Mechanistic Wound Healing and Antioxidant Potential of Moringa oleifera Seeds Extract Supported by Metabolic Profiling, In Silico Network Design, Molecular Docking, and In Vivo Studies

Nourhan Hisham Shady; Nada M Mostafa; Shaimaa Fayez; Islam M Abdel-Rahman; Sherif A Maher; Ahmed Zayed; Entesar Ali Saber; Manal M Khowdiary; Mahmoud A Elrehany; Mubarak A Alzubaidi; Faisal H Altemani; Ahmed M Shawky; Usama Ramadan Abdelmohsen

doi:10.3390/antiox11091743

Mechanistic Wound Healing and Antioxidant Potential of Moringa oleifera Seeds Extract Supported by Metabolic Profiling, In Silico Network Design, Molecular Docking, and In Vivo Studies

Antioxidants (Basel). 2022 Sep 1;11(9):1743. doi: 10.3390/antiox11091743.

Authors

Affiliations

¹ Department of Pharmacognosy, Faculty of Pharmacy, Deraya University, Universities Zone, New Minia City 61111, Egypt.
² Department of Pharmacognosy, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt.
³ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Deraya University, Minia 61519, Egypt.
⁴ Department of Biochemistry, Faculty of Pharmacy, Deraya University, Universities Zone, New Minia City 61111, Egypt.
⁵ Pharmacognosy Department, College of Pharmacy, Tanta University, Elguish Street (Medical Campus), Tanta 31527, Egypt.
⁶ Institute of Bioprocess Engineering, Technical University of Kaiserslautern, Gottlieb-Daimler-Straβe 49, 67663 Kaiserslautern, Germany.
⁷ Department of Histology and Cell Biology, Faculty of Medicine, Minia University, Minia 61519, Egypt, Delegated to Deraya University, Universities Zone, New Minia City 61111, Egypt.
⁸ Chemistry Department, Faculty of Applied Science, Umm Al-Qura University, Al-Lith Branch, Makkah 24211, Saudi Arabia.
⁹ Department of Biochemistry, Faculty of Medicine, Minia University, Minia 61519, Egypt.
¹⁰ Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
¹¹ Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia.
¹² Science and Technology Unit (STU), Umm Al-Qura University, Makkah 21955, Saudi Arabia.
¹³ Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.

Abstract

Moringa oleifera Lam. (Moringaceae) is an adaptable plant with promising phytoconstituents, interesting medicinal uses, and nutritional importance. Chemical profiling of M. oleifera seeds assisted by LC-HRMS (HPLC system coupled to a high resolution mass detector) led to the dereplication of 19 metabolites. Additionally, the wound healing potential of M. oleifera seed extract was investigated in male New Zealand Dutch strain albino rabbits and supported by histopathological examinations. Moreover, the molecular mechanisms were investigated via different in vitro investigations and through analyzing the relative gene and protein expression patterns. When compared to the untreated and MEBO®-treated groups, topical administration of M. oleifera extract on excision wounds resulted in a substantial increase in wound healing rate (p < 0.001), elevating TGF-β1, VEGF, Type I collagen relative expression, and reducing inflammatory markers such as IL-1β and TNF-α. In vitro antioxidant assays showed that the extract displayed strong scavenging effects to peroxides and superoxide free radicals. In silico studies using a molecular docking approach against TNF-α, TGFBR1, and IL-1β showed that some metabolites in M. oleifera seed extract can bind to the active sites of three wound-healing related proteins. Protein−protein interaction (PPI) and compound−protein interaction (CPI) networks were constructed as well. Quercetin, caffeic acid, and kaempferol showed the highest connectivity with the putative proteins. In silico drug likeness studies revealed that almost all compounds comply with both Lipinski’s and Veber’s rule. According to the previous findings, an in vitro study was carried out on the pure compounds, including quercetin, kaempferol, and caffeic acid (identified from M. oleifera) to validate the proposed approach and to verify their potential effectiveness. Their inhibitory potential was evaluated against the pro-inflammatory cytokine IL-6 and against the endopeptidase MMPs (matrix metalloproteinases) subtype I and II, with highest activity being observed for kaempferol. Hence, M. oleifera seeds could be a promising source of bioactive compounds with potential antioxidant and wound healing capabilities.

Keywords: Moringa; antioxidant activity; drug likeness; molecular docking; network screening; wound healing.

Grants and funding

The Deanship of Scientific Research at Umm Al-Qura University for supporting this work by Grant Code: (22UQU4331174DSR18).