Synergistic effect of collagen peptide LR-7 and taurine on ...

Highlights

• •

  Collagen peptide LR-7 alleviates hypertension-induced heart and arterial injury through antioxidant, anti-inflammatory and hypotensive activities.

• •

  The combination of taurine and LR-7 demonstrated a synergistic effect with 1 + 1>2 on the improvement of cardiovascular injury.

• •

  Taurine and LR-7 have synergistic antioxidant, anti-inflammatory, and JP2 and eNOS pathways activation.

• •

  This study enhances our understanding of how these compounds were used cohesively to mitigate cardiovascular damage.

Abstract

Hypertension significantly contributes to adverse cardiovascular outcomes. Our investigation was designed to evaluate the effects of supplementation with collagen peptide (LR-7) and taurine (Tau) on cardiovascular impairment in hypertensive mice induced by an 8% high-salt (HS) diet. Compared to administration of LR-7 (200 μmol/kg) or Tau (200 μmol/kg) alone, the combined treatment of LR-7 (100 μmol/kg) and Tau (100 μmol/kg) exhibited the strongest inhibition of systolic blood pressure elevation, aortic intimal thickening, reduction in myocardial fiber density, and myocardial fibrosis in HS-induced hypertensive mice. Furthermore, the treatment with LR-7+Tau significantly ameliorated the levels of cardiac adhesion factor (intercellular adhesion molecule 1), antioxidant enzymes (catalase and glutathione peroxidase), and inflammatory markers (interleukin-6, interleukin-1β, and nuclear factor kappa-B) in hypertensive mice compared to either LR-7 or Tau alone. To uncover the underlying mechanisms, the calpain 1/junctophilin-2 (JP2) pathway in cardiac tissue was investigated. Our findings revealed that LR-7+Tau treatment reversed the abnormal expression of calpain 1 and JP2 proteins in cardiac tissue. Additionally, it upregulated the endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (p-eNOS) levels in the heart. In summary, LR-7 and Tau collectively exerted a cardiovascular protective effect in HS diet-induced hypertensive mice, demonstrating synergistic efficacy.

Introduction

Hypertension represents a prevalent chronic condition, significantly contributing as a major risk factor for cardiovascular diseases (CVDs) (Burnier & Damianaki, 2023). Numerous studies have established a correlation between high intake of salt and the dysregulation of blood pressure (Dornas et al., 2017; Yang et al., 2021). The pathogenesis of high-salt-induced hypertension was intricately associated with oxidative stress, defined by an imbalance between the production of reactive oxygen species (ROS) and the capacity of antioxidants to neutralize these agents (Chen et al., 2024; Higashi, 2022; Ionică et al., 2021; Mu et al., 2022). Oxidative stress leads to endothelial dysfunction through oxidative damage, which worsens vascular damage and increases blood pressure (Souza Bomfim et al., 2022; Touyz et al., 2020). Given the established association between hypertension and CVDs, uncovering the underlying biological mechanisms between these diseases remains a focal area of contemporary research.

A healthy nutritional strategy play a crucial role in significantly mitigating high blood pressure and reducing the risk of hypertension complications (Singh et al., 2024). Currently, bioactive peptides from different food sources represent a promising frontier for functional foods, which show great potential as nutritional supplement in the management of hypertension and other chronic disease conditions (Auwal et al., 2024). However, due to the limited function and insufficient activity of specific peptide, it was difficult to effectively improve hypertension complications from many aspects by supplementing peptide alone. Bioactive peptides from Ruditapes philippinarum alleviated cardiorenal damage in hypertensive rats, but the levels of antioxidant enzymes and inflammatory factors were improved by only about 30% (Sun et al., 2023). Peptides alleviated the damage of thoracic aorta and heart of hypertensive rats by regulating the balance of NO/ET-1 secretion, but did not exhibit the protective effect by antioxidant and anti-inflammatory effects (Song et al., 2021). Different active substances may exert biological activity more efficiently through synergistic effect in many aspects. Therefore, the use of active peptides in combination with other functional compounds to improve hypertension and its complications more efficiently is a very promising strategy.

Taurine (2-aminoethanesulfonic acid) is a sulfur-containing amino acid widely added to functional foods, exhibits a variety of biological activities, including osmoregulation, antioxidation, and anti-inflammatory actions (Tain et al., 2023). Taurine treatment had been shown to ameliorate the onset and development of many diseases, including hypertension, fatty liver, neurodegenerative diseases and ischemia–reperfusion injury (Wang, Xie, et al., 2024). In the cardiovascular system, diets rich in taurine played an antihypertensive role by increasing the production of taurine-conjugated bile acids (Li et al., 2024). A higher incidence of hypertension and cardiovascular diseases had been reported in people with low taurine diets. Despite these findings, the effects of taurine on myocardial and vascular damage triggered by hypertension have been rarely reported. In addition, whether there is a synergistic effect of taurine and active peptides in ameliorating hypertensive myocardial and arterial damage is unclear and deserves further investigation.

In prior research, we had identified and characterized the collagen peptide LALFVPR (LR-7) from the bones of Harpadon nehereus, demonstrating its protective effects against oxidative stress in hyperglycemia-induced HepG2 cells (He et al., 2023). Building on these findings, the current study focused on the synergistic effects of combining peptide LR-7 with taurine in mitigating high-salt-induced cardiovascular damage. This investigation is critical to enhance our understanding of how the combination of different functional foods might be used to reduce common hypertensive cardiovascular complications from multiple perspectives and mechanisms, providing implications for broader nutritional strategies.

Access through your organization

Check access to the full text by signing in through your organization.

Access through your organization

Section snippets

Materials

The Harpadon nehereus collagen peptide LR-7 was chemically synthesized using solid-phase synthesis technology. Nitrendipine and taurine were purchased from Aladdin Reagent (Shanghai) Co., Ltd. The assay kits for malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) were purchased from Nanjing Jiancheng Bioengineering Institute. All antibodies and enzyme-linked immunosorbent assay kits were purchased from Wuhan

Protective effect of LR-7 and taurine on thoracic aorta in hypertensive mice

The effects of LR-7 and taurine on systolic blood pressure (SBP) and the pathological morphology of the thoracic aorta in hypertensive mice induced by a high-salt diet were investigated. The animal experimental flowchart was depicted in Fig. 1A. Fig. 1B illustrated that mice in the Con group exhibited low and stable SBP. After the high-salt diet, the SBP of mice in the HS group escalated significantly and remained at peak levels. LR-7 and taurine treatment effectively moderated the rise in SBP,

Discussion

Hypertension is a major risk factor for cardiovascular disease (CVD), which can both cause and result from endothelial dysfunction (Nemecz et al., 2016; Tsai et al., 2020). Studies have shown that a long-term a high-salt (HS) diet can induce vascular endothelial dysfunction, which is a key environmental factor in hypertension development (Touyz & Briones, 2011; Yoshida et al., 2020). Approximately 50% of hypertensive patients exhibit salt-sensitive increases in blood pressure, which

Conclusion

Our studies demonstrated that collagen peptide LR-7 and taurine synergically improved aortic intimal thickness, total myocardial fiber density, cardiac fibrosis area, and cardiac function indices in HS-induced hypertensive mice, possibly due to their synergistic antioxidant, anti-inflammatory, and blood pressure regulation mediated by the eNOS and Calpain 1/JP2 pathways. This study marked the first attempt to combine collagen peptide and taurine for the prevention of hypertension-induced heart

CRediT authorship contribution statement

Siyi Song: Writing – original draft, Methodology, Investigation. Shuqi He: Methodology, Investigation. Qianxia Lin: Methodology, Data curation. Huoxi Jin: Writing – review & editing, Project administration, Funding acquisition.

Declaration of competing interest

The authors have declared that there is no conflict of interest.

Acknowledgement

This research was supported by the Zhejiang provincial Natural Science Foundation of China under Grant No. LTGY24D060001.

• et al.

  ET-1 from endothelial cells is required for complete angiotensin II-induced cardiac fibrosis and hypertrophy

  Life Sciences

  (2012)

• S.M. Auwal et al.

  Improved systolic blood pressure (SBP)-lowering effect of stone fish-derived angiotensin-I converting enzyme (ACE)-inhibitory peptide entrapped in chitosan-coated alginate nanocomposites

  Food Bioscience

  (2024)

• X. Chen et al.

  Induction of neuroinflammation and brain oxidative stress by brain-derived extracellular vesicles from hypertensive rats

  Antioxidants

  (2024)

• S. He et al.

  Peptides from Harpadon nehereus protect against hyperglycemia-induced HepG2 via oxidative stress and glycolipid metabolism regulation

  Journal of Functional Foods

  (2023)

• A. Iliev et al.

  Hypertension-induced changes in the rat myocardium during the development of cardiac hypertrophy–a comparison between the left and the right ventricle

  Acta Histochemica

  (2019)

• W. Langston et al.

  Regulation of endothelial glutathione by ICAM-1 governs VEGF-A-mediated eNOS activity and angiogenesis

  Free Radical Biology and Medicine

  (2007)

• X.X. Ling et al.

  Xin-Ji-Er-Kang protects myocardial and renal injury in hypertensive heart failure in mice

  Phytomedicine

  (2021)

• J. Mu et al.

  CRH/CRHR1 modulates cerebrovascular endothelial cell permeability in association with S1PR2 and S1PR3 under oxidative stress

  Vascular Pharmacology

  (2022)

• M. Murali et al.

  Endosulfan causes oxidative stress in the liver and brain that involves inhibition of NADH dehydrogenase and altered antioxidant enzyme status in rat

  Ecotoxicology and Environmental Safety

  (2022)

• P. Niu et al.

  Novel polysaccharide identified from Cortinarius purpurascens demonstrated anti-fibrosis effects in cardiac fibroblasts

  Food Bioscience

  (2023)

1

Siyi Song and Shuqi He contributed equally to this work and shared first authorship.

View full text

© 2024 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.