Screening out key compounds of Glechomae Herba for antiurolithic activity and quality control based on spectrum-effect relationships coupled with UPLC-QDA

Glechomae Herba (GH) has been widely used in the treatment of urolithiasis, especially kidney stones, in China and Southeast Asia. Pharmacological studies have suggested that the antioxidant property of GH contributes to its anticalculus effect. CaSR is one of the main locations of kidney stones, and the mechanism of action of CaSR inhibitors in the treatment of kidney stones is similar to that of GH. However, until now, the antiurolithic chemical compounds in GH and their interaction with CaSR remain unknown. In our study, we revealed the interaction between the active compounds in GH and the active compounds in CaSR inhibitors by using spectrum-effect relationship analysis, pharmacodynamics, and molecular docking techniques. The results showed ten common peaks from the fingerprints of GH extracts from different regions. Pharmacological experiments showed that GH could significantly treat renal tissue lesions. Chlorogenic acid (CA), rosmarinic acid (RA), P5, luteolin, apigenin, and P9 were screened after the analysis of spectrum-effect relationships. In vitro validation experiments showed that all the screened compounds had inhibitory effects on the development of kidney stones in our model. The molecular docking results showed that the above compounds could be docked with CaSR in a natural state, and the docking score was less than 7. This work constructs a general model for the combination of UPLC-QDA and antiurolithic drugs, studies the spectrum-effect relationship of GH, and provides a new possibility for the development of new antiurolithic drugs.