Competitive CatSper Activators of Progesterone from Rhynchosia volubilis

Abstract

The root Rhynchosia volubilis was widely used for contraception in folk medicine, although its molecular mechanism on antifertility has not yet been revealed. In human sperm, it was reported that the cation channel of sperm, an indispensable cation channel for the fertilization process, could be regulated by various steroid-like compounds in plants. Interestingly, these nonphysiological ligands would also disturb the activation of the cation channel of sperm induced by progesterone. Therefore, this study aimed to explore whether the compounds in R. volubilis affect the physiological regulation of the cation channel of sperm. The bioguided isolation of the whole herb of R. volubilis has resulted in the novel discovery of five new prenylated isoflavonoids, rhynchones A – E (1 – 5), a new natural product, 5′-O-methylphaseolinisoflavan (6) (1H and 13C NMR data, Supporting Information), together with twelve known compounds (7 – 18). Their structures were established by extensive spectroscopic analyses and drawing a comparison with literature data, while their absolute configurations were determined by electronic circular dichroism calculations. The experiments of intracellular Ca2+ signals and patch clamping recordings showed that rhynchone A (1) significantly reduced cation channel of sperm activation by competing with progesterone. In conclusion, our findings indicat that rhynchone A might act as a contraceptive compound by impairing the activation of the cation channel of sperm and thus prevent fertilization.

The action of physiological and synthetic steroids on the calcium channel CatSper in human sperm

“…Steroids with a hydroxyl group at the C13 or C14 position appeared to be tolerable, and the bulky aliphatic substitutions at the C17 position of the D-ring led to a dramatic decrease in agonist activity. Our results are consistent with those of previous studies that have examined the chemical structures of steroids to determine their affinity for the unknown binding site of CatSper ( Jeschke et al, 2021 ; Carlson et al, 2022a ; Carlson et al, 2022b ; Xiang et al, 2022 ). The use of the SAR information allowed us to identify and test several commercially available synthetic steroids in addition to the steroids we initially screened.…”

Flavonoids From the Aerial Parts of Sophora tonkinensis and Their Potential Anti‐Inflammatory Activities

“…The known flavonoids were identified as 6,8-diprenylkaempferol (5), [19] 8-prenylkaempferol (6), [20] 8-prenylquercetion (7), [21] isoliquiritigenin (8), [22] erythrinin B (9), [23] luteone (10), [24] 2',5',5,7tetrahydroxyisoflavone (11), [25] tectorigenin (12), [26] genistein (13), [27] 3-(4-hydroxyphenyl)-5,7-dihydroxy-8-(2-hydroxy-3methyl-3-butenyl)-4H-chromen-4-one ( 14), [28] irisolidone (15), [29] luteolin ( 16), [30] 7,4'-dihydroxyflavone (17), [30] diosmetin (18), [31] lupinifolinol (19), [32] naringenin (20), [33] and 8-prenylnaringenin (21), [34] using NMR data by comparison with literature values.…”