The influence of variations of furanosesquiterpenoids content of commercial samples of myrrh on their biological properties

Abstract

Myrrh is an oleo-gum-resin produced in the stem of Commiphora myrrha (Burseraceae) and used for centuries for different medicinal purposes. The present work was designed to evaluate the cytotoxic and antioxidant properties of seventeen myrrh samples (S1-S17) obtained from different retail markets of Saudi Arabia and Yemen regions, along with two furanosesquiterpenoids (CM-1 and CM-2). The cytotoxicity assay was carried out on HepG2, MCF-7 and HUVEC cell lines. S2, S5, S10, S12, CM-1, CM-2 exhibited significant cytotoxicity against HepG2/MCF-7 cell lines [IC50 (μg/mL): 13.8/10, 14/10, 14.5/11.3, 18/13.2, 9.5/12.5, 10/15.8, respectively) compare to vinblastin (IC₅₀ (μg/mL): 2/2.5) whereas the remaining samples were found as mild active or inactive. The antioxidant properties of the samples were tested by β-carotene-bleaching and DPPH free radical scavenging methods where the samples S8 (1000 μg/mL) exhibited the highest β-carotene bleaching (76.2%) and free radical scavenging activity (79.8%). The HPTLC analysis was performed on NP-HPTLC plate using toluene, chloroform and glacial acetic acid as mobile phase in ratio of 7:2.9:0.1 (V/V/V). The validated HPTLC method furnished sharp, intense and compact peaks of CM-1 and CM-2 at Rf = 0.39 and 0.44, respectively. The highest/lowest content of CM-1 and CM-2 were found in S12/S5 and S5/S17, respectively. The molecular docking studies of CM-1 and CM-2 with human DNA topoisomerase IIα have shown that both the compounds were bound the active sites of the respective enzymes. Molecular dynamics simulation studies further confirmed that the interactions of CM-1 and CM-2 with topoisomerase were stable in nature. This study will help us in selection of appropriate myrrh sample for the greater benefits of the population in the Middle East region.

Keywords: Antioxidant; Cytotoxicity; Furanosesquiterpenoids; HPTLC; Molecular docking; Myrrh.

Fig. 1

Chemical structures of furanosesquiterpenoids (CM-1 and CM-2).

Fig. 2

Chromatogram of CM-1 and CM-2 in S1–S17 [mobile phase: toluene: chloroform: glacial acetic (7:2.9:0.1, v/v/v)]. (A) Chromatogram of standards CM-1 (Rf = 0.39 ± 0.001) and CM-2 (Rf = 0.44 ± 0.001) at λmax = 530 nm; (B) Pictogram of derivatized TLC plate in day light; (C) Spectral comparison of all tracks at 530 nm.

Fig. 3

Quantification of CM-1 and CM-2 in different myrrh samples (S1–S17) by HPTLC using toluene: chloroform: glacial acetic (7:2.9:0.1, v/v/v) as mobile phase. (A) Chromatogram of S5 [CM-1, spot 8, Rf = 0.39; CM-2, spot 9, Rf = 0.44)]; (B) Chromatogram of S2 [CM-1, spot 4, Rf = 0.39; CM-2, spot 5, Rf = 0.44)]; (C) Chromatogram of S10 [CM-1, spot 4, Rf = 0.39; CM-2, spot 5, Rf = 0.44)]; (D) Chromatogram of S12 [CM-1, spot 5, Rf = 0.39; CM-2, spot 6, Rf = 0.44)].

Fig. 4

Molecular docking of CM-1 (panel A) and CM-2 (panel B) with human DNA topoisomerase IIα.

Fig. 5

Molecular dynamic (MD) simulation of CM-1 and CM-2 with proteins showing variation in root mean square deviations (RMSDs) and radius of gyration (rGyr) with simulation time. Panels A and B show RMSD and rGyr of human DNA topoisomerase IIα respectively.