State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, Yunnan, People's Republic of China; Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming, 650201, Yunnan, People's Republic of China; University of Chinese Academy of Sciences, Beijing, 100049, People's Republic of China.
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, Yunnan, People's Republic of China; Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming, 650201, Yunnan, People's Republic of China.
J Pharm Biomed Anal. 2021 May 10;198:113998. doi: 10.1016/j.jpba.2021.113998. Epub 2021 Feb 26.
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 IC values of 94.6, 136.3, and 157.3 μM, and akebonic acid could inhibit α-glucosidase and PTP1B with IC 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.
牡丹皮(毛茛科),一种主要分布在中国西南部的特有植物,由于其形态和药理学上的相似性,常被用作牡丹皮的替代品。在以前的研究中,已经证实牡丹皮具有降血糖作用,而不同部位的化学成分和降血糖作用尚未研究。本文旨在通过 LCMS 分析和对 α-葡萄糖苷酶、PTP1B、TCPTP 和 DPP4 的抑制作用,阐明牡丹皮的化学成分和降血糖活性。通过对其紫外吸收和 MS 碎片的解释,以及/或与对照品的比较,从牡丹皮的不同部位鉴定出 57 种成分,包括 15 种黄酮类、10 种单萜糖苷、8 种三萜类、7 种没食子酰葡萄糖、6 种含氮化合物、5 种没食子酸、2 种苯乙酮和 4 种其他类型的化合物。此外,根据其 MS/MS 碎片规则,推测出两种新的单萜苷元(42 和 47)和一种新的齐墩果烷三萜(51)。主成分分析(PCA)表明,根心和根皮之间的化学成分相似,而与叶和茎之间的化学成分则通过其特征成分(单萜糖苷、黄酮类和苯乙酮)得到很好的区分。四个部位(200μg/ml)对 α-葡萄糖苷酶和 PTP1B 均有明显抑制作用(81.2%-98.5%),但对 TCPTP 和 DPP4 的抑制作用为中度至弱(19.5%-34.9%)。对代表牡丹属植物五种主要类型成分的 9 种化合物进行了降血糖作用的测定,结果表明黄酮类和三萜类是四种酶的主要活性物质。木犀草素对 α-葡萄糖苷酶、PTP1B 和 TCPTP 的 IC 值分别为 94.6、136.3 和 157.3μM,阿科诺酸对 α-葡萄糖苷酶和 PTP1B 的 IC 值分别为 73.5 和 57.8μM,表现出明显的活性。木犀草素和阿科诺酸被认为是 α-葡萄糖苷酶的竞争性抑制剂,而 PTP1B 的是反竞争性和混合型抑制剂。对接研究表明,阿科诺酸通过与 PTP1B 的催化位点(B/C)结合,成为 PTP1B(优于 TCPTP)的选择性抑制剂。该 LCMS 结合酶比较为牡丹皮的化学成分和降血糖活性提供了新的认识。