An Unprecedented 4,8-Cycloeudesmane, Further New Sesquiterpenoids, a Triterpene, Steroids, and a Lignan from the Resin of Commiphora myrrha and Their Anti-Inflammatory Activity In Vitro.

Myrrh has a long tradition in the treatment of inflammatory diseases. However, many of its (active) constituents are still unknown. In the present study, secondary metabolites were isolated from an ethanolic extract by various separation methods (liquid-liquid partition, silica and RP18 flash chromatography, CPC, and preparative HPLC), their structures were elucidated with NMR spectroscopy and mass spectrometry, and the selected compounds were tested for their effect on LPS-induced NO production by RAW 264.7 murine macrophages. Among the isolated substances are 17 sesquiterpenes (1-17) including the first 4,8-cycloeudesmane (1), a triterpene (38), two phytosterols (39, 40) and one lignan (43), which were previously unknown as natural products. Numerous compounds are described for the first time for the genus Commiphora. Eight of the eleven compounds tested (1, 29, 31, 32, 34-37) showed a statistically significant, concentration-dependent weak to moderate anti-inflammatory effect on NO production in the LPS-stimulated RAW 264.7 macrophages in vitro. For the reference substance, furanoeudesma-1,3-diene, an IC50 of 46.0 µM was determined. These sesquiterpenes might therefore be part of the multi-target molecular principles behind the efficacy of myrrh in inflammatory diseases.

Terpenoids from Myrrh and Their Cytotoxic Activity against HeLa Cells.

The oleo-gum resin of Commiphora myrrha (Nees) Engl. has a long history of medicinal use, although many of its constituents are still unknown. In the present investigation, 34 secondary metabolites were isolated from myrrh resin using different chromatographic techniques (silica flash chromatography, CPC, and preparative HPLC) and their structures were elucidated with NMR spectroscopy, HRESIMS, CD spectroscopy, and ECD calculations. Among the isolated substances are seven sesquiterpenes (1-7), one disesquiterpene (8), and two triterpenes (23, 24), which were hitherto unknown, and numerous substances are described here for the first time for C. myrrha or the genus Commiphora. Furthermore, the effects of selected terpenes on cervix cancer cells (HeLa) were studied in an MTT-based in vitro assay. Three triterpenes were observed to be the most toxic with moderate IC50 values of 60.3 (29), 74.5 (33), and 78.9 µM (26). Due to the different activity of the structurally similar triterpenoids, the impact of different structural elements on the cytotoxic effect could be discussed and linked to the presence of a 1,2,3-trihydroxy substructure in the A ring. The influence on TNF-α dependent expression of the intercellular adhesion molecule 1 (ICAM-1) in human microvascular endothelial cells (HMEC-1) was also tested for 4-6, 9-11, 17, 18, 20, and 27 in vitro, but revealed less than 20% ICAM-1 reduction and, therefore, no significant anti-inflammatory activity.