Paeonol Ameliorates Chronic Itch and Spinal Astrocytic Activation via CXCR3 in an Experimental Dry Skin Model in Mice

Abstract

Paeonol is a bioactive phenol presents mainly in Paeonia suffruticosa Andr. (Paeoniaceae), Paeonia lactiflora Pall., and Dioscorea japonica Thunb. (Dioscoreaceae), harboring various pharmacological activities including anti-inflammatory, antioxidant, immune regulatory activity and reverse chemoresistance. Recent reports revealed paeonol exhibited good effects on chronic dermatitis, such as atopic dermatitis (AD) and psoriasis. However, whether paeonol is effective for dry skin disease and its mechanism of action still remain unclear. In this study, we analysed the effects of paeonol on a mouse model of dry skin treated with acetone-ether-water (AEW), which showed impressive activities in reducing scratching behavior and skin inflammation. To elucidate the underlying molecular targets for the anti-pruritic ability of paeonol, we screened the expression of possible chemokine pathways in the spinal cord. The expression of CXCR3 was significantly alleviated by paeonol, which increased greatly in the spinal neurons of AEW mice. In addition, treatment of paeonol significantly inhibited AEW-induced expression of astrocyte activity-dependent genes including Tlr4, Lcn2 and Hspb1 et al. The inhibitory effects of paeonol on scratching behavior and astrocytic activation in the spinal cord induced by AEW were abolished when CXCR3 was antagonized or genetically ablated. Taken together, our results indicated that paeonol can ameliorate AEW-induced inflammatory response and itching behavior, and reduce the expression of spinal astrocyte activity-dependent genes induced by AEW, which are driven by CXCR3.

Paeonol alleviates placental inflammation and apoptosis in preeclampsia by inhibiting the JAK2/STAT3 signaling pathway

“…Afterward, a total of 72 female mice were randomly divided into six groups: control group ( n = 12), PE group ( n = 12), PE mice administered a low dose (50 mg/kg/d) of Pae (PE + Pae 10 group [ n = 12]) from GD0 to GD17, PE mice administered a medium dose (100 mg/kg/d) of Pae (PE + Pae 100 group [ n = 12]) from GD0 to GD17, PE mice administered a high dose (150 mg/kg/d) of Pae (PE + Pae 150 group [ n = 12]) from GD0 to GD17, and Pae‐treated PE mice intraperitoneally injected with 8 mg/kg of SC‐39100 on GD17 (SC‐39100 + PE + Pae 150 [ n = 12]). The dosages of Pae and SC‐39100 were selected in accordance with previous documents 18–20 . On GD18, all mice were sacrificed, and the placental tissues were collected and stored in liquid nitrogen at −80°C for later use.…”

“…The dosages of Pae and SC-39100 were selected in accordance with previous documents. [18][19][20] On GD18, all mice were sacrificed, and the placental tissues were collected and stored in liquid nitrogen at À80 C for later use.…”

Paeonia × suffruticosa (Moutan Peony)—A Review of the Chemical Composition, Traditional and Professional Use in Medicine, Position in Cosmetics Industries, and Biotechnological Studies

“…P. × suffruticosa bark root extracts also have scientifically proven cosmetic properties, such as: antioxidant, anti-aging and skin brightening [ 86 , 87 ]. Recent reports revealed paeonol from P. × suffruticosa exhibited good effects on chronic dermatitis, such as atopic dermatitis (AD) and psoriasis [ 88 ].…”

“…The results showed impressive activities in reducing scratching behavior and skin inflammation. The studies indicated that paeonol can ameliorate AEW-induced inflammatory response and itching behavior and reduce the expression of spinal astrocyte activity-dependent genes induced by AEW, reducing the expression of spinal astrocyte activity-dependent genes induced by AEW [ 88 ].…”

Paeonol inhibits chronic constriction injury‐induced astrocytic activation and neuroinflammation in rats via the HDAC/miR‐15a pathway

“…In diabetes rats, PAE‐treatment repressed the expression of NF‐κB and MCP‐1 and alleviated diabetes‐induced sciatic nerve damage (Adki & Kulkarni, 2021). Additionally, PAE efficiently restrained CXCR3 pathway‐activated astrocytes in mouse model of dry skin (Wang et al, 2021). However, whether PAE could suppress astrocytes activation and the potential underlying mechanisms in NP are still unknown.…”