Bioactive compounds of Shuang-Huang-Lian prescription and an insight into its binding mechanism by β₂-adrenoceptor chromatography coupled with site-directed molecular docking

Abstract

Owing to the promising clinical efficacy and relatively simple composition, Shuang-Huang-Lian prescription is widely prescribed for the treatment of acute upper respiratory tract infection and acute bronchitis in practice. This necessitates the understanding of the bioactive compounds of the prescription and their binding mechanism to β -adrenoceptor, which mediates the aforementioned ailments. In this work, a column containing immobilized β -adrenoceptor was prepared using a diazonium salt reaction. The bioactive compound collected from the β -adrenoceptor column was identified as chlorogenic acid by using high-performance liquid chromatography coupled with ion trap mass spectrometry. Using an injection amount dependent method, chlorogenic acid proved the binding to β -adrenoceptor through two kinds of sites. The numbers of the sites were (1.42 ± 0.03) × 10 and (9.06 ± 0.49) × 10 M. The association constants were (2.72 ± 0.01) × 10 and (2.80 ± 0.01) × 10 M , respectively. Molecular docking analysis of the interaction between chlorogenic acid and β -adrenoceptor indicated that the binding mainly occurred on Ser , Ser , and Phe of β -adrenoceptor. These results paved the way to screen bioactive compounds of other traditional medicines by receptor chromatography.

Screening Bioactive Compounds of Siraitia grosvenorii by Immobilized β2-Adrenergic Receptor Chromatography and Druggability Evaluation

“…Our group proposed a concept-guided methodology named as receptor chromatography (Li et al, 2015; Wang et al, 2017a; Zeng et al, 2018) to address the limitations of the above assays. In most cases, this method has immobilized the main target like G-protein-coupled receptor of approved drugs onto solid support to achieve column using the immobilized target as stationary phases.…”

“…by β 2 -AR chromatography. Wang et al (2017a) analyzed Shuang-Huang-Lian prescription and identified chlorogenic acid as the bioactive compound. This work utilized β 2 -AR chromatographic method for the pursuit of bioactive compounds targeting the receptor from the aqueous extract of LHG.…”

“…Biomedical chromatography (Li et al, 2015; Wang et al, 2017a; Han et al, 2018) has the property of incorporating the specificity of target–drug recognition into the separating procedure of chromatographic analysis. It is believed to be a powerful tool for analyzing complex samples regarding the purpose of screening bioactive compounds specifically binding to the immobilized target.…”

Chinese herbal medicine for acute upper respiratory tract infections and reproductive safety: A systematic review

“…Together, the reduction in neutrophil infiltration and excessive levels of inflammatory mediators alleviate pulmonary cellular injury (29). Screening of SHL in vitro revealed that chlorogenic acid is the main bioactive ingredient that specifically binds to β2-adrenoceptor (30), which participates in smooth muscle relaxation and bronchodilation.…”

Rapidly identifying bioactive compounds from Zhisou oral liquid by immobilized receptor‐based high‐performance affinity chromatography

“…Affinity chromatography (AC) [7–10] is an extension of LC that employs various biomacromolecules‐coated supports as the stationary phase. This technique combines the separation capacity of chromatography and the specificity of receptor‐ligand binding, which makes the targeted screening of potentially bioactive compounds in a reliable, fast, and high throughput manner, thus widely applicable in analyzing bioactive compounds interacting with the specific target from complex samples [11–15].…”