Bioactive components, pharmacological effects, and drug development of traditional herbal medicine Rubus chingii Hu (Fu-Pen-Zi).

Rubus chingii Hu (Chinese Raspberry), known as Fu-Pen-Zi in Chinese, a woody perennial plant of the genus Rubus in the Rosaceae family, has specific nutritional and medicinal values, which is considered food-medicine herb in China for thousands of years to treat impotence, premature ejaculation, enuresis, frequent urination, and other diseases. This review aims to summarize recent advances in the bioactive components, pharmacological effects, and drug development and utilization of Rubus chingii Hu, hoping to provide useful support for its further research and clinical application. The bioactive components in Rubus chingii Hu contain mainly terpenoids, flavonoids, alkaloids, phenolic acids, polysaccharides, and steroids. The main pharmacological effects are their anti-oxidant, anti-inflammatory, and anti-tumor capacity on human health. Rubus chingii Hu is a very valuable food-medicine herb. The development of Rubus chingii Hu-related drugs is relatively single, which is limited to traditional Chinese medicine and prescriptions. Therefore, it is vital to pay interest to Rubus chingii Hu and its bioactive components in the future and extend its scientific application.

Yiqi Huoxue Recipe Regulates Autophagy through Degradation of Advanced Glycation End Products via mTOR/S6K1/LC3 Pathway in Diabetic Nephropathy.

BACKGROUND: Yiqi Huoxue recipe can delay the progression of diabetic nephropathy, but its treatment mechanism is still unclear. We aimed to explore the effects of Yiqi Huoxue recipe on autophagy in diabetic nephropathy and its underlying mechanism. METHODS: All rats were randomly divided into seven groups. The body weight, kidney weight, blood glucose, glycated hemoglobin, urine protein, urine microprotein, creatinine, urea nitrogen, triglyceride, and lipoprotein were analyzed. HE, Masson, and periodic acid-Schiff staining were used to detect the severity of pathological changes in kidneys. The level of advanced glycation end products was assessed by the ELISA. Immunofluorescence staining was performed to check the expressions of podocin and nephrin. The expression levels of mTOR/S6K1/LC3 pathway-related proteins and mRNA were detected by qRT-PCR and western blotting. RESULTS: Yiqi Huoxue recipe significantly elevated body weight and significantly decreased kidney weight and kidney index. Yiqi Huoxue recipe significantly affected the levels of biochemical indicators in diabetic nephropathy and showed a regulatory effect on kidney damage and lipid metabolism disorders. ELISA showed that Yiqi Huoxue recipe significantly reduced the level of advanced glycation end products. The expressions of nephrin and podocin increased significantly, depending on the dosage of Yiqi Huoxue recipe. Additionally, Yiqi Huoxue recipe regulated the expression levels of p-AKT, mTOR, S6K1, and LC3. CONCLUSION: Yiqi Huoxue recipe regulates podocyte autophagy to promote the degradation of advanced glycation end products through mTOR/S6K1/LC3 pathway. It has a certain guiding significance for the diagnosis and treatment of diabetic nephropathy.

Alisol B 23-Acetate Ameliorates Lipopolysaccharide-Induced Cardiac Dysfunction by Suppressing Toll-Like Receptor 4 (TLR4)/NADPH Oxidase 2 (NOX2) Signaling Pathway.

BACKGROUND Cardiac dysfunction during endotoxemia is a major cause of cardiovascular disease with high morbidity and mortality. Alisol B 23-acetate (AB23A) is a triterpenoid extracted from the Rhizoma Alismatis, a kind of traditional Chinese medicine, exhibits anti-inflammatory activity on endotoxemia. This investigation aimed to uncover the protective effects of AB23A against sepsis-induced cardiac dysfunction. MATERIAL AND METHODS Adult male C57BL/6 mice received lipopolysaccharide (LPS) (20 mg/kg intravenous) stimulation, with or without pre-treatment of AB23A (10 mg/kg, 20 mg/kg, or 40 mg/kg). Histopathological staining and cardiac function were performed 4 hours after LPS stimulation. Then the levels of interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-alpha were monitored with enzyme-linked immunosorbent assay (ELISA). In addition, H9C2 cells were treated with LPS (5 µg/mL) with or without pre-treated with AB23A (0.1 µM, 1 µM, or 10 µM), and the production of reactive oxygen species (ROS) was detected by DCFH-DA combined with flow cytometry. The expression of Toll-like receptor 4 (TLR4), NADPH oxidase 2 (NOX2), NOX4, P38, p-P38, extracellular-signal-regulated kinase (ERK), and p-ERK were assessed by western blotting. RESULTS AB23A improved the survival rate and ameliorated myocardial injury, decreased inflammatory infiltration and the level of IL-6, IL-1ß, and TNF-alpha in the LPS-stimulated mouse model. Moreover, AB23A inhibited the ROS production in LPS-treated H9C2 cells. In addition, AB23A suppressed the levels of TLR4 and NOX2 as well as the activation levels of P38 and ERK both in vivo and in vitro. CONCLUSIONS AB23A reduced LPS-induced myocardial dysfunction by inhibiting inflammation and ROS production through the TLR4/NOX2 pathway.

[Effect of echinacoside on replication and antigen expression of hepatitis B virus].

To verify the effect of echinacoside on replication and antigen expression of hepatitis B virus (HBV) by using HBV-transfected HepG2. 2. 15 cells as the in vitro model. The ELISA method was used to determine HBeAg and HBsAg levels in cellular supernatants. The effect of echinacoside on HBV replication was studied by using HBV transgenic mice as the in vivo model. First of all, the HBV DNA level in hepatic tissues was quantified with PCR method. Meanwhile, the serum transaminase levels and hepatic pathological changes were also evaluated. Subsequently, HBV transgenic mice were divided into five groups: the control group, the lamivudine group (50 mg · kg(-1)) and echinacoside high, medium and low dose group (50, 25 and 12.5 mg · kg(-1)). The mice were orally administered with drugs once per day for 30 days. At the 31st day, the mice serum was separated to measure HBsAg, HBeAg and HBV DNA. Additionally, the liver HBV DNA level and histopathological change were detected. The results indicated that echinacoside at 50 and 100 mg · L(-1) suppressed significantly HBsAg and HBeAg expressions on the sixth day, with the maximum inhibition ratios of 42.68% and 46.29%; And echinacoside at 100 mg · L(-1) also showed an inhibitory effect on HBV DNA. Besides, echinacoside at 50 mg · kg(-1) inhibited significantly HBsAg and HBeAg expressions of HBV transgenic mice, with the inhibition ratios of 42.82% and 29.12%, and reduced markedly the serum HBV DNA level in HBV transgenic mice. In conclusion, the study suggested that echinacoside has a strong effect against HBV replication and antigen expression.

Dynamic correlation between induction of the expression of heme oxygenase-1 and hepatitis B viral replication.

Heme oxygenase­1 (HO­1) possesses significant potential as a drug target for hepatitis B, which may be transferable to patient therapy. The aim of the present study was to clarify the dynamic correlation between the hepatitis B virus (HBV) and HO­1. The levels of HBV replication and expression of HO­1 were investigated in HepG2.2.15 hepatoma cells following exposure to 5­50 µM hemin for 1­6 days. The mRNA expression levels of HO­1 were then detected using reverse transcription­quantitative polymerase chain reaction (RT­qPCR). HBV replication levels were determined by enzyme­immunoassay and a PCR­fluorescence quantitation assay. The results of the present study demonstrated that the mRNA expression levels of HO­1 increased in a dose­dependent manner in the HepG2.2.15 cells, following exposure to 5­50 µM hemin. The mRNA expression levels of HO­1 reached a peak following exposure of the cells to hemin for three days, subsequently the expression of HO­1 decreased. Following exposure to hemin at an optimal concentration of 50 µM for 1­6 days, the levels of the hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) in the cells were significantly reduced. This marked reduction in the expression of HBsAg and HBeAg reached its peak on the first day, following which the inhibition weakened as the duration of exposure increased. In addition, the inhibition of HBV DNA replication increased with the a longer duration of exposure. Furthermore, HBV DNA levels were significantly decreased following exposure to hemin for 3­6 days. In conclusion, the present study demonstrated that induced expression of HO­1 interfered with HBV replication in a dose and time­dependent manner, implying that a reduction of the HBV viral load may contribute to upregulation in the expression of HO­1.

Evaluation of hepatocyteprotective and anti-hepatitis B virus properties of Cichoric acid from Cichorium intybus leaves in cell culture.

Hepatitis B is the most common serious liver infection in the world. To date, there is still no complete cure for chronic hepatitis B. Natural caffeic acid analogues possess prominent antiviral activity, especially anti-hepatitis B virus (HBV) and anti-human immunodeficiency virus effects. Cichoric acid is a caffeic acid derivative from Cichorium intybus. In the study, the anti-hepatitis B property of cichoric acid was evaluated by the D-galactosamine (D-GalN)-induced normal human HL-7702 hepatocyte injury model, the duck hepatitis B virus (DHBV)-infected duck fetal hepatocytes and the HBV-transfected cell line HepG2.2.15 cells, respectively. The results showed that cichoric acid attenuated significantly D-GalN-induced HL-7702 hepatocyte injury at 10-100 µg/mL and produced a maximum protection rate of 56.26%. Moreover, cichoric acid at 1-100 µg/mL inhibited markedly DHBV DNA replication in infected duck fetal hepatocytes. Also, cichoric acid at 10-100 µg/mL reduced significantly the hepatitis B surface and envelope antigen levels in HepG2.2.15 cells and produced the maximum inhibition rates of 79.94% and 76.41%, respectively. Meanwhile, test compound at 50-100 µg/mL inhibited markedly HBV DNA replication. In conclusion, this study verifies the anti-hepatitis B effect of cichoric acid from Cichorium intybus leaves. In addition, cichoric acid could be used to design the antiviral agents.