Preventing H2O2-induced toxicity in primary cerebellar granule neurons via activating the PI3-K/Akt/GSK3β pathway by kukoamine from Lycii Cortex

Li, Yuan Yuan; Hu, Songhua; Huang, Yuanhao; Han, Yifan; Cheung, Hon-Yeung

doi:10.1016/j.jff.2015.06.029

Cited by 11 publications

(5 citation statements)

References 52 publications

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“…[ [256][257][258] Kukoamine A was demonstrated to inhibit human glioblastoma cell growth and migration in vitro and in vivo through apoptosis induction and epithelial-mesenchymal transition attenuation (Figure 44B). [259] Thanks to these both activities, 139 was studied to prevent the detrimental effect of ionizing radiation used during radiotherapy on hippocampal neurons and demonstrated to be neuroprotective compound against radiation-induced brain injury though inhibiting neuronal oxidative stress and apoptosis (Figure 44C).…”

Section: Vi-1-kukoamine Amentioning

confidence: 99%

Synthesis and Biological Activities of Naturally Functionalized Polyamines: An Overview

Negrel

Brunel

2021

CMC

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Section: Vi-1-kukoamine Amentioning

confidence: 99%

Synthesis and Biological Activities of Naturally Functionalized Polyamines: An Overview

Negrel

Brunel

2021

CMC

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“…In fact, many pharmaceuticals commonly used today are structurally derived from natural molecules, such as metformin. Some natural products, such as flavonoids, polyphenols, and organic acids, have shown in vitro efficacy involving actions of reducing glucose absorption (Zhang et al, 2016), alleviating insulin resistance (Zhang et al, 2012), oxidative stress (Ramful et al, 2010; Li et al, 2015), and inflammation (Zagotta et al, 2015). However, in-depth and holistic in vivo studies are still required to validate the efficacies and safety and to understand the modes of action, because T2DM is a systemic metabolic disorder.…”

Section: Introductionmentioning

confidence: 99%

“…Our previous study revealed that kukoamines, especially kukoamine B, are the major compounds of LyC, accounting for approximately 2% of the herbal dry mass (Li et al, 2014). Recent research from our group and other research groups has revealed that KB (or its isomer kukoamine A) has bioactivities in anti-oxidation, anti-inflammation, and anti-insulin resistance (Liu et al, 2011; Li et al, 2015, 2017), which are highly associated with diabetes; however, direct in vivo evidence showing the beneficial effect of KB on T2DM from the viewpoint of metabolomics has not yet been found.…”

Section: Introductionmentioning

confidence: 99%

A Metabolomics Approach to Investigate Kukoamine B—A Potent Natural Product With Anti-diabetic Properties

Stewart

Ye³

et al. 2019

Front. Pharmacol.

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Due to the surge in type 2 diabetes mellitus (T2DM), treatments for chronic metabolic dysregulations with fewer side-effects are sought. Lycii Cortex (LyC), a traditional Chinese Medicine (TCM) herb has a long history of being widely prescribed to treat T2DM as alternative medicine; however, the bioactive molecules and working mechanism remained unknown. Previous studies revealed kukoamine B (KB) as a major and featured compound for LyC with bioactivities for anti-oxidation and acute inflammation, which may be related to anti-diabetes properties. This study aims to understand the efficacy and the mode of action of KB in the diabetic (db/db) mouse model using a metabolomics approach. Parallel comparison was conducted using the first-line anti-diabetic drugs, metformin and rosligtazone, as positive controls. The db/db mice were treated with KB (50 mg kg−1 day−1) for 9 weeks. Bodyweight and fasting blood glucose were monitored every 5 and 7 days, respectively. Metabolomics and high-throughput molecular approaches, including lipidomics, targeted metabolomics (Biocrates p180), and cytokine profiling were applied to measure the alteration of serum metabolites and inflammatory biomarkers between different treatments vs. control (db/db mice treated with vehicle). After 9 weeks of treatment, KB lowered blood glucose, without the adverse effects of bodyweight gain and hepatomegaly shown after rosiglitazone treatment. Lipidomics analysis revealed that KB reduced levels of circulating triglycerides, cholesterol, phosphatidylethanolamine, and increased levels of phosphatidylcholines. KB also increased acylcarnitines, and reduced systemic inflammation (cytokine array). Pathway analysis suggested that KB may regulate nuclear transcription factors (e.g., NF-κB and/or PPAR) to reduce inflammation and facilitate a shift toward metabolic and inflammatory homeostasis. Comparison of KB with first-line drugs suggests that rosiglitazone may over-regulate lipid metabolism and anti-inflammatory responses, which may be associated with adverse side effects, while metformin had less impact on lipid and anti-inflammation profiles. Our research from holistic and systemic views supports the conclusion that KB is the bioactive compound of LyC for managing T2DM, and suggests KB as a nutraceutical or a pharmaceutical candidate for T2D treatment. In addition, our research provides insights related to metformin and rosiglitazone action, beyond lowering blood glucose.

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“…Kukoamines are a series of plant polyamines composed of a polymethylenepolyamine backbone (i.e., putrescine, spermidine, and spermine) and at least one dihydrocaffeic acid fragment. , They were first discovered in lycii cortex (LyC) , and then subsequently found in other plants of the Solanaceae family, such as potato, tomato, and tobacco . Due to their versatile bioactivities, such as antihypertension, antitrypanosome, antilipid peroxidation and lipoxygenase, antisepsis, , and neuroprotection, kukoamines have received attention in recent years as functional foods and drug candidates. Because the polymethylenepolyamine backbone may conjugate with different phenolic moieties to form diverse derivatives, investigation of its molecular diversity is crucial for understanding kukoamine biosynthesis and metabolism, which are meaningful for drug discovery.…”

Section: Introductionmentioning

confidence: 99%

Identification and Characterization of Kukoamine Metabolites by Multiple Ion Monitoring Triggered Enhanced Product Ion Scan Method with a Triple-Quadruple Linear Ion Trap Mass Spectrometer

Wang

Zhao

et al. 2015

J. Agric. Food Chem.

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Kukoamines are a series of bioactive phytochemicals conjugated by a polyamine backbone and phenolic moieties. Understanding the structural diversity of kukoamine metabolites in plants is meaningful for drug discovery. In this study, an LC-MS/MS method was established for kukoamine profiling and characterization from lycii cortex (LyC) via a triple-quadrupole linear ion trap mass spectrometry (Q-TRAP). On the basis of the typical fragmentation of kukoamine, a diagnostic ion, which represents the features of the backbone and phenolic substitute, was chosen as the product ion for precursor ion scan, and then the screened precursor ions were applied to a successive multiple ion monitoring triggered enhanced product ion scan (MIM-EPI) to simultaneously present the profile survey and MS/MS acquisition. Because the MIM narrowed the ion scan range in Q1 and the ion trap enhanced the ion fragments passing through Q2, the qualitative capability of quadrupole MS can be greatly improved, especially for capture of the uncommon metabolites. There are 12 kukoamine metabolites identified from LyC, with either spermine or spermidine backbone and with conjugation of one to three dihydrocaffeoyls or other kinds of phenolic moieties. Except for kukoamines A and B, other metabolites were identified in LyC for the first time. This approach can be utilized for metabolite identification in other substrates.

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Preventing H2O2-induced toxicity in primary cerebellar granule neurons via activating the PI3-K/Akt/GSK3β pathway by kukoamine from Lycii Cortex

Cited by 11 publications

References 52 publications

Synthesis and Biological Activities of Naturally Functionalized Polyamines: An Overview

Synthesis and Biological Activities of Naturally Functionalized Polyamines: An Overview

A Metabolomics Approach to Investigate Kukoamine B—A Potent Natural Product With Anti-diabetic Properties

Identification and Characterization of Kukoamine Metabolites by Multiple Ion Monitoring Triggered Enhanced Product Ion Scan Method with a Triple-Quadruple Linear Ion Trap Mass Spectrometer

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