Elsevier

Biomedicine & Pharmacotherapy

Volume 94, October 2017, Pages 880-889
Biomedicine & Pharmacotherapy

Original research article
Ameliorative effects of Artemisia pallens in a murine model of ovalbumin-induced allergic asthma via modulation of biochemical perturbations

https://doi.org/10.1016/j.biopha.2017.08.017Get rights and content

Highlights

  • Airway hyperresponsiveness (AHR) was induced in rats by ovalbumin (OVA).

  • APME significantly attenuated OVA-induced alteration in lung functions.

  • APME inhibited serum IgE, TNF-α, IL’s, TGF-β levels and decreased lung fibrosis.

  • APME significantly inhibited oxido-nitrosative stress and increased lung Nrf2 level.

  • Artemisia pallens exhibits its anti-asthmatic potential in OVA-induced AHR.

Abstract

Introduction

Asthma is a chronic, heterogeneous airway disorder characterized by airway inflammatory and remodeling. Artemisia pallens has been reported to possess antioxidant, anti-inflammatory and Anti-allergic potential.

Objective

To evaluate the anti-asthmatic effects of methanolic extract of Artemisia pallens (APME) against ovalbumin (OVA)-induced airway hyperresponsiveness (AHR) in rats.

Materials and method

AHR was induced in male Sprague-Dawley rats (180–200 g) by intraperitoneal (i.p.) injection of OVA and boosted with an identical OVA solution (s.c.) on day 7. Rats were either treated orally with vehicle (10 mg/kg), montelukast (10 mg/kg) or APME (100, 200 and 400 mg/kg) for next 28 days. At the end treatments, various biochemical, molecular (RT-PCR and ELISA analysis) and histological parameters were evaluated.

Results

APME (200 and 400 mg/kg) significantly attenuated (p < 0.05) OVA-induced alteration in lung functions measured by Whole-body plethysmography. Increased Bronchoalveolar Lavage (BAL) fluid differential cell count, as well as total protein and albumin in BAL fluid and lungs, was significantly decreased (p < 0.05) by APME. It also significantly attenuated (p < 0.05) elevated lung oxido-nitrosative stress, myeloperoxidase, and serum IgE levels. OVA-induced down-regulation in lung Nrf2 and upregulation in TNF-α, IL-1β, IL-4, IL-6, TGF-β mRNA expression was significantly attenuated (p < 0.05) by APME (200 and 400 mg/kg) treatment. Histopathological analysis of lung tissue showed that APME treatment reduced OVA-induced inflammatory influx and fibrosis.

Conclusion

Artemisia pallens simultaneously orchestrate plethora of mechanisms viz. modulations of IgE, TGF-β, TNF-α, IL’s and Nrf-2 levels to exhibit its anti-asthmatic potential in OVA-induced AHR in rats.

Introduction

Asthma is a heterogeneous disease characterized by chronic airway inflammation. It is a chronic respiratory condition affecting 1% to 18% of the population in different countries [1]. According to the Global Burden of Disease Study (GBD), the total number of people suffering from asthma in the world may be as high as 334 million [2]. Allergens, exercise, cold air, upper respiratory tract infection are the possible precipitating factors for asthma [3]. Symptoms which define asthma including wheezing, coughing lead to an impediment of normal activities and narrowing of the airway reduces the efficiency of movement of air to and from the alveoli [4]. Airway hyperresponsiveness (AHR) and airway inflammation, usually accompany asthma, but these are not necessary or sufficient to make the diagnosis [1].

It has been reported that inflammatory cells played a vital role in induction and maintenance of pathogenesis of asthma [5]. Inflammatory infiltration at the site of allergic infection enhances the inflammatory responses that are resulting into tissue damage, and dysfunctioning could be due to the liberation of mediators such as platelet-activating factor, leukotrienes, prostaglandins, histamine, cytokines, chemokines, and cationic proteins [6], [7]. It has been reported that serotonin is an important mediator of asthma which releases from mast cells and platelets in plasma resulted in a contraction of airway smooth muscles [8]. Furthermore, T helper cell induced type 2 immune responses in mast cell are also leading to the production of cytokines, interleukin (IL)-4, IL-5, IL-9 and IL-13, eosinophil inflammation and immunoglobulin E [9], [10]. This type of immune response triggers due to airborne particles which could be allergic (e.g., dust mites, cockroach residue, furred animals, moulds, pollens) and non-allergic (e.g., infections, tobacco smoke, cold air, exercise) results in AHR. Severe, long-standing asthma changes the architecture of the airway which includes smooth muscle hypertrophy, and broncho-fibrosis can lead to an irreversible decrement in pulmonary function.

Animal models play an important role in the development of therapeutic moieties in allergens induced AHR and chronic airway inflammation [11]. Ovalbumin (OVA)-induced asthma model mimics clinicopathological features of asthma including the airway edema, goblet cell hyperplasia, increased mucus production, persistent bronchospasm along with inflammatory influx which may result in anaphylactic shock [7]. In OVA-induced asthma, aluminum hydroxide is used as adjuvant and OVA as an allergen. Aluminum hydroxide when exposed to the presence of antigen, it promotes the development of Th2 phenotype resulted in asthma [12].

Effective treatment of allergic asthma includes β2-agonists, anticholinergics, oral corticosteroids, immunomodulators, anti-leukotrienes or leukotriene modifiers and mast cell stabilizers [13]. Montelukast, a cysteinyl leukotriene receptor (CysLTR)1 antagonist which is widely used for the treatment of allergic asthma via modulation of Th2 cytokines and growth factors [14]. However, these treatment regimens provide mitigation in only to a small number of patients and also associated with side effect thus limit their implication in the treatment of asthma [15]. Literature cited with evidence suggests that, the drugs from herbal origin play an important role in inhibition of development of asthma [13].

Artemisia pallens Walls. ex DC (Davana) (Asteraceae) found abundantly in the southern part of India including Karnataka, Tamil Nadu, Andhra Pradesh and Maharashtra [16], [17]. It is an aromatic herb which has been used by tribal people for various ailments. It possesses an array of pharmacological properties including anthelmintic, tonic, antioxidant, analgesic, antipyretic, antifungal, antibacterial, antimicrobial, antidiabetic, and anti-inflammatory activities [18], [19]. The researcher also reported its hepatoprotective and nephroprotective potentials against acetaminophen-induced toxicity [17]. It has been reported that Artemisia pallens contain sesquiterpene lactone as an active constituent [19]. Moreover, previously sesquiterpene lactones have been found to be effective against asthma in laboratory animals [20]. Hence, the aim of present study was to evaluate the effect of Artemisia pallens against OVA-induced asthma by assessing various behavioral, biochemical, molecular and histological parameters in laboratory animals.

Section snippets

Preparation of methanolic extract of Artemisia pallens (APME)

The APME was prepared by macerating air dried and course powdered plant of Artemisia pallens with methanol according to previously reported methods [16], [17].

Animals

Adult male Sprague-Dawley rats (180–200 g) were obtained from the National Institute of Biosciences, Pune (India). They were maintained at 24 ± 1 °C, with a relative humidity of 45–55% and 12:12 h dark/light cycle. The animals had free access to standard pellet chow (Pranav Agro-industries Ltd., Sangli, India) and water throughout the

Effect of APME treatment on OVA-induced alteration in body weight, relative lung weight, hemodynamic parameters and percent oxygen saturation of rats

OVA-induced AHR is associated with reduced body weight and increased lung weight. Also, administration of OVA resulted in decreased fraction of oxygen-saturated hemoglobin which was determined by evaluating percent oxygen saturation. In the present investigation, there was significantly decreased (p < 0.05) in body weight, heart rate and percent oxygen saturation in OVA control group whereas significant increased (p < 0.05) in relative lung weight, SBP, DBP and MABP in OVA control group as compared

Discussion

Asthma is a chronic, complex, immune-inflammatory disorder and thus various animal models played a vital role in the understanding the mechanism as well as evaluation of various therapeutic moieties against asthma. It has been well documented that allergen-induced asthma is associated with chronic inflammation and remodeling of airways. Thus, an array of agents such as corticosteroid, dexamethasone, leukotriene modifiers and mast cell stabilizers has employed to suppress inflammation in this

Conclusion

Taken together, the results of present investigation suggests that administration of APME in OVA-induced AHR rats exerted its anti-asthmatic potential via a plethora of mechanisms including inhibition of oxido-nitrosative stress, IgE, TGF-β, TNF-α, IL’s along with an increase in Nrf-2 level in rats. This finding may open novel landscapes in therapeutic option for the phytoconstituent like artemisinin with the antioxidant potential to treat allergen-induced asthma.

Grants, sponsors, and funding sources

None.

Conflict of interest

The authors declare that there are no conflicts of interest.

Acknowledgements

The authors acknowledge Dr. S. S. Kadam, Vice Chancellor, and Dr. K. R. Mahadik, Principal, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Pune, India, for providing the necessary facilities to carry out the study.

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