Evidence map›Paper›PMID 42579630›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

Molecular Editing Reveals a Bilobalide Chemotype that Attenuates Prolyl Endopeptidase (PREP)-Linked Neuroinflammation.

Chanin Sillapachaiyaporn, Wenjing Wang, Yao Qin, Lili Yan, Stephan Scheeff, Xu He, Qiong Wu, Yue Lin, Jinsai Shang, Xin Ye and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors.

Chanin SillapachaiyapornGuangdong-Hong Kong-Macao Joint Laboratory for New Drug Screening, School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.ORCID https://orcid.org/0000-0003-1868-4079
Wenjing WangGuangdong-Hong Kong-Macao Joint Laboratory for New Drug Screening, School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
Yao QinGuangdong-Hong Kong-Macao Joint Laboratory for New Drug Screening, School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
Lili YanGuangdong-Hong Kong-Macao Joint Laboratory for New Drug Screening, School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
Stephan ScheeffGuangdong-Hong Kong-Macao Joint Laboratory for New Drug Screening, School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
Xu HeGuangdong-Hong Kong-Macao Joint Laboratory for New Drug Screening, School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
Qiong WuSchool of Basic Medical Sciences, Guangzhou National Laboratory, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, China.
Yue LinSchool of Basic Medical Sciences, Guangzhou National Laboratory, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, China.
Jinsai ShangSchool of Basic Medical Sciences, Guangzhou National Laboratory, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, China.
Xin YeCipher Gene Ltd, Chengdu, China.
Jing LiuCipher Gene Ltd, Chengdu, China.
Kailei SunCenter for Protein Science and Crystallography, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China.
Chun Wai YeungCenter for Protein Science and Crystallography, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China.
Junzhe HuangLi Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
Zhenghui ChenState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Xiaodong LiuLi Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
Yiqun GengState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Shannon Wing Ngor AuCenter for Protein Science and Crystallography, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China.
Bonaventure Y IpLi Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
Ho KoLi Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
Billy Wai-Lung NgGuangdong-Hong Kong-Macao Joint Laboratory for New Drug Screening, School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.ORCID https://orcid.org/0000-0003-2892-6318

Funding

CUHK FIA2020/A/03Gerald Choa Neuroscience InstituteGuangdong Natural Science Foundation 2021QN020451Guangzhou National Laboratory GZNL2023A02012Healthy Longevity Catalyst Awards HLCA/P-407/22National Natural Science Foundation of China 22304036National Natural Science Foundation of China 82170473Peter Hung Pain Research Institute 8423006Peter Hung Pain Research Institute 8423018SSFCRS 3136020
6 · The paper itself

Abstract

Natural products offer privileged three-dimensional chemotypes for drug discovery, yet scaffold lability and limited analogue space often impede mechanism-guided optimization. Herein, we show that molecular editing can reveal a natural product-derived chemotype that attenuates neuroinflammation via prolyl endopeptidase (PREP) inhibition. BB10, a chemically stabilized bilobalide analogue generated via lactone-to-lactam molecular editing, significantly suppressed LPS-induced microglial activation and reduced levels of key inflammatory mediators. Unbiased cellular target identification (CETSA-MS) identified PREP as the top thermally stabilized target, supporting cellular target engagement. BB10 inhibited PREP activity in both cellular and recombinant enzyme assays, implicating PREP inhibition as a mechanism contributing to its anti-neuroinflammatory activity. Guided by this target-based insight, structural optimization afforded a fluorinated analogue, BB56, with improved PREP inhibition and superior anti-inflammatory efficacy. Mechanistically, BB56 attenuated p38/NF-κB signaling and reduced NLRP3 upregulation, and PREP knockdown abrogated the anti-inflammatory effects. Finally, BB56 provided functional rescue in a zebrafish model of neuroinflammation. Collectively, this work establishes a molecular editing-enabled approach to a natural product chemotype that modulates neuroinflammation through PREP inhibition.

Indexed as

bilobalidenatural product modificationneuroinflammationPREPprolyl endopeptidasetarget identification

Identifiers

PMID42579630
PMCPMC13460414

What Socratic holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.