Encyclopedia
Please note this is a comparison between Version 1 by Tsun-Thai Chai and Version 2 by Wendy Huang.
Numerous bioactive peptides have been identified from edible insect species, including peptides that were enzymatically liberated from insect proteins and endogenous peptides that occur naturally in insects. The peptides exhibited diverse bioactivities, encompassing antioxidant, anti-angiotensin-converting enzyme, anti-dipeptidyl peptidase-IV, anti-glucosidase, anti-lipase, anti-lipoxygenase, anti-cyclooxygenase, anti-obesity, and hepatoprotective activities. Such findings point to their potential contribution to solving human health problems related to inflammation, free radical damage, diabetes, hypertension, and liver damage, among others. Bioactive peptides may have a positive impact on body functions and thus benefit human health. New information reporting their beneficial effects on the health of livestock and plants is also emerging. Bioactive peptides may be produced endogenously in humans, animals, and plants.
- antioxidant
- antimicrobial
- bioactivity
- entomophagy
- livestock
- nutraceutical
- peptide purification
- protein hydrolysate
- protein hydrolysate
1. Introduction
Bioactive peptides may have a positive impact on body functions and thus benefit human health [1][2][1,2]. New information reporting their beneficial effects on the health of livestock and plants is also emerging. Bioactive peptides may be produced endogenously in humans, animals, and plants. Furthermore, such peptides can also be released from protein sources by enzymatic hydrolysis or prepared by chemical synthesis [3][4][3,4]. While bioactive peptides identified from hydrolyzed food proteins often range between two and twenty amino acid residues, longer endogenous peptides that occur naturally in humans and animals have been discovered [5]. The composition and sequence of amino acids determine the activity of bioactive peptides [6]. Bioactive peptides play important roles in the cardiovascular, immune, nervous, digestive, and endocrine systems. They represent a new generation of bioactive regulators, displaying hormone or drug-like activities, and exhibiting antioxidant, anticancer, antithrombotic, antihypertensive, anti-obesity, anti-inflammatory, opioid, mineral binding, immunomodulatory, antiaging, and antimicrobial effects [7][8][9][10][11][7,8,9,10,11]. Bioactive peptides exhibit high specificity in terms of target tissues and consequently possess low or no toxicity. Importantly, they are effective at even relatively low concentrations, which is especially important in the treatment of chronic diseases [5].
2. Purification and Identification of Bioactive Peptides from Insect Protein Hydrolysates
In the past 10 years, enzymatic hydrolysis has been frequently adopted as a means of producing bioactive peptides from the proteins of edible insects. In such studies, silkworm pupae were relatively popular for the purpose of bioactive peptide discovery [12][13][14][15][16][29,30,31,32,33]. Figure 1 shows a general workflow employed by many studies in the discovery of bioactive peptides.
Figure 1.
General workflow commonly adopted by researchers in the discovery of bioactive peptides from insect protein hydrolysates.
Among the numerous commercially available proteases, alcalase, flavourzyme, and Promod 278P were found to effectively generate functional hydrolysate/peptides from edible insects, leading to the discovery of antioxidant, anti-angiotensin-converting enzyme (ACE), anti-dipeptidyl peptidase-IV (DPP-IV), anti-obesity and hepatoprotective peptides (Table 1). However, alcalase received the most attention as it produced more potent peptides [12][13][17][29,30,34]. This could be because alcalase exhibits both endo- and exo-protease activities, which allows a broad specificity in hydrolysis sites [12][29], thus providing relatively extensive hydrolysis of the insect proteins. Furthermore, some studies used multiple proteases to generate insect protein hydrolysates, either through sequential hydrolysis with different proteases or in vitro simulation of gastrointestinal digestion in which a combination of multiple gastrointestinal proteases was used. Such use of multiple proteases could improve the degree of hydrolysis and yield more low-molecular-weight peptides when compared to only using a single enzyme in the hydrolysis of insect proteins [14][15][16][18][31,32,33,35].
Table 1.
Examples of purification and identification methodologies used in the discovery of bioactive peptides from insect hydrolysates.
| Insect | Peptide Sequence (Validated Activity) | Enzymatic Hydrolysis | Peptide Purification Strategy | Peptide Identification | Reference |
|---|---|---|---|---|---|
| Larva of the Japanese rhinoceros beetle ( | Allomyrina dichotoma | ) | EIAQDFKTDL (Anti-obesity) AGLQFPVGR (Hepatoprotective) |
Promod 278P *, pepsin, trypsin, protease NP, pancreatin, alphalase NP, alkaline protease, alcalase, neutrase, protamex |
[24][25][44,45,46]. As a result, the development of agents that reduce oxidative stress has piqued the interest of both academic research and the pharmaceutical industry. Many antioxidant peptides have been isolated from edible insects. Most of the examined edible insects’ antioxidant capacities were investigated primarily using 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays. The peptide FDPFPK is one of the most potent antioxidant peptides among those listed in Table 2. This synthetic peptide isolated from baked locusts (Schistocerca gregaria) showed strong ABTS•+ and DPPH• scavenging capacity with IC50 values of 0.08 and 0.35 mg/mL, respectively [26][27][47,48]. The antioxidant activity of Egyptian cotton leafworm hydrolysate produced by simulated gastrointestinal digestion (SGD) has been studied more thoroughly using cellular and in vivo antioxidant assays [28][49]. The in vivo Caenorhabditis elegans antioxidant model is regarded as an effective model organism for nutritional evaluation, including bioactive peptides. These nematodes have advantages over other in vivo models due to their short life span and, most notably, their high level of gene conservation relative to humans. Therefore, the antioxidant activity of Egyptian cotton leafworm hydrolysate, as measured by the in vivo Caenorhabditis elegans antioxidant model, could be regarded as promising and potentially translatable for human health applications.
Table 2.
Edible insects used for the generation of bioactive peptides and their potential applications in human health management.
| Insect | Peptide/Hydrolysate | Bioactivity * | Potential Application | References | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cricket ( | Gryllodes sigillatus | ) | IIAPPER |
|
|
|
Anti-hypertension, antidiabetic, weight control, antioxidant, and anti-inflammation | [26][27] | [47,48] | [19][20] | [36,37] | ||||||
| Larva of the white-spotted flower chafer ( | Protaetia brevitarsis | ) | SY, PF, YPY, WI (Anti-ACE) |
||||||||||||||
| LAPSTIK |
| Flavourzyme |
|
|
| [21] | [38] | ||||||||||
| Mealworm ( | Tenebrio molitor | ) | LPDQWDWR, APPDGGFWEWGD (Anti-DPP-IV) |
Flavourzyme *, alcalase, papain, trypsin | |||||||||||||
| VAPEEHPV |
|
|
| [22] | [39] | ||||||||||||
|
| Mealworm ( | Tenebrio molitor | ) | LE, AKKHKE (Hepatoprotective) |
Alcalase *, flavourzyme, neutrase | |||||||||||
| KVEGDLK |
|
|
| [17] | [34] | ||||||||||||
| Asian weaver ant larva and pupa mixture ( | Oecophylla smaragdina | ) | ||||||||||||||
| Mealworm ( | Tenebrio molitor | ) | FFGT, LSRVP (Anti-ACE) CTKKHKPNC (Antioxidant) |
SGD (Pepsin and trypsin) | NYVADGLG |
|
|
| [18] | [35] | |||||||
| Silkworm pupa ( | Bombyx mori | ) | AAEYPA, AKPGVY (Antioxidant) |
Alcalase *, papain, trypsin | |||||||||||||
| AAAPVAVAK |
|
|
|
| [13] | [30] | |||||||||||
| Silkworm pupa ( | Bombyx mori | ) | SWFVTPF, NDVLEF (Antioxidant) |
||||||||||||||
| YDDGSYKPH |
| Alcalase *, Prolyve, Flavourzyme, Brewers Clarex |
|
|
| [12] | [29] | ||||||||||
| Silkworm pupa ( | Bombyx mori | ) | FKGPACA, SVLGTGC (Antioxidant) |
||||||||||||||
| AGDDAPR |
| Acidic protease, followed by neutral protease |
|
|
| [16] | [33] | ||||||||||
| Silkworm pupa ( | Bombyx mori | ) | |||||||||||||||
| Locust | ASL (Anti-ACE) |
SGD (pepsin, trypsin, and α-chymotrypsin) | ( | Schistocerca gregaria | ) | GKDAVIV |
|
|
| [15] | [32] | ||||||
| Silkworm pupa ( | Bombyx mori | ) | GNPWM (Anti-ACE) |
Neutral protease | |||||||||||||
| AIGVGAIER |
|
|
| [14] | [31] |
* Enzyme generating the most active hydrolysate, which was selected for peptide purification. ACE: Angiotensin-I-converting enzyme, DPP-IV: Dipeptidyl peptidase-IV, GFC: Gel filtration chromatography, IEC: Ion exchange chromatography, LC: Liquid chromatography, MALDI: Matrix Assisted Laser Desorption/Ionization, MS: Mass spectrometry, MS-MS: Tandem mass spectrometry, RP-HPLC: Reversed-phase High-Performance Liquid Chromatography, SGD: Simulated gastrointestinal digestion, UF: Ultrafiltration.
3. Applications in Human Health Management
A wide variety of pathological conditions, including chronic obstructive pulmonary disease (COPD), diabetes complications, obesity, and cancer, have been linked to oxidative stress [23]
| FDPFPK | ||||||||||||||
| ||||||||||||||
| ||||||||||||||
| ||||||||||||||
| ||||||||||||||
| YETGNGIK |
| |||||||||||||
| Silkworm pupa ( | Bombyx mori | ) | AAEYPA |
| Antioxidant | [13] | [30] | |||||||
| AKPGVY |
| |||||||||||||
| Silkworm pupa ( | Bombyx mori | ) | SWFVTPF NDVLFF |
| Antioxidant | [12] | [29] | |||||||
| Silkworm pupa ( | Bombyx mori | ) | FKGPACA SVLGTGC |
| Antioxidant | [16] | [33] | |||||||
| Silkworm pupa ( | Bombyx mori | ) | ASL |
| Anti-hypertension | [15] | [32] | |||||||
| Silkworm pupa ( | Bombyx mori | ) | GNPWM WW |
| Anti-hypertension | [14] | [31] | |||||||
| Silkworm pupa ( | Bombyx mori | ) | PNPNTN |
| Immunomodulation | [29] | [52] | |||||||
| Asian weaver ant ( | Oecophylla smaragdina | ) | FFGT LSRVP |
| Anti-hypertension | [18] | [35] | |||||||
| CTKKHKPNC |
| Antioxidant | ||||||||||||
| Mealworm ( | Tenebrio molitor | ) | LPDQWDWR APPDGGFWEWGD |
| Antidiabetic | [22] | [39] | |||||||
| Larva of the Japanese rhinoceros beetle ( | Allomyrina dichotoma | ) | EIAQDFKTDL | In vivo model: HFD mouse model |
| In vitro model: 3T3-L1 cells |
| Anti-obesity, weight control | [20] | [37] | ||||
| Larva of the Japanese rhinoceros beetle ( | Allomyrina dichotoma | ) | AGLQFPVGR | In vivo model: HFD mouse model |
| Anti-obesity, weight control, hepatoprotective | [19] | [36] | ||||||
| Cotton leafworm ( | Spodoptera littoralis | ) | VF AVF |
In vivo model: SHR rat model |
| Anti-hypertensive | [30] | [53] | ||||||
| Egyptian cotton leafworm ( | Spodoptera littoralis | ) | SGD hydrolysate | In vivo model: Caenorhabditis elegans |
| Antioxidant | [28] | [49] | ||||||
| Cricket ( | Gryllodes sigillatus | ) | Cationic peptide fraction from sequential alcalase and SGD hydrolysates |
| Antidiabetic and anti-hypertension | [31] | [54] | |||||||
| Yellow mealworms ( | Tenebrio molitor | ) | RP-HPLC fraction of pepsin and trypsin hydrolysate |
| Antithrombotic | [32] | [55] | |||||||
| Mexican katydid ( | Pterophylla beltrani | ) | SGD hydrolysate |
| Anti-hypertension | [33] | [56] | |||||||
| <3 kDa fraction of SGD hydrolysate |
| Antidiabetic, Anti-hypertension, |
* All bioactivities were results obtained from in vitro models unless otherwise stated. AAPH: 2,2′-Azobis(2-amidinopropane) dihydrochloride, ABTS: 2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), ACE: Angiotensin-converting enzyme, COX: Cyclooxygenase, DPPH: 2,2-Diphenyl-1-picrylhydrazyl, DPP-IV: Dipeptidyl peptidase IV, GPx: Glutathione peroxidase, GR: Glucocorticoid receptor, HDL: High-density lipoprotein cholesterol, HFD: High-fat diet, LDL: Low-density lipoprotein cholesterol, LOX: Lipoxygenases, ORAC: Oxygen radical antioxidant capacity, SGD: Simulated gastrointestinal digestion, SHR: Spontaneously hypertensive rat, SOD: Superoxide dismutase, TC: Total cholesterol, TG: Triglycerides, VLDL: Very low-density lipoprotein cholesterol.
