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2,3,5,4'-Tetrahydroxystilbene-2-O-β-d-glucoside (THSG) is the major active ingredient in Plygonum multiflorum that displays a great deal of health-benefits including anti-oxidation, anti-hyperlipidemia, anti-cancer, anti-inflammation and neuroprotection. However, it is unclear whether THSG exerts neuroprotective functions by regulating neurotrophic factors and their associated signaling pathways. In this study, hippocampal neurons were challenged with staurosporine (STS) to establish a neural damage model. We found that STS-induced cytotoxicity introduced significant morphological collapse and initiating cell apoptosis, along with the down regulation of BDNF and TrkB/Akt signaling axis. In contrast, neurons pretreated with THSG showed resistance to STS-induced toxicity and maintained cell survival. THSG rescued STS induced dysfunctions of BDNF and its associated TrkB/Akt signaling, and restored the expression of Bcl-2 and Caspase-3. However, inhibition of TrkB activity by K252a or Akt signaling by LY294002 abolished the neuroprotective effects of THSG. Therefore, BDNF and TrkB/Akt signaling axis is a promise target for THSG mediated neuroprotective functions.

Ginsenoside Rg1 is the main active ingredient of Panax ginseng with the activity of neuroprotective, antioxidant and strengthening the immune system. Therefore, we hypothesized that Rg1 may afford anti-aging effects although the mechanism remains to be elucidated. In this study, chemically induced aging mice were established by consecutive administration of D-galactose and AlCl3. We found that Rg1 effectively ameliorates spatial learning and memory deficits in aging mice demonstrated by their improved performance in step down avoidance tests and Morris water maze experiments. Rg1 restored aging-induced decline of FGF2 and BDNF, reactivated TrkB/Akt signaling pathways in the hippocampus and prefrontal cortex to inhibit apoptosis, for the expression of anti-apoptotic protein Bcl-2 and apoptosis promoting enzyme cleaved-Caspase3 were antagonistically restored. Therefore, these results established the anti-aging effects of Rg1, and FGF2, BDNF and associated signaling pathways might be promising targets. Our data may provide a new avenue to the pharmacological research and diet therapeutic role of ethnic products such as Rg1 in anti-aging and aging associated diseases.

Salidroside (SAL) is a marker glycoside of Rhodiola rosea with significant antioxidant, anti-inflammatory, and other health benefits. In this study, we determined its neuroprotective effects against Cd-induced toxicity in cultured cells and mice.GL261 cell and Cd-intoxicated mouse model were used. ICP-MS and MWM were performed to measure Cd content and Cd-induced cognitive impairment in mice, respectively.SAL attenuated Cd toxicity in GL261 cells as well as protected mice from substantial organic damage and cognitive deficits. SAL treatment alleviated Cd-induced oxidative stress, glial cell activation, and elevation of pro-inflammatory factors including TNF-α, IL-1β, and IL-6. Cd-induced cognitive deficits observed in the Morris water maze in mice were rescued by SAL. At the mechanistic level, SAL maintained the activity of antioxidant enzymes such as SOD and GSH-Px in the serum and brain, and scavenged the peroxidation product MDA, thereby restoring redox homeostasis in vivo, attenuating neuronal damage, and ultimately antagonized Cd-induced toxicity. Furthermore, Cd activated the RIP1-driven inflammatory signaling pathway and Notch/HES-1 signaling axis in the brain, leading to inflammation and neuronal loss, which could be attenuated by SAL.SAL is a natural product with good anti-Cd effects, indicating that Rhodiola rosea is promising plant that is worthy of cultivation for health and economic benefits.

Astragalin (AST) is a natural flavonoid with excellent antioxidant and anti-inflammatory activities. However, whether AST is an effective chemical for neuronal protection and its underlying mechanisms remain to be elucidated. In this study, we established a mouse model of cognitive impairment and aging-like phenotype induced by sequential administration of AlCl

OBJECTIVE Gisenoside Rg1 is a potent neuroprotectant in ginseng. The aim of this study was to investigate the elimination effect of Rg1 on cadmium (Cd)-induced neurotoxicity. MATERIALS AND METHODS A cumulative Cd exposure mouse model was established. Also, the toxicity of Cd and the protective effect of Rg1 were examined in vitro using cultured neurons and microglia. RESULTS We found that Cd-intoxicated mice exhibited significant injury in the liver, kidney, small intestine, and testis, along with cognitive impairment. Antioxidant enzymes such as SOD, GSH-Px and CAT were reduced in the blood and brain, and correspondingly, the lipid peroxidation product MDA was elevated. In the brain, astrocytes and microglia were activated, characterized by an increase in inflammatory factors such as TNF-α, IL-1β and IL-6, as well as their protein markers GFAP and IBA1. However, Rg1 eliminated Cd-induced toxicity and restored oxidative stress and inflammatory responses, correspondingly restoring the behavioral performance of the animals. Meanwhile, the BDNF-TrkB/Akt and Notch/HES-1 signaling axes were involved in the Rg1-mediated elimination of Cd-induced toxicity. CONCLUSION Rg1 is a promising agent for the elimination of Cd-induced toxicity.

The neurotoxicity caused by cadmium (Cd) is well known in humans and experimental animals. However, there is no effective treatment for its toxicity. In this study, we established Cd toxicity models in cultured cells or mice to investigate the detoxification effect of edaravone (Eda). We found that Eda protected GL261 cells from Cd toxicity and prevented the loss of cell viability. In Cd-exposed mice, liver, kidney and testicular damage, as well as cognitive dysfunction were observed. Oxidative stress and inflammatory responses, such as decreased SOD and CAT, increased LDH and MDA, and abnormal changes in the inflammatory factors TNF-α, IL-1β, IL-6 and IL-10 were detected in serum and brain tissue. Eda protected mice from Cd-induced toxicity and abrogated oxidative stress and inflammatory responses. Also, Eda prevented inflammatory activation of microglia and astrocytes and was accompanied by restoration of the neuronal marker protein MAP2, indicating restoration of neuronal function. In addition, the BDNF-TrkB/Akt and Notch/HES-1 signaling axes were involved in the response of Eda to the elimination of Cd toxicity. In conclusion, Eda does contribute to the clearance of Cd-induced toxicity.

Parkinson's disease is the second most common neurodegenerative disease. Researchers have shown that oxidative stress and apoptosis play an important role in the Parkinson's disease process. Isoquercitrin (quercetin-3-O-β-d-glucopyranoside) is a natural flavonol compound and one of the main active ingredients of agricultural waste apple pomace. Increasing evidence indicates that this compound possesses anti-oxidation, anti-aging, and anti-inflammation properties. In this study, isoquercitrin was purified from apple pomace by high-speed countercurrent chromatography and its neuroprotective effect on Parkinson's disease was investigated in MPTP-induced acute mouse models. It was found that isoquercitrin ameliorated the animal behaviors against MPTP-induced neurotoxicity, mitigated the loss of dopamine neurons induced by MPTP, increased tyrosine hydroxylase and dopamine transporter expression, reduced the pro-apoptotic signaling molecule bax expression and inhibited MPTP-triggered oxidative stress. Our results demonstrated that isoquercitrin has protective effects on the MPTP subacute model mouse, which might be partially mediated through the actions of anti-oxidation and anti-apoptosis. Isoquercitrin might be a new promising protective drug for the improvement of Parkinson's disease.

Edaravone (Eda) is a free radical scavenger used in clinical trials for the treatment of ischemic stroke and amyotrophic lateral sclerosis. However, how Eda exerts its neuroprotective effects remains to be elucidated. We investigated the neuroprotective effects of Eda in cultured hippocampal neurons and in a mouse model of AlCl

Semen Cuscutae, called Tu-si-zi in Chinese, is a kind of dried mature seed in the Convolvulaceae family. It mainly distributes in China, Korea, Pakistan, Vietnam, India and Thailand. It is used as a kidney-tonifying drug for treatment of aging related diseases such as osteoporosis in traditional Chinese medicine. However, the exact mechanisms on bone resorption are poorly studied.The aim of this study was to investigate the potential effect of Semen Cuscutae on ovariectomy (OVX)-induced osteoporosis in mice and clarify the exact mechanisms by which Semen Cuscutae exert the anti-osteoporosis effect.Qualitative and quantitative analyses of Semen Cuscutae were performed by UPLC-Q-TOF-MS and HPLC-MS/MS, respectively. Changes in bone mineral density (BMD) induced by OVX in mice were measured by dual-energy X-ray absorptiometry and micro-computed tomography (μCT). Tartrate-resistant acid phosphatase (TRAP) staining as well as hematoxylin and eosin (HE) staining were used to observe bone microarchitectural changes. ELISA kits were used to assess the therapeutic effects of Semen Cuscutae on the serum levels of osteoprotegerin (OPG), tartrate-resistant acid phosphatase 5b (TRACP-5b), and receptor activator of nuclear factor-κB (RANKL). The effect of Semen Cuscutae on primary cell viability was assessed using CCK-8 and anti-tartrate phosphatase assays. TRAP staining and actin ring staining were used to observe the effect of Semen Cuscutae on osteoclast differentiation. Western blotting was used to measure the effects of Semen Cuscutae on expressions of NFATC1, c-Src kinase, and c-fos.Results from UPLC-Q-TOF-MS showed that the main components of Semen Cuscutae were flavonoid compounds that included quercitrin, quercetin, hyperoside, caffeic acid, rutin, chlorogenic acid, luteolin, apigenin, kaempferol, isoquercetin, cryptochlorogenic acid, isorhamnetin-3-O-glucoside, and astragalin. After the Semen Cuscutae extract was orally administered to OVX mice, bone density increased (P 0.01) and bone microstructure was significantly improved (P 0.01 or 0.05). Additionally, Semen Cuscutae exhibited a significant descending effect in the levels of serum TRACP-5b and RANKL, while there was a significant increase in OPG in the Semen Cuscutae group compared with the OVX group, especially at high doses. Moreover, we found that increasing of c-fos, c-Src kinase, and NFATC1 protein expressions were reversed by Semen Cuscutae in vitro and in vivo.Our results showed that Semen Cuscutae exhibited anti-osteoporosis effects through the c-fos/c-Src kinase/NFATC1 signaling pathway.

Erzhi formula (EZF) consists of Ecliptae herba (EH) and Fructus Ligustri Lucidi (FLL) at a ratio 1:1, and constitutes a well-known formula in China that is commonly used for treating menopausal diseases.In this study, we explored the pharmacologic actions and potential molecular mechanisms underlying EZF's action in preventing and treating osteoporosis.The active components and related targets of EZF's anti-osteoporotic effects were predicted by network pharmacology, and functional enrichment analysis was also performed. We then used an osteoporosis model of ovariectomized (OVX) mice to detect the effects of EZF on osteoporosis.The results from network pharmacology identified a total of 10 active ingredients from EH and 13 active ingredients from FLL that might affect 65 potential therapeutic targets. GO enrichment analysis revealed that EZF affected bone tissue primarily via hormone (particularly estradiol)-related pathways and bone resorption by osteoclast differentiation. KEGG analysis demonstrated that bone-related factors such as Runt-related transcription factor 2 (Runx2), Ca2, estrogen receptor1 (ESR1), androgen receptors (AR), and TNFα served as the primary targets during osteoclastic differentiation. In vivo experiments showed that the formula significantly improved the diminution in estrogen and the subsequent uterine atrophy induced by ovariectomy (P 0.01 or 0.05), implying that the EZF exerted its actions via regulation of estradiol and the nourishing effects of the uterus in OVX mice. Dual-energy X-ray absorptiometry and micro-CT showed that EZF significantly inhibited bone loss and improved bone micro-architecture by statistically increasing the number of bone trabeculae and decreasing the separation of bone trabeculae in OVX mice (P 0.01 or 0.05); EZF also inhibited bone loss and enhanced bone-fracture load. Furthermore, we confirmed that EZF reduced the calcium concentrations, augmented protein and mRNA levels for Runx2 in the bone marrow, and reduced PPARγ levels. RANKL-a key downstream regulatory protein of many targets that was referred to in our results of network pharmacology as being involved in the regulation of osteoclastogenesis-was significantly diminished by EZF; it also elevated OPG content. In addition, we used monocytes of bone-marrow origin to detect the effects of the potential components of EZF on osteoclast differentiation and found that wedelolactone, oleanolic acid, echinocystic acid, luteolin, and luteolin-7-o-glucoside significantly inhibited osteoclast differentiation from monocytes induced by 25 ng/mL MCSF and 50 ng/mL RANKL (P 0.01 or 0.05).Our present study indicated that EZF significantly inhibited the bone loss induced by OVX in mice by its regulation of estradiol combined with the nourishing effect of the uterus, and that it also attenuated bone resorption by decreasing the RANKL/OPG ratio so as to inhibit osteoclast maturation.

Ethnopharmacological relevance Tibetan ginseng named Wangla (tuber of Coeloglossum viride var. bracteatum) is a traditional tonic that has Yang-strengthening and qi-enhancing, tranquilizing, intelligence-enhancing and longevity-enhancing properties. It has been used to treat impotence, spermatorrhea, anemia and insomnia. Therefore, its characteristic components and neuronal modulating effects were studied. Aim of the study: To investigate the elimination of Aβ-induced toxicity by CE and to elucidate the molecular mechanisms involving BDNF, FGF2, and their related signaling axis, and the RIP1-driven inflammatory pathway. Materials and methods We established Aβ-induced toxicity models in cultured neurons and ICR mice, respectively. MWM and fear conditioning tests were performed for behavioral analysis of cognitive functions in mice. Western blot was used to investigate the levels of BDNF, FGF2, and their downstream effector TrkB/Akt/Bcl-2, as well as the RIP1-driven RIP1/RIP3/MLKL pathway. Immunofluorescence assay is used to examine the status of glial cells. Results CE abrogated Aβ toxicity and inhibited apoptosis in cultured neurons, mainly by regulating the BDNF, FGF2, and TrkB/Akt signaling pathways as well as RIP1-driven inflammation and necroptosis. Similarly, mice injected intracerebrally with Aβ exhibited cognitive deficits and had elevated oxidative stress and inflammatory factors detected in their serum and brain. However, CE-treated mice showed recovery of cognitive abilities and quelled levels of oxidative stress and inflammatory factors. Moreover, Aβ toxicity led to a reduction in BDNF, FGF2, and related signaling regulators in the hippocampus and prefrontal cortex, accompanied by activation of RIP1-driven inflammatory signaling pathways, and a reduction in TBK1 and Bcl-2. However, CE restored the levels of BDNF, FGF2, and TrkB/Akt signaling pathway, while inhibiting RIP1-induced RIP1/RIP3/MLKL pathway, thereby antagonizing apoptosis and maintaining neuronal activity. Conclusions CE effectively eliminated the toxicity of Aβ in cultured neurons and mouse models, which holds promise for drug development.

The major bioactive ingredient THSG of Polygonum multiflorum is well established for its anti-oxidation, anti-aging and anti-inflammation properties. Increasing evidence supports the capacity of THSG to ameliorate the biochemistry of neurotrophins and their downstream signaling axis in mouse models to attenuate neurodegenerative diseases such as Alzheimer's and Parkinson's disease. In this study, the neuroprotective effects of THSG were studied in vitro and in vivo. In cultured mesencephalic dopamine neurons and SH-SY5Y cell line, it was found that THSG protected the integrity of the cell body and neurite branching from MPP+-induced toxicity by restoring the expression of FGF2 and BDNF and their downstream signaling pathways to inhibit apoptosis and promote cell survival. The inhibition of Akt signaling by LY294002 or TrkB activity by K252a eliminated the neuroprotective effects of THSG. In the MPTP-induced mouse models of Parkinson's disease, THSG ameliorated the animal behaviors against MPTP-induced neurotoxicity, which was demonstrated by the pole test and the tail suspension test. Biochemical and immunohistochemical analysis verified the THSG-mediated restoration of the FGF2-Akt and BDNF-TrkB signaling axis in the substantia nigra and corpus striatum and the recovery of dopaminergic neurons. These results establish the neuroprotective effects of THSG in vitro and in vivo and unravel the underlying mechanism against toxin-induced neural atrophy, providing a new avenue for the use and pharmacological research of edible medicine for anti-neurodegenerative diseases.

Depression is a long term inhibitory mood that heavily disabled human beings. We have previously demonstrated anti-depression effect of 2,3,5,4'-tetrahydroxystilbene-2-O-β-d-glucoside (THSG) in chronic-restraint stress (CRS) induced depressive-like mice by restoring the oxidative pathway and neuroinflammation. In this study, we examine the conditions of neurotrophins in CRS-induced depressive-like mice and whether THSG could be an antidepressant by ameliorating the neurotrophins and their associated signaling axis. CRS produced downregulation of antioxidants, the decline of brain-derived neurotrophic factor (BDNF), fibroblast growth factor 2 (FGF2) and associated signaling regulators in the hippocampus and prefrontal cortex, corresponding to the behavioral inability and anhedonia. Administration of THSG restored the expression of antioxidants and neurotrophins BDNF, FGF2. Besides, THSG recovered the Akt signaling pathway and antagonistically restored the expression of Bcl-2 and cleaved-caspase-3 to inhibit apoptosis. Consistently, behavioral performances were recovered from CRS-induced motor inability and anhedonia. In summary, THSG is effective to attenuate stress-induced depression by ameliorating the biochemistry of neurotrophins and their related signaling pathways. These results may provide an avenue to take BDNF as a target to explore folk medicine for anti-depression.

Neuropathic pain is of serious clinical concern and only about half of patients achieve partial relief with currently-available treatments, so it is critical to find new drugs for this condition. Recently, the cellsurface trafficking of pain-related receptors has been suggested as an important mechanism underlying persistent neuropathic pain. Here, we used the short peptide GluA2-3y, which specifically inhibits the GluA2-dependent endocytosis of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, and tested its anti-nociceptive effect in the periaqueductal grey (PAG) of intact rats and rats with neuropathic pain. Intra-PAG injection of 0.15, 1.5, 7.5, and 15 pmol of GluA2-3y induced dose-dependent increases in hindpaw withdrawal latencies to noxious thermal and mechanical stimuli in intact rats, suggesting that GluA2 cell-surface trafficking in the PAG is involved in pain modulation. Furthermore, GluA2-3y had much stronger anti-nociceptive effects in rats with neuropathic pain induced by sciatic nerve ligation. Interestingly, the intra-PAG injection of 15 pmol GluA2-3y had an analgesic effect similar to 10 μg (35 nmol) morphine in rats with neuropathic pain. Taken together, our results suggested that GluA2 trafficking in the PAG plays a critical role in pain modulation, and inhibiting GluA2 endocytosis with GluA2-3y has potent analgesic effects in rats with neuropathic pain. These findings strongly support the recent hypothesis that targeting receptor trafficking could be a new strategy for the treatment of neuropathic pain.

The excessive release and accumulation of glutamate in the brain is known to be associated with excitotoxicity. CE, an extract derived from the plant Coeloglossum viride var. Bracteatum, exerted neuroprotective effects against amyloid toxicity and oxidative stress in cortical neurons. The aims of this study are to examine whether CE also attenuates glutamate neurotoxicity in rat primary cultured cortical neurons and to determine the effect of CE in vivo. According to the results of MTT, LDH release, and TUNEL assays, the CE treatment significantly reduced glutamate-induced neurotoxicity in a dose-dependent manner. Moreover, the protective effects of CE were blocked by an Akt inhibitor, LY294002, suggesting that the PI3K/Akt signalling pathway is involved in the neuroprotective effects of CE. In addition, CE might regulate the PKC-GluA2 axis to prevent neuronal apoptosis. CE also protected against dopaminergic neuronal loss in a mouse model of MPTP-induced PD. Based on our results, CE exerted neuroprotective effects both in vitro and in vivo, thus providing a potential therapeutic target for the treatment or prevention of neurodegeneration.

Investigation on diversity of culturable fungi mainly focused on sponges and corals, yet little attention had been paid to the fungal communities associated with zoanthid corals. In this study, a total of 193 culturable fungal strains were isolated from the zoanthid Palythoa haddoni collected in the South China Sea, of which 49 independent isolates were identified using both morphological characteristics and internal transcribed spacer (ITS) sequence analyses. Thirty-five strains were selected for phylogenetic analysis based on fungal ITS sequences. The results indicated that 18 genera within eight taxonomic orders of two phyla (seven orders of the phylum Ascomycota and one order of the phylum Basidiomycota) together with one unidentified fungal strain have been achieved, and Cladosporium sp. represented the dominant culturable genus. Particularly, 14 genera were isolated from a zoanthid for the first time. The antibacterial activities of organic extracts of mycelia and fermentation broth of 49 identified fungi were evaluated, and 29 (59.2 %) of the isolates displayed broad-spectrum or selective antibacterial activity. More interestingly, more than 60 % of the active fungal strains showed strong activity against two aquatic pathogenic bacteria Nocardia brasiliensis and Vibrio parahaemolyticus, compared with other pathogenic bacteria, indicating that zoanthid-derived fungi may protect its host against pathogens. This is the first report of systematically phylogenetic diversity and extensively antibacterial activity of zoanthid-derived fungi.

The present study explored the effect of 2,3,5,4′-tetrahydroxystilbene-2-O-β- d -glucoside (THSG) on the staurosporine (STS)-induced toxicity in cultured rat hippocampal neurons. The results showed that administration of 200 μM of THSG significantly protected against 0.3 μM of STS-induced apoptosis in cultured rat hippocampal neurons tested by methyl thiazolyl tetrazolium (MTT) and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assays. Furthermore, when the Akt signaling pathway was blocked by LY294002, an inhibitor of Phosphatidyl Inositol 3-kinase (PI3K), the protective effects of THSG against STS-induced neurotoxicity were abrogated. We further examined the involvement of PI3K/Akt signaling pathway in THSG protection against STS-induced cytotoxicity on cultured neurons and found that administration of THSG significantly inhibited the STS-induced decreases in the content of phosphorylated AKt (p-Akt). Moreover, we found that THSG rescued the down-regulation of B cell lymphoma/lewkmia-2 (Bcl 2 ) and pro-caspase-3 (pro-Csp3) caused by STS in the neurons. These results indicate that THSG protect the cultured rat hippocampal neurons against STS-induced cytotoxicity and the PI3K/Akt signaling and mitochondrial apoptotic pathways are involved in the THSG-induced protective effects.

Green tea polyphenols are a natural product which has antioxidative and antiapoptotic effects. It has been shown that glutamate excitotoxicity induced oxidative stress is linked to neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. In this study we explored the neuroprotective effect of green teen polyphenols against glutamate excitotoxicity in the primary cultured cortical neurons. We found that green tea polyphenols protected against glutamate induced neurotoxicity in the cortical neurons as measured by MTT and TUNEL assays. Green tea polyphenols were then showed to inhibit the glutamate induced ROS release and SOD activity reduction in the neurons. Furthermore, our results demonstrated that green tea polyphenols restored the dysfunction of mitochondrial pro- or antiapoptotic proteins Bax, Bcl-2, and caspase-3 caused by glutamate. Interestingly, the neuroprotective effect of green tea polyphenols was abrogated when the neurons were incubated with siBcl-2. Taken together, these results demonstrated that green tea polyphenols protected against glutamate excitotoxicity through antioxidative and antiapoptotic pathways.

The present study was performed to explore the effect of green tea polyphenols on the intracellular Aβ (iAβ)-induced toxicity to cultured rat primary prefrontal cortical neurons. Administration of 100 nM, 1 μM or 10 μM of green tea polyphenols significantly inhibited the iAβ-induced toxicity to cultured rat primary prefrontal cortical neurons tested by MTT and LDH release assays. We further studied the involvement of neuroprotective pathway protein AKT in green tea polyphenols protection against iAβ-induced cytotoxicity on cultured rat primary prefrontal cortical neurons. The results demonstrated that the content of p-AKT decreased significantly after iAβ treatment, while administration of green tea polyphenols significantly inhibited the iAβ-induced decrease in the content of p-AKT. Moreover, blockade of AKT signalling inhibited the protective effects of green tea polyphenols against iAβ-induced neurotoxicity. The results suggest that green tea polyphenols may play a protective effect on cultured rat primary prefrontal cortical neurons against iAβ-induced cytotoxicity and AKT is involved in the green tea polyphenols-induced protective effects.

Recently the neuronal toxicity of intracellular amyloid beta (iAbeta) in Alzheimer's disease is attracting more and more attention. The present study explored the effects of curcumin on the iAbeta-induced toxicity in primary cultured rat prefrontal cortical neurons. The cell viability of primary cultured prefrontal cortical neurons decreased significantly after virus driven transfection of Abeta from 1 day to 7 days. Interestingly, administration of 1 microM, 10 microM or 20 microM of curcumin significantly inhibited the iAbeta-induced toxicity in primary cultured rat prefrontal cortical neurons tested by MTT and LDH release assays. We further studied the involvements of apoptotic or neuroprotective pathway proteins in curcumin protection against iAbeta-induced cytotoxicity in primary cultured rat prefrontal cortical neurons. The results demonstrated that the contents of activated caspase-3 increased significantly by iAbeta, while curcumin significantly inhibited the iAbeta-induced increases of activated caspase-3 tested by Western blot. And the contents of p-AKT decreased significantly after iAbeta treatment, while administration of curcumin significantly inhibited the iAbeta-induced decreases in the contents of p-AKT. The results suggest that curcumin may play a protective effect in primary cultured rat prefrontal cortical neurons against iAbeta-induced cytotoxicity, and both AKT and caspase-3 are involved in the curcumin-induced protective effects.

The present study explored the effect of curcumin against amyloid beta (Abeta)-induced toxicity on cultured rat primary prefrontal cortical neurons. The results showed that administration of 10 microM of curcumin induced significantly protection against 20 microM of Abeta(25-35)-induced toxicity on the cultured rat primary prefrontal cortical neurons tested by MTT and TUNEL assays. We further examined the involvements of the apoptotic or anti-apoptotic proteins in curcumin protection against Abeta(25-35)-induced cytotoxicity on cultured neurons and found that the content of apoptotic protein caspase-3 was increased and the content of anti-apoptotic factor Bcl2 was decreased significantly after Abeta(25-35) treatments, while administration of curcumin significantly inhibited the Abeta(25-35)-induced increases in the content of caspase-3 and inhibited the Abeta(25-35)-induced decreases in the content of Bcl2 tested by Western blot. The results suggest that curcumin protects cultured rat primary prefrontal cortical neurons against Abeta-induced cytotoxicity, and both Bcl2 and caspase-3 are involved in the curcumin-induced protective effects.

To observe the effect of acupuncture stimulation of "Dazhui" (GV 14), bilateral "Fengmen" (BL 12) and "Feishu" (BL 13) on the thickness of the bronchial tubal wall and smooth muscle and expression of transforming growth factor-beta1 (TGF-beta1) in asthma rats so as to reveal its mechanism underlying improvement of asthma.Forty SD rats were randomly assigned to control, model, acupuncture and medication groups. The asthma model was induced by subcutaneous injection of 1% egg albumin solution and forced inhalation of atomized ovalbumin. Rats of the acupuncture group were treated by acupuncture stimulation of GV 14, bilateral BL 12 and BL 13 (once daily for 10 days), and rats of the medication group treated by intraperitoneal injection of Aminophylline Injection (100 mg/kg, once daily for 10 days). The thickness of the bronchial tubal wall and airway smooth muscle of the lung tissue were measured by image analyzer for assessing the degree of airway remodeling. The expression of TGF-beta1 in the small airway was detected by immunohistochemistry.Compared to the control group, the thickness of the airway wall and smooth muscle, and the expression level of TGF-beta1 were remarkably increased in the model group (P0.01). After acupuncture intervention and medication treatment, the thickness of the airway wall and smooth muscle, and the expression level of TGF-beta1 were remarkably down-regulated in both groups in comparison with those of the model group (P0.05, P0.01), and the expression of TGF-beta1 in the acupuncture group was obviously lower than that of the medication group (P0.05).Acupuncture stimulation of GV 14, bilateral BL 12 and BL 13 can down-regulate bronchial asthma-induced increase of TGF-[, expression in the lung tissue in asthma rats, which may contribute to its effect in improving airway remodeling.

Curcumin is extracted from the turmeric plant (Curcuma longa Linn.) and is widely used as a food additive and traditional medicine. The present study investigated the activity of curcumin against staurosporine (STS) toxicity in cell culture.Rat hippocampal neurons in primary culture were exposed to STS (20 μmol/L) and treated with curcumin (20 μmol/L). Cell viability was tested by MTT assay and reactive oxygen species (ROS) were measured using the MitoSOX™ red mitochondrial superoxide indicator. Western blot was used to assess changes in the levels of caspase-3 (Csp3), heat shock protein 70 (Hsp70) and Akt.The results showed that curcumin protects against STS-induced cytotoxicity in rat hippocampal neurons. Csp3, Hsp70, Akt and ROS activation may be involved in this protection.Curcumin could be a potential drug for combination with STS in cancer treatment to reduce the unwanted cytotoxicity of STS.

Background and Aim: Tanshione IIA (TSN) is the major active component of Salvia miltiorrhiza, a traditional Chinese Medicine. TSN protects against antioxidant-induced liver injury, although the exact mechanism is not well understood.Materials and Methods: In this study, the protective effects of TSN was examined by enzyme-linked immunosorbent assay (ELISA) and histochemistry of several cytokines.Results: TSN is found to significantly reduce plasma alanin aminotransferase and aspartate amino transferase levels in mice with concanavalin A-induced immune-mediated liver injury. TSN increases T lymphocyte subset CD3+, CD4+ and CD8+ ratios.Also, TSN significantly reduces inflammatory cytokines, including interleukin-2, interleukin-4, interferon-gamma and tumor necrosis factor alpha, while elevates anti-inflammatory cytokine, interleukin-10.Conclusions: TSN may provide a potential drug candidate for liver injury therapeutics.

The aim of the present study was to study the Effects of 11,12-epoxyeicosatrienoic acid (11,12-EET) on cardioplegia and reperfusion arrhythmias in the isolated perfused immature rabbit hearts.Isolated immature rabbit hearts were randomly divided into two groups: group 1 (St. Thomas No.2 solution control n = 8) and group 2 (St. Thomas No.2 solution plus 11,12-EET n = 8). By means of Langendorff technique, these isolated rabbit hearts underwent (15 degrees C) hypothermia, 2 hours of ischemia after infusion of cardioplegic solution and 1 hour of reperfusion (37 degrees C). The mean times until the cessation of both electrical and mechanical activity were measured after infusion of cardioplegia. The same index until occurrence of both electrical and mechanical activity after reperfusion was observed too. We also measured the arrhythmias score, heart rate, coronary blood flow during the reperfusion and the myocardial water content, myocardial calcium content at the endpoint of the reperfusion period.The times until electrical [(9.3 +/- 0.9) s vs (13.6 +/- 1.9) s, P0.01] and mechanical [(4.5 +/- 1.7) vs (7.3 +/- 2.1) s, P0.05] activity arrest were significantly shorter in the group 2 than those in the control group. 11,12-EET also provided significantly better myocardial water content [(84 +/- 4)% vs (90 +/- 5)%, P0.01], arrhythmia scores (2.03 +/- 0.83 vs 3.88 +/- 1.25, P0.01), coronary blood flow and myocardial calcium content [(3.22 +/- 0.33) micro mol/gram dry weight (gdw) vs (3.97 +/- 0.26) micro mol/gdw, P0.01] compared with control. There were no significant changes with heart rate and the mean times until occurrence of both electrical and mechanical activity after reperfusion.These data suggest that 11,12-EET added to the cardioplegic solution of St. Thomas No.2 has better cardioplegia effects and lower incidence of reperfusion arrhythmias.

To explore the effects of curcumin (CMN) on hepatic injury induced by acetaminophen (APAP) in vivo.Male mice were randomly divided into three groups: group I (control) mice received the equivalent volumes of phosphate-buffered saline (PBS) intraperitoneally (ip); Group II [APAP + carboxymethylcellulose (CMC)] mice received 1% CMC (vehicle) 2 h before APAP injection; Group III (APAP + CMN) mice received curcumin (10 or 20 mg/kg, ip) 2 h before before or after APAP challenge. In Groups II and III, APAP was dissolved in pyrogen-free PBS and injected at a single dose of 300 mg/kg. CMN was dissolved in 1% CMC. Mice were sacrificed 16 h after the APAP injection to determine alanine aminotransferase (ALT) levels in serum and malondialdehyde (MDA) accumulation, superoxide dismutase (SOD) activity and hepatocyte apoptosis in liver tissues.Both pre- and post-treatment with curcumin resulted in a significant decrease in serum ALT compared with APAP treatment group (10 mg/kg: 801.46 ± 661.34 U/L; 20 mg/kg: 99.68 ± 86.48 U/L vs 5406.80 ± 1785.75 U/L, P0.001, respectively). The incidence of liver necrosis was significantly lowered in CMN treated animals. MDA contents were significantly reduced in 20 mg/kg CMN pretreatment group, but increased in APAP treated group (10.96 ± 0.87 nmol/mg protein vs 16.03 ± 2.58 nmol/mg protein, P0.05). The decrease of SOD activity in APAP treatment group and the increase of SOD in 20 mg/kg CMN pretreatment group were also detected (24.54 ± 4.95 U/mg protein vs 50.21 ± 1.93 U/mg protein, P0.05). Furthermore, CMN treatment efficiently protected against APAP-induced apoptosis via increasing Bcl-2/Bax ratio.CMN has significant therapeutic potential in both APAP-induced hepatotoxicity and other types of liver diseases.