Sclareol exerts an anti-inflammatory effect, possibly through COXs inhibition pathway: In vivo and in silico studies

Abdullah Al Shamsh Prottay , Mehedi Hasan Bappi , Md Showkoth Akbor , Afia Ibnath Asha , Md Shimul Bhuia , Aqib Adnan Shafin , Md Nayem Mia , Mohammad S. Mubarak , Micheline de Azevedo Lima , Henrique Douglas Melo Coutinho , Muhammad Torequl Islam
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Abstract

Chronic and severe inflammation results in many diseases and disorders in humans. Currently, available conventional anti-inflammatory drugs have numerous mild-to-severe side effects. Thus, there is a need for safe, effective, affordable, and alternative anti-inflammatory drugs. This study aimed to evaluate the anti-inflammatory effect of sclareol (SCL), a diterpene alcohol that is the principal ingredient in the refined oil of Salvia sclarea (L.), through in vivo and in silico studies. First, we examined the individual and combined effects of SCL (5, 10, and 20 mg/kg) and standard drugs celecoxib (CXB) or ketoprofen (KPN) at 42 mg/kg (p.o.) on the formalin-induced inflammatory Swiss mice. Additionally, an in silico analysis was conducted to evaluate the potential anti-inflammatory mechanism of this study. For this, we examined the potentiality of SCL and standards to interact with cyclooxygenase (COX) -1 and COX-2 receptors. Our findings suggest that SCL exhibits a dose-dependent anti-inflammatory effect in mice. SCL-20 mg/kg significantly reduced the number of paw licks and paw edema diameters. Moreover, SCL-20 combined with CXB-42 and KPN-42 demonstrated better anti-inflammatory effects. In comparison to the standards, SCL revealed a comparable binding interaction with COX-1 and COX-2 receptors in the molecular docking study. Furthermore, SCL displayed remarkable pharmacokinetic characteristics. In conclusion, SCL significantly and dose-dependently reduced the number of paw licks and edema diameters in animals. Thus, SCL may be responsible for producing an anti-inflammatory effect by interacting with COX-1 and COX-2 receptors.

Sclareol发挥抗炎作用,可能通过COXs抑制途径:体内和计算机研究
慢性和严重的炎症导致人类许多疾病和失调。目前,可用的传统消炎药有许多轻微到严重的副作用。因此,需要一种安全、有效、负担得起的替代性消炎药。本研究旨在通过体内实验和体外实验,评价其抗炎作用。sclareol (SCL)是一种二萜醇,是鼠尾草(L.)精炼油中的主要成分。首先,我们检测了SCL(5、10和20 mg/kg)和标准药物塞来昔布(CXB)或酮洛芬(KPN) 42 mg/kg (p.o)对福尔马林诱导的炎症瑞士小鼠的单独和联合作用。此外,还进行了计算机分析,以评估本研究的潜在抗炎机制。为此,我们研究了SCL和标准物与环氧化酶(COX) -1和COX-2受体相互作用的可能性。我们的研究结果表明,SCL在小鼠中表现出剂量依赖性的抗炎作用。SCL-20 mg/kg显著降低舔爪次数和足水肿直径。SCL-20联合CXB-42、KPN-42抗炎效果更好。与标准对照相比,在分子对接研究中,SCL与COX-1和COX-2受体的结合相互作用相似。此外,SCL表现出显著的药动学特征。综上所述,SCL显著且剂量依赖性地减少了动物的舔爪次数和水肿直径。因此,SCL可能通过与COX-1和COX-2受体相互作用而产生抗炎作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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