Promoting Effects on Hepatocyte Growth Factor Production of Daphnane Diterpenoids from Daphne odora

Nakasone, Rie; Kurisu, Manami; Onodera, Manami

doi:10.3987/com-13-12687

Cited by 4 publications

(2 citation statements)

References 12 publications

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“…Colorless oil; [α] D 25 + 52.5 ( c 0.42, MeOH); 1 H NMR (CDCl 3 , 400 MHz) δ H 7.92 (2H, m), 7.60 (1H, m), 7.48 (2H, m), 7.47 (2H, m), 6.69 (1H, dd, J = 15.5, 10.7 Hz), 6.06 (1H, dd, J = 15.5, 10.7 Hz), 5.88 (1H, m), 5.68 (1H, d, J = 15.5 Hz), 5.52 (1H, s), 5.19 (1H, s), 5.02 (1H, s), 5.01 (1H, s), 4.90 (1H, d, J = 2.5 Hz), 4.75 (1H, d, J = 12.0 Hz), 3.98 (1H, m), 3.68 (1H, d, J = 2.5 Hz), 3.52 (1H, s), 2.47 (1H, q, J = 7.2 Hz), 2.13 (3H, s), 2.11 (1H, m), 2.02 (3H, s), 1.87 (3H, s), 1.74 (3H, br s), 1.40 (2H, m), 1.34 (3H, d, J = 7.2 Hz), 0.89 (3H, t, J = 6.6 Hz); 13 C NMR (CDCl 3 , 100 MHz) δ C 10.0, 14.0, 18.1, 18.8, 20.6, 20.7, 22.5, 28.7, 31.3, 32.7, 35.8, 43.9, 47.9, 59.5, 64.2, 66.4, 68.4, 71.7, 77.9, 78.9, 80.2, 83.9, 113.7, 117.2, 122.0, 128.5, 128.6, 129.5, 129.8, 133.3, 135.2, 137.1, 139.5, 143.0, 158.1, 165.4, 168.9, 170.6, 205.5; ESIMS m / z 733.3 [M + H] + , 777.2 [M + Cl] − . These data were consistent with those reported …”

Section: Methodssupporting

confidence: 94%

Discovery of the First Raptor (Regulatory-Associated Protein of mTOR) Inhibitor as a New Type of Antiadipogenic Agent

et al. 2023

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Raptor, a regulatory-associated protein of mTOR, has been genetically proved to be an important regulator in lipogenesis. However, its druggable potential is rarely investigated, largely due to the lack of an inhibitor. In this study, the antiadipogenic screening of a daphnane diterpenoid library followed by target fishing led to the identification of a Raptor inhibitor, 1c (5/7/6 carbon ring with orthoester and chlorine functionalities). Pharmacodynamic studies verified that 1c is a potent and tolerable antiadipogenic agent in vitro and in vivo. Mechanistic studies revealed that the targeting of Raptor by 1c could block the formation of mTORC1 and then downregulate the downstream S6K1- and 4E-BP1-mediated C/EBPs/PPARγ signaling, eventually retarding adipocyte cell differentiation at the early stage. These findings suggest that Raptor can be explored as a novel therapeutic target for obesity and its related complications, and 1c as the first Raptor inhibitor may provide a new therapeutic option for these conditions.

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Section: Methodssupporting

confidence: 94%

Discovery of the First Raptor (Regulatory-Associated Protein of mTOR) Inhibitor as a New Type of Antiadipogenic Agent

et al. 2023

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“…The name odoratin is confusing because there are no fewer than six different compounds called odoratin, issued from different plants [ 51 , 52 ]. Parenthetically, there is another daphnane diterpenoid with the same molecular formula as odoracin and called odoratrin (both C 37 H 44 O 10 ), also isolated from Daphne odora [ 47 , 53 ]. The name gnidilatidin has been used occasionally in a few publications.…”

Section: Yuanhuacin a Potent Anticancer Agentmentioning

confidence: 99%

Yuanhuacin and Related Anti-Inflammatory and Anticancer Daphnane Diterpenes from Genkwa Flos—An Overview

Bailly

2022

Biomolecules

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The dried flower buds of the plant Daphne genkwa Sieb. et Zucc. have been largely used in traditional Chinese medicine for the treatment of inflammatory diseases. Numerous diterpenoids have been isolated from the Genkwa Flos (yuanhua in Chinese), including a series of daphnane-type diterpene designated as yuanhuacin (YC, often improperly designated as yuanhuacine) and analogues with a patronymic name. The series includes ten daphnane-type diterpenes: yuanhuacin, yuanhuadin (YD), yuanhuafin (YF), yuanhuagin (YG), yuanhuahin (YH), yuanhuajin (YJ), yuanhualin (YL), yuanhuamin (YM), yuanhuapin (YP), and yuanhuatin (YT). They are distinct from the rare flavonoid yuanhuanin. The series comprises several anticancer agents, such as the lead compound YC, which has revealed potent activity in vitro and in vivo against models of lung and breast cancers. The main signaling pathways implicated in the antitumor effects have been delineated. Protein kinase C is a key factor of activity for YC, but in general the molecular targets at the origin of the activity of these compounds remain little defined. Promising anticancer effects have been reported with analogues YD and YT, whereas compounds YF and YP are considered more toxic. The pharmacological activity of each compound is presented, as well as the properties of Genkwa Flos extracts. The potential toxic effects associated with the use of these compounds are also underlined.

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Cyanidin 3-Glucoside Induces Hepatocyte Growth Factor in Normal Human Dermal Fibroblasts through the Activation of β₂-Adrenergic Receptor

Krama¹,

Tokura²,

Isoda

et al. 2022

ACS Omega

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Hepatocyte growth factor (HGF) is expressed in various organs and involved in the fundamental cellular functions such as mitogenic, motogenic, and morphogenic activities. Induction of HGF may be therapeutically useful for controlling organ regeneration, wound healing, and embryogenesis. In this study, we examined the stimulation effect of cyanidin 3-glucoside (C3G), an anthocyanidin derivative, on HGF production in normal human dermal fibroblasts (NHDFs) and the underlying mechanisms. C3G induced HGF production at both mRNA and protein levels in NHDF cells and enhanced the phosphorylation of cAMP-response element-binding protein. We also observed that treatment with C3G increased intracellular cAMP level and promoter activity of cAMP-response element in HEK293 cells expressing β 2 -adrenergic receptor (β 2 AR). In contrast, cyanidin, an aglycon of C3G, did not show the activation of β 2 AR signaling and HGF production. These results indicate that C3G behaves as an agonist for β 2 AR signaling to activate the protein kinase A pathway and induce the production of HGF.

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Promoting Effects on Hepatocyte Growth Factor Production of Daphnane Diterpenoids from Daphne odora

Cited by 4 publications

References 12 publications

Discovery of the First Raptor (Regulatory-Associated Protein of mTOR) Inhibitor as a New Type of Antiadipogenic Agent

Discovery of the First Raptor (Regulatory-Associated Protein of mTOR) Inhibitor as a New Type of Antiadipogenic Agent

Yuanhuacin and Related Anti-Inflammatory and Anticancer Daphnane Diterpenes from Genkwa Flos—An Overview

Cyanidin 3-Glucoside Induces Hepatocyte Growth Factor in Normal Human Dermal Fibroblasts through the Activation of β₂-Adrenergic Receptor

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Promoting Effects on Hepatocyte Growth Factor Production of Daphnane Diterpenoids from Daphne odora

Cited by 4 publications

References 12 publications

Discovery of the First Raptor (Regulatory-Associated Protein of mTOR) Inhibitor as a New Type of Antiadipogenic Agent

Discovery of the First Raptor (Regulatory-Associated Protein of mTOR) Inhibitor as a New Type of Antiadipogenic Agent

Yuanhuacin and Related Anti-Inflammatory and Anticancer Daphnane Diterpenes from Genkwa Flos—An Overview

Cyanidin 3-Glucoside Induces Hepatocyte Growth Factor in Normal Human Dermal Fibroblasts through the Activation of β2-Adrenergic Receptor

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Cyanidin 3-Glucoside Induces Hepatocyte Growth Factor in Normal Human Dermal Fibroblasts through the Activation of β₂-Adrenergic Receptor