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Effects of Sulawesi Propolis Extract on Lesion Growth, Apoptotic and Inflammatory Activity of the Rat Endometriosis Tissue

Early Phase 1
Completed
Conditions
Endometriosis; Peritoneum
Endometriosis
Interventions
Registration Number
NCT04374006
Lead Sponsor
Indonesia University
Brief Summary

This study aims to evaluating inflammatory and apoptotic activity in rat's endometriosis lesion treated by Propolis compared to Dienogest

Detailed Description

Propolis has known of having various efficacy. The main benefits are as antimicrobial, antioxidant, anti-inflammatory, immunomodulatory and antiapoptotic.Propolis has even been shown to have an antibacterial effect in vitro, without requiring human immunological reactions.

The immunological effect of propolis is generated through immune suppression directly and decreasing cytokine production which stimulates immune process. Although proven to have a various efficacy, propolis can't be used as a therapeutic drug due to the difficulty of obtaining standard chemical composition as a requirement to be the drug's substances. Therefore, it is necessary to have biological composition in each propolis prepartions written down before comparing the efficacy.

Anti tumor activity by propolis, which has been tested in animal previously, showed that propolis can inhibit DNA synthesis in tumor cells, induce cell apoptosis and activate macrophage to produce factors which regulate the function of B, T, as well as NK cell.

Dienogest, is the next choice of progestin drug class. It has high selectivity binding in progesterone receptors, inhibits cytokine secretion in endometriosis stroma cell and induces apoptosis in endometriosis cell. Dienogest also has slight inhibitory effect against estradiol, so it can deminisce the symptoms due to hypoestrogenic such as decresing in bone mass density.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
120
Inclusion Criteria
  • female ratus rat type
  • having normal estrus cycle
Exclusion Criteria
  • nothing

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
waterplacebowe do sonde everyday to the rat that given 0,2 ml water placebo for 2, 4, and 6 weeks
sham groupplaceboafter the 2nd laparotomy, we do nothing about sonde, just giving food and drink everyday
propolis 100Propoliswe do sonde everyday to the rat that given treatment of 100mg/kg propolis for 2, 4, and 6 weeks
propolis 50Propoliswe do sonde everyday to the rat that given treatment of 50mg/kg propolis for 2, 4, and 6 weeks
dienogestDienogestwe do sonde everyday to the rat that given treatment of 25mg/kg dienogest for 2, 4, and 6 weeks
Primary Outcome Measures
NameTimeMethod
The normality of estrus cycle after the treatmentduring the procedure

Vaginal discharge of the rat obtained through vaginal lavage was fixed using 90% alcohol solution and stained using Giemsa. The specimen was examined microscopically to determined its estrous cycle

mRNA expressions of Bax, Bcl, Cleaved Caspase 3, IL-1B, and PGE 2through study completion, an average of 6 months

The expression of Bax, Bcl-2, ad Caspase 3, IL-1B, PGE2 mRNA was carried out by isolating the RNA samples of endometriosis tissue based on the modified QIAamp RNA Blod Mini Handbook protocol. RNA spectrophotometric measurments and cDNA synthesis were carried out based on the Instruction Manual ReverTra Ace qPCR RT Master Mix with gDNA Remover protocol (Toyobo 2017: 2). In real-time PCR examination, the melting temperature (Tm) was determined to perform Quantitative Real-time PCR (Q-PCR) based on the QuantiTech SYBR Green PCR Handbook protocol (Qiagen 2011: 11) using a 3-step cycling cycle. The results were then compared with the standard curve and analyzed

Mollecular dockingduring the procedure

Twenty-three compounds contained in Propolis were tested by screening using rule of 5 (Lipinski's rule), screening results determine which compounds can enter the body and can work in endometriosis tissue. Furthermore, the three-dimensional shape is made of compounds which have passed the first stage. This process was created using the Marvin Sketch program. Furthermore, the compound that has been formed is stored as a ligand with extension pdb (protein data bank). Look for NFĸB receptor proteins, estrogen A, estrogen B, progesterone A and progesterone B in the protein data bank, which will be stored as protein. Ligands and proteins are tested using standard Lamarckian algorithms in the Autodock program. The results obtained are in the form of bond energy (ΔG), where smaller results indicate a higher likelihood of interaction

Lession sizeduring the procedure

In the second laparotomy (before the treatment are given) the investigators take a picture of the lession (as the beginning lession). Then the investigators give the treatment. After the treatment are done, the investigators do the necropsy to take a picture after the treatment was given to compare it with the beginning

Secondary Outcome Measures
NameTimeMethod
Organs morpholgy after the treatmentthrough study completion, an average of 6 months

In the necropsy, the investigators take ovarium, uterus, and peritonium to see if there's any change in morphology after the treatment was given

Trial Locations

Locations (1)

Animal Laboratory of Indonesia University

🇮🇩

Jakarta, Capital Special Region, Indonesia

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