The water-soluble subfraction from Artemisia argyi alleviates LPS-induced inflammatory responses via multiple pathways and targets in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: As a traditional Chinese medicine, Artemisia argyi has been used medicinally and eaten for more than 2000 years in China. It is widely reported in treating inflammatory diseases such as eczema, dermatitis, arthritis, allergic asthma and colitis. Although several studies claim that its volatile oil and organic reagent extracts have certain anti-inflammatory effects, the water-soluble fractions and molecular mechanisms have not been studied. AIM OF THE STUDY: To evaluate the therapeutic effect of A. argyi water extract (AAWE) on lipopolysaccharide (LPS)-induced inflammatory responses and to identify the most effective water-soluble subfractions. Moreover, the relevant pharmacological and molecular mechanisms by which the active subfraction mitigates inflammation were further investigated. MATERIALS AND METHODS: Firstly, RAW 264.7 cells stimulated with LPS were treated with AAWE (50, 100, and 200 µg/mL) or the water-soluble subfractions separated by D101 macroporous resin (AAWE1-AAWE4, 100 µg/mL), and NO production and mRNA levels of inflammatory genes were evaluated to determine the most effective water-soluble subfractions. Secondly, the chemical components of the active subfraction (AAWE4) were analyzed by UPLC-QTOF-MS. Thirdly, transcriptome and network pharmacology analysis, RT-qPCR and Western blotting assays were conducted to explore the underlying anti-inflammatory mechanism and active compounds of AAWE4. Subsequently, the binding ability of the potential active components in AAWE4 to the core targets was further determined by molecular docking. Eventually, the in vivo anti-inflammatory activity of AAWE4 (1.17, 2.34 and 4.68 g/kg, administered per day for 7 d) was evaluated in mice with LPS-induced systemic inflammation. RESULTS: In this study, AAWE showed excellent anti-inflammatory effects, and its water-soluble subfraction AAWE4 exhibited the strongest inhibitory effect on NO concentration and inflammatory gene mRNA expression after LPS stimulation, indicating that it was the most effective subfraction. Thereafter, four main compounds in AAWE4 were confirmed or tentatively identified by UPLC-QTOF-MS, including three flavonoid glycosides and one phenolic acid. Furthermore, the transcriptome and network pharmacology analysis showed that AAWE4 inhibited inflammation via multiple pathways and multiple targets. Based on the RT-qPCR and Western blotting results, AAWE4 downregulated not only the p38, PI3K, CCL5, MMP9, AP-1, and BCL3 mRNA expression levels activated by LPS but also their upstream and downstream protein expression levels and protein phosphorylation (p-AKT/AKT, p-p38/p38, p-ERK/ERK, p-JNK/JNK). Moreover, four identified compounds (isochlorogenic acid A, vicenin-2, schaftoside and isoschaftoside) could significantly inhibit NO content and the overexpression of inflammatory factors TNF-α, IL-1ß, iNOS and COX-2 mRNA induced by LPS, and the molecular docking confirmed the high binding activity of four active compounds with selected core targets (p38, AKT1, MMP9, and CCL5). In addition, the mRNA expression and immunohistochemical analysis showed that AAWE44 could inhibit lung inflammation via multiple pathways and multiple targets in vivo. CONCLUSIONS: The findings of this study suggest that the water-soluble subfraction AAWE4 from A. argyi ameliorated the inflammation caused by LPS through multiple pathways and multiple targets in vitro and in vivo, providing scientific support for the medicinal use of A. argyi. Importantly, it shows that the A. argyi subfraction AAWE4 can be developed as an anti-inflammatory drug.

An unusual case of non-reentrant atrioventricular nodal tachycardia.

INTRODUCTION: Although uncommonly encountered, dual atrioventricular nodal non-reentrant tachycardia (DAVNNRT) is a well-described arrhythmia that can manifest in patients with dual atrioventricular nodal pathways physiology. This arrhythmia is characterized on electrocardiogram (ECG) by a single P wave followed by two conducted QRS complexes (so-called "double fire"), and on intracardiac electrograms by a single atrial electrogram followed by two separate His deflections and ventricular electrograms. METHODS/RESULTS: We report a rare case of "triple-fire" atrioventricular non-reentrant tachycardia in which a patient was found to have three distinct atrioventricular nodal pathways and multiple triple fire responses, both on surface ECG and intracardiac electrograms. CONCLUSION: Multiple pathways physiology and it's clinical ramifications are discussed.

Mulberry leaf (Morus alba L.): A review of its potential influences in mechanisms of action on metabolic diseases.

The leaves of Morus alba L. (called Sangye in Chinese, ML), which belong to the genus Morus., are highly valuable edible plants in nutrients and nutraceuticals. In Asian countries including China, Japan and Korea, ML are widely used as functional foods including beverages, noodles and herbal tea because of its biological and nutritional value. Meanwhile, ML-derived products in the form of powders, extracts and capsules are widely consumed as dietary supplements for controlling blood glucose and sugar. Clinical studies showed that ML play an important role in the treatment of metabolic diseases including the diabetes, dyslipidemia, obesity, atherosclerosis and hypertension. People broadly use ML due to their nutritiousness, deliciousness, safety, and abundant active benefits. However, the systematic pharmacological mechanisms of ML on metabolic diseases have not been fully revealed. Therefore, in order to fully utilize and scale relevant products about ML, this review summarizes the up-to-date information about the ML and its constituents effecting on metabolic disease.

Mechanisms dissection of the combination GRS derived from ShengMai preparations for the treatment of myocardial ischemia/reperfusion injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Recently, a new drug combination GRS comprising ginsenoside Rb1 (G-Rb1), ruscogenin (R-Rus) and schisandrin (S-SA) was screened based on ShengMai preparations, which exhibited a prominent cardioprotective effects against myocardial ischemia/reperfusion (MI/R) injury. AIM OF THE STUDY: To investigate their systemic and individual mechanism of each compound in combination GRS. MATERIALS AND METHODS: The mice model of MI/R and hypoxia/reoxygenation (H/R)-induced cardiomyocytes injury were performed to explore the respective characteristics of each compound in GRS against myocardial injury. RESULTS: Each component in the combination GRS attenuated MI/R injury as evidenced by decreased myocardial infarct size, ameliorated histological features, and improved biochemical indicators. Meanwhile, ingredient G, R and S in combination also individually performed a significant decrease of apoptotic index in MI/R mice and H/R-induced cardiomyocytes injury. Mechanistically, component G in GRS could markedly increase the ATP content in cardiomyocytes through activation of AMPKα phosphorylation. Interestingly, the anti-apoptotic actions of G were profoundly attenuated by knockdown of AMPKα, while no alteration was observed on composition R and S. Moreover, component R in GRS significantly reduced the IL-6 and TNF-α mRNA expression, as well as the content of IL-6 via the modulation of NF-κB signaling pathway. Further, component S exhibited the most powerful anti-oxidative capacity in GRS and remarkably decreased the production of MDA and ROS, and potential mechanisms might at least in part through activating the Akt-14-3-3 signaling pathway and inhibiting the phosphorylation of Bad and ERK1/2. CONCLUSIONS: Our results indicated that the respective mechanism of each compound in combination GRS against MI/R injury might closely associated with energy metabolism modulation, suppression of inflammation and oxidative stress.

Research Progress on Pharmacological Mechanism of Danhong Injection in Treatment of Cardiovascular and Cerebrovascular Diseases / 中国实验方剂学杂志

Cardiovascular and cerebrovascular diseases are one of the major diseases endangering human health， and its morbidity and mortality are still in the rising stage in our country. Traditional Chinese medicine （TCM） injections play an important role in the prevention and treatment of cardiovascular and cerebrovascular diseases due to their advantages of rapid onset， remarkable curative effect， and convenient use. Among them， Danhong injection （DHI）， a Chinese medicine injection for promoting blood circulation and removing blood stasis， is widely used in the clinical treatment of cardio-cerebrovascular diseases. DHI is composed of Salviae Miltiorrhizae Radix et Rhizoma （Danshen in Chinese） and Carthami Flos （Honghua in Chinese）， and mainly contains phenolic acids， tanshinones and flavonoids. A large number of studies have shown that DHI has a significant effect in the treatment of ischemic cardio-cerebrovascular diseases， is a representative drug of co-therapy of brain and heart of TCM， its pharmacological effects related to many aspects such as anti-inflammatory， anti-oxidation， anti-coagulation. At the same time， Other studies have also explained the protective effects of DHI on cardiovascular and cerebrovascular diseases through the overall regulation and intervention of multiple targets and pathways. However， DHI has a wide range of clinical applications， there are still many unknown pharmacological effects to be further explored. Therefore， this article summarizes the current researches on the chemical components of DHI， the multi-target and multi-path pharmacological mechanisms of DHI in the treatment of cardiovascular and cerebrovascular diseases， and introduces the latest pharmacological research progress， so as to provide theoretical guidance for clinical rational drug use and subsequent in-depth research.

Impact of Red Yeast Rice on Metabolic Diseases: A Review of Possible Mechanisms of Action.

Metabolic diseases constitute a major public health burden and are linked with high morbidity and mortality. They comprise atherosclerosis dyslipidemia, diabetes, hypertension, and obesity. However, there is no single drug that can simultaneously treat multiple diseases with complex underlying mechanisms. Therefore, it is necessary to identify a class of adjuvant drugs that block the development of metabolic diseases from a preventive perspective. Red yeast rice is a food fermentation product widely used to promote blood circulation and remove blood stasis. Modern pharmacology has shown that red yeast rice exerts potential protective effects on the liver, pancreas, blood vessels, and intestines. Therefore, this study was carried out to analyze and summarize the effect of red yeast rice on several metabolic diseases and the mechanisms of action involved. It was found that red yeast rice may be beneficial in the prevention and treatment of metabolic diseases.