Diabetes mellitus and Alzheimer's disease: GSK-3β as a potential link.

Arctigenin (AR) and its glycoside, arctiin, are two major active ingredients of Arctium lappa L (A lappa), a popular medicinal herb and health supplement frequently used in Asia. In the past several decades, bioactive components from A lappa have attracted the attention of researchers due to their promising therapeutic effects. In the current article, we aimed to provide an overview of the pharmacology of AR and arctiin, focusing on their anti-inflammatory effects, pharmacokinetics properties and clinical efficacies. Compared to acrtiin, AR was reported as the most potent bioactive component of A lappa in the majority of studies. AR exhibits potent anti-inflammatory activities by inhibiting inducible nitric oxide synthase (iNOS) via modulation of several cytokines. Due to its potent anti-inflammatory effects, AR may serve as a potential therapeutic compound against both acute inflammation and various chronic diseases. However, pharmacokinetic studies demonstrated the extensive glucuronidation and hydrolysis of AR in liver, intestine and plasma, which might hinder its in vivo and clinical efficacy after oral administration. Based on the reviewed pharmacological and pharmacokinetic characteristics of AR, further pharmacokinetic and pharmacodynamic studies of AR via alternative administration routes are suggested to promote its ability to serve as a therapeutic agent as well as an ideal bioactive marker for A lappa.

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Overview of the anti-inflammatory effects, pharmacokinetic properties and clinical efficacies of arctigenin and arctiin from Arctium lappa L.

Lignans and Neolignans: Plant secondary metabolites as a reservoir of biologically active substances.

Alzheimer's disease (AD) and Parkinson's disease (PD) are two typical neurodegenerative diseases that increased with aging. With the emergence of aging population, the health problem and economic burden caused by the two diseases also increase. Phosphatidylinositol 3-kinases/protein kinase B (PI3K/AKT) signaling pathway regulates signal transduction and biological processes such as cell proliferation, apoptosis and metabolism. According to reports, it regulates neurotoxicity and mediates the survival of neurons through different substrates such as forkhead box protein Os (FoxOs), glycogen synthase kinase-3β (GSK-3β), and caspase-9. Accumulating evidences indicate that some natural products can play a neuroprotective role by activating PI3K/AKT pathway, providing an effective resource for the discovery of potential therapeutic drugs. This article reviews the relationship between AKT signaling pathway and AD and PD, and discusses the potential natural products based on the PI3K/AKT signaling pathway to treat two diseases in recent years, hoping to provide guidance and reference for this field. Further development of Chinese herbal medicine is needed to treat these two diseases.

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PI3K/AKT Signal Pathway: A Target of Natural Products in the Prevention and Treatment of Alzheimer's Disease and Parkinson's Disease.

// Qingmei Kang 1, 2, * , Yue Xiang 1, 2, * , Dan Li 1, 2 , Jie Liang 1, 2 , Xiong Zhang 2 , Fanlin Zhou 1, 2 , Mengyuan Qiao 1, 2 , Yingling Nie 1, 2 , Yurong He 1, 2 , Jingyi Cheng 1, 2 , Yubing Dai 3 , Yu Li 1, 2 1 Department of Pathology, Chongqing Medical University, Chongqing, 400016, China 2 Center for Molecular Medicine Testing, Chongqing Medical University, Chongqing, 400016, China 3 Department of Neurosurgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, China * These authors contributed equally to this work Correspondence to: Yu Li, email: liyu100@163.com Keywords: miR-124-3p, tau, caveolin-1, PI3K/Akt/GSK3β, Alzheimer's disease Received: November 02, 2016      Accepted: January 24, 2017      Published: February 07, 2017 ABSTRACT Hyperphosphorylation of Tau forming neurofibrillary tangles has been considered as a crucial event in the pathogenesis of Alzheimer's disease (AD). MiR-124-3p belongs to microRNA (miRNA) family and was markedly decreased in AD, however, the functions of miR-124-3p in the pathogenesis of AD remain unknown. We observed that the expression of miR-124-3p was significantly decreased in N2a/APP695swe cells; and transfection of miR-124-3p mimics not only attenuated cell apoptosis and abnormal hyperphosphorylation of Tau protein without any changes of total Tau protein, but also increased expression levels of Caveolin-1, phosphoinositide 3-kinase (PI3K), phospho-Akt (Akt-Ser473)/Akt, phospho-glycogen synthase kinase-3 beta (GSK-3β-Ser9)/GSK-3β in N2a/APP695swe cells. We further found that miR-12-3p directly targeted Caveolin-1; miR-124-3p inhibited abnormal hyperphosphorylation of Tau by regulating Caveolin-1-PI3K/Akt/GSK3β pathway in AD. This study reveals that miR-124-3p may play a neuroprotective role in AD, which may provide new ideas and therapeutic targets for AD.

/pdf/mir-124-3p-attenuates-hyperphosphorylation-of-tau-protein-1j8d7nn3wl.pdf

MiR-124-3p attenuates hyperphosphorylation of Tau protein-induced apoptosis via caveolin-1-PI3K/Akt/GSK3β pathway in N2a/APP695swe cells.

Arctigenin is a phenylpropanoid dibenzylbutyrolactone lignan compound possessing antitumor, anti-inflammatory, anti-influenza, antioxidant, antibacterial, and hypoglycaemic activities. Our previous study demonstrated that arctigenin exerts neuroprotective effects both in vitro and in vivo in a Parkinsonʼs disease model. However, the exact mechanism through which arctigenin improves amyloid beta-induced memory impairment by inhibiting the production of the hyperphosphorylated tau protein is unknown. Amyloid β 1–42 was slowly administered via the intracerebroventricular route in a volume of 3 µL (≈ 410 pmmol/mouse) to mice. The mice were administered arctigenin (10, 40, or 150 mg/kg) or vehicle starting from the second day after amyloid β 1–42 injection to the end of the experiment. Behavioural tests were performed from days 9 to 15. On day 16 after the intracerebroventricular administration of amyloid β 1–42 , the mice were sacrificed for biochemical analysis. Arctigenin (10–150 mg/kg) significantly attenuated the impairment of spontaneous alternation behaviours in the Y-maze task, decreased the escape latency in the Morris water maze test, and increased the swimming times and swimming distances to the platform located in the probe test. Arctigenin attenuated the level of phosphorylated tau at the Thr-181, Thr-231, and Ser-404 sites in the hippocampus, and increased the phosphorylation levels of phosphatidylinositol-3-kinase, threonine/serine protein kinase B, and glycogen synthase kinase-3 β . Arctigenin effectively provides protection against learning and memory deficits and in inhibits hyperphosphorylated tau protein expression in the hippocampus. The possible mechanism may occur via the phosphatidylinositol-3-kinase/protein kinase B-dependent glycogen synthase kinase-3 β signalling pathway.

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Arctigenin Attenuates Learning and Memory Deficits through PI3k/Akt/GSK-3β Pathway Reducing Tau Hyperphosphorylation in Aβ-Induced AD Mice.

Thirteen trace elements and active constituents of 40 batches of Lonicera japonica flos and Lonicera flos were comparatively studied using inductively coupled plasma mass-spectrometry (ICP-MS) and high-performance liquid chromatography-photodiode array (HPLC-PDA). The trace elements were 24Mg, 52Cr, 55Mn, 57Fe, 60Ni, 63Cu, 66Zn, 75As, 82Se, 98Mo, 114Cd, 202Hg, and 208Pb, and the active compounds were chlorogenic acid, 3,5-O-dicaffeoylquinc acid, 4,5-O-dicaffeoylquinc acid, luteolin-7-O-glucoside, and 4-O-caffeoylquinic acid. The data of 18 variables were statistically processed using principal component analysis (PCA) and discriminate analysis (DA) to classify L. japonica flos and L. flos. The validated method was developed to divide the 40 samples into two groups based on the PCA in terms of 18 variables. Furthermore, the species of Lonicera was better discriminated by using DA with 12 variables. These results suggest that the method and statistical analysis of the contents of trace elements and chemical components can classify the L. japonica flos and L. flos using 12 variables, such as 3,5-O-dicaffeoylquincacid, luteolin-7-O-glucoside, Cd, Mn, Hg, Pb, Ni, 4-O-caffeoyl-quinic acid, 4,5-O-dicaffeoylquinc acid, Fe, Mg, and Cr.

Comparison of the Trace Elements and Active Components of Lonicera japonica flos and Lonicera flos Using ICP-MS and HPLC-PDA

The invention discloses a medicine composition, and particularly relates to a medicine composition containing active ingredients of jujube kernel tranquilizing pellets. The composition is prepared from spina date seed aqueous extract, salviae miltiorrhizae aqueous extract and lignan extract of fructus schizandrae, wherein the weight ratio of spina date seed to salviae miltiorrhizae to fructus schizandrae is (5-20):(1-5):(1-5); the spina date seed aqueous extract is prepared by purifying water reflux extract of spina date seeds by means of macroporous adsorption resin; the salviae miltiorrhizae aqueous extract is a total phenolic acid extract prepared by purifying water reflux extract of salviae miltiorrhizae by means of macroporous adsorption resin; and the lignan extract of fructus schizandrae is prepared by carrying out CO2 supercritical extraction on fructus schizandrae. The composition is determined by early pharmacodynamic material basis researches and is a natural ingredient composition capable of improving sleeping very well.

Yue Qi

Papers

Arctigenin Attenuates Learning and Memory Deficits through PI3k/Akt/GSK-3β Pathway Reducing Tau Hyperphosphorylation in Aβ-Induced AD Mice.

Comparison of the Trace Elements and Active Components of Lonicera japonica flos and Lonicera flos Using ICP-MS and HPLC-PDA

Medicine composition containing active ingredients of jujube kernel tranquilizing pellets