IN-SILICO dynamic analysis of Sulawesi propolis as anti-endometriosis drug: Interaction study with TNF alpha receptor, NF-kB, estrogen receptor, progesterone receptor and prostaglandin receptor

Abstract

Introduction Endometriosis is a disease that impacts around 10% of all women in reproductive age, with pelvic pain and infertility as its main clinical features. Current medical treatment targeting lowering estrogen activity has not shown sufficient result due its side effects and reproductive function suppression. Propolis has been widely studied, showing anti inflammation and pro-apoptosis property, that could potentially be used in the treatment of endometriosis. This study investigates the interaction between Sulawesi Propolis’ active components and receptors and protein related to endometriosis pathogenesis. Methods Active components of Sulawesi Propolis were initially identified with their targeted protein receptors. Lipinski rules were used to screen potential components. The ligands and proteins were tested using Autodock program to predict the most active compound and possible binding sites between propolis and some target proteins associated with inflammatory and apoptotic activity in endometriosis models. Receptor modelling is then performed using Swiss-Model. Results These active components of Sulawesi Propolis showed a strong binding potential towards TNF- α, NF-kb, Estrogen-α, Estrogen-β, progesterone B, PGE2 EP2 and EP3 subtype respectively: Sanggenon C, Sanggenon H, Epicryptoacetalide, Chrysin-7-O-β-D-glucopyranodside, Irilone, Polydatin and Epicryptoacetalide. Compared to its negative ligand, Sulawesi Propolis displayed a stronger binding capacity to TNF-α, Estrogen-α, and Progesterone B receptors. Conclusion Sulawesi Propolis has the ability to interact with receptors related to reproductive function, apoptotic reactions and inflammatory processes, a significant factor associated with the pathogenesis of endometriosis.

What do the Transcriptome and Proteome of Menstrual Blood-derived Mesenchymal Stem Cells Tell us about Endometriosis?

“…Another study with peritoneal fluid from women with endometriosis showed that TNFA signaling can increase EGR1 expression and collaborate with the establishment and maintenance of the disease [71]. In addition, TNFA can be increased by NFkB accelerating the prolonged inflammatory process responsible for the reduction of apoptosis activity in endometriosis [72], making sense for TNFA signaling via the NFkB pathway in our findings.…”

What Do the Transcriptome and Proteome of Menstrual Blood-Derived Mesenchymal Stem Cells Tell Us about Endometriosis?

“…Another study with peritoneal fluid from women with endometriosis showed that TNFA signaling could increase EGR1 expression and collaborate with establishing and maintaining the disease [ 76 ]. In addition, TNFA can be increased by NFkB, accelerating the prolonged inflammatory process responsible for the reduction of apoptosis activity in the disease [ 77 ], making sense for TNFA signaling via the NFkB pathway in our findings.…”

“…Our findings highlight primary changes in the endometriosis MenSCs that may favor the tissue implantation at the ectopic site. The global expression profile enriched critical pathways already related to the endometriosis condition, such as PI3K signaling via AKT to mTORC1 [ 63 , 64 , 65 ], mTORC1 signaling [ 97 ], TNFA signaling via NFkB [ 76 , 77 ], IL6 STAT3 signaling [ 75 ], TGF beta signaling [ 72 , 73 ], and hypoxia via HIF1A targets [ 74 ]. These dysregulations suggest that the chronic inflammatory endometrial microenvironment [ 26 ] can modulate these cells and provide opportunities for the etiopathogenesis of the disease.…”

Obstetri̇de Ve Ji̇nekoloji̇de Api̇terapi̇ni̇n Kullanimi

“…Çalışma sonucunda propolis, endometriyozis ile ilgili reseptörlere karşı güçlü bir bağlanma potansiyeli göstermesine rağmen, gerçek biyolojik bir etki gösterememiştir. Çalışmada propolisin endometriyozis dokusu üzerindeki etkili dozunu saptamak amacıyla farklı klinik deneysel çalışmalara ihtiyaç olduğu vurgulanmıştır (55).…”