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Olmesartan niosomes ameliorates the Indomethacin-induced gastric ulcer in rats: Insights on MAPK and Nrf2/HO-1 signaling pathway

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Abstract

Aims

Gastric ulcer is a continuous worldwide threat that inquires protective agents. Olmesartan (OLM) has potent anti-oxidant and anti-inflammatory characters, yet having limited bioavailability. We targeted the gastro-protective potential and probable mechanism of OLM and its niosomal form against indomethacin (IND) induced-gastric ulcer in rats.

Main methods

we prepared OLM niosomes (OLM-NIO) with different surfactant: cholesterol molar ratios. We evaluated particle size, zeta-potential, polydispersity, and entrapment efficiency. In-vitro release study, Fourier transform infrared spectroscopy, differential scanning calorimetry, and transmission electron microscopy were performed for selected niosomes. In-vivo, we used oral Omeprazole (30 mg/kg), OLM or OLM-NIO (10 mg/kg) for 3 days before IND (25 mg/kg) ingestion. We assessed gastric lesions, oxidative and inflammatory markers.

Key findings

OLM-NIO prepared with span 60:cholesterol ratio (1:1) showed high entrapment efficiency 93 ± 2%, small particle size 159.3 ± 6.8 nm, low polydispersity 0.229 ± 0.009, and high zeta-potential −35.3 ± 1.2 mV, with sustained release mechanism by release data. In-vivo macroscopical and histological results showed gastro-protective effects of OLM pretreatment, which improved oxidative stress parameters and enhanced the gastric mucosal cyclooxygenase-1 (COX-1) and prostaglandin E2 (PGE2) contents. OLM pretreatment suppressed interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) contents and translocation of p38 mitogen-activated protein kinase (p38-MAPK). Besides, OLM substantially promoted the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) protective pathway. OLM-NIO furtherly improved all previous outcomes.

Significance

We explored OLM anti-ulcerative effects, implicating oxidative stress and inflammation improvement, mediated by the Nrf2/HO-1 signaling pathway and p38-MAPK translocation. Meanwhile, the more bioavailable OLM-NIO achieved better gastro-protective effects compared to conventional OLM form.

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Authors and Affiliations

  1. Biochemistry Department, Faculty of Pharmacy, Ain-Shams University, Abassia, Cairo, 11566, Egypt

    Al-Aliaa M. Sallam

  2. Biochemistry Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, 11829, Cairo, Egypt

    Al-Aliaa M. Sallam

  3. Department of Pharmacology & Toxicology, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt

    Samar F. Darwish

  4. Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt

    Walaa A. El-Dakroury

  5. Department of Medical Biochemistry, Faculty of Medicine, Assiut University, 71515, Assiut, Egypt

    Eman Radwan

  6. Department of Biochemistry, Faculty of Pharmacy, Sphinx University, New Assiut City, Assiut 10, Egypt

    Eman Radwan

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  1. Al-Aliaa M. Sallam
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Al-Aliaa M. Sallam-Alia.sallam@pharma.asu.edu.eg-Writing - Original Draft, Resources, Methodology, Validation, Conceptualization

Samar F. Darwish-Samar.fathy@buc.edu.eg-Supervision, Writing - Review & Editing, Formal analysis, Investigation, Software, Visualization

Walaa A. El-Dakroury-w_dakroury@yahoo.com-Visualization, Writing - Original Draft, Formal analysis, Investigation, Software

Eman Radwan-Emanradwan@aun.edu.eg-Data Curation, Methodology, Conceptualization

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Correspondence to Samar F. Darwish.

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Sallam, AA.M., Darwish, S.F., El-Dakroury, W.A. et al. Olmesartan niosomes ameliorates the Indomethacin-induced gastric ulcer in rats: Insights on MAPK and Nrf2/HO-1 signaling pathway. Pharm Res 38, 1821–1838 (2021). https://doi.org/10.1007/s11095-021-03126-5

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  • DOI: https://doi.org/10.1007/s11095-021-03126-5

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