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大麻二酚作为特应性皮炎模型中Th2细胞因子和JAK/STAT信号通路激活的新型抑制剂。

Cannabichromene as a Novel Inhibitor of Th2 Cytokine and JAK/STAT Pathway Activation in Atopic Dermatitis Models.

作者信息

Kim Ki Chan, Jeong Ga Hee, Bang Chul Hwan, Lee Ji Hyun

机构信息

Department of Medical Sciences, Graduate School of The Catholic University of Korea, Seoul #222 Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea.

Department of Dermatology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul #222 Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea.

出版信息

Int J Mol Sci. 2024 Dec 18;25(24):13539. doi: 10.3390/ijms252413539.

DOI:10.3390/ijms252413539
PMID:39769302
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11677870/
Abstract

Cannabichromene (CBC) is one of the main cannabinoids found in the cannabis plant, and although less well known than tetrahydrocannabinol (THC) and cannabidiol (CBD), it is gaining attention for its potential therapeutic benefits. To date, CBC's known mechanisms of action include anti-inflammatory, analgesic, antidepressant, antimicrobial, neuroprotective, and anti-acne effects through TRP channel activation and the inhibition of inflammatory pathways, suggesting that it may have therapeutic potential in the treatment of inflammatory skin diseases, such as atopic dermatitis (AD), but its exact mechanism of action remains unclear. Therefore, in this study, we investigated the effects of CBC on Th2 cytokines along with the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways involved in AD pathogenesis. We used a 2,4-Dinitrochlorobenzene (DNCB)-induced BALB/c mouse model to topically administer CBC (0.1 mg/kg or 1 mg/kg). The results showed that skin lesion severity, ear thickness, epithelial thickness of dorsal and ear skin, and mast cell infiltration were significantly reduced in the 0.1 mg/kg CBC-treated group compared with the DNCB-treated group ( < 0.001). In addition, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis showed a significant decrease in the mRNA expression of Th2 cytokines (, , ) and inflammatory mediators (, , , , , and ) ( < 0.05). Western blot analysis also revealed a significant decrease in JAK1, JAK2, STAT1, STAT2, STAT3, and STAT6 protein expression ( < 0.05). These results suggest that CBC is a promising candidate for the treatment of AD and demonstrates the potential to alleviate AD symptoms by suppressing the Th2 immune response.

摘要

大麻二酚(CBC)是大麻植物中发现的主要大麻素之一,尽管其知名度不如四氢大麻酚(THC)和大麻二酚(CBD),但因其潜在的治疗益处而受到关注。迄今为止,CBC已知的作用机制包括通过激活TRP通道和抑制炎症途径产生抗炎、镇痛、抗抑郁、抗菌、神经保护和抗痤疮作用,这表明它可能在治疗炎症性皮肤病如特应性皮炎(AD)方面具有治疗潜力,但其确切作用机制仍不清楚。因此,在本研究中,我们研究了CBC对AD发病机制中涉及的Th2细胞因子以及Janus激酶(JAK)/信号转导和转录激活因子(STAT)途径的影响。我们使用2,4-二硝基氯苯(DNCB)诱导的BALB/c小鼠模型局部给予CBC(0.1mg/kg或1mg/kg)。结果显示,与DNCB治疗组相比,0.1mg/kg CBC治疗组的皮肤病变严重程度、耳厚度、背部和耳部皮肤上皮厚度以及肥大细胞浸润均显著降低(<0.001)。此外,实时定量逆转录聚合酶链反应(qRT-PCR)分析显示Th2细胞因子(、、)和炎症介质(、、、、和)的mRNA表达显著降低(<0.05)。蛋白质印迹分析还显示JAK1、JAK2、STAT1、STAT2、STAT3和STAT6蛋白表达显著降低(<0.05)。这些结果表明,CBC是治疗AD的有希望的候选药物,并证明了通过抑制Th2免疫反应缓解AD症状的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae8/11677870/88dab940838f/ijms-25-13539-g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae8/11677870/88dab940838f/ijms-25-13539-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae8/11677870/5cbf9da069b2/ijms-25-13539-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae8/11677870/0590aa7b08dc/ijms-25-13539-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae8/11677870/4fd46662ae42/ijms-25-13539-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae8/11677870/88dab940838f/ijms-25-13539-g006.jpg

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