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Peer-reviewedCC BY 4.0Frontiers in Pharmacology

Amomum tsao-ko volatile oil alleviates renal fibrosis in 5/6 nephrectomy rats through TGF-β1/SMAD3 and PI3K/AKT signaling pathways

6 affiliations
  1. 1School of Pharmacy/Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education/Institute for Safflower Industry Research/School of Chemistry and Chemical Engineering, Shihezi University
  2. 2School of Pharmaceutical Sciences, Shenzhen Technology University
  3. 3International Cooperative Laboratory of Traditional Chinese Medicine Modernization, Innovative Drug Development of Chinese Ministry of Education (MOE), College of Pharmacy, Jinan University
  4. 4Department of Medicinal Chemistry and Natural Medicine Chemistry (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University
  5. 5Xinjiang Academy of Forestry, Key Laboratory of Forest Resources and Utilization in Xinjiang of National Forestry and Grassland Administration
  6. 6Xishuangbanna Dai Medicine Research Institute Co., Ltd.

Abstract

Introduction: Renal fibrosis is the main cause of many kidney diseases and a common outcome of many chronic kidney diseases. The dried mature fruit of Amomum tsao-ko is widely used to treat various diseases, including those characterized by diuresis and detumescence. Amomum tsao-ko volatile oil (AO) may be the active ingredient responsible for its main pharmacological action, and its protective effect and mechanism in kidney injury models are unclear. Therefore, based on transcriptomics and animal experiments, this study discusses the mechanism of AO through TGF‑ β 1/SMAD3 and PI3K/AKT signaling pathways in renal fibrosis of 5/6 nephrectomy rats.

Methods: Seventy-two healthy SD rats were randomly divided into 6 groups. The rat renal fibrosis model was established by 5/6 nephrectomy. Different doses of AO were given by gavage. After 28 days of continuous administration, the levels of creatinine and urea nitrogen in serum of rats were detected. The total RNA of rat kidney tissue was extracted for transcriptomics determination and analysis showed the expression of differential genes in each group. The core targets related to chronic kidney injury were docked with the main components of the AO. HE, PAS and Masson staining were used to observe the pathological morphology of renal tissue in rats. Western Blot was used to detect the expression of p-PI3K, PI3K, AKT, p-AKT, SMAD3, TGF- β 1, MMP-9 and TIMP-1 in renal tissue.

Results: Compared with the Sham group, the transcriptome results showed that there were 823 genes with significant differences in expression; the levels of SCr and BUN in the model group were significantly increased. HE, PAS and Masson found that 5/6 Nx could develop interstitial fibrosis. At the same time, a large number of renal tubular epithelial cells were atrophied, deformed and exfoliated, and a large number of inflammatory cells infiltrated in the interstitium. Western Blot results showed that the expression of PI3 K, AKT, TIMP-1, SMAD3, TGF- β 1 and other proteins in the 5/6 Nx group increased significantly, and the expression of MMP-9 protein decreased significantly. Compared with the 5/6 Nx group, there were 1,009 genes with significant differences in expression after treatment with AO, and the levels of SCr and BUN decreased. The infiltration of inflammatory cells in renal tissue was improved. The expression of PI3K, AKT, TIMP-1, SMAD3 and TGF- β 1 was significantly decreased, and the expression of MMP-9 was significantly increased.

Conclusion: AO can further inhibit the phosphorylation level by inhibiting the TGF- β 1/SMAD3 and PI3K/AKT signaling pathways in 5/6 Nx rats, thus effectively improving the pathological damage of renal tissue.

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BibTeX
@article{cui2026amomum,
  title = {{Amomum tsao-ko volatile oil alleviates renal fibrosis in 5/6 nephrectomy rats through TGF-β1/SMAD3 and PI3K/AKT signaling pathways}},
  author = {Huanyue Cui and Meiru Shi and Qing Xu and Shangwen Zhou and Xin Li and Hangyu Wang and Dahong Yao and Ke Zhang and Pinghua Sun and Jinhui Wang},
  journal = {Frontiers in Pharmacology},
  year = {2026},
  month = oct,
  doi = {10.3389/fphar.2026.1819932},
  url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1819932/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Amomum tsao-ko volatile oil alleviates renal fibrosis in 5/6 nephrectomy rats through TGF-β1/SMAD3 and PI3K/AKT signaling pathways
AU  - Huanyue Cui
AU  - Meiru Shi
AU  - Qing Xu
AU  - Shangwen Zhou
AU  - Xin Li
AU  - Hangyu Wang
AU  - Dahong Yao
AU  - Ke Zhang
AU  - Pinghua Sun
AU  - Jinhui Wang
PY  - 2026
DA  - 2026/10/08
JO  - Frontiers in Pharmacology
DO  - 10.3389/fphar.2026.1819932
UR  - https://www.frontiersin.org/articles/10.3389/fphar.2026.1819932/full
AB  - Introduction: Renal fibrosis is the main cause of many kidney diseases and a common outcome of many chronic kidney diseases. The dried mature fruit of Amomum tsao-ko is widely used to treat various diseases, including those characterized by diuresis and detumescence. Amomum tsao-ko volatile oil (AO) may be the active ingredient responsible for its main pharmacological action, and its protective effect and mechanism in kidney injury models are unclear. Therefore, based on transcriptomics and animal experiments, this study discusses the mechanism of AO through TGF‑ β 1/SMAD3 and PI3K/AKT signaling pathways in renal fibrosis of 5/6 nephrectomy rats.  Methods: Seventy-two healthy SD rats were randomly divided into 6 groups. The rat renal fibrosis model was established by 5/6 nephrectomy. Different doses of AO were given by gavage. After 28 days of continuous administration, the levels of creatinine and urea nitrogen in serum of rats were detected. The total RNA of rat kidney tissue was extracted for transcriptomics determination and analysis showed the expression of differential genes in each group. The core targets related to chronic kidney injury were docked with the main components of the AO. HE, PAS and Masson staining were used to observe the pathological morphology of renal tissue in rats. Western Blot was used to detect the expression of p-PI3K, PI3K, AKT, p-AKT, SMAD3, TGF- β 1, MMP-9 and TIMP-1 in renal tissue.  Results: Compared with the Sham group, the transcriptome results showed that there were 823 genes with significant differences in expression; the levels of SCr and BUN in the model group were significantly increased. HE, PAS and Masson found that 5/6 Nx could develop interstitial fibrosis. At the same time, a large number of renal tubular epithelial cells were atrophied, deformed and exfoliated, and a large number of inflammatory cells infiltrated in the interstitium. Western Blot results showed that the expression of PI3 K, AKT, TIMP-1, SMAD3, TGF- β 1 and other proteins in the 5/6 Nx group increased significantly, and the expression of MMP-9 protein decreased significantly. Compared with the 5/6 Nx group, there were 1,009 genes with significant differences in expression after treatment with AO, and the levels of SCr and BUN decreased. The infiltration of inflammatory cells in renal tissue was improved. The expression of PI3K, AKT, TIMP-1, SMAD3 and TGF- β 1 was significantly decreased, and the expression of MMP-9 was significantly increased.  Conclusion: AO can further inhibit the phosphorylation level by inhibiting the TGF- β 1/SMAD3 and PI3K/AKT signaling pathways in 5/6 Nx rats, thus effectively improving the pathological damage of renal tissue.
SN  - 1663-9812
ER  -