Clinical effects and mechanisms of a Chinese patent medicine, Tongxinluo capsule, as an adjuvant treatment in coronary heart disease.

Coronary heart disease (CHD) is the leading cause of death globally, posing a serious threat to human health. However, the current treatment approaches available for CHD fall short of the ideal results. Tongxinluo (TXL) is a traditional Chinese medicine (TCM) that has been employed in the clinical treatment of cardiovascular and cerebrovascular diseases (such as angina pectoris, stroke, etc.) in China for many years and holds great potential as a prospective treatment. TXL either as a standalone treatment or in combination with interventions recommended in CHD guidelines has been shown to be effective and well tolerated in clinical trials for CHD. Drawing on the evidence from clinical trials and experimental studies, this review will focus on the cardiovascular protective properties and related mechanisms of TXL. By searching 8 Chinese and English databases, more than 4000 articles were retrieved. These articles were categorized, then read, and finally written into this review. In this review, the pharmacological properties of TXL include regulation of blood lipids, improvement of endothelial function, anti-inflammatory, antioxidant, inhibition of apoptosis and regulation of autophagy, anti-fibrosis, promotion of angiogenesis, and modulation of exosome communication. The information provided in this review will help the reader to comprehend better the insights that TCM has developed over time in practice and provide new perspectives for the treatment of CHD.

Trichosanates A-G and cucurbitacins W-Y, anticomplement monoterpenoids and cucurbitane-type triterpenoids from the pericarps of Trichosanthes kirilowii.

The pericarps of Trichosanthes kirilowii are often used to treat cough in traditional Chinese medicine, and its ethanol extract exhibited effective therapeutic effects on acute lung injury (ALI) in vivo caused by H1N1. An anticomplement activity-guided fractionation on the extract resulted in the isolation of ten new terpenoids, including seven monoterpenoids, trichosanates A-G (1-7), and three cucurbitane-type triterpenoids, cucurbitacins W-Y (8-10), as well as eleven known terpenoids (11-21). The new terpenoids' structures were determined by spectroscopic analysis, X-ray crystallographic analysis (1), electronic circular dichroism (ECD) analysis and calculations (2-10). Twelve monoterpenoids (1-7 and 11-15) and five cucurbitane-type triterpenoids (8-10, 18, and 20) exhibited anticomplement activity in vitro. For the monoterpenoids, the long aliphatic chain substituents might enhance their anticomplement activity. Additionally, two representative anticomplement terpenoids, 8 and 11, obviously attenuated H1N1-induced ALI in vivo by inhibiting complement overactivation and reducing inflammatory responses.

Electroacupuncture Zusanli (ST36) Relieves Somatic Pain in Colitis Rats by Inhibiting Dorsal Root Ganglion Sympathetic-Sensory Coupling and Neurogenic Inflammation.

Referred somatic pain triggered by hyperalgesia is common in patients with inflammatory bowel disease (IBD). It was reported that sprouting of sympathetic nerve fibers into the dorsal root ganglion (DGR) and neurogenic inflammation were related to neuropathic pain, the excitability of neurons, and afferents. The purpose of the study was to explore the potential and mechanism of electroacupuncture (EA) at Zusanli (ST36) for the intervention of colon inflammation and hyperalgesia. Sprague-Dawley (SD) was randomly divided into four groups, including control, model, EA, and sham-EA. Our results showed EA treatment significantly attenuated dextran sulfate sodium- (DSS-) induced colorectal lesions and inflammatory cytokine secretion, such as TNF-α, IL-1ß, PGE2, and IL-6. EA also inhibited mechanical and thermal pain hypersensitivities of colitis rats. Importantly, EA effectively abrogated the promotion effect of DSS on ipsilateral lumbar 6 (L6) DRG sympathetic-sensory coupling, manifested as the sprouting of tyrosine hydroxylase- (TH-) positive sympathetic fibers into sensory neurons and colocalization of and calcitonin gene-related peptide (CGRP). Furthermore, EA at Zusanli (ST36) activated neurogenic inflammation, characterized by decreased expression of substance P (SP), hyaluronic acid (HA), bradykinin (BK), and prostacyclin (PGI2) in colitis rat skin tissues corresponding to the L6 DRG. Mechanically, EA treatment reduced the activation of the TRPV1/CGRP, ERK, and TLR4 signaling pathways in L6 DRG of colitis rats. Taken together, we presumed that EA treatment improved colon inflammation and hyperalgesia, potentially by suppressing the sprouting of sympathetic nerve fibers into the L6 DGR and neurogenic inflammation via deactivating the TRPV1/CGRP, ERK, and TLR4 signaling pathways.

A comparative UHPLC-Q/TOF-MS-based metabolomics approach coupled with machine learning algorithms to differentiate Keemun black teas from narrow-geographic origins.

Geographic-label is a remarkable feature for Chinese tea products. In this study, the UHPLC-Q/TOF-MS-based metabolomics approach coupled with chemometrics was used to determine the five narrow-geographic origins of Keemun black tea. Thirty-nine differentiated compounds (VIP > 1) were identified, of which eight were quantified. Chemometric analysis revealed that the linear discriminant analysis (LDA) classification accuracy model is 91.7%, with 84.7% cross-validation accuracy. Three machine learning algorithms, namely feedforward neural network (FNN), random forest (RF) and support vector machine (SVM), were introduced to improve the recognition of narrow-geographic origins, the performances of the model were evaluated by confusion matrix, receiver operating characteristic curve (ROC) and area under the curve (AUC). The recognition of RF, SVM and FNN for Keemun black tea from five narrow-geographic origins were 87.5%, 94.44%, and 100%, respectively. Importantly, FNN exhibited an excellent classification effect with 100% accuracy. The results indicate that metabolomics fingerprints coupled with chemometrics can be used to authenticate the narrow-geographic origins of Keemun black teas.

Efficacy of add-on Danhong injection in patients with unstable angina pectoris: A double-blind, randomized, placebo-controlled, multicenter clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Danhong injection (DHI)，which is extracted from Salviae miltiorrhizae and Flos carthami，has been widely prescribed to patients with unstable angina pectoris (UAP) in China. However, a high quality clinical trial is needed. AIM OF THE STUDY: To determine whether DHI can relieve symptoms of transient myocardial ischemia in patients with unstable angina pectoris. MATERIALS AND METHODS: A double-blind, placebo-controlled, randomized clinical trial was conducted in nine hospitals in China. Inpatients with UAP with blood stasis syndrome (BSS) were randomized 1:1 to receive DHI or placebo. The primary outcome was improvement rate in the quantification score of angina pectoris. Secondary outcomes included blood stasis syndrome scale, nitrates use, electrocardiogram recordings, PCI procedures, Seattle Angina Questionnaire (SAQ) and biochemical indexes. RESULTS: 160 participants were enrolled and 159 were analyzed. There was no significant difference in primary outcome as compared with control group at the end of 7-day treatment, but significant difference at 28-day follow up (70.53% [95% CI, 59.97-81.09%] and 54.34% [95% CI, 42.68-65.99%]; P = 0.0423). The BSS score was significantly lower in the DHI group than that in the control group at day 28 (6.49 [6.96] vs 10.53 [9.07], P = 0.0034). In addition, DHI was significantly superior to placebo in the angina stability score of SAQ (91.10 [17.37] versus 78.21 [22.08], P < 0.001). There were no significant differences in other secondary outcome measures. CONCLUSIONS: A small decrease in the total effective rate and an increase in the angina stability score were observed 28 days after implementation of DHI in UAP with a total blood stasis syndrome score decrease, but the efficacy was not observed at day 7. The findings support that DHI may potentially relieve clinical symptoms and can benefit angina stability. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02007187.

Glycoproteins From Rabdosia japonica var. glaucocalyx Regulate Macrophage Polarization and Alleviate Lipopolysaccharide-Induced Acute Lung Injury in Mice via TLR4/NF-κB Pathway.

Background and Aims: Rabdosia japonica var. glaucocalyx is a traditional Chinese medicine (TCM) for various inflammatory diseases. This present work aimed to investigate the protective effects of R. japonica var. glaucocalyx glycoproteins on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the potential mechanism. Methods: Glycoproteins (XPS) were isolated from R. japonica var. glaucocalyx, and homogeneous glycoprotein (XPS5-1) was purified from XPS. ANA-1 cells were used to observe the effect of glycoproteins on the secretion of inflammatory mediators by enzyme-linked immunosorbent assay (ELISA). Flow cytometry assay, immunofluorescence assay, and Western blot analysis were performed to detect macrophage polarization in vitro. The ALI model was induced by LPS via intratracheal instillation, and XPS (20, 40, and 80 mg/kg) was administered intragastrically 2 h later. The mechanisms of XPS against ALI were investigated by Western blot, ELISA, and immunohistochemistry. Results: In vitro, XPS and XPS5-1 downregulated LPS-induced proinflammatory mediators production including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-6, and nitric oxide (NO) and upregulated LPS-induced IL-10 secretion. The LPS-stimulated macrophage polarization was also modulated from M1 to M2. In vivo, XPS maintained pulmonary histology with significantly reducing protein concentration and numbers of mononuclear cells in bronchoalveolar lavage fluid (BALF). The level of IL-10 in BALF was upregulated by XPS treatment. The level of cytokines including TNF-α, IL-1ß, and IL-6 was downregulated. XPS also decreased infiltration of macrophages and polymorphonuclear leukocytes (PMNs) in lung. XPS suppressed the expression of key proteins in the TLR4/NF-κB signal pathway. Conclusion: XPS was demonstrated to be a potential agent for treating ALI. Our findings might provide evidence supporting the traditional application of R. japonica var. glaucocalyx in inflammation-linked diseases.

Metabolics and ionomics responses of tea leaves (Camellia sinensis (L.) O. Kuntze) to fluoride stress.

Tea plant (Camellia sinensis (L.) O. Kuntze) is known to accumulate high concentrations of fluoride (F) in its leaves; however, the underlying mechanism of F accumulation remains unclear. The main objective of this study was to investigate the homeostatic self-defense mechanisms of tea leaves to F supplementation (0, 5, 20, and 50 mgL-1) by metabolomics and ionomics. We identified a total of 96 up-regulated and 40 down-regulated metabolites in tea leaves treated with F. Of these different compounds, minor polypeptides, carbohydrates and amino acids played valuable roles in the F-tolerating mechanism of tea plant. After F treatments, the concentrations of sodium (Na), ferrum (Fe), manganese (Mn), and molybdenum (Mo) were significantly increased in tea leaves, whereas the aluminum (Al) was decreased. These findings suggest that the ionic balance and metabolites are attributable to the development of F tolerance, providing new insight into tea plant adaptation to F stress.

Flavonoids from Houttuynia cordata attenuate H1N1-induced acute lung injury in mice via inhibition of influenza virus and Toll-like receptor signalling.

BACKGROUND: Influenza virus is one of the most important human pathogens, causing substantial seasonal and pandemic morbidity and mortality. Houttuynia cordata is a traditionally used medicinal plant for the treatment of pneumonia. Flavonoids are one of the major bioactive constituents of Houttuynia cordata. PURPOSE: This study was designed to investigate the therapeutic effect and mechanism of flavonoid glycosides from H. cordata on influenza A virus (IAV)-induced acute lung injury (ALI) in mice. METHODS: Flavonoids from H. cordata (HCF) were extracted from H. cordata and identified by high-performance liquid chromatography. Mice were infected intranasally with influenza virus H1N1 (A/FM/1/47). HCF (50, 100, or 200 mg/kg) or Ribavirin (100 mg/kg, the positive control) were administered intragastrically. Survival rates, life spans, weight losses, lung indexes, histological changes, inflammatory infiltration, and inflammatory markers in the lungs were measured. Lung virus titers and neuraminidase (NA) activities were detected. The expression of Toll-like receptors (TLRs) and levels of NF-κB p65 phosphorylation (NF-κB p65(p)) in the lungs were analysed. The effects of HCF on viral replication and TLR signalling were further evaluated in cells. RESULTS: HCF contained 78.5% flavonoid glycosides. The contents of rutin, hyperin, isoquercitrin, and quercitrin in HCF were 8.8%, 26.7%, 9.9% and 31.7%. HCF (50, 100 and 200 mg/kg) increased the survival rate and life span of mice infected with the lethal H1N1 virus. In H1N1-induced ALI, mice treated with HCF (50, 100 and 200 mg/kg) showed lesser weight loss and lower lung index than the model group. The lungs of HCF-treated ALI mice presented more intact lung microstructural morphology, milder inflammatory infiltration, and lower levels of monocyte chemotactic protein 1 (MCP-1), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α) and malondialdehyde (MDA) than in the model group. Further investigation revealed that HCF exerted antiviral and TLR-inhibitory effects in vivo and in vitro. HCF (50, 100 and 200 mg/kg) reduced lung H1N1 virus titers and inhibited viral NA activity in mice. HCF (100 and 200 mg/kg) elevated the levels of interferon-ß in lungs. HCF also decreased the expression of TLR3/4/7 and level of NF-κB p65(p) in lung tissues. In vitro experiments showed that HCF (50, 100 and 200 µg/ml) significantly inhibited viral proliferation and suppressed NA activity. In RAW 264.7 cells, TLR3, TLR4, and TLR7 agonist-stimulated cytokine secretion, NF-κB p65 phosphorylation, and nuclear translocation were constrained by HCF treatment. Furthermore, among the four major flavonoid glycosides in HCF, hyperin and quercitrin inhibited both viral replication and TLR signalling in cells. CONCLUSION: HCF significantly alleviated H1N1-induced ALI in mice, which were associated with its dual antiviral and anti-inflammatory effects via inhibiting influenzal NA activity and TLR signalling. among the four major flavonoid glycosides in HCF, hyperin and quercitrin played key roles in the therapeutic effect of HCF.

In vivo effect of quantified flavonoids-enriched extract of Scutellaria baicalensis root on acute lung injury induced by influenza A virus.

BACKGROUND: Scutellaria baicalensis root is traditionally used for the treatment of common cold, fever and influenza. Flavonoids are the major chemical components of S. baicalensis root. PURPOSE: To evaluate the therapeutic effects and action mechanism of flavonoids-enriched extract from S. baicalensis root (FESR) on acute lung injury (ALI) induced by influenza A virus (IAV) in mice. METHODS: The anti-influenza, anti-inflammatory and anti-complementary properties of FESR and the main flavonoids were evaluated in vitro. Mice were challenged intranasally with influenza virus H1N1 (A/FM/1/47) 2  h before treatment. FESR (50, 100 and 200  mg/kg) was administrated intragastrically. Baicalin (BG), the most abundant compound in FESR was given as reference control. Survival rates, life spans and lung indexes of IAV-infected mice were measured. Histopathological changes, virus levels, inflammatory markers and complement deposition in lungs were analyzed. RESULT: Compared with the main compound BG, FESR and lower content aglycones (baicalein, oroxylin A, wogonin and chrysin) in FESR significantly inhibited H1N1 activity in virus-infected Madin-Darby canine kidney (MDCK) cells and markedly decreased nitric oxide (NO) production from lipopolysaccharide (LPS)-stimulated RAW264.7 cells. In vitro assays showed that FESR and BG had no anti-complementary activity whereas baicalein, oroxylin A, wogonin and chrysin exhibited obvious anti-complementary activity. Oral administration of FESR effectively protected the IAV-infected mice, increased the survival rate (FESR: 67%; BG: 33%), decreased the lung index (FESR: 0.90; BG: 1.00) and improved the lung morphology in comparing with BG group. FESR efficiently decreased lung virus titers, reduced haemagglutinin (HA) titers and inhibited neuraminidase (NA) activities in lungs of IAV-infected mice. FESR modulated the inflammatory responses by decreasing the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1), and increasing the levels of interferon-γ (IFN-γ) and interleukin-10 (IL-10) in lung tissues. Although showing no anti-complementary activity in vitro, FESR obviously reduced complement deposition and decreased complement activation product level in the lung . CONCLUSION: FESR has a great potential for the treatment of ALI induced by IAV and the underlying action mechanism might be closely associated with antiviral, anti-inflammatory and anti-complementary properties. Furthermore, FESR resulted in more potent therapeutic effect than BG in the treatment of IAV-induced ALI.

Qiangzhi decoction protects mice from influenza A pneumonia through inhibition of inflammatory cytokine storm.

OBJECTIVE: To investigate the preventive effects of Qiangzhi Decoction (, QZD) on influenza A pneumonia through inhibition of inflammatory cytokine storm in vivo and in vitro. METHODS: One hundred ICR mice were randomly divided into the virus control, the Tamiflu control and the QZD high-, medium-, and low-dose groups. Mice were infected intranasally with influenza virus (H1N1) at 10 median lethal dose (LD50). QZD and Tamiflu were administered intragastrically twice daily from day 0 to day 7 after infection. The virus control group was treated with distilled water alone under the same condition. The number of surviving mice was recorded daily for 14 days after viral infection. The histological damage and viral replication and the expression of inflammatory cytokines were monitored. Additionally, the suppression capacity on the secretion of regulated on activation normal T cells expressed and secreted (RANTES) and tumor necrosis factor-α (TNF-α) in epithelial and macrophage cell-lines were evaluated. RESULTS: Compared with the virus control group, the survival rate of the QZD groups significantly improved in a dose-dependent manner (P<0.05), the viral titers in lung tissue was inhibited (P<0.05), and the production of inflammatory cytokines interferon-γ (IFN-γ), interleukin-6 (IL-6), TNF-α, and intercellular adhesion molecule-1 (ICAM-1) were suppressed (P<0.05). Meanwhile, the secretion of RANTETS and TNF-α by epithelial and macrophage cell-lines was inhibited with the treatment of QZD respectively in vitro (p<0.05) CONCLUSIONS: The preventive effects of QZD on influenza virus infection might be due to its unique cytokine inhibition mechanism. QZD may have significant therapeutic potential in combination with antiviral drugs.

[Clinical research on fire filiform needle combined with mild moxibustion for postherpetic neuralgia].

OBJECTIVE: To compare efficacy differences between fire filiform needle combined with mild moxibustion and gabapentin combined with sham acupuncture for postherpetic neuralgia (PHN). METHODS: One hundred cases of PHN were randomly divided into a needle group and a medicine group, 50 cases in each one. In the needle group, pricking method of fire filiform needle was given at the Ashi points, and then mild moxibustion was applied for 15 min. In the medicine group, the oral administration of gabapentin capsule and sham acupuncture at non-acupoints in the distal end of lesions were applied. The treatment was required for 21 days in both groups. The visual analogue score (VAS) was recorded before treatment and on the 1st day, 2nd day, 3rd day, 6th day, 9th day and 12th day of treatment. The most severity of pain within last 24 h, preset severity of pain, immediate analgesia effect and starting time of pain relief were observed, also the efficacy was assessed and improvement of symptoms was observed in the follow-up visit. RESULTS: The total effective rate was 94.0% (47/50) in the fire filiform needle group, which was superior to 86.0% (43/50) in the medicine group (P < 0.05). Compared with medicine group, the VAS of the most severity of pain within last 24 h was obviously reduced after the 2nd treatment in the fire filiform needle group while that of present severity of pain was relieved after the 1st treatment (both P < 0.05). The immediate analgesia effect in the fire filiform needle group was obviously superior to that in the medicine group in the first three times of treatment (all P < 0.05). The average time of pain relief was (3.91 +/- 0.82) days in the fire filiform needle group, which was significantly earlier to (6.53 +/- 1.13) days in the medicine group (P < 0.05). 26 cases were cured in the fire filiform needle group in the follow-up visit, which was superior to 2 cases in the medicine group (P < 0.05). The improvement of VAS, pain range and sleep quality in the needle group were also superior to those in the medicine group (all P < 0.05). The direct medical cost in the fire filiform needle group was (232.32 +/- 48.108) yuan, which was significantly lower than (466.00 +/- 41.09) yuan in the medicine group (P < 0.05). There was only one case of adverse effect in the medicine group during the treatment. CONCLUSION: The fire filiform needle combined with mild moxibustion could obviously relieve the pain in PHN patients, which has superior immediate analgesia effect and pain relieving time compared with gabapentin, which also has less adverse effects and cheap cost.

Effects of aescin on cytochrome P450 enzymes in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Aescin, the main active component found in extracts of horse chestnut (Aesculus hippocastanum) seed a traditional medicinal herb, is a mixture of triterpene saponins. It has been shown to be effective in inflammatory, chronic venous and edematous treatment conditions in vitro and in vivo, and is broadly used to treat chronic venous insufficiency. The purpose of this study was to find out whether aescin influences the effect on rat cytochrome P450 (CYP) enzymes (CYP1A2, CYP2C9, CYP2E1 and CYP3A4) by using cocktail probe drugs in vivo; the influence on the levels of CYP mRNA was also studied. MATERIALS AND METHODS: A cocktail solution at a dose of 5mL/kg, which contained phenacetin (20mg/kg), tolbutamide (5mg/kg), chlorzoxazone (20mg/kg) and midazolam (10mg/kg), was given as oral administration to rats treated with a single dose or multiple doses of intravenous aescin via the caudal vein. Blood samples were collected at a series of time-points and the concentrations of probe drugs in plasma were determined by HPLC-MS/MS. The corresponding pharmacokinetic parameters were calculated by the software of DAS 2.0. In addition, real-time RT-PCR was performed to determine the effects of aescin on the mRNA expression of CYP1A2, CYP2C9, CYP2E1 and CYP3A4 in rat liver. RESULTS: Treatment with a single dose or multiple doses of aescin had inductive effects on rat CYP1A2, while CYP2C9 and CYP3A4 enzyme activities were inhibited. Moreover, aescin has no inductive or inhibitory effect on the activity of CYP2E1. The mRNA expression results were in accordance with the pharmacokinetic results. CONCLUSIONS: Aescin can either inhibit or induce activities of CYP1A2, CYP2C9 and CYP3A4. Therefore, caution is needed when aescin is co-administration with some CYP1A2, CYP2C9 or CYP3A4 substrates in clinic, which may result in treatment failure and herb-drug interactions.

Meta-analysis of the effectiveness of Chinese and Western integrative medicine on medium and advanced lung cancer.

OBJECTIVE: To summarize the effectiveness of Chinese and Western integrative medicine in treating medium and advanced lung cancer, and to provide guidelines for clinical application. METHODS: For this metaanalysis, a comparative search of Chinese medicine data in Chinese National Knowledge Infrastructure (CNKI) and Chinese BioMedical Literature Database (CBM) was undertaken to identify articles related to randomized comparative research of Chinese and Western integrative medicine in treating medium and advanced lung cancer between 1996 to 2006. Quality of life (QOL) was estimated using RevMan 4.2 software for data processing, adopting the odd ratio (OR) and the 95% confidence interval (CI). RESULTS: Through meta-analysis of 10 qualified articles, the results were as follows: the merging effectiveness of QOL [OR=3.80, 95% CI (2.65, 5.47)]; the rate of survival [OR=3.44, 95% CI (2.04, 5.80)]; the tumor response rate [OR=1.88, 95% CI (1.37, 2.58)]; the tumor developing rate [OR=0.33, 95% CI (0.23, 0.48)]. Significant differences existed between the Chinese and Western integrative medicine treatment group and the Western treatment group (P<0.01). CONCLUSIONS: Chinese and Western integrative medicine treatment of medium and advanced lung cancer has shown to improve patients' QOL and survival rate; it also can control tumor development in the short term.

[Studies on the chemical constituents of Laportea bulbifera].

OBJECTIVE: To study the chemical constituents of Laportea bulbifera. METHODS: 70% EtOH was used for constituent extraction, silica gel column chromatography for constituent seperation, physical and chemical properties together with spectroscopic methods for chemical structure identification. RESULTS: six compounds were obtained from root of L. bulbifera. Their chemical structures were elucidated as p3-sitosterol(1) , P-daucosterol (2), 2,2'-oxy-bis(1-phenylethanol (3), 1-(2-phenylcarbonyloxy acetyl) benzene (4) , methyl linoleate(5),1,4-diphenyl-1,4-butanedione(6). CONCLUSION: All compounds are isolated from L. bulbifera and among compounds 3 and 4 are reported as natural products for the first time.

Apigenin inhibits proliferation and induces apoptosis in human multiple myeloma cells through targeting the trinity of CK2, Cdc37 and Hsp90.

BACKGROUND: Multiple myeloma (MM) is a B-cell malignancy that is largely incurable and is characterized by the accumulation of malignant plasma cells in the bone marrow. Apigenin, a common flavonoid, has been reported to suppress proliferation in a wide variety of solid tumors and hematological cancers; however its mechanism is not well understood and its effect on MM cells has not been determined. RESULTS: In this study, we investigated the effects of apigenin on MM cell lines and on primary MM cells. Cell viability assays demonstrated that apigenin exhibited cytotoxicity against both MM cell lines and primary MM cells but not against normal peripheral blood mononuclear cells. Together, kinase assays, immunoprecipitation and western blot analysis showed that apigenin inhibited CK2 kinase activity, decreased phosphorylation of Cdc37, disassociated the Hsp90/Cdc37/client complex and induced the degradation of multiple kinase clients, including RIP1, Src, Raf-1, Cdk4 and AKT. By depleting these kinases, apigenin suppressed both constitutive and inducible activation of STAT3, ERK, AKT and NF-κB. The treatment also downregulated the expression of the antiapoptotic proteins Mcl-1, Bcl-2, Bcl-xL, XIAP and Survivin, which ultimately induced apoptosis in MM cells. In addition, apigenin had a greater effects in depleting Hsp90 clients when used in combination with the Hsp90 inhibitor geldanamycin and the histone deacetylase inhibitor vorinostat. CONCLUSIONS: Our results suggest that the primary mechanisms by which apigenin kill MM cells is by targeting the trinity of CK2-Cdc37-Hsp90, and this observation reveals the therapeutic potential of apigenin in treating multiple myeloma.

Glia atrophy in the hippocampus of chronic unpredictable stress-induced depression model rats is reversed by electroacupuncture treatment.

BACKGROUND: Growing evidence indicates that glia atrophy contributes to the pathophysiology and possibly the pathogenesis of major depressive disorder. Electroacupuncture (EA), one of Chinese traditional therapy, has potent antidepressant-like effect in many clinical studies. The mechanism by which EA improves behavioral deficits is still unclear. METHOD: Chronic unpredictable stress (CUS)-induced depression model rats were used to study the effect of EA treatment. EA was performed on acupoints 'Bai-Hui' (Du 20) and unilateral 'An-Mian' (EX 17) once daily for three consecutive weeks, two weeks post CUS procedure. The antidepressant-like effect of EA treatment was analyzed by physical state (PS) and open field test (OFT). Astrocytic marker glial fibrillary acidic protein (GFAP) level in the hippocampus was detected by immunohistochemistry, Western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Exposure to CUS resulted in a decrease of behavioral activity, whereas a daily session of EA treatment significantly reversed the behavioral deficit of these depression model rats. Moreover, the levels of GFAP mRNA and protein were decreased in the hippocampus of depression model rats. Intriguingly, EA treatment blocked effectively the decreased GFAP level. LIMITATION: The relative small number of the depression model rats may cause some bias of behavioral tests. CONCLUSION: EA has potential antidepressant-like effect on CUS-induced depression model rats, which might be mediated by affecting the glial atrophy in the hippocampus.

Gualou xiebai banxia decoction inhibits NF-kappa B-dependent inflammation in myocardial ischemia-reperfusion injury in rats.

OBJECTIVE: To evaluate the myocardial protective effect of Gualou Xiebai Banxia decoction GXBD) and explore the mechanisms of inhibition of NF-kappa B activation and blockade of inflammatory responses induced by ischemia-reperfusion in rats. METHODS: Twenty-four Sprague Dawley (SD) rats were randomly divided into three groups. Rats in the treatment group received GXBD (13 g crude drug/kg) for three weeks, while rats in the model control and normal control groups received equal volumes of distilled water. On the 22nd day, rats in the ischemia-reperfusion (I/R) control and GXBD-treated groups underwent 30 min occlusion of the left anterior descending (LAD) coronary artery, followed by 120 min reperfusion. Electrocardiogram was recorded, and the activities of cardiac enzymes, cytokines, and NF-kappaB were assessed after I/R. RESULTS: Compared with the I/R control group, GXBD treatment restored the activity of the specific myocardial-injury marker creatine kinase (CK) and lactate dehydrogenase (LDH), and inhibited the inflammatory response involving the nuclear factor-kappaB (NF-KB) pathway, including down-regulation of interleukin (IL)-1beta and IL-6, and up-regulation of IL-10 gene expression. CONCLUSION: GXBD strongly reduced myocardial impairment in our I/R model, including inhibition of NF-kappaB activation and inflammatory cytokine responses.

Characterization of the multiple absorbed constituents in rats after oral administration of Chai-Huang decoction by liquid chromatography coupled with electrospray-ionization mass spectrometry.

A rapid, sensitive, and specific method by high-performance liquid chromatography (HPLC) coupled to diode-array detection (DAD) and tandem mass spectrometry (MS) techniques was developed for the identification of absorbed constituents and their metabolites in rats after the oral administration of a Chai-Huang decoction (CHD), which consists of Bupleurum chinense and Scutellaria baicalensis in the proportion 1 : 1 (w/w). By comparing their retention times and MS data with those of authentic compounds and published data, a total of 14 compounds were identified in the CHD samples. In addition, eleven and seven compounds were characterized in the urine and serum samples of the rats, respectively. The results indicated that the main absorbed constituents were chrysin-6-C-arabinosyl-8-C-glucoside, chrysin-6-C-glucosyl-8-C-arabinoside, baicalin, wogonin-5-O-glucoside, oroxylin A-7-O-glucuronide, wogonoside, saikosaponin A, saikosaponin C, saikosaponin D, baicalein, and wogonin. These compounds might be responsible for the curative effects of the CHD. The findings demonstrated that the proposed method could be used to rapidly and simultaneously analyze and screen the multiple absorbed bioactive constituents in a formula of traditional Chinese medicines (TCM). This is very important not only for the pharmaceutical discovery process and the quality control of crude drugs but also to explain the mechanisms of action of TCM.

[Preliminary study on mechanism of therapeutic effect of Huganjiexian decoction on hepatic fibrosis].

OBJECTIVE: To observe the effects of Huganjiexian decoction on rat hepatic fibrosis and the creation of cytokines. METHODS: Rat hepatic fibrosis was induced by intraperitoneally injection of carbon tetrachloride. At the same time, these rats were treated with different dosages of Huganjiexian decoction. Sho-saiko-to compound treating group and Fufangbiejiarangan Tablets treating group were used as positive controls. After twelve weeks, all rats were executed. Histopathologic changes were observed after H.E and Masson stainings. The expression of collagen type I, collagen type III, TGF-beta 1 and PDGF-BB in liver were detected by immunohistochemical staining. RESULTS: Compared with fibrotic group, hepatic fibrosis in decoction groups was significantly improved. In decoction groups, levels of collagen type I, collagen type III, TGFbeta1 and PDGF-BB were decreased, especially in the low-dose curcumin group. The TGF-beta 1 positive percentage were 7.56%+/-2.18%, 29.25%+/-7.84%, 13.54%+/-4.15%, 21.82%+/-6.64%, 20.06%+/-7.14%, 13.78%+/-4.35%, 12.75%+/-3.98% in liver tissues from normal group, model group, low, middle, high curcumin, Sho-saiko-to compound and Fufangbiejiarangan Tablets treating groups respectively (P less than 0.05); while the PDGF-BB positive percentage were 1.68%+/-0.41%, 11.70%+/-2.28%, 3.65%+/-0.76%, 5.24%+/-1.04%, 6.37%+/-1.12%, 4.16%+/-0.61%, 3.38%+/-0.56% in liver tissues from those groups respectively (P less than 0.05). CONCLUSION: Huganjiexian decoction can improve rat hepatic fibrosis, possibly via inhibiting the expression of collagen type I, collagen type III, TGFbeta1 and PDGF-BB.

[Studies on the chemical constituents of Vaccinium iteophyllum].

7 compounds were isolated from the ethyl-acetate extract of Vaccinium iteophyllum Hance by using repeated silical gel column chromatography. These 7 compounds were identified by means of physico-chemical propertic and spectroscopic analysis as beta-sitosterol (I), ursolic acid (II), taraxerol (III), taraxerone (IV), friedelin (V), friedelinol (VI), 19,24-dihydroxyurs-12-en-3-one-28-oic acid (VII). The chemical constituents from this plant were reported here for the first time.