Rhaponticum carthamoides Improved Energy Metabolism and Oxidative Stress through the SIRT6/Nrf2 Pathway to Ameliorate Myocardial Injury
Abstract
Background Rhaponticum carthamoides (Willd.) Iljin (Rha) is a member of the family Compositae that is widely used in folk medicine as a dietary supplement to treat cardiovascular diseases (CVDs), such as senile cardiac insufficiency, and to restore myocardial function after surgery. Sirtuin 6 (SIRT6), an NAD+-dependent class III histone deacetylase, plays a considerable role in the administration of CVDs. However, the specific effects and mechanism of Rha on myocardial injury remain unknown.Purpose This study aimed to explore the therapeutic potential of Rha against myocardial injury as well as its underlying mechanisms in vivo and in vitro.Methods A myocardial ischaemia model was established in male SD rats by subcutaneously injecting ISO. The rats were gavaged with Rha (40, 80, 160 mg/kg) or Rho (6 ml/kg) for 14 successive days and then injected subcutaneously with ISO or saline solution on the 13th and 14th days. The positive effects of Rha against myocardial injury in rats were evaluated by ECG assessment, BP measurements, H&E staining, and myocardial enzyme detection. Biochemical indicators of energy metabolism and oxidative stress, such as NAD+/NADH, ATP, and MDA, were analysed by assay kits to assess the effects of Rha. The protein and mRNA expression levels of SIRT6 and Nrf2 in the myocardium were determined by western blotting and real-time PCR.Results Our results showed that Rha ameliorated myocardial ischaemia and inhibited energy metabolism disorders (NAD+/NADH ratio, ATP, and LD) and oxidative stress (SOD, ROS, etc.) in rat myocardial tissue and H9c2 cells. In addition, Rha upregulated SIRT6 and Nrf2 expression in myocardial injury. Mechanistic studies then found that SIRT6 knockdown reduced the expression of Nrf2 as well as the effects of Rha on the levels of ATP, LD, and ROS, whereas activation of Nrf2 improved the effects of Rha in cells. In summary, Rha might exert its cardioprotective effects via the SIRT6-mediated Nrf2 signaling pathway.Conclusion The results suggest that Rha regulates energy metabolism and oxidative stress through the SIRT6/Nrf2 signaling pathway to play a protective role in myocardial injury.
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Investigations into Rhaponticum carthamoides revealed that its extracts are low in toxicity.
“The investigations into R. carthamoides revealed that its extracts are low in toxicity [69,121,122,123,124,125,126,127,128,129,130,131,132].”
From Ecdysterone and Turkesterone—Compounds with Prominent Potential in Sport and Healthy Nutrition (2024) · cites this paper as [123]
Extracts from Rhaponticum carthamoides show antibacterial, cytotoxic, anti-adipogenic, and antioxidant activities.
“Extracts from R. carthamoides show a variety of activities, including antibacterial, cytotoxic, anti-adipogenic, and antioxidant [69,121,122,123,124,125,126,127,128,129,130,131,132].”
From Ecdysterone and Turkesterone—Compounds with Prominent Potential in Sport and Healthy Nutrition (2024) · cites this paper as [123]
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Ecdysterone and Turkesterone—Compounds with Prominent Potential in Sport and Healthy Nutrition
Todorova, V., Ivanova, S., Chakarov, D., Kraev, K., & Ivanov, K. (2024) · Nutrients · doi:10.3390/nu16091382 · Cited by 31 · see citing works
“[123] Antimicrobial activity of R. carthamoides and Potentilla fruticosa L. extracts.”
BackgroundAnti-Adipogenic Activity of Rhaponticum carthamoides and Its Secondary Metabolites
Todorova, V., Savova, M. S., Ivanova, S., Ivanov, K., & Georgiev, M. I. (2023) · Nutrients · doi:10.3390/nu15133061 · Cited by 12 · see citing works
- Authors
- Zheng, Z., Xian, Y., Jin, Z., Yao, F., Liu, Y., Deng, Y., Wang, B., Chen, D., Yang, J., Ren, L., & Lin, R.
- Affiliations
- Xi'an Jiaotong University (CN)
- Northwest University (CN)
- Corresponding author
- Lin, Rong
- Venue
- Phytomedicine
- Publisher
- Elsevier BV
- Published
- 2022-10
- Volume
- 105
- Pages
- 154197
- ISSN
- 0944-7113 (ISSN-L)
- OpenAlex
- W4281261592
- Cited by
- 21
- References
- 36
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 5 · 2023: 5 · 2022: 1
- FWCI
- 3.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Phytomedicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81970369)
- Shaanxi Province Department of Science and Technology (2020ZDLSF05-12)
- Key Industry Innovation Chain of Shaanxi
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Health Sciences › Medicine › Complementary and alternative medicine › Traditional Chinese Medicine Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Keywords
- Rhaponticum carthamoides, myocardial injury, SIRT6, Nrf2 signaling, energy metabolism, oxidative stress, myocardial ischemia, cardioprotection, NAD+/NADH ratio, reactive oxygen species, H9c2 cells, cardiovascular disease
- MeSH terms
- Adenosine Triphosphate, Animals, Energy Metabolism, Male, NAD, Myocardial Ischemia, Rats, Sprague-Dawley, Reactive Oxygen Species, Oxidative Stress, Sirtuins, Leuzea, NF-E2-Related Factor 2, Rats
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