Anti-Escherichia coli β-glucuronidase activity constituents from the root of Neolitsea konishii

Diarrhea is one of the most common side effects of chemotherapy. The Escherichia coli β-glucuronidase (eβg) in intestinal caused chemotherapy-induced diarrhea (CID) and decreased patient's chemotherapeutic efficacy. About sixty-three species of Formosan indigenous Lauraceous plants have been screened under the drug-screening platform of ebg inhibitors against CID. The methanolic extract of the root of Neolitsea konishii (Hay.) Kanehira & Sasaki can specifically inhibit the intestinal eβg-activity but not affect the human bg (hβg). Therefore, the aims of this study are the isolation of chemical constituents and evaluation of their anti-eβg activities.

N. konishii is a small evergreen tree and grows in low to medium altitudes forest in Ryukyu and Taiwan. The methanolic extract of the root of N. konishii was partitioned into ethyl acetate-soluble and water-soluble layers. Bioassay-guided fractionation of the active ethyl acetate-soluble layer of the root of N. konishii led to the isolation of two new alkanoids, konishienone A (1) and konishienone B (2), one new lignan, 9,9'-O-di-(E)-feruloyl-(-)-5,5'-dimethoxysecoisolariciresinol (3), and one new sesquiterpenoid, neolikonisin (4), along with 28 known compounds, including 17 sesquiterpenoids, one alkaloid, two amides, one steroid, five lignans, one flavonoid, and one fatty acid. The structures of these new compounds (1–4) were elucidated by 1D, 2D NMR, UV, IR, ESIMS, and HRESIMS analysis. Among the isolates, litseaculane, aesculitannin C, and daibucarboline A can specifically block intestinal eβg-activity but not affect hβg-activity. These three compounds exhibit the potential in developing anti-eβg drug in the future.