New enantiomeric lignans and new meroterpenoids with nitric oxide release inhibitory activity from Piper puberulum

• Published in: Bioorganic chemistry 2022-02, Vol.119, p.105522-105522, Article 105522
• Main Authors: Zheng, Yuan-kun, Wang, Ya-qi, Su, Bao-jun, Wang, Heng-shan, Liao, Hai-bing, Liang, Dong
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - isolation & purification; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-neuroinflammatory; Cell Line; Crystallography, X-Ray; Cytokines - antagonists & inhibitors; Cytokines - metabolism; Dose-Response Relationship, Drug; Lignan; Lignans - chemistry; Lignans - isolation & purification; Lignans - pharmacology; Meroterpenoid; Mice; Models, Molecular; Molecular Structure; Nitric Oxide - antagonists & inhibitors; Nitric Oxide - metabolism; Piper - chemistry; Piper puberulum; Plant Extracts - chemistry; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; RNA, Messenger - antagonists & inhibitors; RNA, Messenger - metabolism; Stereoisomerism; Structure-Activity Relationship; Terpenes - chemistry; Terpenes - isolation & purification; Terpenes - pharmacology
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2021.105522

[Display omitted] •30 compounds were isolated from the stems and leaves of Piper puberulum and 15 compounds showed potent No release inhibitory activity compared to positive control minocycline.•The new lignans come from the polymerization of two molecules of hydroxychavicol with chemical diversity.•Both the absolute configurations of enantiomers lignans 1a, 1b and 2a, 2b were determined by single-crystal X-ray diffraction analysis, comparing their calculated and experimental ECD spectra respectively.•Compound 1a significantly decreased the mRNA levels of inducible nitric oxide synthase (iNOS) than 1b, and 1a inhibited LPS-induced pro-inflammatory factors (IL-1β、IL-6、TNF-α) mRNA expression in BV-2 microglial cells. Six new lignans with various type of linkage between two C6-C3 fragments (1a, 1b, 2a, 2b, 3, 4), two new meroterpenoids (5, 6) and 24 known compounds (7–30) were isolated from an EtOH extract of the stems and leaves of Piper puberulum. The absolute configurations of enantiomers 1a and 1b were determined by single-crystal X-ray diffraction analysis, 2a and 2b were determined by comparing their calculated and experimental ECD spectra. Biogenetically, all the new lignans may come from the polymerization of two molecules of hydroxychavicol (30). In the anti-neuroinflammation activity assay, the IC50 values of fifteen compounds were lower than those of the positive control minocycline, and compound 1a showed good activity, but its enantiomer 1b showed no activity. Compound 1a have notable anti-neuroinflammatory activity, and can significantly decrease mRNA levels of proinflammatory cytokines (IL-1β, IL-6, TNF-α) in a dose-dependent manner.