Xiaoxiu Li

Baicalein exerts neuroprotective effects in 6-hydroxydopamine-induced experimental parkinsonism in vivo and in vitro

Baicalein, a flavonoid obtained from the root of Chinese medicinal herb Scutellaria baicalensis, has been shown to exert a protective effect on neurons against several neuronal insults. The aim of this study was to explore the neuroprotective effect of baicalein in 6-hydroxydopamine (6-OHDA)-induced experimental parkinsonism in vitro and in vivo. In in vitro experiments, we found that baicalein (0.5, 5 microg/mL) could significantly ameliorate the 6-OHDA-induced SH-SY5Y cell apoptosis from 31.56% in the 6-OHDA group to 18.90%, 21.61% respectively, and also promote neurite outgrowth of PC12 cell. In in vivo experiments, baicalein had no effect on apomorphine (APO)-induced rotations, but it could significantly attenuate muscle tremor of 6-OHDA-lesioned rats. The burst frequency and amplitude are 13.43%, 35.18% compared to 6-OHDA group. Moreover, baicalein treatment could also increase tyrosine hydroxylase (TH)-positive neurons to 265.52% of the 6-OHDA group. The neuroprotective action of baicalein was coincident with an attenuated astroglial response within the substantia nigra. Neuroprotective effect of baicalein as demonstrated by the increasing the number of dopaminergic neurons may have been, in part, caused by anti-apoptotic, pro-differentiation and anti-inflammatory mechanisms of baicalein. Therefore, baicalein can be a promising candidate for prevention or treatment of Parkinsons disease, owing to its anti-apoptotic, pro-differentiation and anti-inflammatory action.

Neuroprotective effect of baicalein against MPTP neurotoxicity: Behavioral, biochemical and immunohistochemical profile

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes the damage of dopaminergic neurons as seen in Parkinsons disease (PD). Oxidative stress has been implicated in the pathogenesis of PD. Baicalein, isolated from the traditional Chinese herbal medicine Huangqin (Scutellaria baicalensis Georgi), has been shown to have antioxidant effects. Here we investigated the effect of baicalein on MPTP-induced neurotoxicity in mice. Pretreatment with baicalein for a week was followed by challenge with MPTP for 4 consecutive days; the subsequent behavioral, biochemical and immunohistochemical manifestations in mice were determined and compared to those in untreated mice and mice challenged only with MPTP. The present study showed that baicalein could improve the abnormal behavior in MPTP-treated mice. The protective effect may be caused by increasing the levels of DA and 5-HT in the striatum, increasing the counts of dopaminergic neurons, inhibiting oxidative stress and the astroglia response. These results suggest that baicalein possesses potent neuroprotective activity and may be a potential anti-Parkinsons disease drug that is worthy of further study.

Baicalein protects rat brain mitochondria against chronic cerebral hypoperfusion-induced oxidative damage

This study investigated the effects of baicalein, a natural compound isolated from the root of scutellaria, on cognitive and motor ability impaired by chronic cerebral hypoperfusion in rats, as well as its effects on brain mitochondria. Rats subjected to permanent bilateral common carotid artery occlusion experienced cognitive deficits, oxidative stress and mitochondria dysfunction, which was associated with the elevation of reactive oxygen species level, the decrease of oxidative phosphorylation parameters, the loss of mitochondrial membrane potential, the reduce in Bcl-2/Bax ratio, and the release of cytochrome c. Baicalein alleviated cognitive and motor impairments and decreased mitochondria reactive oxygen species production, in accordance with its improvements on membrane potential level, oxidative phosphorylation process, mitochondrial swelling degree, Bcl-2/Bax ratio and cytochrome c release. These data indicated that baicalein might have therapeutic potential for the treatment of dementia caused by chronic cerebral hypoperfusion, contributed to its protections on brain mitochondrial homeostasis and function.

Baicalein protects the brain against neuron impairments induced by MPTP in C57BL/6 mice

Many studies of Parkinsons disease suggest that oxidative stress is involved in the neurodegenerative process. Baicalein has been shown to have antioxidant effects. The present study examines the effect of baicalein on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in C57BL/6 mice. MPTP treatment impaired spontaneous motor activity and rotarod performance, but baicalein improved this deficit. Moreover, baicalein at 280 and 560 mg/kg exhibited a protective effect against the MPTP-induced decrease in tyrosine hydroxylase (TH)-positive fibers in the substantia nigra, demonstrated by the immunohistological, morphological and behavioral outcomes. MPTP treatment also decreased dopamine levels in the striatum. However, treatment with baicalein attenuated these decreases in dopamine levels by changing dopamine catabolism and inhibiting dopamine turnover. The neuroprotective effect of baicalein on dopaminergic neurons may partly be due to its antioxidant properties. Therefore, we speculate that baicalein might be a promising candidate for prevention or treatment of oxidative stress-related neurodegenerative disorders such as Parkinsons disease.

Protective effects of baicalein against rotenone-induced neurotoxicity in PC12 cells and isolated rat brain mitochondria

Baicalein is one of the major flavonoids obtained from the Scutellaria root. Previous pharmacological studies found that baicalein had neuroprotective effects in animal models of Parkinsons disease. The purpose of this paper was to explore the molecular mechanism of the action of baicalein on PC12 cells and isolated rat brain mitochondria. Firstly, we investigated the effects of baicalein on rotenone-induced toxicity in PC12 cells. The results showed that baicalein suppressed rotenone-induced apoptosis, and inhibited the accumulation of reactive oxidant species, ATP deficiency, mitochondrial membrane potential dissipation, and caspase-3/7 activation in a concentration-dependent manner, indicating that baicalein likely improved mitochondrial function. Furthermore, we used isolated rat brain mitochondria to evaluate the effect of baicalein. Treatment with baicalein prevented rotenone-induced reactive oxidant species production, ATP deficiency and mitochondrial swelling in isolated brain mitochondria. Interestingly, exposure of isolated mitochondria to baicalein promoted mitochondrial active respiration. These results suggest that baicalein may be a mitochondria-targeted antioxidant and exerts neuroprotective effects on rotenone-induced neurotoxicity. This study supports our previous research that baicalein possesses neuroprotective activity in vivo and it is worthy of further study.

Luteolin promotes long-term potentiation and improves cognitive functions in chronic cerebral hypoperfused rats

Processes of synaptic plasticity, such as long-term potentiation (LTP), has been considered a cellular correlate of learning and memory and many neurological disorders accompanied by cognitive deficits exhibit abnormal synaptic function. This emerging concept is exemplified by Alzheimers disease. Mounting evidence suggests that Alzheimers disease begins with subtle alterations of hippocampal synaptic efficacy prior to frank neuronal degeneration, which make it critical to identify LTP enhancers to slow down or stop the progression of Alzheimers disease. In this study, we found flavonoid luteolin could enhance basal synaptic transmission and facilitate the induction of LTP by high frequency stimulation in the dental gyrus of rat hippocampus. Furthermore, we investigated the effects of luteolin on chronic cerebral hypoperfusion-induced spatial learning dysfunction and LTP impairment in rat. The results showed chronic cerebral hypoperfusion produced by 2-vessel occlusion significantly impaired spatial learning and memory, and luteolin reversed the learning and memory deficit. 2-vessel occlusion resulted in dramatic inhibition of LTP formation in the hippocampus and luteolin significantly rescued the LTP impairment. These results demonstrate that luteolin not only directly modulates LTP formation, but also protects synapses from the detrimental effects of chronic cerebral hypoperfusion on LTP formation, which may contribute to the protective effects of luteolin on learning and memory. By immunoblotting, we found the effects of luteolin on LTP and memory may due to the activation of cAMP response element-binding protein (CREB). Therefore, flavonoid luteolin shows great potential as a novel treatment agent for protecting synaptic function and enhancing memory in neurodegenerative disorders.

Effect of valsartan on the pathological progression of hepatic fibrosis in rats with type 2 diabetes.

Currently there is no effective treatment for nonalcoholic fatty liver disease (NAFLD), especially hepatic fibrosis induced by type 2 diabetes. Valsartan maybe has beneficial effect on the liver disease. The aim of the present study was to investigate the effect of valsartan on the pathological progression of hepatic fibrosis in rats with type 2 diabetes. An animal model of hepatic fibrosis with type 2 diabetes was developed using a high-sucrose, high-fat diet and low-dose streptozotocin. Valsartan (15 mg/kg/day, i.g.) was orally administered for four months. The livers were removed to make hematoxylin-eosin (HE) staining and Picric acid-Sirius red staining, and immunohistochemistry staining of α-smooth-muscle-actin (α-SMA), transforming growth factor β1 (TGF-β1), tumor necrosis factor (TNF-α) and monocyte chemotactic protein-1 (MCP-1). Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was performed to detect hepatocyte apoptosis. The liver mitochondria were isolated to measure the mitochondrial respiratory function. The results showed that valsartan significantly alleviated the lesion of hepatic steatosis and hepatic fibrosis by HE staining and Picric acid-Sirius red staining. Immunohistochemical staining suggested that the expression of α-SMA, TGF-β1, TNF-α and MCP-1 in liver tissue of diabetic rats was markedly reduced by valsartan. TUNEL staining showed that there were fewer TUNEL-positive apoptotic hepatocytes in valsartan group. In addition, valsartan restored the injured hepatic mitochondrial respiratory function. The findings demonstrated that valsartan prevented the pathological progression of hepatic fibrosis in type 2 diabetic rats, correlated with reducing α-SMA, TGF-β1, TNF-α and MCP-1 expression, also anti-apoptosis and mitochondria-protective potential.

Salvianolic Acid A Prevents the Pathological Progression of Hepatic Fibrosis in High-Fat Diet-Fed and Streptozotocin-Induced Diabetic Rats

Type 2 diabetes patients have an increased risk of developing hepatic fibrosis. Salvianolic acid A (SalA) has been reported to be a strong polyphenolic anti-oxidant and free radical scavenger. The aim of the present study was to evaluate the effect of SalA on the pathological progression of hepatic fibrosis in high-fat diet (HFD)-fed and streptozotocin (STZ)-induced diabetic rats and to clarify the underlying mechanisms. Type 2 diabetic animal model with hepatic fibrosis was developed by a high-sucrose, HFD and low-dose STZ injection (i.p.). Diabetic rats were randomly divided into SalA group (0.3 mg/kg/day) and diabetic control groups fed with a HFD. After administration for four months, SalA reversed the hyperlipidemia and reduced hepatic triglyceride (TG). Hematoxylin-Eosin (HE) and Picro acid-Sirius red staining results indicated that SalA significantly alleviated the lesions of hepatic steatosis and fibrosis, with the reduction of type I and III collagens. The expression of α-smooth-muscle-actin (α-SMA) and transforming growth factor β1 (TGF-β1) in the liver were markedly down-regulated by SalA treatment. TUNEL staining showed that SalA reduced apoptosis in hepatocytes. In addition, SalA improved hepatic mitochondrial respiratory function in diabetic rats. Taken together, these findings demonstrated that SalA could prevent the pathological progression of hepatic fibrosis in HFD-fed and STZ-induced diabetic rats. The underlying mechanisms may be involved in reducing oxidative stress, suppressing α-SMA and TGF-β1 expression, as well as exerting anti-apoptotic and mitochondria-protective effects.

Development and validation of a high-performance liquid chromatographic method for determination of pinocembrin in rat plasma: application to pharmacokinetic study.

A sensitive and specific reversed-phase high-performance liquid chromatography with ultraviolet detection (RP-UV-HPLC) method has been developed and validated for the identification and quantification of pinocembrin in rat plasma using chrysin as the internal standard. Following protein precipitation with acetonitrile, the analytes were separated by the mobile phase 0.01 M ammonium acetate (pH 4.0)-methanol (35:65, v/v) with an Agilent TC-C18 column (5 microm, 4.6 mm x 150 mm) at a flow rate of 1 ml/min, column temperature 40 degrees C and detection wavelength 290 nm. A good linear relationship was obtained in the concentration range studied (0.07-133.33 microg/ml, r=0.9995). The lowest limit of quantification (LLOQ) was 66.7 ng/ml and the lowest limit of detection (LLOD) was 25 ng/ml. Average recoveries ranged from 93.9 to 97.8% in plasma at the concentrations of 0.33 and 33.33 microg/ml. Intra- and inter-batch relative standard deviations were 0.15-2.03 and 1.18-9.96%, respectively. This method was successfully applied to the pharmacokinetic studies in rats after intravenous administration of pinocembrin.