Resistant effects determination of Lactobacillus supplementation on broilers to consecutive hydrogen sulfide exposure.

Hydrogen sulfide (H2S) is one of the most irritant gases present in rearing stalls that suppress broilers' healthy growth, which is seriously required an effective alleviation method. In this study, Lactobacillus was supplemented to investigate the alleviative effects on broilers reared under consecutive H2S exposure. A total of 180 healthy 1-day-old male AA broilers with similar body weight (40.8 ± 1.0 g) were randomly allotted into the control treatment (CON), the hydrogen sulfide treatment (H2S), and the Lactobacillus supplement under H2S exposure treatment (LAC) for a 42-d-long feeding process. Growth and carcass performances, immunity-related parameters, intestinal development and cecal microbial communities, and blood metabolites were measured. Results showed that Lactobacillus supplement significantly increased the body weight gain (BWG) while reduced the mortality rate, abdominal fat and bursa of fabricius weight during the whole rearing time compared with H2S treatment (P < 0.05). Serum LPS, IL-1ß, IL-2, and IL-6 contents were observed significantly increased after H2S treatment while remarkably decreased after Lactobacillus supplementation(P < 0.05). Intestinal morphology results showed a significant higher in the development of ileum villus height (P < 0.05). Cecal microbiota results showed the bacterial composition was significantly altered after Lactobacillus supplement (P < 0.05). Specifically, Lactobacillus supplement significantly decreased the relative abundance of Faecalibacterium, while significantly proliferated the relative abundance of Lactobacillus, Bifidobacterium, Clostridium, and Campylobacter (P<0.05). Metabolic results indicated that Lactobacillus supplement may alleviate the harmful effects caused by H2S through regulating the pyrimidine metabolism, starch and sucrose metabolism, fructose and mannose degradation, and beta-alanine metabolism. In summary, Lactobacillus supplement effectively increased BWG and decreased mortality rate of broilers under H2S exposure by enhancing the body's immune capacity, proliferating beneficial microbes (e.g., Lactobacillus and Bifidobacterium), and regulating the physiological pyrimidine metabolism, starch and sucrose metabolism, and beta-alanine metabolism.

Unusual 5/5 fused bicyclosesquiterpenoids from Eupatorium adenophorum.

The chemical analysis on the aerial sections of Eupatorium adenophorum Spreng. resulted in the identification of four unprecedented 5/5 fused bicyclosesquiterpenoids, eupatorid A (1), and its analogues named eupatorester A-C (2-4) using various chromatographic techniques. Their structures were unambiguously confirmed by detailed spectroscopic investigations (including 1D, 2D-NMR and HRMS), and single crystal X-ray diffraction. The anti-inflammatory activities, in vitro tumor growth inhibitory activities and antibacterial activities of these compounds were evaluated.

Molecular Mechanism of Crataegi Folium and Alisma Rhizoma in the Treatment of Dyslipidemia Based on Network Pharmacology and Molecular Docking.

Background: Dyslipidemia has become a critical global issue for public health, with elevating prevalence and morbidity closely related to many cardiovascular diseases (CVD) with high incidence rates. Crataegi Folium (known as Shanzhaye in China, SZ, the leaves of Crataegus pinnatifida Bge. var. major N.E. Br. or Crataegus pinnatifida Bge) and Alisma rhizoma (known as Zexie in China, ZX, the dried tuber of Alisma orientale (Sam.) Juzep or Alisma plantago-aquatica Linn), a classic combination of herbs, have been widely used to treat dyslipidemia. However, the therapeutic mechanism of this pair still remains unclear. Hence, this study aimed to elucidate the molecular mechanism of the Shanzhaye-Zexie herb pair (SZHP) in the treatment of dyslipidemia with the use of a network pharmacology analysis approach. Methods: Active compounds, targets of the SZHP, and targets for dyslipidemia were screened based on the public database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed on the database for annotation, visualization, and integrated discovery (DAVID 6.8). The compound-target-disease-pathway network was visualized using the Cytoscape software, and SYBYL was used for molecular docking. Results: Twelve active compounds in the SZHP were screened out, which were closely connected to 186 dyslipidemia-related targets. The network analysis revealed that sitosterol, stigmasterol, isorhamnetin, kaempferol, and quercetin might be candidate agents and CCND1, CASP3, HIF1A, and ESR1 genes were potential drug targets. GO analysis revealed 856 biological processes (BP), 139 molecular functions (MF), and 89 cellular components (CC). The KEGG pathway enrichment analysis indicated that the lipid level and atherosclerosis might influence the treatment of dyslipidemia. Molecular docking showed that quercetin bound well to CCND1, HIF1A, MYC, AKT1, and EGFR genes. These findings were in accord with the prediction obtained through the network pharmacology approach. Conclusions: This study revealed the primary pharmacological effects and relevant mechanisms of the SZHP in treating dyslipidemia. Our findings may facilitate the development of the SZHP or its active compounds as an alternative therapy for dyslipidemia. Still, more pharmacological experiments are needed for verification.

Inhibition of α-glucosidase by Cyclocarya paliurus based on HPLC fingerprinting integrated with molecular docking and molecular dynamics.

Cyclocarya paliurus (CP) extracts have been shown to lower sugar and lipid levels in blood, but the material basis is not clear. We analyzed CP aqueous extracts using high-performance liquid chromatography "fingerprinting", checked their pharmacological parameters using virtual screening, and undertook molecular docking and molecular dynamics simulations. Also, the inhibitory effects of CP components upon α-glucosidase in vitro were evaluated. Fingerprinting and virtual screening showed that the aqueous extract of CP contained the active components protocatechuic acid, chlorogenic acid, caffeic acid and rutin, which were safe and had no side effects in vivo. Molecular docking and molecular dynamics simulations showed that chlorogenic acid and rutin might have a potent inhibitory effect on α-glucosidase. An enzyme-activity assay in vitro showed that the half-maximal inhibitory values of chlorogenic acid and rutin were 398.9 and 351.8 µg/ml, respectively. Chlorogenic acid and rutin had an inhibitory effect on α-glucosidase. Cyclocarya paliurus could be developed as a natural α-glucosidase inhibitor.

Hyperoside ameliorates the progression of osteoarthritis: An in vitro and in vivo study.

BACKGROUND: Osteoarthritis (OA) is a common degenerative joint disease. The pathogenesis of OA is closely related to inflammatory responses and apoptosis of chondrocytes. Hyperoside (Hyp), a natural flavonoid compound, exerts multiple bioactivities in various diseases. PURPOSE: Our study aims to investigate the anti-arthritic effects of Hyp and delineate the potential mechanism at the cellular level. METHODS: Murine chondrocytes were stimulated with interleukin-1ß (IL-1ß) with or without Hyp treatment. CCK-8 assay was used to evaluate the cytotoxic effect of Hyp. DCFH-DA was used to detect intracellular ROS. Annexin V-FITC/PI method was applied to examine apoptosis of chondrocytes. The anti-arthritic effects of Hyp and related mechanisms were investigated by examining and analyzing relative markers through quantitative PCR, western blot analysis and immunofluorescent staining. C57BL/6 mice were performed the destabilized medial meniscus (DMM) surgery to establish OA model and then injected intraperitoneally with Hyp (20 mg/kg)) for 4 or 8 weeks. Finally, mice were sacrificed and knee joints were collected for histological observation and analysis. RESULTS: Hyp inhibited IL-1ß-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Additionally, Hyp attenuated IL-1ß-induced destruction of the extracellular matrix (ECM) by downregulating the expression of MMPs and ADAMTS5, and meanwhile upregulating the expression of collagen II, aggrecan, and SOX9. Also, Hyp pretreatment reduced IL-1ß-induced overproduction of ROS and apoptosis of chondrocytes. Mechanistically, Hypexerted anti-inflammatory effects by partly suppressing the PI3K/AKT/NF-κB and the MAPK signaling pathways, enhancing the Nrf2/HO-1 to limit the activation of NF-κB. Moreover, Hyp played an anti-apoptotic effect via the Nrf2/ROS/BAX/Bcl-xlaxis. In vivo, cartilage degradation was attenuated with a lower OARSI score in Hyp-treated group compared to the DMM group. CONCLUSION: Our study demonstrated that anti-arthritic effects of Hyp in vitro and in vivo, indicating Hyp might serve as a potential agent for the treatment of OA.

Astaxanthin protects against osteoarthritis via Nrf2: a guardian of cartilage homeostasis.

SCOPE: Osteoarthritis (OA) is a progressive disease characterized by cartilage degradation. Astaxanthin (Ast), a natural compound with remarkable antioxidant activity and multiple medical applications due to its activation of Nrf2 signaling, has been studied for application to various degenerative diseases. Currently, however, little is known about its efficacy in treating OA. This study reports the effects of Ast on cartilage homeostasis in OA progression. METHODS: IL-1ß, TNF-α, and tert-butyl hydroperoxide (TBHP) were used to impair cartilage homeostasis. Modulating effects of Ast on the Nrf2 signaling pathway, and damage-associated events including extracellular matrix (ECM) degradation, inflammation, oxidative stress, chondrocyte apoptosis, and in vivo cartilage degradation were examined. RESULTS: Ast attenuated ECM degradation of OA chondrocytes through the Nrf2 signaling, and ameliorated the IL-1ß-induced inflammatory response and ECM degradation via blockade of MAPK signaling. Additionally, Ast alleviated TNF-α-induced ECM degradation and chondrocyte apoptosis by inhibiting the NF-κB signaling, suppressed TBHP-induced oxidative stress, and subsequently reduced chondrocyte apoptosis. In vitro results were finally corroborated in vivo by demonstrating that Ast attenuates the severity of cartilage destruction in a mouse model of OA. CONCLUSIONS: Ast could protect against osteoarthritis via the Nrf2 signaling, suggesting Ast might be a potential therapeutic supplement for OA treatment.