Department of Pharmacology & Toxicology, College of Pharmacy, Jazan University, Saudi Arabia.
Department of Pharmacy Practice, College of Pharmacy, Jazan University, Saudi Arabia.
J Ethnopharmacol. 2022 Jun 28;292:115200. doi: 10.1016/j.jep.2022.115200. Epub 2022 Mar 17.
Rheumatoid arthritis is one of the most common disabling chronic progressive autoimmune diseases affecting the adult world population. Boswellia serrata has been a known anti-inflammatory agent since ancient times. Therefore, research on Boswellia extract based on Acetyl Keto Boswellic Acid (AKBA) content evaluating its efficacy and safety is necessary. The study aimed to find a suitable Boswellia extract rich in AKBA to evaluate its bioavailability, anti-inflammatory, and anti-arthritic effect. In addition, the synergistic action of AKBA extract with methotrexate (MTX) was also assessed on an animal model.
Oral bioavailability of AKBA and the anti-inflammatory activity of 10% AKBA (5, 10, 20, 40 mg/kg b.w) was assessed and compared with 2% AKBA (40 mg/kg) and diclofenac (10 mg/kg). The effect of 10% AKBA at 20 mg/kg and 40 mg/kg was evaluated in the FCA induced arthritis animal model alone and combined with methotrexate (MTX) at 2 mg/kg b.w. Subplantar injection of FCA produced edema within a few hours with progressive arthritis by the 9th day after injection. All the treatments were initiated from the 10th day until the 45th day. Oral administration of 10% AKBA was done daily and MTX by intraperitoneal route once a week from day 10 to day 45. Paw volume, erythrocyte sedimentation rate (ESR), serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP), total bilirubin, oxidative markers (superoxide dismutase (SOD) levels, malondialdehyde (MDA), total proteins and liver histopathology were examined.
10% AKBA provided 8.48-fold, 24.22-fold, 47.36-fold, and 110.53-fold higher AUC (0-α) of AKBA at 5 mg/kg, 10 mg/kg, 20 mg/kg and 40 mg/kg, respectively compared to 2% AKBA at 40 mg/kg. Percentage paw edema inhibition of 10% AKBA at 20 mg/kg and 40 mg/kg were significantly higher than 2% regular AKBA (40 mg/kg) and diclofenac (10 mg/kg). 10% AKBA at a dose of 20 and 40 mg/kg significantly reduced ESR compared with FCA treated group. A combination of methotrexate with 10% AKBA showed the highest reduction in ESR. 10% AKBA at both dose levels significantly reduced hepatic marker enzymes and total bilirubin levels. Treatment with 10% AKBA showed a significant increase in total proteins, antioxidant enzymes and a decrease in malondialdehyde levels. Similarly, 10% AKBA protected the hepatocytes compared with the FCA and FCA + MTX treated group. 10% AKBA was capable of significantly minimizing FCA and FCA + MTX induced changes.
Anti-inflammatory activity of AKBA due to inhibition of lipoxygenase (LOX) enzymes supports the use of AKBA in inflammatory disorders. Combination therapy of 10% AKBA with MTX is effective in inhibiting arthritis and circumventing hepatotoxicity produced by MTX in arthritic animals.
类风湿性关节炎是影响成年人群的最常见的致残性慢性进行性自身免疫性疾病之一。自古以来，乳香就被认为是一种抗炎药物。因此，有必要对基于乙酰基 Keto 乳香酸（AKBA）含量的乳香提取物进行研究，以评估其功效和安全性。本研究旨在寻找一种富含 AKBA 的合适乳香提取物，以评估其生物利用度、抗炎和抗关节炎作用。此外，还评估了 AKBA 提取物与甲氨蝶呤（MTX）在动物模型上的协同作用。
评估 AKBA 的口服生物利用度和 10%AKBA（5、10、20、40mg/kg体重）的抗炎活性，并与 2%AKBA（40mg/kg）和双氯芬酸（10mg/kg）进行比较。评估 10%AKBA 在 20mg/kg 和 40mg/kg 剂量下对 FCA 诱导的关节炎动物模型的单独作用，以及与甲氨蝶呤（MTX）2mg/kg 体重联合作用。FCA 足底注射后数小时内产生水肿，注射后第 9 天出现进行性关节炎。所有治疗均从第 10 天开始，直至第 45 天。口服 10%AKBA 每天一次，MTX 每周一次腹腔内注射，从第 10 天至第 45 天。检测足跖体积、红细胞沉降率（ESR）、血清谷草转氨酶（SGOT）、血清谷丙转氨酶（SGPT）、碱性磷酸酶（ALP）、总胆红素、氧化标志物（超氧化物歧化酶（SOD）水平、丙二醛（MDA）、总蛋白和肝组织病理学。
与 2%AKBA（40mg/kg）相比，10%AKBA 在 5mg/kg、10mg/kg、20mg/kg 和 40mg/kg 时 AKBA 的 AUC（0-α）分别高出 8.48 倍、24.22 倍、47.36 倍和 110.53 倍。10%AKBA 在 20mg/kg 和 40mg/kg 时的足跖肿胀抑制率明显高于 2%常规 AKBA（40mg/kg）和双氯芬酸（10mg/kg）。10%AKBA 可显著降低 ESR，与 FCA 治疗组相比。甲氨蝶呤与 10%AKBA 联合使用时，ESR 降低最明显。10%AKBA 在两个剂量水平下均能显著降低肝标志物酶和总胆红素水平。10%AKBA 治疗组总蛋白、抗氧化酶显著增加，丙二醛水平降低。同样，10%AKBA 可保护肝细胞，使其免受 FCA 和 FCA+MTX 治疗组的影响。10%AKBA 能显著减轻 FCA 和 FCA+MTX 诱导的变化。
AKBA 通过抑制脂氧合酶（LOX）酶的抗炎活性支持 AKBA 在炎症性疾病中的应用。10%AKBA 与 MTX 的联合治疗可有效抑制关节炎，并避免 MTX 在关节炎动物中产生的肝毒性。
