ABSTRACT
The indigenous purplish red fruit, Cleistocalyx nervosum var. paniala (CN), is grown in northern Thailand. The aqueous extract of CN pulp is known to exhibit antioxidant and anticarcinogenic properties. To search for an antioxidant fraction separated from CN, various hydroalcoholic extractions were performed. The acidified ethanolic extract of CN obtained from 0.5% (v/v) citric acid in 80% (v/v) ethanol yielded greater polyphenol content and DPPH radical scavenging activity when compared with other hydroethanolic extracts. Cyanidin-3-glucoside is a major anthocyanin present in the acidified ethanolic extract of CN (AECN). At a dose of 5000 mg/kg bw, an anthocyanin-rich extract was found to be safe when given to rats without any acute toxicity. To examine the hepatoprotective properties of AECN, an overdose of acetaminophen (APAP) was induced in a rat model, while silymarin was used as a standard reference. The administration of AECN at a dose of 300 mg/kg bw for 28 days improved hepatocyte architecture and modulated serum alanine aminotransferase levels in APAP-induced rats. Furthermore, it significantly decreased serum and hepatic malondialdehyde levels but increased hepatic glutathione content, as well as glutathione peroxidase and UDP-glucuronosyltransferase activities. In conclusion, AECN may effectively reduce oxidative stress induced acute hepatotoxicity in overdose APAP-treated rats through the suppression of oxidative stress and the enhancement of the antioxidant system in rat livers.
Subject(s)
Acetaminophen/adverse effects , Antioxidants/pharmacology , Chemical and Drug Induced Liver Injury/prevention & control , Plant Extracts/pharmacology , Protective Agents/pharmacology , Syzygium/chemistry , Alanine Transaminase/blood , Animals , Anthocyanins , Antioxidants/therapeutic use , Antioxidants/toxicity , Chemical and Drug Induced Liver Injury/blood , Chemical and Drug Induced Liver Injury/pathology , Disease Models, Animal , Enzymes/drug effects , Enzymes/metabolism , Ethanol/chemistry , Female , Fruit/chemistry , Glutathione/metabolism , Glutathione Peroxidase/metabolism , Liver/drug effects , Liver/enzymology , Malondialdehyde/metabolism , Oxidative Stress/drug effects , Plant Extracts/therapeutic use , Plant Extracts/toxicity , Polyphenols/analysis , Polyphenols/pharmacology , Polyphenols/therapeutic use , Protective Agents/therapeutic use , Protective Agents/toxicity , Rats, Wistar , Silymarin/pharmacology , Silymarin/therapeutic use , ThailandABSTRACT
A novel series of multitargeted molecules were designed and synthesized by combining the pharmacological role of cholinesterase inhibitor and antioxidant of steroid as potential ligands for the treatment of Vascular Dementia (VD). The oxygen-glucose deprivation (OGD) model was used to evaluate these molecules, among which the most potent compound ML5 showed the highest activity. Firstly, ML5 showed appropriate inhibition of cholinesterases (ChEs) at orally 15 mg/kg in vivo. The further test revealed that ML5 promoted the nuclear translocation of Nrf2. Furthermore, ML5 has significant neuroprotective effect in vivo model of bilateral common carotid artery occlusion (BCCAO), significantly increasing the expression of Nrf2 protein in the cerebral cortex. In the molecular docking research, we predicted the ML5 combined with hAChE and Keap1. Finally, compound ML5 displayed normal oral absorption and it was nontoxic at 500 mg/kg, po, dose. We can draw the conclusion that ML5 could be considered as a new potential compound for VD treatment.
Subject(s)
Central Nervous System Agents/therapeutic use , Cholinesterase Inhibitors/therapeutic use , Dementia, Vascular/drug therapy , Diosgenin/analogs & derivatives , Diosgenin/therapeutic use , Protective Agents/therapeutic use , Acetylcholinesterase/metabolism , Animals , Cell Survival/drug effects , Central Nervous System Agents/chemical synthesis , Central Nervous System Agents/metabolism , Central Nervous System Agents/toxicity , Cholinesterase Inhibitors/chemical synthesis , Cholinesterase Inhibitors/metabolism , Cholinesterase Inhibitors/toxicity , Diosgenin/metabolism , Diosgenin/toxicity , Humans , Kelch-Like ECH-Associated Protein 1/metabolism , Learning/drug effects , Male , Memory/drug effects , Mice, Inbred ICR , Molecular Docking Simulation , NF-E2-Related Factor 2/metabolism , Neuroprotection/drug effects , Protective Agents/chemical synthesis , Protective Agents/metabolism , Protective Agents/toxicity , Protein Binding , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolismABSTRACT
In this study, the association of expressional alterations in neuronal G protein-coupled receptors (GPCRs) with induction of protective response to polystyrene nanoparticles (PS-NPs) was investigated in Caenorhabditis elegans. On the basis of both phenotypic analysis and expression levels, the alterations in expressions of NPR-1, NPR-4, NPR-8, NPR-9, NPR-12, DCAR-1, GTR-1, DOP-2, SER-4, and DAF-37 in neuronal cells mediated the protective response to PS-NPs exposure. In neuronal cells, NPR-9, NPR-12, DCAR-1, and GTR-1 controlled the PS-NPs toxicity by activating or inhibiting JNK-1/JNK MAPK signaling. Neuronal NPR-8, NPR-9, DCAR-1, DOP-2, and DAF-37 controlled the PS-NPs toxicity by activating or inhibiting MPK-1/ERK MAPK signaling. Neuronal NPR-4, NPR-8, NPR-9, NPR-12, GTR-1, DOP-2, and DAF-37 controlled the PS-NPs toxicity by activating or inhibiting DBL-1/TGF-ß signaling. Neuronal NPR-1, NPR-4, NPR-12, and GTR-1 controlled the PS-NPs toxicity by activating or inhibiting DAF-7/TGF-ß signaling. Our data provides an important neuronal basis for induction of protective response to PS-NPs in C. elegans.
Subject(s)
Caenorhabditis elegans/drug effects , Nanoparticles/chemistry , Neurons/drug effects , Polystyrenes/pharmacology , Protective Agents/toxicity , Receptors, G-Protein-Coupled/antagonists & inhibitors , Animals , Caenorhabditis elegans/metabolism , Neurons/metabolism , Polystyrenes/chemistry , Protective Agents/chemistry , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolismABSTRACT
The first description of the medical use of licorice appeared in "Shennong Bencao Jing", one of the well-known Chinese herbal medicine classic books dated back to 220-280 AD. As one of the most commonly prescribed Chinese herbal medicine, licorice is known as "Guo Lao", meaning "a national treasure" in China. Modern pharmacological investigations have confirmed that licorice possesses a number of biological activities, such as antioxidation, anti-inflammatory, antiviral, immune regulation, and liver protection. 18ß-glycyrrhetinic acid is one of the most extensively studied active integrants of licorice. Here, we provide an overview of the protective effects of 18ß-glycyrrhetinic acid against various acute and chronic liver diseases observed in experimental models, and summarize its pharmacological effects and potential toxic/side effects at higher doses. We also make additional comments on the important areas that may warrant further research to support appropriate clinical applications of 18ß-glycyrrhetinic acid and avoid potential risks.
Subject(s)
Glycyrrhetinic Acid/analogs & derivatives , Liver Diseases/prevention & control , Protective Agents/therapeutic use , Animals , Glycyrrhetinic Acid/pharmacology , Glycyrrhetinic Acid/therapeutic use , Glycyrrhetinic Acid/toxicity , Humans , Liver/drug effects , Liver/metabolism , Liver Diseases/metabolism , Protective Agents/pharmacology , Protective Agents/toxicityABSTRACT
INTRODUCTION: Osteoarthritis (OA) is a severe joint degeneration disease in elderly people described by the advanced degradation of articular cartilage, which ultimately leads to chronic pain. Trans-cinnamaldehyde (TCA) exerted its anti-inflammatory function in numerous disease syndromes; however, its role in the pathogenesis of OA remains unknown. The current research aimed to explore the potential protective impact of TCA in the progression of osteoarthritis in vitro. MATERIAL AND METHODS: Human knee articular chondrocytes were treated with 10 ng/ml IL-1b alone for 24 h or in a combination in a pretreatment with TCA at different concentrations (2, 5, 10 µg/mL, 24 h). The viability and cell apoptosis were determined by CCK-8 assay and flow cytometry methods. The protein levels of IL-8, PGE2, and TNF-a and the levels of phosphorylated AKT and PI3K were evaluated using ELISA assay. Moreover, RT-qPCR was used to measure the relative mRNA expression of MMP-13, iNOS, COX-2, and ADAMTS-5 in IL-1b-induced chondrocytes. RESULTS: Our results revealed that the treatment with TCA had no effect on chondrocytes' proliferation and apoptosis. Moreover, the protein levels of IL-8, TNF-a, and PGE2 were considerably reduced in IL-1b-induced chondrocytes treated with different concentrations of TCA. Furthermore, the mRNA expression of MMP-13, iNOS, COX-2, and ADAMTS-5 and the phosphorylation of AKT and PI3K were markedly reduced in IL-1b-induced chondrocytes with the increase in the concentration of TCA. CONCLUSIONS: Trans-cinnamaldehyde inhibited the inflammation induced by IL-1b in chondrocytes through the PI3K/AKT pathway, which suggests that TCA might serve as a potential therapeutic agent for osteoarthritis treatment.
Subject(s)
Acrolein/analogs & derivatives , Inflammation/prevention & control , Osteoarthritis/prevention & control , Protective Agents/pharmacology , Signal Transduction/drug effects , Acrolein/pharmacology , Acrolein/toxicity , Cells, Cultured , Chondrocytes/drug effects , Dinoprostone/metabolism , Humans , Inflammation/chemically induced , Inflammation/metabolism , Interleukin-1beta , Interleukin-8/metabolism , Osteoarthritis/chemically induced , Osteoarthritis/metabolism , Phosphatidylinositol 3-Kinase/metabolism , Protective Agents/toxicity , Proto-Oncogene Proteins c-akt/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Saikosaponin d (SSd), a primary active component of the Chinese herb Bupleurum falcatum, has antitumor and antiliver fibrosis effects. However, the toxicity of SSd at high doses can induce conditions such as metabolic disorders and hemolysis in vivo, thus hampering its clinical use. The present study investigated the toxicity-reducing effects of liposome encapsulation of pure SSd and the therapeutic action of SSd-loaded liposomes (Lipo-SSd) in liver fibrosis in vitro and in vivo. Lipo-SSd (diameter, 31.7 ± 7.8 nm) was prepared at an entrapment efficiency of 94.1%. After 10-day incubation, a slow release profile of 56% SSd from Lipo-SSd was observed. The IC50 of SSd on hepatic stellate cells was approximately 2.9 µM. Lipo-SSd exhibited much lower cytotoxicity than did pure SSd. In the in vivo toxicity assay, Lipo-SSd significantly increased mice survival rate and duration compared with pure SSd at the same dose. These in vitro and in vivo data indicate that liposomal encapsulation can reduce the cytotoxicity of SSd. The histopathological analysis results demonstrated that in mice with thioacetamide-induced liver fibrosis, Lipo-SSd exerted more obvious fibrosis- and inflammation-alleviating and liver tissue-reparative effects than did pure SSd; these effects are potentially attributable to the sustained release of SSd. In conclusion, Lipo-SSd fabricated here have antiliver fibrosis effects and lower toxicity compared with that of pure SSd.
Subject(s)
Chemical and Drug Induced Liver Injury/drug therapy , Liver Cirrhosis, Experimental/drug therapy , Liver/drug effects , Oleanolic Acid/analogs & derivatives , Protective Agents/pharmacology , Saponins/pharmacology , Animals , Apoptosis/drug effects , Cell Line , Cell Survival/drug effects , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/pathology , Delayed-Action Preparations , Dose-Response Relationship, Drug , Drug Compounding , Drug Liberation , Hepatic Stellate Cells/drug effects , Hepatic Stellate Cells/pathology , Humans , Inhibitory Concentration 50 , Liposomes , Liver/metabolism , Liver/pathology , Liver Cirrhosis, Experimental/chemically induced , Liver Cirrhosis, Experimental/metabolism , Liver Cirrhosis, Experimental/pathology , Male , Mice, Inbred C57BL , Oleanolic Acid/chemistry , Oleanolic Acid/pharmacology , Oleanolic Acid/toxicity , Protective Agents/chemistry , Protective Agents/toxicity , Saponins/chemistry , Saponins/toxicity , ThioacetamideABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Polygonum multiflorum (Thunb.) (PMT) is a member of Polygonaceae. Traditional Chinese medicine considers that the processed PMT can tonify liver, nourish blood and blacken hair. In recent years, the processed PMT and its active ingredients have significant therapeutic effects on nonalcoholic fatty liver disease, alcoholic fatty liver disease, viral hepatitis, liver fibrosis and liver cancer. AIM OF THE STUDY: The main purpose of this review is to provide a critical appraisal of the existing knowledge on the clinical application, hepatoprotective pharmacology and hepatotoxicity, it provides a comprehensive evaluation of the liver function of the processed PMT. MATERIALS AND METHODS: A detailed literature search was conducted using various online search engines, such as Pubmed, Google Scholar, Mendeley, Web of Science and China National Knowledge Infrastructure (CNKI) database. The main active components of the processed PMT and the important factors in the occurrence and development of liver diseases are used as key words to carry out detailed literature retrieval. RESULTS: In animal and cell models, the processed PMT and active components can treat various liver diseases, such as fatty liver induced by high-fat diet, liver injury and fibrosis induced by drugs, viral transfected hepatitis, hepatocellular carcinoma, etc. They can protect liver by regulating lipid metabolism related enzymes, resisting insulin resistance, decreasing the expression of inflammatory cytokines, inhibiting the activation of hepatic stellate cells, reducing generation of extracellular matrix, promoting cancer cell apoptosis and controlling the growth of tumor cells, etc. However, improperly using of the processed PMT can cause liver injury, which is associated with the standardization of processing, the constitution of the patients, the characteristics of the disease, and the administration of dosage and time. CONCLUSION: The processed PMT can treat various liver diseases via reasonably using, and the active compounds (2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside, emodin, physcion, etc.) are promising candidate drugs for developing new liver protective agents. However, some components have a "toxic-effective" bidirectional effect, which should be used cautiously.
Subject(s)
Fallopia multiflora , Liver Diseases/prevention & control , Liver/drug effects , Phytotherapy , Plant Extracts/pharmacology , Protective Agents/pharmacology , Animals , Fallopia multiflora/chemistry , Fallopia multiflora/toxicity , Humans , Liver/metabolism , Liver/pathology , Liver Diseases/metabolism , Liver Diseases/pathology , Plant Extracts/isolation & purification , Plant Extracts/toxicity , Protective Agents/isolation & purification , Protective Agents/toxicityABSTRACT
Due to their unique dietary fibre composition, in particular ß-glucan, the consumption of barley may contribute to a healthy diet and the prevention of colon cancer. The aim of the present study was to analyse chemopreventive effects of barley flakes obtained from a ß-glucan-rich barley cultivar. In order to address the impact of heat treatment on potential chemopreventive effects, barley flakes were roasted (160 °C-180 °C, approx. 20 min). The flakes were subjected to in vitro digestion and fermentation. Fermentation supernatants (FS) were analysed for the concentrations of short-chain fatty acids (SCFA) and ammonia. Chemopreventive endpoints (growth inhibition, apoptosis, DNA integrity, gene expression of detoxifying enzymes) were analysed in LT97 colon adenoma cells. Concentrations of SCFA were increased in barley FS (2.5-fold, on average) with a shift of molar ratios towards butyrate production, while ammonia levels were significantly decreased (0.7-fold, on average) compared to the fermentation control. The growth of LT97 cells was significantly reduced by barley FS in a time- and dose-dependent manner, and caspase-3 activity of treated cells was significantly enhanced (up to 6.3-fold, on average). On average, treatment of cells resulted in increased mRNA levels of CAT (2.1-fold), SOD2 (2.2-fold) and GSTP1 (3.9-fold), while expression of GPx1 (0.3-fold) was significantly decreased in some cases. The roasting process did not cause genotoxic effects of barley FS and had no impact on chemopreventive properties. Our results indicate chemopreventive potential of in vitro fermented waxy winter barley, mediated primarily by growth inhibitory and apoptotic effects, which is largely unaffected by roasting.
Subject(s)
Digestion/drug effects , Hordeum , Protective Agents/pharmacology , beta-Glucans/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , Colon/metabolism , Cooking , Humans , Models, Biological , Phytochemicals/chemistry , Phytochemicals/pharmacology , Phytochemicals/toxicity , Protective Agents/chemistry , Protective Agents/toxicity , beta-Glucans/chemistry , beta-Glucans/toxicityABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: In China, Penthorum chinense Pursh (P. chinense) has been used for hundreds of years traditionally for alleviating symptoms by excessive intake of alcohol as well as in the treatment of traumatic injury, edema and liver diseases. Recently, P. chinense and its extract have been developed into tea, drinks or medicines for treatment of liver diseases, including hepatic virus infections, alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD) and liver fibrosis. AIM OF THE STUDY: The main purpose of this review is to provide a critical appraisal of the existing knowledge on the phytochemical data, quality control aspect, pharmacological, as well as toxicological and clinical studies performed on P. chinense, including the identification of scientific gaps. MATERIALS AND METHODS: A detailed literature search was conducted using various online search engines, such as Pubmed, Scopus, Google Scholar, Mendeley, Web of Science as well as China National Knowledge Infrastructure (CNKI) database. RESULTS: In the pharmacological studies, there clearly are links between local/traditional uses and the biomedical investigations. Most pharmacological studies indicated potential liver protective effects in experimental models of chemicals-induced liver injury, acute and chronic alcoholic liver injury, NAFLD, liver fibrosis and viral infection, potentially through antioxidant effects, balancing key liver enzyme levels, inhibition of hepatic virus DNA replication, inhibition of hepatic stellate cells activation and inflammation either in vitro or in vivo. In some models, the effects of P. chinense is comparable with the one of silymarin. Clinical studies have suggested that P. chinense is safe and effective in treating several liver diseases, although most of them are not double-blinded and placebo-controlled studies. Toxicology studies show that P. chinense has no obvious toxicity or side effects in animals or human. Flavonoids, lignans, coumarins, polyphenols and organic acids have been identified. However, only a few studies have investigated the active compounds (mainly flavonoids and lignans) and molecular mechanisms of P. chinense. CONCLUSION: P. chinense seems to be safe and shows relevant liver protecting effects. Therefore, it might be a promising candidate for developing as new hepatoprotective agents. However, a lack of understanding of the active compounds and mechanisms of action needs further attention.
Subject(s)
Liver Diseases/drug therapy , Magnoliopsida , Plant Extracts , Protective Agents , Animals , Humans , Liver Diseases/prevention & control , Medicine, Traditional , Phytochemicals/analysis , Phytochemicals/pharmacology , Phytochemicals/therapeutic use , Phytochemicals/toxicity , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Plant Extracts/toxicity , Protective Agents/chemistry , Protective Agents/pharmacology , Protective Agents/therapeutic use , Protective Agents/toxicityABSTRACT
In searching for more effective and safer antiepileptic drugs, a series of 2,5-disubstituted [1,2,4]-triazolo[1,5-a]pyrimidine-7(4H)-one derivatives were designed and synthesized. Spontaneous Ca2+ oscillations (SCOs) of cortical neurons were used for in vitro phenotypic screening. Maximal electroshock test (MES) and pentylenetetrazole (PTZ) test were used to access their anticonvulsant activity, and rotarod test was used to estimate their neurotoxicity. The active compounds in in vitro model are specifically effective in pentylenetetrazole (PTZ)-induced epilepsy model but not maximal electroshock (MES) model, more importantly with lower neurotoxicity as compared to commonly used drugs. Among them, compound 5c and 5e showed significant anticonvulsant activities in PTZ-induced epilepsy model with ED50 values at 31.81â¯mg/kg and 40.95â¯mg/kg, respectively. These compounds have improved neurotoxicity with protective index (PIâ¯=â¯TD50/ED50) values at 17.22 and 9.09, respectively. Finally we demonstrated that compound 5c and 5e mainly acted on GABAA receptor as positive modulators but not sodium channels. Thus the present study has provided potential candidates for further investigation in epilepsy.
Subject(s)
Anticonvulsants/pharmacology , Motor Activity/drug effects , Protective Agents/pharmacology , Pyrimidines/pharmacology , Receptors, GABA-A/metabolism , Seizures/drug therapy , Triazoles/pharmacology , Animals , Anticonvulsants/chemistry , Anticonvulsants/toxicity , Cells, Cultured , Dose-Response Relationship, Drug , Drug Discovery , Electroshock , Mice , Mice, Inbred C57BL , Molecular Structure , Pentylenetetrazole , Protective Agents/chemistry , Protective Agents/toxicity , Pyrimidines/chemistry , Pyrimidines/toxicity , Seizures/chemically induced , Structure-Activity Relationship , Triazoles/chemistry , Triazoles/toxicityABSTRACT
Rivaroxaban as a small molecule is able to directly and reversibly inhibit the factor Xa. This study was designed to figure out the evaluation effect of rivaroxaban on mitochondria obtained from rat kidneys. We isolated mitochondria from rat kidneys using gradient centrifugation. Then, the toxicity parameters including succinate dehydrogenase (SDH) activity, reactive oxygen species (ROS) formation, mitochondrial swelling, mitochondrial membrane potential (MMP) collapse and cytochrome c release were measured in kidneys mitochondria following the exposure to rivaroxaban. The results showed that rivaroxaban (1.4 and 2.8 mM) raised the reactive oxygen species (ROS) generation, swelling in the mitochondria, collapse in the mitochondrial membrane potential (MMP) and cytochrome c release in the mitochondria isolated from kidneys. While, rivaroxaban at a higher concentration of 5.6 mM showed the opposite effect compared to other lower concentrations. The results indicate that rivaroxaban may have antioxidant effects at high concentrations. The results suggest that rivaroxaban (5.6 mM) has protective effects against oxidative stress and mitochondrial toxicity.
Subject(s)
Antioxidants/administration & dosage , Mitochondria/drug effects , Protective Agents/administration & dosage , Reactive Oxygen Species/metabolism , Rivaroxaban/administration & dosage , Animals , Antioxidants/toxicity , Cytochromes c/metabolism , Dose-Response Relationship, Drug , Kidney/cytology , Kidney/drug effects , Male , Membrane Potential, Mitochondrial/drug effects , Mitochondria/metabolism , Oxidative Stress/drug effects , Protective Agents/toxicity , Rats , Rats, Wistar , Rivaroxaban/toxicity , Toxicity Tests, AcuteABSTRACT
In this work, the cytotoxicity of Beauvericin (BEA), lutein (LUT), zeaxanthin (ZEAX) and goji berries extract (GBE) rich in carotenoids, was investigated, as well as cytoprotective effects of these carotenoids against BEA induced-cytotoxicity on Caco-2 cells. Cytotoxicity was carried out using MTT and protein content (PC) assays during 24 and 48 h of exposure. Only BEA showed cytotoxic effect obtaining a reduction in cell proliferation range from 6.5 to 92.8%. Simultaneous combination of LUT and ZEAX with BEA slightly increased cell proliferation compared to BEA tested alone. LUT, ZEAX and GBE showed cytoprotective effects against cytotoxicity induced by BEA on Caco-2 cells. Pre-treatment assays showed the highest cytoprotection effect at the highest dose of BEA assayed (2.5 µM) in 29%, 31% and 35% for LUT, ZEAX and LUT + ZEAX, respectively; GBE showed a cytoprotection of 20%, for the same dose of BEA. The interaction between LUT, ZEAX and BEA studied by means of CI-isobologram method showed a synergism and antagaonism effect for all the combinations tested. These findings highlight that food containing high level of carotenoids, as goji berries, could contribute to reduce the toxicological risk that natural contaminant as BEA mycotoxin in diet can produce to the humans.
Subject(s)
Depsipeptides/toxicity , Lutein/pharmacology , Lycium/chemistry , Plant Extracts/pharmacology , Protective Agents/pharmacology , Zeaxanthins/pharmacology , Caco-2 Cells , Cytoprotection/drug effects , Drug Synergism , Fruit/chemistry , Humans , Lutein/toxicity , Mycotoxins/toxicity , Plant Extracts/toxicity , Protective Agents/toxicity , Zeaxanthins/toxicityABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Cucumis ficifolius A. Rich is a perennial prostrate herb that stems up to 1â¯m long. Its root is widely used in traditional medicine to treat various diseases including liver diseases. Yet, scientific evidence is lacking to verify its ethno medicinal claims. AIM OF THE STUDY: The present study was conducted to assess the hepatoprotective and radical scavenging activity of 80% methanol crude extract and different fractions of Cucumis ficifolius root. MATERIALS AND METHODS: Radical scavenging activity was done applying the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay while hepatoprotective activity was assessed using pre- and post-treatment models of carbon tetrachloride (CCl4)-induced liver injury in Swiss albino mice of either sex weighing 25-30â¯g. A single oral dose of 2000â¯mg/kg was used for acute toxicity study, doses of 125, 250, and 500â¯mg/kg were used in the pre-treatment model, and 500â¯mg/kg of extract and chloroform fraction were used in the post-treatment model. Biochemical markers and histopathological parameters were used to measure hepatoprotective activities. RESULTS: C. ficifolius crude extract and its solvent fractions showed strong radical scavenging activity and the chloroform fraction had the highest activity. No sign of toxicity was shown in an acute toxicity test of the extract. Hepatoprotective activity evaluation on the crude extract by a pre-treatment model with 125, 250, and 500â¯mg/kg doses revealed a significant (pâ¯<â¯0.05) reduction of the serum level of CCl4-induced liver enzyme markers at the highest tested dose (500â¯mg/kg). The chloroform fraction that had highest radical scavenging activity and the crude extract, both at 500â¯mg/kg, were again evaluated in a post-treatment model and the results revealed that both the extract and the chloroform fraction demonstrated significant (pâ¯<â¯0.05) hepatoprotective activities which support the results of the pre-treatment model. CONCLUSION: The present study verified the hepatoprotective potentials of C. ficifolius extract and its chloroform fraction which might be, at least in part, through radical scavenging action.
Subject(s)
Chemical and Drug Induced Liver Injury/drug therapy , Cucumis , Plant Extracts/therapeutic use , Protective Agents/therapeutic use , Animals , Biphenyl Compounds/chemistry , Carbon Tetrachloride , Chemical and Drug Induced Liver Injury/pathology , Female , Liver/drug effects , Liver/pathology , Male , Mice , Picrates/chemistry , Plant Extracts/chemistry , Plant Extracts/toxicity , Plant Roots , Protective Agents/chemistry , Protective Agents/toxicity , Toxicity Tests, AcuteABSTRACT
Cisplatin is an effective chemotherapeutic agent used in the treatment of various cancers. However, its use is usually complicated by nephrotoxic side effects, which limit its clinical application. Interestingly, DHA supplementation has been found to exhibit anticancer activity without any side effects. It is noted that DHA-PC has been applied in the treatment of kidney diseases. Our aim in the current study was to investigate whether DHA-PC treatment could alleviate cisplatin-induced nephrotoxicity using a Balb/c mice model. Our results showed that DHA-PC could significantly prolong the survival time, while the traditional DHA had no remarkable changes. In addition, short supplements of DHA-PC alleviated the cisplatin-induced kidney dysfunction, such as increased levels of blood urea nitrogen and creatinine. DHA-PC could protect the kidneys against cisplatin-induced toxicity, which might be attributed to the sirtuin 1 activation and the inhibition of oxidative stress and apoptosis. These findings suggest that DHA-PC might be a new dietary strategy for the treatment of nephrotoxicity.
Subject(s)
Cisplatin/toxicity , Docosahexaenoic Acids/chemistry , Docosahexaenoic Acids/pharmacology , Kidney Diseases/chemically induced , Phosphatidylcholines/chemistry , Phosphatidylcholines/pharmacology , Animals , Antineoplastic Agents/toxicity , Apoptosis/drug effects , Gene Expression Regulation/drug effects , Kidney Diseases/prevention & control , Male , Mice , Mice, Inbred BALB C , Mitochondria/drug effects , Protective Agents/toxicity , Signal Transduction/drug effects , Sirtuin 1/genetics , Sirtuin 1/metabolismABSTRACT
Enzootic bovine haematuria, caused by long-term ingestion of ferns, is a chronic disease of hill cattle characterized by neoplastic lesions in the urinary bladder. Objectives of this study were to investigate the toxicity potential of long-term feeding of the fern Dryopteris nigropalaceae and effect of allyl isothiocyanate (AITC) to ameliorate fern toxicity and the associated pathological changes. The LC-MS analysis of the fern showed presence of ptaquiloside (4.5⯱â¯1.0⯵g/g) and pterosin B (39⯱â¯9.1⯵g/g). Groups of animals were fed dried fern powder at the dose of 20% w/w in normal feed and treated with and without AITC at graded doses. Long term feeding of fern induced inflammatory and pre-neoplastic lesions in urinary bladder. The important lesions included cystitis, squamous metaplasia and high-grade dysplasia. Urothelium showed positive immunoreactions for nuclear expression of H-ras and p53. However, no mutation suggestive of neoplastic change was observed on partial mRNA sequences analyses of exon 2 of H-ras and 5 or 7&8 of p53 genes. Strikingly, AITC showed dose-dependent amelioration of pre-neoplastic changes in fern-fed animals. In conclusion, AITC is shown to limit pre-neoplastic changes caused by D. nigropalaceae feeding in guinea pigs.
Subject(s)
Cattle Diseases/drug therapy , Dryopteris/chemistry , Hematuria/veterinary , Isothiocyanates/pharmacology , Protective Agents/pharmacology , Animals , Cattle , Cattle Diseases/genetics , Cattle Diseases/pathology , Female , Guinea Pigs , Hematuria/drug therapy , Hematuria/genetics , Hematuria/pathology , Isothiocyanates/toxicity , Male , Protective Agents/toxicity , Random Allocation , Toxicity Tests, Chronic/veterinaryABSTRACT
Multiple studies revealed the potential application of high quality saffron byproducts as cheap sources of bioactive compounds endowed with antioxidant activity. In the present study, we analyzed the total fatty acids of the anthers, and explored the pharmacological and toxicological potential of anthers, by evaluating genotoxic and protective effects in multiple cell lines, brine shrimps and isolated rat tissues. The phytochemical analyses showed that anthers are rich in long chain fatty acids most of which are unsaturated (80.51%). Particularly, anther water extract revealed to be well tolerated by multiple cell lines, and able to modulate reactive oxygen species (ROS) levels, without exerting either genotoxic or cytotoxic effects. The same extract was also able to blunt lipopolysaccharide (LPS)-induced nitrite and malondialdehyde (MDA) in isolated rat tissues. On the other hand, considering the concomitant null effect on HCT116â¯cell migration, in wound healing experimental paradigm, our findings suggest the efficacy of water anther extract as protective agent without any direct reverting effects on lesioned tissues. Concluding, the promising results, deriving from the pharmacological and toxicological evaluations, support the valorization of saffron anthers as a strategy to optimize and develop the productive chain of Abruzzo saffron.
Subject(s)
Crocus/chemistry , Plant Extracts/administration & dosage , Protective Agents/pharmacology , Waste Products/analysis , Animals , Antioxidants/administration & dosage , Antioxidants/chemistry , Antioxidants/toxicity , Artemia , Cell Movement/drug effects , HCT116 Cells , Humans , Male , Plant Extracts/chemistry , Plant Extracts/toxicity , Protective Agents/chemistry , Protective Agents/toxicity , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolismABSTRACT
The present work investigated the antioxidative, anti-inflammatory and pulmonary protective effects of enzymatic- and acid- hydrolysed mycelia polysaccharides (En-MPS and Ac-MPS) from Oudemansiella radicata on LPS-induced acute lung injury (ALI) mice. The results demonstrated that both En-MPS and Ac-MPS showed potential pulmonary protective effects by decreasing serum levels of hs-CRP and C3, increasing pulmonary enzyme values of SOD, GSH-Px, CAT and the level of T-AOC; reducing the activity of MPO; and down-regulating the contents of MDA and LPO. In addition, the levels of TNF-É, IL-1ß, and IL-6 in BALF of mice treated with En-MPS at a dosage of 400 mg/kg/d were significantly lower than those in the ALI mice. The in vitro antioxidant effects also showed that the En-MPS was more effective than Ac-MPS. Furthermore, the physical properties of polysaccharides were also investigated by GC, HPGPC, FT-IR and NMR. These results indicated that both En-MPS and Ac-MPS possessed potent antioxidant and anti-inflammatory activities, which could be used as an ingestible drug in preventing lung injury.
Subject(s)
Agaricales/chemistry , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antioxidants/therapeutic use , Lung Injury/drug therapy , Mycelium/chemistry , Polysaccharides/therapeutic use , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/toxicity , Antioxidants/chemistry , Antioxidants/toxicity , Cellulase/chemistry , Glucuronidase/chemistry , Hydrolysis , Interleukin-1alpha/metabolism , Interleukin-6/metabolism , Lung/pathology , Lung Injury/pathology , Male , Mice , Multienzyme Complexes/chemistry , Polygalacturonase/chemistry , Polysaccharides/chemistry , Polysaccharides/toxicity , Protective Agents/chemistry , Protective Agents/therapeutic use , Protective Agents/toxicity , Tumor Necrosis Factor-alpha/metabolismABSTRACT
An optimised 1,8-cineole-loaded self-microemulsifying drug delivery system (CIN-SMEDDS) with a mean droplet size, polydispersity index, mean zeta potential and encapsulation efficiency of 38.14⯱â¯1.47â¯nm, 0.208⯱â¯0.036, -9.312⯱â¯1.764â¯mV and 95.35%⯱â¯1.13%, respectively, successfully ameliorated the lipopolysaccharide (LPS)-induced endothelial injury in mice. Acute toxicity assay in mice through the oral administration of CIN-SMEDDS showed that the median lethal dose of CIN-SMEDDS was 2998.9â¯mg/kg. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay indicated that the cytotoxicity of CIN-SMEDDS to Caco-2 cells may be ascribed to the surfactant/co-surfactant mixture. In particular, CIN-SMEDDS remarkably inhibited inflammatory cytokines IL-1ß, IL-6 and IL-8 with a simultaneous increase in IL-10 in LPS-treated mice. Haematoxylin-eosin staining results showed that CIN-SMEDDS attenuated LPS-induced vascular endothelial injury. Western blot results showed that the vascular protective effects of CIN-SMEDDS were associated with the NF-κB and peroxisome proliferator-activated receptor γ signalling pathways. These findings indicated that CIN-SMEDDS can attenuate LPS-induced endothelial injury and thus was proposed as a promising agent for the treatment of inflammatory cardiovascular disease.
Subject(s)
Aorta, Thoracic/drug effects , Eucalyptol/administration & dosage , Protective Agents/administration & dosage , Animals , Aorta, Thoracic/injuries , Caco-2 Cells , Cytokines/blood , Emulsions , Endothelium, Vascular/drug effects , Eucalyptol/toxicity , Female , Humans , Lethal Dose 50 , Lipopolysaccharides , Male , Mice , Protective Agents/toxicityABSTRACT
Chemical skin sensitizers produce allergic contact dermatitis, which is one of the most frequent occupational diseases associated with chemical exposures. Skin exposure is the major route of exposure when using plant protection products (PPPs). Therefore, skin sensitization is an important factor to be addressed during the regulatory risk assessment of PPPs. The main regulatory decision criterion considered when performing risk assessment for skin sensitizers is the dose applied. The equally important criteria "potency of the substance" is insufficiently considered by two potency categories as potency may vary up to five orders of magnitude. "Frequency of exposure" to the skin sensitizer is not considered at all. Consequently, an improved risk assessment methodology is essential to adequately assess health risks from skin sensitizers, especially for agricultural operators using PPPs. A quantitative risk assessment (QRA) approach for addressing PPPs sensitizing potential is proposed here. This QRA combines a methodology to derive a substance-specific threshold for skin sensitizers, a Derived No-Effect Level (DNEL), and an agricultural exposure model used for assessing chronic health risks of PPPs. The proposed QRA for skin sensitizing PPPs is a clear improvement over current risk assessment to ensure the safe use of skin sensitizers in an occupational context.
Subject(s)
Allergens/toxicity , Haptens/toxicity , Occupational Exposure/adverse effects , Protective Agents/toxicity , Agriculture , Dermatitis, Allergic Contact/prevention & control , Models, Theoretical , No-Observed-Adverse-Effect Level , Plant Diseases/prevention & control , Risk AssessmentABSTRACT
OBJECTIVES: To investigate the role of diethyldithiocarbamate (DEDTC) in cyclophosphamide (CP)-induced nephrotoxicity in Sprague-Dawley rat. DEDTC is a known chelating agent for copper and zinc. It is also used as a thiol protecting agent, as nuclear factor kappa-light-chain-enhancer of activated B-cells inhibitor and nitric oxide synthase inhibitor. It is also reported to inhibit superoxide dismutase (SOD) both in vitro and in vivo conditions. Considering this wide range of actions, current study investigated the role of DEDTC in CP-induced nephrotoxicity in experimental rat model. MATERIALS AND METHODS: Thirty-two male rats were randomized into four groups. Group 1, control received only saline ip; Group 2 and 4, received CP at the dose of 150 mg/kg body weight ip on the 4th day, while Group 3 and 4, received DEDTC at the dose of 250 mg/kg alternatively (fractionated dose of 1000 mg/kg). All the experimental animals were sacrificed on the 7th day and organs of interest were collected for biochemical, histopathological, DNA damage, and immunohistochemical assessments. RESULTS: DEDTC administration was found to further exacerbate the condition of CP-induced kidney damage as assessed by several biochemical and histological parameters. Further, the damage was also significantly reflected in the bladder in DEDTC-treated animals as compared to controls. SOD1 (Cu/Zn- dependent enzyme) expression was found to be decreased and this might be due to the action of DEDTC on SOD and other antioxidants. CONCLUSION: The present study indicates that DEDTC administration further exacerbated the CP-induced kidney damage in rat.