Tricetin protects against liver fibrosis through promoting autophagy and Nrf2 signaling in hepatic stellate cells.

AIMS: The study aims to investigate the role and underlying mechanisms of tricetin in regulating hepatic stellate cells (HSCs) activation. MAIN METHODS: We treated human hepatic stellate cells line LX-2 and freshly isolated primary mouse hepatic stellate cells (mHSCs) with tricetin, pharmacological inhibitors and siRNAs, western blot, immunofluorescence, quantitative PCR were used to evaluate the expression of fibrotic markers, autophagy levels and Nrf2 (nuclear factor E2-related factor 2) signaling. KEY FINDINGS: Herein, we demonstrated that tricetin strongly attenuated the proliferation, migration, lipid droplets (LDs) loss and fibrotic markers Col 1a1 (type I α 1 collagen) and α-SMA (α-smooth muscle actin) expression in LX-2 cells. Moreover, tricetin time- and dose-dependently provoked autophagic formation in LX-2 cells. Autophagy inhibition by pharmacological intervention or genetic ATG5 (autophagy related 5) silencing facilitated tricetin-induced downregulation of profibrotic markers in LX-2 cells. Additionally, tricetin treatment reduced reactive oxygen species (ROS) accumulation, promoted Nrf2 signaling in LX-2 cells and pretreatment with ROS scavenger NAC partially reversed tricetin-induced autophagy and enhanced tricetin-mediated HSCs inactivation. Nrf2 silencing partially reversed tricetin-mediated inhibition of α-SMA expression. Finally, utilizing primary mouse hepatic stellate cells (mHSCs), we demonstrated that tricetin also induced autophagy activation, repressed TGF-ß1-induced LDs loss and fibrotic marker expression and pretreatment with CQ further sensitized these effects. SIGNIFICANCE: Our study indicates that tricetin's actions may represent an effective strategy to treat liver fibrosis and help identify novel therapeutic targets, especially in combination with autophagy inhibitors.

Water extract of Fagopyrum dibotrys (D. Don) Hara straw increases selenium accumulation in peach seedlings under selenium-contaminated soil.

To promote the selenium (Se) uptakes in fruit trees under Se-contaminated soil, the effects of water extract of Fagopyrum dibotrys (D. Don) Hara straw on the Se accumulation in peach seedlings under selenium-contaminated soil were studied. The results showed that the root biomass, chlorophyll content, activities of antioxidant enzymes, and soluble protein content of peach seedlings were increased by the F. dibotrys straw extract. The different forms of Se (total Se, inorganic Se, and organic Se) were also increased in peach seedlings following treatment with the F. dibotrys straw extract. The highest total shoot Se content was treated by the 300-fold dilution of F. dibotrys straw, which was 30.87% higher than the control. The F. dibotrys straw extract also increased the activities of adenosine triphosphate sulfurase (ATPS), and adenosine 5'-phosphosulfate reductase (APR) in peach seedlings, but decreased the activity of serine acetyltransferase (SAT). Additionally, correlation and grey relational analyses revealed that chlorophyll a content, APR activity, and root biomass were closely associated with the total shoot Se content. Overall, this study shows that the water extract of F. dibotrys straw can promote Se uptake in peach seedlings, and 300-fold dilution is the most suitable concentration.

The water extract of Fagopyrum dibotrys (D. Don) Hara straw promoted the selenium (Se) uptake in peach seedlings under selenium-contaminated soil. The concentration of F. dibotrys straw extract showed a quadratic polynomial regression relationship with the total root and shoot Se. Furthermore, chlorophyll a content, APR activity, and root biomass were closely associated with the total shoot Se. This study shows that water extract of F. dibotrys straw can promote Se uptake in peach seedlings, and 300-fold dilution is the most suitable concentration.

The impact of food restriction on liver enzyme levels: a systematic review and meta-analysis.

CONTEXT: The relationship between food restriction (FR) and liver enzyme levels, such as alanine transferase (ALT), aspartate transferase (AST), and γ-glutamyl transferase (GGT), has not yet been confirmed. OBJECTIVE: A meta-analysis of research articles was conducted to investigate the association of FR and liver enzyme levels. DATA SOURCES: The PubMed, Web of Science, Embase, and Cochrane Library databases were screened for articles published up to April 30, 2022. DATA EXTRACTION: Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement methodology was used to search for research articles. Publication bias was detected using Begg's test. Finally, 17 trials involving 1982 participants and that reported mean value, mean difference, and standard deviation were identified. DATA ANALYSIS: Data were described as the weighted mean difference of body mass index, body weight, and standardized mean difference (SMD) of ALT, AST, and GGT. A reduction in ALT level was observed after a FR intervention (total SMD, -0.36, 95% confidence interval [CI], -0.68 to -0.05). GGT levels also were decreased in 4 studies (total SMD, -0.23; 95%CI, -0.33 to -0.14). According to subgroup analysis, serum AST levels decreased in the medium-term (between 5 wk and 6 mo) group (subtotal SMD, -0.48; 95%CI, -0.69 to -0.28). CONCLUSION: Existing evidence suggests that dietary restriction improves adult liver enzyme levels. The long-term maintenance of healthy liver enzyme levels, particularly in real-world applications, necessitates additional consideration.

Astaxanthin Alleviates Foam Cell Formation and Promotes Cholesterol Efflux in Ox-LDL-Induced RAW264.7 Cells via CircTPP2/miR-3073b-5p/ABCA1 Pathway.

Atherosclerosis (AS) is a common cardiovascular disease and remains the leading cause of death in the world. It is generally believed that the deposition of foam cells in the arterial wall is the main cause of AS. Moreover, promoting cholesterol efflux and enhancing the ability of reverse cholesterol transport (RCT) can effectively inhibit the formation of foam cells, thereby preventing the occurrence and development of AS. Astaxanthin, with a powerful antioxidant ability, has a potential role in the prevention of atherosclerosis, but how it works in preventing atherosclerosis remains unknown. Here, our experimental results suggest that astaxanthin can upregulate the expression of circular RNA tripeptidyl-peptidase II (circTPP2) and eventually promote cholesterol efflux by modulating ATP-binding cassette subfamily A member 1 (ABCA1). The expression of ABCA1 was significantly suppressed after knocking down circTPP2 in macrophage-derived foam cells. In addition, the experimental results showed that circTPP2 could downregulate the expression of microRNA-3073b-5p (miR-3073b-5p), and ABCA1 was identified as the target gene of miR-3073b-5p. In conclusion, the circTPP2/miR-3073b-5p/ABCA1 axis may be the specific mechanism of astaxanthin promoting cholesterol efflux.

Two Olean-27-carboxylic Acid-Type Triterpenoids as Chemical Markers Isolated from Saxifraga umbellulata.

Two olean-27-carboxylic acid-type triterpenoids (1 and 2) were isolated from Saxifraga umbellulata (Saxifragaceae), representing the first case in the chemical discoveries of genus Saxifraga. Compound 1 was determined to be a new compound named 'Saxifragic acid' based on the comprehensive spectroscopic and X-ray crystallographic analyses. Compound 2 (deacetylated saxifragic acid) is a known compound reported before, but its absolute configuration through X-ray crystallographic analyses was first described here. In addition, their cytotoxicity against five digestive human cancer cell lines (BGC-823, GBC-SD, CCC-9810, HT-29, and HepG2) and hepatoprotective activity against CCl4 -induced L-o2 cell injury in vitro were evaluated. Interestingly, UPLC-QTOFMS analysis showed that these two compounds could be used as chemical markers to discriminate between S. umbellulata and S. tangutica, both of which are used for the treatment of hepatobiliary diseases in traditional Tibetan medicine.