Wheat peptides with different hydrolysis degree have similar relief effect in constipated mice
Graphical abstract
Introduction
Constipation, a common gastrointestinal disorder, is characterized by the infrequent passage of stools or difficulty with the evacuation of stools (Longstreth et al., 2006). Despite the significant global expenditure on constipation treatment research, more than 50% of constipation patients are still unable to be treated, which significantly impacting their quality of life (Nelson et al., 2017). Until now, stool softeners, osmotic or irritating laxatives, as well as secretagogues and prokinetic medicines, have been the most common drugs for treating constipation (Sharma & Rao, 2017; Vazquez Roque & Bouras, 2015). However, these drugs have significant drawbacks that limit their usage in the treatment of constipation, including strong drug dependence, high recurrence rate, poor long-term effect, and expensive cost (Chang, et al., 2014; Miner et al., 2014). Hence, developing safe and effective drugs to treat constipation is on the cutting edge. Natural bioactive substances for the control and prevention of constipation are favored by consumers due to their low toxicity and less adverse effects (Wang et al., 2022a, 2022b; Xia et al., 2022). For instance, bioactive peptides generated from food proteins have been reported to play a prominent role in maintain gut health and function (Bao & Wu, 2021).
In the previous study, we determined that 2 mg/g wheat peptides (WP) effectively relieved constipation in loperamide-induced constipated mice (Wang et al., 2022) . However, as patients may respond differently to WP treatment, an additional dose choice of less than 2 mg is preferred to guarantee that patients with varying degrees of constipation severity (from mild to severe) have a dosing option with WP. The degree of hydrolysis (DH) of bioactivity peptides, on the other hand, may affect their functional characteristics in that peptides with a higher DH are accompany with a lower molecular weight (MW), which enable them to pass through the intestinal barrier to exert their functional properties in vivo (Miao et al., 2018; Sarmadi & Ismail, 2010; You et al., 2012). For instance, high hydrolysis degree sea cucumber peptides with a lower molecular weight displayed a better antioxidant effect in fatigued mice than low hydrolysis degree (Wang et al., 2021). However, no comparative study of the constipation relief effect of WP with different DH has been reported. A comprehensive study of WP with different hydrolysis degree could provide some guidance to the optimization of WP production.
As for the mechanism of wheat peptide in improving constipation, the aspects of water-salt metabolism, intestinal mobility, and gut microbiota were analyzed (Wang, Shen, et al., 2022). However, the etiology of constipation is believed to be multifaceted and has not yet been elucidated in its entirety (Bharucha & Lacy, 2020). The intestinal barrier constituted by intestinal epithelial cells play critical roles on the electrolyte and nutrient absorption, and inhibiting luminal bacteria and undigested food particles from entering the body uncontrolledly (Groschwitz & Hogan, 2009; Turner, 2009). Tight junction proteins are therefore critical for to the process of preserving the structural integrity of the intestinal barrier. Additionally, the homeostatic concentrations of free radicals in intestinal epithelial cells also play essential role in maintaining the function of intestinal barrier (Chaudhari, et al., 2014). The two amino acids that were most abundant in WP were glutamic acid (Glu) and glutamine (Gln) have been closely related to the integrity of intestinal barrier (Zheng et al., 2017). When Gln was depleted, the expression of tight junction proteins was drastically downregulated in Caco-2 cell lines (Li et al., 2004). On the flip side, Glu supplementation improved intestinal barrier function by upregulating the expression of tight junction proteins (Jiao et al., 2015). Moreover, WP was able to exert an effective antioxidant effect and protect against oxidative stress in ethanol-induced gastric mucosal damage (Yang et al., 2020; Zhang, Wen, et al., 2019). Hence, we postulated that the relief of constipation by WP may also be linked to the enhancement of intestinal barrier function and the suppression of oxidative stress.
This study was aimed at: (i) evaluating the efficacy of 1 mg/g wheat peptides dose in loperamide-induced mice; (ii) determining whether there are differences between WP-L and WP-H in alleviating constipation; and (iii) elucidating the possible mechanism of WP-L and WP-H to relieve constipation from the perspective of water-salt metabolism, intestinal barrier, oxidative stress, and intestinal motility.
Section snippets
Materials
WP-L (DH = 7.31%) was graciously provided by Hangzhou Kangyuan Food Science and Technology Co., Ltd. (Hangzhou, China), whereas WP-H (DH = 25.06%) was obtained locally (Hangzhou, China). Loperamide was bought from Xi’an Janssen Pharmaceutical Ltd. (Xi’an, China). The ink preparation operation was executed in accordance with the previously stated method (Chai et al., 2021).
Animals and experimental design
The Ethics Committee of Experimental Animals of Zhejiang Chinese Medical University (20211206-06) authorized the animal
WP-L and WP-H improved defecation function and small intestinal propulsion rate in constipated mice
After induction of constipation, the food intake and weight gain of the mice in the MC group were less than those in the NC group, but the WP-L and WP-H groups reversed the decreasing trends (Fig. 1B and C). The time to the first black stool defecation in the WP-L and WP-H groups were significantly shortened by 25.42% and 27.64% than that of the MC group (P < 0.01) (Fig. 1D). And the number of fecal pellets, fecal wet weight, and fecal water content in the WP-L and WP-H groups were
Discussion
The movement of fecal content in the intestine is chiefly characterized by the small intestine propulsion rate and time to the defection of the first black stool (Hu et al., 2019). WP-L and WP-H significantly increased the small intestine transit rate and shortened the first black stool defecation time, which revealed that both WP-L and WP-H administration effectively accelerated intestinal peristalsis to prevent constipation, and hydrolysis degree of WP did not affect their efficacy. Besides,
Conclusions
The consumption of WP-L and WP-H at the dose of 1 mg/g.bw significantly decreased the first black stool defecation time, increased the number of fecal pellets and fecal water content, promoted the small intestine propulsion rate, balanced the secretion of excitatory and inhibitory factors, and enhanced the activity of antioxidant enzyme in loperamide-induced constipated mice. Meanwhile, WP-L and WP-H have similar relief effect in constipated mice. The underlying mechanisms may involve multiple
Author statement
Qianqian Wang: Conceptualization, Data curation, Investigation, Methodology, Software, Visualization, Writing-original draft; Fei Shen: Investigation, Methodology; Junhui Zhang: Investigation, Methodology; Jiachen Zhuang: Investigation, Methodology; Fengqin Feng: Conceptualization, Project administration, Supervision, Writing-review & editing. All authors read and approved the final manuscript.
Declaration of competing interest
The authors report no declarations of interest.
Acknowledgement
This work was supported by the Ningbo Science and Technology Innovation 2025 Major Special Project [grant numbers 2019B10060].
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