Effects of Ursolic Acid on the Expression of Th1–Th2-related Cytokines in a Rat Model of Allergic Rhinitis After PM2.5 Exposure

Abstract

Background

Allergic rhinitis (AR) is a global health problem and closely related to environmental factors. Ursolic acid (UA) has potential in the treatment of allergic inflammation. The effects of UA intervention on PM2.5-induced AR remain uncertain.

Objective

To assess the effects of UA on nasal symptoms and the expression of T-helper (Th)1–Th2-related cytokines in a rat model of AR after fine particulate matter (particulate matter ≤ 2.5 µm [PM2.5]) exposure.

Methods

A total of 40 healthy female Sprague-Dawley rats were randomly divided into 4 groups: normal control group (NC group), ovalbumin (OVA)- induced AR model (AR group), PM2.5-exposed AR group exposed to 200 g/m³ PM2.5 for 30 days via inhalation (ARE group), and a group with UA intervention to the AR model after PM2.5 exposure (UA group). UA intervention was adopted after PM2.5 exposure in the UA group. Nasal symptoms and levels of Th1–Th2 cytokines in the serum were detected in each individual rat. The pathological changes and expression of Eotaxin in the nasal mucosa of each individual rat were examined by histology.

Results

PM2.5 significantly increased the number of sneezes and nasal rubs in the rats with AR, and UA alleviated these symptoms. UA decreased interleukin (IL)-4, IL-5, IL-13, Eotaxin-1, and OVA Immunoglobulin E (IgE) protein levels. In the AR group, hematoxylin and eosin staining showed disordered arrangement of the nasal mucosa epithelium, cell shedding, eosinophilic infiltration, swelling of the glands, and submucosal vascular congestion. UA group showed reduced eosinophilic infiltration and orderly arrangement of the mucosal epithelium when compared with the ARE group. Immunohistochemical results showed that the expression of Eotaxin in the UA group was lower than that in the ARE group.

Conclusion

UA could relieve nasal symptoms caused by PM2.5 exposure, the possible mechanism of which is to inhibit the expression of Th2 cytokines, eosinophilic infiltration, and specific IgE production.

Keywords

ursolic acid allergic rhinitis PM2.5,cytokines exposure Th1,Th2 intervention immune regulation treatment

Get full access to this article

View all access options for this article.

References

Cheng

Chen

, et al. Chinese Society of Allergy Guidelines for diagnosis and treatment of allergic rhinitis. Allergy Asthma Immunol Res. 2018; 10(4):300–353.

Meltzer

EO.

Allergic rhinitis: burden of illness, quality of life, comorbidities, and control. Immunol Allergy Clin North America. 2016; 36(2):235–248

Hong

Guo

Zhang

, et al. Airborne fine particulate matter induces oxidative stress and inflammation in human nasal epithelial cells. Tohoku J Exp Med. 2016; 239(2):117–125.

Guo

Dong

, et al. T-helper type 1-T-helper type 2 shift and nasal remodeling after fine particulate matter exposure in a rat model of allergic rhinitis. Am J Rhinol Allergy. 2017; 31(3):148–155.

Renwu

Zhiqiang

Ruxin

, et al. Nasal epithelial barrier disruption by particulate matter ≤2.5 µm via tight junction protein degradation. J Appl Toxicol. 2018; 38(5):678–687.

Pironi

de Araujo

Fernandes

, et al. Characteristics, biological properties and analytical methods of ursolic acid: a review[J]. Crit Rev Anal Chem. 2018, 48(1):86–93.

Jang

Yee

Choi

, et al. Ursolic acid enhances the cellular immune system and pancreatic beta-cell function in streptozotocin-induced diabetic mice fed a high-fat diet. Int Immunopharmacol. 2009; 9(1), 113–119.

Kashyap

Sharma

Tuli

Punia

Sharma

AK.

Ursolic acid and oleanolic acid: pentacyclic terpenoids with promising anti-inflammatory activities. Recent Patents Inflamm Allergy Drug Discov. 2016; 10(1):21–33.

Ding

Wang

Zhu

Wei

Ursolic acid ameliorates early brain injury after experimental traumatic brain injury in mice by activating the Nrf2 pathway. Neurochem Res. 2017; 42(2):337–346.

10.

Rai

Yadav

Singh

SP.

Ursolic acid attenuates oxidative stress in nigrostriatal tissue and improves neurobehavioral activity in MPTP-induced parkinsonian mouse model. J Chem Neuroanat. 2016; 71:41–49.

11.

Dong

Liu

Zhang

, et al. Downregulation of miR-21 is involved in direct actions of ursolic acid on the heart: implications for cardiac fibrosis and hypertrophy. Cardiovasc Ther. 2015; 33(4):161–167.

12.

Zhao

Guo

Dong

, et al. Effects of PM2.5 on mucus secretion and tissue remodeling in a rabbit model of chronic rhinosinusitis. Int Forum Allergy Rhinol. 2018; 8(11),1349–1355.

13.

Shanmugam

Dai

Kumar

, et al. Ursolic acid in cancer prevention and treatment: molecular targets, pharmacokinetics and clinical studies[J]. Biochem Pharmacol. 2013; 85(11):1579–1587.

14.

Ramos

Pereira-Wilson

Collins

AR.

Protective effects of ursolic acid and luteolin against oxidative DNA damage include enhancement of DNA repair in Caco-2 cells[J]. Mutat Res/Fund Mol Mech Muta. 2010; 692(1–2):6–11.

15.

Lin

JY.

Anti-inflammatory effects of 27 selected terpenoid compounds tested through modulating Th1/Th2 cytokine secretion profiles using murine primary splenocytes. Food Chem. 2013; 141(2):1104–1113.

16.

Ding

Zhang

, et al. Ursolic acid protects mouse liver against CCl4-induced oxidative stress and inflammation by the MAPK/NF-kappaB pathway[J]. Environ Toxicol Pharmacol. 2014; 37(3):975–983.

17.

Ramirez

Zhang

, et al. In Vitro-in vivo dose response of ursolic acid, sulforaphane, PEITC, and curcumin in cancer prevention[J]. AAPS J. 2017; 20(1):19.

18.

Yuan

Ghosh

Jie

, et al. Effects of desloratadine citrate disodium injection on rat models of ovalbumin-induced allergic rhinitis: involvement of T-cell responses modulation. Int Forum Allergy Rhinol. 2015; 5:1170–1176.

19.

Zhou

Balzar

, et al. MAPK regulation of IL-4/IL-13 receptors contributes to the synergistic increase in CCL11/Eotaxin-1 in response to TGF-beta1 and IL-13 in human airway fibroblasts[J]. J Immunol. 2012; 188(12): 6046–6054.

20.

Kim

Hong

Lee

YC.

Ursolic acid, a potential PPARγ agonist, suppresses ovalbumin-induced airway inflammation and Penh by down-regulating IL-5, IL-13, and IL-17 in a mouse model of allergic asthma. Eur J Pharmacol. 2013; 701(1–3):131–143.