Bioactive Peptides: From Basic Research to Clinical Trials and Commercialization

Duffuler, Pauline; Bhullar, Khushwant S.; Zani, Stepheny C. de Campos; Wu, Jianping

doi:10.1021/acs.jafc.1c06289

Cited by 58 publications

(40 citation statements)

References 147 publications

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“…Similar to IRW, a recently developed drug called teriparatide also exhibited an extremely efficacious osteogenesis effect [54]. It will be interesting to see if IRW supplementation in humans is tolerable and if the osteogenic effects are translated clinically as well [23]. In summary, our experiments align with multiple evidence indicating osteogenic and cytoprotective efficiency of food derived peptides and related molecules.…”

Section: Discussionsupporting

confidence: 70%

“…However, the long-term use of these medications has been associated with serious off-target effects [21]. Therefore, natural and safe treatment and prevention options for bone diseases such as the use of bioactive peptides are gaining attention [22,23]. Bioactive peptides usually contain 2-20 amino acids with the ability to exhibit pharmacological action at the tissue level [24].…”

Section: Introductionmentioning

confidence: 99%

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Tripeptide IRW Protects MC3T3-E1 Cells against Ang II Stress in an AT2R Dependent Manner

Shang

Bhullar

2022

Molecules

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Multiple strategies including the use of bioactive peptides and other nutraceuticals are being adopted to maintain bone health. This study provides an improved and deeper understanding of the pharmacological effects that a bioactive peptide IRW (Ile-Arg-Trp) extends on bone health. Our results showed that IRW treatment protects osteoblasts against Ang II induced decline in cell proliferation and restores protein levels of collagen type I alpha 2 chain (COL1A2) and alkaline phosphatase (ALP) levels in MC3T3-E1 cells (p < 0.05). Apart from augmentation of these mineralization factors, the angiotensin II (Ang II) induced apoptotic stress in osteoblasts was mitigated by IRW as well. At the molecular level, IRW abolished the cytochrome-c release via modulation of pro-and anti-apoptotic genes in MC3T3-E1 cells (p < 0.05). Interestingly, IRW also increased cellular levels of cytoprotective local RAAS factors such as MasR, Ang (1–7), ACE2, and AT2R, and lowered the levels of Ang II effector receptor (AT1R). Further, our results indicated a lower content of inflammation and osteoclastogenesis biomarkers such as cyclooxygenase 2 (COX2), nuclear factor kappa B (NF-κB), and receptor activator of nuclear factor kappa-B ligand (RANKL) following IRW treatment in MC3T3-E1 cells (p < 0.05). The use of an antagonist-guided cell study indicated that IRW contributed to the process of cytoprotection and proliferation of osteoblasts via Runt-related transcription factor 2 (RUNX2) in face of Ang II stress in an AT2R dependent manner. The key findings of our study showed that IRW could potentially have a therapeutic role in the treatment and/or prevention of bone disorders.

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Section: Discussionsupporting

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Tripeptide IRW Protects MC3T3-E1 Cells against Ang II Stress in an AT2R Dependent Manner

Shang

Bhullar

2022

Molecules

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“…However, the lack of clinical data limits the use of PAPs. This is because data from in vitro cell experiments and in vivo animal experiments are difficult to convert into clinical data [ 82 ]. The bioavailability of PAPs and the processes of metabolism and attenuation in vivo are still unknown.…”

Section: Limitations Of Plant-derived Anti-inflammatory Peptidesmentioning

confidence: 99%

Anti-Inflammatory Function of Plant-Derived Bioactive Peptides: A Review

Liu

Chen

et al. 2022

Foods

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Inflammation is considered to be a crucial factor in the development of chronic diseases, eight of which were listed among the top ten causes of death worldwide in the World Health Organization’s World Health Statistics 2019. Moreover, traditional drugs for inflammation are often linked to undesirable side effects. As gentler alternatives to traditional anti-inflammatory drugs, plant-derived bioactive peptides have been shown to be effective interventions against various chronic diseases, including Alzheimer’s disease, cardiovascular disease and cancer. However, an adequate and systematic review of the structures and anti-inflammatory activities of plant-derived bioactive peptides has been lacking. This paper reviews the latest research on plant-derived anti-inflammatory peptides (PAPs), mainly including the specific regulatory mechanisms of PAPs; the structure–activity relationships of PAPs; and their enzymatic processing based on the structure–activity relationships. Moreover, current research problems for PAPs are discussed, such as the shallow exploration of mechanisms, enzymatic solution determination difficulty, low yield and unknown in vivo absorption and metabolism and proposed future research directions. This work aims to provide a reference for functional activity research, nutritional food development and the clinical applications of PAPs.

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“…Recently, probiotics and dietary supplements have emerged as potential treatment options with measurable impact on disease severity documented in clinical research reports [ 6 , 7 ]. Protein hydrolysates consist of a mixture of varying proteins and peptides which are formed by the hydrolysis of intact proteins and are commonly used as an alternative protein source in commercial products [ 8 , 9 ]. Protein hydrolysates are also recognized as a potent source of bioactive peptides that have different molecular weights and varying biological effects, with anti-thrombotic, anti-hypertensive, anti-microbial, anti-cancer, anti-oxidative, and immunomodulatory effects having been identified [ 7 , 8 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…Protein hydrolysates consist of a mixture of varying proteins and peptides which are formed by the hydrolysis of intact proteins and are commonly used as an alternative protein source in commercial products [ 8 , 9 ]. Protein hydrolysates are also recognized as a potent source of bioactive peptides that have different molecular weights and varying biological effects, with anti-thrombotic, anti-hypertensive, anti-microbial, anti-cancer, anti-oxidative, and immunomodulatory effects having been identified [ 7 , 8 , 9 , 10 ]. Soluble protein hydrolysate (SPH) is produced by the enzymatic hydrolysis of salmon offcuts consisting of the head, backbone and skin, and contains a variety of bioactive peptides with reported health benefits including against oxidative stress [ 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Soluble Protein Hydrolysate Ameliorates Gastrointestinal Inflammation and Injury in 2,4,6-Trinitrobenzene Sulfonic Acid-Induced Colitis in Mice

Wei

Tao

et al. 2022

Biomolecules

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Inflammatory bowel diseases (IBD) are chronic, recurring gastrointestinal diseases that severely impair health and quality of life. Although therapeutic options have significantly expanded in recent years, there is no effective therapy for a complete and permanent cure for IBD. Well tolerated dietary interventions to improve gastrointestinal health in IBD would be a welcome advance especially with anticipated favorable tolerability and affordability. Soluble protein hydrolysate (SPH) is produced by the enzymatic hydrolysis of commercial food industry salmon offcuts (consisting of the head, backbone and skin) and contains a multitude of bioactive peptides including those with anti-oxidant properties. This study aimed to investigate whether SPH ameliorates gastrointestinal injury in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced mouse colitis model. Mice were randomly assigned to four groups: Control (no colitis), Colitis, Colitis/CP (with control peptide treatment), and Colitis/SPH (with SPH treatment). Colitis was induced by cutaneous sensitization with 1% TNBS on day −8 followed by 2.5% TNBS enema challenge on day 0. Control peptides and SPH were provided to the mice in the Colitis/CP or Colitis/SPH group respectively by drinking water at the final concentration of 2% w/v daily from day −10 to day 4. Then, the colon was harvested on day 4 and examined macro- and microscopically. Relevant measures included disease activity index (DAI), colon histology injury, immune cells infiltration, pro- and anti-inflammatory cytokines and anti-oxidative gene expression. It was found that SPH treatment decreased the DAI score and colon tissue injury when compared to the colitis-only and CP groups. The protective mechanisms of SPH were associated with reduced infiltration of CD4+ T, CD8+ T and B220+ B lymphocytes but not macrophages, downregulated pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-6), and upregulated anti-inflammatory cytokines (transforming growth factor-β1 and interleukin-10) in the colon tissue. Moreover, the upregulation of anti-oxidative genes, including ferritin heavy chain 1, heme oxygenase 1, NAD(P)H quinone oxidoreductase 1, and superoxide dismutase 1, in the colons of colitis/SPH group was observed compared with the control peptide treatment group. In conclusion, the protective mechanism of SPH is associated with anti-inflammatory and anti-oxidative effects as demonstrated herein in an established mice model of colitis. Clinical studies with SPH as a potential functional food for the prevention or as an adjuvant therapy in IBD may add an effective and targeted diet-based approach to IBD management in the future.

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Bioactive Peptides: From Basic Research to Clinical Trials and Commercialization

Cited by 58 publications

References 147 publications

Tripeptide IRW Protects MC3T3-E1 Cells against Ang II Stress in an AT2R Dependent Manner

Tripeptide IRW Protects MC3T3-E1 Cells against Ang II Stress in an AT2R Dependent Manner

Anti-Inflammatory Function of Plant-Derived Bioactive Peptides: A Review

Soluble Protein Hydrolysate Ameliorates Gastrointestinal Inflammation and Injury in 2,4,6-Trinitrobenzene Sulfonic Acid-Induced Colitis in Mice

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