Topical Nano Clove/Thyme Gel against Genetically Identified Clinical Skin Isolates: In Vivo Targeting Behavioral Alteration and IGF-1/pFOXO-1/PPAR γ Cues

Antimicrobial resistance is a dramatic global threat; however, the slow progress of new antibiotic development has impeded the identification of viable alternative strategies. Natural antioxidant-based antibacterial approaches may provide potent therapeutic abilities to effectively block resistance...

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Main Authors: Jilan A. Nazeam, Ghada M. Ragab, Amira A. El-Gazar, Shereen S. El-Mancy, Lina Jamil, Sahar M. Fayez
Format: Article
Language:English
Published: MDPI AG 2021-09-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/26/18/5608
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author Jilan A. Nazeam
Ghada M. Ragab
Amira A. El-Gazar
Shereen S. El-Mancy
Lina Jamil
Sahar M. Fayez
author_facet Jilan A. Nazeam
Ghada M. Ragab
Amira A. El-Gazar
Shereen S. El-Mancy
Lina Jamil
Sahar M. Fayez
author_sort Jilan A. Nazeam
collection DOAJ
description Antimicrobial resistance is a dramatic global threat; however, the slow progress of new antibiotic development has impeded the identification of viable alternative strategies. Natural antioxidant-based antibacterial approaches may provide potent therapeutic abilities to effectively block resistance microbes’ pathways. While essential oils (EOs) have been reported as antimicrobial agents, its application is still limited ascribed to its low solubility and stability characters; additionally, the related biomolecular mechanisms are not fully understood. Hence, the study aimed to develop a nano-gel natural preparation with multiple molecular mechanisms that could combat bacterial resistance in an <i>acne vulgaris</i> model. A nano-emulgel of thyme/clove EOs (NEG8) was designed, standardized, and its antimicrobial activity was screened in vitro and in vivo against genetically identified skin bacterial clinical isolates (<i>Pseudomonas stutzeri</i>, <i>Enterococcus faecium</i> and <i>Bacillus thuringiensis</i>). As per our findings, NEG8 exhibited bacteriostatic and potent biofilm inhibition activities. An in vivo model was also established using the commercially available therapeutic, adapalene in contra genetically identified microorganism. Improvement in rat behavior was reported for the first time and NEG8 abated the dermal contents/protein expression of IGF-1, TGF-β/collagen, Wnt/β-catenin, JAK2/STAT-3, NE, 5-HT, and the inflammatory markers; p(Ser536) NF-κBp65, TLR-2, and IL-6. Moreover, the level of dopamine, protective anti-inflammatory cytokine, IL-10 and PPAR-γ protein were enhanced, also the skin histological structures were improved. Thus, NEG8 could be a future potential topical clinical alternate to synthetic agents, with dual merit mechanism as bacteriostatic antibiotic action and non-antibiotic microbial pathway inhibitor.
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spelling doaj.art-ca830bf77ba441bd920a1626585a84942023-11-22T14:25:43ZengMDPI AGMolecules1420-30492021-09-012618560810.3390/molecules26185608Topical Nano Clove/Thyme Gel against Genetically Identified Clinical Skin Isolates: In Vivo Targeting Behavioral Alteration and IGF-1/pFOXO-1/PPAR γ CuesJilan A. Nazeam0Ghada M. Ragab1Amira A. El-Gazar2Shereen S. El-Mancy3Lina Jamil4Sahar M. Fayez5Pharmacognosy Department, Faculty of Pharmacy, October 6 University, Giza 12585, EgyptPharmacology and Toxicological Department, Faculty of Pharmacy, Misr University, Giza 12585, EgyptPharmacology and Toxicological Department, Faculty of Pharmacy, October 6 University, Giza 12585, EgyptPharmaceutics Department, Faculty of Pharmacy, October 6 University, Giza 12585, EgyptMicrobiology and Immunology Department, Faculty of Pharmacy, October 6 University, Giza 12585, EgyptPharmaceutics Department, Faculty of Pharmacy, October 6 University, Giza 12585, EgyptAntimicrobial resistance is a dramatic global threat; however, the slow progress of new antibiotic development has impeded the identification of viable alternative strategies. Natural antioxidant-based antibacterial approaches may provide potent therapeutic abilities to effectively block resistance microbes’ pathways. While essential oils (EOs) have been reported as antimicrobial agents, its application is still limited ascribed to its low solubility and stability characters; additionally, the related biomolecular mechanisms are not fully understood. Hence, the study aimed to develop a nano-gel natural preparation with multiple molecular mechanisms that could combat bacterial resistance in an <i>acne vulgaris</i> model. A nano-emulgel of thyme/clove EOs (NEG8) was designed, standardized, and its antimicrobial activity was screened in vitro and in vivo against genetically identified skin bacterial clinical isolates (<i>Pseudomonas stutzeri</i>, <i>Enterococcus faecium</i> and <i>Bacillus thuringiensis</i>). As per our findings, NEG8 exhibited bacteriostatic and potent biofilm inhibition activities. An in vivo model was also established using the commercially available therapeutic, adapalene in contra genetically identified microorganism. Improvement in rat behavior was reported for the first time and NEG8 abated the dermal contents/protein expression of IGF-1, TGF-β/collagen, Wnt/β-catenin, JAK2/STAT-3, NE, 5-HT, and the inflammatory markers; p(Ser536) NF-κBp65, TLR-2, and IL-6. Moreover, the level of dopamine, protective anti-inflammatory cytokine, IL-10 and PPAR-γ protein were enhanced, also the skin histological structures were improved. Thus, NEG8 could be a future potential topical clinical alternate to synthetic agents, with dual merit mechanism as bacteriostatic antibiotic action and non-antibiotic microbial pathway inhibitor.https://www.mdpi.com/1420-3049/26/18/5608antibioticclinical bacterial isolatecloveIGF-1nanogelnon-antibiotic
spellingShingle Jilan A. Nazeam
Ghada M. Ragab
Amira A. El-Gazar
Shereen S. El-Mancy
Lina Jamil
Sahar M. Fayez
Topical Nano Clove/Thyme Gel against Genetically Identified Clinical Skin Isolates: In Vivo Targeting Behavioral Alteration and IGF-1/pFOXO-1/PPAR γ Cues
Molecules
antibiotic
clinical bacterial isolate
clove
IGF-1
nanogel
non-antibiotic
title Topical Nano Clove/Thyme Gel against Genetically Identified Clinical Skin Isolates: In Vivo Targeting Behavioral Alteration and IGF-1/pFOXO-1/PPAR γ Cues
title_full Topical Nano Clove/Thyme Gel against Genetically Identified Clinical Skin Isolates: In Vivo Targeting Behavioral Alteration and IGF-1/pFOXO-1/PPAR γ Cues
title_fullStr Topical Nano Clove/Thyme Gel against Genetically Identified Clinical Skin Isolates: In Vivo Targeting Behavioral Alteration and IGF-1/pFOXO-1/PPAR γ Cues
title_full_unstemmed Topical Nano Clove/Thyme Gel against Genetically Identified Clinical Skin Isolates: In Vivo Targeting Behavioral Alteration and IGF-1/pFOXO-1/PPAR γ Cues
title_short Topical Nano Clove/Thyme Gel against Genetically Identified Clinical Skin Isolates: In Vivo Targeting Behavioral Alteration and IGF-1/pFOXO-1/PPAR γ Cues
title_sort topical nano clove thyme gel against genetically identified clinical skin isolates in vivo targeting behavioral alteration and igf 1 pfoxo 1 ppar γ cues
topic antibiotic
clinical bacterial isolate
clove
IGF-1
nanogel
non-antibiotic
url https://www.mdpi.com/1420-3049/26/18/5608
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