Bioguided isolation of anti-inflammatory and anti-urolithiatic active compounds from the decoction of Cissus gongylodes leaves

• Published in: Journal of ethnopharmacology 2025-01, Vol.337 (Pt 3), p.118950, Article 118950
• Main Authors: Salem, Paula P.O., Silva, Daniele O., Silva, Paulo R.S., Costa, Lara P.D.M., Nicácio, Karen J., Murgu, Michael, Caldas, Ivo S., Leite, Fernanda B., Paula, Ana C.C. de, Dias, Danielle F., Soares, Marisi G., Chagas-Paula, Daniela A.
• Format: Article
• Language: English
• Subjects: anti-inflammatory activity; blood; Brazil; calcium ionophores; calcium oxalate; Cissus; diet; Flavonoids; glycosylation; humans; indigenous peoples; inflammation; leaves; Medicinal plant; metabolomics; NMR; renal calculi; rutin; traditional medicine; urine
• ISSN: 0378-8741; 1872-7573; 1872-7573
• DOI: 10.1016/j.jep.2024.118950

The Cissus gongylodes has traditionally been used in the diet of indigenous people in Brazil and in traditional medicine for kidney stone removal and inflammatory diseases. The active compounds responsible for these pharmacological activities are unknown. This study aims to isolate, for the first time, the compounds in the decoction of C. gongylodes leaves responsible for their anti-inflammatory and anti-urolithiatic ethnopharmacological properties. The most active fractions of the C. gongylodes leaf decoction were fractionated using SPE-C18 and the compounds were purified through HPLC-UV-DAD. The decoction fractions and isolated compounds were evaluated for their anti-inflammatory and anti-urolithiatic activities. The anti-inflammatory activity was assessed using an ex vivo assay in human blood induced by LPS and calcium ionophore, measuring inflammatory mediators, PGE2 and LTB4. The anti-urolithiatic activity was evaluated using an in vitro experimental model with human urine to determine the dissolution of the most recurrent calcium oxalate (CaOx) crystals. Additionally, the decoction was chemically characterized through metabolomic analysis using UHPLC-ESI-HRMS. The isolated compounds from the decoction of C. gongylodes, including rutin, eriodictyol 3′-O-glycoside, and isoquercetin, have demonstrated significant multi-target actions. These components act as anti-inflammatory agents by inhibiting the release of main inflammatory mediators, PGE2 and LTB4. Additionally, they exhibit anti-urolithiatic properties, promoting the dissolution of calcium oxalate (CaOx) crystals. Furthermore, the characterization of the decoction by UHPLC-ESI-HRMS revealed a high content of flavonoids, mainly glycosylated flavonoids. The results support the traditional use of C. gongylodes decoction, identifying the compounds responsible for its anti-inflammatory and anti-urolithiatic effects. The decoction fractions and isolated compounds exhibited dual anti-inflammatory activity, effectively inhibiting key inflammatory pathways and potentially presenting fewer adverse effects while also promoting the dissolution of CaOx crystals associated with urolithiasis. The multi-target action displayed by C. gongylodes is particularly desirable in the treatment of urolithiasis, as inflammation and PGE2 production precede and contribute to the formation of CaOx crystals in the kidneys. Based on these actions, C. gongylodes emerges as a potent source of active compounds for the development