Displaying all 11 publications

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  1. Kanakal MM, Abbas SA, Khan A, Sultana S, Fatima H, Tabasssum R, et al.
    PMID: 39082166 DOI: 10.2174/0118715230309053240718122527
    INTRODUCTION: This research aims to create a gel formulation of Brassica juncea leaf extract and assess its anti-inflammatory properties using an in silico study. The anti-inflammatory activity has been compared with Diclofenac molecules in PDB id: 4Z69. Further, the Absorption, Distribution, Metabolism, Excretion, and Toxicity analysis has been performed to ensure the therapeutic potential and safety of the drug development process. The Quality by Design tool has been applied to optimize formulation development.

    METHODS: The extracted gel is characterized by performing Fourier transformer infrared, zeta potential, particle size, Scanning Electron Microscope, and entrapment efficiency. Further, the formulation is evaluated by examining its viscosity, spreadability, and pH measurement. An In vitro study of all nine extract suspensions was conducted to determine the drug contents at 276 nm.

    RESULTS: The optimized suspension has shown the maximum percentage of drug release (82%) in 10 hours of study. Animal study for anti-inflammatory activity was performed, and results of all five groups of animals compared the % inhibition of paw edema at three hours; gel (56.70%), standard (47.86%), and (39.72%) were found.

    CONCLUSION: The research could conclude that the anti-inflammatory activity of gel formulation is high compared to extract, and a molecular docking study validates the anti-inflammatory therapeutic effects. ADMET analysis ensures the therapeutic effects and their safety.

    Matched MeSH terms: Diclofenac/pharmacology
  2. Moorthy M, Fakurazi S, Ithnin H
    Pak J Biol Sci, 2008 Aug 01;11(15):1901-8.
    PMID: 18983031
    This study was conducted to identify and to compare the mitochondrial morphological alterations in livers of rats treated with various doses of diclofenac and ibuprofen. Hundred and forty-four male Sprague Dawley rats were dosed with 3, 5 and 10 mg kg(-1) diclofenac and ibuprofen in saline via intraperitoneal injection for 15 days. The control group was administered with saline in a similar manner. Four rats were euthanised every 3 days until day 15. While 200 mg kg(-1) diclofenac and ibuprofen-treated rats (n = 4) were euthanized 10 h posttreatment. The livers were removed, cleaned and a section across the right lobe was taken and fixed in 4% (v/v) glutaraldehyde for electron microscopy analysis and the remaining samples were kept at -80 degrees C for Western blot analysis. Five milligram per kilogram and 10 mg kg(-1) diclofenac-administered rats for 15 days revealed the presence of enlarged mitochondria, irregular and ruptured mitochondrial membranes. While rats administered with 10 mg kg(-1) ibuprofen also showed the presence of mitochondria with irregular membrane structure and ruptured membranes. Western blotting analysis of mitochondrial fractions revealed the expression of cytochrome c in all samples and complete absence of cytochrome c expression in the cytosolic fraction of all samples after day 15. Analysis in 200 mg kg(-1) diclofenac and ibuprofen-treated groups, revealed expression of cytochrome c in both mitochondrial and cytosolic fractions. This observation indicates that both diclofenac and ibuprofen may alter the morphology of mitochondria, leading to cytochrome c release into the cytosol. Further studies needs to be conducted to investigate on the activity of the mitochondria following both treatments.
    Matched MeSH terms: Diclofenac/pharmacology*
  3. Goh JZ, Tang SN, Chiong HS, Yong YK, Zuraini A, Hakim MN
    Int J Nanomedicine, 2015;10:297-303.
    PMID: 25678786 DOI: 10.2147/IJN.S75545
    Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory, antinociceptive, and antipyretic activities. Liposomes have been shown to improve the therapeutic efficacy of encapsulated drugs. The present study was conducted to compare the antinociceptive properties between liposome-encapsulated and free-form diclofenac in vivo via different nociceptive assay models. Liposome-encapsulated diclofenac was prepared using the commercialized proliposome method. Antinociceptive effects of liposome-encapsulated and free-form diclofenac were evaluated using formalin test, acetic acid-induced abdominal writhing test, Randall-Selitto paw pressure test, and plantar test. The results of the writhing test showed a significant reduction of abdominal constriction in all treatment groups in a dose-dependent manner. The 20 mg/kg liposome-encapsulated diclofenac demonstrated the highest antinociceptive effect at 78.97% compared with 55.89% in the free-form group at equivalent dosage. Both liposome-encapsulated and free-form diclofenac produced significant results in the late phase of formalin assay at a dose of 20 mg/kg, with antinociception percentages of 78.84% and 60.71%, respectively. Significant results of antinociception were also observed in both hyperalgesia assays. For Randall-Sellito assay, the highest antinociception effect of 71.38% was achieved with 20 mg/kg liposome-encapsulated diclofenac, while the lowest antinociceptive effect of 17.32% was recorded with 0 mg/kg liposome formulation, whereas in the plantar test, the highest antinociceptive effect was achieved at 56.7% with 20 mg/kg liposome-encapsulated diclofenac, and the lowest effect was shown with 0 mg/kg liposome formulation of 8.89%. The present study suggests that liposome-encapsulated diclofenac exhibits higher antinociceptive efficacy in a dose-dependent manner in comparison with free-form diclofenac.
    Matched MeSH terms: Diclofenac/pharmacology*
  4. Chan EWL, Yee ZY, Raja I, Yap JKY
    J Glob Antimicrob Resist, 2017 09;10:70-74.
    PMID: 28673701 DOI: 10.1016/j.jgar.2017.03.012
    OBJECTIVES: Currently, only a few antibiotics are available to treat methicillin-resistant Staphylococcus aureus (MRSA). One alternative approach includes adjuvants to antibiotic therapy. Non-steroidal anti-inflammatory drugs (NSAIDs) are non-antibiotic drugs reported to exhibit antibacterial activity. The objective of this study was to investigate the interaction between NSAIDs with selected antibiotics (cefuroxime and chloramphenicol) against strains of S. aureus.

    METHODS: The antibacterial activity of four NSAIDs (aspirin, ibuprofen, diclofenac and mefenamic acid) were tested against ten pathogenic bacterial strains using the microdilution broth method. The interaction between NSAIDs and antibiotics (cefuroxime/chloramphenicol) was estimated by calculating the fractional inhibitory concentration (FICI) of the combination.

    RESULTS: Aspirin, ibuprofen and diclofenac exhibited antibacterial activity against the selected pathogenic bacteria. The interaction between ibuprofen/aspirin with cefuroxime was demonstrated to be synergistic against methicillin-sensitive S. aureus (MSSA) and the MRSA reference strain, whereas for MRSA clinical strains additive effects were observed for both NSAIDs and cefuroxime combinations. The combination of chloramphenicol with ibuprofen/aspirin was synergistic against all of the tested MRSA strains and displayed an additive effect against MSSA. A 4-8192-fold reduction in the cefuroxime minimum inhibitory concentration (MIC) and a 4-64-fold reduction of the chloramphenicol MIC were documented.

    CONCLUSIONS: Overall, the NSAIDs ibuprofen and aspirin showed antibacterial activity against strains of S. aureus. Although individually less potent than common antibiotics, these NSAIDs are synergistic in action with cefuroxime and chloramphenicol and could potentially be used as adjuvants in combating multidrug-resistant MRSA.

    Matched MeSH terms: Diclofenac/pharmacology
  5. Chew CC, Ng S, Chee YL, Koo TW, Liew MH, Chee EL, et al.
    Invest New Drugs, 2017 08;35(4):399-411.
    PMID: 28285369 DOI: 10.1007/s10637-017-0447-y
    Coadministration of diclofenac and sunitinib, tyrosine kinase inhibitor, led to sex-divergent pharmacokinetic drug-drug interaction outcomes. Male and female mice were administered 60 mg/kg PO sunitinib alone (control groups) or with 30 mg/kg PO diclofenac. Sunitinib concentration in plasma, brain, kidney and liver were determined by HPLC and non-compartmental pharmacokinetic parameters calculated. In male mice, diclofenac decreased AUC0→∞ 38% in plasma (p diclofenac increased the liver uptake efficiency in male (27%, p diclofenac with probable clinical translatability due to potential different effects in male and female patients requiring careful selection of the NSAID and advanced TDM to implement a personalized treatment.
    Matched MeSH terms: Diclofenac/pharmacology*
  6. Rahim H, Sadiq A, Khan S, Khan MA, Shah SMH, Hussain Z, et al.
    Drug Des Devel Ther, 2017;11:2443-2452.
    PMID: 28860715 DOI: 10.2147/DDDT.S140626
    This study was aimed to enhance the dissolution rate, oral bioavailability and analgesic potential of the aceclofenac (AC) in the form of nanosuspension using cost-effective simple precipitation-ultrasonication approach. The nanocrystals were produced using the optimum conditions investigated for AC. The minimum particle size (PS) and polydispersity index was found to be 112±2.01 nm and 0.165, respectively, using hydroxypropyl methylcellulose (1%, w/w), polyvinylpyrrolidone K30 (1%, w/w) and sodium lauryl sulfate (0.12%, w/w). The characterization of AC was performed using zeta sizer, scanning electron microscopy, transmission electron microscopy, powder X-ray diffraction and differential scanning calorimetry. The saturation solubility of the AC nanocrystals was substantially increased 2.6- and 4.5-fold compared to its unprocessed active pharmaceutical ingredient in stabilizer solution and unprocessed drug. Similarly, the dissolution rate of the AC nanocrystals was substantially enhanced compared to its other counterpart. The results showed that >88% of AC nanocrystals were dissolved in first 10 min compared to unprocessed AC (8.38%), microsuspension (66.65%) and its marketed tablets (17.65%). The in vivo studies of the produced stabilized nanosuspension demonstrated that the Cmax were 4.98- and 2.80-fold while area under curve from time of administration to 24 h (AUC0→24 h) were found 3.88- and 2.10-fold greater when compared with unprocessed drug and its marketed formulation, respectively. The improved antinociceptive activity of AC nanocrystals was shown at much lower doses as compared to unprocessed drug, which is purely because of nanonization which may be attributed to improved solubility and dissolution rate of AC, ultimately resulting in its faster rate of absorption.
    Matched MeSH terms: Diclofenac/pharmacology
  7. Bokhari RA, Tantowi NACA, Lau SF, Mohamed S
    Inflammopharmacology, 2018 Aug;26(4):939-949.
    PMID: 29380171 DOI: 10.1007/s10787-017-0432-2
    The effect of Orthosiphon stamineus aqueous (OSA) extract against osteoarthritis (OA) was investigated in explant cartilage culture and in postmenopausal OA rat model. Female rats were bilaterally ovariectomized (OVX). Osteoarthritis was induced after surgical recovery, by intra-articular injection of monosodium iodoacetate (MIA) into the right knee. Rats were grouped (n = 8) into: healthy sham control; non-treated OA; OA + diclofenac (positive control 5 mg/kg); and two doses OSA (150-300 mg/kg). After 4 weeks' treatment, rats were evaluated for OA-related parameters and biomarkers. The OSA reduced proteoglycan and ROS release from the cartilage explants under inflammatory (IL-1b) conditions. In the OA-induced rats' cartilages, the OSA downregulated the mRNA expressions for IL-1β, IL-6, IL-10, TNF-α, NF-κβ, NOS2, PTGS2, PTGER2, ACAN, COL2A1, MMP1, MMP13, ADAMTS4, ADAMTS5 and TIMP1, mostly dose-dependently. The OSA reduced the OA rats' serum levels for PGE2, CTX-II, TNF-α, MMP1, MMP13, PIINP, OPG, RANKL, OC and BALP, but not dose-dependently. The OSA contained polyphenols and flavonoids (tetramethoxyflavone). The OSA alleviated articular cartilage degradation, inflammation, collagenase/aggrecanase activities, to improve joint and subchondral bone structure. O. stamineus mitigated osteoarthritis by downregulating inflammation, peptidases and aggrecanases, at a dose equivalent to about 30 mg/kg for humans.
    Matched MeSH terms: Diclofenac/pharmacology
  8. Tan SY, Wong MM, Tiew AL, Choo YW, Lim SH, Ooi IH, et al.
    Cancer Chemother Pharmacol, 2016 10;78(4):709-18.
    PMID: 27495788 DOI: 10.1007/s00280-016-3120-9
    PURPOSE: Pharmacokinetic interaction of sunitinib with diclofenac, paracetamol, mefenamic acid and ibuprofen was evaluated due to their P450 mediated metabolism and OATP1B1, OATP1B3, ABCB1, ABCG2 transporters overlapping features.

    METHODS: Male and female mice were administered 6 sunitinib doses (60 mg/kg) PO every 12 h and 30 min before the last dose were administered vehicle (control groups), 250 mg/kg paracetamol, 30 mg/kg diclofenac, 50 mg/kg mefenamic acid or 30 mg/kg ibuprofen (study groups), euthanized 6 h post last administration and sunitinib plasma, liver, kidney, brain concentrations analyzed.

    RESULTS: Ibuprofen halved sunitinib plasma concentration in female mice (p Diclofenac and paracetamol female mice showed 45 and 25 % higher plasma concentrations than male mice which were 27 % lower in mefenamic acid female mice. Paracetamol increased 2.2 (p diclofenac, paracetamol, mefenamic acid and ibuprofen (p diclofenac group in male mice (liver, brain) and female mice (liver, kidney).

    CONCLUSIONS: These results portray gender-based sunitinib pharmacokinetic differences and NSAIDs selective effects on male or female mice, with potential clinical translatability.

    Matched MeSH terms: Diclofenac/pharmacology*
  9. Pabreja K, Dua K, Padi SS
    Curr Drug Deliv, 2010 Oct;7(4):324-8.
    PMID: 20695843
    The systemic use of non-steroidal anti-inflammatory drugs (NSAIDs) which act by inhibiting cyclooxygenase (COX) is severely hampered by gastric and peptic ulcers. The topical delivery of NSAIDs has the advantages of avoiding gastric and peptic ulcers and delivering the drug to the inflammation site. Importance of aceclofenac as a new generational NSAID has inspired the development of topical dosage forms. This mode of administration may help to avoid typical side effects of NSAIDs associated with oral and systemic administration such as gastric irritation, particularly diarrhoea, nausea, abdominal pain and flatulence. The aim of this study was to formulate topical gel containing 1% of aceclofenac in carbopol and PEG base and to evaluate it for analgesic and antiinflammatory activity using carrageenan-induced thermal hyperalgesia and paw oedema in rats. Carrageenan administration into the hind paw produced a significant inflammation associated with hyperalgesia as shown by decreased rat paw withdrawal latency in response to a thermal stimulus (47+/-0.5 degrees C) 4 h after carrageenan injection. Topical application of AF1 significantly attenuated the development of hypersensitivity to thermal stimulus as compared to control (P<0.05) and other formulation treated groups (P<0.05). All the AF semisolid formulations, when applied topically 2 h before carrageenan administration, inhibited paw edema in a timedependent manner with maximum percent edema inhibition of 80.33+/-2.52 achieved with AF1 after 5 h of carrageenan administration However, topical application of AF2 markedly prevented the development of edema as compared to other formulation (AF2 and AF3) treated groups (P<0.05). Among all the semisolid formulations, Carbopol gel base was found to be most suitable dermatological base for aceclofenac.
    Matched MeSH terms: Diclofenac/pharmacology
  10. Madzuki IN, Lau SF, Mohamad Shalan NAA, Mohd Ishak NI, Mohamed S
    J Biosci, 2019 Sep;44(4).
    PMID: 31502578
    Chondrosenescence (chondrocyte senescence) and subchondral bone deterioration in osteoarthritic rats were analyzed after treatment with the estrogenic herb Labisia pumila (LP) or diclofenac. Osteoarthritis (OA) was induced in bilaterally ovariectomized (OVX) rats by injecting mono-iodoacetate into the right knee joints. Rats were grouped (n = 8) into nontreated OVX+OA control, OVX+OA + diclofenac (5 mg/kg) (positive control), OVX+OA + LP leaf extract (150 and 300 mg/kg) and healthy sham control. After 8 weeks' treatment, their conditions were evaluated via serum biomarkers, knee joint histology, bone histomorphometry, protein and mRNA expressions. The LP significantly reduced cartilage erosion, femur bone surface alteration, bone loss and porosity and increased trabecular bone thickness better than diclofenac and the non-treated OA. The cartilage catabolic markers' (matrix metalloproteinase (MMP)-13, RUNX2, COL10a, ERa, CASP3 and HIF-2 alpha) mRNA expressions were down-regulated and serum bone formation marker, PINP, was increased by LP in a dose-dependent manner. The LP (containing myricetin and gallic acid) showed protection against chondrosenescence, chondrocyte death, hypoxia-induced cartilage catabolism and subchondral bone deterioration. The bone and cartilage protective effects were by suppressing proteases (collagen break-down), bone resorption and upregulating subchondral bone restoration. The cartilage ER alpha over-expression showed a strong positive correlation with MMP-13, COL10 alpha1, histological, micro-computed tomography evidence for cartilage degradation and chondrosenescence.
    Matched MeSH terms: Diclofenac/pharmacology
  11. Tantowi NACA, Mohamed S, Lau SF, Hussin P
    Daru, 2020 Dec;28(2):443-453.
    PMID: 32388789 DOI: 10.1007/s40199-020-00343-y
    BACKGROUND: Osteoporotic-osteoarthritis is an incapacitating musculoskeletal illness of the aged.

    OBJECTIVES: The anti-inflammatory and anti-catabolic actions of Diclofenac were compared with apigenin-C-glycosides rich Clinacanthus nutans (CN) leaf extract in osteoporotic-osteoarthritis rats.

    METHODS: Female Sprague Dawley rats were randomized into five groups (n = 6). Four groups were bilateral ovariectomised for osteoporosis development, and osteoarthritis were induced by intra-articular injection of monosodium iodoacetate (MIA) into the right knee joints. The Sham group was sham-operated, received saline injection and deionized drinking water. The treatment groups were orally given 200 or 400 mg extract/kg body weight or 5 mg diclofenac /kg body weight daily for 28 days. Articular cartilage and bone changes were monitored by gross and histological structures, micro-CT analysis, serum protein biomarkers, and mRNA expressions for inflammation and catabolic protease genes.

    RESULTS: HPLC analysis confirmed that apigenin-C-glycosides (shaftoside, vitexin, and isovitexin) were the major compounds in the extract. The extract significantly and dose-dependently reduced cartilage erosion, bone loss, cartilage catabolic changes, serum osteoporotic-osteoarthritis biomarkers (procollagen-type-II-N-terminal-propeptide PIINP; procollagen-type-I-N-terminal-propeptide PINP; osteocalcin), inflammation (IL-1β) and mRNA expressions for nuclear-factor-kappa-beta NF-κβ, interleukin-1-beta IL-1β, cyclooxygenase-2; and matrix-metalloproteinase-13 MMP13 activities, in osteoporotic-osteoarthritis rats comparable to Diclofenac.

    CONCLUSION: This study demonstrates that apigenin-C-glycosides at 400 mg CN extract/kg (about 0.2 mg apigenin-equivalent/kg) is comparable to diclofenac in suppressing inflammation and catabolic proteases for osteoporotic-osteoarthritis prevention. Graphical abstract.

    Matched MeSH terms: Diclofenac/pharmacology
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