Effects of ginger constituent 6-shogaol on gastroesophageal vagal afferent C-fibers
Open accessAbstract
Background: Ginger has been used as an herbal medicine worldwide to relieve nausea/vomiting and gastrointestinal discomfort, but the cellular and molecular mechanisms of its neuronal action remain unclear. The present study aimed to determine the effects of ginger constituent 6‐shogaol on gastroesophageal vagal nodose C‐fibers. Methods: Extracellular single‐unit recording and two‐photon nodose neuron imaging were performed, respectively, in ex vivo gastroesophageal‐vagal preparations from wild type and Pirt‐GCaMP6 transgenic mice. The action potential discharge or calcium influx evoked by mechanical distension and chemical perfusions applied to the gastroesophageal vagal afferent nerve endings were recorded, respectively, at their intact neuronal cell soma in vagal nodose ganglia. The effects of 6‐shogaol on nodose C‐fiber neurons were then compared and determined. Key Results: Gastroesophageal application of 6‐shogaol‐elicited intensive calcium influxes in nodose neurons and evoked robust action potential discharges in most studied nodose C‐fibers. Such activation effects were followed by a desensitized response to the second application of 6‐shogaol. However, action potential discharges evoked by esophageal mechanical distension, after 6‐shogaol perfusion, did not significantly change. Pretreatment with TRPA1 selective blocker HC‐030031 inhibited 6‐shogaol‐induced action potential discharges in gastric and esophageal nodose C‐fiber neurons, suggesting that TRPA1 played a role in mediating 6‐shogaol‐induced activation response. Conclusion and Inferences: This study provides evidence that ginger constituent 6‐shogaol directly activates vagal afferent C‐fiber peripheral gastrointestinal endings. This activation leads to desensitization to subsequent application of 6‐shogaol but not subsequent esophageal mechanical distension. Further investigation is required to establish a possible contribution in its anti‐emetic effects.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
A meta-analysis of 13 randomized controlled trials (n = 1174) found that ginger significantly improves overall pregnancy-associated nausea and vomiting.
“A meta-analysis of 13 randomized control trials (n = 1174) found that ginger significantly improves overall pregnancy-associated nausea and vomiting, comparable to vitamin B6 [230] and as effective as standard antiemetics like dimenhydrinate [231].”
From Nutritional Approaches to Enhance GLP-1 Analogue Therapy in Obesity: A Narrative Review (2025) · cites this paper as [230]
Ginger is comparable to vitamin B6 for pregnancy-associated nausea and vomiting.
“A meta-analysis of 13 randomized control trials (n = 1174) found that ginger significantly improves overall pregnancy-associated nausea and vomiting, comparable to vitamin B6 [230] and as effective as standard antiemetics like dimenhydrinate [231].”
From Nutritional Approaches to Enhance GLP-1 Analogue Therapy in Obesity: A Narrative Review (2025) · cites this paper as [230]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Noxious Cold Ion Channel TRPA1 Is Activated by Pungent Compounds and Bradykinin
Bandell, M., Story, G. M., Hwang, S. W., Viswanath, V., Eid, S. R., Petrus, M. J., Earley, T. J., & Patapoutian, A. (2004) · Neuron · doi:10.1016/s0896-6273(04)00150-3 · Cited by 1,822 · see citing works
Julius, D. J. (2013) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-101011-155833 · Cited by 1,152 · see citing works
Gingerols and shogaols: Important nutraceutical principles from ginger
Semwal, R. B., Semwal, D. K., Combrinck, S., & Viljoen, A. M. (2015) · Phytochemistry · doi:10.1016/j.phytochem.2015.07.012 · Cited by 615 · see citing works
Efficacy of ginger for nausea and vomiting: a systematic review of randomized clinical trials
Ernst, E., & Pittler, M. H. (2000) · British Journal of Anaesthesia · doi:10.1093/oxfordjournals.bja.a013442 · Cited by 462 · see citing works
Coupled Activation of Primary Sensory Neurons Contributes to Chronic Pain
Kim, Y. S., Anderson, M. C., Park, K., Zheng, Q., Agarwal, A., Gong, C., Saijilafu, Young, L. M., He, S., LaVinka, P. C., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.07.044 · Cited by 287 · see citing works
Self-citationPirt, a Phosphoinositide-Binding Protein, Functions as a Regulatory Subunit of TRPV1
Kim, A. Y., Tang, Z., Liu, Q., Patel, K., Maag, D., Geng, Y., & Dong, X. (2008) · Cell · doi:10.1016/j.cell.2008.02.053 · Cited by 218 · see citing works
Self-citationGingerols: a novel class of vanilloid receptor (VR1) agonists
Dedov, V. N., Tran, V. H., Duke, C. C., Connor, M. A., Christie, M. J., Mandadi, S., & Roufogalis, B. D. (2002) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0704925 · Cited by 218 · see citing works
The role of vagal neurocircuits in the regulation of nausea and vomiting
Babic, T., & Browning, K. N. (2014) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2013.08.047 · Cited by 216 · see citing works
TRPA1 channels: molecular sentinels of cellular stress and tissue damage
Viana, F. (2016) · The Journal of Physiology · doi:10.1113/jp270935 · Cited by 210 · see citing works
Veldhuis, N. A., Poole, D. P., Grace, M. S., McIntyre, P., & Bunnett, N. W. (2014) · Pharmacological Reviews · doi:10.1124/pr.114.009555 · Cited by 172 · see citing works
Riera, C. E., Menozzi-Smarrito, C., Affolter, M., Michlig, S., Munari, C., Robert, F., Vogel, H., Simon, S. A., & le Coutre, J. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00307.x · Cited by 166 · see citing works
Vagal afferent nerves with nociceptive properties in guinea‐pig oesophagus
Yu, S., Undem, B. J., & Kollárik, M. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2004.079574 · Cited by 147 · see citing works
Self-citationGinger—Mechanism of action in chemotherapy-induced nausea and vomiting: A review
Marx, W., Ried, K., McCarthy, A. L., Vitetta, L., Sali, A., McKavanagh, D., & Isenring, L. (2015) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2013.865590 · Cited by 147 · see citing works
Monitoring activity in neural circuits with genetically encoded indicators
Broussard, G. J., Liang, R., & Tian, L. (2014) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2014.00097 · Cited by 141 · see citing works
Occurrence, biological activity and metabolism of 6-shogaol
Kou, X., Wang, X., Ji, R., Liu, L., Qiao, Y., Lou, Z., Ma, C., Li, S., Wang, H., & Ho, C.-T. (2018) · Food & Function · doi:10.1039/c7fo01354j · Cited by 115 · see citing works
Gingerol and Its Role in Chronic Diseases
Yusof, Y. A. M. (2016) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-41342-6_8 · Cited by 100 · see citing works
Modulation of Transient Receptor Vanilloid 1 Activity by Transient Receptor Potential Ankyrin 1
Spahn, V., Stein, C., & Zöllner, C. (2013) · Molecular Pharmacology · doi:10.1124/mol.113.088997 · Cited by 99 · see citing works
Pertz, H. H., Lehmann, J., Roth-Ehrang, R., & Elz, S. (2011) · Planta Medica · doi:10.1055/s-0030-1270747 · Cited by 93 · see citing works
Metabolism of [6]-gingerol in rats
Nakazawa, T., & Ohsawa, K. (2002) · Life Sciences · doi:10.1016/s0024-3205(01)01551-x · Cited by 93 · see citing works
TRP channel functions in the gastrointestinal tract
Yu, X., Yu, M., Liu, Y., & Yu, S. (2015) · Seminars in Immunopathology · doi:10.1007/s00281-015-0528-y · Cited by 89 · see citing works
Self-citationWalstab, J., Krüger, D., Stark, T., Hofmann, T., Demir, I. E., Ceyhan, G. O., Feistel, B., Schemann, M., & Niesler, B. (2013) · Neurogastroenterology & Motility · doi:10.1111/nmo.12107 · Cited by 81 · see citing works
TRPA1 in bradykinin-induced mechanical hypersensitivity of vagal C fibers in guinea pig esophagus
Yu, S., & Ouyang, A. (2008) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.90530.2008 · Cited by 76 · see citing works
Self-citationMrgprs on vagal sensory neurons contribute to bronchoconstriction and airway hyper-responsiveness
Han, L., Limjunyawong, N., Ru, F., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0074-8 · Cited by 70 · see citing works
Miller, R. E., Miller, R. E., Kim, Y. S., et al. (2017) · Arthritis & Rheumatology · doi:10.1002/art.40342 · Cited by 55 · see citing works
Pharmacokinetics of [6]-shogaol, a pungent ingredient of Zingiber officinale Roscoe (Part I)
Asami, A., Shimada, T., Mizuhara, Y., et al. (2010) · Journal of Natural Medicines · doi:10.1007/s11418-010-0404-y · Cited by 43 · see citing works
Yu, X., Hu, Y., Ru, F., et al. (2015) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00336.2014 · Cited by 32 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Nutritional Approaches to Enhance GLP-1 Analogue Therapy in Obesity: A Narrative Review
Dias, D. D., Vasconcelos, A. R., Souza, A. C. R., Menezes, C. D., Silva, I. S. T. E., & Name, J. J. (2025) · Obesities · doi:10.3390/obesities5040088 · Cited by 8 · see citing works
- Authors
- Huang, Y., Patil, M. J., Yu, M., Liptak, P., Undem, B. J., Dong, X., Wang, G., & Yu, S.
- Affiliations
- Johns Hopkins University (US)
- Jessenius Faculty of Medicine in Martin Comenius University in Bratislava Martin Slovakia
- Wuhan Union Hospital (CN)
- Corresponding author
- Yu, Shaoyong
- ORCID
- Venue
- Neurogastroenterology & Motility
- Publisher
- Wiley
- Published
- 2019-04-04
- Volume
- 31
- Issue
- 6
- Pages
- e13585-e13585
- ISSN
- 1350-1925 (ISSN-L)
- 1365-2982
- PMC
- PMC6522279
- OpenAlex
- W2934700758
- Cited by
- 12
- References
- 26
- Citations by year
- 2026: 2 · 2025: 2 · 2023: 1 · 2022: 3 · 2021: 1 · 2020: 2 · 2018: 1
- FWCI
- 0.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurogastroenterology & Motility (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (DK110366)
- Johns Hopkins University
- Topics
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Keywords
- 6-shogaol, ginger, nodose ganglion, TRPA1, nausea and vomiting, desensitization, calcium influx, esophageal distension
- MeSH terms
- Action Potentials, Animals, Catechols, Esophagus, Male, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Afferent, Nodose Ganglion, Stomach, Nerve Fibers, Unmyelinated, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
