紫花前胡苷对犬特应性皮炎的疗效分析

doi:10.11843/j.issn.0366-6964.2025.03.043

Abstract

Abstract:

Canine atopic dermatitis (CAD) is a complex inflammatory skin disease associated with alterations in the skin microbiota, immunity and skin barrier. Nodakenin is a coumarin glycoside with anti-inflammatory, antimicrobial and antioxidant properties. The aim of this study was to investigate the intervention effect of Nodakenin on 2, 4-dinitrotoluene (DNCB)-induced canine atopic dermatitis as well as the effect of skin microbiota. DNCB-induced canine atopic dermatitis was first established, and nodakenin was administered for 14 days as a topical application treatment. The effect of nodakenin treatment was assessed by body weight indexes, routine blood tests, serum biochemical tests, serum immunoglobulin E (IgE) levels, the degree of skin lesions and itching, and the results of 16S rRNA sequencing of skin microbiota. Compared with the DNCB group, the nodakenin group showed a significant increase in body weight, a significant increase in the total number of leukocytes and the percentage of neutrophils in the routine blood indexes (P < 0.05), while there was no significant difference in the serum biochemical related indexes (P>0.05), a significant decrease in the serum IgE content (P < 0.05), and a significant improvement in the degree of skin lesions and itching (P < 0.01). There were significant differences in both alpha diversity and beta diversity in the skin microbiota (P < 0.05), and at the phylum level, the relative abundance of the thick-walled phylum Firmicutes was significantly restored after nodakenin treatment (P < 0.01). At the genus level, nodakenin treatment significantly increased the relative abundance of Romboutsia, Clostridium_sensu_stricto_1, and Terrisporobacter (P < 0.01 and P < 0.05, respectively) and significantly decreased the relative abundance of Moraxella and Staphylococcus spp. relative abundance (P < 0.05). The application of nodakenin can effectively reduce the degree of skin lesions, alleviate itchy skin, reduce serum IgE levels, and regulate the imbalance of skin microbiota, thus improving the symptoms of canine atopic dermatitis and providing a new idea for drug development for CAD.

Key words: nodakenin, 2, 4-dinitrochlorobenzene(DNCB), canine atopic dermatitis, skin microbiota

CLC Number:

S853.74

WANG Zijiao, LIU Chunxiao, LI Guangyu. Analysis of the Efficacy of Nodakenin in Canine Atopic Dermatitis[J]. Acta Veterinaria et Zootechnica Sinica, 2025, 56(3): 1453-1464.

Figures/Tables 14

Table 1

Table 2

Table 3

Table 4

Table 5

Fig. 1

Fig. 2

Fig. 3

Fig. 4

Fig. 5

Fig. 6

Fig. 7

Fig. 8

Fig. 9

References 35

1	SANTORO D , SARIDOMICHELAKIS M , EISENSCHENK M , et al. Update on the skin barrier, cutaneous microbiome and host defence peptides in canine atopic dermatitis[J]. Vet Dermatol, 2024, 35 (1): 5- 14. doi: 10.1111/vde.13215
2	MARSELLA R , DE BENEDETTO A . Atopic dermatitis in animals and people: an update and comparative review[J]. Vet Sci, 2017, 4 (3): 37.
3	FERNANDES B , ALVES S , SCHMIDT V , et al. Primary prevention of canine atopic dermatitis: breaking the cycle-a narrative review[J]. Vet Sci, 2023, 10 (11): 659.
4	GEDON N K Y , MUELLER R S . Atopic dermatitis in cats and dogs: a difficult disease for animals and owners[J]. Clin Transl Allergy, 2018, 8, 41. doi: 10.1186/s13601-018-0228-5
5	NOLI C . Assessing quality of life for pets with dermatologic disease and their owners[J]. Vet Clin North Am Small Anim Pract, 2019, 49 (1): 83- 93. doi: 10.1016/j.cvsm.2018.08.008
6	FAVROT C , STEFFAN J , SEEWALD W , et al. A prospective study on the clinical features of chronic canine atopic dermatitis and its diagnosis[J]. Vet Dermatol, 2010, 21 (1): 23- 31. doi: 10.1111/j.1365-3164.2009.00758.x
7	BIZIKOVA P , SANTORO D , MARSELLA R , et al. Review: clinical and histological manifestations of canine atopic dermatitis[J]. Vet Dermatol, 2015, 26 (2): 79- e24. doi: 10.1111/vde.12196
8	HENSEL P , SANTORO D , FAVROT C , et al. Canine atopic dermatitis: detailed guidelines for diagnosis and allergen identification[J]. BMC Vet Res, 2015, 11, 196. doi: 10.1186/s12917-015-0515-5
9	MARSELLA R , DOERR K , GONZALES A , et al. Oclacitinib 10 years later: lessons learned and directions for the future[J]. J Am Vet Med Assoc, 2023, 261 (S1): S36- S47. doi: 10.2460/javma.22.12.0570
10	ROEKEVISCH E , SPULS P I , KUESTER D , et al. Efficacy and safety of systemic treatments for moderate-to-severe atopic dermatitis: a systematic review[J]. J Allergy Clin Immunol, 2014, 133 (2): 429- 438. doi: 10.1016/j.jaci.2013.07.049
11	YU S H , DRUCKER A M , LEBWOHL M , et al. A systematic review of the safety and efficacy of systemic corticosteroids in atopic dermatitis[J]. J Am Acad Dermatol, 2017, 78 (4): 733- 740. e11.
12	LIM J Y , LEE J H , YUN D H , et al. Inhibitory effects of nodakenin on inflammation and cell death in lipopolysaccharide-induced liver injury mice[J]. Phytomedicine, 2021, 81, 153411. doi: 10.1016/j.phymed.2020.153411
13	JIN B R , LEE M , AN H J . Nodakenin represses obesity and its complications via the inhibition of the VLDLR signalling pathway in vivo and in vitro[J]. Cell Prolif, 2021, 54 (8): e13083. doi: 10.1111/cpr.13083
14	PARK S J , CHA H S , LEE Y H , et al. Effect of nodakenin on atopic dermatitis-like skin lesions[J]. Biosci Biotechnol Biochem, 2014, 78 (9): 1568- 1571. doi: 10.1080/09168451.2014.923296
15	LEE N Y , CHUNG K S , JIN J S , et al. The inhibitory effect of nodakenin on mast-cell-mediated allergic inflammation via downregulation of NF-κB and caspase-1 activation[J]. J Cell Biochem, 2017, 118 (11): 3993- 4001.
16	肖晓杰, 丁明星, 齐智利, 等. 添加补骨脂提取物的低敏处方粮对犬皮肤健康的影响[J]. 养殖与饲料, 2022, 21 (9): 18- 24.
	XIAO X J , DING M X , QI Z L , et al. Effects of hypoallergenic prescription diet containing psoralea on health and disease in dogs[J]. Animals Breeding and Feed, 2022, 21 (9): 18- 24.
17	TAO R , LI R Y , WANG R J . Dysbiosis of skin mycobiome in atopic dermatitis[J]. Mycoses, 2022, 65 (3): 285- 293.
18	CHAI R R , TAI Z G , ZHU Y J , et al. Symbiotic microorganisms: prospects for treating atopic dermatitis[J]. Expert Opin Biol Ther, 2022, 22 (7): 911- 927.
19	KRAWIEC D R , GAAFAR S M . A comparative study of allergic and primary irritant contact dermatitis with dinitrochlorobenzene (DNCB) in dogs[J]. J Invest Dermatol, 1975, 65 (2): 248- 251.
20	PARAMASIVAN P , LAI C , PICKARD C , et al. Repeated low-dose skin exposure is an effective sensitizing stimulus, a factor to be taken into account in predicting sensitization risk[J]. Br J Dermatol, 2010, 162 (3): 594- 597.
21	LIAO Y , CHEN Z , YANG Y K , et al. Antibiotic intervention exacerbated oxidative stress and inflammatory responses in SD rats under hypobaric hypoxia exposure[J]. Free Radic Biol Med, 2023, 209, 70- 83.
22	张伟, 胡莉萍, 孙艳, 等. 动物应激的评价指标的探讨[J]. 畜牧兽医科技信息, 2018 (3): 5.
	ZHANG W , HU L P , SUN Y , et al. Exploration of evaluation indexes of animal stress[J]. Chinese Journal of Animal Husbandry and Veterinary Medicine, 2018 (3): 5.
23	CZARNOWICKI T , HE H , KRUEGER J G , et al. Atopic dermatitis endotypes and implications for targeted therapeutics[J]. J Allergy Clin Immunol, 2019, 143 (1): 1- 11.
24	HUANG K K , LI F , LIU Y Y , et al. Multi-omics analyses reveal interactions between the skin microbiota and skin metabolites in atopic dermatitis[J]. Front Microbiol, 2024, 15, 1349674.
25	SAVVA M , PAPADOPOULOS N G , GREGORIOU S , et al. Recent advancements in the atopic dermatitis mechanism[J]. Front Biosci (Landmark Ed), 2024, 29 (2): 84.
26	CHERMPRAPAI S , EDERVEEN T H A , BROERE F , et al. The bacterial and fungal microbiome of the skin of healthy dogs and dogs with atopic dermatitis and the impact of topical antimicrobial therapy, an exploratory study[J]. Vet Microbiol, 2019, 229, 90- 99.
27	BRADLEY C W , MORRIS D O , RANKIN S C , et al. Longitudinal evaluation of the skin microbiome and association with microenvironment and treatment in canine atopic dermatitis[J]. J Invest Dermatol, 2016, 136 (6): 1182- 1190.
28	RODRIGUES H A , PATTERSON A P , DIESEL A , et al. The skin microbiome in healthy and allergic dogs[J]. PLoS One, 2014, 9 (1): e83197.
29	KIM J , KIM B E , GOLEVA E , et al. Alterations of epidermal lipid profiles and skin microbiome in children with atopic dermatitis[J]. Allergy Asthma Immunol Res, 2023, 15 (2): 186- 200.
30	THOMSEN M , KUNSTNER A , WOHLERS I , et al. A comprehensive analysis of gut and skin microbiota in canine atopic dermatitis in Shiba Inu dogs[J]. Microbiome, 2023, 11 (1): 232.
31	WANG Y W , HOU J P , TSUI J C , et al. Unique gut microbiome signatures among adult patients with moderate to severe atopic dermatitis in southern Chinese[J]. Int J Mol Sci, 2023, 24 (16): 12856.
32	SUNDE R B , THORSEN J , KIM M , et al. Bacterial colonisation of the airway in neonates and risk of asthma and allergy until age 18 years[J]. Eur Respir J, 2024, 63 (1): 2300471.
33	NAKATSUJI T , CHEN T H , NARALA S , et al. Antimicrobials from human skin commensal bacteria protect against Staphylococcus aureus and are deficient in atopic dermatitis[J]. Sci Transl Med, 2017, 9 (378): eaah4680.
34	IWAMOTO K , MORIWAKI M , MIYAKE R , et al. Staphylococcus aureus in atopic dermatitis: Strain-specific cell wall proteins and skin immunity[J]. Allergol Int, 2019, 68 (3): 309- 315.
35	HERZ U , SCHNOY N , BORELLI S , et al. A human-SCID mouse model for allergic immune response bacterial superantigen enhances skin inflammation and suppresses IgE production[J]. J Invest Dermatol, 1998, 110 (3): 224- 231.

病变程度 Lesion level	评分 Score
无明显变化 No significant change	0
红斑 Erythema	1
红斑、皮肤苔藓化或丘疹 Erythema, mossy skin or pimples	2
红斑、皮肤苔藓化和更严重反应 Erythema, mossy skin and more severe reactions	3

瘙痒程度 Itchiness	评分 Score
没有瘙痒 No itch	0
轻度瘙痒 Mild itch	1~2
中度瘙痒 Moderate itch	3~4
持续且剧烈瘙痒 Constant and intense itch	5

时间 Time	组别Group
时间 Time	Ctrl	DNCB	DNCB+NK
第0天Day 0	15.06±1.77	16.25±2.78	16.86±1.18
第7天Day 7	15.28±1.84	15.60±2.60	16.44±1.29
第14天Day 14	15.27±1.72	15.88±3.01	16.46±1.41
第21天Day 21	15.35±2.10	15.84±2.52	16.60±1.47

检测项目 Item	组别Group			参考范围 Reference scope
检测项目 Item	Ctrl	DNCB	DNCB+NK	参考范围 Reference scope
白细胞总数/(10⁹·L^-1) WBC	16.06±1.27	11.89±2.32^##	14.42±1.36^*	6.0~17.0
淋巴细胞数量/(10⁹·L^-1) LYM	2.13±0.65	1.65±1.05	1.89±0.20	1.0~4.8
单核细胞数量/(10⁹·L^-1) MON	1.20±0.42	0.99±0.29	1.21±0.24	0.2~1.5
中性粒细胞数量/(10⁹·L^-1) NEU	9.48±1.12	6.40±1.52^#	8.78±1.95	3~12
嗜酸性粒细胞数量/(10⁹·L^-1) EOS	0.95±0.31	0.78±0.18	0.84±0.38	0~0.9
嗜碱性粒细胞数量/(10⁹·L^-1) BAS	0.07±0.03	0.02±0.01	0.03±0.02	0~0.4
淋巴细胞百分比/% LYM	18.26±3.72	19.03±3.55	17.77±4.97	12~30
单核细胞百分比/% MON	8.40±1.93	9.96±1.88^##	9.78±1.88	3~14
中性粒细胞百分比/% NEU	74.32±6.27	61.02±5.13^#	68.09±6.26^*	60~80
嗜酸性粒细胞百分比/% EOS	6.37±0.49	6.03±2.07	6.56±2.59	0~10
嗜碱性粒细胞百分比/% BAS	0.38±0.06	0.18±0.05	0.21±0.08	少有
红细胞总数/(10¹²·L^-1) RBC	5.83±0.74	4.85±1.48	5.13±0.63	5.5~8.5
血红蛋白浓度/(g·L^-1) HGB	137.25±32.33	130.00±38.57	138.75±15.76	120~180
红细胞压积/% HCT	35.50±7.83	33.63±6.74	32.08±5.72	30~55
平均红细胞体积/fL MCV	68.25±1.23	68.50±2.15	68.80±0.14	60~77
平均红细胞血红蛋白含量/pg MCH	26.78±0.59	27.53±0.90	26.73±0.13	19.5~26.5
平均红细胞血红蛋白浓度/(g·L^-1) MCHC	385.25±12.28	386.25±5.32	391.50±6.45	310~390
红细胞体积分布宽度变异系/% RDWc	13.48±0.13	14.05±0.84	13.60±0.50	————
血小板总数/(10⁹·L^-1) PLT	284.67±109.71	203.75±51.60	240.50±62.78	165~500

检测项目 Item	组别Group
检测项目 Item	Ctrl	DNCB	DNCB+NK
丙氨酸氨基转氨酶/[nmol· (min·mL)^-1] ALT	3.41±0.81	3.32±1.25	3.65±1.09
天冬氨酸氨基转氨酶/[nmol· (min·mL)^-1] AST	1.58±0.76	1.51±1.24	1.45±0.77
肌酐/(μmol·L) ^-1 CRE	39.36±4.79	36.13±4.79	40.88±2.89
白蛋白/(g·L) ^-1 ALB	30.48±3.29	33.47±2.05	31.81±0.82
碱性磷酸酶/[μmol· (min·mL)^-1] AKP	0.55±0.06	0.28±0.01^##	0.33±0.09
葡萄糖/(mg·mL) ^-1 GLU	61.24±6.20	49.41±3.99^#	51.62±5.82
血中γ-谷氨酰转移酶/(U·L) ^-1 γ-GT	7.18±0.48	8.65±1.87	8.62±1.22
钙含量/(mmol·L) ^-1 Ca	2.57±0.13	2.62±0.13	2.60±0.04

Analysis of the Efficacy of Nodakenin in Canine Atopic Dermatitis

RichHTML

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 14

References 35

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	JIN Ruwen, WANG Yingjie, JIANG Quanxing, LIU Tianqiang, DENG Yang, LUO Jie, ZHAO Ling, YE Gang, SHI Fei, LI Yinglun, TANG Huaqiao. Effects of Modified Zhizhu Powder on Intestinal Mucosal Barrier and Antioxidant Capacity of Weaned Rabbits [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(12): 5825-5838.
[2]	Qilin HUANG, Chen LIU, Xiaohan JING, Lina HUANG, Xiangyi PAN, Xiongwei SHI, Zhengying QIU, Ruihua XIN. Naringin Repairs Actinobacillus pleuropneumoniae-induced Lung Epithelial Barrier Damage in Mice via Multiple Pathways [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(11): 5299-5309.
[3]	Qi FENG, Yigang LIU, Qin HE, Zelong LI, Yingcai MA, Pengfei YI, Na LI, Yawei SUN, Rulong CHEN, Gang YAO, Xuelian MA. Evaluation of the Inhibitory Activity of Folium Isatidis Aqueous Extract on the in vitro Proliferation of Infectious Bovine Rhinotracheitis Virus [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(11): 5287-5298.
[4]	Qingxin YUAN, Kuo LIU, Xuhua BAO, Dongyang GAO, He LI, Jun SONG, Zhixin ZHOU. The Mechanism of Chelerythrine against Methicillin-resistant Staphylococcus aureus [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(10): 4670-4678.
[5]	Anlin WEN, Yunyun YANG, Yongrong LUO, Ying YANG, Zhentao CHENG, Deyuan OU, Ming WEN. Network Pharmacologic Analysis and Experimential Verification on the Mechanism of Coptidis Rhizoma in Preventing Duck Viral Enteritis [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(7): 3225-3233.
[6]	Meiyan LI, Xiaoying XING, Na LI, Yeli ZHANG, Hongping QIAO, Xiaoying WU. Regulation of Glycyrrhizol Polysaccharide Alleviate LPS-induced Orchitis in Mice [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(6): 2741-2750.
[7]	CHEN Fubin, XU Guowei, WANG Lei, LIU Qin, FENG Haipeng, ZHANG Kang, GUO Zhiting, HAN Songwei, LIU Jiahui, GU Xueyan, ZHANG Jingyan, LI Jianxi, HUUB F. J. Savelkoul. Effects of Astragalus Polysaccharides on Transcriptome and Metabolome of HD11 Chicken Macrophages [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(3): 1290-1301.
[8]	WEI Miaoyi, WU Shihai, YANG Fulin, YU Chenyun, SUN Zhigang, LIU Xinyuan, XU Yuanyuan, LIANG Bingbing, LI Fuhuang, SUN Hong, LIU Xiaoye, DONG Hong. Clinical Efficacy of Herbal Gentian Combat Trichomonas pigeon [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(2): 785-796.
[9]	XIAO Le, LIU Junyuan, ZENG Wenyu, WANG Qin, HAN Wenjue, LIU Yanling, FAN Yu, XU Yuting, YANG Beini, XIAO Xiong, WANG Zili. Microbiome and Transcriptome Analyses Revealed the Regulatory Mechanism of Xiangsha Liujunzi Decoction on Ileal Injury Induced by ETEC in Weaned Piglets with Diarrhea [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(2): 797-808.
[10]	XUE Linli, SUN Rui, HAO Xiaojing, CAO Xiaorui, WANG Haidong, LU Jiayin. The Promoting Effect Analysis of Danshensu on Skeletal Muscle Repair and Regeneration after Skeletal Muscle Injury in Mice based on a Mouse Skeletal Muscle Injury Model [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(12): 5252-5263.
[11]	CHI Xingzi, LI Yaoxing, WANG Huiting, YAN Ming’en, YANG Shijing, YANG Bowen, SUN Han, GUO Shining, SHI Dayou, WU Li, LIU Cui. Effect of Echinacea purpurea Extract Combined with Sulfasalazine on Immune Imbalance of Th17/Treg in Rats with Damp-Heat Syndrome [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(11): 4817-4826.
[12]	ZHANG Xumei, WEI Yurong, XU Chenghui, YANG Tong, SHI Huijun, FU Qiang, YANG Li. To Analyze the Mechanism of Berberine in the Treatment of Salmonella Gallinarum Infection Based on Network Pharmacology and Experimental Verification [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(8): 3557-3570.
[13]	GONG Zhiguo, ZHAO Jiamin, GU Baichen, REN Peipei, YU Zhuoya, BAI Yunjie, LIU Xinyu, WANG Chao, LIU Bo. Exploring the Mechanism of Codonopsis pilosula in Alleviation of Acute Lung Injury in Escherichia coli Infected Mice Based on Network Pharmacology [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(8): 3571-3581.
[14]	PAN Chanyuan, ZHAO Zixuan, DUAN Mingjie, JIANG Linshu, TONG Jinjin. The Mechanism of Artemisia carvifolia Alleviating Dairy Cow Oxidative Stress Predicted by Network Pharmacology [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(3): 1071-1084.
[15]	CHANG Yingyan, ZHAO Hongyan, HU Maozhi, LIU Zongping. Protective Effect of Aurantiamide Acetate on Cd-induced Apoptosis of Osteoblasts in vitro [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(3): 1273-1280.