TL;DR
It was evaluated in this study that aripiprazole showed inhibition of protein degradation and stability of human red blood cell membrane in concentration gradient manner, demonstrating maximum activity at concentration of 6400 µg/ml.
BACKGROUND Rheumatoid arthritis is a systemic autoimmune disorders of joints. Its available therapies having serious adverse effects, high cost and poor patient compliance. OBJECTIVE The present study aimed to evaluate the anti-inflammatory and anti-arthritic potential of 3, 4-dimethoxybenzoic acid or Veratric acid (VA) by in-vitro and in-vivo assays. Additionally, acute toxicity of VA was performed. METHODOLOGY The anti-inflammatory activity was assessed by Xylene-induced ear edema, and Carrageenan-induced paw edema models in Wistar rats. The VA was given at doses of 20, 40, and 80 mg/kg, with Piroxicam (10mg/kg) as standard drug. For anti-arthritic action, 0.1 ml of Complete Freund's adjuvant was intradermally inoculated in left posterior paw on first day while treatment with VA at 20, 40, 80, and VA 80 mg/kg + methotrexate and methotrexate (1 mg/kg) as standard drug were given orally on the 8th day for 21 days. RESULTS Treatment with VA exhibited a substantial reinstatement of body weight, paw edema, arthritic scores, and oxidative stress in difference to disease control. All treatment groups exhibited notable down-regulation (p < .0001) of IL-6, TNF-α, IL-β, COX-2, and NF-κB and up-regulation of IL-10, 1-κβ, IL-4 in contrast to disease control. The combination group had exhibited noticeable anti-arthritic potential in comparison to individual treatment groups. In acute toxicity study, LD50 of VA was greater than 2000 mg/kg. CONCLUSION It can be inferenced from data that VA can be safely used to treat arthritis especially in combination with MTX but it should be further evaluated in combination for long term use.
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that is accompanied by progressive joint destruction, pain and functional disability. The main objective of the present study was to examine the antiarthritic activity of aqueous (ZAAQ) and ethanolic (ZAE) extract of Zanthoxylum armatum in both in-vitro and in-vivo experimental models. Preliminary phytochemical screening of the extracts showed the presence of alkaloids, flavonoids, tannins, terpenoids, phenolic compounds and glycosides, which are known to possess antiinflammatory properties. The protein denaturation and human red blood cell (HRBC) membrane stabilization assays were used to assess in-vitro anti-arthritic activity at concentration of (50-2000µg/mL). Strong membrane stabilization and protein denaturation inhibition effects were obtained by both extracts in a concentrationdependent manner, similar to diclofenac sodium. The in-vivo evaluation was performed on Wistar rats with the induction of rheumatoid arthritis (RA) using Freund's Complete Adjuvant (FCA). The extracts were orally given after 28 days at doses of 200, 400 and 600 mg/kg. The decrease in paw edema and joint diameter produced by treatment with ZAAQ and ZAE compared to the disease control group was significant and the increase in body weight in arthritic rats was also significantly improved. The therapeutic activity of the higher doses of both extracts was higher, with aqueous extract having comparatively higher activity. The result indicated that Zanthoxylum armatum has significant anti-inflammatory and anti-arthritic property which may be attributed to the combination effect of various phytoconstituents present in the plant. Hence, the plant can be a promising natural therapeutic agent for the control of RA.
Background . Currently, the main groups of anti-inflammatory drugs used in medical practice are steroidal (glucocorticoids) and non-steroidal agents. However, despite their widespread use, these groups of anti-inflammatory drugs have a fairly wide range of negative side effects, which makes the search for low-toxic substances with anti-inflammatory effects currently relevant. The aim . To study anti-inflammatory, antinociceptive activity and acute toxicity of individual representatives of indenopyrroles and indenopyridazines. Methods . The acute toxicity of the studied compounds was studied using the method of Prozorovsky VB. Anti-inflammatory activity was assessed in a carrageenan-induced rat paw edema model. The production of active oxygen radicals by leukocytes was evaluated using luminol-dependent chemiluminescence. The antinociceptive activity of the compounds was assessed using the “writhing” and “hot plate” tests in mice. Results. The obtained results allowed the studied compounds to be classified as “practically nontoxic” (LD50 > 1000 mg/kg). Compounds 1в of the indenopyrrole series and indenopyridazines 2а-в were found to exhibit anti-inflammatory activity, reducing the severity of exudative inflammation. Compound 2a exhibited the greatest antiexudative activity, reducing edema by more than 60 % (p < 0.01). Compounds 2a-в and compound 1в reduced the production of reactive oxygen species by more than 40 % (p < 0.05) compared to the control. In the “hot plate” test, the studied compounds 1a, 1в, 2a-в exhibited an antinociceptive effect comparable to nimesulide; in the “acetic acid-induced writhing” test, the effect of compounds 1a, 2б, 2в was comparable to nimesulide, and the effect of compound 2a exceeded the comparison drug by 32.96 % (p < 0.05). Conclusion . The studied compounds of the indenopyrrole series and their indenopyridazine derivatives are virtually non-toxic compounds, exhibit an anti-inflammatory effect and reduce the severity of pain associated with inflammation.
BACKGROUND Rheumatoid arthritis is a chronic autoimmune disorder that causes severe pain and inflammation that gradually destroys joints. OBJECTIVES Tetrahydropyrimidine-5-carboxylate (THP) has been investigated for its anti-inflammatory and anti-arthritic effects using both in vitro and in vivo approaches. METHODS In vitro anti-inflammatory activity of THP was assessed using protein denaturation and membrane stabilization assays at various concentrations. For in vivo anti-inflammatory activity, carrageenan-induced paw edema and xylene-induced ear edema models were performed in rats. For anti-arthritic potential, all rats except normal control group, were given an injection of Complete Freund's Adjuvant (CFA; 0.15 mL) into the left hind paw on day one. Treatment with THP at 25, 50 and 100 mg/kg was started orally from 8th day till 28th day. Methotrexate (1 mg/kg) was the standard treatment; the normal and disease groups received vehicle. The effects of treatment on body weight, paw edema, pain, blood chemistry, neurotransmitters and oxidative stress biomarkers were assessed. RESULTS THP exhibited significant In-vitro and in-vivo anti-inflammatory potential in dose dependent manner. THP (25-100mg/kg) treatment significantly decreased paw edema, arthritic index and pain, while restoring body weight, muscular strength, oxidative stress biomarkers and blood parameters in treated rats compared with the disease control. Treatment with THP notably modulated the mRNA expression of RANKL, OPG, MMP-13, COX-2, TNF-α, IL-6 and IL-4 compared with disease control, as evidenced by histology of the ankle joint of treated rats. THP-treated rats exhibited higher levels of serotonin and noradrenaline in sciatic nerve homogenates. CONCLUSION The results showed that THP had significant dose-dependent anti-inflammatory, anti-arthritic, antioxidant and analgesic effects, suggesting that it could be a safe therapy for inflammatory and arthritic diseases, as it showed an LD50 > 2000mg/kg.
This study aims to evaluate the anti‐nociceptive activity of isoquercetin (IQN) in rats and to determine its mechanism of action using molecular docking. The preliminary study was conducted to determine physicochemical and pharmacological parameters of IQN, an in vitro method was used to assess its antioxidant capacity. Behavioral tests were carried out to evaluate its anti‐nociceptive activity and an in silico molecular docking study was performed to understand the molecule's mechanism of action. The preliminary study demonstrated that IQN is nontoxic to metabolism and organs, with an LD50 of 5000 mg/kg, and does not present neuromuscular toxicity. Furthermore, the molecule showed a strong antioxidant capacity. The evaluation of anti‐nociceptive activity in rats revealed a significant anti‐inflammatory effect of IQN. The molecular docking identified a specific action on cyclooxygenases. Thus, IQN appears to be a promising candidate for the treatment of inflammatory pain, supported by its wide safety margin, potent antioxidant.