Nuciferine alleviates collagen-induced arthritic in rats by inhibiting the proliferation and invasion of human arthritis-derived fibroblast-like synoviocytes and rectifying Th17/Treg imbalance.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder marked by persistent synovial inflammation and joint degradation, posing challenges in the development of effective treatments. Nuciferine, an alkaloid found in lotus leaf, has shown promising anti-inflammatory and anti-tumor effects, yet its efficacy in RA treatment remains unexplored. This study investigated the antiproliferative effects of nuciferine on the MH7A cell line, a human RA-derived fibroblast-like synoviocyte, revealing its ability to inhibit cell proliferation, promote apoptosis, induce apoptosis, and cause G1/S phase arrest. Additionally, nuciferine significantly reduced the migration and invasion capabilities of MH7A cells. The therapeutic potential of nuciferine was further evaluated in a collagen-induced arthritis (CIA) rat model, where it markedly alleviated joint swelling, synovial hyperplasia, cartilage injury, and inflammatory infiltration. Nuciferine also improved collagen-induced bone erosion, decreased pro-inflammatory cytokines and serum immunoglobulins (IgG, IgG1, IgG2a), and restored the balance between T helper (Th) 17 and regulatory T cells in the spleen of CIA rats. These results indicate that nuciferine may offer therapeutic advantages for RA by decreasing the proliferation and invasiveness of FLS cells and correcting the Th17/Treg cell imbalance in CIA rats.

Gastrodin Attenuates Colitis and Prevents Tumorigenesis in Mice by Interrupting TLR4/MD2/NF-ΚB Signaling Transduction.

INTRODUCTION: Chronic inflammation is one of the causative factors for tumorigenesis. Gastrodin is a main active ingredient isolated from Gastrodia elata Blume, a famous medicinal herb with a long edible history. AIM: This study aimed to explore the effects of gastrodin on colitis-associated carcinogenesis (CRC) in mice and to elucidate its potential molecular mechanisms. METHODS: Balb/c mice were induced with azoxymethane (AOM) and dextran sulfate sodium (DSS) for 12 weeks. Gastrodin (50 mg/kg) was administered via oral gavage three times per week until the end of the experiment. Disease indexes, including body weight, bloody diarrhea, colon length, histopathological score, and tumor size, were measured. Tumor cell proliferation was evaluated by BrdU incorporation assay and tumor cell cytotoxicity was assessed by cell counting kit (CCK-8). The expression levels of toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-ΚB) signaling molecules, NF-ΚB luciferase, and pro-inflammatory cytokines were determined by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), immunoblotting, immunohistochemistry (IHC), enzyme-linked immunosorbent assay (ELISA), or reporter gene assays. The binding affinity between gastrodin and myeloid differentiation protein-2 (MD2) was analyzed by molecular docking and cellular thermal shift assay (CETSA). RESULTS: Gastrodin administration was demonstrated to mitigate various CRC-related symptoms in mice, including weight loss, diarrhea, and tissue abnormalities. Notably, gastrodin suppressed tumor cell growth during colitis- associated tumorigenesis, resulting in fewer and smaller adenomas in the colon. Unlike irinotecan, a broadspectrum antitumor drug, gastrodin did not exhibit apparent cytotoxicity in various colorectal adenocarcinoma cell lines. Additionally, gastrodin downregulated TLR4/NF-ΚB signaling molecules and pro-inflammatory mediators in mice and macrophages. Molecular docking and CETSA experiments suggested that gastrodin binds to the MD2 protein, potentially interfering with the recognition of lipopolysaccharide (LPS) by TLR4, leading to NF-ΚB pathway inhibition. CONCLUSION: This study provides evidence for the first time that gastrodin attenuated colitis and prevented colitisrelated carcinogenesis in mice, at least partially, by diminishing tumor-promoting cytokines through the interruption of TLR4/MD2/NF-ΚB signaling transduction.

Nutrition therapy in critically ill patients with severe acute pancreatitis.

A significant proportion of patients (10%-20%) with acute pancreatitis develop severe acute pancreatitis characterized by pancreatic necrosis, systemic inflammation, and organ failure, commonly requiring intensive care unit (ICU) admission. In this specific population, nutrition therapy is more challenging than that in the general ICU population, primarily because of inevitable gastrointestinal involvement by pancreatic inflammation. In this review, we discussed several key aspects of nutrition therapy in this population, including key pathophysiology that may impede nutrition therapy, the timing and implementation of enteral nutrition and parenteral nutrition, the importance of specific nutrient supplements, and the long-term outcomes that may be addressed by nutrition therapy.

Medicinal and edible plant Allium macrostemon Bunge for the treatment of testosterone-induced androgenetic alopecia in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Allium macrostemon Bunge (AMB), a widely distributed wild garlic plant, possesses a variety of health-promoting properties. Androgenetic alopecia (AGA) is a common disorder that affects quality of life. AIM OF THE STUDY: We sought to investigate whether AMB stimulates hair regrowth in AGA mouse model, and clarify the underlying molecular mechanisms. MATERIALS AND METHODS: The chemical constituents of AMB water extract were identified by ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q/TOF-MS) analysis. Cell viability assay and Ki-67 immunostaining were undertaken to evaluate the impacts of AMB on human hair dermal papilla cell (HDPC) proliferation. Wound-healing assay was undertaken to assess cell migration. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay were performed to examine cell apoptosis. Western blotting, real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and immunostaining assays were undertaken to determine the impacts of AMB on Wnt/ß-catenin signaling and growth factors expression in HDPC cells. AGA mouse model was induced by testosterone treatment. The effects of AMB on hair regeneration in AGA mice were demonstrated by hair growth measuring and histological scoring. The levels of ß-catenin, p-GSK-3ß, and Cyclin D1 in dorsal skin were measured. RESULTS: AMB promoted proliferation and migration, as well as the expression of growth factors in cultured HDPC cells. Meanwhile, AMB restrained apoptosis of HDPC cells by increasing the ratio of anti-apoptotic Bcl-2/pro-apoptotic Bax. Besides, AMB activated Wnt/ß-catenin signaling and thereby enhancing growth factors expression as well as proliferation of HDPC cells, which was abolished by Wnt signaling inhibitor ICG-001. In addition, an increase of hair shaft elongation was observed in mice suffering from testosterone-induced AGA upon the treatment of AMB extract (1% and 3%). Consistent with the in vitro assays, AMB upregulated the Wnt/ß-catenin signaling molecules in dorsal skin of AGA mice. CONCLUSION: This study demonstrated that AMB promoted HDPC cell proliferation and stimulated hair regrowth in AGA mice. Wnt/ß-catenin signaling activation, which induced production of growth factors in hair follicles and, eventually, contributed to the influence of AMB on the hair regrowth. Our findings may contribute to effective utilization of AMB in alopecia treatment.

BuShen JianGu Fang alleviates cartilage degeneration via regulating multiple genes and signaling pathways to activate NF-κB/Sox9 axis.

BACKGROUND: Osteoarthritis (OA) is an inflammatory response in chondrocytes, causing extracellular matrix (ECM) degradation and cartilage destruction, affecting millions of people worldwide. Chinese herbal formulae BuShen JianGu Fang (BSJGF) has been clinically applied for treating OA-related syndromes, but the underlying mechanism still unclear. METHODS: The components of BSJGF were analyzed by liquid chromatography-mass spectrometry (LC-MS). To make a traumatic OA model, the anterior cruciate ligament of 6-8-week-old male SD rats were cut and then the 0.4 mm metal was used to destroy the knee joint cartilage. OA severity was assessed by histological and Micro-CT. Mouse primary chondrocytes were utilized to investigate the mechanism of BSJGF alleviate osteoarthritis, which was examined by RNA-seq technology combined with a series of functional experiments. RESULTS: A total 619 components were identified by LC-MS. In vivo, BSJGF treatment result in a higher articular cartilage tissue area compared to IL-1ß group. Treatment also significantly increased Tb.Th, BV/TV and BMD of subchondral bone (SCB), which implied a protective effect on maintaining the stabilization of SCB microstructure. In vitro results indicated BSJGF promoted chondrocyte proliferation, increased the expression level of cartilage-specific genes (Sox9, Col2a1, Acan) and synthesized acidic polysaccharide, while inhibiting the release of catabolic enzymes and production of reactive oxygen species (ROS) induced by IL-1ß. Transcriptome analysis showed that there were 1471 and 4904 differential genes between IL-1ß group and blank group, BSJGF group and IL-1ß group, respectively, including matrix synthesis related genes (Col2a1, H19, Acan etc.), inflammation related genes (Comp, Pcsk6, Fgfr3 etc.) and oxidative stress related genes (Gm26917, Bcat1, Sod1 etc.). Furthermore, KEGG analysis and validation results showed that BSJGF reduces OA-mediated inflammation and cartilage damaged due to modulation of NF-κB/Sox9 signaling axis. CONCLUSION: The innovation of the present study was the elucidation of the alleviating cartilage degradation effect of BSJGF in vivo and in vitro and discovery of its mechanism through RNA-seq combined with function experiments, which provides a biological rationale for the clinical application of BSJGF for OA treatment.

Effects of Dietary Ferulic Acid on Intestinal Health and Ileal Microbiota of Tianfu Broilers Challenged with Lipopolysaccharide.

Lipopolysaccharide (LPS) has been considered the primary agent to establish animal models of inflammation, immunological stress, and organ injury. Previous studies have demonstrated that LPS impaired gastrointestinal development and disrupted intestinal microbial composition and metabolism. Ferulic acid (FA) isolated from multiple plants exhibits multiple biological activities. This study investigated whether FA ameliorated intestinal function and microflora in LPS-challenged Tianfu broilers. The results showed that LPS challenge impaired intestinal function, as evidenced by decreased antioxidant functions (p < 0.05), disrupted morphological structure (p < 0.05), and increased intestinal permeability (p < 0.05); however, these adverse effects were improved by FA supplementation. Additionally, FA supplementation preserved sIgA levels (p < 0.05), increased mRNA expression levels of CLDN and ZO-1 (p < 0.05), and enhanced epithelial proliferation (p < 0.05) in the ileal mucosa in LPS-challenged chickens. Moreover, FA supplementation rectified the ileal microflora disturbances in the LPS-challenged broilers. The results demonstrate that dietary FA supplementation decreased LPS-induced intestinal damage by enhancing antioxidant capacity and maintaining intestinal integrity. Furthermore, FA supplementation protects intestinal tight junctions (TJs), elevates secretory immunoglobulin A (sIgA) levels, and modulates ileal microflora composition in LPS-challenged broilers.

Salvia miltiorrhiza polysaccharide and its related metabolite 5-methoxyindole-3-carboxaldehyde ameliorate experimental colitis by regulating Nrf2/Keap1 signaling pathway.

The roots of Salvia miltiorrhiza have been used in Traditional Chinese Medicine for thousands of years. However, tons of aerial parts of this plant are usually discarded in the production of roots preparation. To make better use of these plant resources, the polysaccharide isolated from the aerial part of S. miltiorrhiza was investigated for its potential protection against intestinal diseases. A pectic polysaccharide (SMAP-1) was isolated and characterized being composed of homogalacturonan as the main chain and rhamnogalacturonan type I as ramified region, with side chains including arabinans and possible arabinogalactan type I and II. SMAP-1 exhibited robust protective effects against dextran sodium sulfate (DSS)-induced colitis and restored colitis symptoms, colonic inflammation, and barrier functions. Anti-oxidative effects were also observed by up-regulating Nrf2/Keap1 signaling pathway. Additionally, the level of serum 5-methoxyindole-3-carboxaldehyde (5-MC) was restored by SMAP-1 identified in metabolomic analysis, being correlated with the aforementioned effects. Protection against oxidative stress on intestinal porcine enterocyte cells (IPEC-J2) by 5-MC was observed through the activation of Nrf2/Keap1 system, as also shown by SMAP-1. In conclusion, SMAP-1 could be a promising candidate for colitis prevention, and 5-MC could be the signal metabolite of SMAP-1 in protecting against oxidative stress in the intestine.

Sesquiterpenes from Artemisia annua and Their Cytotoxic Activities.

Artemisia annua is a well-known traditional Chinese medicine. Due to its highest antimalarial efficacy, China has a long history of cultivating A. annua, and it is used for "clearing heat and detoxicating". Several, studies have shown that the A. annua extract exerts cytotoxicity. In order to clarify the basis of the cytotoxic effect of A. annua, 18 sesquiterpenes were isolated from the herb, including 2 new sesquiterpenes and 16 known analogues. The structures of new compounds were elucidated by comprehensive spectroscopic analyses, including HR-ESI-MS, NMR experiments, single-crystal X-ray, and DP4+ and electronic circular dichroism (ECD) calculations. Cytotoxic activity screening revealed three compounds that exhibited cytotoxicity in a dose-dependent manner. Additional exploration showed that compound 5 significantly inhibited the proliferation of CT26 and HCT116 cells and induced apoptosis of HCT116 cells after 24 h. These chemical constituents contributed to elucidating the mechanism of action of the cytotoxic activity of A. annua.

Phosphorus flow analysis of different crops in Dongying District, Shandong Province, China, 1995-2016.

Investigating the phosphorus (P) sources, pathways, and final sinks are important to reduce P pollution and improve P management. In this study, substance flow analysis (SFA) was performed for P flow analysis from 1995 to 2016 in different crops of Dongying District, a core region of the alluvial delta at the estuary of the Yellow River. The results showed that P input steadily increased from 1.48 × 104 t in 1995 to 2.16 × 104 t in 2007, and then decreased from 1.90 × 104 t in 2010 to 1.78 × 104 t in 2016. Chemical fertilizers made the highest contribution to P input. The cotton with the highest P load was on the top of P load risk ranks. More importantly, this study applied the Partial Least Squares Path Modeling (PLS-PM) model for P flow analysis and established the numerical relationship between the variables (including fertilizers, straws return-to-field, harvested grains, discarded straw, and P erosion and runoff), P use efficiency (PUE) and P load. The analysis revealed that fertilizer and crop production are the key factors affecting the PUE. Therefore, optimizing the use of P-fertilizer whilst maintaining yields can be an effective strategy to improve the local region PUE.

Peanut skin extract ameliorates high-fat diet-induced atherosclerosis by regulating lipid metabolism, inflammation reaction and gut microbiota in ApoE-/- mice.

Atherosclerosis (AS) is a serious threat to the health and life of humans worldwide. The mitigating effect of polyphenol compounds from peanut skin extract (PSE) on AS has attracted great research attention. However, the mechanism underlying this mitigating effect remains poorly understood. This study aims to investigate the preventive effect of PSE on high-fat diet-induced AS in mice and explore the underlying mechanisms. PSE treatment significantly reduced atherosclerotic plaques, particularly at high doses. Dietary PSE intervention obviously alleviated the lipid metabolism disorder in ApoE-/- mice by reducing the serum TC and LDL-C contents and increasing the HDL-C content. In addition, PSE intervention significantly decreased the level of pro-inflammatory cytokines TNF-α and IL-6 and increased that of anti-inflammatory IL-10, thus exhibiting a significant anti-inflammatory effect. More interestingly, analysis of the 16S rRNA gene sequence revealed that PSE could significantly alter the community composition of the gut microbiota. Specifically, PSE enhanced the abundance of Roseburia, Rothia, Parabacteroides and Akkermansia, and reduced that of Bilophila and Alistipes. Some of these intestinal bacteria exhibited good anti-inflammatory effects, which are related to the production of short chain fatty acids. Thus, the anti-atherosclerotic effect of PSE may be partly attributed to changes in the composition and function of gut microbiota, which may be closely associated with its anti-inflammatory effect. Moreover, untargeted metabolomics analysis indicated that PSE could regulate the levels of differential metabolites in the liver, serum and fecal samples.

Restorative Effects of Inulin From Codonopsis pilosula on Intestinal Mucosal Immunity, Anti-Inflammatory Activity and Gut Microbiota of Immunosuppressed Mice.

An inulin (CPPF), isolated from a traditional Chinese herbal medicine Codonopsis pilosula, was characterized and demonstrated with potential prebiotic activity in vitro before. Based on its non-digested feature, the intestinal mucosa and microbiota modulatory effects in vivo on immunosuppressed mice were investigated after oral administration of 200, 100 and 50 mg/kg of CPPF for 7 days. It was demonstrated that the secretions of sIgA and mucin 2 (Muc2) in ileum were improved by CPPF, and the anti-inflammatory activities in different intestine parts were revealed. The intestine before colon could be the target active position of CPPF. As a potential prebiotic substance, a gut microbiota restorative effect was also presented by mainly modulating the relative abundance of Eubacteriales, including Oscillibacter, unidentified Ruminococcus and Lachnospiraceae after high-throughput pyrosequencing of V4 region of 16S rRNA analysis. All these results indicated that this main bioactive ingredient inulin from C. pilosula was a medicinal prebiotic with enhancing mucosal immune, anti-inflammatory and microbiota modulatory activities.

Characterization of an antioxidant pectic polysaccharide from Platycodon grandiflorus.

Platycodonis Radix is widely used as homology of medicine and food in China; polysaccharides are thought to be one of its functional constituents. In this study, a pectic polysaccharide, PGP-I-I, was obtained from the root of the traditional medicine plant Platycodon grandiflorus through ion exchange chromatography and gel filtration. This was characterized being mainly composed of 1,5-α-L-arabinan and both arabinogalactan type I (AG-I) and II chains linked to rhamnogalacturonan I (RG-I) backbone linked to longer galacturonan chains. In vitro bioactivity study showed that PGP-I-I could restore the intestinal cellular antioxidant defense under the condition of hydrogen peroxide (H2O2) treatment through promoting the expressions of cellular antioxidant genes and protect against oxidative damages.

Effects of different types of microbial inoculants on available nitrogen and phosphorus, soil microbial community, and wheat growth in high-P soil.

Irrational application of chemical fertilizers causes soil nutrient imbalance, reduced microbial diversity, soil diseases, and other soil quality problems and is one of the main sources of non-point pollution. The application of microbial inoculant (MI) can improve the soil environment and crop growth to reduce problems caused by irrational application of chemical fertilizers. Field experiments were carried out in high-phosphorus soils to study the effects of the addition of various MIs combined with chemical fertilizers on soil properties, wheat growth, and soil microbial composition and structure. The MIs consisted of one fungal agent: Trichoderma compound agent (TC) and five bacterial agents, namely soil remediation agent (SR), anti-repeat microbial agent (AM), microbial agent (MA), plant growth-promoting rhizobacteria (PG), and biological fertilizer agent (BF). The wheat yield increased by 15.2-33.4% with the addition of MIs, and PG with Bacillus subtilis as the core microorganism had the most obvious effect on increasing the production (p < 0.05). For the entire growth period of wheat, all MIs applied significantly increased the available nitrogen (AN) (p < 0.05) but did not significantly affect the available phosphorus (AP). BF has the best effect on increasing AN in the soil. The 16S rRNA sequencing results indicated that the dominant phyla of soil bacteria were Proteobacteria, Acidobacteria, Bacteroidetes, Actinobacteria, and Verrucomicrobia. The addition of MIs increased the relative abundance of Acidobacteria, Actinobacteria, Chloroflexi and decreased Proteobacteria and Bacteroidetes. The diversity of soil bacterial community (Chao1) was significantly higher in the soil added with TC than that added with BF (p < 0.05). All bacterial agents significantly enriched various genera (p < 0.05), while the fungal agent (TC) did not enrich the genera significantly. pH and AN, but not TP, were closely related to the dominant bacteria phylum in high-P soil. The application of MIs improved AN in soil, increased the wheat yield, and changed the relative abundance of the soil dominant phylum, and these changes were closely related to the type of MIs. The results provide a scientific basis for rational use of different types of MIs in high-P soil.

Characterization of inulin-type fructans from two species of Radix Codonopsis and their oxidative defense activation and prebiotic activities.

BACKGROUND: Codonopsis pilosula and C. tangshen are both plants widely used in traditional Chinese medicine. Polysaccharides, which are their primary active components, are thought to be important in their extensive use. In this study, two neutral polysaccharide fractions of C. pilosula (CPPN) and C. tangshen (CTPN) were obtained by fractionation on a DEAE-Sepharose column and characterized. RESULTS: It was confirmed that the neutral polymers CPPN and CTPN were ß-(2,1)-linked inulin-type fructans with non-reducing terminal glucose, and degree of polymerization (DP) of 19.6 and 25.2, respectively. The antioxidant and prebiotic activities in vitro were assayed based on IPEC-J2 cell lines and five strains of Lactobacillus. Results indicated that the effects of CPPN and CTPN were increased antioxidant defense in intestinal epithelial cells through enhanced cell viability, improved expression of total antioxidant capacity, glutathione peroxidase, superoxide dismutase and catalase, and reduced levels of malondialdehyde and lactic dehydrogenase. The prebiotic activity of CPPN and CTPN was demonstrated by the promoting effect on Lactobacillus proliferation in vitro. The different biological activities obtained between the two fractions are probably due to the different DP and thus molecular weights of CPPN and CTPN. CONCLUSION: The inulin fractions from C. pilosula and C. tangshen were natural sources of potential intestinal antioxidants as well as prebiotics, which will be valuable in further studies and new applications of inulin-containing health products. © 2020 Society of Chemical Industry.

Anticoccidial effect of Fructus Meliae toosendan extract against Eimeria tenella.

CONTEXT: Fructus Meliae toosendan extracts (FMTE) have a good therapeutic effect on coccidiosis, but there is no relevant research on its prophylactic effect on coccidiosis. OBJECTIVE: This study comprehensively evaluates the anticoccidial effect of FMTE. MATERIALS AND METHODS: In vitro, the unsporulated oocysts were treated with serial dilutions of FMTE and incubated for 7 d, and the sporulated oocysts were counted for calculating the median lethal concentration (LC50) of FMTE. In vivo, 180 10-day-old broiler chickens free of coccidiosis were weighted and randomly distributed into six groups: normal group, untreated group, 4 protective groups (positive group and three FMTE groups). From day 10 to day 21, chickens in the three FMTE groups were pre-treated with FMTE at the dosage of 2.5, 5 and 10 g/kg/d, respectively, and chickens in the positive group were pre-treated with qiuliling (10 g/kg/d). On day 14, chickens in all groups except the normal group were orally infected with 1.5 × 104 sporulated oocysts. The clinical symptoms were observed from day 10 to day 21, the anticoccidial index (ACI), tissue lesions, and intestinal microflora were determined on day 21. RESULTS: FMTE showed anti-sporulation effect against E. tenella and the LC50 value was 245.83 µg/mL in vitro. In vivo, FMTE at the dosage of 10 g/kg/d was effective against E. tenella infection, and its ACI value was 162.56, which was higher than the value of positive drug qiuliling (128.81). Discussion and conclusions: FMTE have potent anticoccidial effects, and it presents an alternative anticoccidial agent for avian coccidiosis control.

A Polysaccharide Isolated from Codonopsis pilosula with Immunomodulation Effects Both In Vitro and In Vivo.

In this study, an acidic polysaccharide from Codonopsis pilosula Nannf. var. modesta (Nannf.) L. T. Shen (WCP-I) and its main fragment, WCP-Ia, obtained after pectinase digestion, were structurally elucidated and found to consist of a rhamnogalacturonan I (RG-I) region containing both arabinogalactan type I (AG-I) and type II (AG-II) as sidechains. They both expressed immunomodulating activity against Peyer's patch cells. Endo-1,4-ß-galactanase degradation gave a decrease of interleukine 6 (IL-6) production compared with native WCP-I and WCP-Ia, but exo-α-l-arabinofuranosidase digestion showed no changes in activity. This demonstrated that the stimulation activity partly disappeared with removal of ß-d-(1→4)-galactan chains, proving that the AG-I side chain plays an important role in immunoregulation activity. WCP-Ia had a better promotion effect than WCP-I in vivo, shown through an increased spleen index, higher concentrations of IL-6, transforming growth factor-ß (TGF-ß), and tumor necrosis factor-α (TNF-α) in serum, and a slight increment in the secretory immunoglobulin A (sIgA) and CD4+/CD8+ T lymphocyte ratio. These results suggest that ß-d-(1→4)-galactan-containing chains in WCP-I play an essential role in the expression of immunomodulating activity. Combining all the results in this and previous studies, the intestinal immune system might be the target site of WCP-Ia.

Modification, Antitumor Activity, and Targeted PPARγ Study of 18ß-Glycyrrhetinic Acid, an Important Active Ingredient of Licorice.

Licorice is a traditional Chinese medicine, which is often used as sweetener and cosmetic ingredients in food and pharmaceutical industries. Among them, glycyrrhetic acid is one of the most important agents. Studies have shown that glycyrrhetic acid exhibited antitumor activities as PPARγ agonist. However, the limited number of PPARγ glycyrrhetinic agonists and their high toxicity greatly limit the design based on the structure. Therefore, clarifying the binding mode between PPARγ and small molecules, we focused on the introduction of a natural active piperazine skeleton in the position of glycyrrhetinic acid C-3. According to the Combination Principle and the Structure-Based Drug Design, 19 glycyrrhetic acid derivatives were designed and synthesized as potential PPARγ agonists. Compounds 4c and 4q were screened as high-efficiency and low-toxicity lead compounds.

Effect of copper nanoparticles on brain cytochrome P450 enzymes in rats.

The aim of the present study was to evaluate the long­term effect of copper nanoparticles (CuNPs) on cytochrome P450 (CYP450) enzymes in the rat brain. Rats were repeatedly gavaged with different forms of copper sources for 28 days, and the levels of oxidative stress and CYP450 mRNA and protein expression in the rat brain were subsequently analyzed. The results demonstrated that a high dose of CuNPs (200 mg/kg) induced severe oxidative stress in the rat brain along with a decrease in the levels of total superoxide dismutase and glutathione, and an increase in hydroxyl radicals and malondialdehyde. A medium dose of CuNPs reduced CYP450 2C11 and CYP450 3A1 protein expression in the rat brain, whereas high doses of CuNPs resulted in decreased expression of most CYP450 enzyme proteins, and inhibition of pregnane X receptor and constitutive androstane receptor expression. The results suggested that CuNPs may inhibit CYP450 enzyme expression by increasing the levels of oxidative stress and decreasing the expression of nuclear receptors in the rat brain, which affects the metabolism of drugs and endogenous hormones in the brain.

A new approach to examining the extraction process of Zhishi and Zhiqiao considering the synergistic effect of complex mixtures by PAMPA.

Zhishi (ZS) and Zhiqiao (ZQ) are two important traditional Chinese medicines (TCMs) that exert various pharmacological functions due to their active ingredients. However, the oral absorption of these ingredients requires further study. At the early drug discovery stage, the high-throughput parallel artificial membrane permeability assay (PAMPA) is one of the most frequently used to predict transcellular passive absorption in in-vitro models. This study aims to establish a new approach to examine an optimal extraction process that can take into account not only the concentration of active ingredients but also the overall absorption properties of the mixtures extracted from TCMs. A high-performance liquid chromatography triple-quadrupole mass spectrometry (HPLC-QqQ-MS/MS) method was validated for the determination of the effective permeability value (Pe) applied to the above experimental medium. The PAMPA experiment showed that certain active ingredients such as diosmin, rhoifolin, eriocitrin, narirutin, naringin, hesperidin and neohesperidin were not detected in the permeability assay of mono-constituents but were well detected and achieved a better absorption in the permeability assay of the mixture, indicating that certain unknown ingredients may act as cosolvents to improve the solubility or permeability of other ingredients. Furthermore, solid phase extraction (SPE) as an enrichment and purification process enhances absorption. In the present study, a novel in vitro approach was developed to decipher the potential role of TCMs in global absorption, and the extraction process for complex TCMs was described and systematically optimized.

Compatibility between weak gel and microorganisms in weak gel-assisted microbial enhanced oil recovery.

To investigate weak gel-assisted microbial flooding in Block Wang Long Zhuang in the Jiangsu Oilfield, the compatibility of weak gel and microbe was evaluated using laboratory experiments. Bacillus sp. W5 was isolated from the formation water in Block Wang Long Zhuang. The rate of oil degradation reached 178 mg/day, and the rate of viscosity reduction reached 75.3%. Strain W5 could produce lipopeptide with a yield of 1254 mg/L. Emulsified crude oil was dispersed in the microbial degradation system, and the average diameter of the emulsified oil particles was 18.54 µm. Bacillus sp. W5 did not affect the rheological properties of the weak gel, and the presence of the weak gel did not significantly affect bacterial reproduction (as indicated by an unchanged microbial biomass), emulsification (surface tension is 35.56 mN/m and average oil particles size is 21.38 µm), oil degradation (162 mg/day) and oil viscosity reduction (72.7%). Core-flooding experiments indicated oil recovery of 23.6% when both weak gel and Bacillus sp. W5 were injected into the system, 14.76% when only the weak gel was injected, and 9.78% with strain W5 was injected without the weak gel. The results demonstrate good compatibility between strains W5 and the weak gel and highlight the application potential of weak gel-assisted microbial flooding.