Network Pharmacology of the Phytochemical Content of Sunflower Seed (Helianthus annuus L.) Extract from LC-MS on Wound-Healing Activity and the In Vitro Wound Scratch Assay

TL;DR

Sunflower seed extract promotes wound healing by enhancing cell migration and has antioxidant properties, with chlorogenic acid being a key compound.

Contribution

This study identifies bioactive compounds in sunflower seed extract and their mechanisms in wound healing using network pharmacology and molecular docking.

Findings

Sunflower seed extract at 10 µg/mL achieved complete wound closure in 24 hours in HaCaT cells.

Chlorogenic acid showed the highest binding affinity to wound-healing targets like NF-κB1, EGFR, and MMP9.

The extract exhibited moderate-to-strong antioxidant activity and favorable pharmacokinetic properties.

Abstract

Sunflower seeds have been reported to be a healthy natural source of polyphenols. This study aimed to explore the mechanisms of potential compounds in sunflower seed extract involved in wound healing; major compounds were investigated through network pharmacology and molecular docking. In an in vitro wound-healing assay applied using an immortalised human keratinocyte (HaCaT) cell model, 10 µg/mL of the sunflower seed extract promoted cell migration in HaCaT cells and led to complete wound closure after 24 h; at a 1 µg/mL concentration, it led to complete wound closure after 72 h. The sunflower seed extract presented moderate-to-strong antioxidant activity. Liquid chromatography–mass spectrometry and high-performance liquid chromatography were used to identify the major compounds present in the sunflower seed extract. Forty-seven compounds were identified, among which chlorogenic acid was the most abundant phenolic compound. Network pharmacology was used to identify wound-healing-related targets. In total, 252 proteins were linked to the 47 compounds. Cyto-Hubba analysis identified 10 hub proteins with a strong correlation with wound healing. Molecular docking was used to assess the ability of the major compounds in the sunflower seed extract to combat NF-κB1, EGFR, and MMP9. Chlorogenic acid showed higher binding affinity to all targets. Moreover, its pharmacokinetic properties were well distributed in the plasma (VDss = 0.377 log L/kg), and they were not a carcinogen and did not cause skin sensitisation. In conclusion, the findings suggest that the sunflower seed extract is a potential source of bioactive compounds that can enhance wound healing and can be developed to create a transdermal application.

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