A metabolomics study: Reveals the protective effect and mechanism of Terminalia chebula Retz on the cardiotoxicity induced by radix Aconiti kusnezoffii Reichb.

To reveal the protective effect of Terminalia chebula Retz (TCR) on cardiotoxicity induced by radix of Aconitum kusnezoffii Reichb (AKR). Control, AKR, AKR-TCR 1:3, AKR-TCR 1:1, AKR-TCR 3:1 and TCR-prepared AKR groups were set up. After treatment, the heart tissues were observed by H&E staining and transmission electron microscope. Serum myoglobin (MB) and troponin (cTn) were detected by ELISA. UPLC-Q Exactive/MS analysis was performed to detect the metabolic difference among the groups. ELISA results showed that the MB and cTn values of AKR group were significantly higher than Control group (P<0.05), while those of the other groups were lower than AKR group. TCR-prepared AKR group had similar MB and cTn contents to the Control group. Histopathological examination also indicated better detoxifying effects in the TCR-prepared AKR and AKR-TCR 1:1 group. The serum metabolomics analysis showed obvious distinction between the AKR and Control groups, while AKR-TCR combination reversed the metabolomics changes induced by AKR. Through multivariate statistical analysis, 9 metabolic markers related to energy, nucleic acid and amino acid metabolism were identified. Conclusively, AKR-induced cardiotoxicity may be related to energy, nucleic acid and amino acid metabolism, and TCR can reduce the cardiotoxicity by regulating the relative metabolism pathways.

The synergistic effect of Angelica sinensis (Oliv.) Diels and Rehmannia glutinosa (Gaertn.) DC. on antioxidant activity and protective ability against cell injury.

Oxidative stress-induced dysfunction of nerve cells has been implicated as a crucial cause of cell death in neurodegenerative diseases. In Asian countries, herbs, such as Angelica sinensis (Oliv.) Diels (DG) and Rehmannia glutinosa (Gaertn.) DC. (SDH), have long be considered to have antiaging abilities. The herbs act as neuro protectants that rescue nerve cells from oxidative stress damage and apoptosis. Thus, developing herbal formulas can potentially lead to new treatments for neurodegenerative diseases. In this study, we compared the effective active components and antioxidant properties of extractive of DG and SDH (DG-SDH) when formulated at different ratios. DG-SDH formulated at a ratio of 3:2 (DG-SDH [3:2]) produced the highest content of polysaccharides, polyphenols, and flavonoids. It also showed the best ability in removing DPPH and hydroxyl free radicals compared to single herb or other compounding ratio. The antioxidant activity of DG-SDH (3:2) showed best synergistic effects in scavenging activity assays of DPPH free radicals and hydroxyl free radicals. DG-SDH (3:2) could increase the cell viability of SHSY-5Y cells, PC-12 cells, and BV-2 cells. In particular, DG-SDH (3:2) protected SHSY-5Y cells from H2 O2 -induced cell injury by inhibiting excessive expression of reactive oxygen species (ROS), reducing the rate of apoptosis and restoring mitochondrial membrane potential. Actin-Tracker Green and DAPI staining and fluorescence microscope observation confirmed that DG-SDH (3:2) helped in preserving cell morphology under oxidative stress. These findings support that DG-SDH (3:2) promote the neuroprotection against hydrogen peroxide and can serve as a novel therapy for neurodegenerative diseases. PRACTICAL APPLICATIONS: This is the first study to investigate DG and SDH interaction between effective ingredients. These findings support that DG-SDH (3:2) has the best synergistic effects in antioxidant activity and promote the neuroprotection against hydrogen peroxide. Hence, DG-SDH (3:2) will be an excellent candidate to be developed as a functional food ingredients or nutraceuticals for neurodegenerative diseases.

Nano-lanthanum hydroxide, a novel phosphate binder, for treating hyperphosphatemia: A preclinical study.

This study is to determine the pharmacological effects of nano-lanthanum hydroxide (nano-LH) in the treatment of hyperphosphatemia, in comparison with other phosphate binders. Rat models of chronic renal failure and hyperphosphatemia were induced by adenine, which were treated with nano-LH (0.15, 0.10, and 0.05 g/Kg/d), lanthanum carbonate (0.30 g/Kg/d), and normal-size lanthanum hydroxide (0.10 g/Kg/d), respectively. To investigate the therapeutic effects, the serum levels of phosphorus, Scr, Ucr, BUN, UUN, PTH, and other hyperphosphatemia-related biochemical indicators were determined. A novel phosphorus-binding agent, nano-LH, was synthesized herein, which was rod-like particle with the length of 30-50 nm, width of 10-20 nm, and diameter of 5-10 nm. In vitro phosphorus binding experiments showed that nano-LH had better binding rate. Pharmacodynamic experiments confirmed that the therapeutic effects of lanthanum-hydroxide (0.10 g/kg/d) were superior to other existing phosphate binders in rat models of hyperphosphatemia, in lowering the blood phosphate level and improving the renal function. In the term of drug safety, our preliminary results showed that the nano-LH at appropriate dose did not cause death cases in mice, and the serum levels of alkaline phosphatase and lactate dehydrogenase were not significantly changed, indicating good oral safety. Nano-LH has high potency compared with several phosphate binders, which might be a promising therapeutic agent for the treatment of hyperphosphatemia in clinic.