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

Abstract

As the first and key step of traditional Chinese medicine (TCM)-guided drug development, lead discovery necessitates continuous exploration of new methodology for screening bioactive compounds from TCM. This work intends to establish a strategy for rapidly recognizing β 2-adrenergic receptor (β 2-AR) target compounds from the fruit of Siraitia grosvenorii (LHG). The method involved immobilization of β 2-AR onto amino-microsphere to synthesize the receptor column, the combination of the column to high-performance liquid chromatography (HPLC) to screen bioactive compounds of LHG, the identification of the compounds by HPLC coupled with mass spectrometry (MS), and the evaluation of druggability through pharmacokinetic examination by HPLC-MS/MS. Mogroside V was screened and identified as the β 2-AR-targeted bioactive compounds in LHG. This compound exhibited desired pharmacokinetic behavior including the time to reach peak plasma concentrations of 45 min, the relatively low elimination of 138.5 min, and the high bioavailability. These parameters indicated that mogroside V has a good druggability for the development of new drugs fighting β 2-AR-mediated respiratory ailments like asthma. The combination of the methods in this work is probably becoming a powerful strategy for screening and early evaluating the bioactive compounds specifically binding to G-proteincoupled receptor target from complex matrices including TCM.

A comprehensive review of Siraitia grosvenorii (Swingle) C. Jeffrey: chemical composition, pharmacology, toxicology, status of resources development, and applications

“…A study established an affinity chromatography strategy to evaluate the anti-asthmatic effects of SGEs using immobilized toxomatine 3 acetylcholine receptor (M3R). The results showed that the flavor components in SGEs that bind to this receptor are Mog V and 11-O-Mog V. The anti-asthmatic effects of these ingredients when used in concert were more significant than SGEs alone ( Jia et al, 2019 ). These findings collectively underscore the promise of Mog V and 11-O-Mog V as candidates for functional food additives.…”

Phytochemical composition and pharmacological impact of natural non-calorie sweetener- monk fruit (Siraitia grosvenorii): a review

“…While, glycosides of the 11a-hydroxy series (R4: a-OH) taste sweet, while mogrosides I, mogrosides II, glycosides of the 11b -hydroxy (R4: b -OH) are tasteless; dehydro derivatives and 11-oxo compounds (more in unripe fruit) taste bitter (Kasai et al, 1988). In addition, a novel iso-mogroside V has been identified with high potency sweetener (500 times sweeter than sucrose) and flavor enhancer (Jia and Yang, 2014).…”

“…Several studies have examined that the administration of mogrosides derived from the monk fruit exhibited inhibitory response against the inflammation. Mogroside V is the key compound involved in declining the inflammatory effects in asthma ensuring efficient drug ability properties for the preparation of new drug-combating b 2AR-mediated respiratory ailments (Jia et al, 2019). Likewise, studies have shown the shielding action of mogroside V on the ovalbumin-induced experimental asthma caused by allergy in the mice.…”

Development and evaluation of poly adenosine 5′‐diphosphate‐ribose polymerase 1 immobilization‐based receptor chromatography

“…immobilized β 2 ‐adrenoceptor ( β 2 ‐AR), an important drug target for respiratory diseases, onto macroporous silica gel by various immobilization methods [15–18]. The affinity columns were used to screen the bioactive compounds from TCMs, such as Siraitia grosvenorii [19] and Rhodiola crenulate [20]. They identified rosamaric acid, mogroside V, and salidroside as the bioactive compounds in the three herbal medicines that target β 2 ‐AR, respectively.…”