Perilla peptides delay the progression of kidney disease by ...

Highlights

• •

  Perilla peptides can improve apoptotic kidney damage.

• •

  Perilla peptides can improve antioxidant capacity in mice.

• •

  Perilla peptides can affect intestinal microorganisms in mice.

• •

  Perilla peptides can maintain intestinal barrier function in mice.

Abstract

Chronic kidney disease has become one of the most threatening diseases to human health worldwide. Kidney lesions can lead to a series of diseases such as damage to other organs and elevated blood lipids. In this study, perilla peptide, a small molecule peptide prepared by enzymatic digestion of perilla protein, ameliorated adenine-induced apoptotic kidney injury and oxidative stress, attenuated organ inflammatory response, and improved kidney injury status. In addition, perilla peptides maintained the integrity of intestinal barrier function in mice, increased the expression of intestinal tight junction proteins, and reduced the multiplication of multiple pathogenic bacteria in the intestine, thus reducing the accumulation of endotoxins in the blood. In conclusion, this study demonstrated that perilla peptides have positive ameliorative effects in kidney diseases and have potential applications in the development of functional foods.

Introduction

The kidney is a highly metabolic organ responsible for the removal of endogenous waste products, maintenance of acid-base and electrolyte balance, and endocrine function(Cargill & Sims-Lucas, 2020). Metabolic disorders and electrolyte imbalance result when the kidneys are damaged(Long et al., 2019). CKD can be caused by a variety of reasons, such as old age, diabetes, hypertension, etc. CKD has become one of the most threatening diseases to human health worldwide(Li et al., 2020), affecting more than 200 million people worldwide(Abdelrahman et al., 2019).

Traditionally, the main factor in evaluating the quality of dietary protein is its nutritional value. However, specific protein fragments have been found to have specific physiological effects and can influence physical health(Miner-Williams, Stevens, & Moughan, 2015), including antihypertensive, antithrombotic, immunomodulatory, antioxidant, etc. Due to these effects of peptides, they have attracted great interest as a functional food(Chakrabarti, Guha, & Majumder, 2018). It has been shown that dipeptides and tripeptides can pass directly through the intestinal wall without being hydrolyzed and are absorbed 70–80% more than similar free amino acids(Miner-Williams et al., 2015).

High concentrations of adenine are converted by xanthine oxidase to DHA, which has low solubility. DHA can be deposited in the kidney tubules and interstitium, blocking the tubules and causing tubular atrophy and interstitial fibrosis, thus causing kidney function impairment(Abdelrahman et al., 2019). Adenine increases oxidative stress production and inflammatory factors in the kidney, elevates serum urea nitrogen, creatinine, and uric acid levels cause a significant decrease in serum calcium ion concentration and a significant increase in potassium ion concentration, as well as elevated lipids and apoptotic kidney lesions that closely resemble the progression of human kidney disease(Abdelrahman et al., 2019; Diwan, Brown, & Gobe, 2018; Diwan, Mistry, Gobe, & Brown, 2013), and is a widely used model of kidney injury.

Perilla peptides are small molecular peptides obtained by enzymatic digestion of perilla proteins, and the physiological functions of perilla peptides have been reported to include antioxidant(Agbor et al., 2018; Kim, Liceaga, & Yoon, 2019), and improvement of muscle synthesis in mice(Liu et al., 2020). In the present study, we used adenine to induce kidney injury in mice to mimic human kidney disease, aiming to investigate the positive role of perilla peptides in adenine-induced kidney injury. We found that perilla peptides alleviated the oxidative stress state of organs, improved kidney inflammation and apoptotic injury restored electrolyte metabolism, and improved hyperlipidemia. In addition, perilla peptides increased the expression of intestinal tight junction protein in mice and maintained the integrity of intestinal barrier function, while reducing the multiplication of pathogenic bacteria in the intestine and thus the accumulation of endotoxins in the blood. In conclusion, perilla peptides have shown potential application value in alleviating kidney injury and its complications.

Access through your organization

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

Access through your organization

Section snippets

Chemicals and reagents

The peptides used in this experiment were prepared in the laboratory; the kits used for the detection of serum biochemical parameters were purchased from Jiancheng Bioengineering Institute (Nanjing, China). ELISA kits for IL-1β, IL-6, and TNF-α were purchased from Biokits tech lnc. (Beijing, China). The kits for SOD, CAT, GSH-Px, GSH, and MDA assays were also purchased from Jiancheng Bioengineering Institute (Nanjing, China). The Zo-1 Monoclonal Antibody, Claudin 1 Polyclonal Antibody, Occludin

Perilla peptides improved organ indexes

After adenine treatment, the body weight of mice in all groups was significantly lower compared to the control group (p < 0.05). After modeling, the intervention of different doses of perilla peptides did not have a significant effect on the body weight gain of mice, and the body weights of mice between groups did not show significant differences (p > 0.05) during the intervention of perilla peptides (Fig. 1A); from the results of organ index measurements, there were no significant differences

Discussion

Many studies have mimicked kidney disease in humans by varying adenine concentration and treatment duration(Rahman et al., 2018). The present experiment similarly caused kidney injury in mice by gavage of 50 mg/kg of adenine for 10 consecutive days.

Adenine has been reported to cause some degree of liver damage and to increase serum ALT and AST levels in mice(Za’abi. et al., 2015; Zhang, Liu, Luo, & Li, 2018), as well as to decrease serum albumin levels(Y. Wu et al., 2019). ALT and AST are

Authorship contribution statement

Mingliang Li and Ying Wei: experimental design, data processing, and paper writing.

Ruizeng Gu and Xingchang Pan: amino acid analysis.

Mingliang Li and Muyi Cai: animal housing and treatment.

Jinmin Du: manuscript examination.

Conflict of interest

The authors declare that they have no conflict of interest.

Acknowledgments

This work was funded by the National Key Research and Development Program of China, Grant/Award Number: 2016YFD0400604.

• Food-derived bioactive peptides potentiating therapeutic intervention in rheumatoid arthritis

  2024, Heliyon

  Disease cure and delay processes using selected foods could be achieved. For instance, Li et al. [125] showed that Perilla peptides could delay the progression of kidney disease through apoptotic injury and oxidative stress improvement and maintenance of intestinal barrier function. In this section, we take a look at food-derived bioactive peptides (FDPs) and their potential therapeutic effects on RA based on documented evidence in the literature.

View all citing articles on ScopusView full text

© 2021 Elsevier Ltd. All rights reserved.