Chrysin promotes angiogenesis in rat hindlimb ischemia: Impact on PI3K/Akt/mTOR signaling pathway and autophagy
Autor: | Rehab Kamel, Engy M. El Morsy, Marwa E. Elsherbiny, Mahmoud Nour‐Eldin |
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Rok vydání: | 2022 |
Předmět: |
Flavonoids
Sirolimus Vascular Endothelial Growth Factor A TOR Serine-Threonine Kinases Arterial Occlusive Diseases Hindlimb Rats Phosphatidylinositol 3-Kinases Ischemia Transforming Growth Factor beta Drug Discovery Autophagy Animals Angiogenesis Inducing Agents Beclin-1 Proto-Oncogene Proteins c-akt Signal Transduction |
Zdroj: | Drug Development Research. 83:1226-1237 |
ISSN: | 1098-2299 0272-4391 |
DOI: | 10.1002/ddr.21954 |
Popis: | Limb ischemia occurs due to obstruction of blood perfusion to lower limbs, a manifestation that is associated with peripheral artery disease (PAD). Angiogenesis is important for adequate oxygen delivery. The present study investigated a potential role for chrysin, a naturally occurring flavonoid, in promoting angiogenesis in hindlimb ischemia (HLI) rat model. Rats were allocated into four groups: (1) sham-operated control, (2) HLI: subjected to unilateral femoral artery ligation, (3) HLI + chrysin: received 100 mg/kg, i.p. chrysin immediately after HLI, and (4) HLI + chrysin + rapamycin: received 6 mg/kg/day rapamycin i.p. for 5 days then subjected to HLI and dosed with 100 mg/kg chrysin, i.p. Rats were killed 18 h later and gastrocnemius muscles were collected and divided into parts for (1) immunohistochemistry detection of CD31 and CD105, (2) qRT-PCR analysis of eNOS and VEGFR2, (3) colorimetric analysis of NO, (4) ELISA estimation of TGF-β, VEGF, ATG5 and Beclin-1, and (5) Western blot analysis of p-PI3K, PI3K, p-Akt, Akt, p-mTOR, mTOR, and HIF-1α. Chrysin significantly enhanced microvessels growth in HLI muscles as indicated by increased CD31 and CD105 levels and decreased TGF-β. Chrysin's proangiogenic effect is potentially mediated by increased VEGF, VEGFR2 and activation of PI3K/AKT/mTOR pathway, which promoted eNOS and NO levels as it was reversed by the mTOR inhibitor, rapamycin. Chrysin also inhibited autophagy as it decreased ATG5 and Beclin-1. The current study shows that chrysin possesses a proangiogenic effect in HLI rats and might be useful in patients with PAD. |
Databáze: | OpenAIRE |
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