Next Article in Journal
Preparation and Evaluation of an Oral Administration System of Albendazole-Metal-Organic Framework Based on Dual Response to pH and Enzymes
Previous Article in Journal
Triple Non-Statin Therapy with Ezetimibe, Inclisiran, and Bempedoic Acid in Patients with Genetically Confirmed Statin-Induced Rhabdomyolysis: A Dual Case Report
Previous Article in Special Issue
Nicotinamide Mononucleotide and Nicotinamide Riboside Improve Dyslipidemia and Fatty Liver but Promote Atherosclerosis in Apolipoprotein E Knockout Mice
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Metabolites from the Dendrobium Endophyte Pseudomonas protegens CM-YJ44 Alleviate Insulin Resistance in HepG2 Cells via the IRS1/PI3K/Akt/GSK3β/GLUT4 Pathway

1
Key Laboratory of Agro-Products Quality and Safety Control in Storage and Transport Process, Ministry of Agriculture and Rural Affairs, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, No. 2, Yuanmingyuan West Road, Haidian District, Beijing 100193, China
2
National Nanfan Research Institute (Sanya), Chinese Academy of Agricultural Sciences, Sanya 572024, China
*
Authors to whom correspondence should be addressed.
Pharmaceuticals 2025, 18(6), 817; https://doi.org/10.3390/ph18060817
Submission received: 18 April 2025 / Revised: 20 May 2025 / Accepted: 24 May 2025 / Published: 29 May 2025

Abstract

Background/Objectives: Endophytes can produce bioactive metabolites similar to their host plants. CM-YJ44 (Pseudomonas protegens CHA0, 99.24% similarity), an endophyte from Dendrobium officinale, has not yet validated hypoglycemic potential. This study aimed to evaluate its anti-insulin resistance (IR) activity and metabolite profile. Methods: The fermentation broth of CM-YJ44 was separated into three fractions (CM-YJ44-1, -2, and -3) using semi-preparative high-performance liquid chromatography (pre-HPLC). An IR HepG2 cell model was constructed to evaluate their glucose uptake capacity. CM-YJ44-3 was further tested for oxidative stress, inflammatory, and insulin signaling pathway activation. Metabolites in CM-YJ44-3 were preliminarily identified using the Q Exactive Focus LC-MS system (QE), and the dendrobine content was quantified by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). Molecular docking was performed to predict the binding affinities between dendrobine and target proteins. Results: Among the three fractions, CM-YJ44-3 significantly reduced nitric oxide (NO) and reactive oxygen species (ROS) levels in IR cells, enhanced glycogen synthesis, upregulated the activities of pyruvate kinase (PK) and hexokinase (HK), and suppressed the expression of inflammatory factors. Its mechanism of action was mainly through activation of the IRS1/PI3K/Akt/GSK3β/GLUT4 signaling pathway. QE analysis preliminarily identified 24 metabolites in CM-YJ44-3. Quantitative analysis by UPLC-MS/MS showed that the dendrobine content was 78.73 ± 4.29 ng/mL. Molecular docking results indicated that dendrobine exhibited binding energies below −5 kcal/mol with multiple target proteins involved in this signaling pathway, suggesting it may be a key bioactive component responsible for the anti-IR effect. Conclusions: This study provides the first evidence of hypoglycemic bioactive metabolite production by strain CM-YJ44, indicating its potential as a novel microbial candidate for alleviating IR.
Keywords: Dendrobium endophyte; insulin resistance; PI3K/Akt Pathway; molecular docking Dendrobium endophyte; insulin resistance; PI3K/Akt Pathway; molecular docking

Share and Cite

MDPI and ACS Style

Qin, L.; Zhou, Y.; Fan, B.; Zheng, J.; Diao, R.; Liu, J.; Wang, F. Metabolites from the Dendrobium Endophyte Pseudomonas protegens CM-YJ44 Alleviate Insulin Resistance in HepG2 Cells via the IRS1/PI3K/Akt/GSK3β/GLUT4 Pathway. Pharmaceuticals 2025, 18, 817. https://doi.org/10.3390/ph18060817

AMA Style

Qin L, Zhou Y, Fan B, Zheng J, Diao R, Liu J, Wang F. Metabolites from the Dendrobium Endophyte Pseudomonas protegens CM-YJ44 Alleviate Insulin Resistance in HepG2 Cells via the IRS1/PI3K/Akt/GSK3β/GLUT4 Pathway. Pharmaceuticals. 2025; 18(6):817. https://doi.org/10.3390/ph18060817

Chicago/Turabian Style

Qin, Luqi, Yixia Zhou, Bei Fan, Jiahuan Zheng, Rao Diao, Jiameng Liu, and Fengzhong Wang. 2025. "Metabolites from the Dendrobium Endophyte Pseudomonas protegens CM-YJ44 Alleviate Insulin Resistance in HepG2 Cells via the IRS1/PI3K/Akt/GSK3β/GLUT4 Pathway" Pharmaceuticals 18, no. 6: 817. https://doi.org/10.3390/ph18060817

APA Style

Qin, L., Zhou, Y., Fan, B., Zheng, J., Diao, R., Liu, J., & Wang, F. (2025). Metabolites from the Dendrobium Endophyte Pseudomonas protegens CM-YJ44 Alleviate Insulin Resistance in HepG2 Cells via the IRS1/PI3K/Akt/GSK3β/GLUT4 Pathway. Pharmaceuticals, 18(6), 817. https://doi.org/10.3390/ph18060817

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop