Bioactive enmein-type 6,7-seco-ent-kaurane diterpenoids: natural products, synthetic derivatives and apoptosis related mechanism

Li, Haonan; Sun, Baojia; Wang, Mingying; Hu, Xu; Gao, Xiang; Xu, Shengtao; Xu, Yongnan; Xu, Jinyi; Hua, Hui‐Ming; Li, Dahong

doi:10.1007/s12272-018-1078-3

Cited by 11 publications

(6 citation statements)

References 81 publications

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“…Thus, the suppression of neuroinflammation could be another mechanism that explains the neuroprotection exerted by enmein against KA-induced excitotoxicity. Our findings are consistent with those of previous studies that have reported the anti-inflammatory properties of enmein [ 16 ]. Accumulated evidence from animal models suggests that anti-inflammatory drugs may have potential neuroprotective effects for several neurological diseases.…”

Section: Discussionsupporting

confidence: 94%

“…Diterpenoids are important and widely distributed natural compounds with various biological effects, including antitumor, anti-inflammatory, and immune modulation effects [ 32 ]. Enmein is a diterpenoid extracted from Isodon japonicus Hara that exhibits antitumor, anti-inflammatory, and immune modulation effects [ 16 , 17 , 33 ]. The present study provides the first description of the role of enmein in the central glutamate system, including its ability to regulate glutamate release from rat cerebrocortical nerve terminals and exhibit neuroprotective effects in a rat model of KA-induced glutamate excitotoxicity.…”

Section: Discussionmentioning

confidence: 99%

“…Enmein is a diterpenoid derived from the plant Isodon japonicus Hara that is widely used in dietary supplements and folk medicine [ 14 ]. Enmein has antibacterial [ 15 ], anti-inflammatory [ 16 ], antitumor [ 17 ], and immunosuppressive effects [ 18 ]. There is currently no data to support the effects of enmein on the central glutamate system.…”

Section: Introductionmentioning

confidence: 99%

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Enmein Decreases Synaptic Glutamate Release and Protects against Kainic Acid-Induced Brain Injury in Rats

Huang

Chiu

et al. 2021

IJMS

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This study investigated the effects of enmein, an active constituent of Isodon japonicus Hara, on glutamate release in rat cerebrocortical nerve terminals (synaptosomes) and evaluated its neuroprotective potential in a rat model of kainic acid (KA)-induced glutamate excitotoxicity. Enmein inhibited depolarization-induced glutamate release, FM1-43 release, and Ca2+ elevation in cortical nerve terminals but had no effect on the membrane potential. Removing extracellular Ca2+ and blocking vesicular glutamate transporters, N- and P/Q-type Ca2+ channels, or protein kinase C (PKC) prevented the inhibition of glutamate release by enmein. Enmein also decreased the phosphorylation of PKC, PKC-α, and myristoylated alanine-rich C kinase substrates in synaptosomes. In the KA rat model, intraperitoneal administration of enmein 30 min before intraperitoneal injection of KA reduced neuronal cell death, glial cell activation, and glutamate elevation in the hippocampus. Furthermore, in the hippocampi of KA rats, enmein increased the expression of synaptic markers (synaptophysin and postsynaptic density protein 95) and excitatory amino acid transporters 2 and 3, which are responsible for glutamate clearance, whereas enmein decreased the expression of glial fibrillary acidic protein (GFAP) and CD11b. These results indicate that enmein not only inhibited glutamate release from cortical synaptosomes by suppressing Ca2+ influx and PKC but also increased KA-induced hippocampal neuronal death by suppressing gliosis and decreasing glutamate levels by increasing glutamate uptake.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Enmein Decreases Synaptic Glutamate Release and Protects against Kainic Acid-Induced Brain Injury in Rats

Huang

Chiu

et al. 2021

IJMS

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“…A third mode of complexity generation is the cleavage of a C−C bond leading to a truncated or ring‐opened carbon skeleton [9–16] . This process gives rise to nor ‐ and seco ‐terpenoids, and leads to increased chemical diversity in a cluster of related secondary metabolites by modification of the parent carbocyclic core.…”

Section: Introductionmentioning

confidence: 99%

seco‐Labdanes: A Study of Terpenoid Structural Diversity Resulting from Biosynthetic C−C Bond Cleavage

Grant

Brimble

2021

Chemistry A European J

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The cleavage of a C−C bond is a complexity generating process, which complements oxidation and cyclisation events in the biosynthesis of terpenoids. This process leads to increased structural diversity in a cluster of related secondary metabolites by modification of the parent carbocyclic core. In this review, we highlight the diversifying effect of C−C bond cleavage by examining the literature related to seco‐labdanes—a class of diterpenoids arising from such C−C bond cleavage events.

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“…In the process of drug design and discovery, molecular design based on natural products is the most efficient and promising strategy to search for high activity and securely molecular structures, which have a variety of advantages such as extensive bioactivity, low cytotoxicity, [1] novel structures [2] and environment friendliness. [3] Natural stilbenes are an important class of biologically active metabolites with the presence of a 1,2-diphenylethylene skeleton, which are widespread in many trees species. [4] Stilbenes and its derivatives display broad spectrum of biological activities such as antimicrobial, [5] anti-HIV, [6] antioxidant, [7] anti-inflammatory, [8] antiviral [9] and anticancer activities.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis and Biological Evaluation of Stilbene Derivatives Containing a 1,3‐Benzodioxole Moiety

et al. 2020

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Stilbene is an important class of biologically active metabolites with diarylethene scaffold, and which have a broad range of biological activities as the lead for drug discovery. In this study, a novel series of stilbene derivatives bearing 1,3-benzodioxole moiety was designed and synthesized via a convenient method with good to excellent yields, and their structures were characterized by 1 H NMR, 13 C NMR, ESI-MS spectrum. These newly prepared compounds were evaluated for their potential biological activities including fungicidal, insecticidal, and cytotoxic activities.

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Bioactive enmein-type 6,7-seco-ent-kaurane diterpenoids: natural products, synthetic derivatives and apoptosis related mechanism

Cited by 11 publications

References 81 publications

Enmein Decreases Synaptic Glutamate Release and Protects against Kainic Acid-Induced Brain Injury in Rats

Enmein Decreases Synaptic Glutamate Release and Protects against Kainic Acid-Induced Brain Injury in Rats

seco‐Labdanes: A Study of Terpenoid Structural Diversity Resulting from Biosynthetic C−C Bond Cleavage

Design, Synthesis and Biological Evaluation of Stilbene Derivatives Containing a 1,3‐Benzodioxole Moiety

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