Potential traditional Chinese medicines with anti-inflammation in the prevention of heart failure following myocardial infarction.

Inflammation plays an important role in the development of heart failure (HF) after myocardial infarction (MI). Suppression of post-infarction inflammatory cascade has become a new strategy to delay or block the progression of HF. At present, there are no approved anti-inflammatory drugs used to prevent HF following MI. Traditional Chinese medicine (TCM) has been used clinically for cardiovascular disease for a long time. Here, we summarized the recent progress about some TCM which could both improve cardiac function and inhibit inflammation in patients or experimental models with MI or HF, in order to provide evidence for their potential application in reducing the onset of HF following MI. Among them, single Chinese medicinal herbs (eg. Astragalus and Salvia miltiorrhiza) and Chinese herbal formulas (eg. Gualou Xiebai Decoction and Sini Tang) are discussed separately. The main targets for their anti-inflammation effect are mainly involved the TLR4/NF-κB signaling, as well as pro-inflammatory cytokines IL-1ß, IL-6 or TNF-α. It is worthy of further evaluating their potential, experimentally or clinically, in the prevention or delay of HF following MI.

Non-carcinogenic/non-nephrotoxic aristolochic acid IVa exhibited anti-inflammatory activities in mice.

Aristolochic acid (AA)-containing herbs have been prescribed for thousands of years as anti-inflammatory drugs, despite the active pharmaceutical ingredients remaining unclear. However, exposure to AAI and AAII has been proven to be a significant risk factor for severe nephropathy and carcinogenicity. AAIVa, an analogue abundant in AA-containing herbs, showed neither carcinogenicity nor nephrotoxicity in our study and other reports, implying that the pharmacological effects of AAIVa on inflammation are worth studying. Herein, we employed RAW 264.7 cells, the ear edema mouse model, and the lipopolysaccharide (LPS)-induced systematic inflammation model in TNF-IRES-Luc mice (tracking TNFα luciferase activities in real-time) to evaluate the anti-inframammary effect of AAIVa. Our results showed that AAIVa could decrease pro-inflammatory cytokines (TNFα and IL-6) production in LPS-stimulated RAW 264.7 cells, indicating its anti-inflammatory effects in vitro. Furthermore, the application of AAIVa (400 and 600 µg/ear) could significantly inhibit phorbol 12-myristate 13-acetate-induced ear edema, suggesting its topical anti-inflammatory activity in vivo. Moreover, LPS-stimulated TNF-IRES-Luc mice were used to investigate the onset and duration of AAIVa on systematic inflammation. A single dosage of AAIVa (100 mg/kg, i.g.) could suppress LPS-triggered inflammation, by decreasing luciferase activities of TNFα at 3 h in TNF-IRES-Luc mice. In addition, the online pharmacological databases predicted that AAIVa might target the regulation of T cell activation-related protein (ADA, ADORA2A, ERBB2) to exhibit anti-inflammatory effect. In conclusion, we demonstrated that AAIVa had anti-inflammatory effect for the first time; our findings are constructive for further studies on pharmacological mechanism of AAIVa.

Progress on the role of traditional Chinese medicine in therapeutic angiogenesis of heart failure.

ETHNOPHARMACOLOGICAL RELEVANCE: Cardiovascular diseases are still the leading cause of death worldwide. Heart failure (HF), as the terminal stage of many cardiovascular diseases, has brought a heavy burden to the global medical system. Microvascular rarefaction (decreased myocardial capillary density) with reduced coronary flow reserve is a hallmark of HF and therapeutic myocardial angiogenesis is now emerging as a promising approach for the prevention and treatment in HF. Traditional Chinese medicine (TCM) has made remarkable achievements in the treatment of many cardiovascular diseases. Growing evidence have shown that their protective effect in HF is closely related to therapeutic angiogenesis. AIM OF THE STUDY: This review is to enlighten the therapeutic effect and pro-angiogenic mechanism of TCM in HF, and provide valuable hints for the development of pro-angiogenic drugs for the treatment of HF. MATERIALS AND METHODS: The relevant information about cardioprotective TCM was collected from electronic scientific databases such as PubMed, Web of Science, ScienceDirect, and China National Knowledge Infrastructure (CNKI). RESULTS: The studies showed that TCM formulas, extracts, and compounds from herbal medicines can provide therapeutic effect in HF with their pro-angiogenic activity. Their actions are achieved mainly by regulating the key angiogenesis factors particularly VEGF, as well as related regulators including signal molecules and pathways, non-coding miRNAs and stem cells. CONCLUSION: TCM and their active components might be promising in therapeutic angiogenesis for the treatment of HF.

Erythromycin has therapeutic efficacy on muscle fatigue acting specifically on orosomucoid to increase muscle bioenergetics and physiological parameters of endurance.

At present, there are still no official or semi-official recommendations for the treatment of muscle fatigue. We previously reported that acute phase protein orosomucoid (ORM) can enhance muscle endurance and exert anti-fatigue effect. In attempting to seek anti-fatigue drugs that target ORM, we found macrolide antibiotics, particularly erythromycin, were effective. Erythromycin can significantly prolong the time of mice forced-swimming and treadmill running, increase muscle fatigue index, alleviate fatigue-induced tissue damage, and elevate glycogen content, mitochondria function and ATP level in the muscle. Also, erythromycin increases ORM protein expression in a dose- and time- dependent manner both in vitro and in vivo. Further studies found that erythromycin could increase the activity of ORM promoter and the stability of ORM mRNA, which might both be responsible for the ORM up-regulation. ORM knockdown or knockout could abolish the promoting effect of erythromycin in mice forced-swimming time, muscle fatigue index and glycogen level. Furthermore, those effects were also abolished in mice with C-C motif chemokine receptor 5 (CCR5) antagonist administration or AMPKα2 deficiency. Therefore, erythromycin could enhance muscle glycogen and endurance via up-regulating the level of ORM and activating CCR5-AMPK pathway, indicating it might act as a potential drug to treat muscle fatigue.

An updated role of astragaloside IV in heart failure.

Heart failure (HF) has become a worldwide public health problem that seriously threatens human's health. Due to "multi-target" effect, traditional Chinese medicine (TCM) has unique advantages in this field. Chinese herb-derived active components would provide valuable candidate compounds for new drug development. Astragaloside IV(AS-IV) is a main effective ingredient of Astragalus membranaceus, a commonly used Chinese patent medicine for the patients with chronic heart failure(CHF). Our aim is to review the recent progresses of AS-IV in HF, and provide potential evidence for its clinical application. Data showed that AS-IV could protect myocardial ischemia, regulate sarcoplasmic reticulum Ca2+ pump, promote angiogenesis, improve energy metabolism, inhibit cardiac hypertrophy and fibrosis, reduce myocardial cell apoptosis, etc, which are direct or indirect involved in the beneficial effects of AS-IV in rodents or cellular models of HF. AS-IV or its derivatives may act as a potential therapeutic drug in the clinical treatment of HF.

[Combined Process of DNBF-O3-GAC for Nitrogen and Phosphorus and Metabolite Advanced Removal].

To improve the quality of the tailings water from a wastewater treatment plant (WWTP), a denitrification biofilter (DNBF) with a composite filler composed of a new slow-release organic-carbon source (SOC-F), sponge iron, and activated carbon was tested. Studies were conducted in the combined process of DNBF-O3-GAC to explore the efficiency of the advanced removal of nitrogen, phosphorus, and microbial metabolite by using synthetic effluent made from running water and chemicals. Corresponding comparative studies were conducted by using the secondary effluent from the WWTP. The microbial population structure in the biofilm of the denitrification biofilter was analyzed by adopting MiSeq high-throughput sequencing technologies. The results indicated that the combination process achieved high efficiency removal of nitrogen, phosphorus, and microbial metabolite. The average removal rate of NO3--N in the simulated and actual water period reached 88.87% and 79.99%, respectively; the average removal rate of TP reached 87.67% and 65.51%, respectively; and the average removal rate of UV254 reached 45.51% and 49.23%, respectively. Each processing unit had different functions. The changes in NO3--N, TN, TP, and TFe mainly occurred in the denitrification biofilter, and the removal of UV254 and the change in the three-dimensional fluorescence intensity mainly occurred in the ozone-activated carbon reactor. The cluster analysis at the genus level indicated that the denitrification system had sulfur autotrophic denitrifying bacteria and heterotrophic denitrifying bacteria. Sulfur autotrophic denitrification increased obviously in the actual water period when relatively lack of carbon sources, and the proportion of Thiobacillus increased from 7.44% to 29.62%. The complementary effect of sulfur autotrophic denitrification and heterotrophic denitrification had extended the use of the new slow-release carbon source.

[Effects of Temperature on the Characteristics of Nitrogen and Phosphorus Removal and Microbial Community in SCSC-S/Fe].

In order to investigate the effect of temperature on the cellulose-degrading bacteria and denitrifying bacteria, the denitrification and phosphorus removal of solid carbon source of cellulose corncob+sulfur/sponge iron nitrogen and phosphorus removal composite system, abbreviated as SCSC-S/Fe, was analyzed under different temperature conditions, and the surface structure and microbial properties of corncob before and after reaction were analyzed by scanning electron microscope (SEM) and MiSeq high-throughput sequencing technologies. The results indicated that when temperature increased from 15, 20, 25 to 30℃, the average TN removal rate of the system increased from 78.88% to 92.70%, the average removal rate of TP increased from 82.58% to 89.15%;microbial properties showed that the surface reaction after corncob was dominated by spherical and rod-shaped microorganisms; the proportion of cellulose-degrading bacteria was 11.01% higher at 30℃ than 20℃, and the proportion of denitrifying bacteria decreased by 21.26%. It can be seen that the cellulose -degrading bacteria were more sensitive to the temperature than the denitrification bacteria, and more obviously affected by the temperature.

The Acute-Phase Protein Orosomucoid Regulates Food Intake and Energy Homeostasis via Leptin Receptor Signaling Pathway.

The acute-phase protein orosomucoid (ORM) exhibits a variety of activities in vitro and in vivo, notably modulation of immunity and transportation of drugs. We found in this study that mice lacking ORM1 displayed aberrant energy homeostasis characterized by increased body weight and fat mass. Further investigation found that ORM, predominantly ORM1, is significantly elevated in sera, liver, and adipose tissues from the mice with high-fat diet (HFD)-induced obesity and db/db mice that develop obesity spontaneously due to mutation in the leptin receptor (LepR). Intravenous or intraperitoneal administration of exogenous ORM decreased food intake in C57BL/6, HFD, and leptin-deficient ob/ob mice, which was absent in db/db mice and was significantly reduced in mice with arcuate nucleus (ARC) LepR knockdown, whereas enforced expression of ORM1 in ARC significantly decreased food intake, body weight, and serum insulin level. Furthermore, we found that ORM is able to bind directly to LepR and activate the receptor-mediated JAK2-STAT3 signaling in hypothalamus tissue and GT1-7 cells, which was derived from hypothalamic tumor. These data indicated that ORM could function through LepR to regulate food intake and energy homeostasis in response to nutrition status. Modulating the expression of ORM is a novel strategy for the management of obesity and related metabolic disorders.

[Phosphorus Removal Mechanism of Sulfur/Sponge Iron Composite Fillers Based on Denitrification].

In order to improve the phosphorus removal effect in the denitrification and phosphorus synchronous removal process by sulfur/sponge iron composite fillers, the phosphorus removal effect by different fillers with the coupling microorganisms was studied to analyze the denitrifying phosphorus removal mechanism of the microbial coupling sulfur/sponge iron composite fillers. The research result showed that the phosphorus removal ratio of sponge iron/sulfur composite fillers was over 95%, which was increased by 30% as compared to only sponge iron filler. In addition, the effluent TP concentration was reduced to less than 0.1 mg·L-1. The analysis of X-ray diffraction(XRD)and total iron concentration indicated that the main phosphorus removal system products which were produced in the corrosion and phosphorus removal process of sponge iron were FeOOH, FeS and Fe4 (PO4)3 (OH)3 deposits and dissolved iron ions; FeS and FeOOH which were the hydrolysis products of Fe2+ and Fe3+ converted PO43- to Fe4(PO4)3(OH)3 by adsorption and deposition so that phosphorus removal could be achieved. After the reactor of microbial coupling sulfur/sponge iron carbon composite fillers became stable, the removal efficiency of TN and TP could reach 90% and more than 83%, respectively; Corrosion of sponge iron and phosphorus removal process could also be promoted by biological iron and H+ that was produced in the sulfur autotrophic denitrification process, the system could realize the combination of "heterotrophic synergy autotrophic" composite denitrification and chemical phosphorus removal, and efficient denitrifying denitrification synchronous phosphorus removal process could be achieved in the urban sewage treatment plant.

[Effects of Sulfur/sponge Iron Ratio for Deep Denitrification and Phosphorus Removal of Reclaimed Water].

To study the effects of sulfur/sponge iron ratio on denitrification and phosphorus removal, a series of static experiments were conducted using different ratios of sulfur and sponge iron. The results showed that the denitrification and phosphorus removal effect of sulfur/sponge iron composite fillers was significantly higher than that of single filler, and sulfur/sponge iron ratio was one of the key factors influencing nitrogen and phosphorus removal by composite fillers. When the volume ratio was equal to or greater than 1:1, the removal efficiency of TN and TP reached 85% and 97%, respectively. The denitrification and phosphorus removal process of the composite fillers both fitted second-order kinetic equation, the denitrification was dependent on heterotrophic denitrification and sulfur autotrophic denitrification; the phosphorus removal was mainly chemical phosphorus removal caused by sponge iron corrosion.

[Effect of Gingkgo biloba leaf extract induced delayed preconditioning on cytochrome c oxidase expression during myocardial ischemia-reperfusion in rats].

OBJECTIVE: To determine the effect of Gingkgo biloba leaf extract (EGb761) induced delayed preconditioning on cytochrome c oxidase (CcO) expression during myocardial ischemia-reperfusion in rats. METHODS: Four groups (10 in each) of Sprague-Dawley male rats were studied. In the sham group, the rats received no treatment. Rats in the ischemia-reperfusion (IR) group were treated with NS (1.0 mL/kg intravenously) 24 h before ischemia. Rats in the M group were treated with EGb761 (100 mg/kg intravenously) 24 h before the ischemia. In the D group , EGb761-treated rats that received the 5-hydroxydecanoate (5-HD), an inhibitor of mitochondrial KATP channels 15 min before the ischemia. The IR, M, and D groups were subjected to ischemia by 30 min of coronary artery occlusion before 2 h of reperfusion. At the end of the reperfusion, myocardial infarct size was measured. CcO was measured by Western blot. The myocardial ultrastructure was observed under the electron microscope. RESULTS: The infarct size was significantly smaller in the M group [(23.78 ± 4.82)%] than in the I/R group [(37.87 ± 5.92)%] (P<0.05). The CcO protein expression in the myocardium was significantly higher in the M group than in the I/R group(P<0.05). Microscopic examination showed less myocardial damage in the M group than that in the I/R group. The infarct size, CcO protein expression, and myocardial damage had no significant difference between the D group and the I/R group (P>0.05). CONCLUSION: EGb761 induced delayed preconditioning attenuates myocardial ischemia-reperfusion injury possibly through up-regulating CcO expression in rats.

A phospho-directed macroporous alumina-silica nanoreactor with multi-functions.

A phospho-directed nanoreactor with multiple functions is reported. Alumina-functionalized macroporous ordered silica foams (Al-MOSF) have been developed with large pore size, high pore volume (1.6 cm(3)/g), and a surface area of 186 m(2)/g rich in coordination unsaturated Al species, which can be used as phospho-directed nanoreactors for integrated in situ digestion and in situ phosphoisolation. By directly adding Al-MOSF to the conventional in-solution digestion system, both enzymes and proteins are quickly enriched in the macropores of the reactor to achieve a fast proteolysis without increasing the enzyme/protein concentration or using a preimmobilization process, thus the digestion time and the cost can be greatly reduced. Meanwhile, due to the chemo-affinity between alumina and phosphor groups, the Al-MOSF reactor can in situ isolate specific products of the enzymatic reaction (i.e., phosphopeptides) and release the nonspecific peptides to the solution. This strategy is simple, efficient, and successfully applied in the detection of phosphoproteins in real samples.