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Lobetyolin
Natural Products and Bioprospecting · 2025 ·Vol. 15 ·期 1 ·1-15 · IF 4.9

Lobetyolin, an anti-AD factor from the diet campanulaceae source, metabolism regulation and target exploration

Huang Wen,Liu Yihan,Jiang Haixin,Guo Dongxue,Song Yi,Wang Junqi,Li Luqi,Zhang Qiang

Bioactive compounds from food-compatible medicinal herbs have shown promise as preventive agents against age-related neurodegenerative conditions, particularly Alzheimer’s disease (AD). The present work aimed to find Lobetyolin as a new suppressor of Aβ aggregation and its interventions on abnormal metabolism in AD. Aβ-expressing Caenorhabditis elegans (strain CL4176) and wild-type worms were employed to evaluate paralysis onset, lifespan, cerebral Aβ deposition, and intracellular reactive oxygen species (ROS) after Lobetyolin administration. Untargeted ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) metabolomics coupled with RNA-seq transcriptomics was carried out to profile systemic metabolic and gene-expression changes. Differential metabolites and transcripts were subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and pathway-impact analyses; hub targets were prioritized by integrating enrichment scores with in-silico docking. Lobetyolin (12.5–50 µM) markedly protected C. elegans from Aβ-driven toxicity and oxidative stress. In CL2006 worms, β-amyloid deposits fell by 54.8 ± 9.4%, while paralysis in CL4176 was delayed by 20.9 ± 4.5%. Lifespan increased by up to 18.2% in CL4176 and 25.0% in wild-type N2 worms. Concomitantly, intracellular ROS declined maximally by 28.1 ± 8.9% (N2) and 22.4 ± 3.8% (CL4176). Integrative metabolomic–transcriptomic analyses, validated by RT-qPCR, revealed selective remodeling of glutathione metabolism: gst-38 expression was suppressed, whereas gst-1 was elevated. Lobetyolin confers neuroprotective and geroprotective benefits in vivo , primarily through reprogramming glutathione-centered redox metabolism and selectively modulating glutathione-S-transferases (GST) isoforms. These findings position Lobetyolin as a promising dietary lead compound for AD prevention and healthy aging interventions. Graphical

CAS / MDL: 77-86-1 60-24-2
研究领域: 神经科学 · 药理学 · 代谢组学 · 转录组学 · 衰老研究 · 天然产物化学
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JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES · 2026 · IF 2.4

Mechanisms involved in lobetyolin attenuation of cisplatin-induced gastrocnemius muscle atrophy in the mouse

Meng-Yi Chi,Cong-Ying Zhang,Xiao-Yan Gao,Jia Yu,Chun-Ying Bai,Dan-Dan Hao

The chemotherapeutic agent cisplatin for solid tumors frequently induces cancer-associated cachexia characterized by weight loss and decreased skeletal muscle mass. These adverse cisplatin-related symptoms are dose‑limiting, and the ability to counteract drug-initiated muscle atrophy in cancer-associated cachexia remains a pharmacological challenge. The aim of this study was to determine the protective efficacy of lobetyolin, a natural compound derived from Codonopsis pilosula, known to exert antioxidant, anti‑inflammatory, and anti‑apoptotic activities, against cisplatin-induced skeletal muscle wasting and subsequently elucidate a potential underlying molecular mechanism of action using a mouse model. Mice were injected with cisplatin (4 mg/kg, i.p. every other day, 4 doses in total) with concurrent oral lobetyolin (20 or 40 mg/kg daily) for 8 days. Lobetyolin inhibited cisplatin-induced reductions in body weight and grip strength, ameliorated gastrocnemius muscle atrophy, and preserved myofiber cross‑sectional area. Mechanistically, lobetyolin restored superoxide dismutase (SOD) activity and glutathione (GSH) levels while diminishing malondialdehyde (MDA) content in gastrocnemius muscle. Lobetyolin was found to activate the AKT signaling axis as evidenced by enhanced phosphorylation of AKT (Ser473) and FoxO3α (Thr32), which suppressed FoxO3α nuclear translocation and downregulated the E3 ubiquitin ligase Fbx32, thereby diminishing proteasomal protein degradation. Concurrently, lobetyolin normalized the Bax/Bcl‑2 ratio to inhibit myocyte apoptosis. These findings demonstrated that lobetyolin may be considered as a multi‑targeted therapeutic candidate to counteract oxidative injury, protein catabolism, and myocyte apoptosis initiated by cisplatin. Data suggest that lobetyolin’s potential as a safe adjunctive agent against chemotherapy‑induced muscle wasting might involve AKT/FoxO3α pathway.

✓ 已验证 DOI PubMed 高影响因子
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LWT-FOOD SCIENCE AND TECHNOLOGY · 2026 · IF 7.1

Probing binding sites, conformational alterations and techno-functionalities of soybean protein isolate–lobetyolin complexes

Yijia Jia,Ping Wang,Jiali Liu,Yajie Li,Kemin Shen,Hui Song,Yanli Zhai

The soybean protein isolate (SPI)–lobetyolin complexes were prepared, and the binding mechanism, structural alterations and techno-functionalities of the prepared complexes were further measured using multi-spectral technologies and molecular interaction analyses. Lobetyolin displayed strong affinity for SPI and induced static quenching of the intrinsic fluorescence. Hydrophobic contacts, hydrogen bonding, and van der Waals forces were involved in the interaction between SPI and lobetyolin. The complexes exhibited high lobetyolin binding capacity (maximum binding amount of 173 μg/mg), with decreases in free sulfhydryl and free amino group contents compared to SPI. The lobetyolin binding perturbed the microenvironment around tyrosine (Tyr) and tryptophan (Trp) residues, and thereby altered SPI secondary structure with increased β-turn content and decreased β-sheet content. The complexes (at a concentration of 400 μg/mL) exhibited DPPH•- and ABTS •+ -scavenging activities of 56.9% and 69.8%, respectively. Furthermore, the emulsifying stability index (ESI) of the complexes was improved compared to that of SPI. The use of lobetyolin enables the rational construction of food-medicinal protein-based ingredients whose techno-functional attributes can be precisely tailored. Chemical compounds investigated in this research Lobetyolin (PubChem CID: 14655097).

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JOURNAL OF ETHNOPHARMACOLOGY · 2026 · IF 6.8

Lobetyolin reinforces endothelial cytoskeletal integrity to alleviate Pseudomonas aeruginosa-induced acute lung injury via targeting ACTN1

Jinling Zhang,Zhenzhen Wang,Shangtao Wang,Yuqi Yan,Xiaoyu Wang,Man Zhang,Yuanyuan Hou,Gang Bai

Ethnopharmacological relevance Codonopsis Radix (CR), known as Dangshen in traditional Chinese medicine,is frequently used to tonify Qi and strengthen the spleen and lung. Clinically, "Lung- Qi deficiency" manifests as respiratory weakness and susceptibility to infection. The traditional action of "consolidating Qi to protect the exterior" parallels the physiological preservation of the pulmonary endothelial barrier. However, the bioactive basis linking this traditional efficacy to barrier reinforcement remains unclear. Aim of the study This study evaluates the protective effects of CR against Pseudomonas aeruginosa -induced acute lung injury (ALI), identifies the primary bioactive component responsible for barrier protection, and elucidates its molecular mechanism involving cytoskeletal stabilization. Materials and methods A P. aeruginosa -induced ALI mouse model was established to assess the efficacy of CR extract (CRE) and its polyacetylene glycoside, lobetyolin (LBT). Lung injury severity, inflammatory responses, and endothelial barrier function were systematically evaluated. Bioactivity-guided fractionation screened for active constituents. The mechanism was investigated using integrated transcriptomics, chemical proteomics, and molecular docking, validated by in vitro and in vivo experiments. Results Both CRE and LBT significantly attenuated lung histopathology, diminished pulmonary edema, and suppressed leukocyte infiltration and pro-inflammatory cytokine production. LBT was identified as the key bioactive constituent restoring endothelial barrier integrity, evidenced by upregulated expression and junctional localization of VE-Cadherin, ZO-1, and Claudin-5. Mechanistically, LBT directly targets α-actinin-1 (ACTN1). Functioning as a "molecular stabilizer", LBT enhances ACTN1-F-actin affinity, promoting cortical actin organization and stabilizing intercellular junctions under inflammatory stress. Conclusions This study identifies LBT as a novel structural consolidator of the vascular endothelial barrier. By demonstrating that LBT reinforces endothelial cytoskeletal organization via ACTN1, our findings offer a compelling modern scientific interpretation of the traditional efficacy of CR in "tonifying Lung- Qi ": physically strengthening the biological barrier. Furthermore, targeting ACTN1-mediated cytoskeleton modulation presents a promising strategy for treating ALI and vascular leakage disorders.

✓ 已验证 DOI PubMed 高影响因子
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MICROCHEMICAL JOURNAL · 2021 · IF 4.821

Simultaneous determination of lobetyolin and atractylenolide III in Codonopsis Radix by dispersive liquid-liquid microextraction based on hydrophobic deep eutectic solvent

Yun-e Bai,Xiao-ting Zhang,Rui-ming Zhang,Jing Hou,Yuan-jing Niu,Shuang Hu,Jian-ping Gao

In order to achieve the determination and quantification of trace lobetyolin and atractylenolide III in Codonopsis Radix, a procedure of dispersive liquid-liquid microextraction utilizing a hydrophobic deep eutectic solvent as the extractant combined with high performance liquid chromatography was developed. The primary variables affecting the extraction process, including the type, ratio and volume of extractant, pH and salt concentration in sample phase, type and volume of dispersant, extraction time, centrifugal speed and time were optimized. In this experiment, the deep eutectic solvent prepared by methyltrioctylammonium chloride and n -butanol was the best extractant. The both target analytes showed good linearity ( r 2  > 0.990) in their respective linear ranges (0.01–2.5 µg/mL and 0.009–2.0 µg/mL). And the limits of detection and quantification were 6 × 10 −4 and 2 × 10 −3 µg/mL for lobetyolin, 3 × 10 −3 and 9 × 10 −3 µg/mL for atractylenolide III. The enrichment factors were 37 for lobetyolin and 154 for atractylenolide III respectively. The relative standard deviations of precision were 1.2–6.4% and the spiked recovery values were in the range of 87.6–114.7% with the relative standard deviations of 1.5–4.7%. It is successful to objectively and clearly distinguish the three origins of Codonopsis Radix by comparing the contents of the both analytes with proposed method.

研究领域: 分析化学 · 生药学 · 中药学
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