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

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.

Keywords

Inflammation / Sclareol / Cyclooxygenase / Anti-Inflammatory effect / Molecular docking simulation

CRediT authorship contribution statement

Abdullah Al Shamsh Prottay: Conceptualization, Methodology, Software, First Draft of the Manuscript; Mehedi Hasan Bappi: Methodology, Software; Md. Showkoth Akbor: Methodology; Afia Ibnath Asha: Data curation; Md. Shimul Bhuia: Resources; Aqib Adnan Shafin: First Draft of the Manuscript; Md. Nayem Mia: Software; Mohammad S. Mubarak: Supervision; Henrique Douglas Melo Coutinho: Project administration; Muhammad Torequl Islam: Supervision. All the authors have read and agreed to the published version of the manuscript.

Data availability statement

This published article contains the data collected or studied during this investigation. Information will be provided upon valid request.

Funding

No funding.

Ethics approval

Experimental design and procedures were approved by the Animal and Human Ethics Committee of BSMRSTU (#2023-33).

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

The authors extend their appreciation to the Deanship of Scientific Research at King Khalid University for funding this work through a large group research project under grant number: RGP2/362/44.

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