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Journal of Ethnopharmacology May 2024Opuntia monacantha belongs to the cactus family Cactaceae and is also known by cochineal prickly pear, Barbary fig or drooping prickly pear. It was traditionally used to...
Opuntia monacantha: Validation of the anti-inflammatory and anti-arthritic activity of its polyphenolic rich extract in silico and in vivo via assessment of pro- and anti-inflammatory cytokines.
ETHNOPHARMACOLOGICAL RELEVANCE
Opuntia monacantha belongs to the cactus family Cactaceae and is also known by cochineal prickly pear, Barbary fig or drooping prickly pear. It was traditionally used to treat pain and inflammation. O. monacantha cladodes showed pharmacological effects such as antioxidant potential owing to the presence of certain polysaccharides, flavonoids, and phenols.
AIM OF THE STUDY
This research aimed to evaluate the anti-inflammatory as well as the anti-arthritic potential of ethanol extract of Opuntia monacantha (E-OM).
MATERIALS AND METHODS
In vivo edema in rat paw was triggered by carrageenan and used to evaluate anti-inflammatory activity, while induction of arthritis by Complete Freund's Adjuvant (CFA) rat model was done to measure anti-arthritic potential. In silico studies of the previously High performance liquid chromatography (HPLC) characterized metabolites of ethanol extract was performed by using Discovery Studio 4.5 (Accelrys Inc., San Diego, CA, USA) within active pocket of glutaminase 1 (GLS1) (PDB code: 3VP1; 2.30 Å).
RESULTS
EOM, particularly at 750 mg/kg, caused a reduction in the paw edema significantly and decreased arthritic score by 80.58% compared to the diseased group. It revealed significant results when histopathology of ankle joint was examined at 28th day as it reduced inflammation by 18.06%, bone erosion by 15.50%, and pannus formation by 24.65% with respect to the diseased group. It restored the altered blood parameters by 7.56%, 18.47%, and 3.37% for hemoglobin (Hb), white blood count (WBC), and platelets, respectively. It also reduced rheumatoid factor RF by 13.70% with concomitant amelioration in catalase (CAT) and superoxide dismutase (SOD) levels by 19%, and 34.16%, respectively, in comparison to the diseased group. It notably decreased mRNA expression levels of COX-2, IL-6, TNF-α, IL-1, NF-κβ and augmented the levels of IL-4 and IL-10 in real time PCR with respect to the diseased group and piroxicam. HPLC analysis previously performed showed that phenolic acids and flavonoids are present in E-OM. Molecular docking studies displayed pronounced inhibitory potential of these compounds towards glutaminase 1 (GLS1), approaching and even exceeding piroxicam.
CONCLUSIONS
Thus, Opuntia monacantha could be a promising agent to manage inflammation and arthritis and could be incorporated into pharmaceuticals.
Topics: Rats; Animals; Cytokines; Plant Extracts; Opuntia; Glutaminase; Piroxicam; Molecular Docking Simulation; Rats, Sprague-Dawley; Arthritis, Experimental; Anti-Inflammatory Agents; Ethanol; Inflammation; Edema; Flavonoids
PubMed: 38350502
DOI: 10.1016/j.jep.2024.117884 -
Journal of the College of Physicians... Feb 2024To evaluate the analgaesic efficacy of tenoxicam and dexketoprofen in patients admitted to the Emergency Medicine (EM) Clinic with severe acute pain due to primary... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To evaluate the analgaesic efficacy of tenoxicam and dexketoprofen in patients admitted to the Emergency Medicine (EM) Clinic with severe acute pain due to primary dysmenorrhea (PD).
STUDY DESIGN
Randomised-controlled trial. Place and Duration of the Study: Emergency Medicine Clinic, Health Sciences University, Adana City Training and Research Hospital, Adana, Turkiye, from January to December 2022.
METHODOLOGY
Patients presenting with PD, were divided into two groups of 60 each, administered 50 mg dexketoprofen and 20 mg tenoxicam intravenously. Visual analogue scale (VAS) scores were recorded at the 15th, 30th, 60th, and 120th minutes. VAS scores and ΔVAS scores were compared with the effectiveness of drugs, the need for rescue drugs and its side-effects.
RESULTS
Intravenous (IV) dexketoprofen was administered to 60 of the patients and IV tenoxicam was administered to another 60. At the time of admission, mean VAS scores of the patients were 8.8 ± 0.9 for the dexketoprofen group and 8.6 ± 0.8 for the tenoxicam group. The VAS scores of the dexketoprofen group were found to be statistically significantly lower after 30 minutes with lower need for rescue analgaesics. ΔVAS scores of the dexketoprofen group were statistically significantly higher from the 30th minute.
CONCLUSION
According to the VAS scoring, IV dexketoprofen was a more effective drug than IV tenoxicam in patients who were admitted to the EM clinic with severe pain due to PD.
KEY WORDS
Dexketoprofen, Primary dysmenorrhea, VAS score.
Topics: Female; Humans; Acute Pain; Anti-Inflammatory Agents, Non-Steroidal; Double-Blind Method; Dysmenorrhea; Ketoprofen; Pain, Postoperative; Piroxicam; Tromethamine
PubMed: 38342865
DOI: 10.29271/jcpsp.2024.02.160 -
International Journal of Clinical... May 2024
Topics: Female; Humans; Levonorgestrel; Contraceptives, Postcoital; Piroxicam; Contraceptives, Oral, Combined; Ethinyl Estradiol
PubMed: 38329915
DOI: 10.5414/CP204537 -
Drug and Therapeutics Bulletin Feb 2024Li RHW, Lo SST, Gemzell-Danielsson K, et al. Oral emergency contraception with levonorgestrel plus piroxicam: a randomised double-blind placebo-controlled trial... (Randomized Controlled Trial)
Randomized Controlled Trial
Li RHW, Lo SST, Gemzell-Danielsson K, et al. Oral emergency contraception with levonorgestrel plus piroxicam: a randomised double-blind placebo-controlled trial [correction appears in 2023;402:850]. 2023;402:851-8.
Topics: Humans; Contraception, Postcoital; Levonorgestrel; Piroxicam; Double-Blind Method
PubMed: 38326010
DOI: 10.1136/dtb.2024.000011 -
Frontiers in Pharmacology 2023Current therapies for RA have limitations and side effects, leading to a growing need for safer treatment options. Natural compounds from plants are gaining attention...
Current therapies for RA have limitations and side effects, leading to a growing need for safer treatment options. Natural compounds from plants are gaining attention for their therapeutic benefits and fewer side effects. One such compound is the campesterol derivative, a steroid derivative occurring in plants. Studies have shown that this derivative has anti-inflammatory properties and can impact the expression of pro-inflammatory factors. The primary objective of this study was to explore and assess the potential therapeutic effects of Campesterol Ester Derivatives (CED) utilizing a rat model of arthritis induced by Complete Freund's Adjuvant (CFA). The rats were divided into specific experimental groups and treated with either CED or piroxicam (as a positive control) for a duration of 28 days. We determined the effects of CED on various parameters including paw edema, thermal hyperalgesia, and mechanical allodynia at different time points. Furthermore, serum levels of inflammatory cytokines, oxidative stress markers and histological analyses were performed. Additionally, mRNA expression levels of inflammatory markers, both pro-inflammatory (such as TNF-α, NF-κB, IL-6, COX-1, COX-2, and IL-4) and anti-inflammatory were analyzed. In the arthritic rat model, CED exhibited significant anti-inflammatory effects and resulted in a notable reduction in paw edema levels compared to the control group. Histopathological examination of the treated rats' paws confirmed a decrease in inflammation and tissue damage, including reduced pannus formation and bone erosion. Importantly, there were no observable signs of damage to the liver and kidneys following CED treatment, indicating its safety profile and potential for organ protection. At the molecular level, CED treatment downregulated mRNA expression levels of pro-inflammatory markers, indicating its ability to suppress inflammation. Conversely, certain anti-inflammatory markers were upregulated following CED treatment, suggesting a positive influence on the immune response. The positive effects of CED were not limited to joint inflammation; it also showed systemic benefits by positively influencing hematological and biochemical parameters. CED demonstrated promising therapeutic potential as an anti-inflammatory intervention for arthritis in the experimental rat model. Its ability to reduce inflammation, protect tissues, and improve organ function indicates its multifaceted benefits.
PubMed: 38322703
DOI: 10.3389/fphar.2023.1346054 -
Heliyon Jan 2024Traditional non-steroidal anti-inflammatory drugs (NSAIDs) show serious adverse effects during clinical use, which limits their usage. Oxicams (e.g., piroxicam,...
Traditional non-steroidal anti-inflammatory drugs (NSAIDs) show serious adverse effects during clinical use, which limits their usage. Oxicams (e.g., piroxicam, meloxicam) are widely used as NSAIDs. However, selectivity to cyclooxygenase (COX) 2 may cause cardiovascular problems considering the long-term use of the drugs. Therefore, it is important to develop new non-steroidal compounds as anti-inflammatory drugs. In the present study, we evaluated the anti-inflammatory activity of a newly developed nonsteroidal drug XK01. Our data showed that XK01 reduced the contents of nitric oxide (NO) and reactive oxygen species (ROS)and inhibited the transcription levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β in a dose-dependent manner in lipopolysaccharide (LPS)-stimulated mouse RAW264.7 macrophages. XK01 showed no significant inhibitory effect on COX-1, but inhibited the expression of COX-2. At molecular level, XK01 prevented the translocation of p65 protein from the cytoplasm to the nucleus and inhibited the phosphorylation of p65, IκB, and MAPKs proteins. And high concentration of XK01 also inhibited the phosphorylation of JNK, p38 and ERK, showing stronger effect than that of meloxicam. In addition, the anti-inflammatory activity of XK01 was further validated in Xylene-induced mouse ear swelling model. Thus, this study verified that XK01 inhibits the expression of inflammatory mediators and COX-2, and exhibits potential anti-inflammatory effects via suppressing the NF-κB and MAPK pathway.
PubMed: 38312593
DOI: 10.1016/j.heliyon.2024.e24004 -
BMC Pharmacology & Toxicology Feb 2024Methotrexate (MTX) is the cornerstone of rheumatoid arthritis (RA) treatment and is highly effective with low-dose intermittent administration. MTX is occasionally used...
Drug-drug interaction assessment based on a large-scale spontaneous reporting system for hepato- and renal-toxicity, and thrombocytopenia with concomitant low-dose methotrexate and analgesics use.
BACKGROUND
Methotrexate (MTX) is the cornerstone of rheumatoid arthritis (RA) treatment and is highly effective with low-dose intermittent administration. MTX is occasionally used in combination with non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen (APAP)/paracetamol for pain or inflammation control. With MTX treatment, the side effects, such as hepatotoxicity, renal failure, and myelosuppression should be considered. These are also seen with analgesics treatment.
METHODS
We used a large spontaneously reported adverse event database (FAERS [JAPIC AERS]) to analyze whether the reporting of adverse events increased upon MTX and analgesic therapy in patients with RA.
RESULTS
After identifying RA cases, the crude reporting odds ratios (cRORs) for hepatotoxicity, renal failure, and thrombocytopenia associated with the use of MTX, APAP, or NSAIDs were calculated by disproportionality analysis, which revealed significantly higher cRORs for these events. No analgesics showed consistent positive signals for drug-drug interaction (DDI) with concomitant low-dose MTX analyzed using four algorithms for DDI interaction (the Ω shrinkage measure, additive or multiplicative, and combination risk ratio models). However, in renal failure and thrombocytopenia, loxoprofen (Ω = 0.08) and piroxicam (Ω = 0.46), and ibuprofen (Ω = 0.74) and ketorolac (Ω = 3.52), respectively, showed positive signals in the Ω shrinkage measure model, and no consistency was found among adverse events or NSAIDs.
CONCLUSIONS
Studies using spontaneous reporting systems have limitations such as reporting bias or lack of patient background; however, the results of our comprehensive analysis support the results of previous clinical or epidemiological studies. This study also demonstrated the usefulness of FAERS for DDI assessment.
Topics: Humans; Methotrexate; Antirheumatic Agents; Acetaminophen; Anti-Inflammatory Agents, Non-Steroidal; Analgesics; Arthritis, Rheumatoid; Thrombocytopenia; Drug Interactions; Chemical and Drug Induced Liver Injury; Renal Insufficiency
PubMed: 38303016
DOI: 10.1186/s40360-024-00738-6 -
JMIR Public Health and Surveillance Jan 2024Drug-induced suicide (DIS) is a severe adverse drug reaction (ADR). Although clinical trials have provided evidence on DIS, limited investigations have been performed on... (Review)
Review
BACKGROUND
Drug-induced suicide (DIS) is a severe adverse drug reaction (ADR). Although clinical trials have provided evidence on DIS, limited investigations have been performed on rare ADRs, such as suicide.
OBJECTIVE
We aimed to systematically review case reports on DIS to provide evidence-based drug information.
METHODS
We searched PubMed to obtain case reports regarding DIS published until July 2021. Cases resulting from drugs that are no longer used or are nonapproved, substance use, and suicidal intentions were excluded. The quality of each case report was assessed using the CASE (Case Reports) checklist. We extracted data regarding demographics, medication history, suicide symptoms, and symptom improvement and evaluated the causality of DIS using the Naranjo score. Furthermore, to identify the potential suicidal risk of the unknown drugs, we compared the results of the causality assessment with those of the approved drug labels.
RESULTS
In 83 articles, we identified 152 cases involving 61 drugs. Antidepressants were reported as the most frequent causative drugs of DIS followed by immunostimulants. The causality assessment revealed 61 cases having possible, 89 cases having probable, and 2 cases having definite relationships with DIS. For approximately 85% of suspected drugs, the risk of suicidal ADRs was indicated on the approved label; however, the approved labels for 9 drugs, including lumacaftor/ivacaftor, doxycycline, clozapine, dextromethorphan, adalimumab, infliximab, piroxicam, paclitaxel, and formoterol, did not provide information about these risks.
CONCLUSIONS
We found several case reports involving drugs without suicide risk information on the drug label. Our findings might provide valuable insights into drugs that may cause suicidal ADRs.
Topics: Humans; Doxycycline; Drug Labeling; Drug-Related Side Effects and Adverse Reactions; Suicidal Ideation; Suicide; Case Reports as Topic
PubMed: 38289650
DOI: 10.2196/49755 -
Odontology Jan 2024This study explored the antimicrobial effects of ketoprofen, piroxicam, and celecoxib alone or combined with calcium hydroxide (CH) against two strains of Enterococcus...
Evaluation of the antimicrobial efficacy of different nonsteroidal anti-inflammatory drugs alone or in combination with calcium hydroxide intracanal medicament: an in vitro study.
This study explored the antimicrobial effects of ketoprofen, piroxicam, and celecoxib alone or combined with calcium hydroxide (CH) against two strains of Enterococcus faecalis (E. faecalis) and assessed the influence of such combinations on the pH of CH. Minimum inhibitory concentrations (MICs) of the three tested NSAIDs were determined. Tested pastes were placed into wells punched in seeded agar plates and the bacterial inhibition zones were measured. Antibiofilm activity was assessed against 3 weeks of biofilm induced in bovine dentine blocks. The pH of the pastes was measured at four-time intervals. MIC values were 3.12, 25, and 25 mg/ml for ketoprofen, piroxicam, and celecoxib, respectively, and were similar for both bacterial strains except for celecoxib, which showed 8% growth at the highest tested concentration against vancomycin-resistant E. faecalis. Ketoprofen had the largest mean inhibition zone that was comparable to CH. None of the six tested pastes exhibited antibiofilm activity of a significant level in comparison to CH. A noticeable increase in the antibiofilm activity was found when 20% NSAIDs were added to CH while maintaining an alkaline pH. Ketoprofen was found to be the most effective among the tested NSAIDs. Although its effect was comparable to CH, adding ketoprofen at a ratio of 20% resulted in 50% higher antimicrobial action than CH alone. Accordingly, incorporating NSAIDs in inter-appointment dressing has the potential to utilize their anti-inflammatory, local analgesic, and antibacterial actions, which overcome the limitations of CH and improve the outcome of root canal treatment.
PubMed: 38265514
DOI: 10.1007/s10266-023-00892-z -
Pakistan Journal of Pharmaceutical... Nov 2023Scutellaria sibthorpii is used in treatment of bacterial infections, pains and inflammations. The leaf was extracted by maceration and then partitioned with hexane,...
Scutellaria sibthorpii is used in treatment of bacterial infections, pains and inflammations. The leaf was extracted by maceration and then partitioned with hexane, ethyl acetate and n-butanol. The extract was screened for phytochemicals. The antioxidant activity was assayed using DPPH, HO and β-carotene. The total phenolic and flavonoid contents were estimated using Folin-Ciocalteu's and AlCl. The crude extract/fractions were tested on E. coli, S. typhi, B. subtilis and S. aureus using agar disk diffusion. Lorke's method was used to determine the LD. The analgesic activity was determined using ethanoic acid-induced writhing, hotplate and formalin-induced nociception. Anti-inflammatory activity was investigated by means of formalin-induced acute inflammation. The antipyretic activity was studied using Brewer's yeast. The ethyl acetate fraction (EtFSs) had IC of 0.4352mg/mL in the HO and IC of 0.00014mg/mL. The MIC of EtFSs against S. aureus was 1.25mg/mL and 2.5mg/mL on S. typhi. LD of the CrESs/fractions were greater than 5000mg/Kg. The analgesic and anti-inflammatory activities were higher in EtFSs when compared to piroxicam. The fractions decrease the rectal temperature of the rats in the same way as paracetamol at 200mg/Kg. This research has for the first time validated the used of Scutellaria sibthorpii traditionally as analgesic, anti-inflammatory and antipyretic.
Topics: Animals; Rats; Antipyretics; Cyprus; Escherichia coli; Hydrogen Peroxide; Staphylococcus aureus; Formaldehyde; Anti-Inflammatory Agents; Analgesics; Scutellaria; Acetates
PubMed: 38264889
DOI: No ID Found