Chalcone derivatives from the root bark of Morus alba L. act as inhibitors of PTP1B and α-glucosidase

Ha, Manh Tuan; Seong, Su Hui; Dat, Nguyen Tien; Cho, Won‐Kyung; Ah, Kim Jeong; Yeul, Jin; Woo, Mi Hee; Choi, Jae Sue; Min, Byung Sun

doi:10.1016/j.phytochem.2018.08.001

Cited by 80 publications

(69 citation statements)

References 43 publications

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“…The strongest H-bond interaction, however, was observed between the nitrogen group of Gly183 and the hydroxyl group in C-9 (ring B) of 1, with a bond distance of 2.86 Å. In addition, 1 also displayed hydrophobic interactions with some reported catalytic residues of PTP1B, such as Tyr46, Trp179, and Gln266 [23,24], which further stabilized the enzyme-inhibitor interaction (▶ Fig. 6, Table 4).…”

Section: Resultsmentioning

confidence: 99%

“…The 1 H NMR spectrum (▶ Table 1) showed signals for a pair of meta-coupled aromatic protons at δ H 6. 23 phatic fragment to form a ring (ring C) was needed to satisfy the 11 degrees of unsaturation of 1.…”

Section: Resultsmentioning

confidence: 99%

“…Many studies have indicated that the binding of ligand with residues in the α3 and α7 helices of PTP1B could lead to allosteric inhibition of enzyme activity [8,[23][24][25]. Leu192, Asn193, Phe196, Phe280 residues were frequently reported as the interacting residues for some PTP1B allosteric inhibitors [23][24][25]. From our docking results, the enzyme-inhibitor complexes of all tested compounds at the allosteric site of PTP1B exhibited high binding affinity (− 4.54, − 5.96, − 4.66, − 5.14, and − 5.21 kcal/mol, respectively) (▶ Table 4).…”

Section: Resultsmentioning

confidence: 99%

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Unusual Prenylated Stilbene Derivatives with PTP1B Inhibitory Activity from Artocarpus styracifolius

Zhang

et al. 2019

Planta Med

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In an effort to identify agents from natural products that inhibit protein tyrosine phosphatase 1B (PTP1B), 5 new prenylated stilbenes, (±)-styrastilbene A (1), styrastilbene B (2), and (±)-styrastilbenes C – E (3, 4, and 7), along with 4 known structurally related compounds (5, 6, 8, and 9), were isolated from the roots of Artocarpus styracifolius. Their structures were elucidated by spectroscopic methods, including 1D and 2D nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass spectrometry (HRESIMS), ultraviolet (UV), and infrared (IR). Based on these isolates, a new plausible biosynthetic pathway for the unusual stilbene derivatives 3–8 with a tetracyclic ring system is proposed. Among these compounds, 1–3, 8, and 9 displayed significant PTP1B inhibitory effects with IC50 values ranging from 2.40 (95% confidence interval [CI]: 2.21 – 2.59) to 8.80 (95% CI: 8.28 – 9.32) µM. Moreover, kinetic analysis and molecular docking simulations were performed to provide insight into the inhibition type as well as the interaction and binding mode of these active isolates with PTP1B. Our results revealed mixed-type PTP1B inhibition for all compounds tested. Docking simulations of these stilbene derivatives showed negative binding energies and close proximity to residues at the allosteric and catalytic sites of PTP1B. These findings suggest that these compounds may have a potential to be further developed as agents for the management of type 2 diabetes mellitus.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Unusual Prenylated Stilbene Derivatives with PTP1B Inhibitory Activity from Artocarpus styracifolius

Zhang

et al. 2019

Planta Med

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“…Traditionally, the leaves of M. alba have been used as herbal tea with important bioactivities such as antioxidant, antidepressant, hypoglycemic, and hepatoprotective effects (Choi et al 2013 ; Sánchez-Salcedo et al 2017 ). Pharmacological properties of the root bark extract of M. alba include anti-Alzheimer, anti-asthmatic, antibacterial, anti-cancer, anti-depressant, anti-inflammatory, anti-obesity, antioxidant, anti-tyrosinase, cardio-protective, hypoglycaemic, myocardial protective, neuroprotective, and pancreatic lipase inhibitory activities (Yang et al 2014 ; Ha et al 2016 , 2018 ; Kuk et al 2017 ). 2-Arylbenzofurans are especially known as the principal constituent of Morus plants and usually comprised of some substituents such as prenyl, geranyl, and farnesyl groups (Fig.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of PTP1B by farnesylated 2-arylbenzofurans isolated from Morus alba root bark: unraveling the mechanism of inhibition based on in vitro and in silico studies

Shrestha

Trần

et al. 2020

Arch. Pharm. Res.

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acid (IC 50 = 11.34 µM)]. Besides, two 2-arylbenzofurans [morusalfurans A (1) and F (6)], one flavonoid [morusalnol B (9)], and one geranylated stilbene [morusibene A (11)] exhibited PTP1B inhibition with IC 50 values ranging from 11.02 to 26.56 µM. Kinetic studies revealed compounds 2, 3, 6, and 11 as mixed type PTP1B inhibitors, while 1 and 9 are known as noncompetitive. Molecular docking simulations demonstrated that these active compounds can bind with the respective catalytic or/and allosteric sites of PTP1B with negative binding energies and the results are in accordance with that of the kinetic studies. To the best of our knowledge, this is the first time, the PTP1B inhibitory activity of eleven compounds (1-11), as well as the mechanism of action underlying the effects on PTP1B enzyme of the active compounds, were investigated. In vitro and in silico results suggest that the farnesylated 2-arylbenzofurans from M. alba may potentially be utilized as an effective treatment therapy for type 2 diabetes mellitus and its associated complications.

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“…No previous reports have considered the root bark of M. alba. In our recent work, we reported the antidiabetic [20,21], anti-Alzheimer's disease activity [22,23], and antioxidant and anti-browning property [24] of Diels-Alder-type adducts and arylbenzofurans from M. alba root bark. More recently, kuwanon G and albanin G from the root bark were hypothesized as the components responsible for the appetite suppression activity of root-bark extract via cannabinoid (CB1) receptor antagonism [25].…”

Section: Introductionmentioning

confidence: 99%

Novel Diels–Alder Type Adducts from Morus alba Root Bark Targeting Human Monoamine Oxidase and Dopaminergic Receptors for the Management of Neurodegenerative Diseases

Paudel

Park

Seong

et al. 2019

IJMS

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In this study, we delineate the human monoamine oxidase (hMAO) inhibitory potential of natural Diels–Alder type adducts, mulberrofuran G (1), kuwanon G (2), and albanol B (3), from Morus alba root bark to characterize their role in Parkinson’s disease (PD) and depression, focusing on their ability to modulate dopaminergic receptors (D1R, D2LR, D3R, and D4R). In hMAO-A inhibition, 1–3 showed mild effects (50% inhibitory concentration (IC50): 54‒114 μM). However, 1 displayed moderate inhibition of the hMAO-B isozyme (IC50: 18.14 ± 1.06 μM) followed by mild inhibition by 2 (IC50: 57.71 ± 2.12 μM) and 3 (IC50: 90.59 ± 1.72 μM). Our kinetic study characterized the inhibition mode, and the in silico docking predicted that the moderate inhibitor 1 would have the lowest binding energy. Similarly, cell-based G protein-coupled receptors (GPCR) functional assays in vector-transfected cells expressing dopamine (DA) receptors characterized 1–3 as D1R/D2LR antagonists and D3R/D4R agonists. The half-maximum effective concentration (EC50) of 1–3 on DA D3R/D4R was 15.13/17.19, 20.18/21.05, and 12.63/‒ µM, respectively. Similarly, 1–3 inhibited 50% of the DA response on D1R/D2LR by 6.13/2.41, 16.48/31.22, and 7.16/18.42 µM, respectively. A computational study revealed low binding energy for the test ligands. Interactions with residues Asp110, Val111, Tyr365, and Phe345 at the D3R receptor and Asp115 and His414 at the D4R receptor explain the high agonist effect. Likewise, Asp187 at D1R and Asp114 at D2LR play a crucial role in the antagonist effects of the ligand binding. Our overall results depict 1–3 from M. alba root bark as good inhibitors of hMAO and potent modulators of DA function as D1R/D2LR antagonists and D3R/D4R agonists. These active constituents in M. alba deserve in-depth study for their potential to manage neurodegenerative disorders (NDs), particularly PD and psychosis.

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Chalcone derivatives from the root bark of Morus alba L. act as inhibitors of PTP1B and α-glucosidase

Cited by 80 publications

References 43 publications

Unusual Prenylated Stilbene Derivatives with PTP1B Inhibitory Activity from Artocarpus styracifolius

Unusual Prenylated Stilbene Derivatives with PTP1B Inhibitory Activity from Artocarpus styracifolius

Inhibition of PTP1B by farnesylated 2-arylbenzofurans isolated from Morus alba root bark: unraveling the mechanism of inhibition based on in vitro and in silico studies

Novel Diels–Alder Type Adducts from Morus alba Root Bark Targeting Human Monoamine Oxidase and Dopaminergic Receptors for the Management of Neurodegenerative Diseases

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