Zhen Ouyang

Polysaccharides purified from Cordyceps cicadae protects PC12 cells against glutamate-induced oxidative damage

Two polysaccharides CPA-1 and CPB-2 were isolated purified from Cordyceps cicadae by hot water extraction, ethanol precipitation and purification using anion exchange and gel filtration chromatography. Preliminary structural characterization of CPA-1 and CPB-2 were performed. The protective effect of CPA-1 and CPB-2 against glutamate-induced oxidative toxicity in PC12 cells was analyzed. The results indicated that pretreatment of PC12 cells with CPA-1 and CPB-2 significantly increased cell survival, Ca(2+) overload and ROS generation. CPA-1 and CPB-2 also markedly up-regulated the antioxidant status of pretreated PC12 cells. Our results suggested that Cordyceps cicadae polysaccharides can protect PC12 cells against glutamate excitotoxicity and might serve as therapeutic agents for neuronal disorders.

Cordycepin protects PC12 cells against 6-hydroxydopamine induced neurotoxicity via its antioxidant properties.

Parkinsons disease (PD) is a progressive neurodegenerative disorder that is characterized by degeneration and loss of dopaminergic neurons of the substantia nigra. Increasing evidence has indicated that oxidative stress plays a pivotal role in the pathogenesis of Parkinsons disease (PD). Therapeutic options that target the antioxidant machinery may have potential in the treatment of PD. Cordycepin, a nucleoside isolated from Cordyceps species displayed potent antioxidant, anti-inflammatory and anticancer properties. However, its neuroprotective effect against 6-OHDA neurotoxicity as well as underlying mechanisms is still unclear. In this present study, we investigated the protective effect of cordycepin against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity and its underlying mechanism. We observed that cordycepin effectively inhibited 6-OHDA-induced cell death, apoptosis and mitochondrial dysfunction. Cordycepin also inhibited cell apoptosis induced by 6-OHDA as observed in the reduction of cytochrome c release from the mitochondrial as well as the inhibition of caspase-3. In addition cordycepin markedly reduced cellular malondialdehyde (MDA) content and intracellular reactive oxygen species (ROS) level. Cordycepin also significantly increased the antioxidant enzymes; superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in 6-OHDA-treated cells. The results obtained unambiguously demonstrated that cordycepin protects PC12 cells against 6-OHDA-induced neurotoxicity through its potent antioxidant activity.

Neuroprotective effects of adenosine isolated from Cordyceps cicadae against oxidative and ER stress damages induced by glutamate in PC12 cells

Glutamate has been proven to induce oxidative stress through the formation of reactive oxygen species (ROS) and increased calcium overload which results in neuronal injury, development of neurodegenerative diseases and death. Adenosine is one of the bioactive nucleosides found in Cordyceps cicadae and it has displayed several pharmacological activities including neuroprotection. In this study, the protective effects of adenosine from C. cicadae against glutamate-induce oxidative stress in PC12 cells were evaluated. The exposure of PC12 cells to glutamate (5mM) induced the formation of ROS, increased Ca(2+) influx, endoplasmic reticulum (ER) stress and up regulated the expression of pro-apoptotic factor Bax. However, pretreatment with adenosine markedly increased cell viability, decreased the elevated levels of ROS and Ca(2+) induced by glutamate. Furthermore adenosine increased the activities of GSH-Px and SOD, as well as retained mitochondria membrane potential (MMP), increased Bcl-2/Bax ratio, and reduced the expression of ERK, p38, and JNK. Overall, our results suggest that adenosine may be a promising potential therapeutic agent for the prevention and treatment of neurodegenerative disorders.

Chemical constituents from the water-soluble fraction of wild Sargentodoxa cuneata

Aim nTo study the chemical constituents from the water-soluble fraction of wild Sargentodoxa cuneata.

Pharmacokinetic-pharmacodynamic Modeling of Monoamine Oxidase A Inhibitory Activity and Behavior Improvement by Curcumin in the Mouse Forced Swimming Test

Abstract Aim To characterize the pharmacokinetic, pharmacodynamic and efficacy profiles of curcumin in animal model of depression. Methods The forced swimming test (FST) in mice was used in this study. The single and repeated (hourly for three times) oral administration of 2.5, 5 and 10 mg·kg−1 curcumin was performed in the FST. Brain monoamine oxidase A (MAO-A) in vitro and in vivo as well as behaviors were determined. The plasma curcumin concentration was analyzed using high performance liquid chromatography (HPLC) method. The pharmacokinetics of curcumin was described by a two-compartment pharmacokinetic model with a lag time in the mouse FST. Results The peak plasma concentration was observed at 0.75 h (single) and 2.75–3 h (repeated) after oral curcumin administration, and the plasma concentration was around detection limit at 6 h (single) and 14 h (repeated), respectively. Curcumin at nanogram concentrations showed monoamine oxidase A (MAO-A) inhibitory activity and behavioral improvement in the mouse FST. The maximum behavioral effects of climbing, swimming and immobility were achieved at 1–2 h (single) and 3–4 h (repeated), which paralleled that of the maximum MAO-A inhibitory effects in frontal cortex and hippocampus after oral curcumin administration in the mouse FST, respectively. Conclusion These results suggest that curcumin may indirectly produce behavioral improvement, and its antidepressant potency may not be dependent on its plasma concentration.

Accumulation of Flavonoid Glycosides and UFGT Gene Expression in Mulberry Leaves (Morus alba L.) before and after Frost

In order to determine the molecular mechanism underlying the influence of frost on chemical changes in mulberry leaves, the UFGT activity, expression level, and accumulation of flavonoid glycosides in mulberry leaves (Morus alba L.) were studied. The expression of UFGT gene was investigated by quantitative real‐time PCR (qRT‐PCR) and the UFGT activity, accumulation of flavonoid glycosides was studied by high performance liquid chromatography. Then, the correlation between the expression level of UFGT, the UFGT activity, and the flavonoid glycosides accumulation with temperature was explored. The accumulation of isoquercitrin and astragalin is significantly positively correlated with UFGT gene expression and UFGT activity. On the contrary, the average temperature was significantly negatively correlated with the level of UFGT gene expression and UFGT activity. The results show that after frost, low temperature can induce the expression of UFGT gene in mulberry leaves, resulting in the accumulation of flavonoid glycosides.

Atractylodes lancea rhizome water extract reduces triptolide-induced toxicity and enhances anti-inflammatory effects

The present study was designed to explore the influence of water extracts of Atractylodes lancea rhizomes on the toxicity and anti-inflammatory effects of triptolide (TP). A water extract was prepared from A. lancea rhizomes and co-administered with TP in C57BL/6 mice. The toxicity was assayed by determining serum biochemical parameters and visceral indexes and by liver histopathological analysis. The hepatic CYP3A expression levels were detected using Western blotting and RT-PCR methods. The data showed that the water extract of A. lancea rhizomes reduced triptolide-induced toxicity, probably by inducing the hepatic expression of CYP3A. The anti-inflammatory effects of TP were evaluated in mice using a xylene-induced ear edema test. By comparing ear edema inhibition rates, we found that the water extract could also increase the anti-inflammatory effects of TP. In conclusion, our results suggested that the water extract of A. lancea rhizomes, used in combination with TP, has a potential in reducing TP-induced toxicity and enhancing its anti-inflammatory effects.

Effects of tetrahydroberberine and tetrahydropalmatine on hepatic cytochrome P450 expression and their toxicity in mice

The aim of this study was to investigate the effects of tetrahydroberberine (THB) and tetrahydropalmatine (THP) on the expression of mouse liver cytochrome P450s, and evaluate their liver toxicity in mice. Real-time polymerase chain reaction (PCR) and western blot analyses were used to analyze the expression of major P450 isoforms. Liver toxicity was evaluated by measuring serum biochemical parameters and performing histopathological analysis. The real-time PCR results showed that THB induced Cyp1a2 (1.66xa0±xa00.34 fold, Pxa0<xa00.05), Cyp3a11 (1.57xa0±xa00.24 fold, Pxa0<xa00.05), and Cyp2e1 (1.75xa0±xa00.97 fold, Pxa0<xa00.05) mRNA expression, while THP inhibited Cyp1a2 (0.66xa0±xa00.12 fold, Pxa0<xa00.05) mRNA expression. The western blot results confirmed that the expression of CYP1A2, CYP3A, and CYP2E1 proteins in the mouse liver was induced by THB, whereas that of CYP1A2 was inhibited by THP. Toxicological studies showed that THB (40xa0mg/kg, oral gavage) increased mouse serum aspartate transaminase and total bilirubin, and liver malondialdehyde levels, and induced liver edema. No obvious changes in serum and liver tissue biochemical parameters were found and no significant pathological changes were detected in liver tissues after THP administration. Our results provide more information on the toxicity of THB and THP, and their related drug-drug interactions.

A NEW DITERPENOID GLUCOSIDE FROM AERIAL PARTS OF Rabdosia excisa

A new diterpenoid glucoside, isodonin C (1), was isolated from the aerial parts of Rabdosia excisa, as well as three known diterpenoids, excisanin B (2), kamebakaurin (3), and kamebanin (4). Their structures were elucidated on the basis of spectral analysis as well as chemical methods. Compounds 1 and 2 remarkably suppressed the NF-κB pathway.

Ultrasound-assisted Extraction of Kamebakaurin from Rabdosia excisa by Response Surface Methodology

For the efficient extraction of kamebakaurin(KA), the ultrasound-assisted extraction(UAE) of KA from Rabdosia excisa(R. excisa) via response surface methodology(RSM) was investigated with high-performance liquid chromatography(HPLC). Effects of the experimental parameters such as extraction solvent, ratio of liquid to plant material, extraction time and extraction temperature on the extracting efficiency of KA from R. excisa were evaluated, and the purity of KA in residual was calculated. The optimized conditions were 65.5%(volume fraction) acetone, 35 °C, time of 24.6 min with ultrasound of 80 W/L, 40 kHz, ratio of liquid to plant material at 30:1(mL/g). The maximum yield of KA is 0.708 mg/kg, with mean purity of 6.09%, indicating that ultrasound-assisted extraction is a feasible and useful method for extracting KA from R. excisa.