ABSTRACT
Halophytes are the native inhabitants of saline environment. Their biomass can be considered as a potential substrate for the production of microbial enzymes. This study was intended at feasible utilization of a halophytic biomass, Cressia cretica, for pectinase production using a halo- and thermo-tolerant bacterium, Bacillus vallismortis MH 10. The data from fractionation of the C. cretica biomass revealed presence of 17% pectin in this wild biomass. Seven different factors (temperature, agitation, pH, inoculum size, peptone concentration, substrate concentration, and incubation time) affecting pectinase production using C. cretica were assessed through a statistical tool, Plackett-Burman design. Consequently, two significant factors (incubation time and peptone concentration) were optimized using the central composite design. The strain produced 20 IU mL-1 of pectinase after 24 h under optimized conditions. The enzyme production kinetics data also confirmed that 24 h is the most suitable cultivation period for pectinase production. Fourier transform infrared spectroscopy and scanning electron microscopy of C. cretica biomass ascertained utilization of pectin and structural changes after fermentation. The purification of pectinase by using DEAE column yielded specific activity and purification fold of 88.26 IU mg-1 and 3.2, respectively. The purified pectinase had a molecular weight of >65 kDa. This study offers prospects of large-scale production of pectinase by halotolerant strain in the presence of economical and locally grown substrate that makes the enzyme valuable for various industrial operations.
Subject(s)
Peptones , Polygalacturonase , Polygalacturonase/chemistry , Polygalacturonase/metabolism , Biomass , Fermentation , Pectins/metabolismABSTRACT
Traditional Chinese medicine (TCM) has a good curative effect, but its disadvantages include complex components, poor drug stability, potential drug interaction, etc. Therefore, it is particularly important to construct a novel drug delivery system that can load Chinese medicine monomers to solve this problem. Silk fibroin is a kind of natural polymer material with unique properties. It can be used as a carrier material to load Chinese medicine monomers to prepare novel drug delivery systems that significantly affect treating diseases without toxic and side effects. However, there is still a lack of a review on silk fibroin as a carrier material to load Chinese medicine monomers to explore and analyze the current research results and progress. Here, our article focuses on the in-depth excavation and analysis of the recent research on novel drug delivery systems prepared by silk fibroin and TCM monomers. Besides, the characteristics, existing problems, and prospects of silk fibroin are discussed and explained. It is hoped that this research can provide a reference and basis for the modernization of TCM, the design of novel drug delivery systems, the research and development of new drugs in the future, and contribute to the innovation of silk protein.
Subject(s)
Fibroins , Medicine, Chinese Traditional , Drug Delivery Systems/methods , SilkABSTRACT
Cancer is one of the most fatal diseases globally, however, advancement in the field of nanoscience specifically novel nanomaterials with nano-targeting of cancer cell lines has revolutionized cancer diagnosis and therapy and has thus attracted the attention of researchers of related fields. Carbon Dots (CDs)-C-based nanomaterials-have emerged as highly favorable candidates for simultaneous bioimaging and therapy during cancer nano-theranostics due to their exclusive innate FL and theranostic characteristics exhibited in different preclinical results. Recently, different transition metal-doped CDs have enhanced the effectiveness of CDs manifold in biomedical applications with minimum toxicity. The use of group-11 (Cu, Ag and Au) with CDs in this direction have recently gained the attention of researchers because of their encouraging results. This review summarizes the current developments of group-11 (Cu, Ag and Au) CDs for early diagnosis and therapy of cancer including their nanocomposites, nanohybrids and heterostructures etc. All The manuscript highlights imaging applications (FL, photoacoustic, MRI etc.) and therapeutic applications (phototherapy, photodynamic, multimodal etc.) of Cu-, Ag- and Au-doped CDs reported as nanotheranostic agents for cancer treatment. Sources of CDs and metals alogwith applications to give a comparative analysis have been given in the tabulated form at the end of manuscript. Further, future prospects and challenges have also been discussed.
ABSTRACT
Transfersomes (TFS) are the promising carriers for transdermal delivery of various low and high molecular weight drugs, owing to their self-regulating and self-optimizing nature. Herein, we report synthesis and characterization of TFS loaded with meloxicam (MLX), an NSAID, and dexamethasone (DEX), a steroid, for simultaneous transdermal delivery. The different formulations of TFS containing varying amounts of lecithin, Span 80, and Tween 80 (TFS-1 to TFS-6) were successfully prepared by thin-film hydration method. The size of ranged between 248 and 273 nm, zeta potential values covering from -62.6 to -69.5 mV, polydispersity index (PDI) values in between 0.329 and 0.526, and entrapment efficiency of MLX and DEX ranged between 63-96% and 48-81%, respectively. Release experiments at pH 7.4 demonstrated higher cumulative drug release attained with Tween 80 compared to Span 80-based TFS. The scanning electron microscopy (SEM) of selected formulations -1 and TFS-3 revealed spherical shape of vesicles. Furthermore, three optimized transfersomal formulations (based on entrapment efficiency, TFS-1, TFS-3, and TFS-5) were incorporated into carbopol-940 gels coded as TF-G1, TF-G3, and TF-G5. These transfersomal gels were subjected to pH, spreadability, viscosity, homogeneity, skin irritation, in vitro drug release, and ex vivo skin permeation studies, and the results were compared with plain (nontransfersomal) gel having MLX and DEX. TFS released 71.72% to 81.87% MLX in 12 h; whereas, DEX release was quantified as 74.72% to 83.72% in same time. Nevertheless, TF-based gels showed slower drug release; 51.54% to 59.60% for MLX and 48.98% to 61.23% for DEX. The TF-G systems showed 85.87% permeation of MLX (TF-G1), 68.15% (TF-G3), and 68.94% (TF-G5); whereas, 78.59%, 70.54%, and 75.97% of DEX was permeated by TF-G1, TF-G3, and TF-G5, respectively. Kinetic modeling of release and permeation data indicated to follow Korsmeyer-Peppas model showing diffusion diffusion-based drug moment. Conversely, plain gel influx was found mere 26.18% and 22.94% for MLX and DEX, respectively. These results suggest that TF-G loaded with MLX and DEX can be proposed as an alternate drug carriers for improved transdermal flux that will certainly increase therapeutic outcomes.
Subject(s)
Dexamethasone , Lecithins , MeloxicamABSTRACT
Farsetia hamiltonii Royle is a medicinal plant of Cholistan desert, Pakistan, traditionally used for treating diabetes, oxidative stress, arthritis, fever, gastrointestinal and respiratory diseases. This study represents unprecedented phytochemical, enzymatic and biological properties of F. hamiltonii root extracts to prove floric uses. Evaluation of Phytochemical constituents was done by screening, total flavonoid, phenolic contents and gas chromatography-mass spectrometry. The phytochemical screening revealed the presence of glycosides, bounded anthraquinones, flavonoids, saponins, steroids, coumarins and diterpenes in root extracts. Eight compounds were identified in dichloromethane extract, whereas one compound was identified in methanol extract of root part of F. hamiltonii. The dichloromethane extract possesses significant lipoxygenase, chymotripsin and cholinesterase enzyme inhibition activities, whereas methanol extract possess lipoxygenase, alpha glucosidase, chymotrypsin and acetylcholinesterase enzyme inhibition activities. The antibacterial activity of methanol extract was significant against selected five microbial strains. Nine compounds were reported in root part of F. hamiltonii first time. The enzyme inhibition assays on anti-cholinesterase, anti-alpha glucosidase, antilipoxygenase, antichymotripsin and antibacterial activities were found significant for the extracts of root parts of F. hamiltonii. Therefore, results of this study justify folkloric therapeutic potential of F. hamiltonii root in treating diabetes, inflammations and infectious diseases.
Subject(s)
Brassicaceae , Saponins , Acetylcholinesterase , Anthraquinones , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antioxidants/pharmacology , Cholinesterase Inhibitors/pharmacology , Chymotrypsin , Coumarins , Flavonoids/analysis , Glycosides , Lipoxygenases , Methanol , Methylene Chloride , Phytochemicals/pharmacology , Plant Extracts/chemistry , Plant Extracts/pharmacology , alpha-GlucosidasesABSTRACT
Pterostilbene is a stilbene flavonoid that occurs naturally in various plants as well as produced by genetic engineering. It exhibits anti-inflammatory, analgesic, anti-oxidant and neuroprotective activities. This research was aimed to determine the potential of pterostilbene against arthritis and peripheral neuropathy in Complete Freund's Adjuvant (CFA) induced arthritis. Rat hind paw was injected with 0.1 ml CFA to induce arthritis. Standard control animals received oral methotrexate (3 mg/kg/week). Pterostilbene at 12.5, 25 and 50 mg/kg was given orally to different groups of arthritic rats from day 7-28 for 21 days. Pterostilbene significantly reduced paw diameter and retarded the decrease in body weight of arthritic rats. It profoundly (p < 0.05-0.0001) reduced lipid peroxidation and nitrites, while increased superoxide dismutase (SOD) in the liver tissue. Pterostilbene treatment significantly (p < 0.0001) reduced TNF-α and IL-6 levels. Pterostilbene markedly improved (p < 0.05-0.001) motor activity and showed analgesic effect in arthritic rats at 25 and 50 mg/kg as compared to disease control rats. Furthermore, it notably (p < 0.05-0.0001) increased SOD activity, nitrites, noradrenaline and serotonin levels in the sciatic nerve of arthritic rats. Treatment with pterostilbene also ameliorated the CFA-induced pannus formation, cartilage damage and synovial hyperplasia in the arthritic rat paws. It is determined from the current study that pterostilbene was effective in reducing CFA-induced arthritis in rats through amelioration of oxidative stress and inflammatory mediators. It was also effective to treat peripheral neuropathy through modulation of oxidative stress and neurotransmitters in sciatic nerves.
Subject(s)
Arthritis, Experimental , Peripheral Nervous System Diseases , Stilbenes , Animals , Rats , Analgesics/pharmacology , Arthritis, Experimental/drug therapy , Arthritis, Experimental/chemically induced , Cytokines , Freund's Adjuvant , Neurotransmitter Agents/pharmacology , Nitrites , Oxidative Stress , Rats, Wistar , Stilbenes/pharmacology , Superoxide DismutaseABSTRACT
While lung cancer poses a serious threat to human health, non-small-cell lung cancer (NSCLC) is the most common type of lung cancer. Danggui Buxue Decoction (DBD) is a classical traditional antitumor medicine commonly used in China. However, the potential mechanism of DBD against NSCLC has not yet been expounded. Therefore, this study clarified the potential molecular mechanism and key targets of DBD in NSCLC treatment through several technological advances, such as network pharmacology, molecular docking, and bioinformatics. Firstly, the relative active ingredients and key DBD targets were analyzed, and subsequently, a drug-ingredient-target-disease network diagram was constructed for NSCLC treatment with DBD, resulting in the identification of five main active ingredients and ten core targets according to the enrichment degree. The enrichment analysis revealed that DBD can achieve the purpose of treating NSCLC through the AGE-RAGE signaling pathway in diabetic complications. Secondly, the molecular docking approach predicted that quercetin and hederagenin have the best working mechanisms with PDE3A and PTGS1, while the survival analysis results depicted that high PDE3A gene expression has a relatively poor prognosis for NSCLC patients (p < 0.05). Additionally, PDE3A is mainly distributed in the LU65 cell line that originated from Asian population. In summary, our study results showed that DBD can treat NSCLC through the synergistic correlation between multiple ingredients, multiple targets, and multiple pathways, thus effectively improving NSCLC prognosis. This study not only reflected the medicinal value of DBD but also provided a solid structural basis for future new drug developments and targeted therapies.
Subject(s)
Antineoplastic Agents/pharmacology , Carcinoma, Non-Small-Cell Lung/drug therapy , Computational Biology , Drugs, Chinese Herbal/pharmacology , Lung Neoplasms/drug therapy , Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/mortality , Cell Line, Tumor , Drug Interactions , Drugs, Chinese Herbal/therapeutic use , Humans , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Lung Neoplasms/mortality , Molecular Docking Simulation , Prognosis , Survival AnalysisABSTRACT
In this article, formulation studies for terbinafine hydrochloride nanoemulsions, prepared by high-energy ultrasonication technique, are described. Pseudo-ternary phase diagram was constructed in order to find out the optimal ratios of oil and surfactant/co-solvent mixture for nanoemulsion production. Clove and olive oils were selected as oil phase. Based on the droplet size evaluation, maximum nanoemulsion region were determined for formulation development. Further characterization included polydispersity index (PDI), zeta potential, Fourier transform infrared (FT-IR) spectroscopy, morphology, pH, viscosity, refractive index, ex vivo skin permeation, skin irritation, and histopathological examination. Droplet sizes of optimized formulations were in colloidal range. PDI values below 0.35 indicated considerably homogeneous nanoemulsions. Zeta potential values were from 13.2 to 18.1 mV indicating good stability, which was also confirmed by dispersion stability studies. Ex vivo permeation studies revealed almost total skin permeation of terbinafine hydrochloride from the nanoemulsions (96-98%) in 6 hours whereas commercial product reached only 57% permeation at the same time. Maximum drug amounts were seen in epidermis and dermis layers. Skin irritation and histopathological examination demonstrated dermatologically safe formulations. In conclusion, olive oil and clove oil-based nanoemulsion systems have potential to serve as promising carriers for topical terbinafine hydrochloride delivery.
Subject(s)
Antifungal Agents/pharmacology , Clove Oil/chemistry , Nanoparticles/chemistry , Olive Oil/chemistry , Terbinafine/pharmacology , Administration, Topical , Animals , Antifungal Agents/administration & dosage , Antifungal Agents/adverse effects , Antifungal Agents/pharmacokinetics , Chemistry, Pharmaceutical , Drug Carriers , Emulsions/chemistry , Hydrogen-Ion Concentration , Mice , Particle Size , Skin Absorption/drug effects , Solubility , Surface Properties , Terbinafine/administration & dosage , Terbinafine/adverse effects , Terbinafine/pharmacokinetics , ViscosityABSTRACT
BACKGROUND: Bistorta amplexicaulis of the genus Polygonum (Polygonaceae) has been reported for its antioxidant and anticancer activities. However, the low cellular uptake of the compounds in its extract limits its therapeutic application. OBJECTIVES: The present study aimed at developing a nanoliposomal carrier system for B. amplexicaulis extracts for improved cellular uptake, thus resulting in enhanced anticancer activity. METHODS: Ultra Pressure Liquid Chromatography (UPLC) was used to identify major compounds in the plant extract. Nanoliposomes (NLs) were prepared by employing a thin-film rehydration method using DPPC, PEG2000DSPE and cholesterol, followed by characterization through several parameters. In vitro screening was performed against breast cancer cell line (MCF-7) and Hepatocellular carcinoma cell line (HepG-2) using MTT-assay. Raw extract and nanoliposomes were tested on Human Umbilical Vein Endothelial Cells (HUVEC). Moreover, molecular docking was performed to validate the data obtained through wet lab. RESULTS: The UHPLC method identified gallic acid, caffeic acid, chlorogenic acid and catechin as the major compounds in the extract. The NLs with a size ranging between 140-155 nm, zeta potential -16.9 to -19.8 mV and good polydispersity index of < 0.1 were prepared, with a high encapsulation efficiency of 81%. The MTT assay showed significantly (p > 0.05) high uptake and cytotoxicity of NLs as compared to the plant extract. Moreover, reduced toxicity against HUVEC cells was observed as compared to the extract. Also, the docking of identified compounds suggested a favorable interaction with the SH2 domain of both STAT3 and STAT5. CONCLUSION: Overall, the results suggest NLs as a potential platform that could be developed for the improved intracellular delivery of plant extract, thus increasing the therapeutic outcomes.
Subject(s)
Carcinoma, Hepatocellular , Polygonaceae , Carcinoma, Hepatocellular/drug therapy , Endothelial Cells , Humans , Liposomes , MCF-7 Cells , Molecular Docking Simulation , Plant Extracts/pharmacologyABSTRACT
BACKGROUND: Euphorbia helioscopia, conventionally known as sun spurge, has been used as a traditional medicine to treat different diseases owing to its reported antitumor, antiviral and antioxidant activities. METHODS: The current research was formulated to assess the in-vitro antioxidant and antidiabetic ability of Euphorbia helioscopia subsequent to the phytochemical analysis of its various extracts. For this purpose, methanol, ethanol and aqueous extracts were prepared using the whole dried plant. Phytochemical analysis of the extracts was done to evaluate the total flavonoid components (TFC) and total phenolic components (TPC) in the extracts. A total of seven phenolic and three flavonoid contents were documented and quantified using HPLC. Antioxidant values were found by DPPHâ assay, FRAP and ABTS assays. The antidiabetic potential of the extracts was evaluated by measuring the inhibition ability of the activity of enzymes α amylase and α glucosidase. RESULTS: After analyzing statistically, the results showed that methanolic extract possesses the highest TFC and TPC values while aqueous extract encompassed the lowest level of these contents. Invitro results showed that methanolic extract of the Euphorbia helioscopia has the maximum antioxidant capability since it showed the highest scavenging ability towards the DPPHâ (IC50 value = 0.06 ± 0.02 mg/ml), FRAP (758.9 ± 25.1 µMFe+ 2/g), and ABTS (689 ± 25.94 µMTEq/g) due to the presence of high TPC (24.77 ± 0.35 mgGAEq/g) and TFC (17.95 ± 0.32 mgQEq/g) values. Antidiabetic activity in terms of inhibition potential of α amylase and α glucosidase activity was also observed maximum in methanolic extract having lowest IC50 value (0.4 ± 0.01 mg/ml and 0.45 ± 0.01 mg/ml respectively) and minimum in the aqueous extract (IC50 value = 0.57 ± 0.02 mg/ml and 0.76 ± 0.1 mg/ml respectively). CONCLUSION: The experiment outcomes have shown that Euphorbia helioscopia extracts used in the current study contain antioxidant and antidiabetic activities; however, it is highest in its methanolic extract. The presence of the same trend towards the highest antidiabetic activity of the methanolic extract in terms of maximum inhibiting activity of α amylase and α glucosidase enzymes suggests a close association of TFC and TPC in minimizing diabetes.
Subject(s)
Antioxidants , Euphorbia/chemistry , Hypoglycemic Agents , Plant Extracts , Antioxidants/chemistry , Antioxidants/pharmacology , Biphenyl Compounds/chemistry , Flavonoids/analysis , Flavonoids/chemistry , Flavonoids/pharmacology , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Methanol , Phenols/analysis , Phenols/chemistry , Phenols/pharmacology , Phytochemicals/analysis , Phytochemicals/chemistry , Phytochemicals/pharmacology , Picrates/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , alpha-Amylases/metabolism , alpha-Glucosidases/metabolismABSTRACT
OBJECTIVES: This study was aimed to evaluate the toxicity profile of hydrogels of plant-derived mucilage from Aloe vera and Artemisia vulgaris used for various drug delivery applications, yet no such toxicity study has been reported for the toxicity evaluation of 3 D structures. New Drug carriers should be harmless for drug delivery applications. METHODS: Acute and sub-acute (repeated dose) oral toxicity studies were conducted following OECD 407 and 425 guidelines. In vitro toxicity through hemolysis and MTT assay were checked against RBC's and human macrophages respectively. RESULTS: The hemolysis and MTT assay showed good compatibility of hydrogels with blood components. Mutagenicity testing showed no genotoxic effects of hydrogels. In vivo toxicity evaluation was done in female albino rats and rabbits. General behavior, adverse effects, clinical signs and symptoms, and mortality were recorded for 14 days post-treatment which showed no significant (p < 005) abnormality. Hematological and biochemical parameters including LFTs and RFTs appeared to be normal with slight variations in the treated groups. The normal architecture of kidney, liver, heart and intestine was evident upon histopathological analyses. CONCLUSION: Hence, the results suggested that the 3 D structure of Aloe vera and Artemisia vulgaris based hydrogels are safe upon ingestion and can be used for drug delivery science being cheap, natural and biocompatible.
Subject(s)
Aloe , Artemisia , Aloe/chemistry , Animals , Biocompatible Materials/toxicity , Female , Hemolysis , Hydrogels/toxicity , Plant Extracts/toxicity , Rabbits , RatsABSTRACT
BACKGROUND: The incidence of multidrug-resistant (MDR), extreme drug resistant (XDR), and pan drug-resistant (PDR) Acinetobacter are increasing throughout the world. The therapeutic management and control of Acinetobacter are difficult due to the emergence of drug resistance and its enduring capacity to survive in the environment. The present study was designed to appraise the efficacy of Polymyxins and Tigecycline against multidrugresistant Acinetobacter isolates from surgical and burn wounds. METHODS: During the study, the specimens were collected from various types of wounds from inpatients and outpatients of the tertiary care hospitals of Lahore, Pakistan in 2017 and 2018. The bacterial pathogens were isolated and identified using standard microbiological procedures and molecular confirmation of Acinetobacter species was examined by PCR using specific primers. The antibiotic susceptibility profiling of Acinetobacter isolates was studied against 18 antibiotics as per Clinical and Laboratory Standards Institute (CLSI) guidelines. RESULTS: The Acinetobacter isolates demonstrated extreme resistance especially to ampicillin/sulbactam, piperacillin/tazobactam, cephalosporins, carbapenems, fluoroquinolones, and aminoglycosides. However, the colistin, polymyxin, and tigecycline remained the most effective antimicrobial agents against Acinetobacter isolates. CONCLUSIONS: The results highlight the extent of drug resistance and therapeutic potential of Polymyxins and Tigecycline for wound infections caused by MDR and XDR Acinetobacter species. The wiser use of antimicrobials, incessant surveillance of antimicrobial resistance, and stringent adherence to infection control guidelines are critical to reducing major outbreaks in the future.
Subject(s)
Acinetobacter/drug effects , Drug Resistance, Multiple, Bacterial , Polymyxins/pharmacology , Tigecycline/pharmacology , Wound Infection/microbiology , Acinetobacter Infections/microbiology , Anti-Bacterial Agents/pharmacology , Humans , Microbial Sensitivity Tests , PakistanABSTRACT
A facile, green synthesis of selenium doped zinc oxide nano-antibiotic (Se-ZnO-NAB) using the Curcuma longa extract is reported to combat the increased emergence of methicillin-resistant Staphylococcus aureus (MRSA). The developed Se-ZnO-NAB were characterized for their physicochemical parameters and extensively evaluated for their toxicological potential in an animal model. The prepared Se-ZnO-NABs were characterized via Fourier transformed infrared spectroscopy to get functional insight into their surface chemistry, scanning electron microscopy revealing the polyhedral morphology with a size range of 36 ± 16 nm, having -28.9 ± 6.42 mV zeta potential, and inductively coupled plasma optical emission spectrometry confirming the amount of Se and Zn to be 14.43 and 71.70 mg L-1 respectively. Moreover, the antibacterial activity against MRSA showed significantly low minimum inhibitory concentration at 6.2 µg mL-1 when compared against antibiotics. Also, total protein content and reactive oxygen species production in MRSA, under the stressed environment of Se-ZnO-NAB, significantly (p < 0.05) decreased compared to the negative control. Moreover, the results of acute oral toxicity in rats showed moderate variations in blood biochemistry and histopathology of vital organs. The teratogenicity and fetal evaluations also revealed some signs of toxicity along with changes in biochemical parameters. The overall outcomes suggest that Se-ZnO-NAB can be of significant importance for combating multi-drug resistance but must be used with extreme caution, particularly in pregnancy, as moderate toxicity was observed at a toxic dose of 2000 mg kg-1.
Subject(s)
Anti-Bacterial Agents/pharmacology , Metal Nanoparticles/chemistry , Plant Extracts/pharmacology , Animals , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/radiation effects , Anti-Bacterial Agents/toxicity , Curcuma/chemistry , Female , Green Chemistry Technology , Light , Metal Nanoparticles/radiation effects , Metal Nanoparticles/toxicity , Methicillin-Resistant Staphylococcus aureus/drug effects , Microbial Sensitivity Tests , Plant Extracts/chemistry , Plant Extracts/toxicity , Pregnancy , Rats, Wistar , Selenium/chemistry , Selenium/radiation effects , Selenium/toxicity , Teratogens/chemical synthesis , Teratogens/pharmacology , Teratogens/radiation effects , Teratogens/toxicity , Zinc Oxide/chemistry , Zinc Oxide/radiation effects , Zinc Oxide/toxicityABSTRACT
Increased use of vancomycin for treating infections, and the associated risk of causing nephrotoxicity lead to the present study. The antioxidant and anti-apoptotic potential of Silybum marianum is used along with vancomycin to reduce adverse effects on the kidney. Vero cells (monkey kidney cells) and mice were used to test S. marianum extract on vancomycin induced nephrotoxicity. Vero cells were treated with different concentrations of vancomycin and S. marianum for 24 h for determination of cytotoxic potential and mRNA levels of apoptotic genes p53 , p21, and cyt-c were measured. For in-vivo studies mice were divided into five groups; G1 control (untreated), G2 vehicle (olive oil), G3 vancomycin treated (300 mg/kg body weight), G4 (S. marianum; 400 mg/kg bodyweight and vancomycin 300 mg/kg bodyweight simultaneously) and G5 (S. marianum 400 mg/kg bodyweight and vancomycin 300 mg/kg bodyweight treatment started after day 4 of S. marianum treatment). After 10 days histopathological analysis of mice kidneys was performed, serum urea and creatinine were analysed and mRNA expression of p53 , p21, and cyt-c was evaluated. Expression of p53, p21, and cyt-c in Vero cells was elevated in response to vancomycin treatment, whereas after S. marianum administration expression of these genes reduced. Vancomycin showed apoptosis in cells at the concentration of 6 mg/ml (LC50). Urea and creatinine levels in mice were increased in response to vancomycin administration and kidney histology showed an abnormality in functional units. The apoptotic cells were very visible in kidney structure in vancomycin treated group. These symptoms were however relieved in groups where treatment of S. marianum extract was given. mRNA expression of p53 , p21, and cyt-c also reduced in S. marianum treated groups of mice. S. marianum extract has protective effects against renal damage from vancomycin induced oxidative stress and relieves symptoms may be by downregulating apoptotic genes.
Subject(s)
Kidney/drug effects , Silybum marianum/metabolism , Vancomycin/toxicity , Animals , Antioxidants/metabolism , Apoptosis/drug effects , Chlorocebus aethiops , Flavonoids/pharmacology , Kidney/metabolism , Kidney/pathology , Male , Mice , Oncogene Protein p21(ras)/metabolism , Oxidative Stress/drug effects , Plant Extracts/pharmacology , Renal Insufficiency/pathology , Tumor Suppressor Protein p53/metabolism , Vancomycin/pharmacology , Vero CellsABSTRACT
Consumption of foods rich in dietary fiber has attracted considerable attention for lowering blood cholesterol and triglycerides through attenuation of gut microbiome. Diets rich in fiber may provide substrates for microbes to digest and proliferate. In response, products of microbial digestion enter systemic circulation and support host energy homeostasis. In the present study, rats with hypercholesterolemia (HC) were supplemented with probiotics (PB) and Agaricus bisporus mushroom to examine the antidyslipidemia effects. Forty adult rats were divided into five treatment groups. The rats in the control group were fed only a chow maintenance diet (CON; n = 8), whereas an atherogenic diet (chow diet supplemented with 1.5% cholesterol and 0.5% cholic acid) was offered to the remaining rats to induce hypercholesterolemia (HC group; n = 32). Rats developed HC following a 24-day continuous supplementation with the atherogenic diet. From day 25 onward, the HC group was further divided into HC-CON, HC-PB (supplemented with PB at 1 mg/rat/day), HC-AB (supplemented with A. bisporus at 5% of diet), and HC-AB.PB (supplemented with both A. bisporus and PB). After 6 weeks of supplementation, rats were killed to collect blood to determine serum lipid profile, oxidative stress, and for metagenomics analysis of colon contents. Results showed that all supplementations corrected HC-induced oxidative stress. Furthermore, A. bisporus supplementation corrected HC-induced dyslipidemia (P ≤ .05). Blautia and Bifidobacterium were the most dominant bacterial genera in HC-AB and HC-PB groups, respectively. Phylum Firmicutes and class Clostridia predominantly occupied the gut microbiome in all groups. However, no significant differences were observed in microbiome diversity and clustering patterns among study groups. In conclusion, supplementation of A. bisporus mushroom and probiotics can lower oxidative stress and dyslipidemia with partial effects on the phylogenetic makeup in the gut microbiome.
Subject(s)
Agaricus , Dietary Supplements , Dyslipidemias/therapy , Gastrointestinal Microbiome , Hypercholesterolemia/therapy , Probiotics/therapeutic use , Animals , Bacteria/classification , Bacteria/isolation & purification , Cholesterol/blood , Diet, High-Fat , Female , Male , Metagenomics , Oxidative Stress , Phylogeny , Rats , Rats, Wistar , Triglycerides/bloodABSTRACT
Banana peels (BP), an under-utilized waste material, was studied for the production of xylanase and pectinase by Aspergillus fumigates MS16. The factors affecting the co-production of both the enzymes were separately studied for their influence under submerged (Smf) and solid-state fermentation (SSF) of BP. The strain was cultivated in the presence of mineral salt (MS) solution containing BP powder as a sole source of carbon and physical and nutritional factors varied to observe the change in the enzyme titers. The data revealed that the MS-based medium was appropriate for the production of both the enzymes; therefore, in subsequent experiments, the same medium was used. A temperature of 30-35°C was found better for the production of the two enzymes under Smf; however, the titers of pectinase dropped significantly at 40°C. Contrarily, xylanase production was inhibited at 40°C under SSF but not under Smf. Whereas, supplementation of xylan or pectin to BP induced the production of xylanase and pectinase, respectively. Lowering the pH value favored the production of both the enzymes under Smf; however, the production of pectinase improved significantly when a higher concentration of BP (1%) was used compared to the concentration (0.25%) required for the production of xylanase. Interestingly, the enzyme preparation obtained under SSF exhibited optimal activities of both the enzymes at higher temperatures when compared to those obtained under Smf. The data indicated that the physiology of the fungus differed greatly when the cultivation pattern varied from Smf to SSF and, hence, the enzymes produced were characteristically distinct.Banana peels (BP), an under-utilized waste material, was studied for the production of xylanase and pectinase by Aspergillus fumigates MS16. The factors affecting the co-production of both the enzymes were separately studied for their influence under submerged (Smf) and solid-state fermentation (SSF) of BP. The strain was cultivated in the presence of mineral salt (MS) solution containing BP powder as a sole source of carbon and physical and nutritional factors varied to observe the change in the enzyme titers. The data revealed that the MS-based medium was appropriate for the production of both the enzymes; therefore, in subsequent experiments, the same medium was used. A temperature of 3035°C was found better for the production of the two enzymes under Smf; however, the titers of pectinase dropped significantly at 40°C. Contrarily, xylanase production was inhibited at 40°C under SSF but not under Smf. Whereas, supplementation of xylan or pectin to BP induced the production of xylanase and pectinase, respectively. Lowering the pH value favored the production of both the enzymes under Smf; however, the production of pectinase improved significantly when a higher concentration of BP (1%) was used compared to the concentration (0.25%) required for the production of xylanase. Interestingly, the enzyme preparation obtained under SSF exhibited optimal activities of both the enzymes at higher temperatures when compared to those obtained under Smf. The data indicated that the physiology of the fungus differed greatly when the cultivation pattern varied from Smf to SSF and, hence, the enzymes produced were characteristically distinct.
Subject(s)
Aspergillus fumigatus/enzymology , Culture Media/chemistry , Endo-1,4-beta Xylanases/biosynthesis , Musa/chemistry , Polygalacturonase/biosynthesis , Fermentation , Hot TemperatureABSTRACT
This study describes the fabrication of chemically crosslinked pectin-based LA-co-MAA hydrogels through free radical polymerization technique for the colonic delivery of oxaliplatin. Methylene bisacrylamide was used as a crosslinking agent and ammonium persulfate as an initiator. The successful fabrication and drug loading were confirmed through Fourier transform infrared spectroscopy (FTIR). The thermal investigations through differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) suggested the higher thermal stability of the unloaded and OXP-loaded formulations as compared to the raw materials. X-ray diffraction (XRD) analysis showed a decrease in crystallinity after crosslinking. The swelling, drug loading, and drug release were increased with an increase in the concentration of pectin and lactic acid (LA) while methacrylic acid (MAA) displayed an inverse behavior. The in-vitro biodegradability was evaluated against lysozyme and collagenase. The results showed that the hydrogels were stable against blank PBS as compared to lysozyme and collagenase. MTT-assay proved that the blank hydrogels were cytocompatible while free OXP and OXP-loaded hydrogels displayed dose-dependent effect against Vero, MCF-7, and HCT-116 cell lines. The oral tolerability study in rabbits confirmed that the hydrogel dispersion was well-tolerable up to 3650â¯mg/kg of body weight without causing any histopathological or hematological changes when compared with the control group.
Subject(s)
Drug Delivery Systems , Hydrogels/administration & dosage , Lactic Acid/administration & dosage , Methacrylates/administration & dosage , Oxaliplatin/administration & dosage , Pectins/administration & dosage , Animals , Biocompatible Materials/administration & dosage , Biocompatible Materials/chemistry , Cell Survival/drug effects , Chlorocebus aethiops , Colon/metabolism , Female , HCT116 Cells , Humans , Hydrogels/chemistry , Hydrogen-Ion Concentration , Lactic Acid/chemistry , MCF-7 Cells , Male , Methacrylates/chemistry , Oxaliplatin/chemistry , Pectins/chemistry , Rabbits , Vero CellsABSTRACT
The aim of this study was to develop and characterize a pH sensitive, biodegradable, interpenetrating polymeric network (IPNs) for colon specific delivery of sulfasalazine in ulcerative colitis. It also entailed in-vitro and in-vivo evaluations to optimize colon targeting efficiency, improve drug accumulation at the target site, and ameliorate the off-target effects of chemotherapy. Pectin was grafted with polyethylene glycol (PEG) and methacrylic acid (MAA) by free radical polymerization. Fourier transformed infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), energy dispersion X-ray (EDX) and powder X-ray diffraction (XRD) results confirmed the development of stable pectin-g-(PEG-co-MAA) hydrogels. The swelling and release studies exhibited that the hydrogels were capable of releasing drug specifically at colonic pH (pHâ¯7.4). The toxicological potential of polymers, monomers and hydrogel was investigated using the Balb/c animal model, that confirmed the safety of the hydrogels. In vitro degradation of the hydrogel was evaluated using pectinase enzyme in various simulated fluids and the results showed that the hydrogels were susceptible to biodegradation by the natural microflora of the colon. In-vivo study was performed using Dextran sulphate sodium (DSS) rat model proved the hydrogels to be effective in the management of UC.
Subject(s)
Colitis, Ulcerative/drug therapy , Drug Carriers/chemistry , Drug Carriers/metabolism , Hydrogels/chemistry , Hydrogels/metabolism , Animals , Colitis, Ulcerative/metabolism , Colon/metabolism , Delayed-Action Preparations , Drug Liberation , Female , Hydrogen-Ion Concentration , Male , Methacrylates/chemistry , Mice , Mice, Inbred BALB C , Pectins/chemistry , Polyethylene Glycols/chemistry , Sulfasalazine/chemistry , Sulfasalazine/therapeutic useABSTRACT
The gut microbiota has an important effect on poultry health and production. The aim of this study was to evaluate the effect of Colombian oregano (COO), Lippia origanoides Kunth, essential oil supplementation on broiler chicken performance and their cecal bacterial microbiome by 16S-based sequencing. Essential oil was extracted by steam distillation and analyzed by Gas chromatography/mass spectrometry. Two COO levels in feed, 0 ppm control (C) and 100 ppm (O), were evaluated in 2 groups of broilers either unchallenged (U) or challenged (E) with a viable attenuated Eimeria (coccidia) oocyte vaccine. Four treatments, UC, UO, EC, and EO, were distributed among 720 one-day-old male Ross broilers randomly placed in 24 pens. Cecal contents DNA was extracted and pyrosequencing was performed following a standard procedure. Pyrosequencing data were processed, and sequence reads were phylogenetically classified. Similarity of membership and structure in the communities were calculated. At the end of the study, the greatest COO effect was found in coccidia-challenged broilers, with an OE body weight of 1,889 ± 52.4 g with respect to 1,799 ± 36.2 g for CE (P < 0.01). Broiler cecal samples were consistent in that phylum Firmicutes and class Clostridia were highly prevalent; COO had no effect on these taxa levels between the 4 treatments (P > 0.05). A positive correlation (P < 0.01) was observed between the Firmicutes:Bacteriodetes phyla ratio against body weight at 35 D of age. This study provided both positive and negative correlations between broiler body weight against some bacterial groups identified, offering perspectives regarding bacterial groups and their impact on host health and metabolism. Lippia origanoides Kunth high thymol content showed a beneficial effect on body weight and the feed conversion ratio in broilers under coccidia challenge.
Subject(s)
Chickens , Coccidiosis/veterinary , Eimeria/physiology , Gastrointestinal Microbiome/drug effects , Lippia/chemistry , Oils, Volatile/pharmacology , Poultry Diseases/parasitology , Animal Feed/analysis , Animals , Cecum/microbiology , Coccidiosis/parasitology , Colombia , Diet/veterinary , Dietary Supplements/analysis , Male , Random AllocationABSTRACT
Recent interest in diet-induced modulation of the gut microbiome has led to research on the impact that dietary fibers can have on host health. Lentinus edodes mushroom-derived fibers may act as an appropriate substrate for gut microbe digestion and metabolism. The metabolites that gut microbes excrete can modulate host energy balance, gut absorption, appetite, and lipid metabolism. In the present study, we explored the dynamics of the gut microbiome of hypercholesterolemic rats supplemented with L. edodes. Wistar rats were offered a chow maintenance diet (CMD; CON group) or the same CMD ration with cholesterol (1.5% w/w) and cholic acid (0.5% w/w) added to induce hypercholesterolemia (day 1 to day 24). Hypercholesterolemic rats were subsequently offered either the same cholesterol-cholic acid diet (HC-CON group) or were supplemented with L. edodes (5% w/w; LE group) for 42 days (day 25 to day 66). At the end of the experiment, serum triglycerides, total cholesterol, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol concentrations were determined. Colon digesta were subjected to DNA extraction and subsequent 16S rRNA gene sequencing. Raw sequences were quality filtered and statistically analyzed using QIIME and LEfSe tools. Triglyceride concentrations were lower (P = 0.002) in the LE group than in the CON and HC-CON groups. Total cholesterol and LDL cholesterol concentrations were slightly decreased, whereas HDL cholesterol concentrations were increased by L. edodes supplementation compared with the HC-CON group. The gut microbiome of the LE group had higher species richness characterized by increased abundance of Clostridium and Bacteroides spp. Linear discriminant analysis identified bacterial clades that were statistically different among treatment groups. In conclusion, manipulation of gut microbiota through the administration of L. edodes could manage dyslipidemia.