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Article Open Access

Myrrh ameliorates endometriosis by enhancing ER stress‑related apoptotic cell death

  • Authors:
    • Bo-Sung Kim
    • Minkyoung Cho
    • Jung Ho Han
    • Jung-Sook Jin
    • Sung-Jin Bae
    • Yunju Jo
    • Dongryeol Ryu
    • Yerim Joo
    • Seon Beom Kim
    • Jongkil Joo
    • Inhye Kim
    • Ki-Tae Ha
  • View Affiliations / Copyright

    Affiliations: Research Institute for Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam‑do 50612, Republic of Korea, Department of Parasitology and Tropical Medicine, Institute of Medical Science, College of Medicine, Gyeongsang National University, Jinju, Gyeongsangnam‑do 52727, Republic of Korea, Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam‑do 50612, Republic of Korea, Department of Molecular Biology and Immunology, Kosin University College of Medicine, Busan 49267, Republic of Korea, Department of Microbiology, Wonkwang University School of Medicine, Iksan, Jeollabuk‑do 54538, Republic of Korea, Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea, Department of Food Science and Technology, Pusan National University, Miryang, Gyeongsangnam‑do 50463, Republic of Korea, Department of Obstetrics and Gynecology, Pusan National University School of Medicine and Pusan National University Hospital Biomedical Research Institute, Busan 49241, Republic of Korea
    Copyright: © Kim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 85
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    Published online on: January 29, 2026
       https://doi.org/10.3892/etm.2026.13080
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Abstract

Endometriosis is characterized by ectopic growth of endometrial tissue causing severe abdominal pain and inflammation during disease progression. Myrrh, a resin collected from trees of genus Commiphora known for its anti‑inflammatory and pain‑relieving properties, has not yet been explored for endometriosis treatment. The present study utilized network pharmacology and subsequent in vitro/in vivo experiments to assess myrrh's antiendometriotic potential. In a mouse model, orally administrated myrrh significantly reduced the weight of endometriotic foci at low doses (0.7 or 3.5 mg/kg/day). Myrrh showed higher toxicity in 12Z cells compared with T‑HESCs and triggered mitochondrial‑associated apoptosis by altering the Bcl‑2/Bax ratio. RNA sequencing and bioinformatic analysis revealed that myrrh upregulates pathways such as the unfolded protein response (UPR), proteasomal proteolysis, and endoplasmic reticulum stress. Differentially expressed gene analysis showed an increase in genes essential for the UPR, including PPP1R15A, DDIT3, ATF6, ERN1 and ATF4, which was validated by reverse transcription‑quantitative PCR. Treatment with tauroursodeoxycholic acid, an ER stress inhibitor, was found to abolish myrrh‑induced cytotoxicity. Overall, these findings suggest that myrrh inhibits the growth of endometrial foci by inducing ER stress and subsequent apoptosis. Therefore, myrrh may be a potential therapeutic candidate for endometriosis. 
1. Introduction
View Figures

Figure 1

Network pharmacology analysis
demonstrates the potential therapeutic effect of myrrh on
endometriosis. (A) Venn diagram analysis is performed utilizing
endometriosis-related genes and myrrh targets. (B) Protein-protein
interaction network of the 26 common genes is analyzed in CytoScape
with the STRING plugin.

Figure 2

Identification of components of myrrh
using LC-MS. LC-MS analysis confirmed the presence of (A) oleanolic
acid and (B) oleanonic acid in C. myrrha extract. LC-MS,
Liquid Chromatography-Mass Spectrometry.

Figure 3

Myrrh reduces the weight of ectopic
endometrial lesions in mice. (A) Representation of ectopic
endometrial tissue with and without myrrh treatment. (B) Weight of
endometrial tissue. (C) Number of ectopic endometrial tissues. (D)
TUNEL exhibits red fluorescence and DAPI exhibits blue fluorescence
in the endometriotic foci. Data are presented as mean ± standard
error of the mean. Statistical analysis was performed using one-way
ANOVA followed by Tukey's post hoc test. *P<0.05 and
**P<0.01.

Figure 4

Myrrh reduces the growth of human
endometriotic cells by activating apoptotic signaling pathways.
Endometriotic cells (12Z) and normal endometrial cells (T-HESC)
were treated with the indicated concentrations of myrrh. (A) Cell
viability was analyzed by measuring at 450 nm wavelength using MTT
after 24 h. (B) To assess apoptotic or dead cell populations, 12Z
cells were treated with increasing doses of myrrh for 24 h, and the
percentages of Annexin V-positive and PI-positive cells were
measured (Annexin V: Ex 494/Em 525 nm; PI: Ex 535/Em 617 nm). After
24 h of treatment with each concentration of myrrh,
mitochondria-associated apoptotic proteins were analyzed by
immunoblotting. (C) Representatives immunoblot images of Bax and
Bcl-2 are shown. (D) A major monomeric Bax band at ~21 kDa (monomer
Bax) and higher-molecular-weight bands corresponding to oligomeric
forms (tetramer Bax, ~84 kDa) are indicated. (E) Representative
immunoblot images of caspase-3, caspase-9 and PARP are shown. GAPDH
was used as an internal control. (F) Densitometric analysis of
protein levels. Data are expressed as relative intensity compared
to control. Data are expressed as mean ± standard error of the
mean. Statistical analysis was performed using one-way ANOVA
followed by Tukey's post hoc test. *P<0.05,
**P<0.01 and ***P<0.001. Ex,
excitation; Em, emission; ; PARP, poly(ADP-ribose) polymerase.

Figure 5

RNA sequencing analysis suggests a
molecular mechanism underlying the anti-endometriosis effect of
myrrh. 12Z cells were treated with myrrh (100 µg/ml) for 12 h. The
RNA sequencing data sets provided by a commercial service were
applied to GSEAs. (A) Hallmark and (B) KEGG analysis results are
visualized by bubble plots; key pathways associated with
endometriosis are marked in red. (C) GO analysis data are described
by Cytoscape with enrichment map visualization; cutoff values are
set at P>0.001 and q>0.5. (D) Representative enrichment plots
of GSEAs upon myrrh treatment. GSEA, Gene set enrichment analysis;
KEGG, Kyoto Encyclopedia of Genes and Genomes; GO, Gene
Ontology.

Figure 6

Anti-endometriosis effect of myrrh
related to the UPR response. (A) The DEG analysis is visualized as
log2 (fold change) and -log10 (P-value). Significantly up- or
down-regulated genes are marked with red or blue letters,
respectively. Genes involved in endometriosis-related pathways are
displayed with symbols for each gene. (B) Heatmap analysis is
performed to display the relative expression levels of genes
connected to endometriosis-related pathways. (C) The expression
levels of the genes suggested by the heatmap are validated using
reverse transcription-quantitative PCR. *P<0.05 and
**P<0.01. UPR, unfolded protein response; DEG,
Differentially expressed gene.

Figure 7

Mechanism of action of myrrh in
endometriosis. (A) 12Z were treated with the indicated
concentrations of myrrh and TUDCA (200 µM). Cell viability was
analyzed using MTT after 24 h, measured at a wavelength of 450 nm.
(B) Schematic representation summarizing the experimental results
and the potential mechanism by which myrrh exerts palliative
effects on endometriosis. ***P<0.001. TUDCA,
tauroursodeoxycholic acid; ATF6, activating transcription factor 6;
IRE1α, inositol-requiring enzyme 1 alpha; ATF4, activating
transcription factor 4; CHOP, C/EBP homologous protein; GADD34,
growth arrest and DNA damage-inducible protein 34; Bax,
Bcl-2-associated X protein; Bcl2, B-cell lymphoma 2; Caspase 3,
cysteine-aspartic acid protease 3; Caspase 9, cysteine-aspartic
acid protease 9; PARP, poly(ADP-ribose) polymerase.
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Copy and paste a formatted citation
Spandidos Publications style
Kim B, Cho M, Han JH, Jin J, Bae S, Jo Y, Ryu D, Joo Y, Kim SB, Joo J, Joo J, et al: Myrrh ameliorates endometriosis by enhancing ER stress‑related apoptotic cell death. Exp Ther Med 31: 85, 2026.
APA
Kim, B., Cho, M., Han, J.H., Jin, J., Bae, S., Jo, Y. ... Ha, K. (2026). Myrrh ameliorates endometriosis by enhancing ER stress‑related apoptotic cell death. Experimental and Therapeutic Medicine, 31, 85. https://doi.org/10.3892/etm.2026.13080
MLA
Kim, B., Cho, M., Han, J. H., Jin, J., Bae, S., Jo, Y., Ryu, D., Joo, Y., Kim, S. B., Joo, J., Kim, I., Ha, K."Myrrh ameliorates endometriosis by enhancing ER stress‑related apoptotic cell death". Experimental and Therapeutic Medicine 31.4 (2026): 85.
Chicago
Kim, B., Cho, M., Han, J. H., Jin, J., Bae, S., Jo, Y., Ryu, D., Joo, Y., Kim, S. B., Joo, J., Kim, I., Ha, K."Myrrh ameliorates endometriosis by enhancing ER stress‑related apoptotic cell death". Experimental and Therapeutic Medicine 31, no. 4 (2026): 85. https://doi.org/10.3892/etm.2026.13080
Copy and paste a formatted citation
x
Spandidos Publications style
Kim B, Cho M, Han JH, Jin J, Bae S, Jo Y, Ryu D, Joo Y, Kim SB, Joo J, Joo J, et al: Myrrh ameliorates endometriosis by enhancing ER stress‑related apoptotic cell death. Exp Ther Med 31: 85, 2026.
APA
Kim, B., Cho, M., Han, J.H., Jin, J., Bae, S., Jo, Y. ... Ha, K. (2026). Myrrh ameliorates endometriosis by enhancing ER stress‑related apoptotic cell death. Experimental and Therapeutic Medicine, 31, 85. https://doi.org/10.3892/etm.2026.13080
MLA
Kim, B., Cho, M., Han, J. H., Jin, J., Bae, S., Jo, Y., Ryu, D., Joo, Y., Kim, S. B., Joo, J., Kim, I., Ha, K."Myrrh ameliorates endometriosis by enhancing ER stress‑related apoptotic cell death". Experimental and Therapeutic Medicine 31.4 (2026): 85.
Chicago
Kim, B., Cho, M., Han, J. H., Jin, J., Bae, S., Jo, Y., Ryu, D., Joo, Y., Kim, S. B., Joo, J., Kim, I., Ha, K."Myrrh ameliorates endometriosis by enhancing ER stress‑related apoptotic cell death". Experimental and Therapeutic Medicine 31, no. 4 (2026): 85. https://doi.org/10.3892/etm.2026.13080
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