Lonicerin, an anti-algE flavonoid against Pseudomonas aeruginosa virulence screened from Shuanghuanglian formula by molecule docking based strategy

Ethnopharmacological relevance: The Shuanghuanglian formula (SF) is a famous antimicrobial and Antiviral traditional Chinese medicine that is made of Lonicera japonica Thunb., Scutellaria baicalensis Georgi, and Forsythia suspensa (Thunb.) Vahl. According to the Chinese Pharmacopoeia, the SF is commonly administered in the forms of oral liquid, tablets, and injection. It has long been used to treat acute respiratory tract infections, especially lung Infection.

Aim of the study: In the LIGHT of the increasing incidence of multidrug resistance to conventional Antibiotics, the aim of this study was to screen potential anti-virulence agents against Pseudomonas aeruginosa from the extract of the SF.

Materials and methods: The SF was used for effective compounds screening via the combination of the molecule docking approach and ultra-high-performance liquid chromatography-quadrupole/time of flight mass spectrometry. Fifty-one anti-virulence-related proteins were docked, 26 identified compounds were from SF. Subsequently, the top-scoring screened compound was assessed via bioactive-related assays, including the quantification of alginate biosynthesis, anti-biofilm assays, and the A549 human lung cells Infection.

Result: A flavonoid Lonicerin was found to be bonded with the active site of the alginate secretion protein (AlgE) with the highest score in molecule docking. Furthermore, we validated that Lonicerin could significantly reduce alginate secretion (25 μg/mL) and biofilm formation (12.5 μg/mL) at a sub-MIC concentration without inhibiting the proliferation of P. aeruginosa or influencing the expression of AlgE, which suggested that Lonicerin may directly inhibit AlgE. In addition, Lonicerin was proven to inhibit the Infection of P. aeruginosa in the A549 cells.

Conclusion: This work reported on the first potential AlgE antagonist that was derived from herbal resources. Lonicerin was proven to be an effective inhibitor in-vitro of P. aeruginosa Infection.