Naringin Ameliorates Monocrotaline-Induced Pulmonary Arterial Hypertension Through Endothelial-To-Mesenchymal Transition Inhibition

Abstract

Pulmonary arterial hypertension (PAH) caused by enhanced arterial pressure increases vessel resistance in the lung. Endothelial-to-mesenchymal transition (EndMT) plays key roles in the vascular remodeling in PAH. Naringin, a protective gaseous mediator is commonly extracted from tomatoes and citrus fruits (such as grapefruits), and demonstrates anti-inflammation, anti-oxidant, anti-proliferation, and anti-tumor effects. Meanwhile, the association of Naringin and the process of EndMT is still unclear. In this study, monocrotaline (MCT) administration (60 mg/kg) was delivered for the induction of PAH in rats. Following this, Naringin (concentrations: 25, 50, and 100 mg/kg/day) was used for treatments. Human Umbilical Vein Endothelial Cells (HUVECs) were stimulated with Naringin and transforming growth factor β1 (TGFβ1, 10 ng/ml). As the result, Naringin was demonstrated to inhibit EndMT and alleviate PAH progression. In particular, in HUVECs, Naringin significantly suppressed the mesenchymal marker expression induced by TGFβ1 treatment, enhanced the endothelial marker expression, and inhibited the activation of ERK and NF-κB signaling pathways. To conclude, this study provided novel evidence suggesting the beneficial effects of Naringin in PAH through the inhibition of the ERK and NF-κB signaling pathways and the EndMT progression in pulmonary arteries.

Citrus junos Tanaka Peel Extract and Its Bioactive Naringin Reduce Fine Dust-Induced Respiratory Injury Markers in BALB/c Male Mice

“…To determine whether the administration of CPE and naringin could alleviate PM 10 -induced lung inflammation, mice were subjected to oral administration of CPE and naringin for 7 days; after this, to induce pneumonitis phenotypes, the mice were subjected to intranasal injection of PM 10 (100 mg/kg body weight) at the last day and sacrificed after 6 h. The naringin and low-dose CPE concentration (i.e., 100 mg/kg body weight) were determined on the basis of the work of previous papers using similar samples (i.e., naringin and natural product extracts), and the higher dose of CPE was chosen to confirm the dose-dependent response of CPE [ 11 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. As an initial response against PM 10 , inflammatory immune cells (e.g., eosinophils and neutrophils) are recruited on the site, followed by air space enlargement and detachment, all of which are typical pneumonitis manifestations [ 34 , 35 ].…”

Targeting Oxidative Stress and Inflammation in Intervertebral Disc Degeneration: Therapeutic Perspectives of Phytochemicals

“…Naringin is a bioflavonoid found in the tangerine peel ( Lavrador et al, 2018 ). It reportedly has a wide range of pharmacological activities, including antioxidant ( Long et al, 2020 ; Bao et al, 2022 ) and anti-inflammatory effects ( Zhao et al, 2020 ; Wu et al, 2021 ). Naringin has been confirmed to increase autophagy flux by activating the AMPK/SIRT1 pathway, thereby protecting NP cells from inflammatory response, oxidative stress, and impaired cellular homeostasis ( Chen R. et al, 2022 ).…”

Bioactive Wound Healing 3D Structure Based on Chitosan Hydrogel Loaded with Naringin/Cyclodextrin Inclusion Nanocomplex

“…This is achieved by reducing the expression of vascular endothelial growth factor and downregulating the TGF-β pathway, thereby exhibiting a vascular inhibitory effect. 21,22 The absorption of Nar by the human gastrointestinal tract is limited with only 15% being absorbed. Furthermore, its bioavailability is notably low, which restricts its practical application.…”

“…Additionally, Nar has demonstrated the ability to decrease the metastasis and invasion of pancreatic cells. This is achieved by reducing the expression of vascular endothelial growth factor and downregulating the TGF-β pathway, thereby exhibiting a vascular inhibitory effect. , …”

“…This is achieved by reducing the expression of vascular endothelial growth factor and downregulating the TGF-β pathway, thereby exhibiting a vascular inhibitory effect. 21 , 22 …”