Astragaloside IV protects rat retinal capillary endothelial cells against high glucose-induced oxidative injury.

AIM: Diabetic retinopathy is a microvascular complication of diabetes that leads to blindness. Hyperglycemia causes oxidative stress, which is an important cause in the pathogenesis of microangiopathy. The aim of this study was to investigate the potential protective effects of astragaloside IV (AS-IV) in retinal capillary endothelial cells (RCECs) incubated with high glucose conditions. METHODS AND RESULTS: Based on rat RCECs cultured with high glucose (30 mM) in vitro, a significant increase in cell viability in rat RCECs incubated with both AS-IV and high glucose for 48 or 72 h by MTT assay. The increased viability was accompanied by decreased glucose transporter-1 expression using immunofluorescent assay. Meanwhile, AS-IV reduced intracellular hydrogen peroxide and superoxide, decreased mitochondrial reactive oxygen species in rat RCECs with high glucose by the fluorescent probes, and lowered malondialdehyde levels. In addition, AS-IV increased the activities of total superoxide dismutase, MnSOD, catalase, and glutathione peroxidase. The glutathione content also increased after AS-IV treatment. Furthermore, AS-IV reduced NADPH oxidase 4 expression by western blot method. CONCLUSION: These results suggest that the main mechanism underlying the protective effects of AS-IV in high glucose-injured RCECs may be related to its antioxidative function.

Effect of compatible herbs on the pharmacokinetics of effective components of Panax notoginseng in Fufang Xueshuantong Capsule.

Fufang Xueshuantong (FXT) is a well-known Chinese herbal formula which has been used to treat cardiovascular and ophthalmic diseases, especially diabetic retinopathy. Panax notoginseng (Burkill) F.H. Chen (PN) is the main herb of FXT, whose major bioactive constituents are ginsenosides. However, the scientific basis of the compatibility of FXT is still ambiguous. The present study investigated the scientific basis of the compatibility of FXT by comparing the pharmacokinetics of marker compounds after oral administrations of PN and FXT. A high performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) method was developed for simultaneous detection of notoginsenoside R1 (NR1), ginsenoside Rg1 (GRg1), and ginsenoside Rb1 (GRb1) in rat plasma. The pharmacokinetic studies of FXT and PN were performed using the established method with the pharmacokinetic parameters being determined by non-compartmental analysis. The results showed that the pharmacokinetic parameters (maximum concentration, area under the curve (AUC0-t), clearance, and mean residence time) of NR1, GRg1, and GRb1 were significantly different after oral administration of FXT (P<0.05) compared with PN. The AUC0-t values of GRg1 and GRb1 were 1.7- and 3.4-fold greater, respectively, in FXT than in PN. The compatible herbs of FXT could prolong the retention time and increase the systemic exposure of NR1, GRg1, and GRb1 compared with PN in vivo, providing some scientific basis for the compatibility and clinical use of FXT.

New perspectives on dietary-derived treatments and food safety-antinomy in a new era.

Despite the advances in science and technology and wide use of chemical drugs, dietary intervention (or food therapy) remains useful in preventing or treating many human diseases. A huge body of evidence shows that the dietary pattern or habit is also an important contributing factor to the development of chronic diseases such as hypertension, type 2 diabetes, hyperlipidemia, and cancers. In recent years, over-the-counter health foods, nutraceuticals, and plant-derived medicinal products have been gaining popularity all over the world, particularly in developed countries. Unfortunately, owing to the contamination with various harmful substances in foods and the presence of toxic food components, food-borne diseases have also become increasingly problematic. Incidents of food poisonings or tainted food have been increasing worldwide, particularly in China and other developing countries. Therefore, the government should put in a greater effort in enforcing food safety by improving the surveillance mechanism and exerting highest standards of quality control for foods.

Historical perspective of traditional indigenous medical practices: the current renaissance and conservation of herbal resources.

In recent years, increasing numbers of people have been choosing herbal medicines or products to improve their health conditions, either alone or in combination with others. Herbs are staging a comeback and herbal "renaissance" occurs all over the world. According to the World Health Organization, 75% of the world's populations are using herbs for basic healthcare needs. Since the dawn of mankind, in fact, the use of herbs/plants has offered an effective medicine for the treatment of illnesses. Moreover, many conventional/pharmaceutical drugs are derived directly from both nature and traditional remedies distributed around the world. Up to now, the practice of herbal medicine entails the use of more than 53,000 species, and a number of these are facing the threat of extinction due to overexploitation. This paper aims to provide a review of the history and status quo of Chinese, Indian, and Arabic herbal medicines in terms of their significant contribution to the health promotion in present-day over-populated and aging societies. Attention will be focused on the depletion of plant resources on earth in meeting the increasing demand for herbs.

Nardosinone improves the proliferation, migration and selective differentiation of mouse embryonic neural stem cells.

In this study, we investigated the impact of Nardosinone, a bioactive component in Nardostachys root, on the proliferation and differentiation of neural stem cells. The neural stem cells were isolated from cerebrums of embryonic day 14 CD1 mice. The proliferation of cells was monitored using the cell counting kit-8 assay, bromodeoxyuridine incorporation and cell cycle analysis. Cell migration and differentiation were investigated with the neurosphere assay and cell specific markers, respectively. The results showed that Nardosinone promotes cells proliferation and increases cells migration distance in a dose-dependent manner. Nardosinone also induces the selective differentiation of neural stem cells to neurons and oligodendrocytes, as indicated by the expression of microtubule-associated protein-2 and myelin basic protein, respectively. Nardosinone also increases the expression of phospho-extracellular signal-regulated kinase and phospho-cAMP response element binding protein during proliferation and differentiation. In conclusion, this study reveals the regulatory effects of Nardosinone on neural stem cells, which may have significant implications for the treatment of brain injury and neurodegenerative diseases.

[Nardosinone reduces neuronal injury induced by oxygen-glucose deprivation in primary cortical cultures].

The aim of the study is to investigate the effect of nardosinone (Nar) on neuronal injury induced by oxygen-glucose deprivation (OGD) in primary cortical cultures isolated from embryos at gestational day 14. MTT method was used to determine the dosage regimen of Nar in primary neuronal cultures and observe the influence of Nar on the neurons suffering OGD; Western blotting analysis was used to detect expressions of protein kinase A (PKA), Ras related protein 1 (Rap1), mitogen-activated protein kinase kinase 1 (MEK1) and phospho-extracellular signal-regulated kinase 1/2 (p-ERK1/2) of OGD-injured or uninjured primary cultured neurons after Nar treatment. Results showed that Nar (50 and 100 micromol x L(-1)) improved the cell viability during OGD damage (P < 0.01) and increased the expression of PKA, Rap1, MEK1 and p-ERK1/2 in injured neurons. Additionally, elevations of PKA, Rapl, MEK1 and p-ERK1/2 in uninjured neurons were caused by Nar (50, 100 and 200 micromol x L(-1)) with a dose-dependent tenclency as well (P < 0.01). In conclusion, Nar could protect against the neuronal injury exposed to OGD, which may be relevant to the promotion of PKA and ERK signaling pathway.

New Perspectives on How to Discover Drugs from Herbal Medicines: CAM's Outstanding Contribution to Modern Therapeutics.

With tens of thousands of plant species on earth, we are endowed with an enormous wealth of medicinal remedies from Mother Nature. Natural products and their derivatives represent more than 50% of all the drugs in modern therapeutics. Because of the low success rate and huge capital investment need, the research and development of conventional drugs are very costly and difficult. Over the past few decades, researchers have focused on drug discovery from herbal medicines or botanical sources, an important group of complementary and alternative medicine (CAM) therapy. With a long history of herbal usage for the clinical management of a variety of diseases in indigenous cultures, the success rate of developing a new drug from herbal medicinal preparations should, in theory, be higher than that from chemical synthesis. While the endeavor for drug discovery from herbal medicines is "experience driven," the search for a therapeutically useful synthetic drug, like "looking for a needle in a haystack," is a daunting task. In this paper, we first illustrated various approaches of drug discovery from herbal medicines. Typical examples of successful drug discovery from botanical sources were given. In addition, problems in drug discovery from herbal medicines were described and possible solutions were proposed. The prospect of drug discovery from herbal medicines in the postgenomic era was made with the provision of future directions in this area of drug development.

New perspectives on complementary and alternative medicine: an overview and alternative therapy.

Since 1990, tremendous progress in the medical sciences has precipitated significant improvements in health care. However, with the aging of populations worldwide, more people suffer from noncommunicable disease (NCD), incurable diseases, and/or poor health. The World Health Organization estimated that of the 57 million global deaths in 2008, 36 million were due to NCDs. These pose a considerable challenge to clinicians worldwide, particularly in developed nations. Complementary and alternative medicine (CAM) provides an array of treatment modalities for health promotion. CAM therapy can be divided into two major strategies; namely, herb-based CAM therapy and non-herb based CAM therapy. In the current commentary, we suggest a new understanding of CAM therapy and propose a new classification for CAM therapy as well as alternative therapies. With such information, CAM can be better utilized to benefit to populations worldwide.

[Regulation of microglia on neurogenesis in adult mammals].

Adult neurogenesis had been confirmed in rodents and other mammals for decades. The mechanisms underlying neurogenesis have been investigated extensively in recent years. Microglial cells, an immuno-cell in the central nervous system, have been found playing important roles in modulating the process of adult neurogenesis. The inflammatory microenvironment contributed by microglia are harmful to the survival of new born neurons. On the other hand, by interacting with T cells, microglia could act as a trophic factor for neurogenesis, most possibly by releasing growth factors. We reviewed the progress on how microglia regulating adult neurogenesis in variant pathological conditions. To understand the relationship between microglia and neurogenesis will help us to approach for promising therapeutic strategy for neuronal injury.

[Salvianolic acid B alleviate the disruption of blood-brain barrier in rats after cerebral ischemia-reperfusion by inhibiting MAPK pathway].

The aim of the study is to investigate the effect of salvianolic acid B (SalB) on blood-brain barrier (BBB) in rats after cerebral ischemia-reperfusion, and to illustrate its possible mechanisms. Cerebral ischemia-reperfusion was induced by middle cerebral artery occlusion in rats. The break-down of BBB was indicated by extravasations of immunoglobulin (IgG) monitored with immunohistochemistry. The expression of MMP-9 and NOS2 in the brain was determined by immunohistochemistry, and the expression of p-p38 and p-ERK1/2 was detected by Western blotting. It was shown that on day 2 after ischemia-reperfusion the IgG accumulated around the vascular boundary zone, suggesting the break-down of BBB, and the expression of MMP-9 and NOS2 up-regulated at the same time. The result of Western blotting suggested that the expression of p-p38 and p-ERK1/2 increased. On day 7 after ischemia-reperfusion the. expression of MMP-9 and NOS2 was about the same level as day 2, the expression of p-p38 was higher than that on day 2 and the expression of p-ERK1/2 was slightly lower than that on day 2. SalB (1 and 10 mg x kg(-1)) significantly alleviated the extravasations of immunoglobulin induced by cerebral ischemia-reperfusion (P < 0.05). On day 2 and day 7 SalB attenuated the expression of MMP-9 and NOS2 (P < 0.05). SalB (10 mg x kg(-1)) reduced the expression of p-p38 and p-ERK1/2 apparently on day 2 and 7 after ischemia-reperfusion (P < 0.05). SalB (1 mg x kg(-1)) inhibited the expression of p-p38 on day 7 after ischemia-reperfusion (P < 0.05). The results indicate that SalB protects blood-brain barrier in rats after cerebral ischemia-reperfusion by inhibiting the MAPK pathway.

[Effect of salvianolic acid B on neural cells damage and neurogenesis after brain ischemia-reperfusion in rats].

This study is to observe the effect of salvianolic acid B (Sal B) on neural cells damage and neurogenesis in sub-granular zone (SGZ) and sub-ventricular zone (SVZ) after brain ischemia-reperfusion (I/R) in rats. A modified middle cerebral artery occlusion (MCAO) model of focal cerebral ischemia-reperfusion was used. The rats were divided into four groups: sham control group, ischemia-reperfusion group, Sal B 1 and 10 mg x kg(-1) groups. Sal B was consecutively administrated once a day by ip injection after MCAO. The neurogenesis in SGZ and SVZ was investigated by BrdU method 7 days after MCAO. The Nissl staining for neurons in the hippocampal CA1 and cerebral cortex was performed 14 days after MCAO. A beam-walking test was used to monitor the motor function recovery. We found that brain ischemia resulted in an increase of BrdU positive cells both in ipsilateral SGZ and SVZ at 7th day after MCAO. Sal B (10 mg x kg(-1)) significantly increased further the number of BrdU positive cells both in SGZ and SVZ (P < 0.01). Ipsilateral hippocampal neuron damage occurred and CA1 almost lost 14 days after MCAO. Sal B (10 mg x kg(-1)) obviously attenuated the neuron damage and increased the number of neuron both in ipsilateral CA1 and cerebral cortex (P < 0.01). We also observed an obvious improvement of motor function recovery when Sal B (10 mg x kg(-1)) administrated. From the results above we concluded that Sal B stimulated neurogenesis process both in SGZ and SVZ after brain ischemia, and also alleviated neural cells loss and improved motor function recovery after brain ischemia in rats.

Effect of salvianolic acids from Radix Salviae miltiorrhizae on regional cerebral blood flow and platelet aggregation in rats.

This study was conducted to observe the effect of salvianolic acids (SA) on regional cerebral blood flow (rCBF) in rats and on platelet aggregation in vitro and in vivo. Cerebral ischemia was produced in rats by occluding of the right middle cerebral artery, together with the right common carotid artery. rCBF was monitored by H2 clearance method with a tissue blood-flow meter. Platelet aggregation induced by collagen, ADP, and AA was measured in vitro and in vivo by platelet aggregometer. Doses of SA at 6 and 10 mg/kg body wt. (i.v.) improved rCBF in rats after ischemia, but had no obvious effect on normal rCBF. In vitro, SA inhibited significantly the platelet aggregation induced by collagen, ADP, and AA with IC50 values of 0.197, 2.22 and 3.29 x 10(3) mg/l, respectively. In vivo, doses of SA at 6 and 10 mg/kg body wt. inhibited significantly the platelet aggregation induced by collagen, and SA at 10 mg/kg body wt. inhibited remarkably platelet aggregation induced by ADP. The results suggest that SA could improve rCBF in the ischemic hemisphere and inhibit platelet aggregation in rats.