Pectin Nanoparticle-Loaded Soft Coral Nephthea sp. Extract as In Situ Gel Enhances Chronic Wound Healing: In Vitro, In Vivo, and In Silico Studies

Abstract

This study shed light for the first time on the in vivo diabetic wound healing potential activity of natural marine soft coral polymeric nanoparticle in situ gel using an excision wound model. A Nephthea sp. methanol–methylene chloride extract loaded with pectin nanoparticles (LPNs) was created. For the preparation of in situ gel, ion-gelation techniques, the entrapment efficiency, the particle size, the polydispersity index, the zeta potential, the in-vitro drug release, and a transmission electron microscope were used and the best formula was selected. Using (UPLC-Q/TOF-MS), 27 secondary metabolites responsible for extract biological activity were identified. Isolation and identification of arachidic acid, oleic acid, nervonic acid, and bis-(2-ethylhexyl)-phthalate (DEHP) of Nephthea sp. was firstly reported here using NMR and mass spectral analyses. Moreover, LPN in situ gel has the best effects on regulating the proinflammatory cytokines (NF-κB, TNF-α, IL-6, and IL-1β) that were detected on days 7 and 15. The results were confirmed with an in vitro enzymatic inhibitory effect of the extract against glycogen synthase kinase (GSK-3) and matrix metalloproteinase-1 (MMP-1), with IC50 values of 0.178 ± 0.009 and 0.258 ± 0.011 µg/mL, respectively. The molecular docking study showed a free binding energy of −9.6 kcal/mol for chabrolosteroid E, with the highest binding affinity for the enzyme (GSK-3), while isogosterone B had −7.8 kcal/mol for the enzyme (MMP-1). A pharmacokinetics study for chabrolohydroxybenzoquinone F and isogosterone B was performed, and it predicted the mode of action of wound healing activity.

Approaches to Control and Monitor Protease Levels in Chronic Wounds

“…[194] Hassan et al aimed to develop a formulation based on the extract of a soft coral, Nephthea sp., for the treatment of chronic wounds; they assessed the inhibitory effect of the extract on MMP-1 and reported an IC 50 value of 0.26 μg mL −1 . [196] Chin et al assessed the influence of doxycycline and tetracycline on the proteolytic activity of exudates obtained from chronic wounds by using azocollagen (azocoll) as the substrate. [94] They found that both of them dose-dependently reduced the proteolytic activity, which was ≈90% and 60% for doxycycline and tetracycline, respectively, at a 5 mM concentration.…”

Genus Litophyton: A Hidden Treasure Trove of Structurally Unique and Diversely Bioactive Secondary Metabolites

“…The alcyonarian Litophyton viridis was observed to provide chemical protection for the fish Abudefduf leucogaster [18]. In addition to the ecological role, the extracts of several soft corals of the genus Litophyton have been biologically screened and showed a variety of potent bioactivities, such as antioxidant [19], genotoxic [20], cytotoxic [19,21,22], HIV-1 enzyme inhibitory [21], antibacterial [22], anti-inflammatory [23], antifungal [24], and wound healing [25] activities. Chemical investigations on Litophyton soft corals were carried out by researchers worldwide and revealed that soft corals of the genus Litophyton are prolific producers of bioactive secondary metabolites.…”