Mirra, un antiinflamatorio natural, reduce el crecimiento de la endometriosis al mejorar la muerte celular apoptótica...

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.