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1.
Molecules ; 28(14)2023 Jul 16.
Article in English | MEDLINE | ID: mdl-37513307

ABSTRACT

The goal of an antiviral agent research is to find an antiviral drug that reduces viral growth without harming healthy cells. Transformations of the virus, new viral strain developments, the resistance of viral pathogens, and side effects are the current challenges in terms of discovering antiviral drugs. The time has come and it is now essential to discover a natural antiviral agent that has the potential to destroy viruses without causing resistance or other unintended side effects. The pharmacological potency of thymoquinone (TQ) against different communicable and non-communicable diseases has been proven by various studies, and TQ is considered to be a safe antiviral substitute. Adjunctive immunomodulatory effects in addition to the antiviral potency of TQ makes it a major compound against viral infection through modulating the production of nitric oxide and reactive oxygen species, decreasing the cytokine storm, and inhibiting endothelial dysfunction. Nevertheless, TQ's low oral bioavailability, short half-life, poor water solubility, and conventional formulation are barriers to achieving its optimal pharmacologic benefits. Nano-formulation proposes numerous ways to overcome these obstacles through a small particle size, a big surface area, and a variety of surface modifications. Nano-based pharmaceutical innovations to combat viral infections using TQ are a promising approach to treating surmounting viral infections.


Subject(s)
Antiviral Agents , Benzoquinones , Antiviral Agents/pharmacology , Benzoquinones/pharmacology , Solubility , Particle Size
2.
Nanomaterials (Basel) ; 13(5)2023 Feb 26.
Article in English | MEDLINE | ID: mdl-36903746

ABSTRACT

Diabetes mellitus is linked to both short-term and long-term health problems. Therefore, its detection at a very basic stage is of utmost importance. Research institutes and medical organizations are increasingly using cost-effective biosensors to monitor human biological processes and provide precise health diagnoses. Biosensors aid in accurate diabetes diagnosis and monitoring for efficient treatment and management. Recent attention to nanotechnology in the fast-evolving area of biosensing has facilitated the advancement of new sensors and sensing processes and improved the performance and sensitivity of current biosensors. Nanotechnology biosensors detect disease and track therapy response. Clinically efficient biosensors are user-friendly, efficient, cheap, and scalable in nanomaterial-based production processes and thus can transform diabetes outcomes. This article is more focused on biosensors and their substantial medical applications. The highlights of the article consist of the different types of biosensing units, the role of biosensors in diabetes, the evolution of glucose sensors, and printed biosensors and biosensing systems. Later on, we were engrossed in the glucose sensors based on biofluids, employing minimally invasive, invasive, and noninvasive technologies to find out the impact of nanotechnology on the biosensors to produce a novel device as a nano-biosensor. In this approach, this article documents major advances in nanotechnology-based biosensors for medical applications, as well as the hurdles they must overcome in clinical practice.

3.
Cell Mol Biol (Noisy-le-grand) ; 68(7): 75-84, 2022 Jul 31.
Article in English | MEDLINE | ID: mdl-36495515

ABSTRACT

Protein tyrosine phosphatase-1B (PTP-1B) is a well-known therapeutic target for diabetes and obesity as it suppresses insulin and leptin signaling. PTP-1B deletion or pharmacological suppression boosted glucose homeostasis and insulin signaling without altering hepatic fat storage. Inhibitors of PTP-1B may be useful in the treatment of type 2 diabetes, and shikonin, a naturally occurring naphthoquinone dye pigment, is reported to inhibit PTP-1B and possess antidiabetic properties. Since the cell contains a large number of phosphatases, PTP-1B inhibitors must be effective and selective. To explore more about the mechanism underlying the inhibitor's efficacy and selectivity, we investigated its top four pharmacophores and used site-directed mutagenesis to insert amino acid mutations into PTP-1B as an extension of our previous study where we identified 4 pharmacophores of shikonin. The study aimed to examine the site-directed mutations like R24Y, S215E, and S216C influence the binding of shikonin pharmacophores, which act as selective inhibitors of PTP-1B. To achieve this purpose, docking and molecular dynamics simulations of wild-type (WT) and mutant PTP-1B with antidiabetic compounds were undertaken. The simulation results revealed that site-directed mutations can change the hydrogen bond and hydrophobic interactions between shikonin pharmacophores and many residues in PTP-1B's active site, influencing the drug's binding affinity. These findings could aid researchers in better understanding PTP-1B inhibitors' selective binding mechanism and pave the path for the creation of effective PTP-1B inhibitors.


Subject(s)
Diabetes Mellitus, Type 2 , Humans , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/genetics , Phosphoric Monoester Hydrolases/therapeutic use , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , Protein Binding , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use
4.
Molecules ; 27(19)2022 Oct 05.
Article in English | MEDLINE | ID: mdl-36235145

ABSTRACT

Cancer is one of the leading causes of morbidity and mortality around the globe and is likely to become the major cause of global death in the coming years. As per World Health Organization (WHO) report, every year there are over 10 and 9 million new cases and deaths from this disease. Chemotherapy, radiotherapy, and surgery are the three basic approaches to treating cancer. These approaches are aiming at eradicating all cancer cells with minimum off-target effects on other cell types. Most drugs have serious adverse effects due to the lack of target selectivity. On the other hand, resistance to already available drugs has emerged as a major obstacle in cancer chemotherapy, allowing cancer to proliferate irrespective of the chemotherapeutic agent. Consequently, it leads to multidrug resistance (MDR), a growing concern in the scientific community. To overcome this problem, in recent years, nanotechnology-based drug therapies have been explored and have shown great promise in overcoming resistance, with most nano-based drugs being explored at the clinical level. Through this review, we try to explain various mechanisms involved in multidrug resistance in cancer and the role nanotechnology has played in overcoming or reversing this resistance.


Subject(s)
Antineoplastic Agents , Neoplasms , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Humans , Nanotechnology , Neoplasms/drug therapy , Neoplasms/metabolism
5.
Cell Mol Biol (Noisy-le-grand) ; 67(4): 248-263, 2022 Jan 02.
Article in English | MEDLINE | ID: mdl-35809281

ABSTRACT

Adhatoda vasica (L.), Nees belonging to the family Acanthaceae is a shrub with opposite ascending branches. The plant has been used in the indigenous system of medicine in India for near about 2500 years. It is a well-known plant as a drug in Ayurvedic and Unani medicines. Traditionally it was used for the treatment of various acute and chronic diseases and showed strong pharmacological activity particularly for bronchial infections, cough, bacterial infections, reproductive disorders, cardiac diseases and many more. Various phytochemicals like alkaloids, flavonoids, tannins, etc. were obtained from Adhatoda vasica (A. vasica). The active constituent of the plant is vasicine, l-vasicinone, deoxyvasicine, maiontone, vasicinolone and vasicinol etc. This review consists of updated information on the phyto-constituents isolated from A. vasica and their potential role in the treatment of various ailments traditionally and medically. Based on the critical review it was concluded that there is not sufficient scientifically strong evidence to explain that A. vasica extract, could be harmful to human beings especially in pregnant women. Major data on traditional uses as well as toxicological studies, evaluated various correctness, relevance, importance, and reliability for the overall evaluation of A. vasica safety. Numerous clinical trials are conducted around the globe on the herbal formulations of vasaka. This review includes strong data about phytochemical and ethnopharmacological studies that indicate that A. vasica is a versatile native plant of the Indian subcontinent having a commercial reputation and thus can be encouraged for diversified applications like medicinal and other potential uses.


Subject(s)
Justicia , Ethnobotany , Female , Flavonoids , Humans , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Pregnancy , Reproducibility of Results
6.
Biomed Pharmacother ; 150: 112985, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35658219

ABSTRACT

Diabetes is a complicated multifactorial disorder in which the patient generally observes polyphagia, polydipsia, and polyuria due to uncontrolled growth in blood sugar levels. For its management, the pharmaceutical industry is working day and night to find a better drug with no or least toxicity. That's why nowadays a more focused branch is to use herbal phytoconstituents for its prevention. Shikonin is a naphthoquinone natural dye that is isolated from the plants of the Boraginaceae family and has proven its role as an anti-cancer, anti-inflammatory, and anti-gonadotrophic agent. In our previous study, we have published its anti-diabetic action by inhibiting the enzyme protein tyrosine phosphatase 1B. In this study, we were more focused on finding out the role of Shikonin and its pharmacophores by inhibiting the action of aldose reductase (AR) enzyme. The study was conducted using pharmacophore modeling, molecular docking, and molecular dynamics simulation studies. The absorption, distribution, metabolism, excretion (ADME), and toxicity profile were also evaluated in this study. Along with all the computational biology parameters we also focused on the in vitro activity and kinetic study of inhibitory activity of Shikonin against aldose reductase.


Subject(s)
Diabetes Mellitus , Naphthoquinones , Aldehyde Reductase/metabolism , Diabetes Mellitus/drug therapy , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/therapeutic use , Humans , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Molecular Docking Simulation , Naphthoquinones/pharmacology , Naphthoquinones/therapeutic use
7.
Plants (Basel) ; 11(9)2022 Apr 25.
Article in English | MEDLINE | ID: mdl-35567159

ABSTRACT

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.

8.
Semin Cancer Biol ; 86(Pt 3): 652-665, 2022 11.
Article in English | MEDLINE | ID: mdl-34020027

ABSTRACT

Cancer is one of the leading global causes of death in both men and women. Colorectal cancer (CRC) alone accounts for ∼10 % of total new global cases and poses an over 4% lifetime risk of developing cancer. Recent advancements in the field of biotechnology and microbiology concocted novel microbe-based therapies to treat various cancers, including CRC. Microbes have been explored for human use since centuries, especially for the treatment of various ailments. The utility of microbes in cancer therapeutics is widely explored, and various bacteria, fungi, and viruses are currently in use for the development of cancer therapeutics. The human gut hosts about 100 trillion microbes that release their metabolites in active, inactive, or dead conditions. Microbial secondary metabolites, proteins, immunotoxins, and enzymes are used to target cancer cells to induce cell cycle arrest, apoptosis, and death. Various approaches, such as dietary interventions, the use of prebiotics and probiotics, and fecal microbiota transplantation have been used to modulate the gut microbiota in order to prevent or treat CRC pathogenesis. The present review highlights the role of the gut microbiota in CRC precipitation, the potential mechanisms and use of microorganisms as CRC biomarkers, and strategies to modulate microbiota for the prevention and treatment of CRC.


Subject(s)
Colorectal Neoplasms , Gastrointestinal Microbiome , Microbiota , Probiotics , Male , Humans , Female , Colorectal Neoplasms/etiology , Colorectal Neoplasms/therapy , Colorectal Neoplasms/metabolism , Prebiotics , Probiotics/therapeutic use
9.
Plants (Basel) ; 10(11)2021 Oct 24.
Article in English | MEDLINE | ID: mdl-34834641

ABSTRACT

Rauwolfia serpentina (R. serpentina), belonging to the family Apocynaceae, is a renowned medicinal herb for its different pharmacological activities such as antibacterial, antifungal, anti-inflammatory, and antiproliferative characteristics. This study has done a comparative assessment of the antibacterial, antioxidant, and anti-cancer activity of R. serpentina aqueous leaf extract (RSALE) with encapsulated gold nanoparticles (R-AuNPs). The R-AuNPs are prepared so that they are significant in size, monodispersed, and extremely stable. Their characterization was done by numerous parameters, including UV-visible spectroscopy (528 nm), transmission electron microscopy (~17 d. nm), dynamic light scattering (~68 d. nm), and zeta-potential (~-17 mV). Subsequently, a potent antibacterial activity was depicted via RSALE and R-AuNPs when examined by disc diffusion against various Gram-positive and Gram-negative bacterial strains. The obtained zones of inhibition of RSALE (100 mg/mL) were 34 ± 0.1, 35 ± 0.1, 28.4 ± 0.01, and 18 ± 0.01, although those of R-AuNPs (15 mg/mL) were 24.4 ± 0.12, 22 ± 0.07, 20 ± 0.16, and 17 ± 0.3 against Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), Bacillus subtilis (MTCC 8114), and Streptococcus pyogenes (ATCC 19615), respectively. However, no zone of inhibition was obtained when tested against Proteus vulgaris (MTCC 1771). Furthermore, the obtained MIC values for Staphylococcus aureus were 0.91, 0.61, and 1.15 mg/mL; for Escherichia coli, 0.79, 0.36, and 1.02 mg/mL; for Bacillus subtilis 0.42, 0.27, and 0.474 mg/mL; and for Streptococcus pyogenes, 7.67, 3.86, and 8.5 mg/mL of pure RSALE, R-AuNPs, and Amoxicillin (control), respectively, incorporating that R-AuNPs have been shown to have a 1.4-fold, 2.1-fold, 1.5-fold, and 1.9-fold enhanced antibacterial activity in contrast to pure RSALE tested against Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Streptococcus pyogenes, and Proteus vulgaris, respectively. Additionally, an enhanced antioxidant potential was detected in R-AuNPs compared to RSALE evaluated by the 2,2-Diphenyl-1-Picryl Hydrazyl Radical Scavenging (DPPH) Ferric reducing antioxidant power (FRAP) assay. The determined IC 50 values of RSALE and R-AuNPs were 0.131 ± 0.05 and 0.184 ± 0.02 mg/mL, and 0.110 ± 0.1 and 0.106 ± 0.24 mg/mL via the FRAP and DPPH assays, respectively. In addition, the anti-cancer activity against the human cervical cancer (Hela) cell line was evaluated, and the MTT assay results revealed that R-AuNPs (IC50 88.3 µg/mL) had an enhanced anti-cancer potential in contrast to RSALE (171.5 µg/mL). Subsequently, the findings of this study indicated that R. serpentina leaves and their nanoformulation can be used as a potent source for the treatment of the above-mentioned complications and can be used as a possible agent for novel target-based therapies for the management of different ailments.

10.
Molecules ; 26(13)2021 Jun 30.
Article in English | MEDLINE | ID: mdl-34208908

ABSTRACT

Diabetes mellitus is a multifactorial disease that affects both developing and developed countries and is a major public health concern. Many synthetic drugs are available in the market, which counteracts the associated pathologies. However, due to the propensity of side effects, there is an unmet need for the investigation of safe and effective drugs. This research aims to find a novel phytoconstituent having diminished action on blood glucose levels with the least side effects. Shikonin is a naturally occurring naphthoquinone dying pigment obtained by the roots of the Boraginaceae family. Besides its use as pigments, it can be used as an antimicrobial, anti-inflammatory, and anti-tumor agent. This research aimed to hypothesize the physicochemical and phytochemical properties of Shikonin's in silico interaction with protein tyrosine phosphate 1B, as well as it's in vitro studies, in order to determine its potential anti-diabetic impact. To do so, molecular docking experiments with target proteins were conducted to assess their anti-diabetic ability. Analyzing associations with corresponding amino acids revealed the significant molecular interactions between Shikonin and diabetes-related target proteins. In silico pharmacokinetics and toxicity profile of Shikonin using ADMET Descriptor, Toxicity Prediction, and Calculate Molecular Properties tools from Biovia Discovery Studio v4.5. Filter by Lipinski and Veber Rule's module from Biovia Discovery Studio v4.5 was applied to assess the drug-likeness of Shikonin. The in vitro studies exposed that Shikonin shows an inhibitory potential against the PTP1B with an IC50 value of 15.51 µM. The kinetics studies revealed that it has a competitive inhibitory effect (Ki = 7.5 M) on the enzyme system, which could be useful in the production of preventive and therapeutic agents. The findings of this research suggested that the Shikonin could be used as an anti-diabetic agent and can be used as a novel source for drug delivery.


Subject(s)
Enzyme Inhibitors/chemistry , Hypoglycemic Agents/chemistry , Molecular Docking Simulation , Naphthoquinones/chemistry , Protein Tyrosine Phosphatase, Non-Receptor Type 1 , Allosteric Regulation , Humans , Protein Tyrosine Phosphatase, Non-Receptor Type 1/antagonists & inhibitors , Protein Tyrosine Phosphatase, Non-Receptor Type 1/chemistry , Structure-Activity Relationship
11.
J Food Biochem ; : e13807, 2021 Jun 21.
Article in English | MEDLINE | ID: mdl-34152002

ABSTRACT

The aim was to investigate whether thymoquinone (TQ) attenuates hyperglycemia-induced insulin resistance in experimental type 2 diabetes. Type 2 diabetes mellitus (T2DM) was induced by injection of streptozotocin (STZ, 40 mg/kg) in high fat diet (HFD) rats. The levels of glucose, insulin, area under curve (AUC) of glucose, lipid profile parameters, homeostasis model assessment of insulin resistance (HOMA-IR), peroxisome proliferator-activated receptor-γ (PPARγ), and dipeptidyl peptidase peptidase-IV (DPP-IV) were evaluated in HFD + STZ-induced type 2 diabetic rats. TQ treatment significantly reduced elevated levels of glucose, AUC of glucose, insulin, and DPP-IV in diabetic-treated groups. In addition, TQ treatment significantly reduced high levels of triglycerides (TG) and cholesterols (total, low-density and very low-density lipoprotein) accompanied by significant augmentation in high-density lipoprotein (HDL) levels in diabetic-treated groups. However, TQ treatment significantly improved insulin sensitivity in diabetic-treated groups, which was confirmed by increased level of PPARγ and decreased level of HOMA-IR. Molecular docking of TQ exhibited substantial binding affinity with PPARγ and DPP-IV target proteins, which is supported by in vivo results. These results demonstrate that TQ attenuates hyperglycemia-induced insulin resistance by counteracting hyperinsulinemia, improving lipid profile, insulin sensitivity, and inhibiting DPP-IV. PRACTICAL APPLICATIONS: T2DM results in relentless hyperglycemia which eventually progress to a state of insulin resistance. TQ is an active principle compound found in Nigella sative seed, having myriad of traditional medicinal values. Administration of TQ significantly prevented hyperglycemia, hyperinsulinemia, hyperlipidemia, insulin resistance, and inhibited DPP-IV in experimental type 2 diabetes. The in vivo results are also supported by molecular docking study of PPARγ and DPP-IV target proteins. Thus, we hypothesize that TQ can be used as an alternative natural drug in the management of hyperglycemia-induced insulin resistance in T2DM.

12.
Mini Rev Med Chem ; 21(19): 2860-2873, 2021.
Article in English | MEDLINE | ID: mdl-33797374

ABSTRACT

As winter is approaching us, the possibility of respiratory tract infection is rising in the current scenario due to the lack of Covid-19 prophylaxis. So no one could be safe until everyone is safe. Researchers are looking for the vaccine to remove the need for social distancing, mask-wearing, and social gathering worldwide. We cannot say about the vaccine's effectiveness if the vaccine is available. Several drugs are being tested to save people's life from the pandemic; azithromycin is one of them. This work is a review article with the updated findings of azithromycin in the context of COVID-19. The option of azithromycin regarding COVID-19 is justified by its anti-inflammatory, immunomodulatory, and anti-fibrotic effects and their pharmacokinetic properties, leading to effective concentrations in the target tissue. Azithromycin tends to be an effective candidate for SARS-CoV-2 replication inhibition that blocks the initial stage of the viral life cycle. Clinical trials at a preliminary scale and final stage show the significant results of azithromycin in supportive care therapy. Azithromycin was an early candidate for the medication of Covid-19 with or without hydroxychloroquine. It is exercised mainly as an outpatient antibiotic in COVID-19. In summing up, any primary anti-viral and antibiotic treatment is not the only possibility of fighting COVID-19 pharmacologically. It will be an injustice to those who require broader spectrum antibiotics if we do not use azithromycin. So significant research priority is needed to determine whether azithromycin is useful in the treatment of COVID-19.


Subject(s)
Azithromycin/pharmacology , Azithromycin/therapeutic use , COVID-19 Drug Treatment , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , COVID-19/immunology , COVID-19/pathology , COVID-19/virology , Humans , SARS-CoV-2/drug effects , SARS-CoV-2/growth & development
13.
Pharmaceutics ; 13(3)2021 Mar 10.
Article in English | MEDLINE | ID: mdl-33802156

ABSTRACT

Recently, drug delivery using natural biological carriers has emerged as one of the most widely investigated topics of research. Erythrocytes, or red blood cells, can act as potential carriers for a wide variety of drugs, including anticancer, antibacterial, antiviral, and anti-inflammatory, along with various proteins, peptides, enzymes, and other macromolecules. The red blood cell-based nanocarrier systems, also called nanoerythrosomes, are nanovesicles poised with extraordinary features such as long blood circulation times, the ability to escape immune system, the ability to release the drug gradually, the protection of drugs from various endogenous factors, targeted and specified delivery of drugs, as well as possessing both therapeutic and diagnostic applications in various fields of biomedical sciences. Their journey over the last two decades is escalating with fast pace, ranging from in vivo to preclinical and clinical studies by encapsulating a number of drugs into these carriers. Being biomimetic nanoparticles, they have enhanced the stability profile of drugs and their excellent site-specific targeting ability makes them potential carrier systems in the diagnosis and therapy of wide variety of tumors including gliomas, lung cancers, breast cancers, colon cancers, gastric cancers, and other solid tumors. This review focuses on the most recent advancements in the field of nanoerythrosomes, as an excellent and promising nanoplatform for the novel drug delivery of various drugs particularly antineoplastic drugs along with their potential as a promising diagnostic tool for the identification of different tumors.

14.
Saudi Pharm J ; 29(3): 213-222, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33850422

ABSTRACT

The risk of Coronavirus infection continues, and the fear of resurgence indicates the lack of a successful therapeutic strategy. In severe COVID-19 infection, many immune cells and their products are involved, making management difficult. The abundant release of cytokines and chemokines in severe COVID-19 patients leads to profound hyper inflammation and the mobilization of immune cells, triggering the cytokine storm. The complications associated with the cytokine storm include severe respiratory distress, intravascular coagulation, multi-organ failure, and death. The enormous formation of interleukin (IL)-6 and hemopoietic factors such as granulocyte-macrophage colony-stimulating factor (GM-CSF) are implicated in the severity of the infection. Moreover, these inflammatory cytokines and factors signal through the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway causing the activation of cytokine-related genes. The neutralization of these proteins could be of therapeutic help in COVID-19 patients and could mitigate the risk of mortality. IL-6 antagonist, IL-6 receptor antagonists, GM-CSF receptor inhibitors, and JAK-STAT inhibitors are being investigated to prevent intense lung injury in COVID-19 patients and increase the chances of survival. The review focuses the role of IL-6, GM-CSF, and JAK-STAT inhibitors in regulating the immune response in severely affected COVID-19 patients.

15.
Plants (Basel) ; 10(5)2021 Apr 21.
Article in English | MEDLINE | ID: mdl-33919084

ABSTRACT

The fruits of Spondias mangifera (S. mangifera) have traditionally been used for the management of rheumatism in the northeast region of India. The present study explores the probable anti-arthritis and anti-inflammatory potential of S. mangifera fruit extract's ethanolic fraction (EtoH-F). To support this study, we first approached the parameters in silico by means of the active constituents of the plant (beta amyrin, beta sitosterol, oleonolic acid and co-crystallised ligands, i.e., SPD-304) via molecular docking on COX-1, COX-2 and TNF-α. Thereafter, the absorption, distribution, metabolism, excretion and toxicity properties were also determined, and finally experimental activity was performed in vitro and in vivo. The in vitro activities of the plant extract fractions were evaluated by means of parameters like 1,1-Diphenyl-2- picrylhydrazyl (DPPH), free radical-reducing potential, albumin denaturation, and protease inhibitory activity. The in vivo activity was evaluated using parameters like COX, TNF-α and IL-6 inhibition assay and arthritis score in Freund Adjuvant (CFA) models at a dose of 400 mg/kg b.w. per day of different fractions (hexane, chloroform, alcoholic). The molecular docking assay was performed on COX-1, COX-2 and TNF-α. The results of in vitro studies showed concentration-dependent reduction in albumin denaturation, protease inhibitors and scavenging activity at 500 µg/mL. Administration of the S. mangifera alcoholic fraction at the abovementioned dose resulted in a significant reduction (p < 0.01) in arthritis score, paw diameters, TNF-α, IL-6 as compared to diseased animals. The docking results showed that residues show a critical binding affinity with TNF-α and act as the TNF-α antagonist. The alcoholic fraction of S. mangifera extract possesses beneficial effects on rheumatoid arthritis as well as anti-inflammatory potential, and can further can be used as a possible agent for novel target-based therapies for the management of arthritis.

16.
Curr Med Chem ; 28(39): 8036-8067, 2021.
Article in English | MEDLINE | ID: mdl-33881968

ABSTRACT

Cancer is a multi-factorial health condition involving uncontrolled cell divisions. The disease has its roots in genetic mutation. This disease affects men, women, and even children. Chemotherapy, photodynamic, photothermal, and hormonal therapies have been used to treat this deadliest disease, but a huge percentage of patients have chances of disease recurrence or resistance. Nowadays, dysregulation in miRNAs is considered one of the key factors for the development and progression of different types of cancers as they control the expression of genes responsible for cell proliferation, growth, differentiation, and apoptosis. Dietary phytochemicals with anticancer properties have been gaining focus for cancer treatment since they have been found more effective in targeting cancer via regulating miRNAs expression. These phytochemicals have no side effects and are readily available at a low cost. Several dietary phytochemicals with regulatory effects on the expression of miRNAs have been reported, including curcumin, diallyl disulfide, 3, 30-diindolylmethane, ellagic acid, genistein, indole-3-carbinol, quercetin, resveratrol, and sulforaphane. They exert their regulatory effects against different cancers either by upregulating or downregulating different cancer signalling pathways and inhibiting their progression. Curcumin down-regulates SHH pathways, epigallocatechin-3-gallate regulates the Notch pathway and inhibits TGFß1/SMAD signalling, and resveratrol regulates the Wnt/ß-catenin pathway and carnosic acid-induced apoptosis in colon cancer cell via JAK2/STAT3 signalling pathway. The miRNAs are used for the treatment of cancer as essential modulators in cellular pathways. Therefore, identifying the miRNAs and their targets and countering them with specific phytochemicals provide a safe and effective mechanism for the treatment of cancer.


Subject(s)
Curcumin , Diet , MicroRNAs , Neoplasms , Curcumin/pharmacology , Female , Humans , MicroRNAs/genetics , Neoplasm Recurrence, Local , Neoplasms/drug therapy , Neoplasms/genetics , Phytochemicals/pharmacology , Signal Transduction
17.
Curr Pharm Des ; 27(13): 1579-1587, 2021.
Article in English | MEDLINE | ID: mdl-33155905

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has changed the global scenario. To date, there are no treatment or preventive options. The discovery of a new drug will take time. In addition, the new drug will have side effects, and the virus will gradually become resistant to it. Therefore, it is important to search for a drug with a natural origin. OBJECTIVE: In this review, we analyzed and summarized various ethnomedicinal plants and their bioactive compounds as a source of antiviral agents for COVID-19 prevention and treatment. METHODS: From the literature, we selected different natural compounds that can act as potential targets at low cost with broad-spectrum antiviral activity. RESULTS: Of the 200 Chinese herbal extracts tested for their possible role against SARS-CoV, Lycoris radiata, Artemisia annua, Pyrrosia lingua, and Lindera aggregate showed anti-SARS-CoV effects with the median effective concentration = 2.4-88.2 µg/mL. CONCLUSION: Ethnomedicinal herbs can be used as an alternative source of novel, promising antiviral agents that might directly or indirectly inhibit the COVID-19 progression.


Subject(s)
COVID-19 , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Humans , Pandemics , SARS-CoV-2
18.
Plants (Basel) ; 11(1)2021 Dec 28.
Article in English | MEDLINE | ID: mdl-35009147

ABSTRACT

We are sorry to report that some images in Figure 1 reported in our recently published paper [...].

19.
3 Biotech ; 10(11): 493, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33134011

ABSTRACT

Obesity is an alarming sign and considered as a threat word wide. Since it not only hurt the human body but plays as a basis for other serious diseases like cardiovascular and many more. The 50% hydro-ethanolic extract of Dalbergia latifolia bark (D. latifolia) (DLBE; %yield = 16.34) and methanolic extract (4.32%) of D. latifolia were made. The DLBE was used for the acute oral toxicity and anti-obesity activity in the rodent. However, methanolic extract was used for characterization by high-performance thin layer chromatography (HPTLC) method. During acute toxicity study, it was shown that certainly there was no mortality or morbidity observed up to the maximum dose of 2000 mg/kg after administration of DLBE. The ultimate body weight, food intake, liver weight, total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), triglycerides (TG), aspartate aminotransferase (AST), alanine transaminase (ALT), serum creatinine and blood urea nitrogen (BUN) of rats treated with DLBE at a dose of 200 and 400 mg/kg respectively was considerably diminished to p < 0.01 and p < 0.05 as compared with high-fat diet (HFD) induced obese animals. However, DLBE treated with quite smaller dose revealed a non-significant (p > 0.05) effects on above parameters. The histopathological findings of the study from the cross section of liver and kidney show normal architecture in the cells treated with DLBE at a dose of 200 and 400 mg/kg respectively. Thus we can conclude that the bark extract of D. latifolia can be used for the treatment of obesity and a novel approach for further investigations of its pathology.

20.
Plants (Basel) ; 9(3)2020 Mar 11.
Article in English | MEDLINE | ID: mdl-32168878

ABSTRACT

The present study was designed to explore the neuroprotective properties of Aconitum napellus (Ranunculaceae). The plant detoxification was done using either water, or cow or goat milk as per the Ayurvedic shodhana method. The evaluation of the neuroprotective role of A. napellus was performed on diabetic neuropathy induced by streptozotocin in Sprague Dawley (SD) rats. Body mass, blood sugar level, oral glucose tolerance test, hyperalgesia, cold allodynia, motor co-ordination test, and locomotor activity, oxidative biomarkers (TBARS, reduced glutathione, catalase and superoxide dismutase) and sciatic nerve histomorphology were assessed. The in vitro studies were done on human neuroblastoma cell line SHSY-5Y and used an MTT assay to assess the antiproliferative activity of different extracts. Results suggest that the goat milk treated chloroform extract has less percentage of aconitine. After administration of the detoxified chloroform extract to the diabetic animals, there was a significant improvement in the myelination and degenerative changes of the nerve fibers along with behavioral changes (p < 0.05 as compared with diabetic control group). The findings of the in vitro research show an effective neuroprotective role of A. napellus. This suggests that A. napellus should be further investigated for its effect in diabetic pathology.

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