6-Shogaol

• CAS: 555-66-8
• Catalog Number: ACM555668-2
• Category: Main Products
• Molecular Weight: 276.37
• Molecular Formula: C17H24O3
• Synonyms: 4-Decen-3-one, 1-(4-hydroxy-3-methoxyphenyl)
• IUPAC Name: (E)-1-(4-hydroxy-3-methoxyphenyl)dec-4-en-3-one
• Canonical SMILES: CCCCC/C=C/C(=O)CCC1=CC(=C(C=C1)O)OC
• InChI: InChI=1S/C17H24O3/c1-3-4-5-6-7-8-15(18)11-9-14-10-12-16(19)17(13-14)20-2/h7-8,10,12-13,19H,3-6,9,11H2,1-2H3/b8-7+
• InChI Key: OQWKEEOHDMUXEO-BQYQJAHWSA-N
• Boiling Point: 427.5±35.0 °C
• Density: 1.0448 g/ml
• Appearance: Powder
• Exact Mass: 276.17300
• Hazard Statements: Xn
• pKa: 10.01±0.20
• Supplemental Hazard Statements: H302
• Symbol: GHS07

Case Study

6-Shogaol Attenuates Cisplatin-Induced Emesis by Inhibiting the mtDNA-cGAS-STING Signaling Pathway

Kan S, et al. Journal of Ethnopharmacology, 2025, 340, 119251.

In a rat pica model, 6-shogaol effectively mitigates cisplatin-induced gastrointestinal inflammation and improves pica behavior, a key indicator of nausea. The underlying mechanism of this action involves the inhibition of the mitochondrial DNA (mtDNA)-cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway, which is activated by mtDNA damage caused by cisplatin.
The study reveals that 6-shogaol suppresses the activation of key inflammatory mediators such as NF-κB and IL-1β, while enhancing the expression of base-excision repair enzymes like OGG1 and reducing the level of the endonuclease FEN1. These actions help to repair mtDNA damage and prevent the activation of the cGAS-STING axis, which otherwise contributes to inflammatory responses in the gastrointestinal tract. Additionally, 6-shogaol reduces oxidative stress markers, such as 8-hydroxy-desoxyguanosine (8-OHdG), further supporting its role in mitigating inflammation. This study underscores 6-shogaol's potential as a therapeutic agent for chemotherapy-induced nausea and vomiting (CINV), offering a promising treatment strategy by targeting the mtDNA-cGAS-STING signaling pathway.

6-Shogaol Enhances Sorafenib Cytotoxicity Against Colorectal Cancer Cells by Modulating Cellular Accumulation and Metabolism

Mehanna M. G, et al. Pathology - Research and Practice, 2024, 262, 155520.

This study investigates the synergistic effects of 6-shogaol in enhancing the cytotoxicity of sorafenib, a multi-targeted kinase inhibitor, in colorectal cancer (CRC) cell lines (HT-29, HCT-116, CaCo-2, LS174T). The combination of 6-shogaol and sorafenib resulted in a significant reduction of the IC50 values in CRC cell lines, demonstrating its potential as a chemosensitizer. The mechanistic study revealed that 6-shogaol increased the concentrations of cleaved caspase-3 and c-PARP in HCT-116 cells, suggesting the induction of apoptosis. Moreover, 6-shogaol significantly altered the cell cycle distribution, with a reduction in the G1 phase and an increase in apoptotic cells. Notably, 6-shogaol modulated P-glycoprotein (P-gp) efflux activity, enhancing intracellular accumulation of sorafenib in CRC cells. These findings highlight the potential of 6-shogaol to improve the therapeutic efficacy of sorafenib by modifying its cellular uptake and metabolism, thus providing a promising combination strategy for CRC treatment. Further studies are needed to optimize the dosing regimen and assess the safety and efficacy of this combination in animal models.

6-Shogaol Alleviates Hepatic Steatosis Induced by High-Fat Diet via miR-3066-5p/Grem2 Pathway

Jiao W, et al. Food Chemistry, 2024, 457, 140197.

In a study using C57BL/6 J mice, oral administration of 6-shogaol for 12 weeks effectively improved liver lipid levels, liver function, and reduced oxidative damage induced by HFD. Through miRNA-mRNA transcriptome co-analysis, the study identified the miR-3066-5p/Grem2 signaling pathway as a key mechanism through which 6-shogaol exerts its protective effects. High-throughput sequencing revealed several miRNA-mRNA pairs involved in hepatic steatosis, with miR-3066-5p and Grem2 emerging as critical targets. Validation in liver tissues and AML12 cells confirmed the role of this pathway in modulating hepatic lipid metabolism. This study elucidates a novel molecular mechanism by which 6-shogaol alleviates metabolic disorders, providing new insights into its potential as a therapeutic agent for fatty liver diseases and related metabolic conditions.

6-Shogaol Attenuates Age-Related Cognitive and Motor Declines by Suppressing p75 Neurotrophin Receptor in Aged Mice

Eo H, et al. Journal of Functional Foods, 2024, 113, 106025.

In a study involving 25-month-old mice, 6-shogaol treatment (10 mg/kg for one month) significantly improved locomotion and cognitive performance, as assessed by open field and Y-maze tests. Furthermore, 6-shogaol attenuated neurodegeneration and neuroinflammation in the brain, as evidenced by reduced microgliosis and astrocytosis in the striatum and hippocampus. The compound also promoted neurogenesis in the subventricular zone, highlighting its regenerative potential. Mechanistically, 6-shogaol inhibited the expression of the p75 neurotrophin receptor (p75NTR), a key factor involved in neurodegeneration and age-related cognitive decline. These findings suggest that 6-shogaol can effectively rejuvenate the aged brain by modulating neuronal health, synaptic plasticity, and neuroinflammatory processes.