Sildenafil and metformin combination attenuates monocrotaline- induced pulmonary hypertension via TNF-α and ERK1/2 modulation

Cahyono, Agus and Irwanto, Irwanto and Rahman, Mahrus Abdur and Widjiati, Widjiati (2026) Sildenafil and metformin combination attenuates monocrotaline- induced pulmonary hypertension via TNF-α and ERK1/2 modulation. Journal of Pharmacy & Pharmacognosy Research (JPPRes), 14 (01). p. 2507. ISSN 0719-4250

PDF jppres_14.1.2507.pdf Download (924kB)

Abstract

Context: Pediatric pulmonary hypertension (PH) is associated with poor outcomes and limited US-approved pharmacotherapies. Aims: To evaluate the effects of sildenafil, metformin, and their combination on hemodynamics, inflammatory mediators, and vascular remodeling in monocrotaline (MCT)-induced PH. Methods: Male Wistar rats received MCT (60 mg/kg, s.c.). Beginning 24 h later, animals were assigned to MCT-control, sildenafil (5 mg/kg), metformin (100 mg/kg), or combined therapy for 21 days. On day 22, right-heart catheterization was performed. Serum TNF-α and ERK1/2 were measured by ELISA, and pulmonary arterial remodeling was assessed by HE and α-SMA staining with intima-media thickness measurements. Results: Relative to MCT-control, all treatments lowered mPAP; the combination group exhibited the most considerable reductions in TNF-α and ERK1/2, and a partial reduction in intima-media thickness. Conclusions: Sildenafil and metformin, particularly in combination, improved pulmonary hemodynamics and attenuated inflammation in MCT-PH. Confirmation in lung tissue (e.g., p-ERK1/2) and cell-specific analyses is warranted.

Item Type:	Article
Uncontrolled Keywords:	extracellular signal-regulated kinase; metformin; monocrotaline; pulmonary hypertension; sildenafil; tumor necrosis factor-α.
Subjects:	R Medicine > R Medicine (General)
Divisions:	Faculty of Medical
Depositing User:	BAMBANG SEPTIAWAN
Date Deposited:	27 Jan 2026 02:52
Last Modified:	27 Jan 2026 02:52
URI:	http://repository.ubaya.ac.id/id/eprint/50197

Actions (login required)

View Item