Punicalagin Prevents Hypoxic Pulmonary Hypertension via Anti-Oxidant Effects in Rats

Abstract

Punicalagin (PG), a major bioactive ingredient in pomegranate juice, has been proven to have anti-oxidative stress properties and to exert protective effects on acute lung injuries induced by lipopolysaccharides. This study aimed to investigate the effects of PG treatment on hypoxic pulmonary hypertension (HPH) and the underlying mechanisms responsible for the effects. Rats were exposed to 10% oxygen for 2 wk (8 h/day) to induce the HPH model. PG (5, 15, 45[Formula: see text]mg/kg) was orally administered 10[Formula: see text]min before hypoxia each day. PG treatments at the doses of 15 and 45[Formula: see text]mg/kg/d decreased the mean pulmonary arterial pressure (mPAP) and alleviated right ventricular hypertrophy and vascular remodeling in HPH rats. Meanwhile, PG treatment attenuated the hypoxia-induced endothelial dysfunction of pulmonary artery rings. The beneficial effects of PG treatment were associated with improved nitric oxide (NO)-cGMP signaling and reduced oxidative stress, as evidenced by decreased superoxide generation, gp91[Formula: see text] expression and nitrotyrosine content in the pulmonary arteries. Furthermore, tempol's scavenging of oxidative stress also increased NO production and attenuated endothelial dysfunction and pulmonary hypertension in HPH rats. Combining tempol and PG did not exert additional beneficial effects compared to tempol alone. Our study indicated for the first time that PG treatment can protect against hypoxia-induced endothelial dysfunction and pulmonary hypertension in rats, which may be induced via its anti-oxidant actions.

Gastroprotective Effect of Punicalagin against Ethanol-Induced Gastric Ulcer: The Possible Underlying Mechanisms

“…These violent actions lead to stasis of blood flow and disruption of gastric microvessel in the other hand, although pre-treatment with PCG significantly elevated mucosal level of NO, it failed to change level of PGE2, indicating involvement of NO and passive role of PGE2 in the mechanism of PCG's gastroprotective effects. PCG improved NO-cGMP signaling [33] as well it quenched of the superoxide anion which consumes NO for the generation of the cytotoxic peroxynitrite [34]. Furthermore, NO enhanced maintenance of mucosal blood flow [35] resulting in improving in gastric mucosal defense as shown in the current study.…”

Medicinal Plants and Phytochemicals for the Treatment of Pulmonary Hypertension

“…Punicalagin is a phytochemical isolated from pomegranate juice and has many pharmacological activities due to its high antioxidant content (Xu et al, 2015); also it has been reported that punicalagin used for treatment of lung diseases in animal models (Peng et al, 2015). Shao et al (2016) during an investigation on hypoxia induced PH in rats shows that treatment with punicalagin improves hemodynamic indicators and induce relaxation by enhancing NO-cGMP signaling pathway in PAs. Also this phytochemical reduces oxidative stress and raises mRNA expression of MMP-9, HIF-1a, VEGFA, NF-kB and TNF-a in lung tissue of animals.…”

Pulmonary hypertension: Molecular aspects of current therapeutic intervention and future direction

“…Chinese herb Naofeikang and Ruscogenin have additional therapeutic potential against PH by down regulating the inflammatory reaction and macro phase infiltration (Bi et al, ; Han et al, ). Radix Astragali (Fabaceae) (Chen, Ruan, Xi, Si, & Zhang, ), Allium sativum (Amaryllidaceae) (Sun & Ku, ), Luteolin (Lamiaceae) (Occhiuto & Limardi, ), Rhoifolin (Rutaceae) (Occhiuto & Limardi, ), and Punicalagin (Punica granatum) (Shao et al, ) have reported for producing the measurable reduction in mean arterial blood pressure, pulmonary vascular remodeling and collagen deposition, which are significantly liable to the pathogenesis of PH. Erigeron breviscapus (Asteraceae) has potent antiproliferative action on smooth muscle cells (Zheng, Xie, Gao, & Zhang, ).…”

“…Whereas, Tetrandrine upregulate the expression of protein kinase 1, superoxide dismutase, glutathione in MCT-induced PH in rats (Wang et al, 2016). Moreover, Levosimendan, (Calcium sensitizer and new dual acting non-arrhythmogenic drug) was reported to revert right ventricular failure in PH (Hansen et al, 2017).…”

“…Radix Astragali (Fabaceae) (Chen, Ruan, Xi, Si, & Zhang, 1997), Allium sativum (Amaryllidaceae) (Sun & Ku, 2006), Luteolin (Lamiaceae) (Occhiuto & Limardi, 1994), Rhoifolin (Rutaceae) (Occhiuto & Limardi, 1994), and Punicalagin (Punica granatum) (Shao et al, 2016) and may open the new possibility of novel signaling modulator which can restore the pathological events and improve PH.…”