EC Pharmacology and Toxicology

Background: Acute systemic anaphylaxis is a severe, acute allergic response to an allergen/antigen that is rapid in onset, characterized by life-threatening airway obstruction and hypotension - involving an inflammatory response of multiple organ systems. Medicinal plants have been used for centuries as a pharmacologic alternative/complementary mode of therapy in the prevention and treatment of many allergic disorders. The present study aims to evaluate the effects of WS extract on acute systemic anaphylaxis in mice.

Methods: Female BALB/c mice (20 - 25g) were divided into four groups (n = 8/group). On day 1, mice of all groups were sensitized with an intraperitoneal (i.p.) injection of 50 μg ovalbumin (OVA) an 1 mg of AL(OH)₃ in 0.5 ml saline, and on day 14, mice were challenged with 50 μg OVA in 0.5 ml saline. The mortality was checked on day 14 at 2 hr post-OVA challenge. 24 hr after the OVA challenge, all animals were anesthetized, the abdomen was cut-opened, and the mesentery was dissected from the small intestine. Fragments of mesentery were mounted on a glass slide, fixed and examined microscopically (x10) and the percentage of degranulated and intact mast cells was evaluated.

Results: After 2 hr of OVA challenge in mice, a higher mortality rate was observed in the disease control (OVA) group (75%). Pretreatment with a higher dose of WS extract (400 mg/kg) reduced mortality in mice to 37%, whereas the mortality in mice treated with a lower dose (200 mg/kg) was 50%. In addition, pre-treatment with WS extract (200 and 400 mg/kg) exerted significant percentage protection of mast cells’ degranulation in a dose-dependent manner as compared to the disease control (OVA) group. These results were comparable with those seen after dexamethasone treatment (1 mg/kg).

Conclusion: Our study results indicated that WS extract showed significant protection of mast cell degranulation, and it reduced mortality rate in mice in a dose-dependent manner in an allergic mouse model. Thus, WS could have therapeutic potential in allergic conditions such as asthma.

Keywords: Mast Cells; Anaphylaxis; Withania somnifera; Ovalbumin

1. Krystel-Whittemore M., et al. “Mast Cell: A Multi-Functional Master Cell”. Frontiers in Immunology 6 (2016): 620.
2. Eskandari N., et al. “Regulation of human skin mast cell histamine release by PDE inhibitors”. Allergologia et Immunopathologia 1 (2015): 37-41.
3. Lyons JJ and Yi T. “Mast cell tryptases in allergic inflammation and immediate hypersensitivity”. Current Opinion in Immunology 72 (2021): 94-106.
4. Balzar S., et al. “Mast cell phenotype, location, and activation in severe asthma: Data from the Severe Asthma Research Program”. American Journal of Respiratory and Critical Care Medicine 3 (2011): 299-309.
5. Mukai K., et al. “Mast cells as sources of cytokines, chemokines, and growth factors”. Immunological Reviews 1 (2018): 121-150.
6. Aware CB., et al. “Natural bioactive products as promising therapeutics: A review of natural product-based drug development”. South African Journal of Botany 151 (2022): 512-528.
7. Alzobaidi N., et al. “Bioactive Compounds and Traditional Herbal Medicine: Promising Approaches for the Treatment of Dementia”. Degenerative Neurological and Neuromuscular Disease 11 (2021): 1-14.
8. Bentaiba K., et al. “Effectiveness of Withania frutescens root extract on testicular damage induced by lead acetate in adult albino rats”. Reproductive Toxicology 115 (2023): 102-110.
9. Bui TT., et al. “Bupleurum chinense extract ameliorates an OVA-induced murine allergic asthma through the reduction of the Th2 and Th17 cytokines production by inactivation of NFκB pathway”. Biomedicine and Pharmacotherapy 91 (2017): 1085-1095.
10. Marco-Martín G., et al. “Differences in the Anaphylactic Response between C3H/HeOuJ and BALB/c Mice”. International Archives of Allergy and Immunology 4 (2017): 204-212.
11. Komi DEA., et al. “Mast Cell Biology at Molecular Level: a Comprehensive Review”. Clinical Reviews in Allergy and Immunology 3 (2020): 342-365.
12. Parmar G., et al. “Amelioration of anaphylaxis, mast cell degranulation and bronchospasm by Euphorbia hirta extracts in experimental animals”. Beni-Suef University Journal of Basic and Applied Sciences 7.1 (2018): 127-134.
13. Reber LL., et al. “The pathophysiology of anaphylaxis”. Journal of Allergy and Clinical Immunology 2 (2017): 335-348.
14. Possa SS., et al. “Eosinophilic inflammation in allergic asthma”. Frontiers in Pharmacology 4 (2013): 46.
15. Vijayalaxmi RG., et al. “Anti-Allergic Effect of Sildenafil and Tadalafil in Ovalbumin Induced Bronchial Asthma in Rats”. International Journal of Plant, Animal and Environmental Sciences 2 (2021): 342-351.
16. Agarwal R., et al. “Studies on immunomodulatory activity of Withania somnifera (Ashwagandha) extracts in experimental immune inflammation”. Journal of Ethnopharmacology 1 (1999): 27-35.
17. Girish C. “Evaluation of antianaphylactic activity of various extracts of Withania somnifera”. International Journal of Pharmaceutical Sciences and Research 4 (2017): 1717-1722.