EXPLORING THE ANTI-INFLAMMATORY PROPERTIES OF METFORMIN IN EXPERIMENTAL HEMORRHOID MODELS

DARMAWI DARMAWI; MUHAMMAD YULIS HAMIDY; SORAYA SORAYA; NURUL AZIZAH; LALU MUHAMMAD IRHAM; BAIQ LENY NOPITASARI; INA F. RANGKUTI; A. A. MUHAMMAD NUR KASMAN; WIRAWAN ADIKUSUMA

doi:10.22159/ijap.2025v17i2.53174

Authors

DARMAWI DARMAWI 1 Department of Histology, Faculty of Medicine, Universitas Riau, Pekanbaru, Indonesia
MUHAMMAD YULIS HAMIDY 2 Department of Pharmacology, Faculty of Medicine, Universitas Riau, Pekanbaru, Indonesia https://orcid.org/0000-0003-3412-4063
SORAYA SORAYA 3 Master Program in Biomedical Sciences, Faculty of Medicine, Universitas Riau, Pekanbaru, Indonesia
NURUL AZIZAH 3 Master Program in Biomedical Sciences, Faculty of Medicine, Universitas Riau, Pekanbaru, Indonesia
LALU MUHAMMAD IRHAM Faculty of Pharmacy, Universitas Ahmad Dahlan, Yogyakarta, Indonesia
BAIQ LENY NOPITASARI Department of Pharmacy, Faculty of Health Science, Universitas Muhammadiyah Mataram, Mataram, Indonesia
INA F. RANGKUTI Department of Pathology Anatomy, Faculty of Medicine, Universitas Riau, Pekanbaru, Indonesia
A. A. MUHAMMAD NUR KASMAN Research Center for Applied Zoology, Research Organization for Life Sciences and Environment, National Research and Innovation Agency (BRIN), Cibinong, Indonesia. 8 Department of Midwifery, Faculty of Health Science, Universitas Muhammadiyah Mataram, Mataram, Indonesia https://orcid.org/0000-0003-2511-4920
WIRAWAN ADIKUSUMA 5 Department of Pharmacy, Faculty of Health Science, Universitas Muhammadiyah Mataram, Mataram, Indonesia. 9 Research Center for Computing, Research Organization for Electronics and Informatics, National Research and Innovation Agency (BRIN), Cibinong, Indonesia https://orcid.org/0000-0001-9165-690X

DOI:

https://doi.org/10.22159/ijap.2025v17i2.53174

Keywords:

Anti-inflammatory effects, Gene expression, Hemorrhoids, Leukocyte infiltration, metformin

Abstract

Objective: This study investigated the anti-inflammatory potential of metformin as a therapeutic agent in an experimental hemorrhoid model using Sprague-Dawley rats.

Methods: Rats were assigned to six groups: normal control, negative control (hemorrhoid-induced without treatment), positive control (hemorrhoid-induced and treated with aspirin), and three metformin-treated groups receiving 3 mg/kg, 9 mg/kg, and 15 mg/kg body weight doses. Metformin's effects were assessed through macroscopic observation, qPCR analysis of IL-6, TNF-α, IL-10, and COX-2 gene expression, and histopathological examination of leukocyte infiltration and venule diameter.

Results: qPCR analysis revealed significant reductions in IL-6 and TNF-α expression in metformin-treated groups compared to the negative control. Specifically, the 9 mg/kg dose achieved a 99% reduction in IL-6 and over 98% reduction in TNF-α expression. COX-2 expression was also significantly decreased in metformin-treated groups (p<0.0001), while IL-10 expression remained unchanged (p=0.3973). Histopathological analysis showed a dose-dependent reduction in leukocyte infiltration, with the 15 mg/kg dose exhibiting the most significant decrease (p<0.0001). Additionally, metformin treatment resulted in a significant reduction in venule diameter, particularly at the 15 mg/kg dose (p<0.0001).

Conclusion: These results suggest that metformin, especially at higher doses, has significant anti-inflammatory effects in experimental hemorrhoid models, indicating its potential as a promising therapeutic option for hemorrhoid treatment.

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