Inhibition of albendazole and 2-(2-aminophenyl)-1H-benzimidazole against tyrosinase: mechanism, structure-activity relationship, and anti-browning effect.

BACKGROUND: Tyrosinase is the key enzyme involved in enzymatic browning of plant-derived foods. Inhibition of tyrosinase activity contributes to the control of food browning. Due to safety regulations or other issues, most identified tyrosinase inhibitors are not suitable for practical use. Therefore, it is necessary to search for novel tyrosinase inhibitors. In this study, the anti-tyrosinase activity and mechanism of albendazole and 2-(2-aminophenyl)-1H-benzimidazole (2-2-A-1HB) were investigated through ultraviolet-visible absorption spectroscopy, fluorescence spectra, molecular docking, and molecular dynamic (MD) simulation. The anti-browning effect of albendazole on fresh-cut apples was then elucidated. RESULTS: Albendazole and 2-2-A-1HB were both efficient tyrosinase inhibitors with IC50 of 51 ± 1.5 and 128 ± 1.3 µmol L-1 , respectively. Albendazole suppressed tyrosinase non-competitively and formed tyrosinase-albendazole complex statically. Hydrogen bond and hydrophobic interaction were major driving forces in stabilizing the tyrosinase-albendazole complex. While 2-2-A-1HB inhibited the enzyme competitively and quenched its intrinsic fluorescence through a static mechanism, it generated strong binding affinity with tyrosinase through hydrophobic interaction. MD simulations further validated that albendazole/2-2-A-1HB could form stable complexes with tyrosinase and loosened its basic framework structure, leading to a change in secondary structure and conformation. In addition, albendazole could delay the browning of fresh-cut apples by inhibiting the activity of polyphenol oxidase, peroxidase and phenylalanine ammonia-lyase, and reducing the oxidation of phenolic compounds. CONCLUSION: This research might provide a deep view of tyrosinase inhibition by benzimidazole derivatives and a theoretical basis for developing albendazole as a potential fresh-keeping agent. © 2023 Society of Chemical Industry.

Study on the interaction between 4-(1H-indol-3-yl)-2-(p-tolyl)quinazoline-3-oxide and human serum albumin.

An organic small-molecular drug, 4-(1H-indol-3-yl)-2-(p-tolyl)quinazoline-3-oxide 1a was synthesized. It was employed to investigate the binding interaction and mechanism with human serum albumin (HSA). The experimental results indicated that the fluorescence quenching of HSA by 1a is a static quenching process and formation 1a-HSA complex. The site competition experiments revealed that the combination of 1a on HSA are hydrophobic interactions in the IIA domain and hydrogen bonds in IIIA domain of HSA, and the hydrophobic interactions of 1a on HSA are stronger than that of hydrogen bonds. These results were also confirmed by molecular docking theoretic analysis and ANS-hydrophobic fluorescent probe experiment. Synchronous fluorescence experiments showed that the polarity of HSA microenvironment was increase in the interaction process of 1a with HSA. The results of binding distance explored indicated that the combination distance between 1a and HSA is 3.63 nm, which is between 0.5R0 and 1.5R0, revealing the energy transfer between HSA and 1a is non-radiative. These results are very helpful for people to screen out high efficient indoloquinazoline drugs.

Quinazolinone derivatives: Synthesis and comparison of inhibitory mechanisms on α-glucosidase.

In this study, eight quinazolinone derivatives were designed and synthesized. Their inhibitory activities on α-glucosidase were assessed in vitro. Two compounds: 2-(4-chlorophenyl)-quinazolin-4(3H)-one (CQ) and 2-(4-bromophenyl)-quinazolin-4(3H)-one (BQ) were found to be potent inhibitors of α-glucosidase with IC50 values of 12.5±0.1µM and 15.6±0.2µM, respectively. Spectroscopy methods were performed to analyze the inhibitory mechanisms of both compounds on α-glucosidase. The results revealed that they reversibly inhibited α-glucosidase in a non-competitive manner. CQ and BQ could statically quench the fluorescence spectra by formation of an inhibitor-α-glucosidase complex. The interaction between CQ and α-glucosidase depended on hydrogen bonds, electrostatic and hydrophobic force, while the driving force of the binding between BQ and the enzyme was hydrophobic. The docking results showed that BQ was less active than CQ against α-glucosidase because of its weaker interaction with the enzyme. In brief, the quinazolinone derivatives identified in this work were potentially promising candidates for developing as novel anti-diabetic agents.

2-(4-Fluorophenyl)-quinazolin-4(3H)-one as a novel tyrosinase inhibitor: Synthesis, inhibitory activity, and mechanism.

2-(4-Fluorophenyl)-quinazolin-4(3H)-one (FQ) was synthesized, and its structure was identified with (1)H nuclear magnetic resonance ((1)H NMR), (13)C nuclear magnetic resonance ((13)C NMR), fourier transform infrared spectroscopy (FTIR), and high resolution mass spectrometry (HRMS). From the enzyme analysis, the results showed that it could inhibit the diphenolase activity of tyrosinase (IC50=120±2µM). Furthermore, the results of kinetic studies showed that the compound was a reversible mixed-type inhibitor, and that the inhibition constants were determined to be 703.2 (KI) and 222.1µM (KIS). The results of fluorescence quenching experiment showed that the compound could interact with tyrosinase and the substrates (tyrosine and l-DOPA). Molecular docking analysis revealed that the mass transfer rate was affected by FQ blocking the enzyme catalytic center. In brief, current study identified a novel tyrosinase inhibitor which deserved further study for hyperpigmentation drugs.

6,7-Bis-(2-methoxyethoxy)-4(3H)-quinazolinone as a novel inhibitor of tyrosinase and potential anti-browning agent of fresh-cut apples.

6,7-Bis-(2-methoxyethoxy)-4(3H)-quinazolinone (BMEQ) was selected from quinazolinones for its strong tyrosinase inhibitory activity (IC50 = 160 ± 6 µM). It suppressed tyrosinase activity in a competitive way and quenched the fluorescence of the enzyme through a static mechanism. The binding of BMEQ to tyrosinase increased the hydrophobicity of the latter and facilitated non-radiative energy transfer between them. The formation of BMEQ-tyrosinase complex was driven by hydrogen bonds and hydrophobic interactions, and it loosened the basic framework structure of tyrosinase, affecting the conformation of the enzyme, and leading to a decrease in tyrosinase activity. In addition, the BMEQ postponed the oxidation of phenolics and flavonoids by inhibiting polyphenol oxidase (PPO) and peroxidase (POD), which resulted in the inhibition of the browning of fresh-cut apples. This study identified a novel tyrosinase inhibitor BMEQ and verified its potential application for improving the preservation of postharvest fruits.

Inhibitory effect and molecular mechanism on tyrosinase and browning of fresh-cut apple by longan shell tannins.

Tyrosinase is a biological macromolecule closely related to browning of fruit and vegetables, melanin production, and tyrosinase inhibitors are usually used to prevent browning and pigmentation. In this study, longan shell tannins (LSTs) were screened as tyrosinase inhibitors and their structures were proved to be mixtures of procyanidins (condensed tannins) and ellagitannins (hydrolyzed tannins). Enzymatic experiments verified that LSTs were efficient inhibitors, and the IC50 values for monophenolase and bisphenolase were 176.04 ± 10 and 59.94 ± 5 µg mL-1, respectively. Fluorescence detections and molecular docking revealed that the combination of LSTs to tyrosinase was mainly driven by hydrogen bonding, hydrophobic interaction, as well as van der Waals force, which changed the microenvironment of tyrosine and tryptophan residues as well as enzyme conformation. Circular dichroism and molecular dynamics simulation showed that LSTs affected secondary structures of tyrosinase, resulting in structural stretching and conformational modification of the enzyme. In addition, preservation studies demonstrated that LSTs owned the ability to delay the browning of fresh-cut apples by inhibiting phenolic metabolism, strengthening the antioxidant system, and reducing lipid peroxidation. This paper testified that LSTs are exteaordinary tyrosinase inhibitors, and offered a scientific foundation for the application of LSTs in food industry and medicine.

Relationships between degree of polymerization and activities: A study on condensed tannins from the bark of Ficus altissima.

Condensed tannins were isolated from the bark of Ficus altissima and fractionated into four subcomponents on a Sephadex LH-20 column with 60 %, 80 %, 100 % methanol, and 70 % acetone, separately. Their structures were characterized by MALDI-TOF MS coupled with HPLC-ESI-MS and confirmed to be polymers of B-type procyanidin glucosides, procyanidins, and prodelphinidin glucosides. The degree of polymerization (DP) of these polymers was as high as 21, and the mDPs of the four subcomponents were calculated as 2.4, 6.6, 10.5 and 13.4, respectively. They competitively or noncompetitively suppressed the activities of tyrosinase and α-glucosidase through hydrogen bonding and hydrophobic interaction. And they also showed a powerful antioxidative activity. Correlation analyses verified that the anti-tyrosinase capacity exhibited a significant positive correlation (R2monophenolase = 0.9167 and R2diphenolase = 0.9302) with mDP within the methanol-water system, and the anti-α-glucosidase activity also showed a significant positive correlation with the mDP (R2 = 0.9187). In contrast, the antioxidant capability showed a significant negative correlation with the mDP (R2DPPH = 0.9258, R2ABTS = 0.9372). This study confirmed that condensed tannins from the bark of F. altissima were desirable anti-tyrosinase, anti-α-glucosidase, and antioxidant agents, and elucidated the relationships of their mDP (molecular weight) and activities, which provided a scientific basis for the comprehensive utilization of these polymers in the food, cosmetics, medicine and other fields.

Omeprazole inhibits α-glucosidase activity and the formation of nonenzymatic glycation products: Activity and mechanism.

In this study, the inhibitory effect and mechanism of omeprazole on α-glucosidase and nonenzymatic glycation were investigated in vitro by using multi-spectroscopic methods and molecular docking. Enzyme kinetic results showed that omeprazole inhibited α-glucosidase in a reversible and noncompetitive manner (IC50= 0.595 ± 0.003 mM). The results from fluorescence quenching and thermomechanical analyses signified that omeprazole reduced the fluorescence intensity of α-glucosidase by forming an omeprazole-α-glucosidase complex primarily driven by hydrogen bonds. Molecular docking further confirmed that hydrogen bonds and hydrophobic forces were the major driving forces for omeprazole binding to α-glucosidase. The nonenzymatic glycation assays revealed that omeprazole had a moderate inhibition against the formation of fructosamine, dicarbonyl compounds, and advanced glycation end products (AGEs). This study provides a new inhibitor of both α-glucosidase and nonenzymatic glycation and provides a practicable candidate for treating diabetes and its complications.

5-Methoxy-2-mercaptobenzimidazole as an efficient inhibitor on tyrosinase: Inhibitory activity and mechanism.

In this study, 5-methoxy-2-mercaptobenzimidazole (5-M-2-MB) was confirmed as an efficient tyrosinase inhibitor by methods of enzyme kinetic, fluorescence quenching, ANS-binding, thermodynamics, energy transfer, and molecular docking in combination. The results proved that 5-M-2-MB significantly inhibited the tyrosinase (IC50 = 60 ± 2 nM) in a reversible and competitive way with the Ki value of 80 ± 1 nM. It quenched the intrinsic fluorescence of tyrosinase through a static mechanism, and caused conformational change of the enzyme by increasing the hydrophobic region. Moreover, this compound could bind to tyrosinase and form 5-M-2-MB-tyrosinase complex by hydrogen bond and hydrophobic interaction. The interactions were generated between 5-M-2-MB and specific amino acid residues (Trp-358, Thr-308, Glu-356, and Asp-357) located on the A chain of tyrosinase. Therefore, this study would offer a theoretical foundation for developing the new tyrosinase inhibitor.

Effect of ascorbic acid on tyrosinase and its anti-browning activity in fresh-cut Fuji apple.

Tyrosinase (polyphenol oxidase) is the key enzyme of enzymatic browning in fruits and vegetables. In this research, the impact of ascorbic acid on tyrosinase and its anti-browning effect on fresh-cut Fuji apple were investigated. Ascorbic acid had a dual effect on tyrosinase with a half inhibitory concentration (IC50 ) of 13.40 ± 0.05 µM. Fluorescence assay demonstrated that ascorbic acid interacted with tyrosinase in a dynamic contaction caused by Förster's resonance energy transfer (FRET) and induced a conformational change of the enzyme. Thermodynamic analysis, copper interaction, and molecular docking further confirmed that ascorbic acid could chelate the copper ions located in active center and interact with amino acid residues of tyrosinase via hydrophobic interaction. In addition, ascorbic acid prevented the browning of fresh-cut apples by increasing APX activity and inhibiting PPO and POD activities which reduce the oxidation of total phenolics and flavonoids. PRACTICAL APPLICATIONS: The present study demonstrated that ascorbic acid had a strong inhibitory activity against tyrosinase (IC50 = 13.40 ± 0.05 µM) and anti-browning activity against fresh-cut Fuji apple. It could delay the browning degree of apple juice, increase APX activity, inhibit PPO and POD activities, and reduce the oxidation of total phenolics and flavonoids. These findings provided a basis for the feasible application of ascorbic acid on the preservation of fruits.

Inhibitory potential of 4-hexylresorcinol against α-glucosidase and non-enzymatic glycation: Activity and mechanism.

Inhibition of α-glucosidase as well as non-enzymatic glycation is thought as an effective method for treating type-2 diabetes mellitus. In this study, we investigated the inhibitory potential and mechanism of 4-hexylresorcinol against α-glucosidase and non-enzymatic glycation by using multispectroscopic analyses and molecular docking. The results of enzyme kinetics showed that 4-hexylresorcinol reversibly inhibited α-glucosidase activity in a noncompetitive way. Fluorescence quenching then revealed that it increased the hydrophobicity of α-glucosidase and changed the conformation of the enzyme by forming the α-glucosidase-hexylresorcinol complex. Thermodynamic analysis and molecular docking further demonstrated that the inhibition of 4-hexylresorcinol on the α-glucosidase was mainly dependent on hydrogen bond and hydrophobic interaction. Moreover, the 4-hexylresorcinol moderately inhibited the formation of fructosamine, and strongly suppressed the generation of α-dicarbonyl compounds and advanced glycation end products (AGEs). The interaction between 4-hexylresorcinol and bovine serum albumin was mainly driven by hydrophobic interaction. This study showed a novel inhibitor of α-glucosidase as well as non-enzymatic glycation, and provided a drug candidate for the prevention and treatment of type-2 diabetes.

MALDI-TOF MS analysis of condensed tannins with potent antioxidant activity from the leaf, stem bark and root bark of Acacia confusa.

The structures of the condensed tannins from leaf, stem bark and root bark of Acacia confusa were characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis, and their antioxidant activities were measured using 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and ferric reducing/antioxidant power (FRAP) assays. The results showed that the condensed tannins from stem bark and root bark include propelargonidin and procyanidin, and the leaf condensed tannins include propelargonidin, procyanidin and prodelphinidin, all with the procyanidin dominating. The condensed tannins had different polymer chain lengths, varying from trimers to undecamers for leaf and root bark and to dodecamers for stem bark. The condensed tannins extracted from the leaf, stem bark and root bark all showed a very good DPPH radical scavenging activity and ferric reducing power.

Inhibitory kinetics and mechanism of rifampicin on α-glucosidase: Insights from spectroscopic and molecular docking analyses.

α-Glucosidase is a critical enzyme associated with diabetes mellitus, and the inhibitors of the enzyme play important roles in the treatment of the disease. In this study, the inhibitory effect and mechanism of rifampicin on α-glucosidase were investigated by multispectroscopic methods along with molecular docking technique. The results showed that rifampicin inhibited α-glucosidase activity prominently (IC50 = 135 ±â€¯1.2 µM) in a reversible and competitive-type manner. The fluorescence intensity of α-glucosidase was quenched by rifampicin through forming rifampicin-α-glucosidase complex in a static procedure. And the formation of the rifampicin-α-glucosidase complex was driven spontaneously by hydrophobic forces and hydrogen bonds. The results obtained from molecular docking further indicated that hydrophobic forces were formed between rifampicin and amino acid residues Phe 173, Pro151, and hydrogen bonds were generated by the interactions of rifampicin with residues Ser 180, Asn 414, Gly160, and Gly161 of α-glucosidase. Moreover, it was found that the binding of rifampicin to α-glucosidase could alter the conformation of the enzyme to make it steady, and the binding distance was estimated to be 1.02 nm. Therefore, this study confirmed a novel α-glucosidase inhibitor and possibly contributed to the improvement of newfangled anti-diabetic agent.

Antityrosinase mechanism of ellagic acid in vitro and its effect on mouse melanoma cells.

The activities of ellagic acid in inhibiting mushroom tyrosinase and cell proliferation were evaluated in this research. The results of enzyme kinetics indicated that ellagic acid could effectively inhibit tyrosinase activity. The value of the semi-inhibitory rate (IC50 ) was 0.2 ± 0.05 mM. Ellagic acid inhibited tyrosinase activity in a reversible manner and was a mixed tyrosinase inhibitor. Furthermore, ellagic acid had a good inhibitory effect on the proliferation of mouse melanoma B16 cells and could induce apoptosis. The results acquired from fluorescence spectroscopy revealed that the interaction of ellagic acid with tyrosinase depended on hydrogen bond and electrostatic force. In addition, computational docking showed that ellagic acid interacted with amino acid residues of tyrosinase (Asn19 and Lys372) by hydrogen bond and produced electrostatic interaction with amino residue Lys18. PRACTICAL APPLICATIONS: In the present research, the antityrosinase mechanism of ellagic acid and its effect on mouse melanoma cells were investigated. This study suggested that ellagic acid had a strong inhibitory activity against tyrosinase and cell proliferation,which laid an experimental foundation for the development of new drugs and whitening products. The combined multispectral methods used in this research can be applied to the screening of other antityrosinase inhibitors, further promoting the development and utilization of tyrosinase inhibitors.

Inhibition of α-glucosidase activity and non-enzymatic glycation by tannic acid: Inhibitory activity and molecular mechanism.

The inhibition of α-glucosidase and glycation is considered as an effective approach for the treatment of type 2 diabetes. In this study, multispectroscopic and molecular docking techniques were employed to investigate the inhibition of tannic acid on α-glucosidase and glycation. Kinetics analyses revealed that tannic acid had a significant inhibition on α-glucosidase (IC50 = 0.35 ±â€¯0.02 µM) in a reversible and mixed competitive manner. The results acquired from fluorescence quenching and ANS-binding fluorescence methods revealed that tannic acid could bind to α-glucosidase and reduce the hydrophobic area on the surface of the enzyme. In addition, synchronous fluorescence analysis showed that tannic acid decreased the hydrophobicity of α-glucosidase and changed the conformation of the enzyme. In vitro glycation assays showed that tannic acid had strong inhibitory effects on the formation of fructosamine, dicarbonyl compounds, and fluorescent AGEs. ANS-binding fluorescence analysis showed that tannic acid could bind to BSA and reduce the hydrophobicity of BSA in glycation. Moreover, the results of molecular docking showed the interaction between tannic acid and α-glucosidase was mainly driven by hydrogen bond, electrostatic, and hydrophobic interaction. And the interaction between tannic acid and BSA was mainly driven by hydrogen bond and hydrophobic interaction.

Anti-melanogenesis properties of condensed tannins from Vigna angularis seeds with potent antioxidant and DNA damage protection activities.

Condensed tannins contained in food are known to have many beneficial impacts on human health. In this study, we attempt to evaluate the structural features, antityrosinase effects, anti-melanogenesis properties, antioxidant activity and DNA damage protection activity of condensed tannins purified from the seeds of Vigna angularis (Willd.) Ohwi et Ohashi. MALDI-TOF MS, ESI-Full-MS, and HPLC-ESI-MS demonstrated that condensed tannins are composed of procyanidins, prodelphinidins and their gallates, among which procyanidins are the dominant components. As reversible and mixed-type inhibitors of tyrosinase, condensed tannins from V. angularis strongly inhibited the monophenolase and odiphenolase activities with IC50 values of 130.0 ± 0.5 and 35.1 ± 2.0 µg mL-1, respectively. What's more, condensed tannins had a good inhibitory effect on cell proliferation, cellular tyrosinase activity, and melanogenesis of B16 mouse melanoma cells. Based on fluorescence quenching analyses, these compounds were determined to be effective quenchers of the enzyme and its substrates. According to molecular docking, the strong interaction between condensed tannins and tyrosinase was mainly driven by hydrogen bonding and hydrophobic force. In addition, condensed tannins showed a powerful antioxidant capacity and DNA damage protection activity. Therefore, condensed tannins from V. angularis have feasible applications in food, medicine, and the cosmetics industry.

Antityrosinase mechanism of omeprazole and its application on the preservation of fresh-cut Fuji apple.

Omeprazole was first evaluated for its antityrosinase activity and preservation of fresh-cut apples. The results obtained from enzymic analyses showed that the omeprazole inhibited tyrosinase activity (IC50 = 40 ±â€¯1.2 µM) with a reversible and competitive mechanism. Fluorescence quenching assays demonstrated that the interaction between omeprazole and tyrosinase was driven by hydrophobic forces and hydrogen bonds in a static procedure. Molecular docking further revealed that hydrogen bonds and hydrophobic forces were generated by omeprazole with the amino acid residues located in the A chain of tyrosinase. Moreover, the results from preservation assays showed that omeprazole could inhibit the activities of polyphenol oxidase (PPO) and peroxidase (POD), prevent the oxidation of total phenolics and flavonoid, thereby delay the browning of fresh-cut apples. Hence, this work identified a novel tyrosinase inhibitor and expands its feasible application as a food preservative.

Condensed Tannins from Longan Bark as Inhibitor of Tyrosinase: Structure, Activity, and Mechanism.

In this study, the content, structure, antityrosinase activity, and mechanism of longan bark condensed tannins were evaluated. The findings obtained from mass spectrometry demonstrated that longan bark condensed tannins were mixtures of procyanidins, propelargonidins, prodelphinidins, and their acyl derivatives (galloyl and p-hydroxybenzoate). The enzyme analysis indicated that these mixtures were efficient, reversible, and mixed (competitive is dominant) inhibitor of tyrosinase. What's more, the mixtures showed good inhibitions on proliferation, intracellular enzyme activity and melanogenesis of mouse melanoma cells (B16). From molecular docking, the results showed the interactions between inhibitors and tyrosinase were driven by hydrogen bond, electrostatic, and hydrophobic interactions. In addition, high levels of total phenolic and extractable condensed tannins suggested that longan bark might be a good source of tyrosinase inhibitor. This study would offer theoretical basis for the development of longan bark condensed tannins as novel food preservatives and medicines of skin diseases.

Antityrosinase and antioxidant properties of mung bean seed proanthocyanidins: Novel insights into the inhibitory mechanism.

This study investigated the structure, antioxidant activity, antityrosinase activity and mechanism of proanthocyanidins from mung bean seed [Vigna radiata (L.) Wilczek]. The structural composition were characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), electrospray ionization-full-mass spectrometry (ESI-Full-MS), and high-pressure liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS) techniques. The mung bean seed proanthocyanidins were composed of procyanidins, prodelphinidins, and their rhamnosides. According to enzyme kinetic analysis, these compounds were potent, reversible, and mixed-type inhibitors of tyrosinase. They inhibited the enzyme activity by interacting with enzyme as well as substrates. The results of molecular docking showed that the interaction between mung bean seed proanthocyanidins and tyrosinase was driven by hydrogen bond, hydrophobic and electrostatic interactions. In addition, mung bean seed proanthocyanidins were demonstrated as powerful antioxidants. Therefore, this study confirmed a novel tyrosinase inhibitor and would lay a scientific foundation for their utilization in pharmaceutical and food industries.

Novel Insights into the Inhibitory Effect and Mechanism of Proanthocyanidins from Pyracantha fortuneana Fruit on α-Glucosidase.

Proanthocyanidins were extracted from Pyracantha fortuneana fruit (PFF), and their structures were investigated through 13 C nuclear magnetic resonance (13 C NMR), high performance liquid chromatography (HPLC) and high resolution mass spectrometry (HRMS). The results showed that these compounds were predominantly constituted of procyanidin with A-type and B-type linkage and coexistence of procyanidins glucoside. Spectroscopy methods were used to analyze the inhibitory activity of proanthocyanidins on α-glucosidase. The results demonstrated that these compounds exhibited excellent inhibitory effect on α-glucosidase with the IC50 value of 0.15 ± 0.01 µg/mL, and they reversibly inhibited α-glucosidase in a non-competitive type. The fluorescence quenching analysis revealed that proanthocyanidins statically quenched the fluorescence spectra by forming an inhibitor-α-glucosidase complex. Molecular docking results further indicated that the driving powers of the interaction between proanthocyanidins and α-glucosidase were hydrogen bonds and hydrophobic force. The main inhibitory mechanism of proanthocyanidins on α-glucosidase may be due to the insertion of proanthocyanidins into the pocket of the enzyme altering the catalytic configuration of the active site in a manner, thus reducing substrate binding affinity. The findings of this work provided a new perspective that proanthocyanidins from PFF with a possibility to be used as novel natural anti-diabetic agents in functional food industries. PRACTICAL APPLICATION: In this study, Pyracantha fortuneana fruit proanthocyanidins with a yield of 3.05% were identified for the first time as predominantly constituted of procyanidin with A-type and B-type linkage and coexistence of procyanidins glucoside. Proanthocyanidins from P. fortuneana fruit had higher anti-α-glucosidase activity value compared with positive control acarbose, which indicated that P. fortuneana fruit proanthocyanidins with a possibility to be used as novel natural antidiabetic agents in functional food industries.