Food-derived protein hydrolysates and peptides:anxiolytic and antidepressant activities,characteristics,and mechanisms

Globally,the prevalence of anxiety and depression has reached epidemic proportions.Food-derived protein hydrolysates and peptides delivered through dietary supplementation can avoid the negative risks associated with traditional pharmaceuticals while delivering superior anxiolytic and antidepressant effects.This review summarizes current research on food-derived anxiolytic and antidepressant protein hydrolysates and peptides,and subsequently analyses their physicochemical characteristics and elaborates on their mechanisms.The aim of this work is to contribute to the in-depth study and provide a theoretical foundation for the development of related products to better serve patients with anxiety and depression.

Exploration of cyclooxygenase-2 inhibitory peptides from walnut dreg proteins based on in silico and in vitro analysis

Walnut dreg protein hydrolysates(WDPHs)exhibit a variety of biological activities,however,the cyclooxygenase-2(COX-2)inhibitory peptide of WDPHs remain unclear.The aim of this study was to rapidly screen for such peptides in WDPHs through a combination of in silico and in vitro analysis.In total,1262 peptide sequences were observed by nano liquid chromatography/tandem mass spectrometry(nano LC-MS/MS)and 4 novel COX-2 inhibitory peptides(AGFP,FPGA,LFPD,and VGFP)were identified.Enzyme kinetic data indicated that AGFP,FPGA,and LFPD displayed mixed-type COX-2 inhibition,whereas VGFP was a non-competitive inhibitor.This is mainly because the peptides form hydrogen bonds and hydrophobic interactions with residues in the COX-2 active site.These results demonstrate that computer analysis combined with in vitro evaluation allows for rapid screening of COX-2 inhibitory peptides in walnut protein dregs.

Effect of high-protein peptide-based formula compared with isocaloric isonitrogenous polymeric formula in critically ill surgical patient

BACKGROUND Malnutrition is common in critically ill patients,and it is associated with an increased risk of complications.Early enteral nutrition with adequate caloric and protein intake is critical nevertheless it is difficult to achieve.Peptide-based formulas have been shown to be beneficial in patients with feeding intolerance.However,there are limited studies showing the efficacy and safety of high-protein peptide-based formula in critically ill surgical patients.AIM To determine the effects of a high-protein peptide formulation on gastrointestinal tolerance,nutritional status,biochemical changes,and adverse events in patients in the surgery intensive care unit(SICU)compared to an isocaloric isonitrogenous standard polymeric formulation.METHODS This study was a multi-center double-blind,randomized controlled trial.We enrolled adult patients in the surgical intensive care unit,age≥15 years and expected to receive enteral feeding for at least 5-14 d post-operation.They were randomly assigned to receive either the high-protein peptide-based formula or the isocaloric isonitrogenous standard formula for 14 d.Gastric residual volume(GRV),nutritional status,body composition and biochemical parameters were assessed at baseline and on days 3,5,7,9,11,and 14.RESULTS A total of 19 patients were enrolled,9 patients in the peptide-based formula group and 10 patients in the standard formula group.During the study period,there were no differences of the average GRV,body weight,body composition,nutritional status and biochemical parameters in the patients receiving peptide-based formula,compared to the standard regimen.However,participants in the standard formula lost their body weight,body mass index(BMI)and skeletal muscle mass significantly.While body weight,BMI and muscle mass were maintained in the peptide-based formula,from baseline to day 14.Moreover,the participants in the peptide-based formula tended to reach their caloric target faster than the standard formula.CONCLUSION The study emphasizes the importance of early nutritional support in the SICU and showed the efficacy and safety of a high-protein,peptide-based formula in meeting caloric and protein intake targets while maintaining body weight and muscle mass.

A matrix metalloproteinase-responsive hydrogel system controls angiogenic peptide release for repair of cerebral ischemia/reperfusion injury

Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.

Novel umami peptides from two Termitomyces mushrooms and molecular docking to the taste receptor T1R1/T1R3

Wild edible Termitomyces mushrooms are popular in Southwest China and umami is important flavor qualities of edible mushrooms.This study aimed to understand the umami taste of Termitomyces intermedius and Termitomyces aff.bulborhizus.Ten umami peptides from aqueous extracts were separated using a Sephadex G-15 gel filtration chromatography.The intense umami fraction was evaluated by both sensory evaluation and electronic tongue.They were identified as KLNDAQAPK,DSTDEKFLR,VGKGAHLSGEH,MLKKKKLA,SLGFGGPPGY,TVATFSSSTKPDD,AMDDDEADLLLLAM,VEDEDEKPKEK,SPEEKKEEET and PEGADKPNK.Seven peptides,except VEDEDEKPKEK,SPEEKKEEET and PEGADKPNK were selectively synthesized to verify their taste characteristics.All these 10 peptides had umami or salt taste.The 10 peptides were conducted by molecular docking to study their interaction with identified peptides and the umami taste receptor T1R1/T1R3.All these 10 peptides perfectly docked the active residues in the T1R3 subunit.Our results provide theoretical basis for the umami taste and address the umami mechanism of two wild edible Termitomyces mushrooms.

Three novel umami peptides derived from the alcohol extract of the Pacific oyster(Crassostrea gigas):identification,characterizations and interactions with T1R1/T1R3 taste receptors

Oyster(Crassostrea gigas),the main ingredient of oyster sauce,has a strong umami taste.In this study,three potential umami peptides,FLNQDEEAR(FR-9),FNKEE(FE-5),and EEFLK(EK-5),were identified and screened from the alcoholic extracts of the oyster using nano-HPLC-MS/MS analysis,i Umami-Scoring Card Method(i Umami-SCM)database and molecular docking(MD).Sensory evaluation and electronic tongue analysis were further used to confirm their tastes.The threshold of the three peptides ranged from 0.38 to 0.55 mg/m L.MD with umami receptors T1R1/T1R3 indicated that the electrostatic interaction and hydrogen bond interaction were the main forces involved.Besides,the Phe592 and Gln853 of T1R3 were the primary docking site for MD and played an important role in umami intensity.Peptides with two Glu residues at the terminus had stronger umami,especially at the C-terminus.These results contribute to the understanding of umami peptides in oysters and the interaction mechanism between umami peptides and umami receptors.

Calcium-chelating peptides from rabbit bone collagen:characterization,identification and mechanism elucidation

This study aimed to characterize and identify calcium-chelating peptides from rabbit bone collagen and explore the underlying chelating mechanism.Collagen peptides and calcium were extracted from rabbit bone by instant ejection steam explosion(ICSE)combined with enzymatic hydrolysis,followed by chelation reaction to prepare rabbit bone peptide-calcium chelate(RBCP-Ca).The chelating sites were further analyzed by liquid chromatography-tandem mass(LC-MS/MS)spectrometry while the chelating mechanism and binding modes were investigated.The structural characterization revealed that RBCP successfully chelated with calcium ions.Furthermore,LC-MS/MS analysis indicated that the binding sites included both acidic amino acids(Asp and Glu)and basic amino acids(Lys and Arg),Interestingly,three binding modes,namely Inter-Linking,Loop-Linking and Mono-Linking were for the first time found,while Inter-Linking mode accounted for the highest proportion(75.1%),suggesting that chelation of calcium ions frequently occurred between two peptides.Overall,this study provides a theoretical basis for the elucidation of chelation mechanism of calcium-chelating peptides.

Andrias davidianus bone peptides alleviates hyperuricemia-induced kidney damage in vitro and in vivo

Hyperuricemia(HUA)is a vital risk factor for chronic kidney diseases(CKD)and development of functional foods capable of protecting CKD is of importance.This paper aimed to explore the amelioration effects and mechanism of Andrias davidianus bone peptides(ADBP)on HUA-induced kidney damage.In the present study,we generated the standard ADBP which contained high hydrophobic amino acid and low molecular peptide contents.In vitro results found that ADBP protected uric acid(UA)-induced HK-2 cells from damage by modulating urate transporters and antioxidant defense.In vivo results indicated that ADBP effectively ameliorated renal injury in HUA-induced CKD mice,evidenced by a remarkable decrease in serum UA,creatinine and blood urea nitrogen,improving kidney UA excretion,antioxidant defense and histological kidney deterioration.Metabolomic analysis highlighted 14 metabolites that could be selected as potential biomarkers and attributed to the amelioration effects of ADBP on CKD mice kidney dysfunction.Intriguingly,ADBP restored the gut microbiome homeostasis in CKD mice,especially with respect to the elevated helpful microbial abundance,and the decreased harmful bacterial abundance.This study demonstrated that ADBP displayed great nephroprotective effects,and has great promise as a food or functional food ingredient for the prevention and treatment of HUA-induced CKD.

Glucagon-like peptide 1 agonists are potentially useful drugs for treating metabolic dysfunction-associated steatotic liver disease

In this editorial,we comment on Yin et al’s recently published Letter to the editor.In particular,we focus on the potential use of glucagon-like peptide 1 receptor agonists(GLP-1RAs)alone,but even more so in combination therapy,as one of the most promising therapies in metabolic dysfunction-associated steatotic liver disease(MASLD),the new definition of an old condition,non-alcoholic fatty liver disease,which aims to better define the spectrum of steatotic pathology.It is well known that GLP-1RAs,having shown outstanding performance in fat loss,weight loss,and improvement of insulin resistance,could play a role in protecting the liver from progressive damage.Several clinical trials have shown that,among GLP-1RAs,semaglutide is a safe,well-studied therapeutic choice for MASLD patients;however,most studies demonstrate that,while semaglutide can reduce steatosis,including steatohepatitis histological signs(in terms of inflammatory cell infiltration and hepatocyte ballooning),it does not improve fibrosis.Combinations of therapies with different but complementary mechanisms of action are considered the best way to improve efficiency and slow disease progression due to the complex pathophysiology of the disease.In particular,GLP-1RAs associated with antifibrotic drug therapy,dual glucose-dependent insulinotropic polypeptide(GIP)/GLP-1RA or GLP-1 and glucagon RAs have promoted greater improvement in hepatic steatosis,liver biochemistry,and non-invasive fibrosis tests than monotherapy.Therefore,although to date there are no definitive indications from international drug agencies,there is the hope that soon the therapeutic lines in the most advanced phase of study will be able to provide a therapy for MASLD,one that will certainly include the use of GLP-1RAs as combination therapy.

Neutrophil peptide 1 accelerates the clearance of degenerative axons during Wallerian degeneration by activating macrophages after peripheral nerve crush injury

Macrophages play an important role in peripheral nerve regeneration,but the specific mechanism of regeneration is still unclear.Our preliminary findings indicated that neutrophil peptide 1 is an innate immune peptide closely involved in peripheral nerve regeneration.However,the mechanism by which neutrophil peptide 1 enhances nerve regeneration remains unclear.This study was designed to investigate the relationship between neutrophil peptide 1 and macrophages in vivo and in vitro in peripheral nerve crush injury.The functions of RAW 264.7 cells we re elucidated by Cell Counting Kit-8 assay,flow cytometry,migration assays,phagocytosis assays,immunohistochemistry and enzyme-linked immunosorbent assay.Axonal debris phagocytosis was observed using the CUBIC(Clear,Unobstructed Brain/Body Imaging Cocktails and Computational analysis)optical clearing technique during Wallerian degeneration.Macrophage inflammatory factor expression in different polarization states was detected using a protein chip.The results showed that neutrophil peptide 1 promoted the prolife ration,migration and phagocytosis of macrophages,and CD206 expression on the surfa ce of macrophages,indicating M2 polarization.The axonal debris clearance rate during Wallerian degeneration was enhanced after neutrophil peptide 1 intervention.Neutrophil peptide 1 also downregulated inflammatory factors interleukin-1α,-6,-12,and tumor necrosis factor-αin invo and in vitro.Thus,the results suggest that neutrophil peptide 1 activates macrophages and accelerates Wallerian degeneration,which may be one mechanism by which neutrophil peptide 1 enhances peripheral nerve regeneration.

Anti-skin aging effects and bioavailability of collagen tripeptide and elastin peptide formulations in young and middle-aged women

Background:Collagen peptides(CP),including tripeptides and elastin peptides(EP),are known for their in vitro and in vivo anti-skin aging effects.Despite positive results in animal models,the combination effects of CP and EP and the bioavailability of CP in human studies,particularly in young and middle-aged women,remain underexplored.Objective:To evaluate the effects of an orally administered collagen drink combining CP and EP on the skin health of young and middle-aged women.Materials and Methods:A single-center,randomized,double-blind,parallel-controlled trial was conducted,utilizing the WONDERLABR fish collagen tripeptide beverage.Participants consumed the drink over an 8-week period.Results:Compared to the placebo group,the collagen drink group showed significant improvements in skin hydration(39.19%increase),transepidermal water loss(33.45%decrease),skin elasticity(25.37%increase),dermal collagen content(21.64%increase),pore size(7.94%decrease),wrinkle length(18.09%decrease),skin smoothness(2.85%improvement),and skin roughness(15.32%decrease).Overall pore volume decreased by 60%,and visual assessments indicated a decrease in skin luminosity by 15.20%and smoothness index by 22.55%.Mass spectrometry demonstrated a significant increase in collagen efficacy components,including blood pH and GPH levels(P<0.05).Conclusion:The study confirmed the combination nourishing and anti-skin aging effects of EP and CP on the skin of young and middle-aged women,demonstrating significant improvements in various skin parameters and good bioavailability of collagen peptides.

Engineering and preliminary evaluation of multiple non-equilibrium nanostructures from a single peptide amphiphile

Compared with thermodynamically equilibrium supramolecular assemblies, non-equilibrium assemblies from the same building blocks have attracted increasing attentions because their diverse structures and dynamic natures may impart the assemblies with novel functionalities. However, facile access to non-equilibrium assemblies remains a formidable challenge. Herein, we endeavored to exploit various solvent-anti-solvent methods to achieve it using peptide amphiphile C16-VVAAEE-NH_(2) as a model. Through systematical utilization of dialysis, ultrasonic and stirring-dropping methods, as well as tuning of processing parameters, we demonstrated the successful formation of diverse non-equilibrium nanostructures with distinct morphologies and structures that significantly deviate from the thermodynamically favored twisted long ribbons. Additionally, these metastable nanostructures ultimately underwent spontaneous transformation into thermodynamically stable states. The transformation processes of three representative non-equilibrium assemblies were also demonstrated and characterized in detail using transmission electron microscopy, circular dichroism spectrum, and thioflavin T fluorescence spectrum. Furthermore, non-equilibrium assemblies exhibited various degrees of cytotoxic effects, which may stem from their spontaneous, dynamic transformation and interactions with cellular membranes. This study offers valuable approaches for direct access to diverse non-equilibrium supramolecular nanostructures from self-assembling peptide, and also has implications for the development of advanced materials with unprecedented biological functions.

Toward Artificial Peptide Nanocapsules

HIGHLIGHTS The formation of peptide nanocapsules is facilitated by a gradient interface,where the differential solvent concentration drives the peptides to preferentially localize and assemble.The peptide nanocapsules,characterized by their hollow structures,demonstrated potential as carriers for targeted drug delivery.1 Introduction Peptide nanocapsules are a type of nanoscale delivery system that encapsulates active substances within a shell composed of peptides,leveraging the unique properties of peptides such as biocompatibility and biodegradability[1].Historically,the development of peptide nanocapsules was inspired primordially by the natural biological processes.

MiR-107-3p/Atp6v0e1 contributes to protective effects of two selenium-containing peptides,TSeMMM and SeMDPGQQ on lead-induced neurotoxicity

Two selenium(Se)-containing peptides from Se-enriched rice,TSeMMM and SeMDPGQQ,possess neuroprotective potency against lead(Pb2+)-induced cytotoxicity.However,the crosstalk between mRNA and microRNAs(miRNA)involved in the neuroprotection mechanism remains to be elucidated.In this study,RNA-sequencing and miRNA-sequencing were used to independently identify differentially expressed mRNAs and small RNAs profiles in Pb^(2+)-treated primary fetal rat cortical neurons and then the correlated miRNA-mRNA target pairs were obtained.It was found that 34 mRNAs related to oxidative phosphorylation could be reversed by pretreatment of TSeMMM and SeMDPGQQ.The protective effect of TSeMMM and SeMDPGQQ was mediated by upregulation of miR-107-3p,which downregulates the ATPase H+transporting V0 subunit e1(Atp6v0e1)mRNA level.A zebrafish model was applied to verify the relevance between the targeted mRNA and miRNA by real-time quantitative PCR.The results indicated that miR-107-3p was a potential therapeutic target to achieve neuroprotection of Se-containing peptides via stimulation of Atp6v0e1.

Food-derived bio-functional peptides for the management of hyperuricemia and associated mechanism

Hyperuricemia,a metabolic disorder related to uric acid metabolism dysregulation,has become a common metabolic disease worldwide,due to changes in lifestyle and dietary structure.In recent years,owing to their high activity and few adverse effects,food-derived active peptides used as functional foods against hyperuricemia have attracted increasing attention.This article aims to focus on the challenge associated with peptide-specific preparation methods development,functional components identification,action mechanism(s)clarification,and bioavailability improvement.The current review proposed recent advances in producing the food-derived peptides with high anti-hyperuricemia activity by protein source screening and matched enzymatic hydrolysis condition adjusting,increased the knowledge about strategies to search antihyperuricemia peptides with definite structure,and emphasized the necessity of combining computer-aided approaches and activity evaluations.In addition,novel action mechanism mediated by gut microbiota was discussed,providing different insights from classical mechanism.Moreover,considering that little attention was paid previously on the structure-activity relationships of anti-hyperuricemia peptides,we collected the sequences from published studies and make a preliminary summary about the structure-activity relationships,which in turn provided guides for enzymatic hydrolysis optimization and bioavailability improvement.Hopefully,this article could promote the development,application and commercialization of food-derived anti-hyperuricemia peptides in the future.

Glucagon-like peptide 1 receptor activation:anti-inflammatory effects in the brain

The glucagon-like peptide 1 is a pleiotropic hormone that has potent insulinotropic effects and is key in treating metabolic diseases such as diabetes and obesity.Glucagon-like peptide 1 exerts its effects by activating a membrane receptor identified in many tissues,including diffe rent brain regions.Glucagon-like peptide 1 activates several signaling pathways related to neuroprotection,like the support of cell growth/survival,enhancement promotion of synapse formation,autophagy,and inhibition of the secretion of proinflammatory cytokines,microglial activation,and apoptosis during neural morphogenesis.The glial cells,including astrocytes and microglia,maintain metabolic homeostasis and defe nse against pathogens in the central nervous system.After brain insult,microglia are the first cells to respond,followed by reactive astrocytosis.These activated cells produce proinflammato ry mediators like cytokines or chemokines to react to the insult.Furthermore,under these circumstances,mic roglia can become chro nically inflammatory by losing their homeostatic molecular signature and,consequently,their functions during many diseases.Several processes promote the development of neurological disorders and influence their pathological evolution:like the formation of protein aggregates,the accumulation of abnormally modified cellular constituents,the formation and release by injured neurons or synapses of molecules that can dampen neural function,and,of critical impo rtance,the dysregulation of inflammato ry control mechanisms.The glucagonlike peptide 1 receptor agonist emerges as a critical tool in treating brain-related inflammatory pathologies,restoring brain cell homeostasis under inflammatory conditions,modulating mic roglia activity,and decreasing the inflammato ry response.This review summarizes recent advances linked to the anti-inflammato ry prope rties of glucagon-like peptide 1 receptor activation in the brain related to multiple sclerosis,Alzheimer’s disease,Parkinson’s disease,vascular dementia,or chronic migraine.

Enhanced extracellular production of alpha-lactalbumin from Bacillus subtilis through signal peptide and promoter screening

Alpha-lactalbumin(α-LA)is a major whey protein found in breast milk and plays a crucial role in the growth and development of infants.In this study,Bacillus subtilis RIK1285 harboring AprE signal peptide(SP)was selected as the original strain for the production ofα-LA.It was found thatα-LA was identified in the pellet after ultrasonic disruption and centrifugation instead of in the fermentation supernatant.The original strain most likely only producedα-LA intracellular,but not extracellular.To improve the expression and secretion ofα-LA in RIK1285,a library of 173 homologous SPs from the B.subtilis 168 genome was fused with target LALBA gene in the pBE-S vector and expressed extracellularly in RIK1285.SP YjcN was determined to be the best signal peptide.Bands in supernatant were observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and purified by nickel column to calculate the highest yield signal peptide.In addition,different promoters(P_(aprE),P_(43),and P_(glv))were compared and applied.The results indicated that the strain RIK1285-pBE-P_(glv)-YjcN-LALBA had the highestα-LA yield,reaching 122.04μg/mL.This study demonstrates successful expression and secretion of humanα-LA in B.subtilis and establishes a foundation for simulating breast milk for infant formulas and developing bioengineered milk.

A plausible pathway to prebiotic peptides via amino acid amides on the primordial Earth

The prebiotic synthesis of peptides prior to ribosome-catalyzed processes remains an enigma.The synthesis of abiotic peptides from amino acids(AAs)is primarily constrained by high activation energies and unfavorable thermodynamics,necessitating the identification of plausible prebiotic alternatives for synthesizing prebiotic peptides.Here we present a plausible pathway to the formation of prebiotic peptides,wherein oligopeptides,oligopeptide amides,and cyclic oligopeptides can be directly synthesized from amino acid amides(AA-NH2)under wet–dry cycle conditions without the need for any enhancers.The subsequent investigation revealed that AA-NH2 demonstrated more favorable thermodynamic reaction effects than AAs in peptide formation.In contrast to the polymerization of AAs,the process of peptide formation through the polymerization of AA-NH2 was significantly simplified.Additionally,AA-NH2 was discovered to function as a“bridge”for the formation of peptides from AAs,thereby facilitating their participation in the synthesis of intricate peptide structures.On the basis of these findings,a plausible mechanism for the prebiotic origin network of peptides under primordial Earth conditions has been proposed.Overall,this research presents a plausible pathway for the generation of prebiotic peptides and peptide libraries within prebiotic environments.

The MtRGF6 Peptide Differentially Regulates Root Development and Symbiotic Nodulation of Medicago truncatula and Lotus japonicus

Rhizobia induces nitrogen-fixing nodules in legumes used in agricultural production,providing a direct source of combined nitrogen to leguminous crops.Small peptides,such as CLAVATA3/EMBRYO SURROUNDING REGION peptides(CLE),are known to regulate the formation and development of nitrogen-fixing nodules in legumes.Root meristem growth factor(RGF)peptides from Medicago truncatula not only regulate root develop-ment but also modulate nodulation symbiosis with Sinorhizobium meliloti.However,the impact of RGF peptides from one leguminous species on the others remains unclear.In this study,we investigate the effects of the RGF family peptide MtRGF6p from M.truncatula on nodulation symbiosis and root development in Lotus japonicus.The MtRGF6 gene is predominantly expressed in the root nodules of M.truncatula and shows low identity with RGF homologous genes from L.japonicus.The gene promoter is active in the primordia of root nodules and lat-eral roots,as well as in young nodules and roots,and the meristem,infection,and nitrogen-fixing regions of the mature nodule.Chemically synthesized MtRGF6p promoted primary root growth in M.truncatula but sup-pressed the growth of L.japonicus primary roots.The peptide negatively affected the initiation of nodule primor-dia,the formation of infection threads,and nodulation in both legumes,with a low dosage showing effects on L.japonicus compared to M.truncatula.These results suggest that the MtRGF6 peptide from M.truncatula may serve as an inter-species signal affecting the root organ development of L.japonicus.

Cath-KP,a novel peptide derived from frog skin,prevents oxidative stress damage in a Parkinson’s disease model

Parkinson’s disease(PD)is a neurodegenerative condition that results in dyskinesia,with oxidative stress playing a pivotal role in its progression.Antioxidant peptides may thus present therapeutic potential for PD.In this study,a novel cathelicidin peptide(Cath-KP;GCSGRFCNLF NNRRPGRLTLIHRPGGDKRTSTGLIYV)was identified from the skin of the Asiatic painted frog(Kaloula pulchra).Structural analysis using circular dichroism and homology modeling revealed a uniqueαββconformation for Cath-KP.In vitro experiments,including free radical scavenging and ferric-reducing antioxidant analyses,confirmed its antioxidant properties.Using the 1-methyl-4-phenylpyridinium ion(MPP^(+))-induced dopamine cell line and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced PD mice,Cath-KP was found to penetrate cells and reach deep brain tissues,resulting in improved MPP^(+)-induced cell viability and reduced oxidative stress-induced damage by promoting antioxidant enzyme expression and alleviating mitochondrial and intracellular reactive oxygen species accumulation through Sirtuin-1(Sirt1)/Nuclear factor erythroid 2-related factor 2(Nrf2)pathway activation.Both focal adhesion kinase(FAK)and p38 were also identified as regulatory elements.In the MPTP-induced PD mice,Cath-KP administration increased the number of tyrosine hydroxylase(TH)-positive neurons,restored TH content,and ameliorated dyskinesia.To the best of our knowledge,this study is the first to report on a cathelicidin peptide demonstrating potent antioxidant and neuroprotective properties in a PD model by targeting oxidative stress.These findings expand the known functions of cathelicidins,and hold promise for the development of therapeutic agents for PD.