Publications by authors named "Najeeb Ur Rehman"

96 Publications

A competitive nature-derived multilayered scaffold based on chitosan and alginate, for full-thickness wound healing.

Carbohydr Polym 2021 Jun 8;262:117921. Epub 2021 Mar 8.

Laboratory for Stem Cell & Regenerative Medicine, Natural and Medical Sciences Research Center, University of Nizwa, Nizwa, P. O. Box: 33, PC 616, Oman. Electronic address:

The aim of this study was to evaluate a bioactive multilayer wound dressing, based on chitosan and alginate. To enhance healing potential, Dracaena Cinnabari and Aloe Vera were loaded as separate layers into the scaffold. The bare and bioactive multilayered scaffolds were fabricated by an iterative layering freeze-drying technique. Following of topographical, chemical, and physical assessment, the performance of the scaffolds was evaluated in vitro and in vivo. The results revealed adequate attachment, and proliferation of human foreskin fibroblasts, indicating excellent biocompatibility of the bioactive scaffold. In vivo, the performance of the multi-layered scaffold loaded with the bioactive materials was comparable with Comfeel plus®. The wounds treated with the bioactive scaffold exhibited superior hypergranulation, fibroblast maturation, epithelization, and collagen deposition, with minimal inflammation, and crust formation. It is concluded that the synergism of extracellular matrix-mimicking multi-layered scaffolding with Aloe Vera and Dracaena Cinnabari could be considered as a supportive wound dressing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.carbpol.2021.117921DOI Listing
June 2021

Role of Oxidative Stress and Inflammatory Cytokines (TNF-α and IL-6) in Acetic Acid-Induced Ulcerative Colitis in Rats: Ameliorated by .

Life (Basel) 2021 Mar 3;11(3). Epub 2021 Mar 3.

Department of Basic Sciences, Preparatory Year Deanship, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that causes irritation, inflammation, and ulceration in the linings of the colon and rectum. is traditionally used to treat various disorders in different parts of the Middle East and sub-Saharan Africa. In the present study, we evaluated the ameliorative effects of crude leaves extract of (OF.Cr) on acetic acid (AA)-induced UC model in Wistar albino rats. Wistar rats were administered orally with either vehicle (10 mL/kg), OF.Cr (200 and 400 mg/kg), or prednisolone (2 mg/kg) once a day for 6 days. On day 6, UC was induced in rats by intrarectal administration of a single dose of 5% AA (1.0 mL). Disease activity index (DAI) was recorded after one day of colitis induction by assessing the symptoms of colitis and then the rats were euthanized by cervical dislocation, and colon tissues were isolated for the histopathological examination and biochemical analysis of oxidative stress parameters and cytokines (Interleukin-6 and Tumor Necrosis Factor-α). OF.Cr pretreatment exhibits significant prevention against UC, as confirmed by a significant decrease of DAI, colonic ulceration, and reduced inflammatory score as compared to the AA-induced colitis rats. Depletion of total glutathione (GSH) levels and catalase (CAT) activities in the colitis group was significantly restored in the OF.Cr treated groups, while increased lipid peroxidation in the colon tissues was significantly reduced. OF.Cr prevented the activation of the IL-6 and TNF-α pathways in the colonic tissues, which were clearly observed by the decreased levels of IL-6 and TNF-α in the OF.Cr treated animals. Hence, OF.Cr could be developed in the future for the treatment of UC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/life11030195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001148PMC
March 2021

Protective Effect of Essential Oil on Cadmium-Induced Nephrotoxicity in Rats, through Suppression of Oxidative Stress and Downregulation of NF-κB, iNOS, and Smad2 mRNA Expression.

Molecules 2021 Feb 26;26(5). Epub 2021 Feb 26.

Department of Basic Sciences, Preparatory Year Deanship, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.

The purpose of the research was to examine the protective effect of essential oil from Hochst. ex Benth. (TSA oil) against cadmium (Cd)-induced renal toxicity. The experimental protocol was designed using 30 healthy adult Wistar albino rats allocated into five groups containing six animals in each group. Group 1 was treated as normal control and groups 2, 3, 4, and 5 were treated with cadmium chloride (CdCl, 3 mg/kg, IP) for 7 days. Group 3 was also treated with silymarin (100 mg/kg, PO) as a standard group, while groups 4 and 5 were administered with TSA oil at doses of 100 and 200 mg/kg PO, respectively. The nephrotoxicity was measured with various parameters such as kidney function markers, oxidative stress markers (glutathione (GSH) and malondialdehyde (MDA)), and messenger ribonucleic acid (mRNA) expression levels of inflammatory factors. The histological studies were also evaluated in the experimental protocol. The CdCl-treated groups showed a significant increase in the levels of serum kidney function markers along with MDA levels in kidney homogenate. However, renal GSH level was found to be reduced significantly. It was found that CdCl significantly upregulated the nuclear factor levels of kappaB (NF-κB p65), inducible nitric oxide synthase (iNOS), and small mothers against decapentaplegic (Smad2) as compared to the normal control group. On the other hand, TSA oil significantly improved the increased levels of serum kidney function markers, non-enzymatic antioxidants, and lipid peroxidation. In addition, TSA oil significantly downregulated the increased expression of NF-κB p65, iNOS, and Smad2 in Cd-intoxicated rats. Moreover, the histological changes in the tissue samples of the kidney of Cd-treated groups were significantly ameliorated in the silymarin- and TSA-oil-treated groups. The present study reveals that TSA oil ameliorates Cd-induced renal injury, and it is also proposed that the observed nephroprotective effect could be due to the antioxidant potential of TSA oil and healing due to its anti-inflammatory action.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules26051252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956168PMC
February 2021

Evaluation of in vitro α-amylase inhibitory activity and antidiabetic effect of Myrica salicifolia in streptozotocin-induced diabetic mice.

Pak J Pharm Sci 2020 Jul;33(4(Supplementary)):1917-1926

Department of Pharmacology & Toxicology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Kingdom of Saudi Arabia.

The study was aimed to evaluate in vitro antioxidant, α-amylase inhibitory and in vivo antidiabetic activities of Myrica salicifolia root extracts. The powdered roots of M. salicifolia were extracted with 80% methanol and then dried. The dried extract was further fractionated into chloroform, ethyl acetate, butanol and aqueous fractions. The phytochemical screening of the crude extract was performed using standard chemical identification tests. The antioxidant activity of the extracts was determined by in vitro method using 2,2-diphenyl-1-picrylhydrazyl (DPPH) as radical scavenging reagent. The in vitro α-amylase inhibitory activity was performed using the chromogenic3,5-dinitrosalicylic (DNSA) method. The antidiabetic activity of M. salicifolia root crude extract (200, 400 and 600 mg/kg) and fractions (400 mg/kg) were evaluated in normal, glucose loaded hyperglycemic and streptozotocin (STZ)-induced diabetic mice. The crude root extract of M. salicifolia showed strong DPPH radical scavenging activity (IC50 = 4.54µg/ml) which was comparable with the standard antioxidant, ascorbic acid. In α-amylase inhibitory activity, the crude extract and butanol fraction showed highest enzyme inhibition. In the antidiabetic activity, daily administration of the crude extract, aqueous and butanol fractions for fifteen days showed highest significant reduction in fasting blood glucose level (BGL) compared to diabetic control in STZ-induced diabetic mice model. The root extract and fractions of M. salicifolia exhibited significant antihyperglycemic, α-amylase inhibitory and antioxidant activity with no sign of toxicity. The antidiabetic effect of the plant could be due to the synergistic effect of various classes of constituents present in the root part of the plant.
View Article and Find Full Text PDF

Download full-text PDF

Source
July 2020

Biosynthetic diversity in triterpene cyclization within the Boswellia genus.

Phytochemistry 2021 Apr 29;184:112660. Epub 2021 Jan 29.

Department of Organic Chemistry, Martin-Luther University Halle-Wittenberg, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany.

This review is not intended to describe the triterpenes isolated from the Boswellia genus, since this information has been covered elsewhere. Instead, the aim is to provide insights into the biosynthesis of triterpenes in Boswellia. This genus, which has 24 species, displays fascinating structural diversity and produces a number of medicinally important triterpenes, particularly boswellic acids. Over 300 volatile components have been reported in the essential oil of Boswellia, and more than 100 diterpenes and triterpenes have been isolated from this genus. Given that no triterpene biosynthetic enzymes have yet been isolated from any members of the Boswellia genus, this review will cover the likely biosynthetic pathways as inferred from structures in nature and the probable types of biosynthetic enzymes based on knowledge of triterpene biosynthesis in other plant species. It highlights the importance of frankincense and the factors and threats affecting its production. It covers triterpene biosynthesis in the genus Boswellia, including dammaranes, tirucallic acids, lupanes, oleananes, ursanes and boswellic acids. Strategies for elucidating triterpene biosynthetic pathways in Boswellia are considered. Furthermore, the possible mechanisms behind wound-induced resin synthesis by the tree and related gene expression profiling are covered. In addition, the influence of the environment and the genotype on the biosynthesis of resin and on variations in the compositions and types of resins will also be reviewed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phytochem.2021.112660DOI Listing
April 2021

Eluxadoline Loaded Solid Lipid Nanoparticles for Improved Colon Targeting in Rat Model of Ulcerative Colitis.

Pharmaceuticals (Basel) 2020 Sep 19;13(9). Epub 2020 Sep 19.

Department of Pharmaceutical Sciences, Faculty of Pharmacy, Jadara University, Irbid 21110, Jordan.

The aim of the current study was to evaluate the therapeutics potential of eluxadoline (ELX) loaded solid lipid nanoparticles (SLNs) in ulcerative colitis. ELX loaded SLNs were prepared using three different lipids according to the solvent emulsification technique. The optimization of prepared SLNs (F1-F3) were carried out based on size, PDI, zeta potential, percent drug entrapment (%EE), and loading (%DL). The lipid (stearic acid) based SLNs (F2) was optimized with particle size (266.0 ± 6.4 nm), PDI (0.217 ± 0.04), zeta potential (31.2 ± 5.19 mV), EE (65.0 ± 4.8%), and DL (4.60 ± 0.8%). The optimized SLNs (F2) was further evaluated by DSC, FTIR, SEM, in vitro release, and stability studies, which confirmed the successful encapsulation of ELX in SLNs. The efficacy of optimized SLNs (F2) in comparison to the pure ELX drug was assessed in acetic acid induced colitis rat models. It was observed that the delivery of ELX by SLNs alleviated the induced acetic acid colitis significantly. Thus, ELX loaded SLNs delivery to the colon has a significant potential to be developed for the treatment of ulcerative colitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ph13090255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559404PMC
September 2020

Analgesic, Anti-inflammatory and Hyaluronidase Inhibitory Properties of the Leaf Extract and Solvent Fractions of (Forssk.) Schweinf. ex Penzig.

Iran J Pharm Res 2020 ;19(1):218-230

Department of Pharmacy, College of Health Sciences, Aksum University, P.O Box 298, Aksum, Ethiopia.

is traditionally used to treat tonsillitis, stomach ache, asthma, arthritis, and febrile illness in different parts of Ethiopia and other countries. In this experiment 70% ethanolic crude extract and fractions of the leaf of (Forssk.) Schweinf. ex Penzig were evaluated for their anti-inflammatory and analgesic activities and hyaluronidase inhibition properties at different concentrations. Tail immersion, acetic acid induced writhing and carrageenan-induced paw edema model were used to assess the analgesic and anti-inflammatory activities, respectively. Swiss albino mice of either sex were randomly divided into five groups of six mice per group and for evaluation of the fractions randomly divided into six groups of six mice per group. The test groups were treated with hydroalcoholic extract of at doses of 100, 200, and 400 mg/kg. The positive control groups received either pethidine 5 mg/kg or aspirin at 100 mg/kg or 150 mg/kg. The negative control groups were orally given sunflower oil. All the fractions were administered at the dose of 400 mg/kg. In all models, the higher dose (400 mg/kg) of the crude extract and chloroform fraction showed a significant central and peripheral analgesic and anti-inflammatory activities with comparable effects to standards used. The hyaluronidase inhibition assay result showed that the test samples displayed concentration-dependent inhibitory activities. These findings indicate that 70% ethanol extract and organic solvent fractions of leaves have potential analgesic, anti-inflammatory, and enzyme inhibitory activities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.22037/ijpr.2019.14657.12569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462514PMC
January 2020

Multiple Mechanisms of Flaxseed: Effectiveness in Inflammatory Bowel Disease.

Evid Based Complement Alternat Med 2020 12;2020:7974835. Epub 2020 Jul 12.

Department of Pharmacology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.

Materials And Methods: Aqueous-methanolic crude extracts of Flaxseed (Fs.Cr) and Flaxseed oil were tested against 6% acetic acid- (AA-) induced colitis in BALB/c mice. Microscopic damage parameters of the hematoxylin and eosin-stained and periodic acid-Schiff-alcian blue-stained sections of the colon were scored to be assessed. Possible antispasmodic mechanism was studied on isolated rabbit jejunum, while antibacterial activity was assessed for microbes implicated in IBD.

Results: In AA-induced colitis, Flaxseed oil was found to be more effective in reducing mortality and colonic ulcers than Fs.Cr at 500 mg/kg dose. Fs.Cr was more efficacious in increasing mucin content as compared to oil, exhibiting slightly greater anti-inflammatory effect (50% vs 35%) and reducing depth of lesion (55% vs 42.31%, respectively). Antispasmodic activity of Fs.Cr (0.03 and 0.1 mg/ml) was mediated by phosphodiesterase inhibitors (PDEI, possibly PDE-4 subtype) with a resultant increase in cAMP levels. Flaxseed oil PDEI activity was mild (1 and 3 mg/ml). Fs.Cr (0.1 and 0.3 mg/ml) was potent in exhibiting anticholinergic activity, similar to dicyclomine, whereas Flaxseed oil showed anticholinergic effect at 1 and 3 mg/ml. Flaxseed oil (9 and 14 g/ml) was bactericidal against enteropathogenic (EPEC), enterotoxigenic (ETEC), and enteroaggregative (EAEC), whereas Fs.Cr exhibited bactericidal effect against EPEC at 100 g/ml.

Conclusions: Results of this study, taken together with previous studies, suggest that Flaxseed possesses anti-inflammatory, antibacterial, and antispasmodic action through multiple pathways and thus offers promising potential to be developed for IBD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/7974835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7374215PMC
July 2020

Multiple Pathway-Mediated Gut-Modulatory Effects of (Gilg) DeWolf.

J Exp Pharmacol 2020 14;12:203-211. Epub 2020 Jul 14.

Department of Pharmacognosy, College of Health Sciences, Mekelle University, Mekelle, Ethiopia.

Background: Gastrointestinal disorders are often poorly managed, especially in developing countries, where there are limited resources and therapeutic options. Despite the rich diversity of medicinal plants that offer effective treatment options with fewer side effects, studies that provide scientific verification are lacking. (Gilg) DeWolf is among the plants claimed to have wide traditional medicine, use, including as a remedy against gastrointestinal problems. Therefore, this work aimed to evaluate the gut-modulatory effects of a crude leaf extract of (MSL.Cr), as well as its possible mechanism of action.

Methods: A castor oil (10 mL/kg)-induced diarrheal mouse model was used to evaluate the antidiarrheal effect of MSL.Cr, and the spasmodic/antispasmodic effect of the extract was assessed using isolated rabbit jejunum with and without addition of standard cholinergic agonists/antagonists to predict the possible mechanism of action.

Results: MSL.Cr exhibited 40% and 80% protection against castor oil-induced diarrhea in mice at doses of 500 and 1,000 mg/kg, respectively. In isolated rabbit jejunum, the extract increased spontaneous contractions at low doses (0.01-0.1 mg/mL), and was sensitive to atropine, whereas it showed complete inhibition at higher doses (0.3-1 mg/mL). It was shown that the relaxant effect was possibly mediated by the involvement of phosphodiesterase-enzyme inhibition and K-channel activation. The extract potentiated the control concentration-response curve of carbachol, shifting it to the left, similarly to the control drug papaverine. The potassium-channel opening-like activity of MSL.Cr was possibly mediated by the involvement of aspecific K-channels inhibition, since tetraethylammonium, anunselective antagonist of K channels, significantly reversed its inhibitory effect.

Conclusion: This study showed that the leaf extract demonstrated gut-modulatory effects, possibly mediated by a combination of muscarinic-receptor stimulation, phosphodiesterase inhibition, and aspecific K-channel activation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/JEP.S254818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368589PMC
July 2020

Heterogeneous Pd/C-catalyzed, ligand free Suzuki-Miyaura coupling reaction furnishes new -terphenyl derivatives.

Nat Prod Res 2020 Jul 13:1-5. Epub 2020 Jul 13.

Natural and Medical Sciences Research Center, University of Nizwa, Nizwa, Oman.

A series of new -terphenyls derivatives have been efficiently synthesized by a ligand-free heterogeneous Pd/C-catalyzed two-fold Suzuki-Miyaura coupling reaction. Methyl 5-bromo-2-iodobenzoate was selected to react with a variety of different aryl boronic acids (). Nine new -terphenyl derivatives (-) were prepared and the structures were confirmed by several analytical techniques including infrared, spectroscopy, H and C NMR spectroscopy, mass spectrometry, and in the case of compound by X-ray diffraction method. The new derivatives were obtained in very good yields (78-91%). This synthetic facile route is envisioned to improve the preparation of -terphenyl-based natural products.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14786419.2020.1791112DOI Listing
July 2020

Secondary metabolites from acridocarpus orientalis inhibits 4T1 cells and promotes mesenchymal stem cells (MSCs) proliferation.

Mol Biol Rep 2020 Jul 4;47(7):5421-5430. Epub 2020 Jul 4.

Laboratory for Stem Cell & Regenerative Medicine, Natural and Medical Sciences Research Center, University of Nizwa, P. O. Box: 33, Nizwa, PC, 616, Oman.

Among medicinal plants, Acridocarpus orientalis (AO) possesses a remarkable anti-cancer potential, possibly because of its anti-oxidant property. In this study, the leaf and stem extracts from AO were assessed to find the bioactive compound with selective anti-cancer properties. The MTT viability and live and dead assays revealed that around 80% and 98% of 4T1 cells survival were declined after 48 h incubation with leaf and stem extracts, respectively. The leaf extract increased stem cell proliferation by 20% whereas the stem extract inhibited around 22% of stem cells proliferation after 48 h treatment. The live and dead assay of MSCs confirmed that 40% of the MSCs died when treated with AO stem extract. On the other hand, there were no dead cells after two days of treatment with the leaf extract. Followed by the induction of cell cycle arrest in G0/G1-phase, the real-time PCR demonstrated apoptosis properties in 4T1 cells through overexpression of Bax and down-regulation of BCL2 genes. Interestingly, within the pure compounds isolated from AO leaf extract, Morin was responsible for the inhibition of 4T1 cells proliferation as well as MSCs expansion, predicting to play an essential role in the treatment of cancer. The promising in vitro anti-cancer and stem cell-inductive properties of morin isolated from AO extract may provide a great potential to produce selective herbal derived drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11033-020-05632-yDOI Listing
July 2020

FT-NIRS Coupled with PLS Regression as a Complement to HPLC Routine Analysis of Caffeine in Tea Samples.

Foods 2020 Jun 24;9(6). Epub 2020 Jun 24.

Department of Biological Sciences & Chemistry, College of Arts and Sciences, University of Nizwa, P.O. Box 33, Nizwa 611, Oman.

Daily consumption of caffeine in coffee, tea, chocolate, cocoa, and soft drinks has gained wide and plentiful public and scientific attention over the past few decades. The concentration of caffeine in vivo is a crucial indicator of some disorders-for example, kidney malfunction, heart disease, increase of blood pressure and alertness-and can cause some severe diseases including type 2 diabetes mellitus (DM), stroke risk, liver disease, and some cancers. In the present study, near-infrared spectroscopy (NIRS) coupled with partial least-squares regression (PLSR) was proposed as an alternative method for the quantification of caffeine in 25 commercially available tea samples consumed in Oman. This method is a fast, complementary technique to wet chemistry procedures as well as to high-performance liquid chromatography (HPLC) methods for the quantitative analysis of caffeine in tea samples because it is reagent-less and needs little or no pre-treatment of samples. In the current study, the partial least-squares (PLS) algorithm was built by using the near-infrared NIR spectra of caffeine standards prepared in tea samples scanned by a Frontier NIR spectrophotometer (L1280034) by PerkinElmer. Spectra were collected in the absorption mode in the wavenumber range of 10,000-4000 cm, using a 0.2 mm path length and CaF sealed cells with a resolution of 2 cm. The NIR results for the contents of caffeine in tea samples were also compared with results obtained by HPLC analysis. Both techniques provided good results for predicting the caffeine contents in commercially available tea samples. The results of the proposed study show that the suggested FT-NIRS coupled with PLS regression algorithun has a high potential to be routinely used for the quick and reproducible analysis of caffeine contents in tea samples. For the NIR method, the limit of quantification (LOQ) was estimated as 10 times the error of calibration (root mean square error of calibration (RMSECV)) of the model; thus, RMSEC was calculated as 0.03 ppm and the LOQ as 0.3 ppm.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/foods9060827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353657PMC
June 2020

Effect of Roflumilast in airways disorders via dual inhibition of phosphodiesterase and Ca-channel.

Saudi Pharm J 2020 Jun 25;28(6):698-702. Epub 2020 Apr 25.

Department of Pharmacology, College of Pharmacy, Jouf University, Sakakah 72341, Saudi Arabia.

The bronchodilator effects of Roflumilast "a selective phosphodiesterase type-4 (PDE4)" inhibitor studied in this experimental protocol. The spiral strips of isolated guinea-pig tracheal chains mounted in organ bath and maintained in Krebs solution ventilated with carbogen at 32 °C and in Ca restricted krebs solution. PDE inhibitory activity was evaluated by recording dose response curves using inhibitory effect of isoprenaline on CCh induced contractions. For confirmation of PDE inhibition the intracellular cAMP levels were also estimated. Roflumilast resulted a sharp inhibition in contractile responses of carbachol (CCh, 1 µM) and K (80 mM) and the results were almost similar to verapamil. In Ca restricted Krebs solution, a rightward shift in the Ca response curves observed in the tracheal chain strips which were pretreated with Roflumilast (0.001-0.003 mg/mL) and the maximum response was suppressed, similarly as with verapamil. PDE inhibitory effect of Roflumilast evaluated by recording dose-dependent (0.03-0.1 mg/mL) responses, the isoprenaline-induced inhibitory dose response curves shifted leftward similar to papaverine (PDE inhibitor). Pretreatment with Roflumilast exhibited elevated intracellular cAMP levels in tracheal strips. Findings of the experiment conclude bronchodilatory influence of Roflumilast via PDE and Ca channel inhibition. Results of current experiment offers comprehensive mechanistic background of Roflumilast in future as therapeutic bronchodilator for hyperactive bronchial airway diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jsps.2020.04.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292871PMC
June 2020

Antiproliferative and Carbonic Anhydrase II Inhibitory Potential of Chemical Constituents from and : Evidence from In Silico Target Fishing and In Vitro Testing.

Pharmaceuticals (Basel) 2020 May 13;13(5). Epub 2020 May 13.

Natural & Medical Sciences Research Center, University of Nizwa, P.O Box 33, 616 Birkat Al Mauz, Nizwa, Sultanate of Oman.

Roem. & Schult and resin of (L.) BURM. F. are commonly used in Omani traditional medication against various ailments. Herein, their antiproliferative and antioxidant potential was explored. Bioassay-guided fractionation of the methanol extract of both plants led to the isolation of 14 known compounds, viz., - from and - from Their structures were confirmed by combined spectroscopic techniques including 1D (H and C) and 2D (HMBC, HSQC, COSY) nuclear magnetic resonance (NMR), and electrospray ionization-mass spectrometry (ESI-MS). The cytotoxic potential of isolates was tested against the triple-negative breast cancer cell line (MDA-MB-231). Compound exhibited excellent antiproliferative activity in a range of 31 μM, followed by compounds -, , and , which depicted IC values in the range of 35-60 μM, while , , and also demonstrated IC values >72 μM. Subsequently, in silico target fishing was applied to predict the most potential cellular drug targets of the active compounds, using pharmacophore modeling and inverse molecular docking approach. The extensive in silico analysis suggests that our compounds may target carbonic anhydrase II (CA-II) to exert their anticancer activities. When tested on CA-II, compounds (IC = 14.4 µM), (IC = 23.3), and (IC = 24.4 µM) showed excellent biological activities in vitro. Additionally, the ethyl acetate fraction of both plants showed promising antioxidant activity. Among the isolated compounds, possesses the highest antioxidant (55 μM) activity followed by (241 μM). The results indicated that compound can be a promising candidate for antioxidant drugs, while compound is a potential candidate for anticancer drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ph13050094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281707PMC
May 2020

Triterpenic Acids as Non-Competitive α-Glucosidase Inhibitors from with Structure-Activity Relationship: In Vitro and In Silico Studies.

Biomolecules 2020 05 12;10(5). Epub 2020 May 12.

Natural & Medical Sciences Research Center, University of Nizwa, P.O Box 33, Birkat Al Mauz, Nizwa 616, Oman.

Fourteen triterpene acids, viz., three tirucallane-type (-), eight ursane-type (-), two oleanane-type (, ) and one lupane type (), along with boswellic aldehyde (), α-amyrine (), epi-amyrine (), straight chain acid (), sesquiterpene () and two cembrane-type diterpenes (, ) were isolated, first time, from the methanol extract of resin. Compound () was isolated for first time as a natural product, while the remaining compounds (‒) were reported for first time from The structures of all compounds were confirmed by advanced spectroscopic techniques including mass spectrometry and also by comparison with the reported literature. Eight compounds (- and ) were further screened for in vitro α-glucosidase inhibitory activity. Compounds - and showed significant activity against α-glucosidase with IC values ranging from 9.9-56.8 μM. Compound (IC = 9.9 ± 0.48 μM) demonstrated higher inhibition followed by (IC = 14.9 ± 1.31 μM), (IC = 20.9 ± 0.05 μM) and (IC = 56.8 ± 1.30 μM), indicating that carboxylic acid play a key role in α-glucosidase inhibition. Kinetics studies on the active compounds - and were carried out to investigate their mechanism (mode of inhibition and dissociation constants ). All compounds were found to be non-competitive inhibitors with values in the range of 7.05 ± 0.17-51.15 ± 0.25 µM. Moreover, in silico docking was performed to search the allosteric hotspot for ligand binding which is targeted by our active compounds investigates the binding mode of active compounds and it was identified that compounds preferentially bind in the allosteric binding sites of α-glucosidase. The results obtained from docking study suggested that the carboxylic group is responsible for their biologic activities. Furthermore, the α-glucosidase inhibitory potential of the active compounds is reported here for the first time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/biom10050751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278020PMC
May 2020

Evaluation of antioxidant and antimicrobial activities on various extracts of Himalayan medicinal plants.

Pak J Pharm Sci 2020 Mar;33(2):695-703

International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.

The DPPH radical scavenging potentials of the fractions were determined in comparison to positive controls such as quercetin with EC = 4.12±1.27, ascorbic acid with EC = 6.20±1.67, gallic acid with EC = 4.75±1.24 and α-tocopherol with EC = 32.50±1.57 μg/mL. The experiment showed that aqueous fractions of the bark extracts of Abies pindrow (fraction: C) and Cedrus deodara (fraction: E2) showed significantly lower EC values of 2.5±0.5 and 2.5±0.6 μg/mL, respectively. In reducing power assay, lower EC values of 5.5 and 4.5μg/mL were recorded for the aqueous fraction (fraction: C ) and final residue (fraction: C), of Abies pindrow, respectively. The ethyl acetate, acetone and final fractions of knot wood of Picea smithiana were found significantly active against all bacterial strains. Of the most sensitive fractions towards all the fungal strains was ethyl acetate fraction obtained from the bark of Cedrus deodara with a zone of inhibition ranging from 75 to 88 % that was more than the standard fluconazole.
View Article and Find Full Text PDF

Download full-text PDF

Source
March 2020

Evaluation of bronchodialatory and antimicrobial activities of A multi-mechanistic approach.

Saudi Pharm J 2020 Mar 31;28(3):281-289. Epub 2020 Jan 31.

Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

, a plant belonging to the family Lamiaceae, is endemic to Ethiopia. In Ethiopian traditional medicine, has been used for the treatment of several respiratory-related disorders. The present study was designed to evaluate the bronchodilatory and antimicrobial activities of leaves crude extract (Of.Cr). Ex-vivo experiments were conducted on guinea-pig trachea provided with physiological oxygenated buffer solution using emkaBath setup. The crude extract was analyzed by gas chromatography-mass spectrometry. Of.Cr, showed the presence of terpenes, fragrance components, saponins, and higher fatty acids. Of.Cr when tested on contracted tracheal chains with carbamylcholine (CCh, 1 µM) and high K (80 mM) produced relaxation by showing higher potency against CCh with incomplete inhibition of high K. Dicyclomine, used as a positive control, also showed selectively higher potency to inhibit CCh when compared with its effect against K. In the anticholinergic curves, Of.Cr at 1 mg/mL deflected CCh-induced concentration-response curves (CRCs) competitively to the right like dicyclomine (0.03 µM) and atropine whereas a higher dose of Of.Cr (3 mg/mL) produced a non-parallel shift in the CCh curves like a higher dose of dicyclomine (0.1 µM). In the calcium channel inhibitory assay, Of.Cr at 3 & 5 mg/mL, deflected CRCs of Ca to the right like verapamil, used as positive control. Of.Cr, at concentrations (1-3 mg/mL) increases cAMP levels in isolated tracheal homogenates, similar to positive control phosphodiesterase inhibitor (papaverine). When tested for antibacterial activity against standard and clinical strains, Of.Cr was found more active (MIC 475 µg/ml) against S. aureus (NCTC 6571), while the maximum inhibition (MIC 625 µg/ml) was observed by the extract when tested against MRSA. These results determine the mechanistic pathways of the observed bronchodilatory effect of with a combination of anticholinergic and dual inhibition of phosphodiesterase and voltage-gated Ca channels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jsps.2020.01.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078568PMC
March 2020

Organic extracts from Cleome droserifolia exhibit effective caspase-dependent anticancer activity.

BMC Complement Med Ther 2020 Mar 6;20(1):74. Epub 2020 Mar 6.

Department of Biochemistry, College of Medicine and Health Sciences, UAE University, Tawam Hospital Complex, P.O. Box 17666, Al Ain, UAE.

Background: This study investigated the anticancer potential of the medicinal herb, Cleome droserifolia (CD), a local plant of the Arabian Peninsula. C. droserifolia is traditionally known for its rubefacient, anti-diabetic, anti-oxidant, and anti-inflammatory properties.

Methods: Organic fractions of the aerial parts of Cleome droserifolia harvested from the Arabian Peninsula were tested in human breast and cervical cancer cell lines for their anticancer potential. This was accomplished by using biochemical and cellular assays, including MTT, caspase Glo, western blot, and annexin V/propidium iodide-based flow cytometry analyses.

Results: Test of the dichloromethane fraction of the methanolic extract of C. droserifolia, (CDD) revealed potent cytotoxic activity (from 70 to 90%) against several human cancer cell lines, including MCF-7, MDA-MB-231, and HeLa. Further characterization of the CDD fraction in MCF-7 cells revealed that it could activate the enzymatic activity of various caspases in a statistically significant manner, and induce cleavage of both caspase 7 and poly ADB ribose polymerase (PARP) proteins, but not the ethyl acetate fraction. Test of the ability of CDD to induce early signs of apoptosis was validated by annexin V/propidium iodide assay using FACS analysis. Induction of apoptosis was completely reversed by the classic pan inhibitor of apoptosis, Z-VAD-FMK, reducing early apoptosis from 29.7 to 0.6%, confirming that CDD could induce caspase-dependent apoptosis.

Conclusions: Altogether, our results reveal that C. droserifolia is a valuable medicinal plant with bioactive molecules that can induce apoptosis in human cancer cells. Thus, this plant should be explored further for its potential as an anticancer natural therapy as well as the isolation of novel molecules with anticancer properties.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12906-020-2858-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076903PMC
March 2020

In Silico, Ex Vivo and In Vivo Studies of Roflumilast as a Potential Antidiarrheal and Antispasmodic agent: Inhibition of the PDE-4 Enzyme and Voltage-gated Ca++ ion Channels.

Molecules 2020 Feb 24;25(4). Epub 2020 Feb 24.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Tishk International University, Erbil 44001, Kurdistan, Iraq.

The aim of the present study was to evaluate the possible gut inhibitory role of the phosphodiesterase (PDE) inhibitor roflumilast. Increasing doses of roflumilast were tested against castor oil-induced diarrhea in mice, whereas the pharmacodynamics of the same effect was determined in isolated rabbit jejunum tissues. For in silico analysis, the identified PDE protein was docked with roflumilast and papaverine using the Autodock vina program from the PyRx virtual screening tool. Roflumilast protected against diarrhea significantly at 0.5 and 1.5 mg/kg doses, with 40% and 80% protection. Ex vivo findings from jejunum tissues show that roflumilast possesses an antispasmodic effect by inhibiting spontaneous contractions in a concentration-dependent manner. Roflumilast reversed carbachol (CCh, 1 µM)-mediated and potassium (K+, 80 mM)-mediated contractile responses with comparable efficacies but different potencies. The observed potency against K+ was significantly higher in comparison to CCh, similar to verapamil. Experiments were extended to further confirm the inhibitory effect on Ca++ channels. Interestingly, roflumilast deflected Ca++ concentration-response curves (CRCs) to the right with suppression of the maximum peak at both tested doses (0.001-0.003 mg/mL), similar to verapamil. The PDE-inhibitory effect was authenticated when pre-incubation of jejunum tissues with roflumilast (0.03-0.1 mg/mL) produced a leftward deflection of isoprenaline-mediated inhibitory CRCs and increased the tissue level of cAMP, similar to papaverine. This idea was further strengthened by molecular docking studies, where roflumilast exhibited a better binding affinity (-9.4 kcal/mol) with the PDE protein than the standard papaverine (-8.3 kcal/mol). In conclusion, inhibition of Ca++ channels and the PDE-4 enzyme explains the pharmacodynamics of the gut inhibitory effect of roflumilast.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules25041008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070291PMC
February 2020

Lophenol and lathosterol from resin of Commiphora kua possess hepatoprotective effects in vivo.

J Ethnopharmacol 2020 Apr 9;252:112558. Epub 2020 Jan 9.

Natural and Medical Sciences Research Center, University of Nizwa, PO Box 33, 616 Birkat Al Mauz, Nizwa, Oman. Electronic address:

Ethnopharmacological Relevance: Drug induced liver damage remains a prevalent concern in healthcare and may reduce the effectiveness of therapy by compromising therapeutic regimens. Many Commiphora species are known for their medicinal properties, and some of them are used traditionally for hepatoprotective effect. In the course of our drugs discovery from natural sources, phytosterols (lophenol (Lop) and lathosterol (Lat)), isolated from Commiphora kua were studied to evaluate their hepatoprotective effects in acetaminophen (APAP) induced hepatotoxicity in mice.

Aims And Objective: To evaluate the hepatoprotective effects of phytosterols isolated from C. kua using in vivo experimental model.

Materials And Methods: Mice of either sex were divided into 7 groups: Vehicle, silymarin (SLY), acetaminophen (APAP), Lop 25, Lop 50, Lat 25, Lat 50 (n = 5). Vehicle group received only vehicle (0.1% DMSO solution) for 7 days, APAP group received single dose of acetaminophen on day 7 and SLY group received silymarin for 7 days. Lop 25 and Lop 50 received low and high doses of Lop (25 μg/kg BW and 50 μg/kg BW), respectively, for 7 days, while Lat 25 and Lat 50 received low and high doses of Lat (25 μg/kg BW and 50 μg/kg BW) for 7 days. On day 7, all animals except Vehicle group kept fasted for 18 h and received APAP i. p. 400 mg/kg BW. After 20 h of APAP administration, the animals anesthetized with light chloroform and scarified by cervical decapitation. The blood serum and liver tissue samples were collected for biochemical and histopathological analysis. Liver function tests (LFTs) including lactate deydrogenase (LDH), alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST) and direct bilirubin) were used as biochemical parameters. While catalase (CAT), superoxide dismutase (SOD) and reduced glutathione (GSH) were taken as anti-oxidant enzymes.

Results: Significant increase in levels of ALT, AST, ALP, LDH and direct bilirubin, and significant decrease in concentration of anti-oxidant enzymes (SOD, CAT and GSH) was observed in APAP-treated group. Similarly, histological slides showed obvious signs of damage to liver cells, reflecting acetaminophen induced hepatotoxicity. Treatment of test animals with phytosterols resulted in significant recovery of LFTs profile and concentration of anti-oxidant enzymes. Similarly, significant improvement of liver tissues was noted in histological analysis.

Conclusions: Both phytosterols possessed hepatoprotective potential and should be further evaluated for acute toxicity studies and pharmacokinetics/pharmacodynamics profile.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2020.112558DOI Listing
April 2020

α-Glucosidase Inhibition and Molecular Docking Studies of Natural Brominated Metabolites from Marine Macro Brown Alga .

Mar Drugs 2019 Nov 26;17(12). Epub 2019 Nov 26.

Natural & Medical Sciences Research Center, University of Nizwa, P.O Box 33, Birkat Al Mauz, 616 Nizwa, Sultanate of Oman.

Bioassay guided isolation of the methanolic extract of marine macro brown alga afforded one new metabolite (ethyl methyl 2-bromobenzene 1,4-dioate, ), one new natural metabolite (diethyl-2-bromobenzene 1,4-dioate, ) along with six known metabolites (-) reported for the first time from this source. The structure elucidation of all these compounds was achieved by extensive spectroscopic techniques including 1D (H and C) and 2D (NOESY, COSY, HMBC and HSQC) NMR and mass spectrometry and comparison of the spectral data of known compounds with those reported in literature. The in vitro α-glucosidase inhibition studies confirmed compound to be the most active against α-glucosidase enzyme with IC value of 30.5 ± 0.41 μM. Compounds and demonstrated good inhibition with IC values of 234.2 ± 4.18 and 289.4 ± 4.91 μM, respectively, while compounds , , and showed moderate to low inhibition. Furthermore, the molecular docking studies of the active compounds were performed to examine their mode of inhibition in the binding site of the α-glucosidase enzyme.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/md17120666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949951PMC
November 2019

Differential Cytotoxic Potential of Leaf and Stem Extracts with the Ability to Induce Multiple Cell Death Pathways.

Molecules 2019 Nov 3;24(21). Epub 2019 Nov 3.

Department of Biochemistry, College of Medicine & Health Sciences, United Arab Emirates (UAE) University, Al Ain, P.O. Box 17666, UAE.

This study systematically analyzed the anticancer potential of (AO), a traditional medicinal plant of the Arabian Peninsula/East Africa known for its anti-inflammatory and pain relief properties. Tests of serial organic fractions from methanolic extracts of its leaves and stems revealed that only some fractions showed anti-proliferative potential with the dichloromethane fraction from leaves (AOD (L)) showing the most cytotoxic effect against both breast (MCF-7 and MDA-MB-231) and cervical (HeLa) cancer cell lines. The -butanol fraction from the stems (AOB (S)), on the other hand, was more effective against cervical cancer cells and did not harm the normal cells. Further characterization of the mode of cell killing revealed that AOD (L) depended more on non-apoptotic pathways for its cytotoxicity in breast cancer cells, while it could activate some apoptosis and necroptosis in HeLa cells. The AOB (S) fraction could primarily activate apoptosis and some necroptosis in HeLa cells. Both fractions perturbed autophagy, but in a dissimilar manner. Thus, different parts of revealed variable potential to induce cell death in cancer cells via apoptotic and non-apoptotic pathways, making a valuable plant for the exploration of anticancer bioactive reagents, some of which may be protective for normal cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules24213976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6864630PMC
November 2019

Loading AKBA on surface of silver nanoparticles to improve their sedative-hypnotic and anti-inflammatory efficacies.

Nanomedicine (Lond) 2019 11 16;14(21):2783-2798. Epub 2019 Oct 16.

Natural & Medical Sciences Research Center, University of Nizwa, PO Box 33, Birkat Al Mauz, Nizwa 616, Sultanate of Oman.

Acetyl-11-keto--boswellic acid (AKBA) is a potent anti-inflammatory compound limited by its low water solubility and bioavailability. To load AKBA on silver nanoparticles (AgNPs) to improve bioavailability and water solubility of the compound. AKBA-AgNPs were chemically synthesized and characterized by UV-Vis spectrophotometry, Fourier transform infrared spectroscopy, scanning electron microscopy and transmission electron microscopy. AKBA and AKBA-Ag were studied for their sedative-hypnotic and anti-inflammatory efficacies. Pretreatment with AKBA or AKBA-Ag caused significant dose-dependent sedative-hypnotic effects at 5 and 10 mg/kg intraperitoneal. The effects of AKBA-loaded AgNPs caused pronounced changes in mice compared with those of AKBA, and the AKBA-AgNPs demonstrated anti-inflammatory effects that were superior to those of AKBA. The loading of AKBA on nanoparticles improved its pharmacokinetic effects, and capacity for drug delivery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/nnm-2019-0211DOI Listing
November 2019

Protective role of Roflumilast against cadmium-induced cardiotoxicity through inhibition of oxidative stress and NF-κB signaling in rats.

Saudi Pharm J 2019 Jul 2;27(5):673-681. Epub 2019 Apr 2.

Department of Basic Sciences, Preparatory Year Deanship, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia.

Cadmium (Cd), a potent cardiotoxic environmental heavy metal, induces oxidative stress and membrane disturbances in cardiac myocytes. Phosphodiesterase (PDEs) retards the positive inotropic effects of β-adrenoceptor activation by decreasing levels of cAMP via degradation. Hence, PDE inhibitors sensitize the heart to catecholamine and are therefore, used as positive inotropic agents. The present study was designed to probe the potential attenuating effects of the selective PDE4 inhibitor (Roflumilast, ROF), on cardiac biomarkers, lipid profile, lipid peroxidation products, antioxidant status and histology of cardiac tissues against Cd-induced cardiotoxicity in rats. Rats were randomly distributed into four different groups: group 1, served as the normal control group. Group 2, served as the toxic control group and were administered Cd (3 mg/kg, i.p.) for next 7 days. Groups 3 and 4, served as treatment groups that received Cd with concomitant oral administration of ROF doses (0.5 and 1.5 mg/kg), respectively for 7 days. Serum samples of toxic control group rats resulted in significant ( < 0.001) increase in lactate dehydrogenase (LDH), creatine phosphokinase (CPK), total cholesterol (TC), triglycerides (TG) and low density lipoproteins (LDL) levels with concomitant decrease in high density lipoproteins (HDL) levels in serum which were found reversed with both of ROF treatment groups. Cd also causes significant increased ( < 0.001) in myocardial malondialdehyde (MDA) contents while cardiac glutathione (GSH) level, superoxide dismutase (SOD) and catalase (CAT) enzyme activities were found decreased whereas both doses of ROF, significantly reversed these oxidative stress markers and antioxidant enzymes. Cardiotoxicity induced by Cd also resulted in enhanced expression of non-phosphorylated and phosphorylated form of NF-κB p65 and decreased expression of glutathione-S-transferase (GST) and NQO1 which were found reversed with ROF treatments, comparable to normal control group. Histopathological changes were also improved by ROF administration as compared to Cd treated rats alone. In conclusion, Roflumilast exhibited attenuating effect against Cd-induced cardiac toxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jsps.2019.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598217PMC
July 2019

Mentha: A genus rich in vital nutra-pharmaceuticals-A review.

Phytother Res 2019 Oct 9;33(10):2548-2570. Epub 2019 Jul 9.

Department of Pharmacology, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi Arabia.

The genus Mentha comprises several aromatic species, which are cultivated world-over due to their distinct aroma and commercial value. In addition to traditional food flavoring uses, Mentha are well recognized for their folk medicinal uses, especially to treat cold, fever, and digestive and cardiovascular disorders. A number of biological activities such as antioxidant, antimicrobial, biopesticidal, antitumor, anticancer, antiviral, antiallergic, antiinflammatory, antihypertensive, and urease inhibitory activity have been ascribed to Mentha. The traditional pharmacological attributes of Mentha herbs can be linked to the occurrence of bioactive phytochemicals such as terpenoids, alcohols, rosmarinic acid, and antioxidant phenolics among others. A rich source of bioactives, different species of Mentha, can be explored as a promising candidate for the development of nutra-pharmaceuticals. This review covers the nutritional, phytochemical, and traditional medicinal aspects and multiple biological activities of some commonly available species of Mentha so as to explore their potential applications for nutra-pharmaceutical and cosmo-nutraceutical industry. Detailed chemical profile and pharmaceutical attributes of various Mentha essential oils are also covered. Moreover, based on computational analysis, quantitative chemical component-antioxidant activity relationship model is reviewed to predict and correlate structure-activity relationship of potential bioactives in selected Mentha essential oils leading to discovery and developmenmt of novel natural drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ptr.6423DOI Listing
October 2019

Secondary metabolites from the resins of Aloe vera and Commiphora mukul mitigate lipid peroxidation.

Acta Pharm 2019 Sep;69(3):433-441

Natural & Medical Sciences Reasearch Center, University of Nizwa, Nizwa, Sultanate ofOman.

Oxidative stress is often considered detrimental for cellular processes and damaging for the lipid bi-layer. Counteracting such stresses with the aid of nature-based chemical constituents can be an ideal therapeutic approach. The current study aimed to investigate the chemical constituents of resins derived from the well-known Aloe vera and less known Commiphora mukul trees and their effect in mitigating the lipid peroxidation (LPO) process. The bio-guided isolation of bio-active fractions from both resins afforded 20 chemical constituents (17 from A. vera and 3 from C. mukul). These compounds belonged to anthraquinones, anthraquinone glycosides, quinones, coumarins, polypodane-type terpenoids and benzene derivatives. Major chemical constituents of the resins of A. vera and C. mukul were from the classes of quinones and terpenoids. Feroxidin (4, from A. vera) showed slightly higher inhibition (IC50 = 201.7 ± 0.9 µmol L-1) than myrrhanone C (18, from C. mukul: IC50 = 210.7 ± 0.0 µmol L-1) and methyl 3-(4-hydroxyphenyl) propionate from A. vera (13, IC50 = 232.9 ± 0.2 µmol L-1) compared to the other compounds. Structure-activity relationship showed that the existence of hydroxyl, methoxy and ether groups might play a major role in countering oxidative stress. To the best of our knowledge, anti-LPO activities of compounds 1-4, 14, 18 and 20 are reported for the first time. Such chemical constituents with high anti-lipid peroxidation activity could be helpful in synthesizing candidate drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2478/acph-2019-0027DOI Listing
September 2019

L. (Black Cumin): A Promising Natural Remedy for Wide Range of Illnesses.

Evid Based Complement Alternat Med 2019 12;2019:1528635. Epub 2019 May 12.

Department of Chemistry, University of Sargodha, Sargodha, Pakistan.

The seed of () has been used in different civilization around the world for centuries to treat various animal and human ailments. So far, numerous studies demonstrated the seed of and its main active constituent, thymoquinone, to be medicinally very effective against various illnesses including different chronic illness: neurological and mental illness, cardiovascular disorders, cancer, diabetes, inflammatory conditions, and infertility as well as various infectious diseases due to bacterial, fungal, parasitic, and viral infections. In spite of limited studies conducted so far, the promising efficacy of against HIV/AIDS can be explored as an alternative option for the treatment of this pandemic disease after substantiating its full therapeutic efficacy. Moreover, the strong antioxidant property of this valued seed has recently gained increasing attention with regard to its potential role as dietary supplement with minimal side effects. Besides, when combined with different conventional chemotherapeutic agents, it synergizes their effects resulting in reducing the dosage of concomitantly used drugs with optimized efficacy and least and/or no toxicity. A number of pharmaceutical and biological properties have been ascribed to seeds of . The present review focuses on the profile of high-value components along with traditional medicinal and biological principles of seed and its oil so as to explore functional food and nutraceutical potential of this valued herb.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2019/1528635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535880PMC
May 2019

Rifampicin conjugated silver nanoparticles: a new arena for development of antibiofilm potential against methicillin resistant and .

Int J Nanomedicine 2019 29;14:3983-3993. Epub 2019 May 29.

Natural and Medical Sciences Research Center, University of Nizwa, Nizwa, Sultanate of Oman.

Infections caused by drug resistant bacteria are a major health concern worldwide and have prompted scientists to carry out efforts to overcome this challenge. Researchers and pharmaceutical companies are trying to develop new kinds of antimicrobial agents by using different physical and chemical methods to overcome these problems. In the present study, rifampicin conjugated silver (Rif-Ag) nanoparticles have successfully been synthesized using a chemical method. Characterization of the nanoparticles was performed using a UV-Vis spectrophotometer, FTIR, SEM, TEM, and AFM. The AFM, SEM, and TEM results showed that the average particle size of Rif-Ag nanoparticles was about 15-18±4 nm. The FTIR spectra revealed the conjugation of -NH and -OH functional moiety with silver nanoparticles surface. Considering the penetrating power of rifampicin, the free drug is compared with synthesized nanoparticle for antimicrobial, biofilm inhibition, and eradication potential. Synthesized nanoparticles were found to be significantly active as compared to drug alone. This study has shown greater biofilm inhibitory and eradicating potential against methicillin resistant and , as evident by crystal violet, MTT staining, and microscopic analysis. So, it will be further modified, and studies for the mechanism of action are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/IJN.S198194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549787PMC
August 2019

Natural urease inhibitors from Aloe vera resin and Lycium shawii and their structural-activity relationship and molecular docking study.

Bioorg Chem 2019 07 27;88:102955. Epub 2019 Apr 27.

Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan.

Bio-assay guided fractionation of the methanolic extract of Aloe vera resin and Lycium shawii stem successively afforded twenty three compounds; fourteen (1-14) from A. vera and nine (15-23) from L. shawii. All these compounds were characterized by 1D and 2D NMR spectroscopic techniques viz., H, C, DEPT, HSQC, HMBC, and COSY, and NEOSY, ESI-MS and compared with the reported literature. These compounds were assessed for their potential as urease inhibitors targeted in peptic ulcer. Among crude extracts and fractions of A. vera resin, n-butanol fraction (23.5 ± 1.7 μg·mL) showed the most potent urease inhibition followed by methanol (30.9 ± 0.3 μg/mL) and ethyl acetate (31.7 ± 0.5 μg·mL). In case of L. shawii, ethyl acetate fraction exhibited the highest urease activity (41.0 ± 1.4 μg/mL) trailed by dichloromethane (55.2 ± 1.5 μg/mL) fraction. Among the isolates, compounds 7, 11 and 23 were found to be excellent urease inhibitors with IC values of 14.5 ± 0.90 µM, (16.7 ± 0.16 µM) and 14.0 ± 0.8 µM, respectively. To the best of our knowledge, this is the first report on the urease enzyme inhibitory activity of the said compounds excluding compound 18. In addition, the urease activity of different fractions of L. shawii stem was also reported for the first time. The molecular docking studies showed that all the active compounds well accommodate in the active site of the urease enzyme by interacting with key amino acids.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2019.102955DOI Listing
July 2019

Evidence for the involvement of a GABAergic mechanism in the effectiveness of natural and synthetically modified incensole derivatives in neuropharmacological disorders: A computational and pharmacological approach.

Phytochemistry 2019 Jul 20;163:58-74. Epub 2019 Apr 20.

Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120 Halle (Saale) Germany.

In the course of our continuing exploration for novel bioactive lead compounds (s) from the species Boswellia, we have recently reported incensole derivatives isolated from Boswellia papyrifera Hochst. Given the known antidepressant-like effects of incensole and incensole acetate, we herein present that the low dose intraperitoneal administration of incensole derivatives, namely, incensfuran and incensone, showed significant antidepressant-like effects in the forced swim test (FST) and tail suspension test (TST). Furthermore, these compounds were evaluated for their anxiolytic potential in the elevated plus maze (EPM) and light dark box (LDB) tests and anticonvulsant effects in pentylenetetrazole (PTZ)-induced seizure tests. In the EPM test, administration of these compounds led to dose-dependent increases in open arm entries and in the time spent in EPM open arms. Similar results were obtained in the LDB test, wherein compounds these caused significant increases in the number of transitions between lit and dark compartments and the time spent in the lit compartment. The anxiolytic-like effects in the EPM were not reversed by pretreatment with flumazenil, whereas PTZ and bicuculline (BIC) completely abolished the anxiolytic effects, showing the involvement of the non-benzodiazepine binding sites of GABA receptors. All four compounds induced significantly elevated brain GABA levels, indicating the involvement of a GABAergic mechanism. Additionally, molecular docking was conducted to elucidate the mode of action for the anxiolytic and anticonvulsant effects of these derivatives. Moreover, these compounds also possess drug-like properties and excellent ADMET profiles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phytochem.2019.04.007DOI Listing
July 2019