Triterpenoid saponins from the roots of Panax notoginseng with protective effects against APAP-induced liver injury.

Five previously undescribed protopanaxatriol-type saponins, notoginsenosides Ta-Te (1-5), together with eighteen known triterpenoid saponins (6-23) were isolated from the roots of Panax notoginseng. The structures of new compounds were determined by HRESIMS and NMR spectroscopic analyses and chemical methods. Compounds 1 and 2 were the first examples of ginsenosides featuring a 6-deoxy-ß-d-glucose moiety from Panax species. Compounds 1-4, 7, 10, 12, 21-22 showed protective effects on L02 cells against the injury of acetaminophen (APAP). Among them, notoginsenoside R1 (12), ginsenoside Rg1 (21), and ginsenoside Re (22) were the most potent ones, with cell viabilities >80%. Moreover, compounds 12 and 22 remarkably alleviated APAP-induced liver injury in mice. These saponins are potential hepatoprotective agents.

A four-step biosynthetic pathway involving C-3 oxidation-reduction reactions from cycloastragenol to astragaloside IV in Astragalus membranaceus.

Astragaloside IV is a significant chemical component derived from the medicinal plant Astragalus membranaceus. Despite the characterization of several glycosyltransferases from A. membranaceus, the complete biosynthetic pathway of astragaloside IV has not been fully elucidated. In this study, we propose a biosynthetic pathway for astragaloside IV that involves a sequence of oxidation-reduction reactions. The biosynthesis pathway from cycloastragenol to astragaloside IV encompasses four key steps: C-3 oxidation, 6-O-glucosylation, C-3 reduction, and 3-O-xylosylation. We identified a hydroxysteroid dehydrogenase AmHSD1 from A. membranaceus. AmHSD1 catalyzes the C-3 oxidation of cycloastragenol, yielding cycloastragenol-3-one, and the C-3 reduction of cycloastragenol-3-one-6-O-glucoside, resulting in cycloastragenol-6-O-glucoside. Additionally, the glycosyltransferases AmGT8 and AmGT1, previously reported by our groups, were identified as catalyzing the 6-O-glucosylation and 3-O-xylosylation steps, respectively. Astragaloside IV was successfully synthesized in transient expression in Nicotiana benthamiana using the combination of AmHSD1, AmGT8 and AmGT1. These results support the proposed four-step biosynthetic pathway and suggest that AmHSD1 probably plays a crucial role in the biosynthesis of astragaloside IV within A. membranaceus.

Characterization of prenylated phenolics in Glycyrrhiza uralensis by offline two-dimensional liquid chromatography/mass spectrometry coupled with mass defect filter.

Prenylated phenolics are an important class of natural products. In this study, an efficient strategy was established to systematically characterize the prenylated phenolics in Glycyrrhiza uralensis, a popular herbal medicine. Firstly, offline two-dimensional liquid chromatography/mass spectrometry (2DLC/MS) coupled with mass defect filter (MDF) technology was used to preliminarily detect 1631 potential prenylated phenolics. Secondly, the tandem mass spectrometry fragmentation features of different types of prenylated phenolics were investigated using 29 reference standards. Diagnostic fragmentations included neutral loss (NL) of 42 Da for the annular type and NL of 56 Da for the catenulate type in the positive ion mode, and NL of 56 Da for A-ring prenyl groups and NL of 69 Da for B-ring prenyl groups in the negative ion mode. As a result, the prenylation types, substitution sites, and adjacent OH and OCH3 substitutions of 320 prenylated phenolics in G. uralensis were rapidly characterized. Moreover, three prenylated dihydrostilbenes were purified from the aerial part of G. uralensis to verify the structural characterizations.

Comparative bioactivity evaluation and chemical profiling of different parts of the medicinal plant Glycyrrhiza uralensis.

Glycyrrhiza uralensis is a popular medicinal plant worldwide. Its roots and rhizomes are used as the traditional Chinese medicine Gan-Cao. However, little is known on medicinal potential and chemistry of the other parts of the plant. In this work, the biological activities and chemical components of the roots, stems, leaves, and seeds of G. uralensis were investigated comparatively. The four parts exhibited different but noticeable biological activities. The chemicals in the four parts were globally characterized by liquid chromatography coupled with mass spectrometry (LC/MS) on a Thermo Vanquish UHPLC system connected to a Q-Exactive quadrupole Orbitrap mass spectrometer. By integrating molecular networking, compound spectral matching, MS2LDA-based substructure recognition, and reference standards comparison, a total of 1301 compounds were rapidly characterized. Three flavonoid C-glycosides were purified and their structures were identified by NMR spectroscopic analysis. Orthogonal partial least squares-discriminate analysis (OPLS-DA) further revealed 196 differential chemicals for the four parts. This work will promote the medicinal resource utilization of G. uralensis.

Chemical Variations among Shengmaisan-Based TCM Patent Drugs by Ultra-High Performance Liquid Chromatography Coupled with Hybrid Quadrupole Orbitrap Mass Spectrometry.

Shengmaisan (SMS) is a famous traditional Chinese medicine (TCM) formula to treat coronary heart diseases. It has been developed into several TCM patent drugs to meet the demands of different patients. In this study, a research strategy was proposed to reveal the chemical variations among four SMS-based patent drugs, including Shengmai Oral Solution (Shengmaiyin, SMY), Shengmai Capsule (Shengmai Jiaonang, SMJN), Yiqi Fumai Injection (YQFMI), and Yiqi Fumai Capsule (Yiqi Fumai Jiaonang, YQJN). Firstly, 227 compounds were tentatively identified using an Orbitrap-MS in the full scan/dd-MS2 mode. Secondly, untargeted metabolomics analysis suggested that ginsenosides, steroidal saponins, and lignans were the main types of differential compounds for the four patent drugs. Finally, the contents of 25 compounds were simultaneously determined in 30 batches of samples in the parallel reaction monitoring (PRM) mode. Partial least squares discriminant analysis (PLS-DA) revealed the contents of ginsenosides Re, Rg1, Rb1, Ro, and Rg3, and schisandrin showed the highest intergroup variations. These compounds were chemical markers to differentiate the SMS-based patent drugs.

Discovery of Polyoxypregnane Derivatives From Aspidopterys obcordata With Their Potential Antitumor Activity.

The bioassay-guided phytochemical study of an ethnic medicinal plant Aspidopterys obcorda ta Hemsl. var. obcordata results in the isolation of eight new polyoxypregnane derivatives, named aspidatasides A-H (1-8), along with ten known analogs (9-18). The series polyoxypregnane derivatives were screened for their cytoxic activity against HL-60 cells, and compound 2 showed the highest potency with an IC50 8.03 µM. Preliminary structure-activity relationship studies displayed that the sugar chain and double bond could notably impact their biological activity.

Two new polyoxy steroidal glycosides from the roots of Dregea sinensis Hemsl.

Two new polyoxy steroidal glycosides, named as 11- O-α-acetyl-12-O-ß-tigloyl- 3ß,14ß-dihydroxy-pregn-5-en-20-one-3-O-ß-D-oleadropyranosyl-(1→4)-ß-D-6-deoxy-3-O-methyl-allopyanoside (1) and 11- O-α-acetyl -12-O-ß-benzoate-3ß, 14ß-dihydroxy-pregn-5-en- 20-one-3-O-ß-D-oleadropyranosyl-(1→4)-ß-D-6-deoxy-3-O-methyl-allopyanoside (2) were isolated from the roots of Dregea sinensis Hemsl. Their structures were elucidated by various spectroscopic techniques including UV, IR, HRESIMS, 1 D and 2 D NMR. All the two compounds were tested for their cytotoxic activity in vitro, and the result showed that compounds 1-2 displayed moderated cytotoxic activity against HL-60 cell line with IC50 values of 18.4 µM and 23.9 µM, respectively. [Formula: see text].