Identification of Picrasidine C as a Subtype-Selective PPARα Agonist.

@article{Zhao2016IdentificationOP,
  title={Identification of Picrasidine C as a Subtype-Selective PPAR$\alpha$ Agonist.},
  author={Shuai Zhao and Yuichiro Kanno and Wei Li and Tatsunori Sasaki and Xiangyu Zhang and Jian Wang and Maosheng Cheng and Kazuo Koike and Kiyomitsu Nemoto and Huicheng Li},
  journal={Journal of natural products},
  year={2016},
  volume={79 12},
  pages={
          3127-3133
        }
}
Picrasidine C (1), a dimeric β-carboline-type alkaloid isolated from the root of Picrasma quassioides, was identified to have PPARα agonistic activity by a mammalian one-hybrid assay from a compound library. Among the PPAR subtypes, 1 selectively activated PPARα in a concentration-dependent manner. Remarkably, 1 also promoted PPARα transcriptional activity by a peroxisome proliferator response element-driven luciferase reporter assay. Furthermore, 1 induced the expression of PPARα-regulated… 
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Computational investigation reveals Picrasidine C as selective PPARα lead: binding pattern, selectivity mechanism and ADME/tox profile
TLDR
The detailed information of binding pattern and affinity for Picrasidine C elucidated here will be valuable for chemical modification and for finding more potent, safe and selective PPARα agonists during structural optimization.
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P proof-of-concept in vivo efficacy in an STZ-induced vascular leakage model (rat) and preliminary pharmacokinetic assessment of a first-generation lead 4a (A91) are reported and a pipeline of candidates positioned for detailed PK/PD and pre-clinical evaluation is identified.
The potential of natural products for targeting PPARα
Anticancer effects of picrasidine I on oral squamous cell carcinoma
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Analysis of MAPK signaling pathway revealed that picrasidine I‐mediated proapoptotic activities by downregulating JNK phosphorylation is identified as a potent anticancer agent that can be used as a therapeutic intervention against oral squamous cell carcinoma.
Alkaloids from Picrasma quassioides: An overview of their NMR data, biosynthetic pathways and pharmacological effects.
Picrasidine I from Picrasma Quassioides Suppresses Osteoclastogenesis via Inhibition of RANKL Induced Signaling Pathways and Attenuation of ROS Production
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It is demonstrated that PI has antiosteoclastogenic effect by inhibiting inflammation induced activation of MAPKs, NF-κB and ROS generation followed by suppressing the gene expression of c-Fos and NFATc1 in osteoclast precursors.
The influence of alkaloids on oxidative stress and related signaling pathways.
A novel cathepsin L inhibitor prevents the progression of idiopathic pulmonary fibrosis.
β-Carboline alkaloid monomers and dimers: Occurrence, structural diversity, and biological activities.
FGFR2 regulation by picrasidine Q inhibits the cell growth and induces apoptosis in esophageal squamous cell carcinoma
TLDR
The results are the first to identify that PQ might be a chemopreventive and chemotherapeutic agent by direct targeting FGFR2 and inhibiting cell proliferation of ESCC cells.
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