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821 KiB

Open AccessArticle

Ent-Abietanoids Isolated from Isodon serra

by Jun Wan, Hua-Yi Jiang, Jian-Wei Tang, Xing-Ren Li, Xue Du, Yan Li, Han-Dong Sun and Jian-Xin Pu

Molecules 2017, 22(2), 309; https://doi.org/10.3390/molecules22020309 - 17 Feb 2017

Cited by 9 | Viewed by 4515

Abstract

Four new ent-abietane diterpenoids, along with four known ones were isolated from the aerial parts of Isodon serra, a traditional Chinese folk medicine. The new diterpenoids were named as serrin K (1), xerophilusin XVII (2), and enanderianins [...] Read more.

Four new ent-abietane diterpenoids, along with four known ones were isolated from the aerial parts of Isodon serra, a traditional Chinese folk medicine. The new diterpenoids were named as serrin K (1), xerophilusin XVII (2), and enanderianins Q and R (3 and 4), while the known ones were identified as rubescansin J (5), (3α,14β)-3,18-[(1-methylethane-1,1-diyl)dioxy]-ent-abieta-7,15(17)-diene-14,16-diol (6), xerophilusin XIV (7), and enanderianin P (8), respectively. Their structures were elucidated by extensive spectroscopic analysis and comparison with the literature. Compound 1 showed remarkable inhibitory activity towards NO production in LPS-stimulated RAW264.7 cells (IC₅₀ = 1.8 μM) and weak cytotoxicity towards five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480). Full article

(This article belongs to the Special Issue Diterpene and Its Significance in Natural Medicine)

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10384 KiB

Open AccessArticle

Penduliflaworosin, a Diterpenoid from Croton crassifolius, Exerts Anti-Angiogenic Effect via VEGF Receptor-2 Signaling Pathway

by Yeyin Liang, Yubo Zhang, Guocai Wang, Yaolan Li and Weihuan Huang

Molecules 2017, 22(1), 126; https://doi.org/10.3390/molecules22010126 - 13 Jan 2017

Cited by 14 | Viewed by 5268

Abstract

Anti-angiogenesis targeting vascular endothelial growth factor receptor-2 (VEGFR-2) has been considered as an important strategy for cancer therapy. Penduliflaworosin is a diterpenoid isolated from the plant Croton crassifolius. Our previous study showed that this diterpenoid possesses strong anti-angiogenic activity by inhibiting vessel [...] Read more.

Anti-angiogenesis targeting vascular endothelial growth factor receptor-2 (VEGFR-2) has been considered as an important strategy for cancer therapy. Penduliflaworosin is a diterpenoid isolated from the plant Croton crassifolius. Our previous study showed that this diterpenoid possesses strong anti-angiogenic activity by inhibiting vessel formation in zebrafish. This study was conducted to further investigate the anti-angiogenic activity and mechanism of penduliflaworosin. Results revealed that penduliflaworosin significantly inhibited VEGF-induced angiogenesis processes including proliferation, invasion, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). Moreover, it notably inhibited VEGF-induced sprout formation of aortic rings and blocked VEGF-induced vessel formation in mice. Western blotting studies showed that penduliflaworosin inhibited phosphorylation of the VEGF receptor-2 and its downstream signaling mediators in HUVECs, suggesting that the anti-angiogenic activity was due to an interference with the VEGF/VEGF receptor-2 pathway. In addition, molecular docking simulation indicated that penduliflaworosin could form hydrogen bonds within the ATP-binding region of the VEGF receptor-2 kinase unit. Finally, cytotoxicity assay showed that penduliflaworosin possessed little toxicity toward both cancer and normal cells. Taken together, our findings demonstrate that penduliflaworosin exerts its anti-angiogenic effect via the VEGF receptor-2 signaling pathway. The anti-angiogenic property and low cytotoxicity of penduliflaworosin suggest that it may be useful in cancer treatments. Full article

(This article belongs to the Special Issue Diterpene and Its Significance in Natural Medicine)

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1496 KiB

Open AccessArticle

Anti-Neuroinflammatory ent-Kaurane Diterpenoids from Pteris multifida Roots

by Jung Wha Kim, Ji Yeon Seo, Won Keun Oh and Sang Hyun Sung

Molecules 2017, 22(1), 27; https://doi.org/10.3390/molecules22010027 - 26 Dec 2016

Cited by 18 | Viewed by 5466

Abstract

Activated microglia are known to be a major source of cellular neuroinflammation which causes various neurodegenerative diseases, including Alzheimer’s disease. In our continuing efforts to search for new bioactive phytochemicals against neuroinflammatory diseases, the 80% methanolic extract of Pteris multifida (Pteridaceae) roots was [...] Read more.

Activated microglia are known to be a major source of cellular neuroinflammation which causes various neurodegenerative diseases, including Alzheimer’s disease. In our continuing efforts to search for new bioactive phytochemicals against neuroinflammatory diseases, the 80% methanolic extract of Pteris multifida (Pteridaceae) roots was found to exhibit significant NO inhibitory activity in lipopolysaccharide (LPS)-activated BV-2 microglia cells. Three new ent-kaurane diterpenoids, pterokaurane M₁ 2-O-β-d-glucopyranoside (4), 2β,16α-dihydroxy-ent-kaurane 2,16-di-O-β-d-glucopyranoside (10), and 2β,16α,17-trihydroxy-ent-kaurane 2-O-β-d-glucopyranoside (12), were isolated along with nine other known compounds from P. multifida roots. The chemical structures of the new compounds were determined by 1D- and 2D-NMR, HR-ESI-MS, and CD spectroscopic data analysis. Among the isolates, compounds 1 and 7 significantly inhibited NO production in LPS-stimulated BV-2 cells reducing the expression of the cyclooxygenase-2 (COX-2) protein and the level of pro-inflammatory mediators such as prostaglandin E₂ (PGE₂), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. These results suggest that ent-kaurane diterpenes from P. multifida could be potential lead compounds that act as anti-neuroinflammatory agents. Full article

(This article belongs to the Special Issue Diterpene and Its Significance in Natural Medicine)

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1507 KiB

Open AccessArticle

Uprolides N, O and P from the Panamanian Octocoral Eunicea succinea

by Daniel Torres-Mendoza, Yisett González, José Félix Gómez-Reyes, Héctor M. Guzmán, José Luis López-Perez, William H. Gerwick, Patricia L. Fernandez and Marcelino Gutiérrez

Molecules 2016, 21(6), 819; https://doi.org/10.3390/molecules21060819 - 22 Jun 2016

Cited by 11 | Viewed by 5750

Abstract

Three new diterpenes, uprolide N (1), uprolide O (2), uprolide P (3) and a known one, dolabellane (4), were isolated from the CH₂Cl₂-MeOH extract of the gorgonian octocoral Eunicea succinea, [...] Read more.

Three new diterpenes, uprolide N (1), uprolide O (2), uprolide P (3) and a known one, dolabellane (4), were isolated from the CH₂Cl₂-MeOH extract of the gorgonian octocoral Eunicea succinea, collected from Bocas del Toro, on the Caribbean coast of Panama. Their structures were determined using spectroscopic analyses, including 1D and 2D NMR and high-resolution mass spectrometry (HRMS) together with molecular modeling studies. Compounds 1–3 displayed anti-inflammatory properties by inhibiting production of Tumor Necrosis Factor (TNF) and Interleukin (IL)-6 induced by lipopolysaccharide (LPS) in murine macrophages. Full article

(This article belongs to the Special Issue Diterpene and Its Significance in Natural Medicine)

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8974 KiB

Open AccessArticle

An Ingenol Derived from Euphorbia kansui Induces Hepatocyte Cytotoxicity by Triggering G0/G1 Cell Cycle Arrest and Regulating the Mitochondrial Apoptosis Pathway in Vitro

by Xiaojing Yan, Li Zhang, Yudan Cao, Weifeng Yao, Yuping Tang and Anwei Ding

Molecules 2016, 21(6), 813; https://doi.org/10.3390/molecules21060813 - 22 Jun 2016

Cited by 17 | Viewed by 7918

Abstract

Natural product lingenol, a purified diterpenoid compound derived from the root of Euphorbia kansui, exerts serious hepatotoxicity; however, the molecular mechanisms remain to be defined. In the present study, cell counting Kit-8 (CCK-8), inverted phase contrast microscope and flow cytometry were used [...] Read more.

Natural product lingenol, a purified diterpenoid compound derived from the root of Euphorbia kansui, exerts serious hepatotoxicity; however, the molecular mechanisms remain to be defined. In the present study, cell counting Kit-8 (CCK-8), inverted phase contrast microscope and flow cytometry were used to demonstrate that lingenol significantly inhibited L-O2 cells proliferation, and induced cell cycle arrest and apoptosis. Moreover, the results investigated that lingenol markedly disrupted mitochondrial functions by high content screening (HCS). In addition, the up-regulation of cytochrome c, AIF and Apaf-1 and activation of caspases were found in L-O2 cells detected by Western blotting and ELISA assay, which was required for lingenol activation of cytochrome c-mediated caspase cascades and AIF-mediated DNA damage. Mechanistic investigations revealed that lingenol significantly down-regulated the Bcl-2/Bax ratio and enhanced the reactive oxygen species (ROS) in L-O2 cells. These data collectively indicated that lingenol modulation of ROS and Bcl-2/Bax ratio led to cell cycle arrest and mitochondrial-mediated apoptosis in L-O2 cells in vitro. All of these results will be helpful to reveal the hepatotoxicity mechanism of Euphorbia kansui and to effectively guide safer and better clinical application of this herb. Full article

(This article belongs to the Special Issue Diterpene and Its Significance in Natural Medicine)

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363 KiB

Open AccessCommunication

Cytotoxic Labdane Diterpenes from Hedychium ellipticum Buch.-Ham. ex Sm.

by Sineenard Songsri and Nuchnipa Nuntawong

Molecules 2016, 21(6), 749; https://doi.org/10.3390/molecules21060749 - 09 Jun 2016

Cited by 19 | Viewed by 5164

Abstract

In order to reveal the constituents and their biological activities, we carried out a phytochemical study on Hedychium ellipticum Buch.-Ham. ex Sm. (Zingiberaceae). Ten labdane diterpenoids (1–10) were isolated from the rhizomes of H. ellipticum for the first time. [...] Read more.

In order to reveal the constituents and their biological activities, we carried out a phytochemical study on Hedychium ellipticum Buch.-Ham. ex Sm. (Zingiberaceae). Ten labdane diterpenoids (1–10) were isolated from the rhizomes of H. ellipticum for the first time. Their structures were identified on the basis of spectroscopic analyses including two-dimensional NMR and comparison with literature data. All of these compounds were evaluated for their antimycobacterial activity against Mycobacterium tuberculosis and cytotoxicity against KB, MCF7, NCI-H187 and Vero cells. The result showed that compounds 1 and 7 exhibited moderate activity against Mycobacterium tuberculosis and compounds 4, 6 and 7 displayed remarkable cytotoxic activity. This is the first report on the presence of all compounds in H. ellipticum and the first time that their structure activity relationship has been discussed. Full article

(This article belongs to the Special Issue Diterpene and Its Significance in Natural Medicine)

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1240 KiB

Open AccessArticle

Antimicrobial Diterpenoids of Wedelia trilobata (L.) Hitchc

by Shi-Fei Li, Jia-Yin Ding, Ya-Ting Li, Xiao-Jiang Hao and Shun-Lin Li

Molecules 2016, 21(4), 457; https://doi.org/10.3390/molecules21040457 - 07 Apr 2016

Cited by 15 | Viewed by 6573

Abstract

Continued interest in the metabolites of Wedelia trilobata (L.) Hitchc, a notoriously invasive weed in South China, led to the isolation of twenty-six ent-kaurane diterpenoids, including seven new ones 1–7. Their structures and relative configuration were elucidated on the basis of extensive [...] Read more.

Continued interest in the metabolites of Wedelia trilobata (L.) Hitchc, a notoriously invasive weed in South China, led to the isolation of twenty-six ent-kaurane diterpenoids, including seven new ones 1–7. Their structures and relative configuration were elucidated on the basis of extensive spectroscopic analysis, including 1D- and 2D-NMR experiments. The antimicrobial activities of all isolated diterpenoids were evaluated against a panel of bacteria and fungi. Full article

(This article belongs to the Special Issue Diterpene and Its Significance in Natural Medicine)

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929 KiB

Open AccessArticle

Labdane Diterpenes from the Fruits of Sinopodophyllum emodi

by Yan-Jun Sun, Mei-Ling Gao, Yan-Li Zhang, Jun-Min Wang, Ya Wu, Yu Wang and Tao Liu

Molecules 2016, 21(4), 434; https://doi.org/10.3390/molecules21040434 - 31 Mar 2016

Cited by 8 | Viewed by 4734

Abstract

Two new labdane diterpenes, sinoditerpene A (1) and B (2), were isolated from the fruits of Sinopodophyllum emodi, along with two known analogues 3 and 4. Their structures were established on the basis of extensive spectroscopic analysis. The isolation of compounds 1–4 [...] Read more.

Two new labdane diterpenes, sinoditerpene A (1) and B (2), were isolated from the fruits of Sinopodophyllum emodi, along with two known analogues 3 and 4. Their structures were established on the basis of extensive spectroscopic analysis. The isolation of compounds 1–4 represents the first report of diterpenes from the genus Sinopodophyllum. The cytotoxic activities of all isolated compounds were evaluated in comparison with 5-fluorouracil against the MCF-7 and HepG2 cell lines, towards which 3 showed more potent cytotoxicity. Full article

(This article belongs to the Special Issue Diterpene and Its Significance in Natural Medicine)

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Review

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Open AccessReview

Anticancer Activities of C₁₈-, C₁₉-, C₂₀-, and Bis-Diterpenoid Alkaloids Derived from Genus Aconitum

by Meng-Yue Ren, Qing-Tian Yu, Chun-Yu Shi and Jia-Bo Luo

Molecules 2017, 22(2), 267; https://doi.org/10.3390/molecules22020267 - 13 Feb 2017

Cited by 27 | Viewed by 5914

Abstract

Cancer is one of the most common lethal diseases, and natural products have been extensively studied as anticancer agents considering their availability, low toxicity, and economic affordability. Plants belonging to the genus Aconitum have been widely used medically in many Asian countries since [...] Read more.

Cancer is one of the most common lethal diseases, and natural products have been extensively studied as anticancer agents considering their availability, low toxicity, and economic affordability. Plants belonging to the genus Aconitum have been widely used medically in many Asian countries since ancient times. These plants have been proven effective for treating several types of cancer, such as lung, stomach, and liver cancers. The main effective components of Aconitum plants are diterpenoid alkaloids—which are divided into C₁₈-, C₁₉-, C₂₀-, and bis-diterpenoid alkaloids—are reportedly some of the most promising, naturally abundant compounds for treating cancer. This review focuses on the progress of diterpenoid alkaloids with different structures derived from Aconitum plants and some of their derivatives with potential anticancer activities. We hope that this work can serve as a reference for further developing Aconitum diterpenoid alkaloids as anticancer agents. Full article

(This article belongs to the Special Issue Diterpene and Its Significance in Natural Medicine)

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