Antioxidant, Redox, and Immunomodulatory Effects of Hypericum perforatum in the Galleria mellonella: A 3R-Oriented Invertebrate Model

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Battal F., Kaya S., Kiraz H. A.

BIOMEDICINES, cilt.14, ss.1-20, 2026 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 14
  • Basım Tarihi: 2026
  • Doi Numarası: 10.3390/biomedicines14061297
  • Dergi Adı: BIOMEDICINES
  • Derginin Tarandığı İndeksler: Scopus, Science Citation Index Expanded (SCI-EXPANDED), BIOSIS, Directory of Open Access Journals
  • Sayfa Sayıları: ss.1-20
  • Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
  • Çanakkale Onsekiz Mart Üniversitesi Adresli: Evet

Özet

Background/Objectives: Hypericum perforatum L. (St. John’sWort) is extensively utilized

in ethnopharmacology due to its anti-inflammatory and immunomodulatory properties.

However, its effects on the interaction between innate immunity and oxidative homeostasis

remain incompletely characterized, particularly in alternative invertebrate models. This

study aimed to evaluate the effects of H. perforatum extract on oxidative homeostasis and

protein metabolism using the Galleria mellonella model, a 3R-compliant and ethically sustainable

platform for preliminary immunological and redox-related screening. Methods:

Last instar G. mellonella larvae were administered increasing concentrations of H. perforatum

extract (0.001–20 mg mL−1) by intrahemocoelic injection. After 24 h, hemolymph samples

were analyzed for total protein (TP), total hemocyte count (THC), encapsulation and

melanization responses, superoxide dismutase (SOD) activity, catalase (CAT) activity, and

malondialdehyde (MDA) levels. The phytochemical profile of the extract was additionally

evaluated using GC–MS analysis. Results: Significant group-dependent alterations were

observed in TP levels and THC values, with the HP-2 group demonstrating the highest

hemocyte counts and enhanced strong encapsulation responses. Higher extract concentrations,

particularly HP-4, were associated with increased weak encapsulation profiles,

suggesting altered cellular immune organization. Melanization responses became significantly

elevated at 24 h following treatment. In contrast, SOD activity, CAT activity, and

MDA levels did not differ significantly among groups, indicating preservation of oxidative

homeostasis under the tested conditions. Conclusions: H. perforatum extract induced

dose-dependent modulation of cellular and humoral immune responses in G. mellonella

without evidence of detectable oxidative disruption during acute exposure. These findings

support the utility of the G. mellonella model for preliminary evaluation of botanical

immunomodulators and suggest that H. perforatum may influence immunophysiological

pathways independently of overt oxidative toxicity.