Protective effect of alizarin on vascular endothelial dysfunction via inhibiting the type 2 diabetes-induced synthesis of THBS1 and activating the AMPK signaling pathway.

BACKGROUND: In this study, we investigated the protective effects of alizarin (AZ) on endothelial dysfunction (ED). AZ has inhibition of the type 2 diabetes mellitus (T2DM)-induced synthesis of thrombospondin 1 (THBS1). Adenosine 5'-monophosphate- activated protein kinase (AMPK), particularly AMPKα2 isoform, plays a critical role in maintaining cardiac homeostasis. PURPOSE: The aim of this study was to investigate the ameliorative effect of AZ on vascular injury caused by T2DM and to reveal the potential mechanism of AZ in high glucose (HG)-stimulated human umbilical vein endothelial cells (HUVECs) and diabetic model rats. STUDY DESIGN: HUVECs, rats and AMPK-/- transgenic mice were used to investigate the mitigating effects of AZ on vascular endothelial dysfunction caused by T2DM and its in vitro and in vivo molecular mechanisms. METHODS: In type 2 diabetes mellitus rats and HUVECs, the inhibitory effect of alizarin on THBS1 synthesis was verified by immunohistochemistry (IHC), immunofluorescence (IF) and Western blot (WB) so that increase endothelial nitric oxide synthase (eNOS) content in vitro and in vivo. In addition, we verified protein interactions with immunoprecipitation (IP). To probe the mechanism, we also performed AMPKα2 transfection. AMPK's pivotal role in AZ-mediated prevention against T2DM-induced vascular endothelial dysfunction was tested using AMPKα2-/- mice. RESULTS: We first demonstrated that THBS1 and AMPK are targets of AZ. In T2DM, THBS1 was robustly induced by high glucose and inhibited by AZ. Furthermore, AZ activates the AMPK signaling pathway, and recoupled eNOS in stressed endothelial cells which plays a protective role in vascular endothelial dysfunction. CONCLUSIONS: The main finding of this study is that AZ can play a role in different pathways of vascular injury due to T2DM. Mechanistically, alizarin inhibits the increase in THBS1 protein synthesis after high glucose induction and activates AMPKα2, which increases NO release from eNOS, which is essential in the prevention of vascular endothelial dysfunction caused by T2DM.

Protective effect of vitamin B6 against doxorubicin-induced cardiotoxicity by modulating NHE1 expression.

Doxorubicin (DOX) has been used to treat various types of cancer, but its application is limited due to its heart toxicity as well as other drawbacks. Chronic inhibition of Na+ /H+ exchanger (NHE1) reduces heart failure and reduces the production of reactive oxygen species (ROS); vitamin B6 (VitB6 ) has been demonstrated to have a crucial role in antioxidant mechanism. So, this study was designed to explore the effect of VitB6 supplement on the DOX-induced cardiotoxicity and to imply whether NHE1 is involved. Ultrasonic cardiogram analysis revealed that VitB6 supplement could alleviate DOX-induced cardiotoxicity; hematoxylin and eosin (HE) and Masson's staining further confirmed this effect. Furthermore, VitB6 supplement exhibited significant antioxidative stress and antiapoptosis effect, which was evidenced by decreased serum malondialdehyde (MDA) content and increased serum superoxide dismutase (SOD) content, and decreased Bcl-2-associated X protein/B-cell lymphoma-2 ratio, respectively. Collectively, VitB6 supplement may exert antioxidative and antiapoptosis effects to improve cardiac function by decreasing NHE1 expression and improve DOX-induced cardiotoxicity.

[Study on relationship between efficacy against lung cancer and different parts of Schizonepeta tenuifolia based on microfluidic chip technology].

In order to further clarify the rational use of different medicinal parts of Schizonepeta, microfluidic technology was used in this study to investigate the differences in drug efficacy against lung cancer in vitro. The ethanol extracts were examined with HPLC to establish their fingerprints in order to analyze the relationship between the spectrum and efficacy index through Grey Correlation software, and a rapid HPLC-Q-TOF/MS method was established. The result in vitro shows that the effect and components of different medicinal parts had a certain differences, and apoptosis and necrosis rate from big to small in turn is leaf, flower, root, stem. The chromatographic peaks of the 26, 12, 2, 6 and 15th are the luteolin, icynaroside, rosmarinic, caffeic acid, and hesperidin, while the 20 and 10th may be dan phenolic acid L and benzoic acid. On the one hand, preliminary study reflects that the root of Schizonepeta tenuifolia may be developed into the medicinal parts in future. On the other hand, the major chemical composition of S. tenuifolia was found to have the anti-lung-tumor effects. This new method was established for the quality control and the rational use of different parts of traditional Chinese medicine.

[Study of cancer cell apoptosis induced by Schizonepeta tenuifolia with microfluidic chip technology].

This study was designed to elucidate the chemical composition and anti-cancer effects of Schizonepeta tenuifolia's ethanol extracts. Microfluidic technology was used in the study of Schizonepeta tenuifolia from 9 different geographic regions. The ethanol extracts were examined with HPLC to establish their Fingerprints in order to analyze the relationship between the spectrum and efficacy index through Grey Correlation software, and a rapid HPLC-Q-TOF/MS method was established. The result shows that chromatographic peaks of the 19, 6, 11, 16, 18th are the representative diosmetin, luteoloside, hesperidin, luteolin, and apigenin. The 10, 12, 20th peaks may be naringenin-7-O-glucuronide or quercitrin, rosmarinate or acetylcorynoline, and 5,7-dihydroxy-6,4-dimethoxy flavone. The major chemical composition of Schizonepeta tenuifolia was found to have the anti-lung-tumor effects. A new method was established for the quality control of traditional Chinese medicine.