Cimifugin ameliorates imiquimod-induced psoriasis by inhibiting oxidative stress and inflammation via NF-κB/MAPK pathway

Abstract

Cimifugin is an important component of chromones in the dry roots of Saposhikovia divaricata for treating inflammatory diseases. However, the possible effect of cimifugin in psoriasis needs further investigation. This current work was designed to evaluate the effects of cimifugin in psoriasis in vivo and in vitro, and unravel the underlying molecular mechanism. Here, we used imiquimod (IMQ) or tumor necrosis factor (TNF)-α to induce a psoriasis-like model in mice or keratinocytes. Obviously, the results showed that cimifugin reduced epidermal hyperplasia, psoriasis area severity index (PASI) scores, ear thickness and histological psoriasiform lesions in IMQ-induced mice. The decreased levels of reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT), and the accumulation of malondialdehyde (MDA) in skin tissues by IMQ were attenuated by cimifugin. Furthermore, it was observed that cimifugin effectively reversed IMQ-induced up-regulation of proinflammatory cytokines, including TNF-α, IL-6, IL-1β, IL-17A, and IL-22. Mechanically, we noticed that cimifugin inhibited IMQ-activated phosphorylation of NF-κB (IκB and p65) and MAPK (JNK, ERK, and p38) signaling pathways. Similar alterations for oxidative stress and inflammation parameters were also detected in TNF-α-treated HaCaT cells. In addition, cimifugin-induced down-regulation of ICAM-1 were observed in TNF-α-treated cells. Altogether, our findings suggest that cimifugin protects against oxidative stress and inflammation in psoriasis-like pathogenesis by inactivating NF-κB/MAPK signaling pathway, which may develop a novel and effective drug for the therapy of psoriasis.

Cimifugin Suppresses NF-κB Signaling to Prevent Osteoclastogenesis and Periprosthetic Osteolysis

“…Previous studies prove that CIM has potential to multiple in ammatory diseases. Liu et al 14 Moreover, all these three studies including the present one only investigate the level of signaling proteins in limited number, so it seems impossible to come to an agreement for now.…”

“…Given this, we investigated a natural compound called Cimifugin (CIM) as one of main components of Saposhnikovia Divaricata or Cimicifuga Racemosa extract 10; 11 . CIM is commonly reported as a bioactive chromone independently or in multiple Chinese medicine formulae with reported properties of antinociception, antiin ammation and lipid metabolism regulation in a spectrum of diseases, including allergy in skin and respiratory system, in ammatory arthropathies, and cerebral ischemia by inhibiting the production of in ammatory factors and NF-kb/MAPK signaling [11][12][13][14][15][16] . However, in term of the treatment for ALP, the bioactivity of CIM has not been investigated in osteoclastogenesis and subsequent periprosthetic osteolysis.…”

“…In comparison, previous studies on the bioactivity of CIM suggested different conclusions. For one, Liu et al14 reported that CIM ameliorates imiquimod-mediated phosphorylation of NF-κB (IκB and p65) and MAPK (JNK, ERK, and p38) signaling in psoriasis models. For another, Han et al12 indicated that CIM exerts inhibitory effect on lipopolysaccharide-induced in ammatory response in RAW264.7 cell by downregulating the generation of p-IκBα, p-p65, p-ERK, and p-p38 of NF-κB and MAPK signaling pathways without detecting the level of JNK.…”

Pharmacokinetic–pharmacodynamic modeling analysis and anti‐inflammatory effect of Wangbi capsule in the treatment of adjuvant‐induced arthritis

“…In addition, the increase of IL-1β can stimulate synovial fibroblasts, chondrocytes and osteoclasts to produce tissue-damaging matrix metalloprotease (MMP), leading to bone loss (Sirikaew et al, 2019). Numerous published reports have shown that osthole, cimifugin, 5-O-methylvisammioside, albiflorin, paeoniflorin and icariin, the active components of WBC, can directly or indirectly regulate nuclear factor kappa-B or other signal pathways and reduce the contents of inflammatory cytokines IL-1β and PGE 2 (Liu et al, 2020;Xu et al, 2018). Therefore, PGE 2 and IL-1β were selected as PD indicators in this study.…”

Natural Compound Mixture, Containing Emodin, Genipin, Chlorogenic Acid, Cimigenoside, and Ginsenoside Rb1, Ameliorates Psoriasis‐Like Skin Lesions by Suppressing Inflammation and Proliferation in Keratinocytes

“…The levels of the phosphorylated forms of ERK1/2 and p38, not JNK, were also significantly higher in the lesional psoriatic skin [ 45 ]. The suppression of MAPK signaling pathways by a natural compound, cimifugin, significantly attenuated inflammation in both in vitro and in vivo models of psoriasis [ 46 ]. In the present study, PSM blocked the phosphorylation of ERK1/2, p38, and STAT3 significantly in M5-stimulated HaCaT cells, suggesting that the therapeutic action of PSM might be through inhibition of the ERK1/2, p38, and STAT3 signaling pathways.…”