Targeting SRD5A1 and MMP-2/NLRP3/TGF-β1 axis alleviates the amlodipine-induced gingival hyperplasia in rats: Emerging role of saw palmetto and folic acid

Manar Mohammed El Tabaa; Mahmoud Moustafa Aboud; Anis Anis; Eman Rashad; Samia Salem Sokar

doi:10.1016/j.fct.2024.114731

Targeting SRD5A1 and MMP-2/NLRP3/TGF-β1 axis alleviates the amlodipine-induced gingival hyperplasia in rats: Emerging role of saw palmetto and folic acid

Food Chem Toxicol. 2024 May 11:189:114731. doi: 10.1016/j.fct.2024.114731. Online ahead of print.

Authors

Manar Mohammed El Tabaa¹, Mahmoud Moustafa Aboud², Anis Anis³, Eman Rashad⁴, Samia Salem Sokar⁵

Affiliations

¹ Pharmacology & Environmental Toxicology, Environmental Studies & Research Institute (ESRI), University of Sadat City, Sadat City, 32897, Menoufia, Egypt. Electronic address: manar.eltabaa@esri.usc.edu.eg.
² Dental Science, Environmental Studies & Research Institute (ESRI), University of Sadat City, Sadat City, 32897, Menoufia, Egypt. Electronic address: Mahmoud.mostafa@esri.usc.edu.eg.
³ Pathology, Faculty of Veterinary Medicine, University of Sadat City, Sadat City, 32897, Menoufia, Egypt. Electronic address: aniszaid@vet.usc.edu.eg.
⁴ Cytology and Histology Department, Faculty of Veterinary Medicine, Cairo University, Egypt. Electronic address: emanrashad@cu.edu.eg.
⁵ Pharmacology & Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt. Electronic address: samya.sokar@pharm.tanta.edu.eg.

PMID: 38740241
DOI: 10.1016/j.fct.2024.114731

Abstract

Saw palmetto (SAW), the herbal drug used to treat prostatic hyperplasia, exerts its antiproliferative effects by blocking steroid 5 alpha-reductase (SRD5A1) activity, that has also been involved in gingival hyperplasia (GH) pathogenesis. Concurrently, folic acid (FA) could reduce GH prevalence via its antioxidant and anti-inflammatory effects. Thus, this study tended to assess the potential therapeutic efficacy of SAW, alone and along with FA, against amlodipine-induced gingival inflammation and overgrowth in rats. Rats were grouped into (CONT, AIGH, SAW, SAW-treated, FA-treated, and SAW + FA-treated). SAW and FA were administered once daily for 4 weeks. Gingival SRD5A1, CTGF, GSK-3β, and NLRP3 expressions, as well as T, DHT, MDA, TAC, ET-1, and MMP2 levels were determined. In addition, histopathological and immunohistochemical analyses of TNF-α, IL-6, TGF-β1, and α-SMA were documented. Results declared that SAW and FA administration markedly ameliorated amlodipine-associated GH and may be presenting a novel therapeutic avenue in the future.

Keywords: Amlodipine; Folic acid; Gingival hyperplasia; MMP-2/NLRP3/TGF-β1 axis; SRD5A1; Saw palmetto.