Activation Effect of 2-β-hydroxy Manoyl Oxide Isolated from Sideritis perfoliata on Carbonic Anhydrase Isoenzymes I and II

Background: Sideritis species were used for the treatment of mental disorders such as Alzheimer’s and dementia traditionally in Turkey. Several in vivo studies report that the mid-polar extract of Sideritis species can develop the brain functions of mice. 2-β-hydroxy manoyl oxide, isolated from ethyl acetate extract of Sideritis perfoliata, was assayed in vitro and in silico on human erythrocytes CA I and CA II. The compound was found to be an activator on two isoenzymes. It has been reported that activators of carbonic anhydrases may be used as a novel approach to treating disorders such as Alzheimer’s and age-related diseases. This study aimed to investigate the activity effect of 2-β-hydroxy manoyl oxide in vitro and in silico on human erythrocytes CA I and CA II (hCA I and hCA II) and to elucidate its pharmacokinetic and physicochemical characteristics. Methods: The test compound was isolated from ethyl acetate extract of Sideritis perfoliata using chromatographic techniques and identified with spectroscopic evidence. Carbonic anhydrase activities were assayed using CO2 substrates. Docking studies were carried out with Molegro Virtual Docker. The compound underwent ADME-Tox prediction by using AdmetSAR and SwissADME software. Results: 2-β-hydroxy manoyl oxide was found to increase the hCA-l and hCAII activity with AC50 values 9 and 19 μM, respectively. These results were further confirmed in silico molecular modeling. It showed favorable pharmacokinetic and physicochemical characteristics as a new drug candidate. Conclusion: These findings demonstrated that 2-β-hydroxy manoyl oxide activated the hCA-l and hCA II. These results provide a novel and alternative activator for the carbonic anhydrase and confirm the traditional usage of the Sideritis perfoliata.