Mechanistic Evaluation of Anti-hemorrhoidal Activity of Newbouldia laevis (P. Beauv) Seem. ex-Bureau Extract via Modulation of NF-κB/Nrf2 Signaling in Experimentally Induced Hemorrhoids in Wistar Rats

¹Department of Pharmacognosy, Faculty of Pharmacy, University of Maiduguri, Maiduguri, Nigeria

*Corresponding author: Cletus Anes Ukwubile, Department of Pharmacognosy, Faculty of Pharmacy, University of Maiduguri, Maiduguri, Nigeria, Phone: +2348036985667, Email: [email protected]; [email protected]

Received Date: September 15, 2026

Publication Date: October 12, 2026

Citation: Ukwubile CA, Makinde AO. (2026). Mechanistic Evaluation of Anti-hemorrhoidal Activity of Newbouldia laevis (P.Beauv.) Seem. ex-Bureau Extract via Modulation of NF-κB/Nrf2 Signaling in Experimentally Induced Hemorrhoids in Wistar Rats. Pharmacogn. 4(1):7.

Copyright: Ukwubile CA and Makinde AO, © (2026).

ABSTRACT

Background and Objectives: It is currently unknown which molecular mechanisms underlie the extensive use of Newbouldia laevis stembark in African traditional medicine to treat hemorrhoids. This study investigated the anti-hemorrhoidal impact of N. laevis stembark extract (NLSBE) via altering the nuclear factor-kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways in experimentally produced hemorrhoids in rats.

Materials and Methods: Wistar rats were treated with croton oil to induce hemorrhoids. The animals received NLSBE (100, 200, and 400 mg/kg, p.o.) or a standard anti-hemorrhoidal drug for 14 consecutive days. Hemorrhoidal severity, histology, oxidative stress indices, inflammatory cytokines, and the expression of genes and proteins associated with the NF-κB/Nrf2 pathway were evaluated using biochemical assays, RT-qPCR, immunohistochemistry, and Western blotting.

Results: The 400 mg/kg group's hemorrhoid index dropped by 71.8% (p < 0.001) in comparison to untreated rats, suggesting that NLSBE significantly and dose-dependently decreased hemorrhoidal severity. Histological study revealed a considerable restoration of anorectal architecture with reduced edema, inflammatory cell infiltration, and vascular congestion. Reduced glutathione (4.28 ± 0.37 to 8.51 µmol/g tissue), glutathione peroxidase (27.3 ± 2.0 to 49.4 ± 3.1 U/mg protein), catalase (21.5 ± 1.8 to 43.6 ± 2.7 U/mg protein), and superoxide dismutase (18.7 ± 1.4 to 3.1 U/mg protein). NLSBE dramatically reduced the expression of NF-κB p65, TNF-α, IL-1β, IL-6, COX-2, and iNOS by 41–68% while increasing Nrf2, HO-1, and NQO1 by 2.1-, 2.8-, and 2.4-fold, respectively, as compared to the disease control.

Interpretation & Conclusion: NLSBE improved experimental hemorrhoids by reducing oxidative damage and promoting tissue healing by blocking NF-κB-mediated inflammation and activating the Nrf2 antioxidant defense mechanism.

Keywords: Newbouldia laevis, Hemorrhoids, NF-κB, Nrf2, Oxidative Stress, Inflammation