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. 2022 Jun 17;27(12):3903.
doi: 10.3390/molecules27123903.

Phytochemical Composition of Commiphora Oleogum Resins and Their Cytotoxicity against Skin Cancer Cells

Affiliations

Phytochemical Composition of Commiphora Oleogum Resins and Their Cytotoxicity against Skin Cancer Cells

Judith Ulrich et al. Molecules. .

Abstract

Oleogum resins of the genus Commiphora have been used in traditional medicines for centuries. More than 200 Commiphora species exhibit highly variable phytochemical compositions. A novel highly selective, sensitive, accurate HPLC-MS/MS method was developed and validated to quantify five characteristic phytosteroids and furanosesquiterpenoids, namely (E)-guggulsterone, (Z)-guggulsterone, curzerenone, furanoeudesma-1,3-diene, and myrrhone. The resulting contents and additionally GC analysis were used to classify and differentiate Commiphora oleogum resins of the species C. myrrha, C. erythraea, C. mukul, C. holtziana, C. confusa, and C. kua, as well as unspecified resins. Interestingly, a Commiphora sample from Ogaden, Ethiopia, comprised 446 ng/mg guggulsterones presumed to be unique to C. mukul from the Indian subcontinent. However, Commiphora from Ogaden differed considerably from C. mukul in respect to guggulsterones isomer's ratio. Moreover, the cytotoxicity of Commiphora extracts, essential oils, botanical drugs containing Commiphora, and pure compounds against the epidermoid carcinoma A431, malignant melanoma RPMI-7951 and SK-MEL-28 cells was investigated in vitro. Thereby, especially C. mukul extract and C. myrrha essential oil exhibited high cytotoxicity against skin cancer cells with IC50 of 2.9-10.9 µg/mL, but were less toxic to normal keratinocytes. In summary, Commiphora oleogum resins and its phytochemicals warrant further investigation aiming at chemotaxonomical classification as well as application in skin cancer treatment.

Keywords: Commiphora; Guggul; Guggulsterone; Myrrh; Terpenoids; skin cancer.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Commiphora tree and lead compounds of the genus Commiphora. (a) Tree of the species C. myrrha in Somalia. Picture with friendly permission from Georg Huber. (b) Chemical structures of lead compounds found in Commiphora species: phytosteroids (E)-guggulsterone and (Z)-guggulsterone and furanosesquiterpenoids curzerenone, furanoeudesma-1,3-diene, and myrrhone.
Figure 2
Figure 2
Contour plots visualizing the effects of variables A (starting concentration of eluent B) and variable B (slope of gradient) on chromatographic resolution R and mean retention time Ø tR of guggulsterones. Numbers (5–12 and 15) demonstrate the individual experiments (described in detail in Table S1). The level conditions of experiment #8 exhibited the required chromatographic resolution R < 1.5 and a rapid run time with Ø tR < 5 min. (a) Effect of variables A and B on the chromatographic resolution R between (E)-guggulsterone and (Z)-guggulsterone. (b) Effect of variables A and B on the averaged retention time Ø tR of (E)-guggulsterone and (Z)-guggulsterone.
Figure 3
Figure 3
Radar charts visualizing the contents of (E)-guggulsterone, (Z)-guggulsterone, curzerenone, furanoeudesma-1,3-diene, and myrrhone in Commiphora oleogum resins from different species and locations as well as two Commiphora botanical drugs, Myrrhinil-Intest® and Gugulipid®. All contents are normalized and logarithmically scaled. (a) Composition of guggulsterones and furanosesquiterpenoids in C. myrrha (blue) and Myrrhinil-Intest® (orange). Annotation and scaling correspond to all other radar charts. (b) C. erythraea. (c) C. mukul (blue) and Gugulipid® (orange). (d) C. kataf. (e) C. holtziana. (f) C. confusa. (g) C. kua. (h) Commiphora oleogum resin from Tarraxo (Somalia). (i) Commiphora oleogum resin from Ogaden (Ethiopia).
Figure 4
Figure 4
Chromatograms of C. mukul olegum resin. Despite a complex biological matrix, HPLC-MS/MS analysis enabled selective quantification of (E)-guggulsterone and (Z)-guggulsterone. Curzerenone, furanoeudsma-1,3-diene, and myrrhone were not detectable in C. mukul. (a) Total wavelength chromatogram (TWC) with detection at 210 nm, 254 nm, and 280 nm. (b) Multiple reaction monitoring (MRM) chromatogram with m/z 313.3/97.1 as quantifier (blue) and m/z 313.3/109.1 as qualifier (red) for both guggulsterone isomers.
Figure 5
Figure 5
Chromatograms of C. holtziana olegum resin. HPLC-MS/MS analysis revealed the presence of curzerenone, furanoeudsma-1,3-diene, and myrrhone in C. holtziana, but no guggulsterones. (a) Total wavelength chromatogram (TWC) with detection at 210 nm, 254 nm, and 280 nm. (b) Multiple reaction monitoring (MRM) chromatogram of curzerenone (tR = 4.32 min) with m/z 231.0/83.0 as quantifier (blue) and m/z 231.0/149.0 as qualifier (red). (c) MRM chromatogram of myrrhone (tR = 6.03 min) with m/z 229.0/159.0 as quantifier (blue) and m/z 229.0/187.2 as qualifier (red). (d) MRM chromatogram of furanoeudesma-1,3-diene (tR = 9.22 min) with m/z 215.0/119.1 as quantifier (blue) and m/z 215.0/105.2 as qualifier (red).
Figure 6
Figure 6
C. mukul extract and C. myrrha essential oil are more toxic to malignant melanoma cell line RPMI-7951 than to normal human keratinocytes. (a) C. mukul extract. (b) C. myrrha essential oil. Cell viability was analyzed by XTT assay in cells treated for, 72 h. All data were mean ± SEM of three biological samples, each analyzed in triplicates.

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