Verbascoside Protects Gingival Cells against High Glucose-Induced Oxidative Stress via PKC/HMGB1/RAGE/NFκB Pathway

Abstract

Impaired wound healing often occurs in patients with diabetes and causes great inconvenience to them. Aside from the presence of prolonged inflammation, the accumulation of oxidative stress is also implicated in the delayed wound healing. In the present study, we tested the effect of verbascoside, a caffeoyl phenylethanoid glycoside, on the improvement of cell viability and wound healing capacity of gingival epithelial cells under high glucose condition. We showed that verbascoside attenuated the high glucose-induced cytotoxicity and impaired healing, which may be associated with the downregulation of oxidative stress. Our results demonstrated that verbascoside increased the activity of the antioxidant enzyme SOD and reduced the oxidative stress indicator, 8-OHdG, as well as apoptosis. Moreover, verbascoside upregulated the PGC1-α and NRF1 expression and promoted mitochondrial biogenesis, which was mediated by suppression of PKC/HMGB1/RAGE/NFκB signaling. Likewise, we showed the inhibitory effect of verbascoside on oxidative stress was via repression of PKC/HMGB1/RAGE/NFκB activation. Also, our data suggested that the PKC-mediated oxidative stress may lead to the elevated production of inflammatory cytokines, IL-6 and IL-1β. Collectively, we demonstrated that verbascoside may be beneficial to ameliorate impaired oral wound healing for diabetic patients.

Globularia alypum L. and Related Species: LC-MS Profiles and Antidiabetic, Antioxidant, Anti-Inflammatory, Antibacterial and Anticancer Potential

“…The latter species, which showed the greatest protective effect in the LDH assay ( Figure 5 ), contained the most 6-hydroxyluteolin glycosides, which were observed in G. alypum as the more potent DPPH radical scavengers (IC 50 = 6.6–12.2 µM) than its phenylethanoids (IC 50 =11.8–15.5 µM) and iridoids (IC 50 = 28.2–76.0 µM), as well as than quercetin (IC 50 = 7.8 µM) and butylated hydroxytoluene (IC 50 = 30.0 µM) [ 35 ]. Verbascoside was recently reported to protect Smulow–Glickman (S–G) gingival epithelial cells against glucose-induced oxidative stress, which may indicate its potential to improve impaired oral wound healing in diabetic patients [ 66 ]. In the same study, it was also observed to enhance mitochondrial function and improve cell survival (50 and 100 µM) in both the LDH assay and the MTT assay.…”

“…The same compound showed potentially useful effects in other experimental diabetic complications, glucose-lowering effect in experimental T1DM and T2DM possibly due to improved glucose utilization in insulin-sensitive tissues and improved mitochondrial biogenesis/function, as well as neuroprotective and cardioprotective effect, which are all potentially linked to its antioxidant and anti-inflammatory activities [ 79 ]. Similarly, verbascoside was reported to reduce the glucose-induced production of inflammatory cytokines, IL-6 and IL-1β in Smulow-Glickman gingival epithelial cells exposed to high glucose concentrations [ 66 ], as well as to reduce cellular inflammation and improve mitochondrial activity and survival of pancreatic β-cells under endoplasmic reticulum-stress [ 82 ]. Asperuloside and asperulosidic acid, which were observed in G. punctata , G. cordifolia and G. meridionalis , significantly decreased the production of NO, PGE 2 , TNF-α, and IL-6, and inhibited the expression of inducible NO synthase (iNOS), COX-2, TNF-α, and IL-6 mRNA in LPS-induced RAW 264.7 cells [ 80 ].…”

Natural Biologics Accelerate Healing of Diabetic Foot Ulcers by Regulating Oxidative Stress

“…Sasa borealis water-extract blocks chronic high glucose-induced endothelial apoptosis by the blunting activation of βII and NADPH oxidase promoted [139]. Furthermore, verbascoside downregulated expression of the inflammatory cytokines IL-6 and IL-1β by inhibiting PKC/HMGB1/RAGE/NFκB signaling and ultimately may be beneficial to oral wound healing in diabetic patients [140]. From these findings, we speculate that these PKC-targeted natural biologics for diabetes and its other complications may be potential strategies for DFU therapy because of their same or similar pathogenesis.…”

Ultrasound-Assisted Extraction of Verbascoside from Clerodendrum glandulosum Leaves for Analysis of Antioxidant and Antidiabetic Activities

“…Verbascoside (VER), a phenylethanoid glycoside, is one of the most widespread and potent among the reported polyphenols . VER was reported to attenuate cytotoxicity induced by elevated glucose levels and to reduce oxidative stress by downregulation of PKC/HMGB1/RAGE/NFκβ signaling . Recently, VER isolated from Odontonema strictum in an aqueous medium showed effective free radical scavenging activities .…”