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Engelhardia roxburghiana Wall. is a traditional Chinese medicine used for treating cardiovascular diseases. Our previous study has implicated potential effects of total flavonoids of Engelhardia roxburghiana Wall. (TFER) against hyperlipidemia. The aim of the study is to uncover the effects and underlying mechanisms of TFER on foam cells formation after atherosclerosis. We used high fat diet (HFD) induced Apoe-/- mice and oxidized density lipoprotein (ox-LDL) induced THP-1 cells to mimic process of atherosclerosis in vivo and in vitro, respectively. Lipid accumulation, inflammation response, autophagosomes formation and expressions of autophagy related target genes were assessed. Our present study demonstrated TFER (500 mg/kg) alleviated macrophage infiltration and lipid accumulation in thoracic aortas of HFD-treated mice. In ox-LDL-treated THP-1 cells, MDC staining and Western blot analysis all indicated that the TFER (200 μg/ml) reduced foam cells formation and IL-1β releasing, activated autophagy through suppressing AKT/mTOR signaling, significantly regulating expressions of AKT, p-AKT, mTOR, p-mTOR, Beclin 1, LC3-II, p62. It is suggested that TFER alleviated atherosclerosis progression in vivo and in vitro through reducing foam cells formation and inflammatory responses, and the possible mechanism may be due to the activation of macrophage autophagy by inhibiting AKT and mTOR phosphorylation.

OBJECTIVE To investigate the antidepressant-like effect of active fraction of Polyrhachis vicina Roger (AFPR) in a rat depression model, and to elucidate the underlying mechanism. METHODS AFPR was extracted with ethanol followed by petroleum ether. Its antidepressant-like effect was investigated in mice by tail suspension test (TST), forced swimming test (FST) and open field test (OPT). A repeated dose of reserpine (0.5 mg/kg, daily for 14 d) was used to establish a rat depression model. Fluoxetine was used as positive control agent. The effect of AFPR on reserpine-induced ptosis, hypothermia and akinesia, the levels of monoamines and their metabolites, and the activity of monoamine oxidase (MAO) in hippocampus and prefrontal cortex were determined. RESULTS Administration of AFPR by gavage at 160 and 320 mg/kg significantly reduced the duration of immobility in the FST and TST, and did not affect locomotor activity in the OPT. In the reserpine-induced depression model, AFPR attenuated anhedonia, demonstrated by reversing hypothermia, akinesia and sucrose consumption. AFPR significantly increased the concentration of monoamines, including dopamine, serotonin, noradrenaline and acetylcholine. CONCLUSION AFPR normalized the metabolism rates of noradrenaline, serotonin and dopamine, and the activity of MAO, which were altered by chronic reserpine exposure. The findings suggest that modulation of the monoaminergic neurotransmitter system likely underlies the antidepressant-like effect of AFPR.

Breast cancer (BC) is a major contributor of cancer-associated mortality in women. It is essential to find new therapeutic targets and drugs. Polyrhachis vicina Rogers is one of the Traditional Chinese Medicine (TCM). Our previous studies have shown an active fraction of Polyrhachis vicina Rogers (AFPR) has significant anti-inflammatory activity, suggesting its anti-cancer effect. Here, we aimed to explore the inhibitory effects of AFPR on BC and reveal its mechanism. The effects of AFPR on BC were examined by cell proliferation assay, wound healing assay, invasion assay and xenograft assay. Microarray sequencing, qRT-PCR, Western blot, chromatin immunoprecipitation assay and luciferase reporter assay were performed to investigate the regulation of AFPR on related genes and underlying mechanisms. As a result, AFPR suppressed BC cell growth, migration and invasion and inhibited tumor growth. LncRNA NKILA was most prominently upregulated in AFPR-treated MCF7 cells. AFPR inactivated NF-κB signaling pathway via regulating NKILA. Furthermore, AFPR regulated the expression of NKILA by inhibiting its transcript suppressor EGR1. This study firstly indicated that AFPR was a potential inhibitor of BC development via regulating EGR1/NKILA/NF-κB axis.

Engelhardia roxburghiana Wall. leaves are widely used to develop herbal teas in southeast of China due to medicinal use for diabetes mellitus and hyperlipidemia. Studies have demonstrated that the total flavonoids of E. roxburghiana leaves (TFER) exhibited regulatory effects on blood glucose and lipids. To clarify the active ingredients of TFER and their targets in treating atherosclerosis, the present study integrated chemical analysis, network pharmacology analysis and animal experimental studies. Firstly, high performance liquid chromatography-mass spectrometry/mass spectrometry (HPLC/MS/MS) was utilized to identify components of TFER. Then, active ingredients were screened by oral bioavailability (OB) and drug-likeness (DL) index. Thirdly, network was constructed to predict major targets of active ingredients against atherosclerosis. Finally, to verify parts of predicted signaling, Apoe-/- mice were used to develop atherosclerosis. Atherosclerotic plaques in aorta were evaluated by echocardiography. Then, serum lipids, target genes expressions in thoracic aorta were determined by qRT-PCR and ELISA methods. Chemical analysis revealed 10 components in TFER sample, 7 of which acted as active ingredients, including naringenin, kaempferol, quercetin, isoengeletin, engeletin, astilbin and quercitrin. KEGG pathway analysis highly enriched in some inflammatory signalings, including NF-κB signaling, Toll-like receptor signaling and TNF signaling. The animal studies indicated that TFER reduced atherosclerotic plaques size in aorta and significantly decreased the serum lipids, down-regulated NF-κB signaling by decreasing mRNA level of NF-κB p65 subunit, TNF-α and VCAM-1, as well as IL-1β expressions in thoracic aorta, eventually alleviating atherosclerosis progression, which was in consistent with our prediction.

Background/Aims: The objective of this study is to evaluate the hypouricemic and nephroprotective effects of an active fraction from Polyrhachis vicina Roger (AFPR) in potassium oxonate-induced hyperuricemic rats. Methods: Hyperuricemia was induced by potassium oxonate in male rats. AFPR was orally administered to hyperuricemic rats for 12 consecutive weeks. Serum, liver and kidney samples were collected for effects and mechanism analysis. The levels of serum uric acid (SUA) were measured by the phosphotungstic acid method, xanthine oxidase (XOD) activity in the hepatic and serum samples were measured by ultraviolet spectrophotometry, serum levels of interleukin-1 (IL-1β), interleukin-1 (IL-6) and tumor necrosis factor-α (TNF-α) were measured by ELISA, the levels of serum creatinine (SCr), blood urea nitrogen (BUN), super oxide dismutase (SOD) and malondialdehyde (MDA) in serum were determined by colorimetric method. Protein expression of renal URAT1, GLUT9, and OAT1 were analyzed by Western blot. Results: AFPR significantly decreased the levels of SUA, serum and hepatic XOD, SCr, BUN, and MDA as well as increased SOD. In addition, AFPR treatment significantly reduced the levels of proinflammatory cytokines in serum, including IL-1β, IL-6 and TNF-α. Moreover, we found the significant decrease in protein expression of URAT1 and GLUT9, and the significant increase in protein expression of OAT1 in the kidney in AFPR treated groups compared to the model groups of hyperuricemia. Conclusion: These findings suggest that AFPR has anti-hyperuricemic activity attributed to the inhibition of uric acid generation in the liver and probably to the enhancement of urate excretion in the kidney, and possess nephroprotective effect in hyperuricemic rats due to its anti-inflammatory and antioxidant activities.

Growing evidence indicates that GQ1b, one of the gangliosides members, contributes to synaptic transmission and synapse formation. Previous studies have shown that GQ1b could enhance depolarization induced neurotransmitter release, while the role of GQ1b in asynchronous release is still largely unknown. Here in our result, we found low concentration of GQ1b, but not GT1b or GD1b (which were generated from GQ1b by plasma membrane-associated sialidases), evoked asynchronous dopamine (DA) release from both clonal rat pheochromocytoma PC12 cells and rat striatal slices significantly. The release peaked at 2 min after GQ1b exposure, and lasted for more than 6 min. This effect was caused by the enhancement of intracellular Ca(2+) and the activation of Pyk2. Inhibition of Pyk2 by PF-431396 (a dual inhibitor of Pyk2 and FAK) or Pyk2 siRNA abolished DA release induced by GQ1b. Moreover, Pyk2 Y402, but not other tyrosine site, was phosphorylated at the peaking time. The mutant of Pyk2 Y402 (Pyk2-Y402F) was built to confirm the essential role of Y402 activation. Further studies revealed that activated Pyk2 stimulated ERK1/2 and p-38, while only the ERK1/2 activation was indispensable for GQ1b induced DA release, which interacted with Synapsin I directly and led to its phosphorylation, then depolymerization of F-actin, thus contributed to DA release. In conclusion, low concentration of GQ1b is able to enhance asynchronous DA release through Pyk2/ERK/Synapsin I/actin pathway. Our findings provide new insights into the role of GQ1b in neuronal communication, and implicate the potential application of GQ1b in neurological disorders.

Ethnopharmacological relevance Ginseng is the dried root of Panax ginseng C.A. Mayer. Since ancient times, ginseng has been used as one kind of treatment drug or tonic in China and even other eastern countries like Korea and Japan. Pharmacological active chemical ingredients and its extract of ginseng are a mixture of triterpenoid saponins, collectively called ginsenosides. Among them, ginsenoside Rg1 is the most pharmacological active one. Aim of the study Based on prior experimental results and the understanding of alcoholic hepatitis, the major aim of this study is to investigate whether Rg1 is beneficial in a rodent model mimic alcoholic hepatic injury associated with binge drinking and explore the underlying possible mechanisms. Materials and methods C57BL/6 mice were given oral consumption of 6 g/kg alcohol 1 h after treated with Rg1 (10, 20 and 40 mg/kg) or dexamethasone (1 mg/kg) for 9 consecutive days. Biochemical analyses were performed and liver fragments were processed for microscopy, immunohistochemistry and western blot analysis. Results According to our data, Rg1 treatment significantly reversed the high mortality rate induced by alcohol consumption and also alleviated liver impairment as evidenced by the decrease of serum parameters. Meanwhile, histological and ultrastructural analysis of alcoholic groups showed hepatocellular impairment but restored in Rg1-treated groups. Overproductive inflammatory cytokines were also suppressed by Rg1 in alcohol-intoxicated mouse livers. In addition, changes of GR related NF-κB pathway, including phospho-IκB-α, were also modulated to normal levels. Conclusion This study demonstrates that Rg1 might promote GR mediating the repression of NF-κB and inhibit the inflammatory reactions in alcoholic hepatitis.

Protopanaxtriol (Ppt) is extracted from Panax ginseng Mayer. In the present study, we investigated whether Ppt could protect against 3-nitropropionic acid (3-NP)-induced oxidative stress in a rat model of Huntington's disease (HD) and explored the mechanisms of action. Male SD rats were treated with 3-NP (20 mg/kg on d 1, and 15 mg/kg on d 2–5, ip). The rats received Ppt (5, 10, and 20 mg/kg, po) daily prior to 3-NP administration. Nimodipine (12 mg/kg, po) or N-acetyl cysteine (NAC, 100 mg/kg, po) was used as positive control drugs. The body weight and behavior were monitored within 5 d. Then the animals were sacrificed, neuronal damage in striatum was estimated using Nissl staining. Hsp70 expression was detected with immunohistochemistry. Reactive oxygen species (ROS) generation was measured using dihydroethidium (DHE) staining. The levels of components in the Nrf2 pathway were measured with immunohistochemistry and Western blotting. 3-NP resulted in a marked reduction in the body weight and locomotion activity accompanied by progressive striatal dysfunction. In striatum, 3-NP caused ROS generation mainly in neurons rather than in astrocytes and induced Hsp70 expression. Administration of Ppt significantly alleviated 3-NP-induced changes of body weight and behavior, decreased ROS production and restored antioxidant enzymes activities in striatum. Moreover, Ppt directly scavenged free radicals, increased Nrf2 entering nucleus, and the expression of its downstream products heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidase 1 (NQO1) in striatum. Similar effects were obtained with the positive control drugs nimodipine or NAC. Ppt exerts a protective action against 3-NP-induced oxidative stress in the rat model of HD, which is associated with its anti-oxidant activity.