ABSTRACT
Two concentrations (6.25 and 1.25 mg/L) were used for two Parkinson's disease medications, Benserazide, and Trihexyphenidyl, to test their effects on the meiobenthic nematofauna. It is predicted that these highly hydrosoluble drugs will end up in marine environments. The results showed that both medications when added alone, induced (i) important changes in the numbers and (ii) taxonomic composition. The impact of Benserazide and Trihexyphenidyl was also reflected in the (iii) functional traits of nematofauna, with the most affected categories following exposure being the trophic group 1B, the clavate tails, the circular amphids, the c-p2 life history, and the body length of 1-2 mm. These results were supported by the molecular interactions of the studied drugs with both GLD-3 and SDP proteins of Caenorhabditis elegans. (iv) The mixtures of both drugs did not show any changes in the nematode communities, suggesting that no synergistic or antagonistic interactions exist between them.
Subject(s)
Antiparkinson Agents , Benserazide , Caenorhabditis elegans , Trihexyphenidyl , Animals , Antiparkinson Agents/pharmacology , Caenorhabditis elegans/drug effects , Caenorhabditis elegans/physiology , Water Pollutants, Chemical , Nematoda/drug effectsABSTRACT
We aim to evaluate the bond strength between resin composite and primary demineralized dentin, pretreated with silver diamine fluoride (SDF) and simultaneous SDF with potassium iodide (KI) after thermal aging. In this in vitro study, human carious-free primary molars were randomly assigned into three groups and prepared by exposing the superficial dentin. The primary dentin of each molar was demineralized. The first group (the control) received saline treatment before bond application. SDF was pretreated for the second group, whereas SDF and KI were used for the third. After that, the pretreated dentin was immediately built with resin composite bonded with a universal adhesive and kept wet for 24 hours. Then, the pretreated molars were prepared into beam specimens for microtensile bond strength (µTBS), 16 for each group, and subjected to thermal aging. Lastly, they were tested using a universal testing machine, and the resulting data were analyzed using one-way analysis of variance (ANOVA) followed by Tukey's post hoc test. It was found that the SDF-KI group had a significant difference with both the control and SDF groups (p < 0.05), while the control and SDF groups showed no significant differences (p = 0.310). The SDF-KI group had the highest mean value of 11.73 ± 4.39 megapascal (MPa). In contrast, the control group had the lowest mean value of 9.31 ± 3.41 MPa. Post hoc pairwise comparison results showed that SDF-KI pretreatment had a significantly higher strength value than the control and SDF groups. Pretreatment of demineralized primary dentin with SDF-KI does not negatively affect the immediate loading of resin composite. However, under the limitation of this study, KI application after SDF pretreatment is recommended to enhance the bond's durability of resin composite to demineralized dentin.
ABSTRACT
Tumor metabolism, an emerging hallmark of cancer, is characterized by aberrant expression of enzymes from various metabolic pathways including glycolysis and PPP (pentose phosphate pathway). Glucose 6 phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD), oxidative carboxylases of PPP, have been reported to accomplish different biosynthetic and energy requirements of cancer cells. G6PD and 6PGD have been proposed as potential therapeutic targets for cancer therapy during recent years due to their overexpression in various cancers. Here, we have employed enzymatic assay based screening using in-house G6PD and 6PGD assay protocols for the identification of mushroom extracts which could inhibit G6PD or 6PGD enzymatic activity for implications in cancer therapy. For the fulfillment of the objectives of present study, nine edible mushrooms were subjected to green extraction for preparation of ethanolic extracts. 6xhis-G6PD and pET-28a-h6PGD plasmids were expressed in BL21-DE3 E. coli cells for the expression and purification of protein of interests. Using purified proteins, in house enzymatic assay protocols were established. The preliminary screening identified two extracts (Macrolepiota procera and Terfezia boudieri) as potent and selective G6PD inhibitors, while no extract was found highly active against 6PGD. Further, evaluation of anticancer potential of mushroom extracts against lung cancer cells revealed Macrolepiota procera as potential inhibitor of cancer cell proliferation with IC50 value of 6.18 µg/ml. Finally, screening of M. procera-derived compounds against G6PD via molecular docking has identified paraben, quercetin and syringic acid as virtual hit compounds possessing good binding affinity with G6PD. The result of present study provides novel findings for possible mechanism of action of M. procera extract against A549 via G6PD inhibition suggesting that M. procera might be of therapeutic interest for lung cancer treatment.
ABSTRACT
Oxalis corniculata (Oxalidaceae) is a small decumbent and delicate appearing medicinal herb flourishing in warm temperate and tropical domains such as Pakistan and India. Main bioactive chemical constituents of Oxalis plant include several alkaloids, flavonoids, terpenoids, cardiac glycosides, saponins, and phlobatannins, along with steroids. Due to its polyphenolic, glycosides and flavonoid profile, it is proved to be protective in numerous ailments and exhibit various biological activities such as anti-fungal, anti-cancer, anti-oxidant, antibacterial, anti-diabetic, and cardioprotective. Moreover, bioactive phytochemicals from this plant possess significant wound healing potential. Our current effort intends to emphasize on the immense significance of this plant species, which have not been the subject matter of clinical trials and effective pharmacological studies, even though its favored usage has been stated. This review proposes that Oxalis corniculata possess a potential for the cure of various diseases. However, further researches on isolation and characterization of bioactive compounds along with pre-clinical trials are compulsory to figure out its pharmacological applications.
Subject(s)
Oxalidaceae , Plants, Medicinal , Anti-Bacterial Agents/pharmacology , Antioxidants , Flavonoids/pharmacology , Oxalidaceae/chemistry , Phytochemicals , Plant Extracts/chemistry , Plants, Medicinal/chemistryABSTRACT
As an antioxidant, lycopene has acquired importance as it prevents autoxidation of fats and related products. Tomatoes are an important agricultural product that is a great source of lycopene. It contains many vitamins and minerals, fiber, and carbohydrates and is associated with various positive effects on health. The antioxidant potential of tomatoes is substantially explained with lycopene compounds. Diet is a major risk factor for heart diseases which is shown as the most important cause of death in the world. It has been observed that the lycopene taken in the diet has positive effects in many stages of atherosclerosis. The serum lipid levels, endothelial dysfunction, inflammation, blood pressure, and antioxidative potential are mainly affected by lycopene. These natural antioxidants, which can also enhance the nutritional value of foods, may lead to new ways if used in food preservation. In this review study, the antioxidant potential and cardiovascular protection mechanism of lycopene are discussed.
Subject(s)
Antioxidants/pharmacology , Cardiovascular Diseases/prevention & control , Lycopene/pharmacology , Animals , Antioxidants/administration & dosage , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/pathology , Food Handling , Humans , Lycopene/administration & dosageABSTRACT
Citrus fruits such as oranges, grapefruits, lemons, limes, tangerines, and mandarins, whose production is increasing every year with the rise of consumer demand, are among the most popular fruits cultivated throughout the globe. Citrus genus belongs to the Rutaceae family and is known for its beneficial effects on health for centuries. These plant groups contain many beneficial nutrients and bioactive compounds. These compounds have antimicrobial, anticancer, antidiabetic, antiplatelet aggregation, and anti-inflammatory activities. Citrus waste, generated by citrus-processing industries in large amounts every year, has an important economic value due to richness of bioactive compounds. The present review paper has summarized the application and properties of Citrus and its waste in some fields such as food and drinks, traditional medicine practices, and recent advances in modern approaches towards pharmaceutical and nutraceutical formulations.
ABSTRACT
The SARS CoV-2 pandemic has affected millions of people around the globe. Despite many efforts to find some effective medicines against SARS CoV-2, no established therapeutics are available yet. The use of phytochemicals as antiviral agents provides hope against the proliferation of SARS-CoV-2. Several natural compounds were analyzed by virtual screening against six SARS CoV-2 protein targets using molecular docking simulations in the present study. More than a hundred plant-derived secondary metabolites have been docked, including alkaloids, flavonoids, coumarins, and steroids. SARS CoV-2 protein targets include Main protease (MPro), Papain-like protease (PLpro), RNA-dependent RNA polymerase (RdRp), Spike glycoprotein (S), Helicase (Nsp13), and E-Channel protein. Phytochemicals were evaluated by molecular docking, and MD simulations were performed using the YASARA structure using a modified genetic algorithm and AMBER03 force field. Binding energies and dissociation constants allowed the identification of potentially active compounds. Ligand-protein interactions provide an insight into the mechanism and potential of identified compounds. Glycyrrhizin and its metabolite 18-ß-glycyrrhetinic acid have shown a strong binding affinity for MPro, helicase, RdRp, spike, and E-channel proteins, while a flavonoid Baicalin also strongly binds against PLpro and RdRp. The use of identified phytochemicals may help to speed up the drug development and provide natural protection against SARS-CoV-2.
ABSTRACT
Nature has provided prodigious reservoirs of pharmacologically active compounds for drug development since times. Physcion and physcion 8-O-ß-D-glucopyranoside (PG) are bioactive natural anthraquinones which exert anti-inflammatory and anticancer properties with minimum or no adverse effects. Moreover, physcion also exhibits anti-microbial and hepatoprotective properties, while PG is known to have anti-sepsis as well as ameliorative activities against dementia. This review aims to highlight the natural sources and anticancer activities of physcion and PG, along with associated mechanisms of actions. On the basis of the literature, physcion and PG regulate multitudinous cell signaling pathways through the modulation of various regulators of cell cycle, protein kinases, microRNAs, transcriptional factors, and apoptosis linked proteins resulting in the effective killing of cancerous cells in vitro as well as in vivo. Both compounds effectively suppress metastasis, furthermore, physcion acts as an inhibitor of 6PGD and also plays an important role in chemosensitization. This review article suggests that physcion and PG are potent anticancer drug candidates, but further investigations on their mechanism of action and pre-clinical trials are mandatory in order to comprehend the full potential of these natural cancer killers in anticancer remedies.
Subject(s)
Antineoplastic Agents/pharmacology , Emodin , Neoplasms , Emodin/analogs & derivatives , Emodin/pharmacology , Glucosides , Humans , Neoplasms/drug therapy , Signal TransductionABSTRACT
Nature has always proved to be a significant reservoir of bioactive scaffolds that have been used for the discovery of drugs since times. Medicinal plants continue to be a solid niche for biologically active and therapeutically effective chemical entities, opening up new avenues for the successful treatment of several human diseases. The contribution of plant-derived compounds to drug discovery, either in their original or in the semi-synthetic derivative form, extends far back in time. This review aims to focus on the sources, biological, and pharmacological profile of a pharmacologically active plant-derived coumarin, osthole, which is an important component of numerous remedial plants such as Cnidium monnieri. Several studies have revealed that osthole possess pharmacological properties such as anticancer, antioxidant, anti-hyperglycemic, neuroprotective, and antiplatelet. Osthole has been reported to regulate various signaling pathways, which in turn modulate several apoptosis-related proteins, cell cycle regulators, protein kinases, transcriptional factors, cytokines, and growth receptors affiliated with inflammation, proliferation and several other ailments. Osthole is known to halt proliferation and metastasis of cancerous cells by arresting the cell cycle and inducing apoptosis. The data in this review paper supports the pharmacological potential of osthole but further experimentation, biosafety profiling and synergistic effects of this compound need to be focused by the researchers to understand the full spectrum of pharmacological potential of this therapeutically potent compound.
Subject(s)
Anti-Inflammatory Agents , Antineoplastic Agents , Antioxidants , Coumarins/pharmacology , Animals , Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents/pharmacology , Antioxidants/pharmacology , Biological Products/pharmacology , Cnidium/chemistry , HumansABSTRACT
BACKGROUND: High blood pressure effects heart and vessels. Development of pathogenesis is the result of oxidative stress. We aimed to investigate the antioxidant effects of propolis, caffeic acid phenethyl ester (CAPE), and pollen on the hearts of rats which chronic nitric oxide synthase (NOS) inhibited through Nω-nitro-L-arginine methyl ester (L-NAME). Paraoxonase 1 (PON1), total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), asymmetric dimethylarginine (ADMA), and nuclear factor-κB (NF-κB) were analyzed on the heart. MATERIAL AND METHODS: Sprague-Dawley rats were divided five groups of seven rats in every group; Group I: Control, Group II: L-NAME, Group III: L-NAME+propolis, Group IV: L-NAME+CAPE and Group V: L-NAME+pollen. L-NAME become dissolved in regular saline (0.9% NaCl w/v). The ethanolic extract of propolis (200 mg/kg/days, gavage), pollen (100 mg/kg/days, by gavage), CAPE (50 µM/kg/days, intraperitoneally), and the NOS inhibitor L-NAME (40 mg/kg, intraperitoneally) had been administered. RESULTS: Blood pressure (BP) of rats treated with propolis, CAP,E and pollen statistically significant decreased. Decreasing in BP of the rats of pollen group was more than CAPE and propolis groups (P < .05). PON1 and TAS levels decreased in L-NAME-treated groups (P < .05), but ranges have been better in propolis, CAPE and pollen groups. TOS, ADMA and NF-κB levels increased (P < .05) in L-NAME group; however, these parameters were lower (P < .05) in propolis and CAPE groups (P < .05). CONCLUSIONS: Vasorelaxant properties and free radical scavenging actions of propolis, CAPE, and pollen may reduce the oxidative stress and blood pressure in the rats chronic NOS inhibited through L-NAME.
Subject(s)
Blood Pressure/drug effects , Caffeic Acids/pharmacology , Free Radical Scavengers/pharmacology , Myocardium/metabolism , Phenylethyl Alcohol/analogs & derivatives , Pollen , Propolis/pharmacology , Animals , Anti-Inflammatory Agents/pharmacology , Antioxidants/metabolism , Arginine/analogs & derivatives , Arginine/metabolism , Aryldialkylphosphatase/metabolism , Male , NF-kappa B/metabolism , NG-Nitroarginine Methyl Ester , Nitric Oxide Synthase/antagonists & inhibitors , Oxidants/metabolism , Oxidative Stress/drug effects , Phenylethyl Alcohol/pharmacology , Rats , Rats, Sprague-DawleyABSTRACT
Nature always remains an inexhaustible source of treasures for mankind. It remains a mystery for every challenge until the completion of the challenge. While we talk about the complicated health issues, nature offers us a great variety of chemical scaffolds and their various moieties packed in the form of natural products e.g., plants, microorganisms (fungi, algae, protozoa), and terrestrial vertebrates and invertebrates. This review article is an update about jaceosidin, a bioactive flavone, from genus Artemisia. This potentially active compound exhibits a variety of pharmacological activities including anti-inflammatory, anti-oxidant, anti-bacterial, antiallergic and anti-cancer activities. The bioactivities and the therapeutic action of jaceosidin, especially the modulation of different cell signaling pathways (ERK1/2, NF-κB, PI3K/Akt and ATM-Chk1/2) which become deregulated in various pathological disorders, have been focused here. The reported data suggest that the bioavailability of this anti-cancer compound should be enhanced by utilizing various chemical, biological and computational techniques. Moreover, it is recommended that researchers and scientists should work on exploring the mode of action of this particular flavone to precede it further as a potent anti-cancer compound.
Subject(s)
Artemisia , Flavones , Animals , Flavones/pharmacology , Flavonoids , Phosphatidylinositol 3-KinasesABSTRACT
Natural products, being richly endowed with curative powers, have become spotlight for biomedical and pharmaceutical research to develop novel therapeutics during recent years. Ginkgetin (GK), a natural non-toxic biflavone, has been shown to exhibit anti-cancer, anti-inflammatory, anti-microbial, anti-adipogenic, and neuroprotective activities. GK combats cancer progression by arresting cell cycle, inducing apoptosis, stimulating autophagy, and targeting many deregulated signaling pathways such as JAK/STAT and MAPKs. GKhalts inflammation mediators like interleukins, iNOS, COX-2, PGE2, NF-κB, and acts as an inhibitor of PLA2. GK shows strong neuroprotection against oxidative stress-promoted cell death, inhibits cerebral micro-hemorrhage, decreases neurologic deficits, and halts apoptosis of neurons. GK also acts as anti-fungal, anti-viral, anti-bacterial, leishmanicidal and anti-plasmodial agent. GK shows substantial preventive or therapeutic effects in in vivo models of many diseases including atherosclerosis, cancer, neurodegenerative, hepatic, influenza, and inflammatory diseases. Based on various computational, in vitro and in vivo evidences, this article demonstrates the potential of ginkgetin for development of therapeutics against various diseases. Although GK has been systematically studied from pharmacological point of view, a vast field of pharmacokinetics, pre-clinical and clinical studies is still open for the researchers to fully validate its potential for the treatment of various diseases.
Subject(s)
Biflavonoids/pharmacology , Biflavonoids/therapeutic use , Animals , Apoptosis/drug effects , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Humans , MAP Kinase Signaling System/drug effects , Wnt Signaling Pathway/drug effectsABSTRACT
Nerium oleander, a member of family Apocynaceae, is commonly known as Kaner in various countries of Asia and Mediterranean region. This plant has been renowned to possess significant therapeutic potential due to its various bioactive compounds which have been isolated from this plant e.g., cardiac glycosides, oleandrin, α-tocopherol, digitoxingenin, urosolic acid, quercetin, odorosides, and adigoside. Oleandrin, a saponin glycoside is one of the most potent and pharmacologically active phytochemicals of N. oleander. Its remarkable pharmacotherapeutic potential have been interpreted as anticancer, anti-inflammatory, anti-HIV, neuroprotective, antimicrobial and antioxidant. This particular bioactive entity is known to target the multiple deregulated signaling cascades of cancer such as NF-κB, MAPK, and PI3K/Akt. The main focus of the current study is to comprehend the action mechanisms of oleandrin against various pathological conditions. The current review is a comprehensive summary to facilitate the researchers to understand the pharmacological position of the oleandrin in the arena of drug discovery, representing this compound as a new drug candidate for further researches. Moreover, in vivo and in silico based studies are required to explore the mechanistic approaches regarding the pharmacokinetics and biosafety profiling of this compound to completely track its candidature status in natural drug discovery.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Cardenolides/pharmacology , Phytochemicals , Signal Transduction/drug effects , Antineoplastic Agents, Phytogenic/chemistry , Cardenolides/chemistry , Cell Cycle , HumansABSTRACT
Anacardium plants have received increasing recognition due to its nutritional and biological properties. A number of secondary metabolites are present in its leaves, fruits, and other parts of the plant. Among the diverse Anacardium plants' bioactive effects, their antioxidant, antimicrobial, and anticancer activities comprise those that have gained more attention. Thus, the present article aims to review the Anacardium plants' biological effects. A special emphasis is also given to their pharmacological and clinical efficacy, which may trigger further studies on their therapeutic properties with clinical trials.
Subject(s)
Anacardium/chemistry , Anti-Bacterial Agents/pharmacology , Antineoplastic Agents/pharmacology , Antioxidants/pharmacology , Ethnopharmacology , Plant Extracts/pharmacology , Animals , HumansABSTRACT
The genus Achillea genus houses more than 100 species, a number of them are popularly used in traditional medicine for spasmodic gastrointestinal, gynecological and hepatobiliary disorders, hemorrhages, pneumonia, rheumatic pain, inflammation, wounds healing etc. Members of the genus contain a wide variety of volatile and non-volatile secondary metabolites, including terpenes, polyphenols, flavonoids and others. Multiple studies have assessed the biological effects and other aspects of Achillea spp. In a number of preclinical studies, Achillea plants and their essential oils have demonstrated promising antibacterial properties against a number of human and plant pathogens. Besides, the plants have displayed strong antioxidative and potent anti-proliferative and anticancer properties in various cellular and animal models. Achillea plants have widely been used as food preservative in food industry. Clinical studies have indicated its potential against multiple sclerosis (MS), irritable bowel syndrome (IBS), ulcerative colitis, episiotomy wound, primary dysmenorrhea, oral mucositis etc. The present work focuses to provide a brief overview on folk knowledge, phytochemistry, biological activity and applications of Achillea plants. There is a close relationship between the traditional ethnobotanical usage and pharmacological and clinical data from different Achillea spp. The application of Achillea plants and their extracts seems to be a promising alternative for antimicrobial and antioxidant purposes in food, pharmaceutical and cosmetic industries.
Subject(s)
Achillea/chemistry , Ethnobotany , Industry , Phytochemicals/analysis , Phytotherapy , Achillea/classification , Animals , Humans , Medicine, Traditional , Phytochemicals/chemistryABSTRACT
Nature's pharmacy has undoubtedly served humans as an affordable and safer health-care regime for a long times. Cardamonin, a chalconoid present in several plants has been known for a longtime to have beneficial properties towards human health. In this review, we aimed to highlight the recent advances achieved in discovering the pharmacological properties of cardamonin. Cardamonin is cardamom-derived chalcone, which plays a role in cancer treatment, immune system modulation, inflammation and pathogens killing. Through the modulation of cellular signaling pathways, cardamonin activates cell death signal to induce apoptosis in malignant cells that results in the inhibition of cancer development. Moreover, cardamonin arrests cell cycle by altering the expression of regulatory proteins during malignant cells division. Due to its relatively selective cytotoxic potential against host malignant cells, cardamonin is emerging as a promising novel experimental anticancer agent. The potential of cardamonin to target various signaling molecules, transcriptional factors, cytokines and enzymes, such as mTOR, NF-κB, Akt, STAT3, Wnt/ß-catenin and COX-2 enhances the opportunity to explore it as a new multi-target therapeutic agent. The pharmacokinetic and biosafety profile of cardamonin favor it as a potentially safe biomolecule for pharmaceutical drug development.
Subject(s)
Chalcones/pharmacology , Neoplasms/metabolism , Signal Transduction , Animals , Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis , Cell Cycle , Cell Line, Tumor , Humans , Immune System , Inflammation , Liver/drug effects , Neoplasms/drug therapy , Neovascularization, Pathologic , STAT3 Transcription Factor/metabolismABSTRACT
Apolipoproteins have important structural and functional roles in several lipoprotein particles. Apolipoproteins regulate lipid metabolism, adipose tissue, and energy production and serve major regulatory roles in both pre- and pro-atherosclerotic mechanisms. They are also involved in protective mechanisms against atherosclerotic plaques. Therefore, accurate quantification of apolipoproteins may serve as a crucial biomarker for cardiovascular diseases. However, most apolipoproteins cannot be detected using standard clinical immunoassays, and multiplexing is not available for some species of apolipoproteins. Herein, we describe a highly robust and quantitative method using liquid chromatography coupled to tandem mass spectrometry to quantify apolipoproteins in plasma. This methodology may add clinical value for profiling cardiovascular risk in vulnerable individuals and enable monitoring of apolipoprotein levels in plasma following intervention strategies.
Subject(s)
Apolipoproteins/blood , Atherosclerosis/blood , Chromatography, Liquid/methods , Plasma/chemistry , Tandem Mass Spectrometry/methods , Biomarkers/blood , Evaluation Studies as Topic , Humans , Lipid Metabolism/physiology , Plaque, Atherosclerotic/blood , RiskABSTRACT
Infundibulicybe geotropa (Bull.) Harmaja is an edible mushroom found in Bolu province in northwestern Turkey. The chemical composition and bioactivity of these mushrooms has not been previously investigated. We examined the phenolic composition, elemental content, and antioxidant and antigenotoxic effects of methanol extracts of fruiting bodies. The phenolic compounds in the fungal samples were determined using high-performance liquid chromatography (HPLC), and element content was determined using atomic absorption spectrophotometry. Total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were determined using the commercially available Rel assay kit. The antigenotoxic effects of the extract were determined using the MTT assay to assess cell viability and the alkaline single-cell gel electrophoresis assay (Comet assay). The total phenolic content (ppm) of I. geotropa was found to be catechin (361 ± 2.31), clorogenic acid (553.54 ± 5.06), and coumaric acid (9.93 ± 0.25). The TAS, TOS, and OSI of the extract were 1.854 ± 0.051 mmol/L, 30.385 ± 0.399 µmol/L, and 1.639 ± 0.067, respectively. The elemental levels were within "normal" range. In HT22 mouse hippocampal neuronal cells, the extract (100 and 200 µg/ml) showed no genotoxic potential and ameliorated hydrogen peroxide- (H2O2-) induced oxidative DNA damage. I. geotropa may be considered a good nutrient due to its phenolic constituents and antioxidant potential.
Subject(s)
Agaricales/chemistry , Antioxidants/therapeutic use , Animals , Antioxidants/pharmacology , Humans , Mice , TurkeyABSTRACT
Reprogrammed metabolism is key biochemical characteristic of malignant cells, which represents one of the emerging hallmarks of cancer. Currently, there is rising contemplation on oxidative pentose phosphate pathway (PPP) enzymes as potential therapeutic hits due to their affiliation with tumor metabolism. 6-Phosphogluconate dehydrogenase (6PGD), third oxidative decarboxylase of PPP, has received a great deal of attention during recent years due to its critical role in tumorigenesis and redox homeostasis. 6PGD has been reported to overexpress in number of cancer types and its hyperactivation is mediated through post-transcriptional and post-translational modifications by YTH domain family 2 (YTHDF2), Nrf2 (nuclear factor erythroid 2-related factor 2), EGFR (epidermal growth factor receptor) and via direct structural interactions with ME1 (malic enzyme 1). Upregulated expression of 6PGD provides metabolic as well as defensive advantage to cancer cells, thus, promoting their proliferative and metastatic potential. Moreover, enhanced 6PGD expression also performs key role in development of chemoresistance as well as radiation resistance in cancer. This review aims to discuss the historical timeline and cancer-specific role of 6PGD, pharmacological and genetic inhibitors of 6PGD and 6PGD as prognostic biomarker in order to explore its potential for therapeutic interventions. We anticipate that targeting this imperative supplier of NADPH might serve as tempting avenue to combat the deadly disease like cancer.
Subject(s)
Carcinogenesis/genetics , Drug Resistance, Neoplasm/genetics , Neoplasms/genetics , Pentose Phosphate Pathway/genetics , Phosphogluconate Dehydrogenase/genetics , Protein Processing, Post-Translational , Antineoplastic Agents/therapeutic use , Carcinogenesis/metabolism , Carcinogenesis/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Proliferation/radiation effects , ErbB Receptors/genetics , ErbB Receptors/metabolism , Gene Expression Regulation, Neoplastic , Humans , Lymphatic Metastasis , NADP/metabolism , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Neoplasms/enzymology , Neoplasms/pathology , Neoplasms/therapy , Pentose Phosphate Pathway/drug effects , Phosphogluconate Dehydrogenase/antagonists & inhibitors , Phosphogluconate Dehydrogenase/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Radiation Tolerance/genetics , Signal Transduction , Vesicular Transport Proteins/genetics , Vesicular Transport Proteins/metabolismABSTRACT
Octaviania asterosperma (hypogeous Basidiomycota) We investigated the phenolic composition, and antioxidant, antimicrobial and antigenotoxic effects of methanol extracts of fruiting bodies from Octaviania asterosperma. The total phenolic content (ppm) of O. asterosperma was found to be catechin (54.73 ± 4.68), epicatechin (123.90 ± 8.52), caffeic acid (4.23 ± 0.97), p-hydroxybenzoic acid (37.72 ± 3.84), cinnamic acid (58.07 ± 5.40), gallic acid (56.64 ± 6.39), clorogenic acid (80.76 ± 4.92) and coumaric acid (2.45 ± 0.15). The total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) were 3.410 ± 0.099 mmol/L, 7.548 ± 0.147 µmol/L and 0.221 ± 0.005 respectively. O. asterosperma showed some promising antimicrobial activity. The extract showed no genotoxic potential and attenuated hydrogen peroxide (H2O2)-induced oxidative DNA damage in neurons. Pre-treatment with O. asterosperma maintained mitochondrial function, reduced expression levels of cleaved-caspase-3 and apoptosis-inducing factor (AIF) when HT22 cells were exposed to pathophysiological concentrations of GLU (25 mM) and modulated protein kinase B (Akt), the mammalian target of rapamycin (mTOR), and the phosphotase and tensin homolog on chromosome ten (PTEN). O. asterosperma is an important food for the treatment or management of neurodegenerative disorders due to its phenolic content and potent antioxidant and anti-excitotoxic effects.