An herbal formulation "Shugan Xiaozhi decoction" ameliorates methionine/choline deficiency-induced nonalcoholic steatohepatitis through regulating inflammation and apoptosis-related pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Shugan Xiaozhi (SGXZ) decoction is a traditional Chinese medicine used for treating nonalcoholic steatohepatitis (NASH). It has been used clinically for over 20 years and proved to be effective; however, the molecular mechanism underlying the effects of SGXZ decoction remains unclear. AIM OF THE STUDY: We analyzed the chemical components, core targets, and molecular mechanisms of SGXZ decoction to improve NASH through network pharmacology and in vivo experiments. MATERIALS AND METHODS: The chemical components, core targets, and related signaling pathways of SGXZ decoction intervention in NASH were predicted using network pharmacology. Molecular docking was performed to verify chemical components and their core targets. The results were validated in the NASH model treated with SGXZ decoction. Mouse liver function was assessed by measuring ALT and AST levels. TC and TG levels were determined to evaluate lipid metabolism, and lipid deposition was assessed via oil red O staining. Mouse liver damage was determined via microscopy following hematoxylin and eosin staining. Liver fibrosis was assessed via Masson staining. Western blot (WB) and immunohistochemical (IHC) analyses were performed to detect inflammation and the expression of apoptosis-related proteins, including IL-1ß, IL-6, IL-18, TNF-α, MCP1, p53, FAS, Caspase-8, Caspase-3, Caspase-9, Bax, Bid, Cytochrome c, Bcl-2, and Bcl-XL. In addition, WB and IHC were used to assess protein expression associated with the TLR4/MyD88/NF-κB pathway. RESULTS: Quercetin, luteolin, kaempferol, naringenin, and nobiletin in SGXZ decoction were effective chemical components in improving NASH, and TNF-α, IL-6, and IL-1ß were the major core targets. Molecular docking indicated that these chemical components and major core targets might interact. KEGG pathway analysis showed that the pathways affected by SGXZ decoction, primarily including apoptosis and TLR4/NF-κB signaling pathways, interfere with NASH. In vivo experiments indicated that SGXZ decoction considerably ameliorated liver damage, fibrosis, and lipid metabolism disorder in MCD-induced NASH mouse models. In addition, WB and IHC verified the underlying molecular mechanisms of SGXZ decoction as predicted via network pharmacology. SGXZ decoction inhibited the activation of apoptosis-related pathways in MCD-induced NASH mice. Moreover, SGXZ decoction suppressed the activation of TLR4/MyD88/NF-κB pathway in MCD-induced NASH mice. CONCLUSION: SGXZ decoction can treat NASH through multiple targets and pathways. These findings provide new insights into the effective treatment of NASH using SGXZ decoction.

Treatment of antibiotic-containing wastewater with self-suspended algae-bacteria symbiotic particles: Removal performance and reciprocal mechanism.

Emerging contaminants such as antibiotics in wastewater have posed a challenge on conventional biological treatment processes. Algae-bacteria symbiotic mode could improve the performance of biological treatment processes. Self-suspended algae-bacteria symbiotic particles (ABSPs) were prepared with Chlorella vulgaris and Bacillus subtilis using the sol-gel method and hollow glass microspheres in this study. The removal effect of nitrogen and phosphorus as well as the feedback mechanism of ABSPs under tetracycline stress were investigated through three-cycles wastewater treatment experiments. The antioxidant enzyme activity and phycosphere extracellular polymeric substance (EPS) content were identified as well. The results indicated that the removal rates of NH4+-N, TP, COD, and tetracycline in the ABSPs group finally reached 96.18%, 95.44%, 81.36%, and 74.20%, respectively, which were higher than the single algae group apparently. The phycosphere EPS content increased by 20.41% and algae cell structure maintained integrity in ABSPs group as compared with that in single algae group. This study demonstrates that the self-suspended ABSPs can improve contaminants removal performance and alleviate the antioxidant stress response of algae through algal-bacterial reciprocity mechanism.

Wumei Pill Ameliorates AOM/DSS-Induced Colitis-Associated Colon Cancer through Inhibition of Inflammation and Oxidative Stress by Regulating S-Adenosylhomocysteine Hydrolase- (AHCY-) Mediated Hedgehog Signaling in Mice.

Wumei Pill (WMP) is a traditional Chinese herbal formulation and widely used to treat digestive system diseases in clinical. S-Adenosylhomocysteine hydrolase (AHCY) can catalyze the hydrolysis of S-adenosylhomocysteine to adenosine and homocysteine in living organisms, and its abnormal expression is linked to the pathogenesis of many diseases including colorectal cancer (CRC). A previous study reported that WMP could prevent CRC in mice; however, the underlying mechanisms especially the roles of AHCY in WMP-induced anti-CRC remain largely unknown. Here, we investigated the regulatory roles and potential mechanisms of AHCY in WMP-induced anti-CRC. WMP notably alleviated the azoxymethane/dextran sulfate sodium- (AOM/DSS-) induced colitis-associated colon cancer (CAC) in mice. Besides, WMP inhibited the inflammation and oxidative stress in AOM/DSS-induced CAC mice. AHCY was high expression in clinical samples of colon cancer compared to the adjacent tissues. WMP inhibited the AHCY expression in AOM/DSS-induced CAC mice. An in vitro study found that AHCY overexpression induced cell proliferation, colony formation, invasion, and tumor angiogenesis, whereas its knockdown impaired its oncogenic function. AHCY overexpression enhanced, while its knockdown weakened the inflammation and oxidative stress in colon cancer cells. Interestingly, WMP potently suppressed the hedgehog (Hh) signaling in AOM/DSS-induced CAC mice. A further study showed that AHCY overexpression activated the Hh signaling while AHCY knockdown inactivated the Hh signaling. Moreover, activation of the Hh signaling reversed the effect of AHCY silencing on inflammation and oxidative stress in vitro. In conclusion, WMP alleviated the AOM/DSS-induced CAC through inhibition of inflammation and oxidative stress by regulating AHCY-mediated hedgehog signaling in mice. These findings uncovered a potential molecular mechanism underlying the anti-CAC effect of WMP and suggested WMP as a promising therapeutic candidate for CRC.

Allelopathic inhibitory effect on the growth of microcystis aeruginosa by improved ultrasonic-cellulase extract of Vallisneria.

The unique and efficient characteristics of allelopathy in submerged plants make it an environmentally friendly method to control harmful algal blooms. Increased research focus has been placed on the improved allelochemical extraction methods of submerged plants because of their cost-utility relationships. In this study, the growth inhibition effect of Vallisneria extract on Microcystis aeruginosa (M. aeruginosa) cells through the combination of enzyme and ultrasonic-assisted extraction method was analyzed. By establishing a co-cultivation experiment, the growth indicators, photosynthetic system, and oxidative stress system of M. aeruginosa were determined. The reactive oxygen species (ROS) and superoxide dismutase (SOD) activity, as well as the catalase (CAT) and Malondialdehyde (MDA) levels of algal cells were found to have increased significantly after co-cultivation, which indicated that the Vallisneria ultrasonic-cellulase extract could induce oxidative stress in Microcystis aeruginosa cells. The Vallisneria extract could promote at low concentrations and inhibit at high concentrations on the growth of Microcystis aeruginosa. The effective suppression of growth of algae cells with the extract was observed at 5 g/L (fresh weight). The results showed that the Vallisneria ultrasonic-cellulase extract had a significant inhibitory effect on M. aeruginosa, making the effective ingredients a useful reference for algae inhibitors.

Mechanism study of the beneficial effect of sodium selenite on metabolic disorders in imidacloprid-treated garlic plants.

As an effective neonicotinoid insecticide, imidacloprid (IMI) has been widely used in crop production, but its residue affects normal plant growth. Selenium (Se) is a non-essential mineral nutrient in higher plants, that acts as the active centre of glutathione peroxidase (GSH-Px), which removes harmful peroxides. In this study, we investigated the mechanism by which selenium improves the growth status of IMI-treated garlic plants through analyses of apparent morphology and antioxidant enzyme activity as well as the dynamic changes in nutrients and metabolites in the plants. The results showed that 80 µg/kg Na2SeO3 had a strong effect on alleviating the damage in garlic plants exposed to IMI (1.2 mg/kg) by increasing the absorption of mineral elements to enhance the synthesis of chlorophyll and antioxidant enzymes. A nontarget metabolomics analysis based on gas chromatography-mass spectrometry (GC-MS) indicated that the addition of Na2SeO3 to IMI-treated garlic could reconstruct the plant metabolic distribution by enhancing the nitrogen and indole metabolism, maintaining lower concentrations of secondary metabolites and maintaining the balance of the plant energy metabolism. Our study provides novel insights into the molecular mechanisms by which garlic plants responds to IMI exposure and suggests the use of selenium with IMI-contaminated plants as a solution for the advancement of sustainable agricultural pesticide use.

The protective effects of selenium-enriched spirulina on the reproductive system of male zebrafish (Danio rerio) exposed to beta-cypermethrin.

Beta-cypermethrin (beta-CYP), which is widely used for the control of indoor and field pests, is a highly lipophilic insecticide with environmental estrogenic effects. Selenium-enriched Spirulina (Se-SP) is a novel natural antioxidant agent with a high nutritional value. This study was aimed at the investigation of the protective effects of Se-SP on the reproductive system of male zebrafish (Danio rerio) exposed to beta-CYP. We determined the protective effect of Se-SP on male zebrafish exposed to 7 nmol L-1 beta-CYP by measuring the activity of sperm and antioxidants, examining tissue sections, measuring hormone secretion levels, and analyzing the expression of related proteins and genes during spermatogenesis. We found that beta-CYP enhanced VTG synthesis and estrogen (E2) secretion, increased the number of spermatogonia and spermatocytes, and decreased the number of spermatids and Sertoli cells. However, treatment with 50 mg L-1 Se-SP (Se: 25 µmol g-1 Se-SP) almost completely ameliorated the deleterious effects of beta-CYP. The protective mechanism of Se-SP in the testes of beta-CYP-treated fish involved an enhancement of antioxidant enzyme activity and an increase in androgen secretion by the downregulation of the expression of cyp19a, nanos2, piwil1, dazl and sycp3, and the upregulation of the expression of odf3b, igf3, insl3 and dmrt1, which affected testosterone production and spermatogenesis. Our study strongly indicates that treatment with Se-SP can effectively prevent the oxidative damage to the reproductive system during spermatocyte differentiation induced by beta-CYP exposure.