Natural constituents from Cortex Mori Radicis as new pancreatic lipase inhibitors

Hou, Xu-Dong; Ge, Guang-Bo; Weng, Zi-Miao; Dai, Zhicheng; Leng, Yue-Hong; Ding, Le-Le; Jin, Lingling; Yu, Yang; Cao, Yun‐Feng; Hou, Jie

doi:10.1016/j.bioorg.2018.07.011

Cited by 54 publications

(27 citation statements)

References 47 publications

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“…This enzyme is responsible for the intestinal digestion of triacylglycerols from the diet, limiting their absorption in the gastrointestinal tract. Thus, this enzyme has become an important therapeutic target in the development of anti-obesity agents [ 2 , 3 ]. Nowadays, the only PL inhibitor approved by the Food and Drug Administration (FDA) is orlistat (tetrahydrolipstatin), recommended for long-term use to reduce the absorption of dietary fat.…”

Section: Introductionmentioning

confidence: 99%

Cocoa (Theobroma cacao L.) Seed Proteins’ Anti-Obesity Potential through Lipase Inhibition Using In Silico, In Vitro and In Vivo Models

Coronado-Cáceres

Rabadán-Chávez

Mojica

et al. 2020

Foods

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The aim of this study was to determine the pancreatic lipase (PL) inhibitory effect of cocoa protein (CP) hydrolysates (CPH) using in silico and in vitro approaches, and an in vivo high-fat diet (HF) obese rat model. The results showed better theoretical affinity on PL for cocoa peptides EEQR, GGER, QTGVQ, and VSTDVNIE released from vicilin and albumins (−6.5, −6.3, −6.2, and −6.1 kcal/mol, respectively). Absorption, distribution, metabolism, and excretion (ADMET) prediction showed the human intestinal absorption (HIA) capacity of orlistat and eight cocoa peptides, demonstrating that they presented a low probability of toxicity with values lower than 0.6, while the orlistat has a high probability of hepatotoxicity with a mean value of 0.9. CPH (degree of hydrolysis of 55%) inhibited PL with an IC50 (concentration needed to inhibit 50% of enzyme activity) value of 1.38 mg/mL. The intragastric administration of 150 mg CP/kg/day to rats increased total lipids and triglycerides excretion in feces, ranging from 11% to 15% compared to the HF-diet. The HF + CP-diet also significantly decreased (p < 0.05) the apparent rate of fat absorption compared with the HF group. These results suggest that CP has anti-obesity potential by inhibiting PL, thus helping to prevent the development of non-communicable diseases.

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Section: Introductionmentioning

confidence: 99%

Cocoa (Theobroma cacao L.) Seed Proteins’ Anti-Obesity Potential through Lipase Inhibition Using In Silico, In Vitro and In Vivo Models

Coronado-Cáceres

Rabadán-Chávez

Mojica

et al. 2020

Foods

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“…In particular, sanggenon D had the strongest inhibitory activity with IC 50 of 0.77 µM and Ki of 0.43 µM. Molecular docking was also performed between sanggenon D and HPL, which resulted in good binding to the active site through hydrogen interactions with Ser152 and hydrophobic interactions with Phe77 [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

Exploring Aurone Derivatives as Potential Human Pancreatic Lipase Inhibitors through Molecular Docking and Molecular Dynamics Simulations

et al. 2020

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Inhibition of human pancreatic lipase, a crucial enzyme in dietary fat digestion and absorption, is a potent therapeutic approach for obesity treatment. In this study, human pancreatic lipase inhibitory activity of aurone derivatives was explored by molecular modeling approaches. The target protein was human pancreatic lipase (PDB ID: 1LPB). The 3D structures of 82 published bioactive aurone derivatives were docked successfully into the protein catalytic active site, using AutoDock Vina 1.5.7.rc1. Of them, 62 compounds interacted with the key residues of catalytic trial Ser152-Asp176-His263. The top hit compound (A14), with a docking score of −10.6 kcal⋅mol−1, was subsequently submitted to molecular dynamics simulations, using GROMACS 2018.01. Molecular dynamics simulation results showed that A14 formed a stable complex with 1LPB protein via hydrogen bonds with important residues in regulating enzyme activity (Ser152 and Phe77). Compound A14 showed high potency for further studies, such as the synthesis, in vitro and in vivo tests for pancreatic lipase inhibitory activity.

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“…It has recently been shown that morusin also serves as an allosteric inhibitor of metabolic enzymes including pancreatic lipase, UDP-glucuronosyltransferase (UGT) and cytochrome p450 (CYP450) [ 16 , 61 ]. Such findings may be clinically relevant, since these enzymes have been implicated in the dysregulation of lipid homeostasis and endoplasmic reticulum stress, which play key roles in the pathogenesis of various metabolic disorders including diabetes [ 62 , 63 ].…”

Section: Resultsmentioning

confidence: 99%

“…Morusin also targets the STAT3 pathway and its downstream targets, including survivin, cyclin B1, to exert antitumor activity in prostate and pancreatic cancers [ 36 , 48 ]. In the case of pancreatic cancer, pancreatic lipase may be another relevant target of morusin, considering (1) the strong association between pancreatic cancer and the levels of pancreatic lipase [ 48 ] and (2) the potential role of morusin in the allosteric regulation of pancreatic lipase [ 61 ].…”

Section: Resultsmentioning

confidence: 99%

The Beneficial Effects of Morusin, an Isoprene Flavonoid Isolated from the Root Bark of Morus

Choi

Cho

Lee

et al. 2020

IJMS

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The root bark of Morus has long been appreciated as an antiphlogistic, diuretic and expectorant drug in Chinese herbal medicine, albeit with barely known targets and mechanisms of action. In the 1970s, the development of analytic chemistry allowed for the discovery of morusin as one of 7 different isoprene flavonoid derivatives in the root bark of Morus. However, the remarkable antioxidant capacity of morusin with the unexpected potential for health benefits over the other flavonoid derivatives has recently sparked scientific interest in the biochemical identification of target proteins and signaling pathways and further clinical relevance. In this review, we discuss recent advances in the understanding of the functional roles of morusin in multiple biological processes such as inflammation, apoptosis, metabolism and autophagy. We also highlight recent in vivo and in vitro evidence on the clinical potential of morusin treatment for multiple human pathologies including inflammatory diseases, neurological disorders, diabetes, cancer and the underlying mechanisms.

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Natural constituents from Cortex Mori Radicis as new pancreatic lipase inhibitors

Cited by 54 publications

References 47 publications

Cocoa (Theobroma cacao L.) Seed Proteins’ Anti-Obesity Potential through Lipase Inhibition Using In Silico, In Vitro and In Vivo Models

Cocoa (Theobroma cacao L.) Seed Proteins’ Anti-Obesity Potential through Lipase Inhibition Using In Silico, In Vitro and In Vivo Models

Exploring Aurone Derivatives as Potential Human Pancreatic Lipase Inhibitors through Molecular Docking and Molecular Dynamics Simulations

The Beneficial Effects of Morusin, an Isoprene Flavonoid Isolated from the Root Bark of Morus

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