Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry - Volume 21, Issue 3, 2022

Osteoarthritis is the most common human joint disease in the world. It is also one of the most common skeletal muscle defects, destructive joint changes, and the leading cause of disability and reduced quality of life. Destructive changes in inflammatory joints are associated with a range of biochemical events, including the overproduction of inflammatory cytokines. Cytokines are protein compounds that play an essential role in causing and regulating inflammation. A balance between pro-inflammatory and anti-inflammatory cytokines is crucial in maintaining a stable body. In some inflammatory diseases, including osteoarthritis, the balance between these compounds is disturbed, and the balance shifts to pre-inflammatory cytokines. For this reason, researchers today are trying to find an effective way to reduce inflammation and treat osteoarthritis by using certain compounds. Current treatments for osteoarthritis, including nonsteroidal antiinflammatory drugs, glucocorticoids, and hyaluronic acid, are mainly based on reducing pain and inflammation. However, they have limited effects in controlling symptoms and improving the patient's quality of life. Also, due to the high level of side effects, synthetic drugs have led to the identification of compounds of natural origin to give patients a chance to use painkillers and antiinflammatory drugs with fewer side effects. This review study aimed to present the role of quercetin as a natural compound in reducing the expression of pro-inflammatory cytokines in osteoarthritis. This study also discusses the relationship between inflammation and cartilage destruction and other inflammation-related factors caused by cytokines.

Background: The pathogenesis of Sjögren’s syndrome involves the activation of NF- ΚB, producing proinflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1α, IL- 1β, IL-6, IL-17, and interferon-γ. Through oxidative stress, they will cause necrosis and apoptosis of lacrimal gland cells, resulting in impaired secretory function or reduced tear production. Moringa oleifera leaf extract is known to have strong anti-inflammatory and antioxidant activities. Objective: To determine the effect of Moringa oleifera leaf extract on lacrimal gland histopathology and secretory function in Sjögren’s syndrome mice model. Methods: The experimental study had a post-test only control group design with 32 eight-week-old male mice of the BALB/c strain divided into four groups, negative control (C−), which was not induced by SS, positive control (C+), treatment 1 (T1), and treatment 2 (T2) induced by Sjögren’s syndrome by immunizing with the 60-kD Ro antigen (SSA) as much as 100 μg. After 42 days, the T1 group was given dexamethasone 1.23 mg/kg BW/day orally for 14 days, whereas T2 was given dexamethasone 1.23 mg/kg BW/day and Moringa oleifera leaf ethanol extract 200 mg/kg BW/day orally for 14 days. At the end of the study, lacrimal gland histopathology and secretory function (tear production) were examined. Statistical analysis using F ANOVA/Kruskal-Wallis was followed by partial difference test with the Least Significant Difference post hoc test/Mann-Whitney. Significant if p < 0.05. Results: The comparison of lacrimal gland histopathology in T1 (p = 0.044) and T2 groups (p = 0.020) obtained significant results (p < 0.05) when compared to C+. However, the comparison of tear production in T1 (p = 0.127) and T2 groups (p = 0.206) was not significant (p > 0.05) when compared to the C+ group. Conclusion: The administration of Moringa oleifera leaf extract 200 mg/kg BW for 14 days could significantly improve lacrimal gland histopathology but was not effective in increasing tear production in Sjögren’s syndrome mice model.

Background: Chamaenerion latifolium is a perennial herbaceous plant of the Onagraceae family. The purpose of this study was to evaluate and compare the volatile chemical components of the aerial parts of Chamaenerion latifolium growing in the Republic of Kazakhstan. Methods: The leaves and stems of Chamaenerion latifolium were extracted with hexane and analysed by gas chromatography-mass spectrometry (GC-MS). Results: The regularisation of peak areas method was used to calculate the concentrations of the sixty-five identified compounds. Conclusion: Among them, the major components are alkanes (leaves 31.339%, stems 48.158%), esters (leaves 10.216%, stems 12.196%), alcohols (leaves 5.483% and stems 5.14%), aldehydes (leaves 3.155%, stems 1.592%), triterpenoids (leaves 2.247% stems 3.785%).

Background: In traditional medicine, Linum usitatissimum treats inflammatory, gastrointestinal, and cardiovascular diseases. Objectives: The present study aims to assess the anti-inflammatory and anti-oxidant effects of total alkaloid extract from Linum usitatissimum seeds (ALU) on the ear histological integrity and oxidant- antioxidant status in a mice model of a sub-chronic inflammation induced by multiapplication of TPA. Methods: Topical TPA treatment induced various inflammatory changes, including edema formation, epidermal thickness, and the excess production of reactive oxygen species. Tissue samples were used for the measurement of reduced glutathione (GSH) and nitric oxide (NO) levels and Myeloperoxidase (MPO) and Catalase (CAT) activities. Results: Oral administration of ALU (50, 100, and 200 mg/kg) produced anti-inflammatory and anti-oxidant effects. Also, ALU significantly reduced ear edema and inflammatory cell infiltration and restored the integrity of the ear. Conclusion: These findings suggest that the total alkaloid extract from Linum usitatissimum seeds presents significant anti-inflammatory and anti-oxidant effects on TPA-induced sub-chronic inflammation model in NMRI mice and can be used as an anti-inflammatory and anti-oxidant agent for the therapeutic management of inflammatory disorders.

Aim: The in vitro effects of commonly used first-line anti-arthritic drugs on early stages of T-cell activation were examined. Methods: The 2B4.11 murine T cell hybridoma cell line recognizing pigeon cytochrome c (PCC) as the antigen was co-cultured with the histocompatible antigen presenting B cell hybridoma line LK35.2, PCC, and anti-arthritic drugs, including methotrexate, hydroxychloroquine, salazopyrine, cyclosporin, and leflunomide. After 16 hours of incubation, the supernatant was removed, and cytokines were assayed. Results: Anti-arthritic drugs inhibited the production of pro-inflammatory cytokines IL-2, IL-6, IFN-γ, GM-CSF, and TNF-α (Th1 cytokines) to a varying extent. Surprisingly, leflunomide, salazopyrine, prednisone and indomethacin as well as blocking Th1 cytokines, stimulated the production of the anti-inflammatory cytokine IL-10, a Th2 cytokine. Conclusion: Anti-arthritic medications can inhibit the production of pro-inflammatory cytokines and in some cases, incite a Th2 response that could potentially inhibit the progression of the immune response.

Background: Non-alcoholic fatty liver disease (NAFLD) is the most frequent cause of chronic liver disease in the world. It is known that there is a pathogenic relation between liver damage and the inflammatory and oxidative environment present in Metabolic Syndrome (MS). Objective: To study the pharmacological action of atorvastatin and metformin in an experimental model of MS. Methods: We used 40 male rats (Wistar) divided into the following groups: Control (A) (n=8), induced MS (B) (n=8), MS + atorvastatin treatment (C)(n=8), MS + metformin treatment (D) (n=8) and MS + combined treatment (E) (n=8). MS was induced by administering 10% fructose in drinking water for 45 days. Atorvastatin 0.035 mg/day/rat, metformin 1.78 mg/day/rat, and a combination of both drugs were administered for 45 days. Metabolic, oxidative (nitric oxide, myeloperoxidase and superoxide dismutase) and inflammatory (fibrinogen) parameters were determined. Histological sections of liver were analyzed by light microscopy. Results: The glycemia, lipid profile and TG/HDL-C index were altered in MS group. After pharmacological treatment, metabolic parameters improve significantly in all treated groups. Inflammatory and oxidative stress biomarkers increase in MS. Treated groups showed an increase in NO bioavailability, no difference in MPO activity and an increase in fibrinogen. Atorvastatin showed a decrease in SOD while Metformin and combination treatment showed an increase in SOD compared to MS. In MS, we observed histological lesions consistent with NAFLD. However, after a combined treatment, we observed total regression of these lesions. Conclusion: Our results showed that there is an important synergy between atorvastatin and metformin in improving liver involvement in MS.