Sulawesi Propolis Induces Higher Apoptotic Activity and Lower Inflammatory Activity in a Rat Endometriosis Model

Overview

Journal Eur J Obstet Gynecol Reprod Biol X

Specialty Gynecology & Obstetrics

Date 2023 Sep 27

PMID 37753513

Authors

H Situmorang

A Hestiantoro

S Purbadi

P E Wuyung

R A Werdhani

A Harahap

W Permadi

M Sahlan

W Hadisaputra

Affiliations

Soon will be listed here.

Abstract

Background: Endometriosis has a major impact on women's quality of life. The two primary pathologies are chronic inflammation and altered apoptotic activity. Sulawesi propolis has been shown to have known anti-inflammatory and pro-apoptotic properties in other diseases.

Objective: To investigate the effects of Sulawesi propolis in the rat endometriosis model.

Methods: An autologous endometriosis model was created in 60 female Wistar rats by laparotomy. Rats were divided into four groups ( = 15 in each group): control group (CG), dienogest group (DG), propolis 50 mg/kg body weight (BW)/day (P50) group, and propolis 100 mg/kg BW/day (P100) group. Each treatment group was divided into three different treatment durations ( = 5 in each treatment group): 2, 4 and 6 weeks. After treatment, laparotomy was performed to determine endometriotic tissue growth, apoptosis [caspase-3 and Bcl-2-associated X/Bcl-2 (Bax/Bcl)] and inflammation [prostaglandin-E2 (PGE2) and interleukin-1B (IL-1B)].

Results: A significant difference was seen in endometriotic tissue growth between the P50 group and the CG, with the greatest reduction in the P50 6-week (P50-6) group, reaching 70.66% of the initial area. Highest Bax/Bcl-2 mRNA expression was shown in the P50-4 and P100-4 groups, highest caspase-3 expression was shown in the P50-2 and P50-4 groups, and lowest IL-1B expression was shown in the P50-4 group; all differed significantly from the CG. No significant difference in PGE2S mRNA was found between the groups.

Conclusion: Sulawesi propolis extract suppressed endometriotic tissue growth in the rat model by increasing apoptotic activity. The effects were time-dependent, with 50 mg/kg BW as the optimal dose.

References

Gonzalez-Ramos R, Defrere S, Devoto L . Nuclear factor-kappaB: a main regulator of inflammation and cell survival in endometriosis pathophysiology. Fertil Steril. 2012; 98(3):520-8. DOI: 10.1016/j.fertnstert.2012.06.021. View

Begnini K, de Leon P, Thurow H, Schultze E, Campos V, Rodrigues F . Brazilian red propolis induces apoptosis-like cell death and decreases migration potential in bladder cancer cells. Evid Based Complement Alternat Med. 2014; 2014:639856. PMC: 4235187. DOI: 10.1155/2014/639856. View

Sahlan M, Devina A, Pratami D, Situmorang H, Farida S, Munim A . Anti-inflammatory activity of species from Indonesia. Saudi J Biol Sci. 2019; 26(7):1531-1538. PMC: 6864151. DOI: 10.1016/j.sjbs.2018.12.008. View

Grandi G, Mueller M, Bersinger N, Cagnacci A, Volpe A, McKinnon B . Does dienogest influence the inflammatory response of endometriotic cells? A systematic review. Inflamm Res. 2015; 65(3):183-92. DOI: 10.1007/s00011-015-0909-7. View

Xu H, Zhang S . Scutellarin-induced apoptosis in HepG2 hepatocellular carcinoma cells via a STAT3 pathway. Phytother Res. 2012; 27(10):1524-8. DOI: 10.1002/ptr.4892. View

Vercellini P, Vigano P, Somigliana E, Fedele L . Endometriosis: pathogenesis and treatment. Nat Rev Endocrinol. 2013; 10(5):261-75. DOI: 10.1038/nrendo.2013.255. View

Situmorang H, Hestiantoro A, Purbadi S, Flamandita D, Sahlan M . 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. Ann Med Surg (Lond). 2021; 67:102459. PMC: 8237281. DOI: 10.1016/j.amsu.2021.102459. View

Xu G, Kuang G, Jiang W, Jiang R, Jiang D . Polydatin promotes apoptosis through upregulation the ratio of Bax/Bcl-2 and inhibits proliferation by attenuating the β-catenin signaling in human osteosarcoma cells. Am J Transl Res. 2016; 8(2):922-31. PMC: 4846936. View

Sawicka D, Car H, Borawska M, Niklinski J . The anticancer activity of propolis. Folia Histochem Cytobiol. 2012; 50(1):25-37. DOI: 10.2478/18693. View

10.

de Figueiredo S, Nogueira-Machado J, Almeida B, Abreu S, de Abreu J, Filho S . Immunomodulatory properties of green propolis. Recent Pat Endocr Metab Immune Drug Discov. 2014; 8(2):85-94. DOI: 10.2174/1872214808666140619115319. View

11.

Lin Y, Chen Y, Chang H, Au H, Tzeng C, Huang Y . Chronic Niche Inflammation in Endometriosis-Associated Infertility: Current Understanding and Future Therapeutic Strategies. Int J Mol Sci. 2018; 19(8). PMC: 6121292. DOI: 10.3390/ijms19082385. View

12.

Taniguchi F, Kaponis A, Izawa M, Kiyama T, Deura I, Ito M . Apoptosis and endometriosis. Front Biosci (Elite Ed). 2011; 3(2):648-62. DOI: 10.2741/e277. View

13.

Klipping C, Duijkers I, Remmers A, Faustmann T, Zurth C, Klein S . Ovulation-inhibiting effects of dienogest in a randomized, dose-controlled pharmacodynamic trial of healthy women. J Clin Pharmacol. 2011; 52(11):1704-13. DOI: 10.1177/0091270011423664. View

14.

Moradi M, Parker M, Sneddon A, Lopez V, Ellwood D . Impact of endometriosis on women's lives: a qualitative study. BMC Womens Health. 2014; 14:123. PMC: 4287196. DOI: 10.1186/1472-6874-14-123. View

15.

Harada T, Taniguchi F, Kitajima M, Kitawaki J, Koga K, Momoeda M . Clinical practice guidelines for endometriosis in Japan (The 3rd edition). J Obstet Gynaecol Res. 2022; 48(12):2993-3044. PMC: 10087749. DOI: 10.1111/jog.15416. View

16.

Miyata R, Sahlan M, Ishikawa Y, Hashimoto H, Honda S, Kumazawa S . Propolis Components from Stingless Bees Collected on South Sulawesi, Indonesia, and Their Xanthine Oxidase Inhibitory Activity. J Nat Prod. 2019; 82(2):205-210. DOI: 10.1021/acs.jnatprod.8b00541. View

17.

Zhang Y, Chen A, Li M, Chen C, Yao Q . Ginkgo biloba extract kaempferol inhibits cell proliferation and induces apoptosis in pancreatic cancer cells. J Surg Res. 2008; 148(1):17-23. PMC: 2924764. DOI: 10.1016/j.jss.2008.02.036. View

18.

Teixeira da Silva J, Ng T . The medicinal and pharmaceutical importance of Dendrobium species. Appl Microbiol Biotechnol. 2017; 101(6):2227-2239. DOI: 10.1007/s00253-017-8169-9. View

19.

Galo S, Zubor P, Szunyogh N, Kajo K, Machalekova K, Biringer K . [TNF-alpha serum levels in women with endometriosis: prospective clinical study]. Ceska Gynekol. 2005; 70(4):286-90. View

20.

Cheung C, Ka-Wing Chung K, Lui J, Lau C, Hon P, Chan J . Leachianone A as a potential anti-cancer drug by induction of apoptosis in human hepatoma HepG2 cells. Cancer Lett. 2007; 253(2):224-35. DOI: 10.1016/j.canlet.2007.01.025. View