Clinical study on the relationship between liver cirrhosis, ascites, and hyponatremia.

BACKGROUND: Cirrhosis is a common liver disease, and ascites is one of the common clinical conditions. However, the clinical manifestations of ascites combined with hyponatremia as a high-risk condition and its relationship to patient prognosis have not been fully studied. AIM: To explore the clinical manifestations, prognostic factors, and relationships of ascites with hyponatremia in patients with cirrhosis to provide better diagnostic and treatment strategies. METHODS: In this study, we retrospectively analyzed the clinical data of 150 patients diagnosed with cirrhosis and ascites between 2017 and 2022. Patients were divided into two groups: ascites combined with hyponatremia group and ascites group. We compared the general characteristics, degree of hyponatremia, complications, treatment, and prognosis between the two groups. RESULTS: In the study results, patients in the ascites combined with hyponatremia group showed an older average age (58.2 ± 8.9 years), 64.4% were male, and had a significantly longer hospitalization time (12.7 ± 5.3 d). Hyponatremia was more severe in this group, with a mean serum sodium concentration of 128.5 ± 4.3 mmol/L, which was significantly different from the ascites group of 137.6 ± 2.1 mmol/L. Patients with ascites and hyponatremia were more likely to develop hepatic encephalopathy (56.2% vs 39.0%), renal impairment (45.2% vs 28.6%) and infection (37.0% vs 23.4%). Regarding treatment, this group more frequently used diuretics (80.8% vs 62.3%) and salt supplements (60.3% vs 38.9%). Multiple logistic regression analysis identified older age [Odds ratio (OR) = 1.06, P = 0.025] and male gender (OR = 1.72, P = 0.020) as risk factors for hyponatremia combined with ascites. Overall, patients with ascites and hyponatremia present a clear high-risk status, accompanied by severe complications and poor prognosis. CONCLUSION: In patients with cirrhosis, ascites with hyponatremia is a high-risk condition that is often associated with severe complications.

4-octyl itaconate protects against oxidative stress-induced liver injury by activating the Nrf2/Sirt3 pathway through AKT and ERK1/2 phosphorylation.

4-octyl itaconate (4-OI) is a cell-permeable itaconate derivative with anti-inflammatory and antioxidant properties. However, its therapeutic potential for oxidative stress-induced liver injury remains unknown. This study investigated the hepatoprotective effects and mechanisms of 4-OI against oxidative damage in in vitro and in vivo models. 4-OI attenuated H2O2-induced cytotoxicity, oxidative stress, and mitochondrial dysfunction in L02 and HepG2 cells. Untargeted metabolomics profiling and pathway analysis identified the PI3K/AKT/mTOR and MAPK pathways as key regulators of 4-OI's protective effects. Specifically, 4-OI induced phosphorylation of AKT and ERK1/2, leading to activation of the Nrf2 signaling pathway. Nrf2 upregulated expression of the mitochondrial deacetylase Sirt3, which subsequently alleviated H2O2-induced cell injury. In mice, 4-OI reduced acetaminophen (APAP)-induced liver injury as evidenced by attenuated hepatocellular necrosis and decreased serum liver enzymes. It also elevated hepatic expression of Nrf2, Sirt3, p-AKT and p-ERK1/2. Inhibition of AKT, ERK1/2 or Nrf2 blocked the protective effects of 4-OI in vitro, suggesting its antioxidant activity is mediated by activating the Nrf2/Sirt3 pathway via AKT and ERK1/2 phosphorylation. In summary, 4-OI exerted antioxidant and hepatoprotective effects by activating the Nrf2/Sirt3 signaling pathway through AKT and ERK1/2 phosphorylation, which were elucidated using in vitro and in vivo oxidative stress models. This provides novel insights into the mechanisms of 4-OI against oxidative stress-related liver diseases.

Therapeutic efficacy and underlying mechanisms of Gastrodia elata polysaccharides on dextran sulfate sodium-induced inflammatory bowel disease in mice: Modulation of the gut microbiota and improvement of metabolic disorders.

Inflammatory bowel disease (IBD) is a chronic inflammatory gastrointestinal disease, and an imbalance in the gut microbiota is a critical factor in its development. Gastrodia elata (G. elata), an Orchidaceae plant, is recognized for its nutritional and medicinal value. Studies have shown that G. elata polysaccharides (GBP) have anti-inflammatory properties that may ameliorate IBD. However, the therapeutic effects of GBP on gut microbiota metabolism remain unknown. Therefore, we aimed to examine the therapeutic potential of G. elata extract and GBP in dextran sulfate sodium (DSS)-induced IBD mice. GBP demonstrated the best therapeutic effect by reducing IBD symptoms in mice to the greatest extent. Administering GBP resulted in significant increases in the relative abundances of bacteria with potential anti-inflammatory effects, such as Ligilactobacillus and Alloprevotella, and decreases in the levels of bacteria associated with proinflammatory responses, such as Bacteroides and Escherichia-Shigella. Furthermore, 36 significant differential metabolites between the model and GBP groups were identified in feces, which were mainly enriched in amino acid metabolism, including tryptophan and cysteine, vitamin B6 metabolism and steroid hormone biosynthesis. Consequently, investigating the metabolic regulation of the gut microbiota is a promising approach to evaluate the therapeutic effect of GBP on IBD.

Anti-inflammation of torachrysone-8-O-ß-á´ -glucoside by hurdling over morphological changes of macrophages.

Macrophages exhibit significant phenotypic plasticity to switch their functional phenotypes during inflammation and recovery. Pro-inflammatory (M1) macrophages transform their morphology from round in M0 phenotype to flat and rapidly adhere to lesion sites to recognize series of molecular patterns: damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs). Macrophages could also reprogram their metabolism to influence their function. Torachrysone-8-O-ß-ᴅ-glucoside (TG), a naphthalene glucoside from Polygonum multiflorum Thunb., exhibited remarkable anti-inflammatory effect. In this study, TG significantly inhibited the Tyr-phosphorylation of focal adhesion kinase (FAK), a key regulator of morphological transformation, and downregulated FAK-mediated transcription of cytoskeleton genes. Thus, TG greatly restrained LPS-induced morphological transformation of macrophage cells into M1 type and reduced their adhesion. The inhibition of TG on FAK phosphorylation also blocked the binding between phosphor-FAK and pyruvate kinase (PK), which contributed to the inhibition of PK activity and limited the high glycolysis rate of M1 metabolic phenotype. Moreover, TG ameliorated defective function of the TCA cycle by markedly increasing of succinate dehydrogenase activity and upregulating the transcription of three rate-limiting enzymes of TCA cycle in M1-polarized macrophage cells. TG enhanced the expression of M2 polarization makers, blunting the sensitivity of RAW 264.7 cells to DAMPs/PAMPs, and inhibited nuclear translocation of NF-κB p65, thus decreased the M1-associated the release of inflammatory factors. These results demonstrated that TG could be a potent anti-inflammatory agent that curbed both the morphological and metabolic phenotype changes of macrophages and warranted further investigations on anti-inflammation effects from angles of morphology, which were unfortunately mostly neglected.

Hepatotoxicity or hepatoprotection of emodin? Two sides of the same coin by 1H-NMR metabolomics profiling.

Emodin is the major anthraquinone component of many important traditional Chinese herbs, such as Rheum palmatum L. and Polygonum multiflorum Thunb. They have been popular health products but recently aroused concerns about their hepatotoxicity, which are believed to be arising from the contained anthraquinones, such as emodin. However, emodin exerts potent hepatoprotective ability, such as anti-fibrotic, anti-oxidative, and anti-inflammatory effects. In this study, 1H NMR based metabolomics approach, complemented with histopathological observation, biochemical measurements, western blotting analysis and real-time quantitative PCR (RT-qPCR), was applied to interpret the paradox of emodin (30 mg/kg, 10 mg/kg BW) using both healthy mice (male, ICR) and chronic CCl4-injured mice (0.1 mL/kg, 0.35% CCl4, 3 times a week for a month). Emodin exerted a weight loss property associated with its lipid-lowing effects, which helped alleviate CCl4-induced steatosis. Emodin effectively ameliorated CCl4-induced oxidative stress and energy metabolism dysfunction in mice liver via regulating glucose, lipid and amino acid metabolism, and inhibited excessive inflammatory response. In healthy mice, emodin only exhibited hepatoxicity on high-dosage by disturbing hepatic anti-oxidant homeostasis, especially GSH and xanthine metabolism. This integrated metabolomics approach identified the bidirectional potential of emodin, which are important for its rational use.

Activation of Adenosine A1 Receptor in Ischemic Stroke: Neuroprotection by Tetrahydroxy Stilbene Glycoside as an Agonist.

Ischemic stroke is the main cause of death/disability, posing a great menace to human health. Though efforts to search for therapeutic drugs are ongoing, few of them have succeeded. Adenosine A1 receptor (A1R) activation could ameliorate ischemic injury, representing a very tempting target for stroke treatment. Tetrahydroxy stilbene glycoside (TSG), a potent antioxidant from the well-known Chinese herb Polygonum multiflorum Thunb., has been reported to have notable neuroprotective activities but the underlying mechanisms are elusive. This study investigated the mechanism of TSG focusing on A1R. TSG markedly decreased mortality, neurological deficit score, cerebral infarct size and brain water content of MCAO rats, and ameliorated the disorders in purine metabolism, energy metabolism and antioxidative defense system. TSG helped the survival of SH-SY5Y cells in OGD/R by alleviating oxidative stress and glutamate release, and by maintaining calcium homeostasis. TSG effects were abolished by A1R antagonist DPCPX. Docking and binding assays confirmed the binding of TSG with A1R. In addition, TSG upregulated the A1R level lowered by MCAO and OGD/R. The downstream signals of A1R activation, ERK1/2, HIF-1α and NF-κB contributed to the neuroprotection of TSG. Moreover, void of "well-known" cardiovascular side effects of classical A1R agonists, TSG showcased its great potential for stroke treatment.

Nuclear magnetic resonance-based metabolomics approach to evaluate preventive and therapeutic effects of Gastrodia elata Blume on chronic atrophic gastritis.

Chronic atrophic gastritis (CAG) is one of the most common digestive system diseases worldwide which defined by WHO as initial step of cancer. Gastrodia elata Blume (GEB) is a traditional herbal with multiple pharmacological activities which was widely used in Asian countries. This study aims to explore the preventive and therapeutical effects of Gastrodia elata Blume on auto-immune induced CAG in rats. Tissues of stomachs were collected and submitted to 1H NMR-based metabolomics analysis and histopathological inspection. The biochemical indexes of MDA, SOD, GSH, NO and XOD were measured. Gastrodia elata Blume could apparently ameliorate the damaged gastric glands and the biochemical parameters, enhance gastric acid secretion, and significantly relieve the inflammation of the stomach. Orthogonal signal correction-partial least squares-discriminant analysis (OSC-PLS-DA) of NMR profiles and correlation network analysis revealed that Gastrodia elata Blume could effectively treat CAG via regulating energy and purine metabolisms, and by anti-oxidation and anti-inflammation effects.