Rhein alleviates advanced glycation end products (AGEs)-induced inflammatory injury of diabetic cardiomyopathy in vitro and in vivo models.

In diabetic patients, diabetic cardiomyopathy (DCM) is one of the most common causes of death. The inflammatory response is essential in the pathogenesis of DCM. Rhein, an anthraquinone compound, is extracted from the herb rhubarb, demonstrating various biological activities. However, it is unclear whether rhein has an anti-inflammatory effect in treating DCM. In our research, we investigated the anti-inflammatory properties as well as its possible mechanism. According to the findings in vitro, rhein could to exert an anti-inflammatory effect by reducing the production of NO, TNF-α, PGE2, iNOS, and COX-2 in RAW264.7 cells that had been stimulated with advanced glycosylation end products (AGEs). In addition, rhein alleviated H9C2 cells inflammation injury stimulated by AGEs/macrophage conditioned medium (CM). In vivo have depicted that continuous gavage of rhein could improve cardiac function and pathological changes. Moreover, it could inhibit the accumulation of AGEs and infiltration of inflammatory factors inside the heart of rats having DCM. Mechanism study showed rhein could suppress IKKß and IκB phosphorylation via down-regulating TRAF6 expression to inhibit NF-κB pathway in AGEs/CM-induced H9C2 cells. Moreover, the anti-inflammation effect of rhein was realized through down-regulation phosphorylation of JNK MAPK. Furthermore, we found JNK MAPK could crosstalk with NF-κB pathway by regulating IκB phosphorylation without affecting IKKß activity. And hence, the protective mechanism of rhein may involve the inhibiting of the TRAF6-NF/κB pathway, the JNK MAPK pathway, and the crosstalk between the two pathways. These results suggested that rhein may be a promising drug candidate in anti-inflammation and inflammation-related DCM therapy.

Qu-Yu-Jie-Du Decoction Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice by Modulation of Neutrophils and Macrophage Infiltration.

Background: Inflammatory bowel disease (IBD) is becoming a global disease. A percentage of IBD patients will not react to therapy or will lose their response. Qu-Yu-Jie-Du Decoction (QYJD) is a traditional Chinese medicine formula commonly used for intestinal diseases. It has been reported that QYJD has an anti-inflammatory effect, but the mechanism is not fully understood. In this study, we mainly evaluated the anti-inflammatory effect of QYJD and explored the possible mechanisms. Methods: Twenty-four BALB/c mice were randomly divided into 4 groups according to their body weight, namely, the control group, the dextran sulfate sodium (DSS) group, the DSS + QYJD group, and the QYJD group. Mice were given 3% DSS drinking water freely, and at the same time, mice were given normal saline or QYJD (4.44 mg/g/d), respectively. Mental state, faeces, and weight were recorded every day. On the 10th day, the mice were sacrificed and collected for investigation. The length of the mice colon was measured. Histological analysis was used to detect the morphological changes in the colon. Immunohistochemistry was used to measure the infiltration of macrophages (F4/80, CD163) and neutrophils (Ly6G). Colorimetry was used to detect the myeloperoxidase (MPO) activity of colon tissues. ELISA was utilized to detect associated inflammatory cytokines and chemokines in colon tissues. Results: QYJD alleviated the weight loss and colitis symptoms of mice caused by DSS. QYJD fought against the shortening of the intestine caused by DSS; that is, it improved the decline of intestinal compliance in mice and had a protective effect on colon tissues. The mechanisms were related to downregulating macrophages and neutrophils in colon tissues of infiltration. Besides, QYJD simultaneously reduced the activity of myeloperoxidase activity (MPO) and the contents of IL-1ß, IL-6, TNF-α, TGF-ß, CCL2, and CXCL2 in colon tissues. Conclusions: QYJD can ameliorate DSS-induced colitis in mice and the mechanism is connected with a reduction in neutrophil and macrophage infiltration.

Shugan Huoxue Huayu Fang attenuates carbon tetrachloride-induced hepatic fibrosis in rats by inhibiting transforming growth factor-ß1/Smad signaling.

OBJECTIVE: To investigate the potential mechanism by which Shugan Huoxue Huayu Fang (SGHXHYF) ameliorates liver fibrosis. METHODS: Liver fibrosis was induced in rats by intraperitoneal injection of carbon tetrachloride (CCl4) in peanut oil solution (40%, 3 mL/kg body weight) twice a week for 8 weeks. A normal control group received the same volume of peanut oil alone. During weeks 5-8, the CCl4-injected rat groups were administered saline (vehicle control), colchicine (0.1 mg/mL, 1 mg/kg, positive control), or SGHXHYF (0.1 mg/mL; 0.3, 0.6 and 1.2 mg/kg) once daily by oral gavage. Rats were sacrificed 24 h after the last treatment. Blood samples were collected for measurement of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin (ALB), collagen Ⅰ and collagen Ⅲ levels. Liver samples were analyzed by histopathological staining, Masson's staining of extracellular matrix proteins, and immune-ohistochemical staining of αsmooth muscle actin (α-SMA). TGF-ß1/Smad protein and mRNA levels were analyzed by Western blot and quantitative reverse transcription-polymerase chain reaction analysis, respectively. In vitro experiments were also performed using rat hepatic stellate cells (HSCs). RESULTS: Compared with the control animals, CCl4-exposed rats exhibited elevated serum levels of ALT, AST, ALP, collagen I, and collagen III; reduced serum levels of ALB; and increased collagen deposition and αSMA expression in liver sections, reflecting liver fibrosis. CCl4 also increased expression of TGF-ß1 and the activated (phosphorylated) forms of Smad2 and Smad3 but reduced expression of the negative regulator Smad7 in the liver. Notably, concomitant administration of SGHXHYF to CCl4-exposed rats was found to significantly reverse or abolish the pro-fibrotic effects of CCl4 in the liver and reduced serum transferase levels. Analysis of HSCs in vitro confirmed that, mechanistically, SGHXHYF inhibited activation of the TGF-ß1/Smad signaling pathway by downregulating phosphorylated Smad2 and Smad3 and upregulating Smad7 levels. CONCLUSION: SGHXHYF ameliorated CCl4-induced liver fibrosis by inhibiting the TGF-ß1/Smad signaling pathway. These findings suggest that SGHXHYF may have clinical utility for the treatment or prevention of liver fibrosis.

Effect of Chinese Herbal Medicine on the Survival of Colorectal Cancer Patients With Liver-Limited Metastases: A Retrospective Cohort Study, 2008 to 2017.

Background: Colorectal cancer (CRC) remains one of the leading contributors to cancer-related mortality and morbidity worldwide. Traditional Chinese medicines have been widely employed to treat various types of cancer in China. This investigation aims to determine the association between Chinese herbal medicine (CHM) therapy and survival outcomes in CRC patients with liver-limited metastases. Methods: A retrospective cohort study was performed among patients with colorectal liver metastases at the First Affiliated Hospital of Guangzhou University of Chinese Medicine in Guangzhou, China. Data from a series of consecutive patients were collected via an electronic medical record system or telephone follow-up. We defined high exposure as a period of CHM therapy lasting more than 6 months. The primary outcome was overall survival. Results: The study included the data of 191 patients from January 2008 to December 2017; 126 patients (65.97%) met the inclusion criteria of high exposure to CHM. Multivariate analyses revealed that high exposure to CHM was associated with better overall survival (hazard ratio = 0.444, 95% confidence interval = [0.213, 0.926], P = .030). The association was further confirmed by a subgroup exploratory analysis. Conclusion: Long-term CHM therapy is correlated with improved survival outcomes in CRC patients with liver-limited metastases.

[Safety and efficacy of ultrasound hyperthermia combined with chemotherapy and radical operation for advanced oral squamous cell carcinoma].

PURPOSE: To explore the safety and efficacy of ultrasound hyperthermia combined with chemotherapy and radical operation for advanced oral squamous cell carcinoma (OSCC). METHODS: Nine patients who had definite pathological diagnosis were enrolled in this clinical trail from 2015 to 2016. All patients underwent ultrasound hyperthermia combined with chemotherapy before radical operation. The treatment regime was as follows: Docetaxel and cisplatin (75mg/m2) used on the first day, fluorouracil (750 mg/m2) infused from 1st to 5th day. All patients received 2 cycles of thermo-chemotherapy, the therapeutic temperature was set to be 40-42 degrees centigrade, ultrasound hyperthermia was performed for 40 minutes every other day for 5 times. The therapeutic outcomes were evaluated by observation of clinical tumor regression. RESULTS: Of the 9 patients, complete response（CR）was seen in 1 case, partial response (PR) was seen in 3 cases, stable disease（SD）was seen in 5 cases. Complications were not severe and tolerable. CONCLUSIONS: Ultrasound hyperthermia combined with chemotherapy (TPF) may improve the therapeutic effect in advanced OSCC without obvious adverse reactions, and the toxicity and side effects are well tolerated.