Immunosuppressive Effects of Annona muricata L. Leaf Extract on Cellular and Humoral Immune Responses in Male Wistar Rats

Abdul Wahab SM 1 , Husain K 1 , Jantan I 2 , Arshad L 3 , Haque MA 4 , Mohd Fauzi N 1 Show all authors , Nafiah MA 5 , Das S 6

Affiliations 

  • 1 Center for Drug and Herbal Development, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, 50300, Malaysia
  • 2 Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia, UKM Bangi, 43600, Selangor, Malaysia
  • 3 Department of Pharmacy, Forman Christian College (A Chartered University), Ferozeour Road, Lahore, 54600, Pakistan
  • 4 Department of Pharmacy International Islamic University, Chittagong, Bangladesh
  • 5 Department of Chemistry, Universiti Pendidikan Sultan Idris, Tanjong Malim, Perak, 35900, Malaysia
  • 6 Department of Human and Clinical Anatomy, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, 123, Sultanate of Oman
Curr Pharm Biotechnol, 2023;24(11):1465-1477.
PMID: 36545731 DOI: 10.2174/1389201024666221221113020

Abstract

BACKGROUND: Annona muricata L. (Annonaceae) (AM)'s remarkable anti-inflammatory and anti-cancer activities make it a targeted plant to be explored for its immunomodulatory properties. Traditional practitioners have employed various components of AM to cure a variety of ailments, including cancer, diabetes, and inflammation.

OBJECTIVE: The present study evaluated the immunosuppressive effects of 80% ethanol extract of of AM leaves in male Wistar rats on different parameters of humoral and cellular immune responses.

METHODS: AM leaf extract (AMLE) was analyzed using UHPLC-MS/MS to profile its secondary metabolites. AMLE was rich in polyphenols which include (epi)catechin-(epi)catechin-(epi) catechin, caffeic acid, coumaroylquinic acid, hyperin, kaempferol, quinic acid and rutin. The rats were administered 100, 200 and 400 mg/kg bw of the extract daily for 14 days. The effects of AMLE on innate immune responses were determined by evaluating phagocytosis, neutrophils migration, reactive oxygen species (ROS) release, CD11b/CD18 integrin expression, and ceruloplasmin, lysozyme and myeloperoxidase (MPO) levels. The adaptive immune parameters were evaluated by immunizing the rats with sheep red blood cells (sRBC) on day 0 and administered orally with AMLE for 14 days.

RESULTS: AMLE established significant immunosuppressive effects on the innate immune parameters by inhibiting the neutrophil migration, ROS production, phagocytic activity and expression of CD11b/CD18 integrin in a dose-dependent pattern. AMLE also suppressed ceruloplasmin, MPO and lysozyme expressions in the rat plasma dose-dependently. AMLE dose-dependently inhibited T and B lymphocytes proliferation, Th1 and Th2 cytokine production, CD4+ and CD8+ co-expression in splenocytes, immunoglobulins (IgM and IgG) expression and the sRBC-induced swelling rate of rat paw in delayed-type hypersensitivity (DTH).

CONCLUSION: The strong inhibitory effects on the different parameters of humoral and cellular responses indicate that AMLE has potential to be an important source of effective immunosuppressive agents.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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