Phytochemical composition, cytotoxicity, antioxidant, and antidiabetic enzyme inhibition potential of Strychnos henningsii Gilg.

• Strychnos henningsii extracts showed high antioxidant and low cytotoxicity. • Methanolic extract inhibited α-glucosidase; alkaloid extract inhibited α-amylase. • Alkaloids were the highest phytochemical content, followed by flavonoids, phenols, and terpenes. • Five bioactive triterpenes showed low to moderate cytotoxicity and enzyme inhibition. The pervasiveness of diabetes mellitus, particularly type II diabetes, is escalating in South Africa, where complications from this condition rank as the second leading cause of natural mortality. Locally, the bark of Strychnos henningsii Gilg. has been traditionally employed to manage type II diabetes, a chronic ailment necessitating continuous attention. This study aims to assess the cytotoxic, antioxidant, and antidiabetic enzyme inhibitory potentials of S. henningsii , based on its perceived antidiabetic properties. The investigation involved HPTLC, UV–vis spectrophotometry, and LC-MS analyses to ascertain the phytochemical composition. In vitro MTT cytotoxicity, DPPH radical scavenging, ORAC, α-glucosidase and α-amylase inhibition were evaluated on the methanolic (MSHB) and total tertiary alkaloid crude extracts (TTA SHB) of S. henningsii. Furthermore, five bioactive pentacyclic triterpenes isolated from S. henningsii were evaluated for their cytotoxicity and antidiabetic enzymatic potential. The phytochemical examination showed a notable occurrence of alkaloids, then came flavonoids, phenols, and terpenes. MSHB and TTA SHB extracts exhibited minimal MTT cytotoxicity, with the lowest percentage inhibition recorded at 79.83 ± 7.66 % for MSHB at 500 µg/mL. Strong antioxidant activity was evident in both extracts, with IC 50 values less than those of ascorbic acid in DPPH radical scavenging assays. α-Glucosidase inhibition was demonstrated in the MSHB extract, while α-amylase inhibition was observed in the TTA SHB extract. The isolated pentacyclic triterpenes displayed low to moderate cytotoxicity, with IC 50 values ranging between 60.69 and 300.5 µg/mL. Moreover, all isolated triterpenes exhibited α-amylase and α-glucosidase inhibition, with alpha-amyrin acetate (SH-4) demonstrating notably higher α-glucosidase inhibition compared to the positive control, reaching 93.34 ± 0.52 % at 500 µM. The findings suggest that S. henningsii and its bioactive pentacyclic triterpenes possess promising attributes, including low cytotoxicity, potent antioxidant properties, and enzymatic inhibition, thereby potentially serving as valuable candidates for developing novel therapeutic interventions targeting type II diabetes. [ABSTRACT FROM AUTHOR]