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Bioaffinity ultrafiltration coupled with HPLC-ESI-MS/MS for screening potential α-glucosidase inhibitors from pomegranate peel.

ABSTRACT: Pomegranate peel (PoP) contains plenty of bioactive compounds and exhibits strong activity to prevent postprandial hyperglycaemia and improve diabetes mellitus. Presently, bioaffinity ultrafiltration coupled with high performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-ESI-MS/MS) is employed to screen and identify the efficient α-glucosidase inhibitors in PoP and the detailed inhibitory mechanisms are further investigated. The results show that many substances, including ellagic acid, kaempferol, gallic acid, and resveratrol in PoP reveal strong activity to inhibit α-glucosidase and ellagic acid (EA) is screened as the most effective compound. Further research indicates that EA plays a competitive and reversible inhibition role against α-glucosidase with the value of Ki was 6.24 × 10⁵ mol/L. EA also directly interacts with the amino acids of α-glucosidase mainly via van der Waals forces and hydrogen bonds, thereby, influencing the secondary structure and stability of α-glucosidase. Finally, the α-glucosidase inhibitory activity of EA is further confirmed to significantly reduce postprandial blood glucose in vivo.

SUBMITTER: Shi R

PROVIDER: S-EPMC9623087 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Bioaffinity ultrafiltration coupled with HPLC-ESI-MS/MS for screening potential α-glucosidase inhibitors from pomegranate peel.

Shi Rujie R Zhou Nong N Zhang Han H Gong Min M Han Lin L

Frontiers in nutrition 20221018

Pomegranate peel (PoP) contains plenty of bioactive compounds and exhibits strong activity to prevent postprandial hyperglycaemia and improve diabetes mellitus. Presently, bioaffinity ultrafiltration coupled with high performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-ESI-MS/MS) is employed to screen and identify the efficient α-glucosidase inhibitors in PoP and the detailed inhibitory mechanisms are further investigated. The results show that many substances, incl ...[more]

PMID: 36330141

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Project description:Dendrobium fimbriatum is a perennial herb, and its stems are high-grade tea and nourishing medicinal materials. Various solvent extracts of D. fimbriatum were evaluated for their anti-inflammatory, anti-acetylcholinesterase (AChE), antioxidant, and anti-α-glucosidase properties. Acetone and EtOAc extracts showed significant antioxidant effects. Acetone, n-hexane, and EtOAc extracts revealed potent inhibition against α-glucosidase. EtOAc, n-hexane, and dichloromethane extracts displayed significant anti-AChE activity. Among the isolated constituents, gigantol, moscatin, and dendrophenol showed potent antioxidant activities in FRAP, DPPH, and ABTS radical scavenging tests. Moscatin (IC50 = 161.86 ± 16.45 μM) and dendrophenol (IC50 = 165.19 ± 13.25 μM) displayed more potent anti-AChE activity than chlorogenic acid (IC50 = 236.24 ± 15.85 μM, positive control). Dendrophenol (IC50 = 14.31 ± 3.17 μM) revealed more efficient anti-NO activity than quercetin (positive control, IC50 = 23.09 ± 1.43 μM). Analysis of AChE and iNOS inhibitory components was performed using molecular docking and/or the bioaffinity ultrafiltration method. In bioaffinity ultrafiltration, the binding affinity of compounds to the enzyme (acetylcholinesterase and inducible nitric oxide synthase) was determined using the enrichment factor (EF). Among the main components of the EtOAc extract from D. fimbriatum stem, moscatin, dendrophenol, gigantol, and batatasin III with acetylcholinesterase exhibited the highest binding affinities, with affinity values of 66.31%, 59.48%, 54.60%, and 31.87%, respectively. Moreover, the affinity capacity of the identified compounds with inducible nitric oxide synthase can be ranked as moscatin (88.99%) > dendrophenol (65.11%) > gigantol (44.84%) > batatasin III (27.18%). This research suggests that the bioactive extracts and components of D. fimbriatum stem could be studied further as hopeful candidates for the prevention or treatment of hyperglycemia, oxidative stress-related diseases, and nervous disorders.

Project description:BackgroundDysosma versipellis (D. versipellis) has been traditionally used as a folk medicine for ages. However, the specific phytochemicals responsible for their correlated anti-inflammatory, anti-proliferative and antiviral activities remain unknown.PurposeThis study aimed to explore the specific active components in D. versipellis responsible for its potential anti-inflammatory, anti-proliferative, and antiviral effects, and further elucidate the corresponding mechanisms of action.MethodsBioaffinity ultrafiltration coupled to liquid chromatography-mass spectrometry (UF-LC/MS) was firstly hired to fast screen for the anti-inflammatory, anti-proliferative and antiviral compounds from rhizomes of D. versipellis, and then further validation was conducted using in vitro inhibition assays and molecular docking.ResultsA total of 12, 12, 9 and 12 phytochemicals with considerable affinities to Topo I, Topo II, COX-2 and ACE2 were fished out, respectively. The anti-proliferative assay in vitro indicated that podophyllotoxin and quercetin exhibited comparably strong inhibitory rates on A549 and HT-29 cells compared with 5-FU and etoposide. Meanwhile, kaempferol displayed prominent dose-dependent inhibition against COX-2 with IC50 value at 0.36 ± 0.02 μM lower than indomethacin at 0.73 ± 0.07 μM. Furthermore, quercetin exerted stronger inhibitory effect against ACE2 with IC50 value at 104.79 ± 8.26 μM comparable to quercetin 3-O-glucoside at 135.25 ± 6.54 μM.ConclusionWe firstly showcased an experimental investigation on the correlations between bioactive phytochemicals of D. versipellis and their multiple drug targets reflecting its potential pharmacological activities, and further constructed a multi-target and multi-component network to decipher its empirical traditional applications. It could not only offer a reliable and valuable experimental basis to better comprehend the curative effects of D. versipellis but also provide more new insights and strategies for other traditional medicinal plants.

Project description:Artemisia genus of Asteraceae family is a source of medicinal plants known worldwide and used as ethnopharmacological remedies for the treatment of diabetes in Northern Asia (Siberia). The aim of this study was to determine the phenolic profile of 12 Siberian Artemisia species (A. anethifolia, A. commutata, A. desertorum, A. integrifolia, A. latifolia, A. leucophylla, A. macrocephala, A. messerschmidtiana, A. palustris, A. sericea, A. tanacetifolia, A. umbrosa) and to test the efficacy of plant extracts and pure compounds for antidiabetic potential. Finally, by HPLC-DAD-ESI-TQ-MS/MS technique, 112 individual phenolic compounds were detected in Artemisia extracts in a wide range of concentrations. Some species accumulated rare plant phenolics, such as coumarin-hemiterpene ethers (lacarol derivatives) from A. latifolia and A. tanacetifolia; melilotoside from A. tanacetifolia; dihydrochalcones (davidigenin analogs) from A. palustris; chrysoeriol glucosides from A. anethifolia, A. sericea, and A. umbrosa; eriodictyol glycosides from A. messerschmidtiana; and some uncommon flavones and flavonols. The predominant phenolic group from Artemisia species herb was caffeoylquinic acid (CQAs), and in all species, the major CQAs were 5-O-CQA (20.28-127.99 μg/g) and 3,5-di-O-CQA (7.35-243.61 μg/g). In a series of in vitro bioassays, all studied Artemisia extracts showed inhibitory activity against principal enzymes of carbohydrate metabolism, such as α-amylase (IC50 = 150.24-384.14 μg/mL) and α-glucosidase (IC50 = 214.42-754.12 μg/mL). Although many phenolic compounds can be inhibitors, experimental evidence suggests that the CQAs were key to the biological response of Artemisia extracts. Mono-, di- and tri-substituted CQAs were assayed and showed inhibition of α-amylase and α-glucosidase, with IC50 values of 40.57-172.47 μM and 61.08-1240.35 μM, respectively, and they were more effective than acarbose, a well-known enzyme inhibitor. The results obtained in this study reveal that Siberian Artemisia species and CQAs possess a pronounced inhibitory activity against α-amylase and α-glucosidase and could become a complement to synthetic antidiabetic drugs for controlling blood glucose level.

Project description:The genus Arbutus (Ericaceae) has been traditionally used in folk medicine due to its phytomedicinal properties, especially Arbutus pavarii Pamp. However, this plant has not been evaluated for its efficacy, quality, and consistency to support the traditional uses, potentially in treating diabetes. Despite previous studies that revealed the biological activities of A. pavarii as antioxidant and α-glucosidase inhibitory agents, scientific reports on the bioactive compounds that contribute to its health benefits are still scarce. Therefore, this research focused on the evaluation of antioxidant and α-glucosidase inhibitory activities of the methanol crude extracts and various fractions of the leaf and stem bark, as well as on metabolite profiling of the methanol crude extracts. The extracts and fractions were evaluated for total phenolic (TPC) and total flavonoid (TFC) contents, as well as the DPPH free radical scavenging, ferric reducing antioxidant power (FRAP), and α-glucosidase inhibitory activities. Methanol crude extracts of the leaf and stem bark were then subjected to UHPLC-ESI-MS/MS. To the best of our knowledge, the comparative evaluation of the antioxidant and α-glucosidase inhibitory activities of the leaf and stem bark of A. pavarii, as well as of the respective solvent fractions, is reported herein for the first time. Out of these extracts, the methanolic crude extracts and polar fractions (ethyl acetate and butanol fractions) showed significant bioactivities. The DPPH free radical and α-glucosidase inhibitions was highest in the leaf ethyl acetate fraction, with IC50 of 6.39 and 4.93 µg/mL, respectively, while the leaf methanol crude extract and butanol fraction exhibited the highest FRAP with 82.95 and 82.17 mmol Fe (II)/g extract. The UHPLC-ESI-MS/MS analysis resulted in the putative identification of a total of 76 compounds from the leaf and stem bark, comprising a large proportion of plant phenolics (flavonoids and phenolic acids), terpenoids, and fatty acid derivatives. Results from the present study showed that the different parts of A. pavarii had potent antioxidant and α-glucosidase inhibitory activities, which could potentially prevent oxidative damage or diabetes-related problems. These findings may strengthen the traditional claim on the medicinal value of A. pavarii.

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Bioaffinity ultrafiltration coupled with HPLC-ESI-MS/MS for screening potential α-glucosidase inhibitors from pomegranate peel.

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Bioaffinity ultrafiltration coupled with HPLC-ESI-MS/MS for screening potential α-glucosidase inhibitors from pomegranate peel.

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