Cystathionine gamma-lyase/H2S system suppresses hepatic acetyl-CoA accumulation and nonalcoholic fatty liver disease in mice

Luo

et al. 2020

Preprint

Background: Hawthorn, a commonly-used traditional Chinese medicine (TCM) for treating dyspepsia，dysmenorrhea and hyperlipidemia, etc., has been proven to improve gastrointestinal motility, avoid food retention. Due to its complex ingredients, the active fractions responsible for the treatment of improving digestion remain largely unknown. To explore the underlying material and interpret its potential mechanism, the therapeutic effect of extract from different polar parts of hawthorn on gastrointestinal motility disorder was studied based on the ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) metabolomics . Materials and Methods: The rat model of gastrointestinal motility disorder was established by subcutaneous injecting with atropine. The modeled rats were then treated with 4 polar parts (T1-4 in descending polarity, corresponding to water, n-butanol, ethyl acetate and petroleum ether extracts, respectively) of hawthorn for 5 consecutive days. The stomach, small intestine, plasma samples were collected and then subjected to related measurement (gastric emptying rate and small intestine propulsion rate), UPLC-MS/MS metabolic profiling and multivariate/univariate statistical analysis. Results: The results showed that T3 had the best therapeutic effect, and T1, T2 and T4 with no obvious therapeutic effect, demonstrating that the effective components of hawthorn should be compounds of medium polarity. T3 achieved good therapeutic effects due to the gastrointestinal motility promotion activity, and by rectifying the disturbed amino acid metabolism in gastrointestinal motility disorder model. Conclusion: This integrated metabolomics approach proved the validity of the therapeutic effect of extract from different polar parts of hawthorn on gastrointestinal motility disorder, providing new insights into the underlying mechanisms, and demonstrating the feasibility of metabolomics to evaluate efficacy of herbal drug, which is often difficult by traditional means.

Section: Discussionmentioning

confidence: 90%

Therapeutic Assessment of Fractions of Hawthorn on Gastrointestinal Motility Disorder by UPLC-MS/MS-based Metabolomics

Luo

et al. 2020

Preprint

“…At the same time, the content of ( R )‐pantothenic acid increased, indicating that the synthesis of CoA increased and the amount of the intermediate, acetyl‐CoA, also increased (Cagin et al, 2016; Sabui et al, 2018). This indicated that the metabolism of the three major nutrients returned to normal and improved the gastrointestinal function of the model rats (Ali et al, 2020; Belew et al, 2019; Zhang et al, 2019).…”

Section: Discussionmentioning

confidence: 95%

LC–MS‐based plasma metabolomics study of the intervention effect of different polar parts of hawthorn on gastrointestinal motility disorder rats

Biomedical Chromatography

Luo

et al. 2021

Dyspepsia, one of the most prevalent diseases of the digestive tract that impacts the quality of patient life, is mainly caused by gastrointestinal motility disorder. Hawthorn is a commonly used traditional Chinese medicine for treating dyspepsia, and has been proven to improve gastrointestinal motility. Herein, a rat model of gastrointestinal motility disorder was established by subcutaneous injection with atropine. The modeled rats were treated with four polar parts (T1–4 in descending polarity, corresponding to water, n‐butanol, ethyl acetate and petroleum ether extracts, respectively) of hawthorn. Through metabolomics analysis, a total of 20 significantly metabolites were identified with significant changes in their abundance levels and these metabolites were related to many metabolic pathways such as amino acid metabolism and primary bile acid biosynthesis. The results showed that T3 had the best therapeutic effect of promoting gastrointestinal motility. Other parts showed no obvious therapeutic effect, demonstrating that the effective components of hawthorn may be compounds of medium polarity. T3 might achieve good therapeutic effects owing to the gastrointestinal motility promotion activity, and by rectifying the disturbed metabolic pathways in the gastrointestinal motility disorder model.

“…It has been reported that H 2 S plays an important role in adipogenesis in white adipose tissue (Yang et al, 2018), suggesting the possibility that the lower body weight in HFD + H 2 S group may be due to less fat tissue. Many studies have shown that H 2 S can stimulate lipid formation in fat tissue but decrease lipid synthesis in the liver, indicating that H 2 S may be involved in lipid secretion from hepatocytes (Mani et al, 2015;Yang et al, 2018;Ali et al, 2020). A recent study has revealed that patients with NAFLD tended to possess upregulated concentrations of TG and TC (Zheng et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…A recent study indicates that exposure of HepG2 cells to free fatty acids or high glucose results in a significant increase in intracellular lipids, while co-incubation with 30 μM NaHS (an H 2 S donor) for 72 h reduces acetyl-CoA contents and lipid accumulation. Furthermore, blockage of CSE activity could promote intracellular lipid accumulation (Ali et al, 2020). In the present study, liver cells were incubated in the medium containing 0.5 mM bovine serum albumin (BSA)-OA complex (1:4, molar ratio), with or without 100 µM NaHS (Sigma, Shanghai, China) for 24 h. The control group was treated with BSA.…”

Section: Cell Culturementioning

confidence: 99%

Hydrogen Sulfide Attenuates High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease by Inhibiting Apoptosis and Promoting Autophagy via Reactive Oxygen Species/Phosphatidylinositol 3-Kinase/AKT/Mammalian Target of Rapamycin Signaling Pathway

Zhong

et al. 2020

Front. Pharmacol.

Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease worldwide. Hydrogen sulfide (H2S) is involved in a wide range of physiological and pathological processes. Nevertheless, the mechanism of action of H2S in NAFLD development has not been fully clarified. Here, the reduced level of H2S was observed in liver cells treated with oleic acid (OA). Administration of H2S increased the proliferation of OA-treated cells. The results showed that H2S decreased apoptosis and promoted autophagy through reactive oxygen species (ROS)-mediated phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) cascade in OA-treated cells. In addition, administration of H2S relieved high-fat diet (HFD)-induced NAFLD via inhibition of apoptosis and promotion of autophagy. These findings suggest that H2S could ameliorate HFD-induced NAFLD by regulating apoptosis and autophagy through ROS/PI3K/AKT/mTOR signaling pathway. Novel H2S-releasing donors may have therapeutic potential for the treatment of NAFLD.