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Record W4412935999 · doi:10.1021/acs.jmedchem.5c00194

Development of Hydrogen Sulfide-Donating Silybin Derivatives with a Type-2 Diabetes Mellitus-Alleviating Effect through Improving Intestinal L-Cell Functions

2025· article· en· W4412935999 on OpenAlexaff
Haonan Li, Qingyinglu Ma, Li Xu, Chao Zheng, Lang Lin, Jia Gu, Xiaofang Huang, Hangao Yang, Huarong Xu, Fanxing Xu, Huiming Hua, Maosheng Cheng, Dahong Li

Bibliographic record

VenueJournal of Medicinal Chemistry · 2025
Typearticle
Languageen
FieldMedicine
TopicSilymarin and Mushroom Poisoning
Canadian institutionsUniversity of TorontoCentre for Addiction and Mental Health
FundersLiaoning Revitalization Talents ProgramDepartment of Science and Technology of Liaoning ProvinceDepartment of Education of Liaoning ProvinceNatural Science Foundation of Liaoning Province
KeywordsChemistryHydrogen sulfideDiabetes mellitusType 2 Diabetes MellitusSulfideBiochemistryPharmacologyOrganic chemistryEndocrinologySulfur

Abstract

fetched live from OpenAlex

GLP-1 is an incretin hormone that maintains glucose homeostasis. Given the reduced plasma H 2 S levels observed in patients with type-2 diabetes mellitus (T2DM) and the stimulatory effect of H 2 S donors on GLP-1 secretion small-molecule gasotransmitter drugs based on H 2 S donors have emerged as an alternative strategy for treating T2DM via increasing GLP-1 levels. In this context, H 2 S donating silybin derivative bin-4 was discovered. By the upregulation of the PI3K/AKT/GSK-3β pathway, bin-4 facilitated Nrf2 nuclear translocation to inhibit oxidative damage and apoptosis in GLUTag cells. Additionally, activation of estrogen receptor α enabled bin-4 to enhance GLP-1 secretion by 30%. In vivo, bin-4 effectively decreased blood glucose levels by 63.1%, enhanced insulin secretion by 90.2%, and boosted GLP-1 production by 91.2%. It also exhibited acceptable toxicity profiles in T2DM mice, with potential metabolites identified and proposed. Overall, bin-4 demonstrated a potent T2DM-alleviating effect, providing the theoretical foundation for the design of candidate gasotransmitter-based drugs.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.060
Threshold uncertainty score0.679

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.010
GPT teacher head0.259
Teacher spread0.249 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2025
Admission routes1
Has abstractyes

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