Galangin Reverses H2O2-Induced Dermal Fibroblast Senescence via SIRT1-PGC-1α/Nrf2 Signaling

Abstract

UV radiation and H2O2 are the primary factors that cause skin aging. Both trigger oxidative stress and cellular aging. It has been reported that deacetylase silent information regulator 1 (SIRT1), a longevity gene, enhances activation of NF-E2-related factor-2 (Nrf2), as well as its downstream key antioxidant gene hemeoxygenase-1 (HO-1), to protect cells against oxidative damage by deacetylating the transcription coactivator PPARγ coactivator-1α (PGC-1α). Galangin, a flavonoid, possesses anti-oxidative and anti-inflammatory potential. In the present study, we applied Ultraviolet B/H2O2-induced human dermal fibroblast damage as an in vitro model and UVB-induced photoaging of C57BL/6J nude mice as an in vivo model to investigate the underlying dermo-protective mechanisms of galangin. Our results indicated that galangin treatment attenuates H2O2/UVB-induced cell viability reduction, dermal aging, and SIRT1/PGC-1α/Nrf2 signaling activation. Furthermore, galangin treatment enhanced Nrf2 activation and nuclear accumulation, in addition to inhibiting Nrf2 degradation. Interestingly, upregulation of antioxidant response element luciferase activity following galangin treatment indicated the transcriptional activation of Nrf2. However, knockdown of SIRT1, PGC-1α, or Nrf2 by siRNA reversed the antioxidant and anti-aging effects of galangin. In vivo evidence further showed that galangin treatment, at doses of 12 and 24 mg/kg on the dorsal skin cells of nude mice resulted in considerably reduced UVB-induced epidermal hyperplasia and skin senescence, and promoted SIRT1/PGC-1α/Nrf2 signaling. Furthermore, enhanced nuclear localization of Nrf2 was observed in galangin-treated mice following UVB irradiation. In conclusion, our data indicated that galangin exerts anti-photoaging and antioxidant effects by promoting SIRT1/PGC-1α/Nrf2 signaling. Therefore, galangin is a potentially promising agent for cosmetic skin care products against UV-induced skin aging.

Modeling of the Senescence-Associated Phenotype in Human Skin Fibroblasts

“…It might be related to the elevated degradation processes inside the prematurely aged fibroblasts and consequent reduction in the total number of viable cells. This would be in line with the MTT results, which showed a significant decrease in viability, suggesting a decrease in the rate of fibroblasts growth (Figure 11), which is supported by data from other research groups [3,[73][74][75].…”

“…Aside from the findings related to the altered cell-cycle regulators in SIPS-induced cells, changes in the proteins associated with apoptosis pathways (BID), metabolic regulation (sirtuins), and components of ECM (collagens, elastin, hyaluronan) were also found (Table 2). These results are widely supported by similar findings in various cell types and tissues [52,75,[80][81][82][83][84][85][86].…”

The Molecular Mechanism of Polyphenols with Anti-Aging Activity in Aged Human Dermal Fibroblasts

“…Interestingly, long-term baicalin incubation of UVB-induced senescent fibroblasts had no effects on cell proliferation. Galangin recovered H 2 O 2 /UVB-induced cell viability loss in HDFs [ 72 ]. The knockdown of SIRT1, PGC-1α, or NRF2 siRNA reversed the anti-aging effects of galangin.…”

Molecular and Cellular Mechanisms of Propolis and Its Polyphenolic Compounds against Cancer

“…On the other hand, one of the biggest challenges in cancer treatment is the ongoing autocrine and paracrine activation of proinflammatory transcription factors, such as NF- κB, signal transducer and activator of transcription 3 (STAT-3), activator protein 1 (AP-1), forkhead box protein M1 (FOXM1), and hypoxia-inducible factor 1α (HIF-1α) that drive the overproduction of diverse mediators of inflammation—inflammatory cytokines, chemokines, cellular adhesion molecules, anti-apoptotic molecules, and iNOS [ 237 , 238 , 239 , 240 , 241 , 242 , 243 , 244 , 245 , 246 , 247 , 248 , 249 , 250 , 251 , 252 ]. Regarding propolis and its components, numerous studies have demonstrated the anti-inflammatory effects of various flavonoids [ 1 , 2 , 3 , 4 , 38 , 174 , 198 , 237 , 238 , 239 , 240 , 241 , 242 , 243 , 244 , 245 , 246 , 247 , 248 , 249 , 250 , 251 , 252 ]. The anti-inflammatory properties of several flavonols (quercetin, rutin, and morin) and flavanones (hesperetin and hesperidin) were examined in animal models of acute and chronic inflammation.…”

“…The observed anti-inflammatory effects of propolis are attributed to the presence of flavonoids, especially galangin. Galangin inhibits COX and LOX activity, and reduces PGE2 release and the expression of the inducible isoform of COX (COX-2) [ 161 , 249 , 250 ]. Besides galangin, many authors [ 240 , 251 , 252 , 253 , 254 ] have emphasized the anti-inflammatory contribution of quercetin.…”