Ginsenoside Rg1 attenuates ultraviolet B-induced glucocortisides resistance in keratinocytes via Nrf2/HDAC2 signalling

Abstract

Oxidative stress, which occurs after ultraviolet (UV) radiation, usually results in Glucocorticoid (GC) resistance and the subsequent development of skin inflammation. One approach to protecting the skin against UV radiation is the use of antioxidants. The ginsenoside Rg1 is a novel natural antioxidant isolated from the medicinal plant Panax ginseng C.A. Mey. We demonstrated that UVB exposure exacerbated inflammation and reduced both the level of the glucocorticoid receptor (GR) and the efficacy of dexamethasone (Dex) in human keratinocytes (HaCaT cells). Pretreatment with Rg1 increased the expression of GR and restored Dex responsiveness to inflammation in UVB-irradiated HaCaT cells. Mechanistically, Rg1 rescued UVB-induced HDAC2 degradation. HDAC2 knockdown partially abolished the Rg1-induced up-regulation of GR and the enhancement of GC sensitivity. In addition, Rg1 reduced the production of reactive oxygen species (ROS), which preceded the up-regulation of HDAC2, and consequent sensitization of cells to Dex. Moreover, Rg1 treatment promoted the translocation and activation of Nrf2. Nrf2 knockdown partially abolished the Rg1-induced decrease of ROS production and increase of HDAC2. Rg1 also potentiated the anti-inflammatory effects of Dex in UVB-irradiated mouse skin. In conclusion, we demonstrated that Rg1 attenuated UVB-induced GC insensitivity. Notably, these effects were partially mediated by the Nrf2/HDAC2 pathway.

Effects of icariin on cell injury and glucocorticoid resistance in BEAS‑2B cells exposed to cigarette smoke extract

“…Due to primary GC resistance in COPD, GCs are unable to effectively inhibit the inflammatory response. Studies have shown that the factors associated with GC resistance include HDAC2, Nrf2 and NF-κB (23,38,39). The present study revealed that CSE significantly decreased the protein and mRNA expression levels of GR, Nrf2 and HDAC2 and increased the protein and mRNA levels of NF-κB.…”

Application of adipose-derived stem cells in photoaging: basic science and literature review

“…Attenuated oxidative stress is concomitant with reduced inflammation because oxidative stress occurs after UVR results in glucocorticoid resistance and the subsequent progress of skin inflammation [ 107 ]. What is more, accumulation of senescent cells causes the increase of proinflammatory molecules such as IL-6, IL-8, and TNF- α that are closely related to chronic inflammation [ 24 ].…”

Mechanisms of ginsenoside Rg1 in preventing ETEC‑induced diarrhea: Maintaining ileal integrity and eliminating inflammation

“…Ginseng is widely used in traditional Chinese medicine because of its anti-oxidant, anti-aging, and antiin ammatory effects [10,11]. Ginseng contains a variety of active ingredients, including ginsenosides, fatty acids, polysaccharides, and mineral oils [12], the pharmacological effects of which are mainly attributed to ginsenosides [13].…”