ABSTRACT:Metabolic reprogramming alters the processes by which tumor cells generate energy and synthesize products, affecting their growth and survival. It also reshapes the tumor microenvironment by influencing immune cell function and interaction. Current literature suggests that the metabolic characteristics of gastric malignancies are closely associated with tumor immune evasion and inflammatory responses, thereby influencing immune cell infiltration, tumor progression, and patient prognosis. Despite some progress, research on metabolic reprogramming in gastric cancer (GC) is challenging, particularly in understanding the specific mechanisms involved and their clinical applications. This review aims to comprehensively explore the mechanisms of metabolic reprogramming in GC and analyze its impact on the tumor immune microenvironment. We also propose potential metabolic-immune therapeutic strategies, such as glutaminase inhibitors, lactate transport blockers, and immune checkpoint therapy combined with metabolic regulators, providing new ideas and directions for immunotherapy in GC.

Agriculture is at the pivot point between anthroposphere, biosphere, and atmosphere. Innovative solutions are needed to reduce agricultural emissions and improve sustainability. Microalgae animal feed could be such a solution. This study aimed to evaluate the effects of 10 freshwater microalgae: Auxenochlorella protothecoides, Chlamydomonas pulvinate, Chlorella luteoviridis, Chlorella variabilis, Euglena mutabilis, Parachlorella kessleri, Stichococcus bacillaris, Tetradesmus acuminatus, Tetradesmus obliquus, and Tetraselmis gracilis, on ruminal methane (CH4) production, nutrient digestibility, and rumen fermentation using the in vitro Hohenheim gas test. The microalgae were cultured in a carbon dioxide (CO2) incubator at 2% CO2, at the optimal conditions for each strain. The highest producers were P. kessleri and T. obliquus, with a biomass concentration of 0.69 and 0.73 g/L·d, respectively. Their PUFA contents ranged from 33.2% to 69.1% of total fatty acids. Microalgae were tested at a 15% replacement in a control basal diet of 40.0% DM grass silage, 40.0% maize silage, 15% hay, and 5% concentrate. Data were analyzed using a mixed model in R. Ruminal CH4 production was reduced by 15.4%, 17.4%, and 16.4% in diets containing A. protothecoides, C. luteoviridis, and P. kessleri, respectively, compared with the control diet. Similarly, these diets reduced in vitro organic matter digestibility by 3.5%, 5.2%, and 5.4%, respectively. However, only A. protothecoides reduced CH4/CO2 ratio by 3.5% compared with the control diet. Propionate molar proportion was decreased by 2.4, 3.0, 2.5, and 2.5 percentage points for diets containing Ch. pulvinate, E. mutabilis, P. kessleri, and T. obliquus, respectively. Marginal effects of dietary variables were analyzed using the generalized additive model framework, revealing a negative relationship between dietary PUFA, sulfur content, and CH4 production, and a negative relationship between dietary PUFA and CH4/CO2 ratio. Incorporating high-PUFA microalgae in ruminant diets shows potential for reducing enteric CH4 emissions, warranting further investigation.

Enteric methane (CH4), the major contributor to on-farm greenhouse gas emissions, is a key mitigation target due to its high short-term global warming potential. The objectives of this study were to investigate the combined effects of 3-nitrooxypropanol (3-NOP) and Acacia mearnsii tannin extract (TAN), and their interactions with dairy cattle breed [Brown Swiss (BS) vs Holstein Friesian (HF)] on lactational performance and CH4 emissions. Sixteen multiparous mid-lactation cows, including 8 BS and 8 HF cows, were used in a split-plot design, with breed as the main plot. Cows within each subplot were arranged in a replicated 4 × 4 Latin Square design with a 2 × 2 factorial arrangement of treatments across four 24-d periods, including 3-d of sampling. The experimental diets were: (1) CON (basal total mixed ration), (2) 3-NOP (60 mg/kg DM), (3) TAN (3% of DM), and (4) 3-NOP + TAN. Spot samples of urine, faeces, and gas emissions (via GreenFeed) were collected at the end of each period 8 times over 3 days. No 3-NOP × TAN × Breed interactions were observed for DM intake (DMI), milk production, or enteric gas emissions, except for CH4 yield (g/kg DMI) and CO2 production. Breed influenced DMI, milk production, and component yields, with HF cows consuming 3.7 kg/d more DMI, producing 9.3 kg/d more milk, and achieving greater feed efficiency and higher milk component yields than BS cows. Milk yield and energy-corrected milk (ECM) tended to increase in HF but tended to decrease in BS cows by 3-NOP. Cows fed TAN had 1 kg/d lower DMI with the tendency for 3-NOP × TAN that showed greater reduction when TAN was fed alone, but milk yield, ECM, and feed efficiency remained unchanged. Cows fed TAN exhibited 18% lower milk urea nitrogen (N) concentration and 23.0% lower urinary N but 36.7% greater faecal N excretions as a percentage of daily N intake. A 3-NOP × Breed interaction was observed in CH4 production (g/d), with a 21.7% reduction in HF, and a 13.0% reduction in BS. Similarly, there were 3-NOP × Breed tendencies in CH4 yield and intensity (g/kg ECM), with reductions in HF cows of 21.8 and 23.4%, respectively, compared to 11.0 and 10.8% in BS cows. In conclusion, there were no synergistic or additive effects between 3-NOP and TAN on enteric CH4 mitigation. The enteric CH4 emission mitigating effect of 3-NOP was more pronounced in HF cows than in BS cows. Further research is needed to understand breed-specific responses and to optimise CH4 mitigation strategies for inclusion in national greenhouse gas inventories.

Guiren Runchang Granules (GRG), a traditional Chinese medicine (TCM) formulation, has demonstrated effectiveness in treating slow transit constipation (STC). This study investigated the therapeutic effects of GRG on constipated mice, focusing on its role in restoring intestinal micro-ecology. The results showed that GRG treatment significantly improved defecation in STC mice and ameliorated intestinal histopathological damage. GRG effectively normalized colonic and serum motility-related hormone levels (5-HT, SP, MTL, and SS) with comparable efficacy to mosapride, a prokinetic agent. In addition, GRG treatment restored the balance of the gut microbiota and increased the levels of short-chain fatty acids (SCFAs). Specifically, the relative abundance of the genera Alloprevotella and Muribaculum increased, while that of Prevotellaceae_NK3B31_group, Ruminococcus, and Lachnospiraceae_UCG-001 decreased. These microbiota changes were significantly correlated with SCFAs level, motility-related hormone concentrations, and defecation phenotype. Our findings highlight GRG’s multi-target mode of action involving microbiota modulation, SCFAs restoration, and hormonal regulation, positioning it as a promising alternative to conventional therapies for STC.

The gut microbiota has emerged as a pivotal regulator of host lipid metabolism and energy homeostasis. A growing body of evidence reveals that variations in the composition and metabolic activity of intestinal microbes are closely associated with differences in adipose tissue deposition across species. Notably, increased abundance of Firmicutes and a reduced proportion of Bacteroidetes and butyrate-producing bacteria have been linked to enhanced fat accumulation. Key microbial metabolites such as short-chain fatty acids (SCFAs) influence lipid metabolism through multiple pathways, including the activation of GPR41/43 receptors, modulation of the bile acid–FXR/TGR5 axis, and regulation of hepatic lipogenesis. Additionally, the gut–brain axis plays a critical role in controlling feeding behavior via neuroendocrine signaling. This review summarizes current advances in understanding the roles of dominant bacterial phyla and beneficial genera—including Clostridium butyricum and Faecalibacterium prausnitzii —in fat metabolism. We further explore the mechanisms by which gut microbiota modulate lipid synthesis and catabolism through SCFA production, bile acid signaling, and AMPK/PPAR-related pathways. These insights highlight the potential of microbiota-targeted strategies to restore lipid metabolic balance, offering novel opportunities for applications in health management, nutritional interventions, and microbial therapeutics. Graphical Abstract

Helicobacter pylori (H. pylori) is a major pathogen implicated in chronic gastritis, peptic ulcers, and gastric cancer. The increasing prevalence of antibiotic resistance and biofilm-associated persistence necessitates alternative therapies. This study aimed to investigate the inhibitory effect of fucoidan (Fuc) from sea cucumber cooking liquid (Fuc-SC) on H. pylori. Fuc-SC, with a molecular weight of 6.75 kDa, comprises 65.94 % fucose and 31.69 % sulfate group. Structural analysis revealed that Fuc-SC was a branched sulfate fucoidan with a backbone of →3)-α-L-Fucp-(1 → 4)-α-L-Fucp-(1→, featuring sulfate groups at C-4 of →3)-α-L-Fucp-(1→ and C-2 or C-3 of →4)-α-L-Fucp-(1→, alongside branches containing fucose, galactose, and glucose. The rare sulfation and branching pattern broaden the structural diversity of Fuc from sea cucumber. AFM analysis revealed that Fuc-SC exhibits an irregular linear chain conformation, while SEM analysis showed a porous sheet structure. The average particle size of Fuc-SC was 36.5 μm, demonstrating outstanding thermal stability within the temperature range of 30-200 °C. Viscosity analysis indicated that the viscosity of Fuc-SC increased with mass concentration and decreased with temperature, displaying shear-thinning behavior typical of hydrocolloids. In vitro antioxidant activity revealed that Fuc-SC exhibited stronger ABTS and DPPH radical scavenging capacities and a higher total antioxidant capacity compared to Laminaria japonica-derived fucoidan (Fuc-LJ). Additionally, Fuc-SC demonstrated a significant inhibition zone against H. pylori Sydney strain 1 (Hp SS1). Notably, Fuc-LJ and desulfurized Fuc-SC did not exhibit a bacteriostatic ring. Fuc-SC also decreased Hp SS1 adhesion by inhibiting urease activity. Furthermore, it protected GES-1 cells from ROS-induced mitochondrial damage and apoptosis by disrupting bacterial structure and inhibiting biofilm formation. The findings highlight its potential for development as a dietary supplement and specialty medical food for the treatment of H. pylori gastrointestinal diseases.

The gastrointestinal bacterial microbiota is essential for maintaining the health of dairy cows and ensuring their production potential, and it may also help explain the breed-related phenotypic differences. Therefore, investigating the differences in gastrointestinal bacterial microbiota between breeds is critical for deciphering the mechanisms behind these differences and exploring the potential for improving milk production by regulating the gastrointestinal bacterial microbiota. This study holistically examined the differences between rumen and hindgut bacterial microbiota in a large cohort of two breeds of dairy cows, comprising 184 Jersey cows and 165 Holstein cows. Significant distinctions were identified between the rumen and hindgut bacterial microbiota of dairy cows, with these differences being consistent across breeds. A total of 20 breed-differentiated microorganisms, comprising 14 rumen microorganisms and 6 hindgut microorganisms, were screened, which may be the primary drivers of the observed differences in lactation performance between Jersey and Holstein cows. The present study revealed the spatial heterogeneity of the gastrointestinal bacterial microbiota of Jersey and Holstein cows and identified microbial biomarkers of different breeds. These findings enhance our understanding of the differences in the gastrointestinal bacterial microbiota between Jersey and Holstein cows and may provide useful information for optimizing the composition of the intestinal bacterial microbiota of the two breeds of dairy cows.

Mycosporine-like amino acids (MAAs) are gaining attention for their UV photoprotective properties and potential applications in biomedical fields, cosmetics, and toiletries. In this study, Nostoc calcicola a genus of cyanobacteria distributed in freshwater were tested for MAA production. This organism was provided by the Freshwater Algae Culture Collection of the Institute of Hydrobiology, the Chinese Academy of Sciences. It was isolated and cultured in the laboratory, in 500 ml glass flasks containing 300 ml of liquid medium BG11 treated on UV-B light 0.1 Wm–2. At different time, cultures were exposed to UV-B light at intensity 0.1 W. m-1 to determine the Maximum PSII photochemical (Fv/Fm). MAAs were extracted using 100% HPLC grade methanol and separated through high-performance liquid chromatography and liquid chromatography/mass spectrometry. Based on liquid chromatography/mass spectrometry analysis, one MAA compound was identified as porphyra. Thus, UV-B treatment of Nostoc calcicola significantly enhanced the production of UV-absorbing mycosporine-like amino acids (MAAs). The content of porphyra could reach up to 8.5 mg/g dry weight in Nostoc calcicola under UV-B treatments for 2 days. The present cyanobacteria could be used for biotechnology research and the UV-absorbing compound porphyra may be of great value in the development of novel sunscreens.

This study aimed to investigate the physicochemical properties of soluble dietary fiber (SDF) and cellulose enriched in Saccharina japonica by-products and to evaluate their anti-colitis effects. The water-holding capacity (WHC), swelling capacity (SC), cation exchange capacity (CEC), and antioxidant properties of SDF were superior to cellulose. The Delta H of SDF and cellulose was 340.73 J/g and 134.56 J/g, and the average particle size of them was 43.858 mu m and 97.350 mu m. The viscosity of SDF was positively correlated with the content. SEM revealed that the microstructure of SDF was porous, whereas cellulose was folded. SDF contained seven monosaccharides such as mannuronic acid and mannose, while cellulose had a single glucose composition. It was also shown that both SDF and cellulose reversed the pathological process of colitis by inhibiting weight loss, preventing colon injury, balancing oxidative stress, and regulating the level of inflammation, with the optimal dose being 1.5 g/kg. The difference was that SDF inhibited the expression of NF- & kcy; B and TNF- alpha, while cellulose up-regulated the expression of PPAR- gamma and IL-10. Additionally, SDF could more positively control the expression of ZO-1, whereas cellulose was superior in improving the expression of Occludin. Interestingly, SDF could restore the structure of norank_f_Muribaculaceae and Lachnospiraceae_NK4A136_group to ameliorate ulcerative colitis (UC), whereas cellulose mainly regulated the abundance of norank_f_Muribaculaceae , Faecalibaculum , Bacteroides and unclassified_f__Lachnospiraceae . The production of short-chain fatty acids (SCFAs) was also found to be restored by SDF and cellulose. Overall, SDF and cellulose can be considered important dietary components for treating and preventing UC.

Mycosporine-glycine (M-Gly), a member of the mycosporine-like amino acid (MAA) family, is known for its potent antioxidant and anti-inflammatory properties. However, its in vivo efficacy in alleviating acute skin photodamage, primarily caused by oxidative stress, has not been well explored. In this investigation, 30 female ICR mice were divided into four groups: a control group and three Ultraviolet B (UVB)-exposed groups treated with saline or M-Gly via intraperitoneal injection for 30 days. At the end of the experiment, UVB exposure caused erythema, wrinkling, collagen degradation, and mast cell infiltration in mouse dorsal skin. M-Gly treatment improved skin appearance and reduced mast cell numbers, while also elevating antioxidant levels, including superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). Furthermore, M-Gly reduced inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β, typically upregulated after UVB exposure. M-Gly also protected skin collagen by upregulating type I procollagen and decreasing MMP-1 levels. Skin metabolomic profiling identified 34 differentially abundant metabolites, and transcriptomic analysis revealed 752 differentially expressed genes. The combined metabolomic and transcriptomic data indicate that M-Gly’s protective effects may involve the regulation of ion transport, cellular repair, metabolic stability, collagen preservation, and the Nrf2/HO-1 pathway. These findings highlight M-Gly’s potential as an endogenous antioxidant for protecting skin from UVB-induced damage.

Indole-3-lactic acid (ILA) has exhibited antimicrobial properties. However, its role in inhibiting Helicobacter pylori infection remains elusive. This study investigated the inhibitory effect of ILA produced by Lacticaseibacillus paracasei on H. pylori, which was further confirmed by cell and animal experiments. 5 mg/mL ILA was sufficient to directly inhibit the growth of H. pylori in vitro, with a urease inhibitory activity reaching 60.94 +/- 1.03%, and the cell morphology and structure were destroyed. ILA inhibited 56.5% adhesion of H. pylori to GES-1 and significantly reduced the number of apoptotic cells. Furthermore, ILA suppresses H. pylori colonization by approximately 38% to 63%, reduced inflammation and oxidative stress in H. pylori-infected mice, and enhanced the enrichment and variety of gut microbiota, notably fostering the growth of beneficial bacteria such as Lactobacillus and Bifidobacterium strains. The results support that ILA derived from Lactobacillus can be applicated as a novel prebiotic in anti-H. pylori functional foods.

Our previous studies have highlighted the potential of silver carp hydrolysate (SCH) in managing chronic diseases. Unfortunately, its fishy smell and bitter taste limited consumer acceptance. Prebiotic oligosaccharides are often used as dietary supplements, ignoring their role as carbonyl ligands in the Maillard reaction to enhance food's sensory and antioxidant properties. This study aimed to improve SCH's sensory attributes and investigate its physicochemical properties and antioxidant activities using prebiotic oligosaccharides via the Maillard reaction. The results showed that xylo-oligosaccharide (XOS) had the highest reactivity among the oligosaccharides tested, and it greatly enhanced the taste and flavor of SCH, as well as its antioxidant activities (0.45 to 16.5 times). Specifically, XOS effectively reduced the fishy smell and bitter taste, imparting a caramel-like flavor and overall acceptability to SCH. The improved flavor profile was attributed to the increased presence of sulfur-containing and nitrogen oxide volatile flavor compounds, such as benzothiazole, methional, and furans, which also contributed to antioxidant effects. Sensory evaluation results indicated that SCH obtained from papain exhibited a stronger bitter taste than that obtained from alcalase. Additionally, XOS imparted a reddish-brown color to SCH due to the higher browning intensity. This study is the first to demonstrate that XOS in the Maillard reaction can effectively improve the undesirable flavor and taste of SCH while enhancing its antioxidant activities, providing a theoretical basis for developing SCH as a market-acceptable functional food ingredient. The sensory properties and antioxidant activities of SCH can be improved by using prebiotic oligosaccharides via the Maillard reaction, providing a theoretical basis for the development of new functional foods, and more possibilities for the sustainable development of the silver carp industry.

Novel angiotensin-converting enzyme (ACE) inhibitory peptides were identified from whey protein hydrolysates (WPH) in vitro in our previous study and the antihypertensive abilities of WPH in vivo were further investigated in the current study. Results indicated that WPH significantly inhibited the development of high blood pressure and tissue injuries caused by hypertension. WPH inhibited ACE activity (20.81%, P < 0.01), and reduced renin concentration (P < 0.05), thereby reducing systolic blood pressure (SBP) (12.63%, P < 0.05) in spontaneously hypertensive rats. The increased Akkermansia, Bacteroides, and Lactobacillus abundance promoted high short chain fatty acid content in feces after WPH intervention. These changes jointly contributed to low blood pressure. The heart weight and cardiomyocyte injuries (hypertrophy and degeneration) were alleviated by WPH. The proteomic results revealed that 19 protein expressions in the heart mainly associated with the wingless/integrated (Wnt) signaling pathway and Apelin signaling pathway were altered after WPH supplementation. Notably, WPH alleviated serum oxidative stress, indicated by the decreased malondialdehyde content (P < 0.01), enhanced total antioxidant capacity (P < 0.01) and superoxide dismutase activity (P < 0.01). The current study suggests that WPH exhibit promising antihypertensive abilities in vivo and could be a potential alternative for antihypertensive dietary supplements.

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Sacha inchi meal (SIM) is a by-product of sacha inchi (considered as a “super-food”) processing. In previous studies, we found that SIM protein hydrolysates exhibited pancreatic lipase inhibition activity. In this study, 10 bioactive peptides from those hydrolysates were identified. The top five peptides (NLYYKVV (NV-7), WWYVK (WK-5), WLLMWPYK (WK-8), EGLLMWPY (EY-8), and FPFFGYVWK (FK-9)) with strong pancreatic lipase inhibition activity had IC50 values of 34.01–246.50 µM, and displayed various inhibition types (mixed, non-competitive, and competitive type) by enzyme inhibition kinetics analysis. Fluorescence quenching analysis demonstrated that the interaction between the peptides and pancreatic lipase was mainly hydrogen bond and van der Waals force. The key residues involved in the peptide–enzyme interaction were determined by molecular docking. Moreover, the top two peptides were found to significantly inhibit fat accumulation and regulate lipid metabolism by alleviating the level of reactive oxygen species in HepG2 cells. Collectively, sacha inchi meal-derived peptides displayed potent lipid-lowering activity and could be used as materials of functional food.

Although it is well recognized that mycosporine-like amino acids (MAAs) are ultraviolet (UV) protective agents that can reduce UV damage, the specific biological mechanism of its role in the skin remains unclear. In this study, we investigated the effect of MAAs extracted from Antarctic diatom Phaeodactylum tricornutum ICE-H on UVB-induced skin damage using a mice model. The MAAs components identified by liquid chromatography-tandem mass spectrometry included 4-deoxygadusol, shinorine, and porphyra-334, which were purified using a Supledean Carboxen1000 solid phase extraction column. The antioxidant activities of these MAA compounds were tested in vitro. For UVB-induced skin photodamage in mice, MAAs alleviated skin swelling and epidermal thickening in this study. We detected the content of reactive oxygen species (ROS), malondialdehyde, and collagen in skin tissue. In addition, quantitative real-time polymerase chain reaction was used to detect nuclear factor-κB (NF-κB), tumor necrosis factor α, interleukin-1β, cyclooxygenase-2, mitogen activated protein kinase (MAPK) family (extracellular signal-regulated kinase, c-Jun amino-terminal kinase, and p38 kinase), and matrix metalloproteinases. The expression of these cytokines and enzymes is related to inflammatory responses and collagen degradation. In comparison to the model group without MAA treatment, the MAA component decreased the concentration of ROS, the degree of oxidative stress in the skin tissue, and the expression of genes involved in the NF-κB and MAPK pathways. In summary, these MAA components extracted from Phaeodactylum tricornutum ICE-H protected against UVB-induced skin damage by inhibiting ROS generation, relieving skin inflammation, and slowing down collagen degradation, suggesting that these MAA components are effective cosmetic candidate molecules for the protection and therapy of UVB damage.

κ-Selenocarrageenan (KSC) is an organic selenium (Se) polysaccharide. There has been no report of an enzyme that can degrade κ-selenocarrageenan to κ-selenocarrageenan oligosaccharides (KSCOs). This study explored an enzyme, κ-selenocarrageenase (SeCar), from deep-sea bacteria and produced heterologously in Escherichia coli, which degraded KSC to KSCOs. Chemical and spectroscopic analyses demonstrated that purified KSCOs in hydrolysates were composed mainly of selenium-galactobiose. Organic selenium foods through dietary supplementation could help regulate inflammatory bowel diseases (IBD). This study discussed the effects of KSCOs on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in C57BL/6 mice. The results showed that KSCOs alleviated the symptoms of UC and suppressed colonic inflammation by reducing the activity of myeloperoxidase (MPO) and regulating the unbalanced secretion of inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10). Furthermore, KSCOs treatment regulated the composition of gut microbiota, enriched the genera Bifidobacterium, Lachnospiraceae_NK4A136_group and Ruminococcus and inhibited Dubosiella, Turicibacter and Romboutsia. These findings proved that KSCOs obtained by enzymatic degradation could be utilized to prevent or treat UC.

In this study, experimental tests, together with computer analyses, were carried out to identify the essential nutritional markers that can offer protein supplementation-based nutrition support for hypertension. In particular, 16 marine shellfish proteins were firstly screened for in silico hydrolysis by gastrointestinal enzymes and then the binding abilities of the obtained oligopeptides to angiotensin-converting enzyme (ACE) were examined. In addition, the ACE inhibition activities of selected oligopeptides were assayed in vitro. It was discovered that mussel-derived NADH dehydrogenase and AMP-activated protein kinase and razor-clam-derived cytochrome b, NADH dehydrogenase, and ATP synthase were excellent sources of protein that are able to release a high amount of ACE-binding peptides. Meanwhile, four oligopeptides (SCCGY, SSGAW, PICQF, and IQPEW) were detected as strong ACE binders, with IC50 values of 0.09, 0.25, 0.41, and 0.60 mM, respectively. Therefore, our findings demonstrate that shellfish proteins can serve as nutritional support for hypertension when patients are supplemented with these markers. In particular, oligopeptides are identified as the most promising compounds.

BACKGROUNDSacha inchi meal (SIM) is a by-product of oil processing. Our previous studies showed that SIM hydrolysates exhibited dipeptidyl peptidase-IV (DPP-IV) inhibition activity. The objective of the present work was to identify and characterize the bioactive peptides from protein hydrolysates of SIM; enzyme kinetics and peptide-enzyme interaction were also investigated. RESULTSFrom SIM hydrolysates, ten peptides responsible for the activity were identified: GPSRGF (GF-6), FPILSPDPA (FA-9), APYRRGGKI (AI-9), WPYH (WH-4), DPATWLALPT (DT-10), NPEDEFRQQ (NQ-9), APESKPVGV (AV-9), LEWRDR (LR-6), APVYWVQ (AQ-7) and LLMWPY (LY-6). The IC50 values of five peptides (GF-6, WH-4, AQ-7, AV-9 and LY-6) with better inhibitory activity on DPP-IV were within the range of 23.43-128.40 mu mol L-1. AQ-7 had the best activity, with an IC50 value of 23.43 mu mol L-1. Enzyme kinetics indicated the presence of various inhibition types (mixed, non-competitive and competitive). Isothermal titration microcalorimetry showed that the main forces of the binding sites between peptide (GF-6 or AQ-7) and DPP-IV were hydrogen bond, hydrophobic interaction and van der Waals force. The key residues involved in peptide-enzyme interaction were determined by molecular docking. Furthermore, at a concentration of 800 mu mol L-1, GF-6 was found to significantly increase the glucose consumption in insulin-resistant HepG2 cells (P < 0.05) compared with the model group. CONCLUSIONSacha inchi meal-derived peptides displayed potent DPP-IV inhibition activity and could be used in the health food industry and as lead compounds for diabetes therapy. (c) 2023 Society of Chemical Industry.