Phenanthrene derivatives from roots and rhizomes of Asarum heterotropoides var. mandshuricum

Abstract

Five new phenanthrene derivatives: 9-ethoxy-7-methoxy-aristololactam IV (1), norcepharadione A N-β-d-glucopyranoside (2), aristololactamoside I (3), aristololactamoside II (4) and aristothiolactoside (5) together with eleven known phenanthrene derivatives (6-16) were isolated from the ethanol extract of the roots and rhizomes of Asarum heterotropoides var. mandshuricum. The aristololactams with substitution of ethoxy at C-9 position (1, 9, and 10) and the sulfur-containing phenanthrene derivative (5) were reported in the genus Asarum for the first time. Furthermore, six phenanthrene glucoside derivatives (2-5, 13 and 14) were also found in this genus for the first time and compounds 7 and 9-15 were isolated from the genus Asarum for the first time. Six of them (1, 2, 9, 10, 13 and 14) were submitted to cytotoxicity test against human renal proximal tubular epithelial cell lines (HK-2) using MTT and LDH assays. Compounds 1 and 10 showed significant cytotoxic activity against HK-2 cell lines with IC₅₀ values of 18.18 and 20.44μmol/L in MTT assay and 84.36 and 35.06μmol/L in LDH assay, respectively. Compound 9 showed moderate cytotoxicity in MTT assay with IC₅₀ values of 95.60μmol/L, but no cytotoxicity in LDH assay. Compounds 2, 13 and 14 showed cytotoxic effect in neither MTT assay nor LDH assay. Considering the other nephrotoxic phenanthrene derivatives (6, 8, 12, 15 and 16) previously tested, the results implied the potency of renal toxicity of this herb used as a medicine.

Keywords: 9-Ethoxy-aristololactam I (PubChem CID: 195368); Aristolochic Acid IVa (PubChem CID: 161218); Aristolochic acid; Aristolochic acid I (PubChem CID: 2236); Aristololactam; Aristololactam I (PubChem CID: 96710); Aristololactam IV (PubChem CID: 5319404); Asarum heterotropoides var. mandshuricum; Cepharadione A (PubChem CID: 94577); Nephrotoxicity; Phenanthrene derivatives.