Discovery of natural AMPK activator from the fruits of Xanthium sibiricum Patr.: Xanthiumine A, protoberberine alkaloid with unique C28 skeleton

  • Bioorg Chem. 2024 Jun 4:150:107527. doi: 10.1016/j.bioorg.2024.107527.
Tie Yao  1 ,  Cuicui Tan  2 ,  Yifang Rong  2 ,  Shi Jie  2 ,  Bingyang Zhang  2 ,  Jiankun Yan  3 ,  Shijie Cao  4 ,  Feng Qiu  5
Affiliations
  • 1. State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China.
  • 2. School of Chinese Materia Medica, and Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China.
  • 3. College of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang 050091, PR China.
  • 4. State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China. Electronic address: [email protected].
  • 5. State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China; School of Chinese Materia Medica, and Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China. Electronic address: [email protected].
PMID: 38876005 DOI: 10.1016/j.bioorg.2024.107527
Abstract

Two Protoberberine Alkaloids with a unique C28 skeleton, named xanthiumines A (1) and B (2), respectively, were isolated from the fruits of Xanthium sibiricum Patr. Their structures including absolute configurations were unequivocally established by the comprehensive NMR and MS spectroscopic data analysis together with gauge-independent atomic orbital (GIAO) NMR calculations, and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 are the first examples of natural protoberberine alkaloid with a phenolic acid group at C-13a. Their plausible biosynthetic pathway was proposed on the basis of the coexisting alkaloid monomer as the precursor. Furthermore, the effects and related molecular mechanism of compound 1 on hepatic lipid accumulation were also investigated in oleic acid (OA)-treated HepG2 cells.

Keywords
AMPK activator; C(28) skeleton; Lipid accumulation; Protoberberine alkaloids; Xanthium sibiricum.
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