Carica Papaya Linn. Leaf Extracts Induced the Proliferation of Mice’s Peritoneal Macrophages and Bone Marrow Cells, Along with Cytokine Modulation in Cell Culture

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Résumé

Purpose: Carica papaya is used alone or with other herbs in traditional medicine to treat infectious diseases; nonetheless,
comprehensive scientific validation of this claim is limited. We conducted this preliminary study to explore its immunomodulatory
potential through cytokine modulation.
Methods: An aqueous ethanolic crude extract of plant leaves was evaluated for phytochemical groups, total flavonoid, and phenolic
content using aluminum chloride and Folin-Ciocalteu’s methods. The crude extract and its derived fractions were compared with thin-
layer chromatography, and antioxidant properties were assessed using the 2,2′-diphenyl-1-picrylhydrazyl radical scavenging assay and
the Ferric Ion Reducing Antioxidant Power assay. Additionally, the effects of the extracts on cell proliferation, cytokine, and nitric
oxide release by mouse peritoneal macrophages and bone marrow multipotent cells in culture were evaluated using the
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the Enzyme-Linked Immunosorbent Assay (ELISA),
and the Griess reagent. The cells were collected from Swiss strain mice (12 mice).
Results: Carica papaya leaf crude extract contained alkaloids, tannins, flavonoids, anthraquinones, and terpenoids. The crude
extract’s total phenolic and flavonoid contents were 14.07±5.76 gallic acid equivalents and 22.58±3.05 quercetin equivalents per
gram of extract. The crude extract showed more potent antioxidant activity. Crude extract and fractions stimulated the proliferation of
peritoneal macrophages at 1–10μg/mL and bone marrow multipotent cells at 0.01–0.3μg/mL in a concentration-dependent manner.
Interleukin-6 and tumor necrosis factor-α production were significantly increased, while interleukin-1β production was inhibited in
treated peritoneal macrophages. Treated bone marrow cells increased granulocyte-macrophage colony-stimulating factor, stem cell
factor, and thrombopoietin secretion and decreased interleukin-3 production. Nitric oxide production was 10–20 times higher in bone
marrow compared to peritoneal macrophage cells.
Conclusion: Carica papaya leaf crude extract and fractions exhibit immunomodulatory effects by promoting cytokine release and
peritoneal macrophage and bone marrow cell proliferation, explaining the use of C. papaya in infectious diseases in traditional
medicine. Further exploration is needed for applications in immune-related diseases.
Plain Language Summary: Carica papaya leaf aqueous ethanolic crude extract and fractions stimulated the proliferation of mice’s
peritoneal macrophages and bone marrow multipotent cells in culture, increased cytokine and NO release, and showed antioxidant
properties. These findings support the traditional use of the plant in treating infectious diseases and suggest potential applications in
immune-related diseases.

Mots-clés

immunomodulator, antioxidant, cytokines, macrophages, bone marrow cells