Steroidal alkaloids from Pachysandra axillaris and evaluation of their cytotoxic activities against colon carcinoma in vitro

• Taking it into consideration that Pachysandra axillaris is a folk medicine. • Eleven new steroidal alkaloids were isolated from the Pachysandra axillaris . • Structures were elucidated by physicochemical properties and spectral data. • Compound 13 inhibited PI3K-AKT pathway by suppressing the protein level of SHP-2. Eleven new steroidal alkaloids ( 1–11 ), together with five known analogues ( 12–16 ) and two known steroids ( 17–18 ) were isolated from Pachysandra axillaris . The structures including absolute configurations were established based on comprehensive spectroscopic, as well as single-crystal X-ray diffraction analyses. Biological assay revealed that compounds 3 and 13 among the isolates exhibited significant inhibition against SW480 and CT26 cell lines. Further investigation indicated that compound 13 has better anticancer activity than compound 3 , in the exploration of the mechanism of compound 13 we found that compound 13 can inhibit the PI3K-Akt pathway by suppressing the protein level of SHP-2, which promotes apoptosis, autophagy, and cell cycle arrest in colorectal cancer cells, and compound 13 promotes the degradation level of SHP-2 mainly by increasing the ubiquitylation modification level of SHP-2. These results suggest that compound 13 isolated from Pachysandra axillaris extract could be a valuable source of anticancer active compounds.