Atractylenolide‑1 alleviates gastroparesis in diabetic rats by activating the stem cell factor/c‑kit signaling pathway
Open accessAbstract
Diabetic gastroparesis (DGP), also known as delayed gastric emptying, is a common complication of diabetes mellitus. There are numerous clinical symptoms associated with DGP, as well as high treatment costs and markedly reduced patient quality of life. However, the pathogenesis of DGP is not clear, thus effective treatment methods are yet to be established. In the present study, a DGP rat model was established in Sprague‑Dawley rats by the intraperitoneal injection of streptozotocin (STZ). DGP model rats were treated with different doses of atractylenolide‑1 to detect alterations in gastrointestinal function, including gastroparesis, gastric emptying, gastric motility, gastric peristalsis and gastric blood flow. Compared with the DGP group, atractylenolide‑1 treatment significantly reduced glycaemia and the level of glycated hemoglobin, as well as restoring gastrointestinal function. Gastroparesis, gastric emptying, gastric motility, gastric peristalsis and gastric blood flow were significantly impaired in the STZ‑induced group compared with the vehicle control group. Moreover, the STZ‑induced group displayed downregulated expression levels of the DGP indicator KIT proto‑oncogene, receptor tyrosine kinase (c‑kit), as investigated by immunohistochemistry, and stem cell factor (SCF) protein, as assessed using ELISA, significantly enhanced rat interstitial cells of Cajal (ICC) apoptosis, and significantly altered levels of oxidative stress‑related markers (malondialdehyde and superoxide dismutase) in the serum and gastric tissues compared with the vehicle control group. By contrast, treatment with atractylenolide‑1 significantly counteracted the effects of DGP on peristalsis, inhibited apoptosis and suppressed oxidative stress by regulating the expression of heme oxygenase 1 in STZ‑induced DGP model rats. Further research indicated that atractylenolide‑1 regulated oxidative stress reactions and improved gastric function by activating the SCF/c‑kit signaling pathway. Collectively, the results of the present study suggested that atractylenolide‑1 promoted ICC survival and preserved the structure of the gastric tissue network in a DGP rat model via the SCF/c‑kit signaling pathway, providing novel insights for the treatment of DGP.
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ICC survival and network integrity depend on tightly regulated signaling pathways, particularly the SCF/c-KIT signal, which regulates ICC proliferation and function.
“ICC survival and network integrity depend on tightly regulated signaling pathways, particularly the SCF/c-KIT signal, which regulates ICC proliferation and function [56, 174, 175].”
From Diabetic gastroparesis: pathophysiology and impact on insulin timing choices (2026) · cites this paper as [174]
In pre-clinical studies, modulation of the SCF/c-KIT pathway has been shown to promote ICC survival, reduce apoptosis, and improve gastric motor function.
“In pre-clinic studies, modulation of the SCF/c-KIT pathway, has been shown to promote ICC survival, reduce apoptosis, and improve gastric motor function [174, 175].”
From Diabetic gastroparesis: pathophysiology and impact on insulin timing choices (2026) · cites this paper as [174]
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- Authors
- Li, H., Cao, W., Zhang, X.-B., Zhang, X.-X., Gu, C., Gu, L.-M., Pan, C.-Y., Tian, Y.-Z., & Lu, M.
- Affiliations
- Nanjing University of Chinese Medicine (CN)
- Department of Gastroenterology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210028, P.R. China
- Nanjing Traditional Chinese Medicine Hospital (CN)
- Corresponding author
- Lu, Min
- Venue
- Molecular Medicine Reports
- Publisher
- Spandidos Publications
- Published
- 2021-08-01
- Volume
- 24
- Issue
- 4
- ISSN
- 1791-2997 (ISSN-L)
- 1791-3004
- PMC
- PMC8365408
- OpenAlex
- W3188068756
- Cited by
- 25
- References
- 38
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 5 · 2023: 3 · 2022: 3
- FWCI
- 2.52
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Molecular Medicine Reports (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81603586)
- Government of Jiangsu Province
- Natural Science Foundation of Jiangsu Province (BK20151046)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal Tumor Research and Treatment
- Health Sciences › Medicine › Surgery › Congenital gastrointestinal and neural anomalies
- Keywords
- diabetic gastroparesis, interstitial cells of Cajal, gastric motility, gastric emptying, oxidative stress, heme oxygenase-1, KIT receptor, streptozotocin-induced diabetes, gastric peristalsis, gastric blood flow, apoptosis
- MeSH terms
- Animals, Diabetes Mellitus, Experimental, Diabetic Neuropathies, Gastric Mucins, Lactones, Male, Quality of Life, Sesquiterpenes, Stomach, Streptozocin, Superoxide Dismutase, Signal Transduction, Rats, Sprague-Dawley, Apoptosis, Oxidative Stress, Gastroparesis, Stem Cell Factor, Rats, Heme Oxygenase-1, Interstitial Cells of Cajal
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