Antidepressive mechanisms of rhynchophylline in mice with chronic unpredictable stress-induced depression.

ETHNOPHARMACOLOGICAL RELEVANCE: Uncaria rhynchophylla ([Mi] Jack) (gouteng) exerts antidepressive effects. Rhynchophylline (RH), a major component of U. rhynchophylla, exerts similar pharmacological effects to those of gouteng. Thus, RH may have antidepressive effects. AIM OF THE STUDY: To investigate the anti-depressive effects of RH in chronic unpredictable mild stress (CUMS)-induced depressive mice. The anti-depressive mechanism of RH determined by measuring the 5-HT levels, the expressions of cAMP-response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in cortex and hippocampus. MATERIALS AND METHODS: The behaviors of CUMS-induced depressive mice were measured using an open field test (OFT), forced swimming test (FST), and tail suspension test (TST). 5-HT levels were measured using an ELISA kits. The expressions of BDNF and CREB were determined using western blot test. RESULTS: RH increased the frequency of rearing and grooming in the OFT and decreased the immobility time in the FST and TST. RH effectively increased the 5-HT level and BDNF and CREB expressions in the cortex and hippocampus. CONCLUSION: Our findings indicate that the antidepressive mechanism of RH is related to increased levels of 5-HT from regulating CREB and BDNF expressions in cortex and hippocampus.

Comparison of area under the curve in various models of diabetic rats receiving chronic medication.

Introduction: The oral glucose tolerance test (OGTT) is widely used as a diagnostic tool for impaired glucose tolerance (IGT) in clinical settings and animal experiments. The area under the curve (AUC) is then developed to quantify the total increase in blood glucose during the OGTT. Similarly, attenuation of the increased AUC indicates the improvement of IGT in animals. Variations in fasting plasma glucose between individuals stimulate the development of incremental area under the curve (iAUC). However, the iAUC determined from subtracting the baseline value of fasting plasma glucose (similar to ΔAUC) has been challenged as problematic without evidence. Material and methods: We developed four different diabetic animal models. In each model, rats were treated with metformin, dapagliflozin, and insulin respectively for 1 week. OGTTs were performed after 7 days of the drug treatment. The acute blood glucose changes induced by one-time treatment of drugs were also compared. Results: After a daily application of each drug at an effective dose for 7 days, results indicated potency in the following order: insulin > dapagliflozin > metformin. This was determined by calculation using the AUC in all diabetic models. However, the order changed when using the calculation with iAUC. Additionally, signals were changed before the OGTT in each model that received repeated treatment of each drug. Notably, drug potency was shown to be the same in OGTT calculated from iAUC and AUC in diabetic rats receiving acute treatment. Conclusions: iAUC seems unsuitable for application in cases where subjects are receiving chronic medication(s).

Chinese Medicine She-Xiang-Xin-Tong-Ning, Containing Moschus, Corydalis and Ginseng, Protects from Myocardial Ischemia Injury via Angiogenesis.

The Chinese patent medicine She-Xiang-Xin-Tong-Ning (SXXTN) is a clinical medication for coronary heart disease (CHD) and angina pectoris. This study aimed to investigate pharmacological effects of SXXTN and elucidate the role in angiogenesis on human umbilical vein endothelial cells (HUVECs) and acute myocardial ischemia (AMI) rats. We prepared SXXTN to treat the cells to reveal their effects on oxidative stress-damaged cell viability, as well as cell proliferation, migration, and tube formation processes. SXXTN was also used to treat coronary artery ligation-induced acute myocardial ischemia rats to confirm whether it had positive effect on myocardial issues by hematoxylin and eosin (HE), 2,3,5-triphenyltetrazolium chloride (TTC) staining and immunohistochemical staining. We measured the levels of peroxidative damage-related enzymes in cytoplasm and serum by biochemical kits and detected vascular endothelial growth factor (VEGF), angiotensin II (Ang II), thromboxane B2 (TXB2), and 6-keto-prostaglandin F1 alpha (6-keto-PGF1α) levels in cells and rats by enzyme-linked immunosorbent assay (ELISA) kits. The results showed that SXXTN protects HUVECs against oxidative stress damage and reversed the decrease of superoxide dismutase (SOD), glutathione (GSH) and increase of creatine kinase (CK), lactate dehydrogenase (LDH) caused by oxidative stress. SXXTN promoted angiogenesis through stimulating cell migration, tube formation, and activating VEGF/VEGFR2 and ERK1/2 pathways. Furthermore, SXXTN reduced infarct size and inhibited PGI2/TXA2 imbalance, preventing atherosclerosis plaque rupture leading to worsening coronary heart disease. Taken together, we report the first in vivo and in vitro evidence that SXXTN reduced oxidative stress-mediated damage and enhanced angiogenesis, which might be useful in treatment of myocardial infarction.

Hepatoprotective Mechanisms of Taxifolin on Carbon Tetrachloride-Induced Acute Liver Injury in Mice.

OBJECTIVE: To investigate the hepatoprotective mechanisms of taxifolin in mice with acute liver injury induced by CCl4. METHODS: ICR (Institute of Cancer research) mice were orally pretreated using taxifolin for 7 consecutive days and were then given single intraperitoneal (i.p.) injections of 0.2% CCl4 (10 mL/kg body weight, i.p.). Liver injury was then determined using assays of serum alanine aminotransferase (sALT) and serum aspartate aminotransferase (sAST). Further, to investigate the hepatoprotective mechanisms of taxifolin, we determined malondialdehyde (MDA) levels and superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GRd) activities. RESULTS: CCl4-induced liver injury led to significant increases in sALT and sAST activities, and these increases were limited by taxifolin and silymarin (Sily) pretreatments. Histological analyses also indicated that taxifolin and Sily decreased the range of liver lesions in CCl4-treated mice and vacuole formation, neutrophil infiltration, and necrosis were visibly reduced. In addition, SOD, GPx, and GRd activities were increased and MDA levels were decreased after taxifolin and Sily treatments. CONCLUSION: The hepatoprotective mechanisms of taxifolin and Sily are related to decreases in MDA levels presumably due to increased antioxidant enzyme activities. These outcomes suggest that taxifolin mitigates acute liver injury resulted from CCl4 in mice, demonstrating the hepatoprotective effects of taxifolin.