Taohe Chengqi decoction alleviated metabolic-associated fatty liver disease by boosting branched chain amino acids catabolism in the skeletal muscles of type 2 diabetes mellitus.

OBJECTIVE: Metabolic-associated fatty liver disease (MAFLD) is the most prevalent liver disease, whereas type 2 diabetes mellitus (T2DM) is considered an independent risk factor for MAFLD incidence. Taohe Chengqi decoction (THCQ) is clinically prescribed for T2DM treatment; however, the hepatoprotective effect of THCQ against MAFLD is still unknown. This study intended to elucidate the therapeutic effect of THCQ on T2DM-associated MAFLD and to investigate the underlying mechanisms. METHODS: THCQ lyophilized powder was prepared and analyzed by UHPLC-MS/MS. A stable T2DM mouse model was established by high-fat diet (HFD) feeding combined with streptozotocin (STZ) injection. The T2DM mice were administered THCQ (2.5 g/kg or 5 g/kg) to explore the pharmacological effects of THCQ on T2DM-associated MAFLD. Liver tissue transcriptome was analyzed and the participatory roles of PPARα/γ pathways were verified both in vivo and in vitro. Serum metabolome analysis was used to explore the metabolome changes and skeletal muscle branched chain amino acid (BCAA) catabolic enzymes were further detected. Moreover, an AAV carrying BCKDHA shRNA was intramuscularly injected to verify the impact of THCQ on skeletal muscle BCAA catabolism and the potential therapeutic outcome on hepatic steatosis. RESULTS: THCQ improved hepatic steatosis in MAFLD. RNA-sequencing analysis showed dysregulation in the hepatic PPARγ-related fatty acid synthesis, while PPARα-dependent fatty acid oxidation was elevated following THCQ treatment. Interestingly, in vitro analyses of these findings showed that THCQ had minor effects on fatty acid oxidation and/or synthesis. The metabolomic study revealed that THCQ accelerated BCAA catabolism in the skeletal muscles, in which knockdown of the BCAA catabolic enzyme BCKDHA diminished the THCQ therapeutic effect on hepatic steatosis. CONCLUSION: This study highlighted the potential therapeutic effect of THCQ on hepatic steatosis in MALFD. THCQ upregulated fatty acid oxidation and reduced its synthesis via restoration of PPARα/γ pathways in HFD/STZ-induced T2DM mice, which is mediated through augmenting BCKDH activity and accelerating BCAA catabolism in the skeletal muscles. Overall, this study provided in-depth clues for "skeletal muscles-liver communication" in the therapeutic effect of THCQ against hepatic steatosis. These findings suggested THCQ might be a potential candidate against T2DM-associated MAFLD.

Delivery of anti-cancer and anti-depression doxepin drug by nickel oxide nanoparticles originated from the Cressa nudicaulis plant extract.

In this research, the extract of Cressa nudicaulis plant has been used as a natural reducing agent in order to prepare stable nickel oxide nanoparticles (NiO NPs) using an aqueous solution of nickel(ii) nitrate under the sol-gel method. Additionally, NiO NPs were distinguished using FT-IR (Fourier transform infrared spectroscopy), XRD (X-ray diffraction), FESEM (field-emission scanning electron microscopy), EDS (energy-dispersive X-ray spectrometry), TEM (transmission electron microscopy), and UV-Vis (ultraviolet-visible spectroscopy) techniques. The integrated NiO NPs were loaded with doxepin drug as an effective medication for head and neck cancer as well as depression. Then, the ideal loading circumstances such as pH of the medium, response time, and amount of nanoparticles were assessed to attain that pH 6, time 12 h, and nanoparticle amount of 0.02 g are optimal to accomplish the best drug loading of around 68%. The drug release properties of drug-loaded NiO were also investigated at pH 6.5 and 37 °C. This study showed that ∼73% of the loaded drug was released after 80 h. Therefore, the introduced delivery system shows sufficiently long targeted-release properties. Besides, the MTT experiment was utilized to investigate the cytotoxicity of NiO NPs on the human hepatocellular carcinoma cell line Huh-7.