<i>Chenopodium murale</i> Juice Shows Anti-Fungal Efficacy in Experimental Oral Candidiasis in Immunosuppressed Rats in Relation to Its Chemical Profile
<i>Chenopodium murale</i> (Syn. <i>Chenopodiastrum murale</i>) (<i>amaranthaceae</i>) 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 minim...
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2023-05-01
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author | Samah A. El-Newary Asmaa S. Abd Elkarim Nayera A. M. Abdelwahed Elsayed A. Omer Abdelbaset M. Elgamal Wael M. ELsayed |
author_facet | Samah A. El-Newary Asmaa S. Abd Elkarim Nayera A. M. Abdelwahed Elsayed A. Omer Abdelbaset M. Elgamal Wael M. ELsayed |
author_sort | Samah A. El-Newary |
collection | DOAJ |
description | <i>Chenopodium murale</i> (Syn. <i>Chenopodiastrum murale</i>) (<i>amaranthaceae</i>) 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 <i>Chenopodium murale</i> 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) <i>Candida albicans</i> infection (3.00 × 10<sup>6</sup> 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 <i>Candida</i> control (5.86 × 10<sup>4</sup> ± 1.21 CFU/Petri), <i>p</i> ≤ 0.001. In addition, CMJ significantly induced neutrophil production (32.92% ± 1.29 and 35.68% ± 1.77) compared to the <i>Candida</i> 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 <i>Candida</i> 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 <i>Candida</i> 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<sub>2</sub>O<sub>2</sub> that can kill <i>Candida</i>; 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. |
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spelling | doaj.art-d2fb106c10c3449cb5b36d4871ab20e22023-11-18T08:14:46ZengMDPI AGMolecules1420-30492023-05-012811430410.3390/molecules28114304<i>Chenopodium murale</i> Juice Shows Anti-Fungal Efficacy in Experimental Oral Candidiasis in Immunosuppressed Rats in Relation to Its Chemical ProfileSamah A. El-Newary0Asmaa S. Abd Elkarim1Nayera A. M. Abdelwahed2Elsayed A. Omer3Abdelbaset M. Elgamal4Wael M. ELsayed5Medicinal and Aromatic Plants Research Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, 33 El Bohouth St., Dokki-Giza-Egypt, Giza 12622, EgyptChemistry of Tanning Materials and Leather Technology Department, National Research Centre, Giza 12622, EgyptChemistry of Natural and Microbial Products Department, Pharmaceutical Industries Institute, National Research Centre, Giza 12622, EgyptMedicinal and Aromatic Plants Research Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, 33 El Bohouth St., Dokki-Giza-Egypt, Giza 12622, EgyptDepartment of Chemistry of Microbial and Natural Products, Pharmaceutical and Drug Industries Research Division, National Research Centre, Giza 12622, EgyptChemistry of Medicinal Plants Department, Pharmaceutical and Drug Industries Research Division, National Research Centre, Giza 12622, Egypt<i>Chenopodium murale</i> (Syn. <i>Chenopodiastrum murale</i>) (<i>amaranthaceae</i>) 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 <i>Chenopodium murale</i> 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) <i>Candida albicans</i> infection (3.00 × 10<sup>6</sup> 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 <i>Candida</i> control (5.86 × 10<sup>4</sup> ± 1.21 CFU/Petri), <i>p</i> ≤ 0.001. In addition, CMJ significantly induced neutrophil production (32.92% ± 1.29 and 35.68% ± 1.77) compared to the <i>Candida</i> 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 <i>Candida</i> 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 <i>Candida</i> 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<sub>2</sub>O<sub>2</sub> that can kill <i>Candida</i>; 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.https://www.mdpi.com/1420-3049/28/11/4304<i>Chenopodium murale</i> juice (CMJ)anti-fungal efficacyimmunosuppressed ratsLC-MS/MS analysisIL-17INF-γ |
spellingShingle | Samah A. El-Newary Asmaa S. Abd Elkarim Nayera A. M. Abdelwahed Elsayed A. Omer Abdelbaset M. Elgamal Wael M. ELsayed <i>Chenopodium murale</i> Juice Shows Anti-Fungal Efficacy in Experimental Oral Candidiasis in Immunosuppressed Rats in Relation to Its Chemical Profile Molecules <i>Chenopodium murale</i> juice (CMJ) anti-fungal efficacy immunosuppressed rats LC-MS/MS analysis IL-17 INF-γ |
title | <i>Chenopodium murale</i> Juice Shows Anti-Fungal Efficacy in Experimental Oral Candidiasis in Immunosuppressed Rats in Relation to Its Chemical Profile |
title_full | <i>Chenopodium murale</i> Juice Shows Anti-Fungal Efficacy in Experimental Oral Candidiasis in Immunosuppressed Rats in Relation to Its Chemical Profile |
title_fullStr | <i>Chenopodium murale</i> Juice Shows Anti-Fungal Efficacy in Experimental Oral Candidiasis in Immunosuppressed Rats in Relation to Its Chemical Profile |
title_full_unstemmed | <i>Chenopodium murale</i> Juice Shows Anti-Fungal Efficacy in Experimental Oral Candidiasis in Immunosuppressed Rats in Relation to Its Chemical Profile |
title_short | <i>Chenopodium murale</i> Juice Shows Anti-Fungal Efficacy in Experimental Oral Candidiasis in Immunosuppressed Rats in Relation to Its Chemical Profile |
title_sort | i chenopodium murale i juice shows anti fungal efficacy in experimental oral candidiasis in immunosuppressed rats in relation to its chemical profile |
topic | <i>Chenopodium murale</i> juice (CMJ) anti-fungal efficacy immunosuppressed rats LC-MS/MS analysis IL-17 INF-γ |
url | https://www.mdpi.com/1420-3049/28/11/4304 |
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