THC (Δ9‐Tetrahydrocannabinol) Exerts Neuroprotective Effect in Glutamate‐affected Murine Primary Mesencephalic Cultures Through Restoring Mitochondrial Membrane Potential and Anti‐apoptosis Involving CB1 Receptor‐dependent Mechanism

Aging‐related neurodegenerative diseases, such as Parkinson's disease (PD) or related disorders, are an increasing societal and economic burden worldwide. Δ9‐Tetrahydrocannabinol (THC) is discussed as a neuroprotective agent in several in vitro and in vivo models of brain injury. However, the mechanisms by which THC exhibits neuroprotective properties are not completely understood. In the present study, we investigated neuroprotective mechanisms of THC in glutamate‐induced neurotoxicity in primary murine mesencephalic cultures, as a culture model for PD. Glutamate was administered for 48 h with or without concomitant THC treatment. Immunocytochemistry staining and resazurin assay were used to evaluate cell viability. Furthermore, superoxide levels, caspase‐3 activity, and mitochondrial membrane potential were determined to explore the mode of action of this compound. THC protected dopaminergic neurons and other cell types of primary dissociated cultures from glutamate‐induced neurotoxicity. Moreover, THC significantly counteracted the glutamate‐induced mitochondrial membrane depolarization and apoptosis. SR141716A, a CB₁ receptor antagonist, concentration‐dependently blocked the protective effect of THC in primary mesencephalic cultures. In conclusion, THC exerts anti‐apoptotic and restores mitochondrial membrane potential via a mechanism dependent on CB₁ receptor. It strengthens the fact that THC has a benefit on degenerative cellular processes occurring, among others, in PD and other neurodegenerative diseases by slowing down the progression of neuronal cell death. Copyright © 2016 John Wiley & Sons, Ltd.     

Schisandra chinensis extract ameliorates age‐related muscle wasting and bone loss in ovariectomized rats

Exercise and healthy diet consumption support healthy aging. Schisandra chinensis (Turcz.) also known as “Baill.” has anti‐inflammatory and antioxidant properties. However, the role of S. chinensis as an antiaging compound has yet to be demonstrated. This study elucidated the antiaging effect of S. chinensis ethanol–hexane extract (C1) and the effect of C1 treatment on muscle and bone following physical exercise in ovariectomized (OVX) rats. RAW 264.7, human diploid fibroblasts (HDFs), C2C12 myoblasts, bone marrow macrophages, and MC3T3‐E1 cells were used for in vitro, and muscle and bone of OVX rats were used for in vivo study to demonstrate the effect of C1. The C1 significantly inhibited the expression of inflammatory molecules, β‐galactosidase activity, and improved antioxidant activity via down‐regulation of reactive oxygen species in RAW 264.7 and aged HDF cells. The C1 with exercise improved muscle regeneration in skeletal muscle of OVX rats by promoting mitochondrial biogenesis and autophagy. C1 induced osteoblast differentiation, and C1 + exercise modulated the bone formation and bone resorption in OVX rats. C1 exhibited anti‐inflammatory, antioxidant, myogenic, and osteogenic effects. C1 with exercise improved age‐related muscle wasting and bone loss. Therefore, S. chinensis may be a potential prevent agent for age‐related diseases such as sarcopenia and osteoporosis.     

Bacopa monnieri‐Induced Protective Autophagy Inhibits Benzo[a]pyrene‐Mediated Apoptosis

Benzo[a]pyrene (B[a]P) is capable of inducing oxidative stress and cellular injuries leading to cell death and associates with a significant risk of cancer development. Prevention of B[a]P‐induced cellular toxicity with herbal compound through regulation of mitochondrial oxidative stress might protect cell death and have therapeutic benefit to human health. In this study, we demonstrated the cytoprotective role of Bacopa monnieri (BM) against B[a]P‐induced apoptosis through autophagy induction. Pretreatment with BM rescued the reduction in cell viability in B[a]P‐treated human keratinocytes (HaCaT) cells indicating the cytoprotective potential of BM against B[a]P. Moreover, BM was found to inhibit B[a]P‐mediated reactive oxygen species (ROS)‐induced apoptosis activation in HaCaT cells. Furthermore, BM was found to preserve mitochondrial membrane potential and inhibited release of cytochrome c in B[a]P‐treated HaCaT cells. Bacopa monnieri induced protective autophagy; we knocked down Beclin‐1, and data showed that BM was unable to protect from B[a]P‐induced mitochondrial ROS‐mediated apoptosis in Beclin‐1‐deficient HaCaT cells. Moreover, we established that B[a]P‐induced damaged mitochondria were found to colocalize and degraded within autolysosomes in order to protect HaCaT cells from mitochondrial injury. In conclusion, B[a]P‐induced apoptosis was rescued by BM treatment and provided cytoprotection through Beclin‐1‐dependent autophagy activation. Copyright © 2016 John Wiley & Sons, Ltd.     

Schisandrin B stereoisomers protect against hypoxia/reoxygenation‐induced apoptosis and associated changes in the Ca2+‐induced mitochondrial permeability transition and mitochondrial membrane potential in AML12 hepatocytes

The effects of the schisandrin B stereoisomers, (±)γ‐schisandrin [(±)γ‐Sch] and (?)schisandrin B [(?)Sch B], on hypoxia/reoxygenation‐induced apoptosis were investigated in AML12 hepatocytes. Changes in cellular reduced glutathione (GSH) levels, Ca²⁺‐induced mitochondrial permeability transitions (MPTs) and mitochondrial membrane potentials (Δψ_m values) were also examined in (±)γ‐Sch‐ and (?)Sch B‐treated cells, without or with hypoxia/reoxygenation challenge. The (±)γ‐Sch/(?)Sch B pretreatments (2.5–5.0 µm ) protected against hypoxia/reoxygenation‐induced apoptosis in AML12 cells in a concentration‐dependent manner, with the (?)Sch B effect being more potent. Drug antiapoptotic effects were further evidenced by suppression of hypoxia/reoxygenation‐induced mitochondrial cytochrome c release and subsequent cleavage of caspase 3 and poly‐ADP‐ribose polymerase by (?)Sch B pretreatment. Whereas hypoxia/reoxygenation challenge increased the extent of Ca²⁺‐induced MPT pore opening, and Δψ_m, in AML12 hepatocytes, cytoprotection afforded by (±)γ‐Sch/(?)Sch B pretreatment against hypoxia/reoxygenation‐induced apoptosis was associated with a decreased sensitivity to Ca²⁺‐induced MPT and an increased Δψ_m in both unchallenged and challenged cells, compared with the drug‐free control. The results indicate that (±)γ‐Sch/(?)Sch B pretreatment protected against hypoxia/reoxygenation‐induced apoptosis in AML12 hepatocytes and that the cytoprotection afforded by (±)γ‐Sch/(?)Sch B may at least in part be mediated by a decrease in sensitivity to Ca²⁺‐induced MPT, which may in turn result from enhancement of cellular GSH levels by drug pretreatments. Copyright © 2009 John Wiley & Sons, Ltd.     

Inhibition of UDP‐Glucuronosyltransferases (UGTs) Activity by constituents of Schisandra chinensis

Structure–activity relationship for the inhibition of Schisandra chinensis's ingredients toward (Uridine‐Diphosphate) UDP‐glucuronosyltransferases (UGTs) activity was performed in the present study. In vitro incubation system was employed to screen the inhibition capability of S. chinensis's ingredients, and in silico molecular docking method was carried out to explain possible mechanisms. At 100 μM of compounds, the activity of UGTs was inhibited by less than 90% by schisandrol A, schisandrol B, schisandrin, schisandrin C, schisantherin A, gomisin D, and gomisin G. Schisandrin A exerted strong inhibition toward UGT1A1 and UGT1A3, with the residual activity to be 7.9% and 0% of control activity. Schisanhenol exhibited strong inhibition toward UGT2B7, with the residual activity to be 7.9% of control activity. Gomisin J of 100 μM inhibited 91.8% and 93.1% of activity of UGT1A1 and UGT1A9, respectively. Molecular docking prediction indicated different hydrogen bonds interaction resulted in the different inhibition potential induced by subtle structure alteration among schisandrin A, schisandrin, and schisandrin C toward UGT1A1 and UGT1A3: schisandrin A > schisandrin > schisandrin C. The detailed inhibition kinetic evaluation showed the strong inhibition of gomisin J toward UGT1A9 with the inhibition kinetic parameter (K_i) to be 0.7 μM. Based on the concentrations of gomisin J in the plasma of the rats given with S. chinensis, high herb–drug interaction existed between S. chinensis and drugs mainly undergoing UGT1A9‐mediated metabolism. In conclusion, in silico‐in vitro method was used to give the inhibition information and possible inhibition mechanism for S. chinensis's components toward UGTs, which guide the clinical application of S. chinensis. Copyright © 2015 John Wiley & Sons, Ltd.     

Manassantin A and B from Saururus chinensis inhibiting cellular melanin production

Hyperpigmentation disorders such as freckles and senile lentigines in the skin are associated with abnormal accumulation of melanin pigments. In this study, two lignan constituents were isolated from Saururus chinensis Baill (Saururaceae) as inhibitors of cellular melanin production by bioassay‐guided fractionations. The active constituents were manassantin A and B that dose‐dependently inhibited melanin production in α‐melanocyte stimulating hormone (α‐MSH)‐activated melanoma B16 cells with IC₅₀ values of 13 nm and 8 nm , respectively. Arbutin as a positive control exhibited an IC₅₀ value of 96 µm on α‐MSH‐induced melanin production. Further, manassantin A inhibited forskolin‐ or 3‐isobutyl‐1‐methylxanthine (IBMX)‐induced melanin production with IC₅₀ values of 14 nm or 12 nm , respectively. Manassantin A decreased cellular amounts of IBMX‐inducible tyrosinase protein but could not affect the catalytic activity of cell‐free tyrosinase, a key enzyme in the biosynthetic pathway of melanin pigments. Finally, this study could provide a pharmacological potential of S. chinensis in hyperpigmentation disorders. Copyright © 2009 John Wiley & Sons, Ltd.     

Schisandrin C Ameliorates Learning and Memory Deficits by Aβ1–42‐induced Oxidative Stress and Neurotoxicity in Mice

Schisandrin C (SCH‐C) is a main and typical antioxidative lignan isolated from the fruits of Schisandra chinensis (Trucz.) Baill (a widely used traditional Chinese medicine). The present study aimed to characterize the effect of SCH‐C on memory impairment and further research on pathological changes in Aβ_1–42‐induced Alzheimer's disease mice. Mice were administration with SCH‐C daily for 5 days in the lateral cerebral ventricles using sterotaxically implanted cannula. Cognitive functions were assessed by Y‐maze test, active avoidance test and Morris water maze test in all groups, and the level of Aβ_1–42 and neuronal injury induced by Aβ_1–42 were reversed remarkably following SCH‐C treatment compared with sham group; meanwhile the impairment of short‐term or working memory was dramatically improved. In addition, SCH‐C significantly inhibited total cholinesterase (ChEtotal), and increased superoxide dismutase (SOD) and glutathione peroxidase (GSH‐px) activity glutathione (GSH) levels in the hippocampus and cerebral cortex. It can be speculated that SCH‐C offers protection against Aβ_1–42‐induced dysfunction in learning and memory by inhibiting ChEtotal and its antioxidant action. Copyright © 2015 John Wiley & Sons, Ltd.     

Apoptosis of BGC823 cell line induced by p‐hydroxymethoxybenzobijuglone,a novel compound from Juglans mandshurica

p‐Hydroxymethoxybenzobijuglone (HMBBJ), a new quinone compound isolated from Juglans mandshurica (by bioassay‐guided fractionation), showed cytotoxic activity in the gastric carcinoma cell line BGC823. The growth of BGC823 cells was inhibited as demonstrated by MTT assay and several cellular characteristic changes, such as cell shrinkage, chromatin condensation and apoptotic body formation with programmed cell death. Flow cytometry analysis revealed that the BGC823 cell cycle was arrested at G2/M phase by HMBBJ, and the apoptotic rate of BGC823 cells increased with respect to HMBBJ in a dose‐dependent manner. HMBBJ also activated caspase‐3, decreased the expression of Bcl‐2 and caused a decrease in the mitochondrial membrane potential (ΔΨ_m). These findings suggest that HMBBJ could significantly induce apoptosis in BGC823 cells and should be considered as a potential candidate for a chemotherapeutic drug against cancer. Copyright © 2008 John Wiley & Sons, Ltd.     

α‐Hederin induces the apoptosis of gastric cancer cells accompanied by glutathione decrement and reactive oxygen species generation via activating mitochondrial dependent pathway

α‐Hederin, a monodesmosidic triterpenoid saponin, exhibited promising antitumor potential against a variety of human cancer cell lines. However, few related studies about effects of α‐hederin on gastric cancer are available. Herein, our results showed that α‐hederin significantly inhibited the proliferation of gastric cancer cells and arrested the cell cycle in G1 phase in vitro (p < .05). Further research of the potential mechanism reflected that α‐hederin could induce intracellular glutathione decrement, adenosine triphosphate level, and mitochondrial membrane potential variation via inducing reactive oxygen species accumulation during the apoptosis of gastric cancer cells. Moreover, the detection of mitochondrial and cytosol proteins with apoptosis‐inducing factor, apoptosis protease activating factor‐1, and cytochrome C showed an increase in the cytosol, followed by a decrease of Bcl‐2 levels and increases of caspase‐3, caspase‐8, caspase‐9, and Bax, which revealed that α‐hederin induced apoptosis via triggering activation of the mitochondrial pathway. Furthermore, the above changes were amplified when pretreated with buthionine sulfoximine, whereas attenuated in the group pretreated with NAC than α‐hederin alone (p < .05). In addition, α‐hederin significantly inhibited the growth of xenografted gastric tumors with favorable safety. In conclusion, α‐hederin could inhibit the proliferation and induce apoptosis of gastric cancer accompanied by glutathione decrement and reactive oxygen species generation via activating mitochondrial dependent pathway.     

Schisandra chinensis ameliorates depressive‐like behaviors by regulating microbiota‐gut‐brain axis via its anti‐inflammation activity

The present study aimed to examine the antidepressant actions of the composition fractions of Schisandra chinensis using LPS‐induced mice. Animals were treated with total extracts (SCE), lignans (SCL), polysaccharides (SCPS), and essential oil (SCVO), and then subjected to behavioral tests. The forced swimming test (FST) and tail suspension test (TST) were used as predictive animal models of antidepressant activity. Total extracts and lignans significantly decreased the duration of immobility in FST and TST. We found that treatment with SCE and SCL could significantly decrease the levels of pro‐inflammatory cytokines both in the periphery and central nervous system (CNS). This was confirmed by the histopathological examination of the colon. The RT‐PCR results demonstrated that SCE and SCL could greatly inhibit the TLR4/NF‐κB/IKKα signaling pathway. In addition, the concentrations of Butyric acid and Propionic acid were upregulated by the administration, and the decreased diversity of intestinal microbiota and alterations of the relative proportions of Bacteroidetes and Firmicutes phylum members, Barnesiella and Lactobacillus genus members in LPS‐induced mice were restored as well. All results suggested that lignans is the effective fraction of S.chinensis to ameliorating depressive disorders, which its anti‐inflammation activity possibly involved in the bidirectional connection between gut microbiota and brain.     

Protective effects of 3′‐deoxy‐4‐O‐methylepisappanol from Caesalpinia sappan against glutamate‐induced neurotoxicity in primary cultured rat cortical cells

To examine the neuroprotective effects of Caesalpinia sappan L., we tested its protection against the glutamate‐induced neurotoxicity in primary cortical cultured neurons. We found that an aqueous extract of this medicinal plant exhibited significant protection against glutamate‐induced toxicity in primary cultured rat cortical cells. In order to clarify the neuroprotective mechanism(s) of this observed effect, isolation was performed to seek and identify active fractions and components. By such fractionation, two known compounds – sappanchalcone and 3′‐deoxy‐4‐O‐methylepisappanol – were isolated from the methanol extracts from the air‐dried and chipped C. sappan. Among these two compounds, 3′‐deoxy‐4‐O‐methylepisappanol exhibited significant neuroprotective activities against glutamate‐induced toxicity, exhibiting cell viability of about 50%, at concentrations ranging from 0.1 μM to 10 μM. Therefore, the neuroprotective effect of C. sappan might be due to the inhibition of glutamate‐induced toxicity by the protosappanin derivative it contains. Copyright © 2009 John Wiley & Sons, Ltd.     

Protective effects of dibenzocyclooctadiene lignans from Schisandra chinensis against beta‐amyloid and homocysteine neurotoxicity in PC12 cells

Aggregated beta‐amyloid (Aβ) and elevated plasma levels of homocysteine have been implicated as critical factors in the pathogenesis of Alzheimer's disease. The neuroprotective effects and possible mechanism of four structurally similar dibenzocyclooctadiene lignans (namely schisandrin, schisantherin A, schisandrin B and schisandrin C) isolated from the fruit of Schisandra chinensis (Turcz.) Baill. (Schisandraceae) against Aβ_25‐35 and homocysteine toxicity in PC12 cells was studied. Exposure of PC12 cells to 0.5 µm Aβ_25‐35 caused significant cell death, increased the number of apoptotic cells, elevated reactive oxygen species, increased the levels of the pro‐apoptotic protein Bax and caspase‐3 activation. All these effects induced by Aβ_25‐35 were markedly reversed by schisandrin B and schisandrin C pretreatment, while schisandrin and schisantherin A had no obvious effects. Meanwhile, schisandrin B and schisandrin C reversed homocysteine‐induced cytotoxicity. The results indicated that schisandrin B and schisandrin C protected PC12 cells against Aβ toxicity by attenuating ROS production and modulating the apoptotic signal pathway through Bax and caspase‐3. Further structure–activity analysis of Schisandra lignans and evaluations of their neuroprotective effects using AD animal models are warranted. Copyright © 2010 John Wiley & Sons, Ltd.     

β‐Sitosterol Enhances Cellular Glutathione Redox Cycling by Reactive Oxygen Species Generated From Mitochondrial Respiration: Protection Against Oxidant Injury in H9c2 Cells and Rat Hearts

Herba Cistanches (Cistanche deserticola Y. C. Ma) is a ‘Yang‐invigorating’ tonic herb in Chinese medicine. Preliminary chemical analysis indicated that β‐sitosterol (BS) is one of the chemical constituents in an active fraction of Herba Cistanches. To investigate whether BS is an active ingredient of Herba Cistanches, the effects of BS on H9c2 cells and rat hearts were examined. The results indicated that BS stimulated the mitochondrial ATP generation capacity in H9c2 cells, which was associated with the increased production of mitochondrial reactive oxygen species. BS also stimulated mitochondrial state 3 and state 4 respiration, with the resultant decrease in coupling efficiency. BS produced an up‐regulation of cellular glutathione redox cycling and protected against hypoxia/reoxygenation‐induced apoptosis in H9c2 cells. However, the protective effect of BS against myocardial ischemia/reperfusion injury was seen in female but not male rats ex vivo. The cardioprotection afforded by BS was likely mediated by an up‐regulation of mitochondrial glutathione redox cycling in female rat hearts. In conclusion, the ensemble of results suggests that BS is an active ingredient of Herba Cistanches. The gender‐dependent effect of BS on myocardial protection will further be investigated. Copyright © 2013 John Wiley & Sons, Ltd.     

Oxidative Inactivation of Liver Mitochondria in High Fructose Diet‐Induced Metabolic Syndrome in Rats: Effect of Glycyrrhizin Treatment

Metabolic syndrome is a serious health problem in the present world. Glycyrrhizin, a triterpenoid saponin of licorice (Glycyrrhiza glabra) root, has been reported to ameliorate the primary complications and hepatocellular damage in rats with the syndrome. In this study, we have explored metabolic syndrome‐induced changes in liver mitochondrial function and effect of glycyrrhizin against the changes. Metabolic syndrome was induced in rats by high fructose (60%) diet for 6 weeks. The rats were then treated with glycyrrhizin (50 mg/kg body weight) by single intra‐peritoneal injection. After 2 weeks of the treatment, the rats were sacrificed to collect liver tissue. Elevated mitochondrial ROS, lipid peroxidation and protein carbonyl, and decreased reduced glutathione content indicated oxidative stress in metabolic syndrome. Loss of mitochondrial inner membrane cardiolipin was observed. Mitochondrial complex I activity did not change but complex IV activity decreased significantly. Mitochondrial MTT reduction ability, membrane potential, phosphate utilisation and oxygen consumption decreased in metabolic syndrome. Reduced mitochondrial aconitase activity and increased aconitase carbonyl content suggested oxidative damage of the enzyme. Elevated Fe²⁺ ion level in mitochondria might be associated with increased ROS generation in metabolic syndrome. Glycyrrhizin effectively attenuated mitochondrial oxidative stress and aconitase degradation, and improved electron transport chain activity. Copyright © 2016 John Wiley & Sons, Ltd.     

Persicarin from water dropwort (Oenanthe javanica) protects primary cultured rat cortical cells from glutamate‐induced neurotoxicity

The n‐BuOH fraction of O. javanica significantly protected the primary cultures of rat cortical cells exposed to glutamate. Four flavonoids yielded from this fraction through bioactivity‐guidance. The isolated compounds, identified as isorhamnetin (1), afzelin (2), hyperoside (3) and persicarin (4), were evaluated in vitro for their neuroprotective activity. Persicarin (4), the main constituent of O. javanica, showed significant neuroprotective activities in glutamate‐injured rat cortical cells. Persicarin diminished calcium influx and inhibited the subsequent overproduction of nitric oxide and intracellular peroxide. In addition, persicarin significantly restored the reduced activities of glutathione (GSH) reductase and glutathione peroxidase, and the contents of GSH induced by glutamate. These results support a conclusion that persicarin greatly contributes to the neuroprotective activities of O. javanica. Copyright © 2009 John Wiley & Sons, Ltd.     

Protective Effects of Turbinaria ornata and Padina pavonia against Azoxymethane‐Induced Colon Carcinogenesis through Modulation of PPAR Gamma,NF‐κB and Oxidative Stress

The aim of this study was to investigate the antiproliferative and protective effects of the brown seaweeds, Turbinaria ornata and Padina pavonia, against azoxymethane (AOM)‐induced colon carcinogenesis in mice. Both algal extracts showed anti‐proliferative effects on the human carcinoma cell line HCT‐116 in vitro, with T. ornata demonstrating a more potent effect. Male albino Swiss mice received intraperitoneal injections of AOM (10 mg/kg) once a week for two consecutive weeks and 100 mg/kg of either T. ornata or P. pavonia extracts. AOM‐induced mice exhibited alterations in the histological structure of the colon, elevated lipid peroxidation and nitric oxide, declined glutathione content and reduced activity of superoxide dismutase and glutathione peroxidase. In addition, AOM induced downregulation of peroxisome proliferator activated receptor gamma (PPARγ) and p53 mRNA expression, with concomitant upregulation of nuclear factor‐kappa B (NF‐κB) in colon tissue. Administration of either algal extract markedly alleviated the recorded alterations. In conclusion, the current study suggests that T. ornata and P. pavonia, through their antioxidant and anti‐inflammatory effects, are able to attenuate colon inflammation by downregulating NF‐κB expression. Furthermore, the protective effects of both algae against AOM‐initiated carcinogenesis were attributed, at least in part, to their ability to upregulate colonic PPARγ and p53 expression. Copyright © 2015 John Wiley & Sons, Ltd.     

Antioxidant activity of AO‐8, a herbal formulation in vitro and in vivo experimental models

The effect of AO‐8, a herbal formulation was evaluated for free radical scavenging activity using in vitro and in vivo experimental models. AO‐8 dose dependently inhibited ferric ion induced lipid peroxidation in vitro at 125–1000 µg. AO‐8 was investigated at dose levels of 250, 500 and 750 mg/kg p.o. in isoproterenol‐induced myocardial infarction and CCl₄‐induced hepatotoxicity in rats. The levels of serum GOT and LDH, cardiac glutathione, SOD and catalase were estimated following induction of myocardial infarction with isoproterenol. The estimation of parameters such as SGOT, SGPT, liver glycogen and lipid peroxidation were carried out in CCl₄‐induced hepatotoxicity. Treatment with AO‐8 for 15 days at a dose of 500 and 750 mg/kg offered marked protection in both in vivo models. The reversal of increased serum enzymes in both the models may be due to the prevention of leakage of the intracellular enzymes by its membrane stabilizing activity. The inhibition of lipid peroxidation and enhancement of antioxidant enzymes by AO‐8 may be due to the direct free radical scavenging activity which could be attributed to the antioxidant potential of various ingredients present in the formulation. Thus it can be concluded that AO‐8 is an effective free radical scavenger and could prove beneficial in the treatment of various disorders associated with the involvement of free radicals. Copyright© 1999 John Wiley & Sons, Ltd.     

Neuroprotective effects of a sesquiterpene lactone and flavanones from Paulownia tomentosa Steud. against glutamate‐induced neurotoxicity in primary cultured rat cortical cells

The neuroprotective effects of Paulownia tomentosa against glutamate‐induced neurotoxicity were studied in primary cultured rat cortical cells. It was found that the aqueous extract of this medicinal plant significantly attenuated glutamate‐induced toxicity. In order to clarify the mechanism(s) underlying this neuroprotective effect, the active fractions and components were isolated and identified. Five compounds were isolated as the methanol extracts from air‐dried flowers of P. tomentosa. Isoatriplicolide tiglate exhibited significant neuroprotective activity against glutamate‐induced toxicity at concentrations ranging from 1 µm to 10 µm , and exhibited cell viability of approximately 43–78%. Therefore, the neuroprotective effect of P. tomentosa might be due to the inhibition of glutamate‐induced toxicity by the sesquiterpene lactone derivative it contains. Copyright © 2010 John Wiley & Sons, Ltd.