The Extract of D. dasycarpus Ameliorates Oxazolone-Induced Skin Damage in Mice by Anti-Inflammatory and Antioxidant Mechanisms

Abstract

Dictamni dasycarpus is a type of Chinese medicine made from the root bark of D. dasycarpus. It has been reported to show a wide spectrum of biological and pharmacological effects, for example, it has been used widely for the treatment of rheumatism, nettle rash, itching, jaundice, chronic hepatitis and skin diseases. In the current study, D. dasycarpus extract was investigated for its antioxidant and anti-inflammatory effects, as well as its capability to alleviate oxazolone-induced skin damage in mice. The possible anti-inflammatory mechanism of D. dasycarpus extract against oxidative challenge was elucidated by measuring the levels of reactive oxygen species (ROS) production, interleukin-6, Tumor necrosis factor-α, NLRP3 (NACHT, LRR and PYD domains-containing protein 3 (NALP3)) inflammasome and interleukin-1β in HaCaT cells. D. dasycarpus extract did not affect cell viability in basal conditions. The extract significantly reduced oxazolone-induced epidermal swelling compared to untreated animal in the hairless albino mice (ICR mice) model. At the molecular level, Western blot assays indicated that the D. dasycarpus extract attenuated oxazolone-induced activation of apoptosis-associated speck-like protein containing CARD (ASC), procaspase-1, NF-κB and mitogen-activated protein kinase (MAPKs) such as c-Jun N-terminal protein kinase (JNK) and p38. This study demonstrates that D. dasycarpus extract could protect skin cells against oxidative and inflammatory insult by modulating the intracellular levels of ROS, TNF-α, interleukin-1, interleukin-6, NLR family pyrin domain containing 3 (NLRP3) inflammasome generation, antioxidant enzyme activity and cell signaling pathways. D. dasycarpus extract also attenuated the expression of NF-κB in HaCaT keratinocytes and thereby effectively downregulated inflammatory responses in the skin. Furthermore, D. dasycarpus extract alleviated oxazolone-induced damage in mice. Our results suggest the potential application of D. dasycarpus extract in preventing inflammatory processes in dermatitis.

L. Cucurbita pepo modulates contact dermatitis in depressed rats through downregulation of proinflammatory cytokines and upregulation of antioxidant status

“…This was in agreement with those reported by Zhou et al [41] in dinitrochlorobenzene-induced allergic CD in BALB/c mice, Kim et al [42] in Benzene-induced skin irritation in rats [33] and in oxazolone-induced CD in mice. Significant up-regulation of Cox-2 immunoexpression in the CD group was among the findings in this study as well as previous studies [37].…”

“…These cytokines have been reported to be elevated in patients with depression and mice showing behavioural despair [34,35]. Although the inflammatory response plays a chief role in the protection of the host and tissue repair, it can also damage the normal skin tissue [36], inhibition of pro-inflammatory cytokine expression was described to improve dermatitis as it protects from extended adaptive immunity [37]. DNFB-induced CD, in this study, was associated with a disturbed oxidants/antioxidants profile presented with increased MDA and decreased SOD, GPX and CAT in the skin and serum.…”

Combined Oral and Topical Application of Pumpkin (Cucurbita pepo L.) Alleviates Contact Dermatitis Associated With Depression Through Downregulation Pro-Inflammatory Cytokines

“…The morphological and histopathological alternations observed in CD in this study were in accordance with those observed by Zhou et al (2016) in dinitrochlorobenzene-induced allergic CD in BALB/c mice ( Alshathly and Alqahtani, 2017 ) in benzene-induced skin irritation in rats and ( Qu et al, 2019 ) in oxazolone-induced CD in mice. Significant upregulation of Cox-2 immunoexpression in CD was among the findings recorded in this study and previous studies ( Chang et al, 2018 ).…”

“…Although the inflammatory response plays a chief role in the protection of the host as well as in tissue repair, it can also damage the normal skin tissue ( Cha et al, 2016 ). Based on that, inhibition of pro-inflammatory cytokine expression was described to improve dermatitis as it protects from extended adaptive immunity ( Chang et al, 2018 ). Another reason for increased TNF-α and IL-6 in the serum in this study was the occurrence of CUMS-induced depression as they have been reported to be elevated in patients with depression and mice showing behavioral despair ( Numakawa et al, 2014 ; Taraz et al, 2015 ).…”

Haplopine Ameliorates 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis-Like Skin Lesions in Mice and TNF-α/IFN-γ-Induced Inflammation in Human Keratinocyte

“…Its root bark, called "Baekseonpi" in Korean, has been used to treat mild skin diseases in traditional medicine in Korea, China, and Japan [13]. D. dasycarpus extracts have been reported to have anti-atopic [14], anti-inflammatory [15], and antioxidant [15], anti-allergic [14] effects, and alkaloids (e.g., dictamine and haplopine) and limonoids (e.g., fraxinellone and obacunone) isolated from D. dasycarpus have been shown to possess anti-inflammatory [16][17][18], antioxidative [18][19][20], and antifungal [21] activities. Although many studies have been conducted on the bioactivity of D. dasycarpus, few have investigated the use of its constituent compounds for the treatment of AD.…”