Chemical profiling and antidiabetic potency of Paeonia delavayi: Comparison between different parts and constituents

Paeonia delavayi (Paeoniaceae), an endemic plant mainly distributed in southwest China, is always used as the substitute of P. suffruticosa due to their morphological and pharmacological similarity. In the previous study, P. suffruticosa was revealed with antidiabetic potency, whereas the chemical difference and antidiabetic property between different parts of P. delavayi has not yet been studied. This paper was designed to clarify the chemical constituents and antidiabetic potency of P. delavayi by LCMS analysis and enzyme inhibition on α-glucosidase, PTP1B, TCPTP, and DPP4. By interpretation of their UV absorptions and MS fragmentations, and/or comparison with reference samples, 57 constituents comprising 15 flavonoids, 10 monoterpene glycosides, eight triterpenoids, seven galloyl glucoses, six N-containing compounds, five gallic acids, two acetophenones, and four other types of compounds were identified from the different parts of P. delavayi. Moreover, two new monoterpene aglycones (42 and 47) and one new noroleanane triterpenoid (51) were speculated by their MS/MS fragmentation rules. Principal component analysis (PCA) suggested the chemical resemblance between root core and root bark which could be well differentiated with the leaves and stems by their characteristic constituents (monoterpene glycosides, flavonoids, and acetophenones). All the four parts (200 μg/mL) showed obvious inhibition on α-glucosidase and PTP1B (81.2%-98.5%), but moderate to weak inhibition on TCPTP and DPP4 (19.5%-34.9%). Nine compounds representing five main types of constituents in Paeonia plants were assayed for their antidiabetic effects, indicating flavonoids and triterpenoids were the main active substances regarding to the four enzymes. Luteolin displayed obvious activity on α-glucosidase, PTP1B, and TCPTP with IC₅₀ values of 94.6, 136.3, and 157.3 μM, and akebonic acid could inhibit α-glucosidase and PTP1B with IC₅₀ values of 73.5 and 57.8 μM. Luteolin and akebonic acid were recognized as competitive inhibitors of α-glucosidase, but anticompetitive and mix-type inhibitors of PTP1B, respectively. Docking study demonstrated akebonic acid as PTP1B (over TCPTP) selective inhibitor by bonding to the catalytic sites (B/C) of PTP1B. This LCMS combined with enzymatic comparison opens new sights for recognizing the chemical profiles and antidiabetic potency of P. delavayi.