found to be naturally caffeine free. The lowest and highest extraction yield among the tea plants was 7.1% for B. saligna and 15.48% for L. scaberrimma respectively. On average, the flavonol content was 12 to 8 QE/g, ORAC 800 µmol TE/g, TEAC 150 µmol TE/g, FRAP 155 µmol AAE/g, polyphenols 40 mg GAE/g, flavanols 0.35 mg CE/g, flavonols 12 mg QE/g and total flavonoid content (TFC) 180 µg QE/mg. The COX activity has been found to be inhibited by a dose-dependent manner by L. scaberrimma, B. saligna and L. javanica. Conclusion: The results further support competitive value of tea plants and need for improved and further development.


Subject(s)
Antioxidants , Teas, Herbal , Antioxidants/chemistry , Caffeine , Cell Hypoxia , Cyclooxygenase Inhibitors , Flavonols , HEK293 Cells , Humans , Nutritive Value , Polyphenols/chemistry , Prostaglandin-Endoperoxide Synthases , South Africa
15.
Inflammopharmacology ; 30(2): 453-463, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35266068

ABSTRACT

Monoamine oxidase inhibitors (MAOI) are presently used to treat depression, parkinsonian, and other psychiatric disorders. The present study was aimed to repurpose the use of MOAI in Rheumatoid Arthritis (RA). The animal model of RA was developed using collagen type II (CII) in Freund's complete adjuvant (FCA) followed by lipopolysaccharide (LPS) and a booster dose of CII in FCA. The effect of MAOI, Selegiline was evaluated whereas the indicators like paw thickness, arthritic score, and the splenic index were measured and compared with the standard drug Methotrexate. Further to explore the molecular mechanism, the expression of serum inflammatory cytokines (IL-6 and TNF-α), radiographical and histopathological study of hind paw were also checked and analyzed. Treatment with MAOI, Selegiline not only reduced the paw thickness, arthritic score, and the splenic index, but also greatly improved the inflammatory biochemical and hematologic parameters and improved the arthritis score. The serum level of IL-6 and TNF-α are considerably decreased dose dependently, however, the notable significant effect (**p < 0.01) observed at concentration of 30 mg/kg b.w. when the RA animals treated by Selegiline. Collectively, Selegiline improved the progression of RA possibly via decreased catecholamine breakdown at synovial fluid resulting decrease hydrogen peroxide (H2O2) generation and inhibition of pro-inflammatory cytokines in situ. Thus, the finding support and indicate the repurposing of MAOI for the treatment of RA meriting further studies on synovial monoamine oxidase as a new therapeutic target to design a new drug for RA.


Subject(s)
Arthritis, Experimental , Arthritis, Rheumatoid , Animals , Arthritis, Experimental/metabolism , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/metabolism , Cytokines/metabolism , Drug Repositioning , Humans , Hydrogen Peroxide/pharmacology , Monoamine Oxidase Inhibitors/pharmacology , Monoamine Oxidase Inhibitors/therapeutic use , Oxidative Stress , Rats , Rats, Wistar
16.
Article in English | MEDLINE | ID: mdl-33618651

ABSTRACT

BACKGROUND: There are anecdotal claims on the use of Cannabis sativa L. in the treatment of Alzheimer's disease, but there is a lack of scientific data to support the efficacy and safety of Cannabis sativa L. for Alzheimer's disease. AIM: The aim of the study was to evaluate the effect of aerial parts of Cannabis sativa L. on the cholinesterases and ß-secretase enzymes activities as one of the possible mechanisms of Alzheimer's disease. METHODS: The phytochemical and heavy metal contents were analysed. The extracts were screened for acetylcholinesterase, butyrylcholinesterase and ß-secretase activity. Cytotoxicity of extracts was performed in normal vero and pre-adipocytes cell lines. The extracts were characterized using high-performance thin layer chromatography and high-performance liquid chromatography for their chemical fingerprints. Alkaloids, flavonoids and glycosides were present amongst the tested phytochemicals. Cannabidiol concentrations were comparatively high in the hexane and dichloromethane than in dichloromethane: methanol (1:1) and methanol extracts. RESULTS: Hexane and dichloromethane extracts showed a better inhibitory potential towards cholinesterase activity, while water, hexane, dichloromethane: methanol (1:1) and methanol showed an inhibitory potential towards ß-secretase enzyme activity. All extracts showed no cytotoxic effect on pre-adipocytes and vero cells after 24- and 48-hours of exposure. CONCLUSION: Therefore, this may explain the mechanism through which AD symptoms may be treated and managed by Cannabis sativa L. extracts.


Subject(s)
Alzheimer Disease , Amyloid Precursor Protein Secretases , Cannabis , Cholinesterase Inhibitors , Plant Extracts , Acetylcholinesterase/metabolism , Alzheimer Disease/drug therapy , Amyloid Precursor Protein Secretases/antagonists & inhibitors , Amyloid Precursor Protein Secretases/metabolism , Animals , Butyrylcholinesterase/metabolism , Cannabis/chemistry , Chlorocebus aethiops , Cholinesterase Inhibitors/chemistry , Cholinesterase Inhibitors/pharmacology , Flowers/chemistry , Hexanes , Methanol , Methylene Chloride , Phytochemicals/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Vero Cells
17.
Curr Diabetes Rev ; 18(3): e300721195147, 2022.
Article in English | MEDLINE | ID: mdl-34376135

ABSTRACT

The risk of type 2 diabetes mellitus (T2DM) is increasing abundantly due to lifestyle-related obesity and associated cardiovascular problems. Presently, Glycogen synthase kinase-3 (GSK-3) has gained considerable attention from biomedical scientists to treat diabetes. Phosphorylation of GSK-3 permits a number of cellular activities like regulation of cell signaling, cellular metabolism, cell proliferation and cellular transport. Inhibiting GSK-3 activity by pharmacological intervention has become an important strategy for the management of T2DM. This review focuses on the schematic representation of fundamental GSK-3 enzymology and encompasses the GSK-3 inhibitors as a future therapeutic lead target for the management of T2DM that may significantly regulate insulin sensitivity to insulin receptor, glycogen synthesis and glucose metabolism. The various signaling mechanisms of inhibiting the GSK-3 by describing insulin signaling through Insulin Receptor Substrate (IRS-1), Phosphatidylinositol-3 Kinase (PI3K) and Protein Kinase B (PKB/ AKT) pathways that may hopefully facilitate the pharmacologist to design for antidiabetic drug evaluation model in near future have also been highlighted.


Subject(s)
Diabetes Mellitus, Type 2 , Insulin Resistance , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/etiology , Diabetes Mellitus, Type 2/metabolism , Glycogen Synthase Kinase 3 , Humans , Insulin/metabolism , Insulin Resistance/physiology , Receptor, Insulin/metabolism
18.
Curr Mol Pharmacol ; 14(4): 509-519, 2021 10 25.
Article in English | MEDLINE | ID: mdl-32867666

ABSTRACT

Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronaviruses 2 (SARS-CoV-2). At present, it is a potentially fatal disease and is of great global public health concern. The pathophysiological understanding of the mode of transmission of COVID-9 and the possible molecular targets are exploring successively to fight against this contagious disease. In this pandemic situation, a large number of countries have been forced to do social distancing and lockdown. The two main pathways of SARS-CoV-2 transmission include (1) droplet infection via the respiratory secretions or by close person to person contact, whereas (2) faecal to oral route transmission is also possible. Thus, the route of entry of SARS-CoV-2 is through the nasal and or oral cavity. Here, we briefly reviewed the current knowledge about COVID-19, considering the potential explanation of the mode of transmission and the different possible molecular drug targets. We highlighted potential approaches to address the antiviral therapy inhibiting the replication of SARS-CoV-2 in the host targeting (a.) RNA-dependent RNA polymerase (b.) serine protease and (c.) proteolytic activation pathways or the cell membrane receptor called the angiotensin- converting enzyme-2 (ACE2). The recently exercised immuno-enhancement therapy to fight against SARS-CoV-2 and treatment strategy using drug combination are also explored here in this review.


Subject(s)
Antiviral Agents/chemistry , COVID-19/pathology , Viral Proteins/chemistry , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/metabolism , Antiviral Agents/metabolism , Antiviral Agents/therapeutic use , COVID-19/therapy , COVID-19/transmission , COVID-19/virology , Drug Therapy, Combination , Humans , Immunotherapy , RNA-Dependent RNA Polymerase/chemistry , RNA-Dependent RNA Polymerase/metabolism , SARS-CoV-2/isolation & purification , SARS-CoV-2/metabolism , Serine Proteases/chemistry , Serine Proteases/metabolism , Viral Proteins/metabolism
19.
Curr Rheumatol Rev ; 17(1): 81-87, 2021.
Article in English | MEDLINE | ID: mdl-32729420

ABSTRACT

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease responsible for maximum human morbidity in modern life, whereas oxidative stress is the ultimate potential biomarker for determining disease activity in patients with RA. OBJECTIVE: The present study scientifically validated the effectiveness of antioxidants commonly present in different food supplements to neutralize the free radicals mediated oxidative stress in isolated peripheral blood mononuclear lymphocytes (PBML) of patients with RA. METHODS: The study population included patients with Rheumatoid arthritis, RA (n =15), who fulfilled the American College of Rheumatology criteria for RA. Peripheral blood was collected, and isolated mononuclear lymphocyte cells (PBML) were pretreated with phorbol myristate acetate (PMS) and furthermore, incubated with different concentrations of Naringenin, ß carotene and Nacetyl cysteine (NAC) in an ex vivo condition. The resultant cell lysate was used for further studies for the determination of other oxidative biomarkers. The increase of superoxide and nitric oxide production was observed when PBML was treated PMS. RESULTS: Importantly, the increased oxidative stress was effectively decreased by the selected plantderived compounds ß-carotene and naringenin. CONCLUSION: The study scientifically evaluated the efficacy of the molecules validated by one-way ANOVA, followed by Dunnett's post hoc test of significance. Collectively, our results indicate that both ß carotene and naringenin may be a promising non-toxic food supplement in attenuating the oxidative stress associated pathology in RA, meriting further pharmacological studies on other inflammatory cells like neutrophils.


Subject(s)
Antioxidants/pharmacology , Arthritis, Rheumatoid/metabolism , Leukocytes, Mononuclear/metabolism , Oxidative Stress/drug effects , Tetradecanoylphorbol Acetate/pharmacology , Adult , Arthritis, Rheumatoid/blood , Cells, Cultured , Dietary Supplements , Female , Humans , Male , Middle Aged , Young Adult
20.
J Adv Pharm Technol Res ; 11(1): 44-52, 2020.
Article in English | MEDLINE | ID: mdl-32154158

ABSTRACT

Drymaria cordata (Caryophyllaceae), commonly known as Abhijalo in Sikkimese-Tibetan, is a creeping herb grown in tropical and subtropical regions of the world. It is used by ethnic groups of Sikkim, North-East India, for the treatment of various diseases including diabetes. This study aimed to investigate the antidiabetic effect of methanol extract from D. cordata leaf (DCME) in streptozotocin (STZ) and nicotinamide (NA)-induced type 2 diabetes in rats. Diabetic Wistar albino rats were treated with DCME at 200 mg/kg and 400 mg/kg orally for 28 days. Metformin (150 mg/kg b.w.) was used as a reference drug. Fasting blood glucose (FBG) level; serum biochemical parameters; and liver, kidney, and antioxidant parameters were estimated, and pancreatic histopathology was performed after 28 days of treatment. Administration of DCME to STZ-NA-induced diabetic rats at 200 mg/kg and 400 mg/kg orally for 28 days exhibited statistically significant (P < 0.05) and dose-dependent reduction of FBG, glycosylated hemoglobin, serum lipid, and hepatorenal antioxidative parameters in DCME-treated groups when compared to those of diabetic controls. Histopathological studies of pancreas in DCME-treated rats showed improvement in ß-cell density compared to diabetic group. The results demonstrate the significant antidiabetic potential of D. cordata leaf in albino rats plausibly by reducing oxidative stress and serum lipids levels, justifying the folkloric use of this plant in the treatment of diabetes.

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