A Protective Role of Paeoniflorin in Fluctuant Hyperglycemia-Induced Vascular Endothelial Injuries through Antioxidative and Anti-Inflammatory Effects and Reduction of PKCβ1

Abstract

Hyperglycemia fluctuation is associated with diabetes mellitus (DM) complications when compared to persistent hyperglycemia. Previous studies have shown that paeoniflorin (PF), through its antiapoptosis, anti-inflammation, and antithrombotic properties, effectively protects against cardiovascular and cerebrovascular disease. However, the mechanism underlying the protection from PF against vascular injuries induced by hyperglycemia fluctuations remains poorly understood. Herein, we investigated the potential protective role of PF on human umbilical vein endothelial cells (HUVECs) subjected to intermittent glucose levels in vitro and in DM rats with fluctuating hyperglycemia in vivo. A remarkable increased apoptosis associated with elevated inflammation, increased oxidative stress, and high protein level of PKCβ1 was induced in HUVECs by intermittently changing glucose for 8 days, and PF recovered those detrimental changes. LY333531, a potent PKCβ1 inhibitor, and metformin manifested similar effects. Additionally, in DM rats with fluctuating hyperglycemia, PF protected against vascular damage as what has been observed in vitro. Taken together, PF attenuates the vascular injury induced by fluctuant hyperglycemia through oxidative stress inhibition, inflammatory reaction reduction, and PKCβ1 protein level repression, suggesting its perspective clinical usage.

Paeoniflorin attenuates gestational diabetes via Akt/mTOR pathway in a rat model

“…Importantly, a recent study reported that paeoniflorin treatment led to reduced blood glucose levels, inhibited inflammatory factors section, and attenuated glomerular hypertrophy in diabetic rats (32). Similar to this finding, another study showed that paeoniflorin exerts a protective effect on vascular endothelial cells from hyperglycemia fluctuation-induced injury through reducing inflammatory reaction and oxidative stress (33). Our results demonstrated that oral administration of paeoniflorin at 15 or 30 mg/ kg after mating and during the gestation significantly decreased the blood glucose and plasma leptin levels, and increased the insulin levels in rats with GDM.…”

<p>Inhibitory Effect of Curcumin on Artery Restenosis Following Carotid Endarterectomy and Its Associated Mechanism in vitro and in vivo</p>

“…21 In addition, the apoptotic endothelial cells can enhance platelet adhesion, promote cell inflammation and lipid infiltration and induce VSMC proliferation, migration, and thrombosis. 22 A previous study has shown that Cur could inhibit intimal hyperplasia and VSMC proliferation following vascular injury. 23 Moreover, it could induce VSMC apoptosis by regulating inflammatory-associated signaling pathways.…”

<p>Paeoniflorin Ameliorates Chronic Hypoxia/SU5416-Induced Pulmonary Arterial Hypertension by Inhibiting Endothelial-to-Mesenchymal Transition</p>

“…23 PF have also been reported to attenuate fluctuant hyperglycemia-induced vascular endothelial injuries, and to improve bleomycin-induced pulmonary fibrosis in rats by suppressing collagen synthesis. 8,24 Besides, the anti-remodeling effect of PF on cardiovascular diseases, including acute myocardial infarction and pressure overload-induced cardiac remodeling, might also contribute to the beneficial effect of PF on PH. 21,25 In the present study, we also found a marked attenuation of the collagen deposition in the pulmonary arterial and RV heart tissue in the PF-treated SuHx rats compared to vehicle-treated SuHx rats.…”

“…5,6 Paeoniflorin (PF), a monoterpene glucoside extracted from the root of Paeonia lactiflora, possesses many pharmacological activities, such as anti-inflammatory, antioxidative, analgesic, anticancer and immunoregulatory effects. [7][8][9][10] PF is widely used in clinical practice for the treatment of rheumatoid arthritis and systemic lupus erythematosus. 11 A recent study demonstrated that PF exerts a direct vasculoprotective effect through antioxidative and anti-inflammatory effects in fluctuant hyperglycemia-induced vascular endothelial injuries.…”

“…11 A recent study demonstrated that PF exerts a direct vasculoprotective effect through antioxidative and anti-inflammatory effects in fluctuant hyperglycemia-induced vascular endothelial injuries. 8 Moreover, it has been documented that PF could protect against lipopolysaccharide, oxidized low-density lipoprotein or radiation-induced endothelial cell dysfunction. [12][13][14] Recently, PF was reported to prevent hypoxia-induced epithelial-mesenchymal transition (EMT) in human breast cancer cells.…”