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1.
ACS Omega ; 9(13): 15573-15589, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38585086

ABSTRACT

Unconventional hydrocarbon exploration is needed in the current oil and gas crisis scenario. Therefore, the development of conditions for unconventional hydrocarbon exploration is needed. In the Upper Indus Basin (UIB), Pakistan, the Patala Formation is one of the potential candidates for this unconventional exploration. It is a proven source rock at the regional level in the Kohat-Potwar sub-basin of UIB. This study aims to evaluate the shale gas potential of the rock in the Minwal-Joyamair area of the sub-basin. Developing a shale rock physics model is important for exploring and developing shale reservoirs due to the difference between unconventional shale and conventional sand reservoirs. These differences include mineral types, mineral characteristics, matrix pores, and fluid properties. To achieve the study's objectives, an integrated strategy provides for evaluating rock physics parameters, petrophysics, and geochemical analyses. This integrated approach indicates that the Patala Formation is a good potential reservoir for shale gas exploration. The Formation has a significant thickness (around 40-50 m), higher total organic carbon content (02-10%), higher brittleness index (0.44-0.56), and relatively shallow depth (2136-3223 m). These research findings suggested that the presence of organic and quartz-rich lithofacies can be considered as highly favorable "sweet spots" for shale-gas exploration in the UIB, Pakistan. Through proper understanding of the spatial and temporal distribution of these "sweet spots", shale-gas exploration can be developed as an effective strategy to exploit shale gas.

2.
Saudi J Biol Sci ; 30(9): 103745, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37588571

ABSTRACT

Nanoparticles are beneficial in many aspects to human life but their excessive use can cause various abnormalities. They dispose in the environment through transport, industrial and agricultural usage and enter in living body through dermal, respiratory route or ingested with the lipsticks and there higher concentration produces toxicity. Therefore, current study characterized ZnO-NPs to evaluate toxic ability by X-rays diffraction (XRD) and Scanning Electron Microscopy (SEM) techniques and showed 29.83 and 35 nm size, respectively with hexagonal crystalline structure. LC50 value of ZnO-NPs was also evaluated as 72.48 ±â€¯10.33 mg/kg BW. Male Sprague Dawley (Post weaning) rats were divided into five groups with five rats in each group. Control (C) group received no treatment, placebo (S) group received normal saline (0.9% sodium chloride) intraperitoneally and three treated groups received different levels of ZnO- NPs intraperitoneally at the dose of either 10 or 20 or 30 mg/kg for 21 days on alternate days and named as 1G1, 1G2 and 1G3, respectively for the assessment of toxicity for better understanding of precautionary measures in future. Oxidative stress enzymes of liver and kidney, hepatorenal function enzymes and hematological parameters along with hepatic histology were measured at the end of the experiment. Results showed highly significant variations in all parameters in a dose dependent manner as compared to control group while groups receiving 10 or 20 mg/kg of ZnO-NPs showed low to moderate pathological changes in both organs. Liver histological analysis showed congestion, necrosis, hemorrhage, RBC's accumulations; inflammatory cells infiltration and severe abnormalities in high dose group while medium, low dose group showed moderate and least effects, respectively. It is concluded that ZnO-NPs are highly toxic at more concentration so their careful usage is needed in daily routine.

3.
Inflammopharmacology ; 30(2): 537-548, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35212850

ABSTRACT

Rheumatoid arthritis is primarily associated with inflammation and increased level of proinflammatory cytokines which are released by immune cells, macrophages or activation of arachidonic acid metabolism. The expression of these cytokines, oxidative free radicals and the activation of COX-2 enzymes are crucial targets for chronic inflammation. On the basis of established anti-inflammatory efficacy of nerolidol, the primary study was further appraised to determine its approach against Freund's complete adjuvant (CFA) rheumatoid model. Arthritis was induced by inoculation of 0.1 mL CFA injection into the left hind footpad of rats. Anti-arthritic potential of nerolidol (at 200, 400 and 800 mg/kg doses) was assessed by measuring the paw volume, body weight, serum analysis, histopathological and radiographs of ankle joints. Expressions of cytokine's panels such as IL-10, IL-4, COX-2, NF-kB, TNF-α, IL-6, PGE-2 and IL-1ß were determined by real-time qPCR. Antioxidant enzyme analyses were conducted by measuring the SOD, POD and catalase activity from serum and equated with arthritic control group. Nerolidol prevented body weight loss, stabilized biochemical and haematological homeostasis and significantly reduced the paw volume. Furthermore, X-ray and histopathological assessment of ankle joints showed an improvement in the joint structure of rats treated with nerolidol. Besides that, overexpression of gene pointers like TNF-α, IL-1ß, IL-6, NF-kB, PGE-2 and COX-2 in CFA-treated control rats were also reversed with nerolidol. This anti-arthritic mechanism was further supported by the increased level of IL-10, IL-4 and serum antioxidant activity. The present findings demonstrate that nerolidol reduced adjuvant arthritis by downregulating the proinflammatory cytokines and upregulating the aforementioned anti-inflammatory cytokines and may be used as a therapeutic substance for the management of human rheumatoid arthritis.


Subject(s)
Arthritis, Experimental , Arthritis, Rheumatoid , Cyclooxygenase 2 , Interleukin-6 , NF-kappa B , Sesquiterpenes , Tumor Necrosis Factor-alpha , Animals , Antioxidants/metabolism , Arthritis, Experimental/pathology , Arthritis, Rheumatoid/metabolism , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Cytokines/metabolism , Interleukin-6/antagonists & inhibitors , Interleukin-6/metabolism , NF-kappa B/antagonists & inhibitors , NF-kappa B/metabolism , Rats , Sesquiterpenes/pharmacology , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Tumor Necrosis Factor-alpha/metabolism
4.
Nat Prod Res ; 36(16): 4227-4230, 2022 Aug.
Article in English | MEDLINE | ID: mdl-34498973

ABSTRACT

The present study demonstrates the pharmacological tendency of Sideroxylon mascatense leaves extracts, fractions and sub-fractions using thin layer chromatography, column chromatography, and phytochemical (phenolics, flavonoids) and biological assays (free radical scavenging, antioxidative, antimicrobial, enzyme inhibition). The results disclosed that fractionation practice accumulated the active phytochemicals in few fractions and finally leads to the isolation of active compounds. The structural elucidation was carried out using spectroscopic 1D (1H, 13C) 2D NMR and spectrometric techniques. The n-hexane fraction led to isolation of lupeol. From the CHCl3 and EtOAc fractions, two compounds were isolated, hentriacontanol, and lupeol, respectively. The isolated compounds were also characterized for biological activities. This study concludes that bioactivity guided isolation can be performed for isolation of active constituents from S. mascatense which can be further explored for drug development.


Subject(s)
Anti-Infective Agents , Sapotaceae , Anti-Bacterial Agents/analysis , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/chemistry , Antioxidants/analysis , Antioxidants/pharmacology , Phytochemicals/analysis , Phytochemicals/pharmacology , Plant Extracts/chemistry , Plant Leaves/chemistry , Sapotaceae/chemistry
5.
Pharm Biol ; 59(1): 964-973, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34347568

ABSTRACT

CONTEXT: Melicope latifolia (DC.) T. G. Hartley (Rutaceae) was reported to contain various phytochemicals including coumarins, flavonoids, and acetophenones. OBJECTIVE: This study investigates the antidiabetic and antioxidant effects of M. latifolia bark extracts, fractions, and isolated constituents. MATERIALS AND METHODS: Melicope latifolia extracts (hexane, chloroform, and methanol), fractions, and isolated constituents with varying concentrations (0.078-10 mg/mL) were subjected to in vitro α-amylase and dipeptidyl peptidase-4 (DPP-4) inhibitory assay. Molecular docking was performed to study the binding mechanism of active compounds towards α-amylase and DPP-4 enzymes. The antioxidant activity of M. latifolia fractions and compounds were determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging and ß-carotene bleaching assays. RESULTS: Melicope latifolia chloroform extract showed the highest antidiabetic activity (α-amylase IC50: 1464.32 µg/mL; DPP-4 IC50: 221.58 µg/mL). Fractionation of chloroform extract yielded four major fractions (CF1-CF4) whereby CF3 showed the highest antidiabetic activity (α-amylase IC50: 397.68 µg/mL; DPP-4 IC50: 37.16 µg/mL) and resulted in ß-sitosterol (1), halfordin (2), methyl p-coumarate (3), and protocatechuic acid (4). Isolation of compounds 2-4 from the species and their DPP-4 inhibitory were reported for the first time. Compound 2 showed the highest α-amylase (IC50: 197.53 µM) and ß-carotene (88.48%) inhibition, and formed the highest number of molecular interactions with critical amino acid residues of α-amylase. The highest DPP-4 inhibition was exhibited by compound 3 (IC50: 911.44 µM). DISCUSSION AND CONCLUSIONS: The in vitro and in silico analyses indicated the potential of M. latifolia as an alternative source of α-amylase and DPP-4 inhibitors. Further pharmacological studies on the compounds are recommended.


Subject(s)
Dipeptidyl-Peptidase IV Inhibitors/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Rutaceae/chemistry , alpha-Amylases/antagonists & inhibitors , Antioxidants/chemistry , Antioxidants/pharmacology , Computer Simulation , Dipeptidyl Peptidase 4 , Humans , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , In Vitro Techniques , Molecular Docking Simulation , Molecular Structure , Phytochemicals/chemistry , Phytochemicals/pharmacology , Plant Bark/chemistry , Plant Extracts/isolation & purification , alpha-Amylases/chemistry
6.
J Enzyme Inhib Med Chem ; 36(1): 109-121, 2021 Dec.
Article in English | MEDLINE | ID: mdl-33249946

ABSTRACT

The inhibition of α-glucosidase and DPP enzymes capable of effectively reducing blood glucose level in the management of type 2 diabetes. The purpose of the present study is to evaluate the inhibitory potential of α-glucosidase and DPP (IV) activity including with the 2-NBDG uptake assay and insulin secretion activities through in vitro studies. The selected of active compounds obtained from the screening of compounds by LC-MS were docked with the targeted enzyme that involved in the mechanism of T2DM. From the results, root extracts displayed a better promising outcome in α-glucosidase (IC50 2.72 ± 0.32) as compared with the fruit extracts (IC50 3.87 ± 0.32). Besides, root extracts also displayed a better activity in the inhibition of DPP (IV), enhance insulin secretion and glucose uptake activity. Molecular docking results revealing that phlorizin binds strongly with α-glucosidase, DPP (IV) and Insulin receptor (IR) enzymes with achieving the lowest binding energy value. The present work suggests several of the compounds have the potential that contribute towards inhibiting α-glucosidase and DPP (IV) and thus effective in lowering post-prandial hyperglycaemia.


Subject(s)
Curculigo/chemistry , Diabetes Mellitus, Type 2/drug therapy , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Glycoside Hydrolase Inhibitors/pharmacology , Hypoglycemic Agents/pharmacology , Plant Extracts/pharmacology , Animals , Cell Survival/drug effects , Cells, Cultured , Diabetes Mellitus, Type 2/metabolism , Dipeptidyl Peptidase 4/metabolism , Dipeptidyl-Peptidase IV Inhibitors/chemistry , Dipeptidyl-Peptidase IV Inhibitors/isolation & purification , Dose-Response Relationship, Drug , Fruit/chemistry , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/isolation & purification , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/isolation & purification , Insulin Secretion , Mice , Molecular Docking Simulation , Molecular Structure , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Rats , Structure-Activity Relationship , alpha-Glucosidases/metabolism
7.
Molecules ; 26(1)2020 Dec 22.
Article in English | MEDLINE | ID: mdl-33374962

ABSTRACT

The present study investigated the antidiabetic properties of the extracts and fractions from leaves and stem bark of M. glabra based on dipeptidyl peptidase-4 (DPP-4) and α-Amylase inhibitory activity assays. The chloroform extract of the leaves was found to be most active towards inhibition of DPP-4 and α-Amylase with IC50 of 169.40 µg/mL and 303.64 µg/mL, respectively. Bioassay-guided fractionation of the leaves' chloroform extract revealed fraction 4 (CF4) as the most active fraction (DPP-4 IC50: 128.35 µg/mL; α-Amylase IC50: 170.19 µg/mL). LC-MS/MS investigation of CF4 led to the identification of trans-decursidinol (1), swermirin (2), methyl 3,4,5-trimethoxycinnamate (3), renifolin (4), 4',5,6,7-tetramethoxy-flavone (5), isorhamnetin (6), quercetagetin-3,4'-dimethyl ether (7), 5,3',4'-trihydroxy-6,7-dimethoxy-flavone (8), and 2-methoxy-5-acetoxy-fruranogermacr-1(10)-en-6-one (9) as the major components. The computational study suggested that (8) and (7) were the most potent DPP-4 and α-Amylase inhibitors based on their lower binding affinities and extensive interactions with critical amino acid residues of the respective enzymes. The binding affinity of (8) with DPP-4 (-8.1 kcal/mol) was comparable to that of sitagliptin (-8.6 kcal/mol) while the binding affinity of (7) with α-Amylase (-8.6 kcal/mol) was better than acarbose (-6.9 kcal/mol). These findings highlight the phytochemical profile and potential antidiabetic compounds from M. glabra that may work as an alternative treatment for diabetes.


Subject(s)
Dipeptidyl Peptidase 4/chemistry , Dipeptidyl-Peptidase IV Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/chemistry , Molecular Docking Simulation , Molecular Dynamics Simulation , Plant Extracts/chemistry , Rutaceae/chemistry , alpha-Amylases/chemistry , Chromatography, Liquid , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Glycoside Hydrolase Inhibitors/pharmacology , Phytochemicals/chemistry , Plant Extracts/pharmacology , Tandem Mass Spectrometry
8.
Naunyn Schmiedebergs Arch Pharmacol ; 393(12): 2453-2461, 2020 12.
Article in English | MEDLINE | ID: mdl-32725284

ABSTRACT

This study reports an effort to synthesize biocompatible zinc oxide nanoparticles using sol-gel method and its influence on hematological and serological profile of Catla catla fish. Hexagonal wurtzite structure and crystallite size of ZnO-NPs was identified by using XRD in the range of 19 to 20 nm. Moreover, the irregular and non-uniform surface of these NPs was found using SEM. The different stretched and vibrational mode (ZnO, OH, CO, and H-O-H) was identified by using FTIR analysis. UV-visible spectroscopy confirmed absorbance of the blue shift in the range 340 nm. Bioassay of ZnO-NPs on Catla catla was performed and nano ZnO was given through intraperitoneal injections at 0, 25, 50, 75, and 100 µg/g body weight doses. Analysis of fish blood samples indicated an increase in WBCs and leukocytes while the differential effect on monocytes. On the other hand in response to varying ZnO concentrations, an increase in RBCs, hemoglobin, and HCT was evident. Serum analysis revealed an increase in urea concentration while a reduction in creatinine, ALT, and AST. In an overall assessment, nano-ZnO supplementation at 25 to 100 µg/g body weight differentially affected hematological and serum biochemical profile of thaila fish. Graphical abstract.


Subject(s)
Metal Nanoparticles/administration & dosage , Zinc Oxide/administration & dosage , Zinc Oxide/blood , Animals , Blood Cell Count/methods , Dose-Response Relationship, Drug , Fishes , Injections, Intraperitoneal , Metal Nanoparticles/chemistry , Zinc Oxide/chemical synthesis
9.
Naunyn Schmiedebergs Arch Pharmacol ; 393(6): 1089-1101, 2020 06.
Article in English | MEDLINE | ID: mdl-31940053

ABSTRACT

The aim of this study is to report the synthesis, characterization, and biocompatibility of lanthanum titanate nanoparticles (LT NPs) in albino mice. Microemulsion method was used to generate LT NPs. Seven-week-old albino mice of both sexes orally received 50 mg/ml saline/kg body weight of nanoparticles for 15 days (group 1) and 29 days (group 2). Control groups were maintained in parallel. Selected behavioral (rotarod, light and dark box, open-field and Morris water maze) tests were conducted, blood biochemical analysis was done, and antioxidants were determined in vital organs of all treatments. Male mice treated with LT NPs for 15 days spent significantly more time in light and less time in dark during light dark box test. While they had made significantly more platform entries and platform maximum visits during acquisition phase of Morris water maze test, they remained unaffected in probe trail performance when compared with control. These male mice had significantly reduced white blood cells, lymphocyte, and monocyte count and significantly increased triglyceride levels in serum than the control group. They had higher level of superoxide dismutase (SOD) in heart and reduced level of malonaldehyde (MDA) in kidney while 15-day LT NP-treated females had significantly higher level of SOD in liver and kidney. Male mice treated with NPs for 29 days had increased anticlockwise rotations during open field, reduced level of triglycerides in serum, and significantly higher level of SOD in kidney and MDA in lungs. In contrast, female mice treated with NPs for 29 days had higher SOD level in liver, kidney, and heart than their control group. Oral supplementation of LT NPs for variable duration improved the exploratory behavior in male but disturbed blood chemistry and antioxidants from vital organs under both experimental conditions.


Subject(s)
Lanthanum/pharmacology , Nanoparticles , Titanium/pharmacology , Animals , Exploratory Behavior/drug effects , Female , Kidney/metabolism , Lanthanum/chemistry , Leukocyte Count , Liver/metabolism , Male , Mice , Mice, Inbred C57BL , Morris Water Maze Test/drug effects , Motor Activity/drug effects , Nanoparticles/chemistry , Sex Characteristics , Superoxide Dismutase/metabolism , Titanium/chemistry
10.
Bioorg Med Chem Lett ; 30(1): 126722, 2020 01 01.
Article in English | MEDLINE | ID: mdl-31732410

ABSTRACT

The inhibition of tyrosinase is an established strategy for treating hyperpigmentation. Our previous findings demonstrated that cinnamic acid and benzoic acid scaffolds can be effective tyrosinase inhibitors with low toxicity. The hydroxyl substituted benzoic and cinnamic acid moieties of these precursors were incorporated into new chemotypes that displayed in vitro inhibitory effect against mushroom tyrosinase. The most active compound, (2-(3-methoxyphenoxy)-2-oxoethyl (E)-3-(4-hydroxyphenyl) acrylate) 6c, inhibited tyrosinase with an IC50 of 5.7 µM, while (2-(3-methoxyphenoxy)-2-oxoethyl 2, 4-dihydroxybenzoate) 4d had an IC50 of 23.8 µM. In comparison, the positive control, kojic acid showed tyrosinase inhibition with an IC50 = 16.7 µM. Analysis of enzyme kinetics revealed that 6c and 4d displayed noncompetitive reversible inhibition of the second tyrosinase enzymatic reaction with Ki values of 11 µM and 130 µM respectively. In silico docking studies with mushroom tyrosinase (PDB ID 2Y9X) predicted possible binding modes in the catalytic site for these active compounds. The phenolic para-hydroxy group of the most active compound 6c is predicted to interact with the catalytic site Cu++ ion. The methoxy part of this compound is predicted to form a hydrogen bond with Arg 268. Compound 6c had no observable toxic effects on cell morphology or cell viability at the highest tested concentration of 91.4 µM. When dosed at 91.4 µM onto B16F10 melanoma cells in vitro6c showed anti-melanogenic effects equivalent to kojic acid at 880 µM. 6c displayed no PAINS (pan-assay interference compounds) alerts. Our results show that compound 6c is a more potent tyrosinase inhibitor than kojic acid and is a candidate for further development. Our exposition of the details of the interactions between 6c and the catalytic pocket of tyrosinase provides a basis for rational design of additional potent inhibitors of tyrosinase, built on the cinnamic acid scaffold.


Subject(s)
Benzoic Acid/therapeutic use , Cinnamates/therapeutic use , Melanoma/drug therapy , Molecular Docking Simulation/methods , Benzoic Acid/pharmacology , Cinnamates/pharmacology , Humans , Structure-Activity Relationship
11.
Pak J Pharm Sci ; 32(5(Supplementary)): 2269-2277, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31894054

ABSTRACT

Medicinal plants of Pakistan are known for their curative properties against snake bite as rural people have been using natural herbs for such injuries for hundreds to thousands of years. People of rural areas of Pakistan are prone to snakebite, and on the whole death due to snakebite has been increasing worldwide. The objective of this study was to test the neutralizing potential of 17 Pakistani medicinal plant extracts against phospholipase A2 activity in Echis carinatus venom. Plant material was extracted by simple maceration and fractionation of active plant extracts. Venom was collected by manual massage of the venom glands. The PLA2 enzymatic assay was performed to map out the venomous activity of Echis carinatus envenomation. Snake venom released fatty acids at different concentrations (0.1-5 mg/ml) of venom in a dose-dependent manner. Reduction of pH by 01 correlated with 133 µmol of fatty acids released at 5mg/ml of venom. All plants extract inhibited PLA2 activity, however, Curcuma longa, Citrullus colocynthis and Rubia cordifolia inhibited maximum of PLA2 activity (⁓78%) comparable to the standard antidote (p>0.5). Medicinal plants possess secondary metabolites and many active compounds that may have neutralizing or inhibiting properties against the PLA2 activity of Echis venom. Further studies such as compound analysis could provide an alternative against snakebites injuries resulting from Echis carinatus venom.


Subject(s)
Phospholipases A2/toxicity , Plant Extracts/pharmacology , Plants, Medicinal , Viper Venoms/toxicity , Blood Proteins/pharmacology , Pakistan , Plants, Medicinal/chemistry , Snake Bites/drug therapy
12.
Eur J Med Chem ; 134: 348-356, 2017 Jul 07.
Article in English | MEDLINE | ID: mdl-28431340

ABSTRACT

Non-small cell lung cancers (NSCLC) harboring anaplastic lymphoma kinase (ALK) gene rearrangements invariably develop resistance to 2nd-generation ALK inhibitors. Lorlatinib (PF-06463922) (6) is a 3rd-generation macrocyclic ALK-TKI that demonstrates many advantages over 2nd-generation ALK inhibitors. Lorlatinib has demonstrated decent kinase selectivity, promising pharmacokinetic profile, selective brain-penetration and strong antiproliferative activity in several ALK/ROS1-driven tumor models. The current review describes the activity spectrum, key events from discovery to clinical applications and the evidences that lorlatinib acts as an ALK/ROS1 inhibitor in clinical settings.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lactams, Macrocyclic/therapeutic use , Lung Neoplasms/drug therapy , Lung/drug effects , Protein-Tyrosine Kinases/antagonists & inhibitors , Proto-Oncogene Proteins/antagonists & inhibitors , Receptor Protein-Tyrosine Kinases/antagonists & inhibitors , Aminopyridines , Anaplastic Lymphoma Kinase , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Clinical Trials, Phase I as Topic , Clinical Trials, Phase II as Topic , Drug Evaluation, Preclinical , Humans , Lactams , Lactams, Macrocyclic/chemistry , Lactams, Macrocyclic/pharmacology , Lung/metabolism , Lung/pathology , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Protein-Tyrosine Kinases/genetics , Protein-Tyrosine Kinases/metabolism , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/metabolism , Pyrazoles , Receptor Protein-Tyrosine Kinases/genetics , Receptor Protein-Tyrosine Kinases/metabolism
13.
Reprod Toxicol ; 64: 86-97, 2016 09.
Article in English | MEDLINE | ID: mdl-27105832

ABSTRACT

Pregnant women often use herbal medicines to alleviate symptoms of pregnancy. The active phytochemicals eugenol (from holy basil) and α-bisabolol (from chamomile) are recommended to promote calmness and reduce stress. There is evidence that both eugenol and α-bisabolol possess pro-apoptotic and anti-proliferative effects and induce reactive oxygen species. The potential effect was examined by monitoring cardiomyocyte contractile activity (differentiation), cell activity, protein content and ROS production for mouse D3 embryonic stem cell and chick embryonic micromass culture. The results showed that eugenol (0.01-80µM) demonstrated effects on cell activity (both systems) and ROS production (stem cell system only), as well as decreasing the contractile activity and protein content at high concentrations in both systems. Additionally, α-bisabolol (0.01-80µM) at high concentrations decreased the contractile activity and cell activity and in the stem cell system induced ROS production and decreased protein content. The results suggest only low concentrations should be ingested in pregnancy. .


Subject(s)
Cell Differentiation/drug effects , Eugenol/toxicity , Mouse Embryonic Stem Cells/drug effects , Myocytes, Cardiac/drug effects , Plant Preparations/toxicity , Sesquiterpenes/toxicity , Animals , Cell Culture Techniques , Cell Line , Chick Embryo , Dose-Response Relationship, Drug , Mice , Monocyclic Sesquiterpenes , Mouse Embryonic Stem Cells/metabolism , Mouse Embryonic Stem Cells/pathology , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Reactive Oxygen Species/metabolism
14.
Reprod Toxicol ; 59: 117-27, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26708230

ABSTRACT

Herbal remedies are often used during the early stages of pregnancy, being considered 'harmless' and 'natural'. There are insufficient data regarding their potential embryotoxicity. The main components of selected herbs, including 6-gingerol from ginger, Ginkgolide A and Ginkgolide B from gingko biloba and Ginsenoside Rg1 from ginseng, have been investigated using chick embryonic heart micromass and Mouse D3 embryonic stem cells. The potential effects were evaluated via alteration in contractility, cell viability, and cell protein content. The myocytes in both systems were also demonstrated by immunocytochemistry using a specific cardiomyocyte marker (α-actinin). For 6-gingerol, Ginkgolide A, Ginkgolide B and Ginsenoside Rg1 in both methods, at moderate to high concentrations, there were alterations in the values for the endpoints. These data indicate that herbal remedies used in the first trimester of pregnancy might not be safe for fetal development.


Subject(s)
Embryonic Stem Cells/drug effects , Heart/drug effects , Myocytes, Cardiac/drug effects , Plant Preparations/toxicity , Actinin/metabolism , Animals , Biomarkers/metabolism , Cell Survival/drug effects , Cells, Cultured , Chick Embryo , Dose-Response Relationship, Drug , Embryonic Stem Cells/metabolism , Embryonic Stem Cells/pathology , Heart/embryology , Heart/physiopathology , Mice , Myocardial Contraction/drug effects , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Plant Preparations/analysis , Risk Assessment
15.
J Ethnopharmacol ; 174: 540-60, 2015 Nov 04.
Article in English | MEDLINE | ID: mdl-26297840

ABSTRACT

ETHNO-PHARMACOLOGICAL RELEVANCE: Cyperus rotundus L. (Cyperaceae) is a medicinal herb traditionally used to treat various clinical conditions at home such as diarrhea, diabetes, pyresis, inflammation, malaria, and stomach and bowel disorders. Currently, it is one of the most widespread, problematic, and economically damaging agronomic weeds, growing wildly in various tropical and subtropical regions of the world. The present paper summarizes the available information that will aid in future medicine preparation by identifying active ingredients and their mode of action for a specific therapeutic activity using the latest technologies. MATERIAL AND METHOD: This review article is based on the information available on the phytochemical, toxicological, and pharmacological studies on and traditional uses of C. rotundus. The present paper covers the literature available particularly from 2000 to 2015 online (Google Scholar, PubMed, ScienceDirect, Scopus, SpringerLink, and Web of Science) and in books on phytochemistry, ethnopharmacology, and botany of this plant. RESULTS: Phytochemical and pharmacological studies revealed the significance of C. rotundus as an antiandrogenic, antibacterial, anticancerous, anticonvulsant, antidiabetic, antidiarrheal, antigenotoxic, anti-inflammatory, antilipidemic, antimalarial, antimutagenic, antiobesity, antioxidant, anti-uropathogenic, hepatoprotective, cardioprotective, neuroprotective, and nootropic agent. This is the most investigated plant worldwide due to the higher concentration of active ingredients in the form of essential oils, phenolic acids, ascorbic acids, and flavonoids in the tuber and rhizomes. Unfortunately, this significant plant species has not been assessed under improved cultivation conditions with the aim of conservation in natural habitats and high quality. CONCLUSION: Reports can be found on the ehtnobotanical use of C. rotundus in atherosclerosis, aging, apoptosis, cancer, cystitis, epilepsy, hirsutism, nociception, prostatitis, and genotoxicity disorders. The phytochemical and pharmacological activities of C. rotundus have supported its traditional as well as prospective uses as a valuable Ayurvedic plant. Previous researches focuses on the phytochemistry, biological properties and clinical application of rhizomes and tubers of C. rotundus. However, such studies on the other parts of this medicinally important plant are still quest to be investigate. Furthermore, future study should aim at confirming the clinical activities and safety of this plant before being used for the development of new therapeutic agent in human subjects.


Subject(s)
Cyperus/chemistry , Medicine, Traditional , Phytotherapy , Animals , Cyperus/toxicity , Ethnopharmacology , Humans , Plant Extracts/pharmacology , Plant Extracts/therapeutic use
16.
Water Res ; 81: 288-93, 2015 Sep 15.
Article in English | MEDLINE | ID: mdl-26081435

ABSTRACT

This paper assesses anaerobic digestion of waste activated sludge (WAS) at low pH to enhance phosphorous solubility. Batch biochemical methane potential tests were conducted at a pH range of 5 to 7.2 in two separate sets (two different WAS samples collected from municipal WWTP). Low pH (<5.7) caused a significant (p = 0.004) decrease in methane potential (B0) up to 33% and 3.6 times increase in phosphorus release compared to neutral pH (7-7.7), but with no major change in methane production rate coefficient (khyd). The loss in methane yield was mainly due to decrease in hydrolytic capability rather than inhibition of methanogenesis with volatile fatty acids being <300 mgCOD L(-1) and soluble COD <1300 mgCOD L(-1) even at low pH. While pH did not influence the acetoclastic community (Methanosaeta dominated), it was the primary driver for the remaining community (p = 0.004), and caused a loss of diversity and shift to Clostridia.


Subject(s)
Bacteria, Anaerobic/growth & development , Methane/metabolism , Phosphorus/chemistry , Sewage/microbiology , Waste Disposal, Fluid/methods , Anaerobiosis , Biodegradation, Environmental , Bioreactors , Fatty Acids, Volatile/metabolism , Hydrogen-Ion Concentration
17.
Article in English | MEDLINE | ID: mdl-23662127

ABSTRACT

Lactuca serriola L. has traditionally been used in folkloric medicine to manage respiratory, gastrointestinal, and multiple other ailments. The present study was undertaken to explore the effect of methanol extract of L. serriola on isolated rabbit tissue preparations, that is, jejunum, trachea, and aorta in an attempt to validate its folkloric use in traditional medicine for gastrointestinal, respiratory, and vascular ailments. The application of the methanol extract to isolated rabbit jejunum preparations exhibited concentration-dependent spasmogenic effect (0.03 to 3.0 mg/mL), but interestingly further increase in concentration (5.0 mg/mL) resulted in complete spasmolytic effect. The pretreatment of the tissue preparations with atropine (0.1 µ M) caused the suppression of the contractile response. Moreover, the same extract also caused relaxation of K(+)-(80 mM) induced spastic contractions of isolated rabbit jejunum preparations (5.0 mg/mL) and shifted the Ca(++) dose response curves towards right at concentration range of 0.3-1.0 mg/mL. Similarly, the extract application to isolated rabbit tracheal preparations relaxed the carbachol-(1 µ M) induced (0.3-1.0 mg/mL) as well as K(+)-(80 mM) induced contractions (3.0 mg/mL). Furthermore, it relaxed the phenylephrine (1 µ M)-induced contractions in isolated rabbit aorta preparations (3.0 mg/mL) and K(+) (80 mM)-induced contractions (1.0 mg/mL). These effects were found comparable to that of dicyclomine, as an antagonist of muscarinic receptors as well as a possible Ca(++) channel blocker. The previously mentioned findings may partially justify the folkloric use of Lactuca serriola in the management of conditions pertaining to spasm of intestine, bronchioles, and vasculature.

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