Abstract
Herbal combinations of Rhei Radix et Rhizoma, Gardeniae Fructus, Cimicifugae Rhizoma, and Ginseng Radix have been used in traditional formulas to treat the symptoms of heat and dryness. This study investigated the therapeutic effects of a natural compound mixture (PSM) of these herbal combinations, containing emodin, genipin, chlorogenic acid, cimigenoside, and ginsenoside Rb1, for the treatment of psoriasis and its underlying molecular mechanisms. PSM was applied topically to the dorsal skin lesions of imiquimod- (IMQ-) induced C57BL/6 mice, and the expression of the proinflammatory mediators was investigated. The topical application of 1% PSM reduced psoriasis-like symptoms in IMQ-induced C57BL/6 mice significantly. PSM also attenuated the production of IFN-γ, IL-1β, and IL-6 in skin lesions. Histological analysis showed that PSM had antipsoriatic effects by reducing the lesional epidermal thickness. Either M5 (IL-1α, IL-17A, IL-22, oncostatin M, and TNF-α, 10 ng/ml each) or IL-22- (100 ng/ml) stimulated HaCaT cells were used to examine the efficacy and underlying mechanism of PSM. In M5-stimulated HaCaT cells, PSM inhibited the production of C-X-C motif chemokine ligand (CXCL) 10 and C-C motif chemokine ligand (CCL) 20 effectively. Moreover, compared to the use of a single compound, it had synergistic inhibitory effects in CXCL8 production. PSM suppressed the phosphorylation of ERK1/2, p38, and STAT3 signaling pathways in M5-stimulated HaCaT cells. Furthermore, PSM reduced the proliferation rate and K16 and K17 expressions in IL-22-stimulated HaCaT cells by inhibiting the Akt/mTOR signaling pathway. These results suggest that PSM may have a therapeutic potential in the treatment of psoriasis lesions.
Highlights
Psoriasis is an inflammatory skin disorder that affects approximately 2% of the world’s population. e hallmarks of psoriasis are chronic inflammation, excessive proliferation, and aberrant differentiation in keratinocytes, leading to erythematous and scaly plaque on the skin [1]
At the end of the six-day treatment period, the dorsal skins of the IMQ-treated mice showed the typical features of psoriasis. e Psoriasis Area Severity Index (PASI) scores were calculated based on measurements of scaling, redness, and thickness in the skin lesion. e PSM treatment attenuated the PASI score significantly compared to the IMQ-treated group (Figure 2(a)). e mice treated with PSM had significantly lower body weights compared to normal control (Figure 2(b))
To evaluate the effects of PSM on skin inflammation, Enzyme-Linked Immunosorbent Assay (ELISA) was performed to measure the levels of cytokines in the skin lesions. ese results showed that IMQ stimulation increased the expression of proinflammatory cytokines IFN-c, IL-1β, and IL-6 in skin lesions
Summary
Psoriasis is an inflammatory skin disorder that affects approximately 2% of the world’s population. e hallmarks of psoriasis are chronic inflammation, excessive proliferation, and aberrant differentiation in keratinocytes, leading to erythematous and scaly plaque on the skin [1]. 17 cells can produce several cytokines, such as IL17A, IL-17F, and IL-22, which activate various inflammatory cascades and keratinocyte proliferation in skin lesions [2]. Topical glucocorticoids are indicated as the first and most effective drugs for the treatment of psoriasis, but the long-term application of glucocorticoids might lead to numerous side effects, including skin atrophy, impairment of skin barrier function, and wound healing [6]. Phototherapy such as exposing the skin to natural sunlight or narrow-band ultraviolet B (NB-UVB) was widely prescribed by a dermatologist to treat psoriasis [7]. A previous study found that a combination of compounds can modulate the complex and diverse pathological factors of psoriasis by acting on multitargets [13]
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