In silico and in vitro elastase inhibition assessment assays of rosmarinic acid natural product from Rosmarinus officinalis Linn.

The use of various herbs and their compounds has been a strategy widely used in the fight against various human diseases. For example, rosmarinic acid, a bioactive phenolic compound commonly found in Rosemary plants (Rosmarinus officinalis Labiatae), has multiple therapeutic benefits in different diseases, such as cancer. Therefore, the study aimed to evaluate in silico and in vitro the inhibition potential of the enzyme Elastase from the porcine pancreas by rosmarinic acid isolated from the plant species R. officinalis Linn. Through Molecular Docking, the mechanism of action was investigated. In addition, rosmarinic acid presented a range of 5-60 µg/mL and significantly inhibited Elastase. At 60 µg/mL, there was an inhibition of 55% on the enzymatic activity. The results demonstrate the inhibition of Elastase by rosmarinic acid, which can lead to the development of new enzyme inhibitors that can be an inspiration for developing various drugs, including anticancer drugs.

Secondary Metabolites from the Cultures of Medicinal Mushroom Vanderbylia robiniophila and Their Tyrosinase Inhibitory Activities.

Vanderbylia robiniophila (Huaier in Chinese) has been used as a traditional herbal medicine in China for over 1600 years. However, the secondary metabolites of V. robiniophila have not been systematically examined. Corresponding chemical investigation in this study led to the discovery of two new compounds, (22E, 24R)-6ß, 7α-dimethoxyergosta-8(14), 22-diene-3ß, 5α-diol (1) and vanderbyliolide A (8), along with eight known ones (2-7, 9-10). Their structures were determined by extensive spectroscopic analyses and electronic circular dichroism (ECD) calculations. The tyrosinase inhibitory activity of all isolated compounds was evaluated, and compound 10 showed a potential tyrosinase inhibitory effect with an IC50 value of 60.47 ± 2.63 µM. Kinetic studies of the inhibition reactions suggested that 10 provides the inhibitory ability on tyrosinase in an uncompetitive way.

Molecular insights into α-glucosidase inhibition and antiglycation properties affected by the galloyl moiety in (-)-epigallocatechin-3-gallate.

BACKGROUND: Diabetes mellitus poses a substantial threat to public health due to rising morbidity and mortality. α-Glucosidase is one of the key enzymes affecting diabetes. Herein, (-)-epigallocatechin-3-gallate (EGCG) and (-)-epigallocatechin (EGC) were applied to clarify the role of the galloyl moiety of tea polyphenols in the inhibition of glycation and α-glucosidase activity. The structure-activity relationship of the galloyl moiety in EGCG on α-glucosidase was investigated in terms of inhibition kinetics, spectroscopy, atomic force microscopy and molecular docking. A bovine serum protein-fructose model was employed to determine the effect of the galloyl moiety on glycation. RESULTS: The results indicated that the introduction of a galloyl moiety enhanced the capacity of EGCG to inhibit glycation and α-glucosidase activity. The IC50 value of EGC is approximately 2400 times higher than that of EGCG. Furthermore, the galloyl moiety in EGCG altered the microenvironment and secondary structure of α-glucosidase, resulting in a high binding affinity of EGCG to α-glucosidase. The binding constant of EGCG to α-glucosidase at 298 K is approximately 28 times higher than that of EGC. CONCLUSION: Overall, the galloyl moiety of EGCG plays a crucial role in inhibiting glycation and α-glucosidase activity, which helps to enhance the molecular understanding of the structure and function of the polyphenol galloyl moiety in the science of food and agriculture. © 2023 Society of Chemical Industry.

Utilization of plant extracts to control the safety and quality of fried foods-A review.

Frying is one of the most common methods of preparing foods. However, it may lead to the formation of potentially hazardous substances, such as acrylamide, heterocyclic amines, trans fatty acids, advanced glycation end products, hydroxymethyl furfural and polycyclic aromatic hydrocarbons, and adversely alter the desirable sensory attributes of foods, thereby reducing the safety and quality of fried foods. Currently, the formation of toxic substances is usually reduced by pretreatment of the raw materials, optimization of process parameters, and the use of coatings. However, many of these strategies are not highly effective at inhibiting the formation of these undesirable reaction products. Plant extracts can be used for this purpose because of their abundance, safety, and beneficial functional attributes. In this article, we focus on the potential of using plant extracts to inhibit the formation of hazardous substances, so as to improve the safety of fried food. In addition, we also summarized the effects of plant extracts, which inhibit the production of hazardous substances, on food sensory aspects (flavor, color, texture, and taste). Finally, we highlight areas where further research is required.

A novel machine learning-based screening identifies statins as inhibitors of the calcium pump SERCA.

We report a novel small-molecule screening approach that combines data augmentation and machine learning to identify Food and Drug Administration (FDA)-approved drugs interacting with the calcium pump (Sarcoplasmic reticulum Ca2+-ATPase, SERCA) from skeletal (SERCA1a) and cardiac (SERCA2a) muscle. This approach uses information about small-molecule effectors to map and probe the chemical space of pharmacological targets, thus allowing to screen with high precision large databases of small molecules, including approved and investigational drugs. We chose SERCA because it plays a major role in the excitation-contraction-relaxation cycle in muscle and it represents a major target in both skeletal and cardiac muscle. The machine learning model predicted that SERCA1a and SERCA2a are pharmacological targets for seven statins, a group of FDA-approved 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors used in the clinic as lipid-lowering medications. We validated the machine learning predictions by using in vitro ATPase assays to show that several FDA-approved statins are partial inhibitors of SERCA1a and SERCA2a. Complementary atomistic simulations predict that these drugs bind to two different allosteric sites of the pump. Our findings suggest that SERCA-mediated Ca2+ transport may be targeted by some statins (e.g., atorvastatin), thus providing a molecular pathway to explain statin-associated toxicity reported in the literature. These studies show the applicability of data augmentation and machine learning-based screening as a general platform for the identification of off-target interactions and the applicability of this approach extends to drug discovery.

Screening and identification of lipase inhibitors extracted from Dioscorea nipponica Makino by UV-vis and HPLC coupled to UPLC-Q-TOF-MS/MS.

Dioscoreae nipponica Makino (D. nipponica) as the rhizome of dioscoreaceae rich in steroidal saponins, has been reported to have the hypolipidemic effects etc. However, it is still unclear which exact active components are primary responsible for the beneficial effects. This study was conducted to fish out the lipase inhibitors from D. nipponica, and evaluate the inhibitory activity on porcine pancreatic lipase (PPL) through in vitro kinetic assay using p-nitrophenyl palmitate as substrate. Accordingly, the ethanolic extract was subjected to D101 macroporous resin purification for spectrophotometric screening, high performance liquid chromatography (HPLC) separation and structural characterization by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Through orlistat validation, the PPL inhibitory activity and IC50 value of the extract were respectively 68.34 ± 1.47 % and 107.05 µg/mL under the optimized inhibition conditions. From 6 steroidal saponins identified, the inhibitory components named the protodioscin, protogracillin, dioscin and gracillin were fished out by grouping separation and HPLC analysis. Furthermore, dioscin and gracillin with the parent structure of diogenin were confirmed as the major inhibitors by virtue of stability tests based on transformation of protodioscin and protogracillin. Finally, the inhibitory mechanism of the major inhibitors toward PPL was further clarified by kinetic analysis and molecular docking analysis. The proposed method not only revealed the PPL inhibitory components in D. nipponica, but also provided an effective approach to hierarchical screening of PPL inhibitors from natural plants.

An innovative strategy to control Microcystis growth using tea polyphenols sustained-release particles: preparation, characterization, and inhibition mechanism.

Allelochemicals have been shown to inhibit cyanobacterial blooms for several years. In view of the disadvantages of "direct-added" mode, natural and pollution-free tea polyphenolic allelochemicals with good inhibitory effect on cyanobacteria were selected to prepare sustained-release particles by microcapsule technology. Results showed that the encapsulation efficiency of tea polyphenols sustained-release particles (TPSPs) was 50.6% and the particle size ranged from 700 to 970 nm, which reached the nanoscale under optimum preparation condition. Physical and chemical properties of TPSPs were characterized to prove that tea polyphenols were well encapsulated and the particles had good thermal stability. The optimal dosage of TPSPs was determined to be 0.3 g/L, at which the inhibition rate on Microcystis aeruginosa in logarithmic growth period could be maintained above 95%. Simultaneous decrease in algal density and chlorophyll-a content indicated that the photosynthesis of algal cells was affected leading to cell death. Significant changes of antioxidant enzyme activities suggested that Microcystis aeruginosa's antioxidant systems had been disrupted. Furthermore, TPSPs increased the concentration of O2- which led to lipid peroxidation of cell membrane and a subsequent increase in malondialdehyde (MDA) content. Meanwhile, the protein content, nucleic acid content, and electrical conductivity in culture medium rose significantly indicating the cell membrane was irreversibly damaged. This work can provide a basis for the utilization of environmentally friendly algal suppressants.

Research Progress of Pectin Methylesterase and its Inhibitors.

As an important pectin enzyme, pectin methylesterase (PME) can hydrolyze methyl esters, release methanol and reduce esterification. It is essential in regulating pollen tube development, root extension, and fruit ripening. Pectin methylesterase inhibitors (PMEI) can specifically bind PME and inhibit its activity, which jointly determines the esterification degree of pectin. PMEI has important application prospects in plant pest control, fruits and vegetable processing fields. In this paper, the gene families, crystal structures, molecular recognition, and applications in plants and industry are reviewed for the PME and PMEI systems. Finally, the semi-rational design of PMEI is discussed and discussed prospected.

Potent Inhibition of Human Cytochrome P450 3A4 by Biflavone Components from Ginkgo Biloba and Selaginella Tamariscina.

CYP3A4-mediated Phase I biotransformation is the rate-limiting step of elimination for many commonly used clinically agents. The modulatory effects of herbal medicines on CYP3A4 activity are one of the risk factors affecting the safe use of drug and herbal medicine. In the present study, the inhibitory effects of nearly hundred kinds of herbal medicines against CYP3A4 were evaluated based on a visual high-throughput screening method. Furthermore, biflavone components including bilobetin (7-demethylginkgetin, DGK), ginkgetin (GK), isoginkgetin (IGK), and amentoflavone (AMF) were identified as the main inhibitory components of Ginkgo biloba L. (GB) and Selaginella tamariscina (P. Beauv.) Spring (ST), which displayed very strong inhibitory effects toward CYP3A4. The inhibitory effects of these biflavones on clinical drugs that mainly undergo CYP3A4-dependent metabolism were evaluated. The IC 50 of GK toward tamoxifen, gefitinib and ticagrelor were found to be of 0.478 ± 0.003, 0.869 ± 0.001, and 1.61 ± 0.039 µM, respectively. These results suggest the potential pharmacokinetic interactions between the identified biflavones and clinical drugs undergoing CYP3A4-mediated biotransformation. The obtained information is important for guiding the rational use of herbal medicine in combination with synthetic pharmaceuticals.

Semysinthetic biflavonoid Morelloflavone-7,4',7″,3‴,4‴-penta-O-butanoyl is a more potent inhibitor of Proprotein Convertases Subtilisin/Kexin PC1/3 than Kex2 and Furin.

BACKGROUND: Garcinia brasiliensis is a species native to the Amazon forest. The white mucilaginous pulp is used in folk medicine as a wound healing agent and for peptic ulcer, urinary, and tumor disease treatments. The activity of the proprotein convertases (PCs) Subtilisin/Kex is associated with the development of viral, bacterial and fungal infections, osteoporosis, hyperglycemia, atherosclerosis, cardiovascular, neurodegenerative and neoplastic diseases. METHODS: Morelloflavone (BF1) and semisynthetic biflavonoid (BF2, 3 and 4) from Garcinia brasiliensis were tested as inhibitor of PCs Kex2, PC1/3 and Furin, and determined IC50, Ki, human proinflammatory cytokines secretion in Caco-2 cells, mechanism of inhibition, and performed molecular docking studies. RESULTS: Biflavonoids were more effective in the inhibition of neuroendocrine PC1/3 than mammalian Furin and fungal Kex2. BF1 presented a mixed inhibition mechanism for Kex2 and PC1, and competitive inhibition for Furin. BF4 has no good interaction with Kex2 and Furin since carboxypropyl groups results in steric hindrance to ligand-protein interactions. Carboxypropyl groups of BF4 promote steric hindrance with Kex2 and Furin, but effective in the affinity of PC1/3. BF4 was more efficient at inhibiting PCl/3 (IC50 = 1.13 µM and Ki = 0,59 µM, simple linear competitive mechanism of inhibition) than Kex2, Furin. Also, our results strongly suggested that BF4 also inhibits the endogenous cellular PC1/3 activity in Caco-2 cells, since PC1/3 inhibition by BF4 causes a large increase in IL-8 and IL-1ß secretion in Caco-2 cells. CONCLUSIONS: BF4 is a potent and selective inhibitor of PC1/3. GENERAL SIGNIFICANCE: BF4 is the best candidate for further clinical studies on inhibition of PC1/3.

Three flavanols delay starch digestion by inhibiting α-amylase and binding with starch.

The study aimed to reveal the different mechanisms of delaying starch digestion by ECG, EGCG and Procyanidin based on the perspective of α-amylase-flavanol interaction and starch-flavanol interaction. The interaction characteristics of flavanols with α-amylase were studied from five aspects: enzyme inhibition, kinetics, fluorescence quenching, circular dichroism (CD) and computer simulation. The IC50 of flavanols (ECG, EGCG and Procyanidin) against α-amylase were 172.21 ± 0.22, 732.15 ± 0.13 and 504.45 ± 0.19 µg/mL according to the results of α-amylase inhibition experiment, respectively. ECG and Procyanidin showed mixed inhibition against α-amylase, while EGCG showed non-competition against α-amylase. However, thermodynamic parameters，computer-based docking and dynamic simulation proved that ECG and EGCG-α-amylase complexs were mainly driven by van der Waals and hydrogen bonds, while Procyanidin-α-amylase complexs was driven by hydrophobic interaction. In addition, it was indicated, by means of starch­iodine complex spectroscopy, that flavanols inhibited the digestion of starch not only through bind with α-amylase but also through bind with starch. Thus, flavanols as a starch-based food additive have the potential to be employed as adjuvant therapy for diabetes.

Calpain-2 participates in the process of calpain-1 inactivation.

Calpain-1 and calpain-2 are highly structurally similar isoforms of calpain. The calpains, a family of intracellular cysteine proteases, cleave their substrates at specific sites, thus modifying their properties such as function or activity. These isoforms have long been considered to function in a redundant or complementary manner, as they are both ubiquitously expressed and activated in a Ca2+- dependent manner. However, studies using isoform-specific knockout and knockdown strategies revealed that each calpain species carries out specific functions in vivo. To understand the mechanisms that differentiate calpain-1 and calpain-2, we focused on the efficiency and longevity of each calpain species after activation. Using an in vitro proteolysis assay of troponin T in combination with mass spectrometry, we revealed distinctive aspects of each isoform. Proteolysis mediated by calpain-1 was more sustained, lasting as long as several hours, whereas proteolysis mediated by calpain-2 was quickly blunted. Calpain-1 and calpain-2 also differed from each other in their patterns of autolysis. Calpain-2-specific autolysis sites in its PC1 domain are not cleaved by calpain-1, but calpain-2 cuts calpain-1 at the corresponding position. Moreover, at least in vitro, calpain-1 and calpain-2 do not perform substrate proteolysis in a synergistic manner. On the contrary, calpain-1 activity is suppressed in the presence of calpain-2, possibly because it is cleaved by the latter protein. These results suggest that calpain-2 functions as a down-regulation of calpain-1, a mechanism that may be applicable to other calpain species as well.

Inhibitory mechanisms and interaction of tangeretin, 5-demethyltangeretin, nobiletin, and 5-demethylnobiletin from citrus peels on pancreatic lipase: Kinetics, spectroscopies, and molecular dynamics simulation.

This study aimed to reveal the interaction and inhibitory mechanisms of tangeretin (TAN), nobiletin (NBT), and their acidic hydroxylated forms, 5-demethyltangeretin (5-DT) and 5-demethylnobiletin (5-DN) on porcine pancreatic lipase (PPL) using spectroscopic techniques and molecular dynamics (MD) simulation. PPL inhibition assay showed that the inhibitory activity of NBT (IC50 value of 3.60 ± 0.19 µM) was superior to those of three polymethoxylated flavones (PMFs), indicating it may be related to the methoxy groups at the 3'-position in its molecular structure. Inhibition kinetic analyses demonstrated that the inhibition types of the 4 PMFs were consistent with the mixed inhibition model, which agreed well with the results from the ultraviolet-visible (UV-Vis) spectroscopy, Circular dichroism (CD), fluorescence spectroscopy, molecular docking, and MD simulation that PMFs could bind to the PPL catalytic site and non-catalytic site, affecting the normal spatial conformation of PPL and weakening its ability to decompose the substrate. All these findings suggest that PMFs are a kind of natural lipase inhibitors, and NBT has the potential as a lipase inhibition precursor because of its unique flavone skeleton structure.

A neutral polysaccharide from green tea: Structure, effect on α-amylase activity and hydrolysis property.

A neutral tea polysaccharide (TPSN) was isolated from green tea. Gas chromatography analysis showed that TPSN was composed of d-glucose, l-arabinose and d-galactose residues at a molar ratio of 90.0: 9.1: 0.9. The weight-averaged molecular weight of TPSN was determined as about 2.0 × 105 g mol-1 using static light scattering analysis. The result of nuclear magnetic resonance (NMR) spectroscopy indicated that TPSN and water-soluble starch had similar structures. TPSN exhibited inhibitory activity towards α-amylase through the noncompetitive inhibition mechanism, but the tertiary structure of α-amylase related to enzymatic activity, analyzed using circular dichroism spectroscopy, was not affected by TPSN. Meanwhile, TPSN exhibited hydrolysis properties catalyzed by α-amylase. Molecular docking analysis revealed that the various behaviors of TPSN to α-amylase could be attributed to that the different chain segments of TPSN combined with different amino acid residues of α-amylase.

Research on the Influences of Five Food-Borne Polyphenols on In Vitro Slow Starch Digestion and the Mechanism of Action.

Inhibiting starch digestion can effectively control postprandial blood sugar level. In this study, the in vitro digestion differences among the mixtures of five polyphenols (i.e., procyanidins [PAs], catechin [CA], tannic acid [TA], rutin [RU], and quercetin [QU]) and starch were analyzed through an in vitro simulation test of starch digestion. The interaction characteristics of these five polyphenols with α-amylase and α-glucosidase were investigated in terms of the inhibition effect, dynamics, fluorescence quenching, and circular dichroism (CD). The results revealed that the rapidly digestible starch (RDS) contents decreased, while the resistant starch (RS) contents increased. All five polyphenols inhibited the α-amylase activity through the noncompetitive approach but inhibited the α-glucosidase activity through the competitive approach. Five polyphenols combined with α-amylase spontaneously by using the hydrophobic effect. The interaction of PAs and QU with α-glucosidase were recognized as van der Waals forces and H bonding, whereas CA and TA interacted with α-glucosidase through the hydrophobic effect. All five polyphenols can cause conformational changes in enzymes.

Water-soluble vitamins for controlling starch digestion: Conformational scrambling and inhibition mechanism of human pancreatic α-amylase by ascorbic acid and folic acid.

The inhibition of human pancreatic α-amylase (HPA) enzyme activity can offer facile routes to ameliorate postprandial hyperglycemia in diabetes via control of starch digestion. The present study utilizes complementary experimental (starch digestion kinetics, fluorescence quenching, Förster resonance energy transfer and X-ray diffraction) and computational (molecular docking and dynamics simulation) methods to evaluate the HPA inhibitory activity of eight water-soluble vitamins, for the first time. In particular, ascorbic acid inhibited HPA activity via non-competitive antagonism from two allosteric sites, by channeling the inhibition towards the active site cavity via the triose-phosphate isomerase (TIM) barrel. In contrast, folic acid inhibited HPA activity by binding competitively to the active site cavity and decreasing the disorder in the neighboring loops 3 and 7, which are important mobile loops in HPA for starch digestion. The infusion of such biocompatible and nutritional water-soluble vitamins alongside starch may offer new avenues for diabetes management.

Suppression, disaggregation, and modulation of γ-Synuclein fibrillation pathway by green tea polyphenol EGCG.

Oligomerization of γ-Synuclein is known to have implications for both neurodegeneration and cancer. Although it is known to co-exist with the fibrillar deposits of α-Synuclein (Lewy bodies), a hallmark in Parkinson's disease (PD), the effect of potential therapeutic modulators on the fibrillation pathway of γ-Syn remains unexplored. By a combined use of various biophysical tools and cytotoxicity assays we demonstrate that the flavonoid epigallocatechin-3-gallate (EGCG) significantly suppresses γ-Syn fibrillation by affecting its nucleation and binds with the unstructured, nucleus forming oligomers of γ-Syn to modulate the pathway to form α-helical containing higher-order oligomers (~158 kDa and ~ 670 kDa) that are SDS-resistant and conformationally restrained in nature. Seeding studies reveal that these oligomers although "on-pathway" in nature, are kinetically retarded and rate-limiting species that slows down fibril elongation. We observe that EGCG also disaggregates the protofibrils and mature γ-Syn fibrils into similar SDS-resistant oligomers. Steady-state and time-resolved fluorescence spectroscopy and isothermal titration calorimetry (ITC) reveal a weak non-covalent interaction between EGCG and γ-Syn with the dissociation constant in the mM range (Kd ~ 2-10 mM). Interestingly, while EGCG-generated oligomers completely rescue the breast cancer (MCF-7) cells from γ-Syn toxicity, it reduces the viability of neuroblastoma (SH-SY5Y) cells. However, the disaggregated oligomers of γ-Syn are more toxic than the disaggregated fibrils for MCF-7cells. These findings throw light on EGCG-mediated modulation of γ-Syn fibrillation and suggest that investigation on the effects of such modulators on γ-Syn fibrillation is critical in identifying effective therapeutic strategies using small molecule modulators of synucleopathies.

Bromein, a Bromelain Inhibitor from Pineapple Stem: Structural and Functional Characteristics.

Bromelain inhibitor, "bromein", is a proteinase-inhibitor specific to the cysteine proteinase bromelain from pineapple stem. In the stem, eight bromein isoforms are known to exist, and each isoform has a short peptide (light chain) and a long one (heavy chain) with five disulfide bonds. The three-dimensional structure of the sixth isoform (bromein-6) is composed of inhibitory and stabilizing domains, and each domain contains a three-stranded antiparallel ß-sheet. The genomic sequence of a bromein precursor encodes three homologous bromein isoform domains, and each isoform domain has a signal peptide, three interchain peptides between the light chain and heavy chain, two interdomain peptides and a propeptide. Interestingly, at the protein level, bromein- 6 appears to share a similar folding and disulfide-bonding connectivity with Bowman-Birk serine proteinase inhibitors and shows weak inhibition toward chymotrypsin and trypsin. However, no significant similarity was found between them at the genomic level. This indicates that they have evolved convergently to possess such a structural similarity. To identify the essential reactive site(s) with bromelain, we investigated the inhibitory activity of 44 kinds of the single/double and insertion/ deletion mutants of bromein-6 towards stem bromelain. As a result, it was shown that both the appropriate positioning and the complete side-chain structure of Leu10 in the light chain are absolutely crucial for the inhibition, with an additional measure of importance for the preceding Pro9. Bromein and stem bromelain coexist in the acidic vacuoles of the stem tissue, and one of the key role of bromein appears to be the regulation of the bromelain activity.

High-throughput screen for inhibitors of protein-protein interactions in a reconstituted heat shock protein 70 (Hsp70) complex.

Protein-protein interactions (PPIs) are an important category of putative drug targets. Improvements in high-throughput screening (HTS) have significantly accelerated the discovery of inhibitors for some categories of PPIs. However, methods suitable for screening multiprotein complexes (e.g. those composed of three or more different components) have been slower to emerge. Here, we explored an approach that uses reconstituted multiprotein complexes (RMPCs). As a model system, we chose heat shock protein 70 (Hsp70), which is an ATP-dependent molecular chaperone that interacts with co-chaperones, including DnaJA2 and BAG2. The PPIs between Hsp70 and its co-chaperones stimulate nucleotide cycling. Thus, to re-create this ternary protein system, we combined purified human Hsp70 with DnaJA2 and BAG2 and then screened 100,000 diverse compounds for those that inhibited co-chaperone-stimulated ATPase activity. This HTS campaign yielded two compounds with promising inhibitory activity. Interestingly, one inhibited the PPI between Hsp70 and DnaJA2, whereas the other seemed to inhibit the Hsp70-BAG2 complex. Using secondary assays, we found that both compounds inhibited the PPIs through binding to allosteric sites on Hsp70, but neither affected Hsp70's intrinsic ATPase activity. Our RMPC approach expands the toolbox of biochemical HTS methods available for studying difficult-to-target PPIs in multiprotein complexes. The results may also provide a starting point for new chemical probes of the Hsp70 system.

[Reviews on α-glucosidase inhibitor from plant secondary metabolites].

α-Glucosidase inhibitor was a new type of antidiabetics which was developed in the late 1970s. By reducing the postprandial blood sugar concentration, it could effectively control the blood sugar levels, thereby reducing the occurrence of diabetic complications. Studies have shown that plant secondary metabolites have important biological functions such as hpyerglycemic, anti-hyperlipidemia, immunomodulatory, and antitumor effects. In this paper, the sources of plant secondary metabolites which are able to inhibit α-glucosidase and their inhibition mechanism would be reviewed to provide references for seeking more safe and efficient plant secondary metabolites of α-glucosidase inhibitors.