Chenopodium murale Juice Shows Anti-Fungal Efficacy in Experimental Oral Candidiasis in Immunosuppressed Rats in Relation to Its Chemical Profile

• Published in: Molecules (Basel, Switzerland) Vol. 28; no. 11; p. 4304
• Main Authors: El-Newary, Samah A, Abd Elkarim, Asmaa S, Abdelwahed, Nayera A M, Omer, Elsayed A, Elgamal, Abdelbaset M, ELsayed, Wael M
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24-05-2023; MDPI
• Subjects: anti-fungal efficacy; Antifungal activity; Bioactive compounds; Candida; Candidiasis; Cell activation; Chenopodium murale; Chenopodium murale juice (CMJ); Clinical trials; Cytotoxicity; Dexamethasone; Drugs; Flavonoids; Fungal infections; Fungi; Fungicides; Glycosides; Hydrogen peroxide; IL-17; Immune system; Immunomodulation; immunosuppressed rats; Immunosuppression; INF-γ; Interleukin 17; Interleukin 2; Kaempferol; LC-MS/MS analysis; Leukocytes; Leukocytes (neutrophilic); Lymphocytes; Lymphocytes T; Metabolites; Natural products; Neutrophils; Nystatin; Offspring; Phagocytosis; Side effects; Ulcers; γ-Interferon; anti-fungal efficacy; LC-MS/MS analysis; Chenopodium murale juice (CMJ); immunosuppressed rats; INF-γ; IL-17
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules28114304

(Syn.
) (
) is used in the rural Egypt to treat oral ulcers in newborn children. The current study aimed to discover new natural products suitable for treating candidiasis disease with minimal side effects. Characterization of bioactive compounds by LC-QTOF-HR-MS/MS from
fresh leaves' juice (CMJ) was carried out in order to elucidate their potential anti-fungal and immunomodulatory effects in oral candidiasis in immunosuppressed rats. An oral ulcer candidiasis model was created in three stages: (i) immunosuppression by drinking dexamethasone (0.5 mg/L) for two weeks; (ii)
infection (3.00 × 10
viable cell/mL) for one week; and (iii) treatment with CMJ (0.5 and 1.0 g/kg orally) or nystatin (1,000,000 U/L orally) for one week. Two doses of CMJ exhibited antifungal effects, for example, through a significant reduction in CFU/Petri (236.67 ± 37.86 and 4.33 ± 0.58 CFU/Petri), compared to the
control (5.86 × 10
± 1.21 CFU/Petri),
≤ 0.001. In addition, CMJ significantly induced neutrophil production (32.92% ± 1.29 and 35.68% ± 1.77) compared to the
control level of 26.50% ± 2.44. An immunomodulatory effect of CMJ at two doses appeared, with a considerable elevation in INF-γ (103.88 and 115.91%), IL-2 (143.50, 182.33%), and IL-17 (83.97 and 141.95% Pg/mL) compared with the
group. LC-MS/MS analysis operated in negative mode was used for tentative identification of secondary (SM) metabolites based on their retention times and fragment ions. A total of 42 phytoconstituents were tentatively identified. Finally, CMJ exhibited a potent antifungal effect. CMJ fought
through four strategies: (i) promotion of classical phagocytosis of neutrophils; (ii) activation of T cells that activate IFN-γ, IL-2, and IL-17; (iii) increasing the production of cytotoxic NO and H
O
that can kill
; and (iv) activation of SOD, which converts superoxide to antimicrobial materials. These activities could be due to its active constituents, which are documented as anti-fungal, or due to its richness in flavonoids, especially the active compounds of kaempferol glycosides and aglycone, which have been documented as antifungal. After repetition on another type of small experimental animal, their offspring, and an experimental large animal, this study may lead to clinical trials.