PTP1B Inhibitory Activity Research Articles

A New Benzofuran from the Roots of Eupatorium chinense L. and Its α-glucosidase and PTP1B Inhibitory Activities

A New Benzofuran from the Roots of Eupatorium chinense L. and Its α-glucosidase and PTP1B Inhibitory Activities

Oleanane triterpenoids with PTP1B and α-glucosidase inhibitory activities from Caulophyllum robustum

Eleven oleanane triterpenoids (1–11) including two new ones (1 and 2) were isolated from the roots and stems of Caulophyllum robustum. Their structures were established by extensive spectroscopic analysis, comparison with literature, and NMR calculations. Compounds 1 and 2 represent the first examples of 23-hydroxy-28-nor-oleanane and 21-hydroxy-olean-3-one triterpenoids, respectively. All isolates were evaluated for their PTP1B and α-glucosidase inhibitory activities in vitro. Among them, the triterpene aglycones 1–5 showed almost equivalent PTP1B inhibitory activities to oleanolic acid and ursolic acid, while 1, 2, and the triterpene saponins 6–11 showed significant α-glucosidase inhibitory activities. Furthermore, compounds 1 and 3 were proved to regulate the expression of proteins implicated the PTP1B/IRS-1/pIRS-1 signalling pathway to improve insulin resistance.

Novel phenanthrene/bibenzyl trimers from the tubers of Bletilla striata attenuate neuroinflammation via inhibition of NF-κB signaling pathway

Five novel (9,10-dihydro) phenanthrene and bibenzyl trimers, as well as two previously identified biphenanthrenes and bibenzyls, were isolated from the tubers of Bletilla striata. Their structures were elucidated through comprehensive analyses of NMR and HRESIMS spectroscopic data. The absolute configurations of these compounds were determined by calculating rotational energy barriers and comparison of experimental and calculated ECD curves. Compounds 5b and 6 exhibited inhibitory effects on LPS-induced NO production in BV-2 cells, with IC50 values of 12.59 ± 0.40 and 15.59 ± 0.83 μmol·L−1, respectively. A mechanistic study suggested that these compounds may attenuate neuroinflammation by reducing the activation of the AKT/IκB/NF-κB signaling pathway. Additionally, compounds 3a, 6, and 7 demonstrated significant PTP1B inhibitory activities, with IC50 values of 1.52 ± 0.34, 1.39 ± 0.11, and 1.78 ± 0.01 μmol·L−1, respectively. Further investigation revealed that compound 3a might inhibit LPS-induced PTP1B overexpression and NF-κB activation, thereby mitigating the neuroinflammatory response in BV-2 cells.

Triterpenoids from the Leaves of Diospyros digyna and Their PTP1B Inhibitory Activity.

Six new 2α-hydroxy ursane triterpenoids, 3α-cis-p-coumaroyloxy-2α,19α-dihydroxy-12-ursen-28-oic acid (1), 3α-trans-p-coumaroyloxy-2α,19α-dihydroxy-12-ursen-28-oic acid (2), 3α-trans-p-coumaroyloxy-2α-hydroxy-12-ursen-28-oic acid (3), 3β-trans-p-coumaroyloxy-2α-hydroxy-12,20(30)-ursadien-28-oic acid (4), 3β-trans-feruloyloxy-2α-hydroxy-12,20(30)-ursadien-28-oic acid (5), and 3α-trans-feruloyloxy-2α-hydroxy-12,20(30)-ursadien-28-oic acid (6), along with eleven known triterpenoids (7-17), were isolated from the leaves of Diospyros digyna. Their chemical structures were elucidated by comprehensive analysis of UV, IR, HRESIMS, and NMR spectra. All the isolated compounds were evaluated for their PTP1B inhibitory activity. 3β-O-trans-feruloyl-2α-hydroxy-urs-12-en-28-oic acid (13) showed the best inhibition activity with an IC50 value of 10.32 ± 1.21 μM. The molecular docking study found that the binding affinity of compound 13 for PTP1B was comparable to that of oleanolic acid (positive control).

Austin-Type Meroterpenoids from Fungi Reported in the Last Five Decades: A Review.

Austin was first isolated as a novel polyisoprenoid mycotoxin from Aspergillus ustus in 1976. Subsequently, some new austin-type meroterpenoids (ATMTs) have been continually found. This review attempts to give a comprehensive summary of progress on the isolation, chemical structural features, biological activities, and fungal biodiversity of 104 novel ATMTs from 5 genera of terrestrial- and marine-derived fungi reported from October 1976 to January 2023. The genera of Penicillium and Aspergillus are the two dominant producers, producing 63.5% and 30.8% of ATMTs, respectively. Moreover, about 26.9% of ATMTs display various pronounced bioactivities, including insecticidal, anti-inflammatory, cytotoxicity, antibacterial, and PTP1B inhibitory activities. The chemical diversity and potential activities of these novel fungal ATMTs are reviewed for a better understanding, and a relevant summary focusing on the source fungi and their taxonomy is provided to shed light on the future development and research of austin-type meroterpenoids.

Eremane, viscidane and isozizaene diterpenoids from the leaves of Eremophila rigida and their absolute configurations

Previously undescribed eremane, viscidane, and isozizaene diterpenoids, eremorigidanes A-F, along with six known O-methylated flavonoids and three known triterpenoids were isolated and identified from the leaves of Eremophila rigida Chinnock by combined use of high-resolution PTP1B inhibition profiling, semipreparative- and analytical-scale HPLC separations, HPLC-PDA-HRMS analysis, and NMR spectroscopy. The absolute configuration of the unreported diterpenoids were determined by comparison of their experimental and calculated ECD spectra as well as by biosynthetic arguments. All isolates were evaluated for their PTP1B inhibitory activities, which revealed the flavonoid penduletin (3) to show inhibition with an IC50 value of 18.3 μM, and the triterpenoids 3,4-seco-olean-12-ene-3,28-dioic acid (15), oleanolic acid (16), and 3-oxo-oleanolic acid (17) to show inhibition with IC50 values of 55.7, 9.9, and 6.3 μM, respectively. The preliminary structure-activity relationship (SAR) of isolated flavonoids and triterpenoids is discussed. Plausible biosynthetic steps involved in eremane and isozizaene metabolism are presented and discussed.

Chiral separation and bioactivities of six pairs of enantiomeric dilignans from Magnolia officinalis var. biloba

Six pairs of enantiomeric dilignans, (+)/(−)-magdiligols A–F, have been isolated from an ethanolic extract of the barks of Magnolia officinalis var. biloba. Their chemical structures were elucidated by extensive spectroscopic analyses, NMR calculation with DP4+ analysis, and the electronic circular dichroism spectra calculation. (+)/(−)-1–3 possessed a dihydrobenzopyran ring, while a propyl chain of 1 was linked via ether bond. (+)/(−)-Magdiligols D and E ((+)/(−)-4 and 5) were dilignans possessing a furan ring. (+)-Magdiligol B ((+)/(−)-2), (+)/(−)-magdiligol C ((+)/(−)-3), and racemes 2, 3, and 5 showed potential hepatoprotective effects against APAP-induced HepG2 cell damage, increased the cell viability from 65.4% to 72.7, 78.7.76.6, 73.9, 77.9 and 73.2%, via decreasing the level of the live enzymes ALH and LDH consistently. (+)/(−)-Magdiligols B–D ((+)/(−)-2–4) and (+)/(−)-magdiligol F ((+)/(−)-6) exhibited significant antioxidative activity. (+)/(−)-Magdiligols B–C ((+)/(−)-2 and 3), (−)-magdiligol D ((−)-4), and (+)-magdiligol E ((+)-5) displayed significant PTP1B inhibitory activity with IC50 values 1.41–3.42 μM. (+)/(−)-Magdiligol B ((+)/(−)-2), and its raceme (2) demonstrated α-glucosidase inhibitory activity with the IC50 values 1.47, 2.88 and 1.85 μM, respectively.

Discovery and biological evaluation of novel dual PTP1B and ACP1 inhibitors for the treatment of insulin resistance

In this study, a virtual screening pipeline comprising ligand-based and structure-based approaches was established and applied for the identification of dual PTP1B and ACP1 inhibitors. As a result, a series of benzoic acid derivatives was discovered, and compound H3 and S6 demonstrated PTP1B and ACP1 inhibitory activity, with IC50 values of 3.5 and 8.2 μM for PTP1B, and 2.5 and 5.2 μM for ACP1, respectively. Molecular dynamics simulations illustrated that H3 interacted with critical residues in the active site, such as Cys215 and Arg221 for PTP1B, and Cys17 and Arg18 for ACP1. Enzymatic kinetic research indicated that identified inhibitors competitively inhibited PTP1B and ACP1. Additionally, cellular assays demonstrated that H3 and S6 effectively increased glucose uptake in insulin-resistant HepG2 cells while displaying very limited cytotoxicity at their effective concentrations. In summary, H3 and S6 represent novel dual-target inhibitors for PTP1B and ACP1, warranting further investigation as potential agents for the treatment of diabetes.

New chromone derivatives bearing thiazolidine-2,4-dione moiety as potent PTP1B inhibitors: Synthesis and biological activity evaluation

A series of chromone derivatives bearing thiazolidine-2,4-dione moiety (5 ∼ 37) were synthesized and evaluated for their PTP1B inhibitory activity, interaction analysis and effects on insulin pathway in palmitic acid (PA)-induced HepG2 cells. The results showed that all derivatives presented potential PTP1B inhibitory activity with IC50 values of 1.40 ± 0.04 ∼ 16.83 ± 0.54 μM comparing to that of positive control lithocholic acid (IC50: 9.62 ± 0.14 μM). Among them, compound 9 had the strongest PTP1B inhibitory activity with the IC50 value of 1.40 ± 0.04 μM. Inhibition kinetic study revealed that compound 9 was a reversible mixed-type inhibitor against PTP1B. CD spectra results confirmed that compound 9 changed the secondary structure of PTP1B by their interaction. Molecular docking explained the detailed binding between compound 9 and PTP1B. Compound 9 also showed 19-fold of selectivity for PTP1B over TCPTP. Moreover compound 9 could recovery PA-induced insulin resistance by increasing the phosphorylation of IRSI and AKT. CETSA results showed that compound 9 significantly increased the thermal stability of PTP1B.

Pharmacological properties of Ensete glaucum seed extract: Novel insights for antidiabetic effects via modulation of oxidative stress, inflammation, apoptosis and MAPK signaling pathways

Ethnophamacological relevanceMedicinal plants are increasingly making important contributions to diabetic treatment. Ensete glaucum seeds have been widely used in folk medicine to treat diabetes. Aim of the studyThe study was aimed to investigate the protective effect and active mechanisms of E. glaucum seed extract (EGSE) against streptozotocin (STZ)-induced hyperglycemia. Materials and methodsHyperglycemic mice were treated with EGSE (25 and 50 mg/kg) or glibenclamide (5 mg/kg) once daily for 7 d. The effects of these treatments on changes in blood biochemical parameters, pancreatic, liver, and kidney histopathology, oxidative stress and inflammatory marker levels in pancreatic, hepatic, and renal tissues were assessed. Expression of several proteins in MAPK signaling pathway related to apoptosis in pancreatic tissue were investigated. Furthermore, ex vivo, in vitro, and in silico biological activities of EGSE and its compounds were also examined. ResultsEGSE and glibenclamide increased notably insulin, reduced significantly glucose, AST, ALT, BUN and creatinine levels in blood. Pancreatic islets, hepatic and renal tissue structure were restored by EGSE or glibenclamide. EGSE showed significant anti-oxidative stress and anti-inflammatory effects by enhancing GSH level and dropping MDA, NF-κB, TNF-α and IL-6 levels in these tissues. Particularly, EGSE exhibited pancreatic protective effect against STZ-induced apoptosis through the MAPK signaling pathway by down-regulation of p-p38 MAPK, ERK1/2, JNK1, p-AMPK, Bax, Bax/Bcl-2, cytochrome c, cleaved-caspase 3 and PARP expression, and slight up-regulation of Bcl-2 expression. Moreover, EGSE inhibited intestinal glucose absorption, PTP1B, α-amylase, and α-glucosidase activities. Its isolated compounds (Afzelechin and coniferaldehyde) showed PTP1B and α-glucosidase inhibitory activities, and potent structure-activity relationships. ConclusionThese findings indicated the hypoglycemic and protective effects of E. glaucum seed extract against the STZ diabetogenic action. E. glaucum seed is a potential candidate for further studies to confirm its activities as a therapeutic agent for diabetic patients.

Diterpenoid and phenolic constituents from corn silk (Zea mays) with PTP1B inhibitory activity

Chemical investigation of corn silk resulted in the isolation of nine secondary metabolites, including a new ent-kaurane diterpenoid, zeamaysditerpene A (1) and eight known compounds, stigmaydene A (2), stigmaydene J (3), stigmaydene L (4), stigmane D (5), demethyltorosaflavone D (6), chrysoeriol 6-C-β-boivinopyranosyl-7-O-β-D-glucopyranoside (7), deoxypodophyllotoxin (8), and α-peltatin glucoside (9). Their structures were elucidated using a combination of spectroscopic methods, including 1D and 2D NMR and HRESIQTOF mass spectra. The absolute configuration of 1 was deduced by applying electronic circular dichroism (ECD) calculation method. Among the isolates, only 6 displayed significant inhibition against PTP1B activity in a dose-dependent manner, with an IC50 value of 10.7 ± 0.1 µM. Furthermore, molecular docking simulation was carried out to explore the action perspective of 6 inside the enzyme PTP1B. This finding suggests that 6 might be a potential lead for the development of a new anti-diabetic agent.

Fungal Metabolites: A Potential Source of Antidiabetic Agents with Particular Reference to PTP1B Inhibitors.

Diabetes is a growing health concern worldwide because it affects people of all age groups and increases the risk of other diseases such as renal impairment and neural and cardiovascular disorders. Oral hypoglycemic drugs mainly control diabetes; however, their associated side effects limit their use in patients with other complications. PTP1B is a viable drug target to explore new antidiabetic drugs. PTP1B acts as a negative regulator of the insulin-signaling pathway, and therefore, PTP1B inhibitors display antihyperglycemic activity. Several classes of compounds from natural and synthetic sources act as PTP1B inhibitors. Fungi are comprehensive in their diversity and recognized as a valuable source for therapeutically active molecules. In recent years, researchers have reported diverse classes of fungal secondary metabolites as potent PTP1B inhibitors. Some metabolites such as 6-O-methylalaternin, fumosorinone A, nordivaricatic acid, and the divarinyl divarate showed good activity and can be taken forward as a lead to develop novel PTP1B inhibitors and antidiabetic drugs. Therefore, the present review focuses on the fungal metabolites identified in the last five years possessing PTP1B inhibitory activity. A total of 128 metabolites are reviewed. Their fungal species and source, chemical structure, and activity in terms of IC50 are highlighted.

Lyonensinols A - C, 24-Norursane-Type Triterpenoids from the Twigs and Leaves of Lyonia doyonensis and Their Potential Anti-inflammatory and PTP1B Inhibitory Activities.

Lyonia doyonensis is a deciduous shrub native to high-altitude regions of Asia. So far, there is no report on any chemical and biological properties of L.doyonensis. An EtOH extract of L.doyonensis twigs and leaves showed inhibitory activities on protein tyrosine phosphatase 1B and lipopolysaccharide-induced inflammation in BV-2 microglial cells. A phytochemical investigation of this extract led to the isolation of a, so far only ambiguously described, 24-norursane-type triterpenoid, now named lyonensinol A (1: ), along with its two new derivatives, lyonensinols B and C (2: and 3: ), and six known triterpenoids (4 - 9: ). Their structures were elucidated by detailed analysis of spectroscopic data. A combination of chemical conversions, electronic circular dichroism, and Mo2(OAc)4-induced electronic circular dichroism was used to confirm their absolute configurations. Lyonensinols B (2: ) and C (3: ) represent the first examples of norursane-type triterpenoids acylated with a p-coumaroyl moiety. The potential anti-inflammatory and protein tyrosine phosphatase 1B inhibitory activities of all the isolates were evaluated. Compounds 3, 7: , and 8: at 10 µM showed potent inhibitory activities on lipopolysaccharide-induced nitric oxide production in BV-2 microglial cells, with nitric oxide levels decreasing to 31.5, 41.9, and 27.1%, respectively, while compounds 3, 4, 7: , and 8: exhibited notable inhibitory activities against protein tyrosine phosphatase 1B, with IC50 values ranging from 1.7 to 18.2 µM. Interestingly, compounds 3: and 8: , bearing a C-3 trans-p-coumaroyl group, showed not only more potent anti-inflammatory effects, but also exhibited stronger protein tyrosine phosphatase 1B inhibition than their respective stereoisomers (2: and 7: ) with a cis-p-coumaroyl group.

854-P: ENT-03, a Centrally Acting Endogenous Spermine Bile Acid with PTP1B Inhibitory Activity, Has Potent Effects on Metabolism and Weight in a Mouse Model of Diet-Induced Obesity (DIO)

Background: We have discovered ENT-03, a spermine-bile acid of unprecedented structure in the brain of neonatal mice. ENT-03 appears postnatally at a time when the maternal supply of milk is inadequate to support maximal growth and development. ENT-03 has PTP1B inhibitory activity and acts centrally to normalize glycemia and reverse obesity. Methods: ENT-03 (25mg/kg), semaglutide (0.04mg/kg) or vehicle were administered subcutaneously twice weekly for 10 weeks to DIO mice (n=5/group). Results: In ENT-03 treated mice on a high fat diet, non-fasting glucose rapidly fell to within normal range prior to any significant weight loss (p=2×10-5), remaining normal thereafter. In contrast, in semaglutide treated mice, glucose fell in proportion to weight loss, remaining elevated throughout (p=0.2). ENT-03 treated mice were restored to lean body weight. Body weight and glucose improved partially in semaglutide treated mice. Body fat decreased by 49% in ENT-03 (p=10-5) and by 19% in semaglutide treated mice (p=0.1). Basal glucose uptake in muscle was increased 3-fold in ENT-03 treated mice compared to controls. Conclusion: ENT-03 is a novel endogenous, centrally acting mammalian steroid which rapidly normalizes glucose, independent of body weight and causes gradual but marked weight loss in DIO mice. Phase 1 studies will begin in Q2 2023. Disclosure D.Barbut: None. J.A.Baur: Consultant; Cytokinetics Inc., Pfizer Inc., Other Relationship; Elysium Health, Research Support; Pfizer Inc., Metro Biotech. P.M.Titchenell: Consultant; Alnylam, Guidepoint, AstraZeneca. J.G.Davis: None. M.B.Zemel: None. G.Fleming: Board Member; NuSirt, Consultant; Amolyt, Oramed Pharmaceuticals, Adocia, Aerami, TixiMed, Biocon, Hagar, CMC Magnetics, AdioPharm. A.C.Moses: Advisory Panel; Enterin, ViaCyte, Inc., GentiBio, TixiMed, Consultant; Virta Health Corp., ARMI (Advanced Regenerative Manufacturing Institute), Stock/Shareholder; Minutia. M.Zasloff: None.

Neo-Clerodane and tiliifolane-type diterpenoids, and other constituents from Salvia pennellii

Two undescribed neo-clerodanes (1 and 2) and a novel tiliifolane (3) diterpenoids, were isolated from the leaves and flowers of Salvia pennellii. Wirikutin (1) and 15-epi-wirikutin (2) were isolated as a C-15 epimeric mixture containing a 5-hydroxyfuran-2(5H)-one moiety in the side chain of the neo-clerodane framework. Wixarikolide (3) was isolated as a Δ3(20) derivative of tiliifodiolide. The structures of compounds 1/2 were deduced through the analyses of their MS spectrometric, and the 1D/2D NMR data. The structure of 3 was determined directly by single crystal X-ray diffraction. The PTP1B inhibitory activity of compounds 1/2 was assayed.

Isosteviol derivatives as protein tyrosine Phosphatase-1B inhibitors: Synthesis, biological evaluation and molecular docking.

Protein tyrosine phosphatase (PTP1B) antagonizes insulin signaling and acts as a potential therapeutic target for insulin resistance associated with obesity and type II diabetes. In this work, a series of isosteviol derivatives 1-28 was synthesized and the inhibitory activity on PTP1B was evaluated by double antibody sandwich ELISA (DAS-ELISA) in vitro. Most isosteviol derivatives showed moderate PTP1B inhibitory activities. Among them, derivatives 10, 13, 24, 27 showed remarkable bioactivities with IC50 values ranging from 0.24 to 0.40µM. Particularly, derivative 24 exhibited the best inhibitory activity against PTP1B (IC50=0.24µM) in vitro; moreover, it showed 7-fold selectivity to PTP1B over T-cell protein tyrosine phosphatase (TCPTP) and 14-fold selectivity to PTP1B over cell division cycle 25 homolog B (CDC25B). Molecular docking studies demonstrated the hydrogen bond interaction between 24 and LYS-116 residue in PTP1B might be essential for the inhibitory activity. The results suggested that derivative 24 has great potential to be employed as drug candidate for the treatment of obesity and type II diabetes.

Characterization of Serrulatane Diterpenoids in Eremophila phyllopoda subsp. phyllopoda by Triple High-Resolution α-Glucosidase/PTP1B/Radical Scavenging Profiling, NMR Spectroscopy, DFT-GIAO NMR, and Electronic Circular Dichroism Calculations.

Extracts of Eremophila phyllopoda subsp. phyllopoda showed α-glucosidase and PTP1B inhibitory activity with IC50 values of 19.6 and 13.6 μg/mL, respectively. High-resolution α-glucosidase/PTP1B/radical scavenging profiling was performed to establish a triple high-resolution inhibition profile that allowed direct pinpointing of the constituents responsible for one or more of the observed bioactivities. Subsequent targeted isolation and purification by analytical-scale HPLC led to the identification of 21 previously undescribed serrulatane diterpenoids, eremophyllanes A-U, as well as two known serrulatane diterpenoids, 1β-trihydroxyserrulatane (8) and 1α-trihydroxyserrulatane (10d), and five known furofuran lignans, (+)-piperitol (6), horsfieldin (7e), (-)-sesamin (9), (+)-sesamin (10h), and asarinin (10i). Their structures were elucidated by extensive analysis of HRMS and 1D and 2D NMR spectroscopic data. The relative configurations of the previously undescribed compounds were established by analysis of ROESY spectra as well as by DFT-GIAO NMR calculations followed by DP4+ probability analysis. The absolute configurations were determined by comparison of experimental and calculated ECD spectra. Serrulatane diterpenoids 7b and 14 exhibited α-glucosidase inhibitory activity with IC50 values of 28.4 and 64.2 μM, respectively, while 11, 12, 14, and 15 exhibited PTP1B inhibitory activity with IC50 values ranging from 16.6 to 104.6 μM. Hypothetical routes for formation of all identified serrulatane diterpenoids are proposed.

Discovery of Novel PTP1B Inhibitors with Once-Weekly Therapeutic Potential for Type 2 Diabetes: Design, Synthesis, and In Vitro and In Vivo Investigations of BimBH3 Peptide Analogues.

Poor medication adherence in patients with type 2 diabetes mellitus has become one of the main causes of suboptimal glycemic control. Once-weekly drugs can markedly improve the convenience, adherence, and quality of life of T2DM patients; thus, they are clinically needed and preferred. PTP1B plays a negative role in both insulin and leptin signaling pathways, which makes it an important target for diabetes. Herein, we design and synthesize 35 analogues of core BimBH3 peptide via lipidation/acylation strategy based on our previous work and evaluate their PTP1B inhibitory activity, obtaining the primary structure-activity relationship. Five compounds with good PPT1B inhibitory activity, target selectivity, and significantly improved stability were selected for molecular docking study and searching candidate molecules with long-acting antidiabetic potential. The in vivo anti-T2DM evaluation validated the once-weekly therapeutic potential of analogues 19, 26, 27, 31, and 33, which were comparable with semaglutide and therefore presented as promising drug candidates.

Root-Extracted lignanamides from Limonium gmelinii (Willd.) Kuntze with a potential PTP1B inhibitory activity by regulating PI3K/AKT signaling pathway

The phytochemical study of Limonium gmelinii roots resulted in the isolation of five lignanamides (1–5). Among them, limoniumins J, K, and M (1, 2, and 4) are undescribed compounds, limoniumin L (3) is a new naturally occurring lignanamide, and limoniumin B (5) is a known compound which showed PTP1B inhibition activity with an IC50 value of 5.05 ± 2.44 μM in our previous work. Spectroscopic data analysis, including 1D and 2D NMR and HRESIMS experiments, established the chemical structures of limoniumins J − M (1–4). Compounds 1–4 showed PTP1B inhibition activity, among which compound 3 showed the most potent PTP1B inhibition with an IC50 value of 2.07 ± 0.05 μM. Compounds 3 and 5 could significantly increase cellular glucose consumption and glucose uptake in L6 muscle cells and could synergize with insulin to promote glucose consumption and glucose uptake in a concentration-dependent manner. The treatment of compound 3 also promoted glycogen synthesis in skeletal muscle cells. Western blot analysis demonstrated that the good hypoglycemic effect of compounds 3 and 5 was achieved by activating PI3K/AKT signaling pathway to promote glucose consumption, glucose uptake, and glycogen synthesis. Furthermore, studies on molecular docking revealed the potent interactions between these bioactive substances and the PTP1B protein.

Phenolic and bisamide derivatives from Aglaia odorata and their biological activities

Three new compounds (1–3), including two bisamide derivatives (1 and 2) and a lignin (3), along with 15 known compounds were isolated from Aglaia odorata. Compound 2 was a pair of enantiomers and successfully resolved into the anticipated enantiomers. Their structures were elucidated by extensive spectroscopic analysis, electronic circular dichroism (ECD) calculations, and X-ray crystallography. Three compounds showed excellent inhibitory activities on α-glucosidase with IC50 values ranging from 54.48 to 240.88 μM, better than that of the positive control (acarbose, IC50 = 590.94 μM). Moreover, compounds 3, 13, and 15 presented moderate inhibitory activities against butyrylcholinesterase. Compound 17 exhibited potent PTP1B inhibitory activity with an IC50 value of 179.45 μM. Representative active compounds were performed for the molecular docking study. Herein, we described the isolation, structure elucidation, the inhibitory effects on three enzymes, and molecular docking of the isolates from the title plant.