The American Journal of Chinese Medicine

To systematically evaluate the efficacy and safety of Danhong injection (DH) in treating acute coronary syndrome (ACS), randomized controlled trials (RCTs) regarding ACS treated by DH were searched in Chinese and English electronic databases from inception until June 2013. Two reviewers independently retrieved RCTs and extracted information. The Cochrane risk of bias method was used to assess the quality of the included studies, and a meta-analysis was conducted with Review Manager 5.2 software. About 26 RCTs with 2660 participants were included. The methodological quality was usually not high, and only one study used a randomized, double-blinded method. The meta-analysis indicated that on the basis of conventional therapy with Western medicine (WM), DH was more effective in increasing the total effective rate [RR = 1.24, 95%CI (1.17, 1.32), p < 0.00001]. Additionally, DH can decrease inflammatory cytokines, including high sensitive C-reactive protein (Hs-CRP) and interleukin-6 (IL-6), lower plasma viscosity, plasma endothelin-1 (ET-1) and brain natriuretic peptide (BNP), reduce the generation of myeloperoxidase (MPO), and decrease the number of T-wave inversion. There were no adverse drug reactions (ADR) reported in the experimental group, while one case occurred in the control group. Based on the systematic review, DH combined with WM was effective in the treatment of ACS. However, the safety of DH in the treatment of ACS should be further carefully interpreted by more large-scale and double-blind RCTs.

We assessed the therapeutic effects of lumbrokinase, a group of enzymes extracted from the earthworm, on peripheral-nerve regeneration using well-defined sciatic nerve lesion paradigms in diabetic rats induced by the injection of streptozotocin (STZ). We found that lumbrokinase therapy could improve the rats' circulatory blood flow and promote the regeneration of axons in a silicone rubber conduit after nerve transection. Lumbrokinase treatment could also improve the neuromuscular functions with better nerve conductive performances. Immunohistochemical staining showed that lumbrokinase could dramatically promote calcitonin gene-related peptide (CGRP) expression in the lamina I–II regions in the dorsal horn ipsilateral to the injury and cause a marked increase in the number of macrophages recruited within the distal nerve stumps. In addition, the lumbrokinase could stimulate the secretion of interleukin-1 (IL-1), nerve growth factor (NGF), platelet-derived growth factor (PDGF), and transforming growth factor-β (TGF-β) in dissected diabetic sciatic nerve segments. In conclusion, the administration of lumbrokinase after nerve repair surgery in diabetic rats was found to have remarkable effects on promoting peripheral nerve regeneration and functional recovery.

The effects of neferine, a bisbenzylisoquinline alkaloid extracted from the seed embryo of the Chinese traditional medicine Nelumbo nucifera Gaertn, on carbon tetrachloride (CCl₄)-induced hepatic fibrosis in mice were evaluated. Adult male Kunming mice were administered with CCl₄ 1 ml/kg via intraperitoneal injection twice a week for 8 weeks. At the beginning of the 9th week, mice were treated with normal saline, colchicine (0.1 mg/kg), and neferine (5, 10, 20 mg/kg) via intraperitoneal injection once a day for 2 weeks. The liver index and histological examination, plasma ALT/AST levels, hydroxyproline and TGF-β1 content of liver tissue were examined. In the model group, the liver index, the hydroxyproline content of liver tissue and plasma ALT/AST levels were increased, and a high expression of TGF-β1 was observed. The abnormal changes could be improved by neferine in a dose-dependent manner. Our data showed that neferine had an antifibrosis effect on CCl₄-induced hepatic fibrosis in mice, possibly partly due to the decreased expression of TGF-β1 in the liver.

Kaempferol is a biologically active component present in various plants. The hepatoprotective effect of kaempferol in drug-induced liver injury has been proven, while its effect against alcoholic liver injury (ALI) remains unclear. Hence, the present study aimed to evaluate the effect of kaempferol against ALI in mice. The experimental ALI mice model was developed and the mice were treated with different doses of kaempferol for 4 weeks. The liver functions were observed by monitoring the following parameters: Aspartate aminotransferase (AST/GOT) and alanine aminotransferase (ALT/GPT) levels in serum; histopathological studies of liver tissue; oxidative stress by hydrogen peroxide (H₂O₂), superoxide dismutase (SOD) and glutathione (GSH); the lipid peroxidation status by malondialdehyde (MDA) and lipid accumulation by triglyceride (TG) level in serum; and the expression levels and activities of a key microsomal enzyme cytochrome 2E1 (CYP2E1), by both in vitro and in vivo methods. The ALI mice (untreated) showed clear symptoms of liver injury, such as significantly increased levels of oxidative stress, lipid peroxidation and excessive CYP2E1 expression and activity. The mice treated with different kaempferol dosages exhibited a significant decrease in the oxidative stress as well as lipid peroxidation, and increased anti-oxidative defense activity. The kaempferol treatment has significantly reduced the expression level and activity of hepatic CYP2E1, thus indicating that kaempferol could down regulate CYP2E1. These findings show the hepatoprotective properties of kaempferol against alcohol-induced liver injury by attenuating the activity and expression of CYP2E1 and by enhancing the protective role of anti-oxidative defense system.

The adipose tissue is an endocrine organ, and its endocrine function is closely related to type 2 diabetes. Edible Chrysanthemum morifolium Ramat. (ECM) possesses several biological properties; however, its effect on adipocytes remains unclear. We investigated the effect of the hot water extract of ECM (HW-ECM) on 3T3-L1 adipocytes. HW-ECM enhanced adipocyte differentiation, adiponectin secretion, and glucose uptake in 3T3-L1 cells. It also increased the mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ), a regulator of adipocyte differentiation, adiponectin transcription, and GLUT4 expression. In addition, HW-ECM increased the mRNA levels of CCAAT/enhancer-binding protein-delta (C/EBPδ), which induces PPARγ expression, but not C/EBPβ, during early adipocyte differentiation. These results suggest that HW-ECM enhances adipocyte differentiation, adiponectin secretion, and glucose uptake through C/EBPδ-induced PPARγ expression. These effects of HW-ECM on adipocytes suggest that HW-ECM is potentially beneficial for type 2 diabetes.

Lobelia chinensis Lour (LcL) is a popular herb that has been widely used as folk medicine in China for the treatment of fever, lung cancer, and inflammation for hundreds of years. Recently, several studies have shown that the anti-inflammatory properties were correlated with the inhibition of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) from the NF-κB pathway. The aim of this study was to evaluate the anti-oxidative and anti-inflammatory activities of L. chinensis. Both suppressive activities on LPS-induced nitric oxide production in RAW264.7 macrophages in vitro and the acute rat lung injury model in vivo were studied. The results showed that the methanol extract of LcL and its fractions within the range of 62.5–250 μg/mL did not induce cytotoxicity (p < 0.001). The ethyl acetate fraction of LcL showed better NO inhibition activity than other fractions. On the other hand, the Lc-EA (62.5, 125, 250 mg/kg) pretreated rats showed a decrease in the pro-inflammatory cytokines (TNF-α, IL-β, IL-6) and inhibited iNOS, COX-2 expression through the NF-κB pathway. These results suggested that L. chinensis exhibited an anti-inflammatory effect through the NF-κB pathways.

Dioscorea nipponica Makino, a popular folk medicine, exerts anti-inflammation properties. The present study investigated the therapeutic effect of the total saponins from Dioscorea nipponica Makino (TSDN) on aplastic anemia (AA) and possible immune regulation mechanisms. Using a mouse model of AA, three different doses of TSDN were orally administrated for 14 consecutive days. We first demonstrated that TSDN was found to be effective in alleviating pancytopenia with a hypocellular bone marrow as compared with AA model group. Moreover, gastrogavage administration of a medium dose of TSDN was found to dramatically increase the percentage of CD4⁺ cells in bone marrow nucleated cells (BMNC) and restore the CD4⁺/CD8⁺ ratio. The pro-inflammatory cytokine concentrations of IL-2 and IFN-γ were significantly decreased, and anti-inflammatory cytokine IL-4 was significantly increased in culture supernatant of BMNC. Further investigations showed that TSDN obviously inhibited Fas–FasL-induced BMNC apoptosis as well as effectively suppressed intracellular apoptosis protein of caspase-3 and -8 expressions. Taken together, these findings suggested that TSDN could alleviate AA by elevating the CD4⁺/CD8⁺ T-cell ratio, inhibiting inflammatory Th1-cytokines, and exerting anti-apoptosis effects.

Ginsenoside Rg1 has been reported to possess anti-inflammatory activities, but the effects of Rg1 on the shear induced MCP-1 upregulation mechanism on endothelial cells (ECs) remain to be determined. In this study, we show that Rg1 down modulates shear induced pro-inflammatory cytokine MCP-1 gene expression and monocytes adhesion without potential cell toxicity. The negative effects on monocytes adhesion is due to a decrease in MCP-1 protein release. Furthermore, the inhibitory effect of Rg1 on the phosphorylation level of ERK, p38, and JNK mitogen-activated protein kinase (MAPK) induced by shear stress (SS) is similar with that of specific chemical inhibitors for MAPK pathways activation. These results demonstrate that ginsenoside Rg1 inhibits the shear induced inflammation by suppressing the MAPK pathway. This suggests that Rg1 may serve as a novel anti-inflammatory agent for inflammation-induced cardiovascular diseases treatment.

Cholinergic dysfunction and oxidation stress are the dominant mechanisms of memory deficit in Alzheimer's disease (AD). This study describes how ferulic acid (FA) ameliorates cognitive deficits induced by mecamylamine (MECA), scopolamine (SCOP), central acetylcholinergic neurotoxin ethylcholine mustard aziridinium ion (AF64A) and amyloid β peptide (Aβ_1-40). This study also elucidates the role of anti-oxidant enzymes and cholinergic marker acetylcholinesterase (AChE) in the reversal of FA from Aβ_1-40-induced cognitive deficits in rats. At 100 mg/kg, FA attenuated impairment induced by MECA and SCOP plus MECA; however, this improvement was not blocked by the peripheral muscarinic receptor antagonist scopolamine methylbromide (M-SCOP). At 100 and 300 mg/kg, FA also attenuated the impairment of inhibitory passive avoidance induced by AF64A. Further, FA attenuated the performance impairment and memory deficit induced by Aβ_1-40 in rats, as did vitamin E/C. FA reversed the deterioration of superoxide dismutase (SOD) and AChE activities, and the glutathione disulfide (GSSG) and glutathione (GSH) levels in the cortex and hippocampus. Vitamin E/C only selectively reversed deterioration in the hippocampus. We suggest that FA reduced the progression of cognitive deficits by activating central muscarinic and nicotinic receptors and anti-oxidant enzymes.

Breast cancer (BC) is the most frequently diagnosed type of cancer all over the world. Angiogenesis, a physiological or pathological process characterized by the sprouting of new blood vessels from existing vessels, plays a vital role in tumor nutrition. In this work, we used JSI-124 (Cucurbitacin I), a selective JAK/STAT3 signaling pathway inhibitor, to investigate the role of STAT3 in tumor angiogenesis of a human BC cell line in vitro. JSI-124 inhibited cell viability, proliferation, adhesion, migration and tube formation of a human BC cell line MDA-MB-468. After transfection with pMXs-Stat3C, a dominant active mutant, the inhibitory effects of JSI-124 on MDA-MB-468 were abolished. Furthermore, JSI-124 reduced the phosphorylation of STAT3. These results suggested that JSI-124 inhibited tumor angiogenesis of the human BC cell line in vitro through the reduction of STAT3 phosphorylation. In addition, JSI-124 could reduce VEGF transcription and secretion, suggesting that JSI-124 is also involved in the inhibition of the VEGF autocrine loop in the tumor microenvironment.

Lung cancer is the leading cause of cancer-related death worldwide. Non-small cell lung cancer (NSCLC) accounts for 80% of lung cancer cases and the reported overall 5-year survival rate is less than 5%. Natural medicines have attracted much attention due to their lower toxicity and fewer side effects. Trichosanthes kirilowii Maxim (TKM) fruits are commonly used in cancer treatment in combination with other Chinese medicinal herbs. However, little is known about their biological functions and mechanisms in NSCLC cells. In this study, we investigated the efficacy of TKM fruits in NSCLC cells using cell proliferation, invasion, migration, and anchorage independent assays and a Xenograft NSCLC tumor model, and explored the possible biological mechanism by flow cytometric analysis, cDNA microarray and real-time PCR. Results showed that TKM fruits significantly suppressed NSCLC cell proliferation, migration, invasion, tumorigenicity and tumor growth, and significantly extended the survival time of NSCLC-bearing mice. Flow cytometric analysis showed that TKM fruits significantly induced G2-M arrest, necrosis and apoptosis in NSCLC cells. cDNA microarray analysis revealed that TKM fruits regulated the differential expression of 544 genes, and the differential expression of selected genes was also confirmed. Gene ontology (GO) analysis showed that 18 of first 20 biological processes were involved in cell cycle and mitosis. These results indicate that TKM fruits have certain inhibitory effect on NSCLC cells through cell-cycle and mitosis arrest, and suggest that TKM fruits may be an important resource for developing new antitumor drugs, and a potent natural product for treating patients with NSCLC.

Numerous evidences have shown that plant flavonoids (naturally occurring substances) have been reported to have chemopreventive activities and protect against experimental carcinogenesis. Kaempferol, one of the flavonoids, is widely distributed in fruits and vegetables, and may have cancer chemopreventive properties. However, the precise underlying mechanism regarding induced DNA damage and suppressed DNA repair system are poorly understood. In this study, we investigated whether kaempferol induced DNA damage and affected DNA repair associated protein expression in human leukemia HL-60 cells in vitro. Percentages of viable cells were measured via a flow cytometry assay. DNA damage was examined by Comet assay and DAPI staining. DNA fragmentation (ladder) was examined by DNA gel electrophoresis. The changes of protein levels associated with DNA repair were examined by Western blotting. Results showed that kaempferol dose-dependently decreased the viable cells. Comet assay indicated that kaempferol induced DNA damage (Comet tail) in a dose-dependent manner and DAPI staining also showed increased doses of kaempferol which led to increased DNA condensation, these effects are all of dose-dependent manners. Western blotting indicated that kaempferol-decreased protein expression associated with DNA repair system, such as phosphate-ataxia-telangiectasia mutated (p-ATM), phosphate-ataxia-telangiectasia and Rad3-related (p-ATR), 14-3-3 proteins sigma (14-3-3σ), DNA-dependent serine/threonine protein kinase (DNA-PK), O⁶-methylguanine-DNA methyltransferase (MGMT), p53 and MDC1 protein expressions, but increased the protein expression of p-p53 and p-H2AX. Protein translocation was examined by confocal laser microscopy, and we found that kaempferol increased the levels of p-H2AX and p-p53 in HL-60 cells. Taken together, in the present study, we found that kaempferol induced DNA damage and suppressed DNA repair and inhibited DNA repair associated protein expression in HL-60 cells, which may be the factors for kaempferol induced cell death in vitro.