Smilax China L. polysaccharide prevents HFD induced-NAFLD by regulating hepatic fat metabolism and gut microbiota.

BACKGROUND: The increasing incidence of nonalcoholic fatty liver disease (NAFLD) has urged the development of new therapeutics. NAFLD is intimately linked to gut microbiota due to the hepatic portal system, and utilizing natural polysaccharides as prebiotics has become a prospective strategy for preventing NAFLD. Smilax china L. polysaccharide (SCP) possesses excellent hepatoprotective and anti-inflammatory activity. However, its protective effects on NAFLD remains unclear. PURPOSE: The goal of this study was to explore the protective effects of SCP on high-fat diet (HFD)-induced NAFLD mice by regulating hepatic fat metabolism and gut microbiota. METHODS: Extraction and isolation from Smilax china L. rhizome to obtain SCP. C57BL/6 J mice were distributed to six groups: Control (normal chow diet), HFD-fed mice were assigned to HFD, simvastatin (SVT), and low-, medium-, high-doses of SCP for 12 weeks. The body, liver, and different adipose tissues weights were detected, and lipids in serum and liver were assessed. RT-PCR and Western blot were used to detect the hepatic fat metabolism-related genes and proteins. Gut microbiota of cecum contents was profiled through 16S rRNA gene sequencing. RESULTS: SCP effectively reversed HFD-induced increase weights of body, liver, and different adipose tissues. Lipid levels of serum and liver were also significantly reduced after SCP intervention. According to the results of RT-PCR and western blot analysis, SCP treatment up-regulated the genes and proteins related to lipolysis were up-regulated, while lipogenesis-related genes and proteins were down-regulated. Furthermore, the HFD-induced dysbiosis of intestinal microbiota was similarly repaired by SCP intervention, including enriching beneficial bacteria and depleting harmful bacteria. CONCLUSION: SCP could effectively prevent HFD-induced NAFLD, might be considered as a prebiotic agent due to its excellent effects on altering hepatic fat metabolism and maintaining gut microbiota homeostasis.

Enhancement of hepatoprotective activity of limonin from citrus seeds against acetaminophen-induced liver injury by HSCCC purification and liposomal encapsulation.

Limonin is a natural tetracyclic triterpenoid compound in citrus seeds that presents hepatoprotective effects but is often discarded as agricultural waste because of its low content and low solubility. Herein, limonin with high purity (98.11%) from citrus seeds was obtained via purification by high-speed counter-current chromatography (HSCCC) and recrystallization. Limonin-loaded liposomes (Lip-LM) prepared by thin film hydration and high pressure homogenization method to enhance its solubility and hepatoprotective effect on APAP-induced liver injury (AILI). Lip-LM appeared as lipid nanoparticles under a transmission electron microscope, and showed well dispersed nano-scale size (69.04 ± 0.42 nm), high encapsulation efficiency (93.67% ± 2.51%), sustained release, fine stability. Lip-LM also exhibited significantly better hepatoprotective activity on AILI than free limonin in vivo. In summary, Lip-LM might be used as a potential hepatoprotective agent in the form of dietary supplement and provide an effective strategy to improve the potential value of citrus seeds.

Dictamnine Ameliorates DNFB-Induced Atopic Dermatitis Like Skin Lesions in Mice by Inhibiting M1 Macrophage Polarization and Promoting Autophagy.

Autophagy and M1 macrophage polarization play important roles in the regulation of inflammation in atopic dermatitis (AD). Dictamnine is one of the main ingredients in Cortex Dictamni, a widely used traditional Chinese medicine for the treatment of dermatitis. In the present study, we investigated the anti-inflammatory effects of dictamnine on AD like skin lesions and M1 macrophage polarization. A 2,4-dinitrofluorobenzene (DNFB) triggered AD like skin lesions models in mice was established to identify the ameliorative effects of dictamnine on AD in vivo. In addition, an M1 macrophage polarization model was co-stimulated by lipopolysaccharide (LPS) and interferon-γ (IFN-γ) using phorbol myristate acetate (PMA) differentiated THP-1 cells, to investigate the effect of dictamnine on promoting autophagy and inhibiting inflammatory factor release. Dictamnine suppressed DNFB-induced skin inflammation by inhibiting M1 macrophage polarization, up-regulating the expression of microtubule-associated protein 1A/1B-light chain 3 (LC3) expression, and promoting macrophage autophagy at inflammatory sites. Dictamnine also could reduce the release of interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and interleukin-8 (IL-8), and down-regulate the mRNA expression of these genes in LPS-IFN-γ triggered M1 polarized macrophages. Dictamnine ameliorates AD like skin lesions by inhibiting M1 macrophage polarization and promoting autophagy. Hence, dictamnine is expected to be a potential therapeutic candidate for AD.

Alpha-linolenic acid improves nasal mucosa epithelial barrier function in allergic rhinitis by arresting CD4+ T cell differentiation via IL-4Rα-JAK2-STAT3 pathway.

BACKGROUND: Allergic rhinitis (AR) defined as inflammation and tissue remodeling of the nasal mucosa in atopic individuals after allergen exposure. Alpha-linolenic acid [cis-9, cis-12, cis-15-octadecatrienoic acid (18:3)] (ALA) as dietary supplementation can reduce inflammation and allergic symptoms. OBJECTIVE: To evaluate the potential therapeutic effect and mechanism of ALA in AR mouse model. METHODS: Ovalbumin sensitized AR mouse model were challenged with oral ALA administration. Nasal symptoms, tissue pathology, immune cell infiltration and goblet cell hyperplasia were investigated. Levels of IgE, TNF-ß, IFN-γ, IL-2, IL-4, IL-5, IL-12, IL-13 and IL-25 were determined by ELISA in serum and nasal fluid. Quantitative RT-PCR and immunofluorescence were performed for occludin and zonula occludens-1 expression. CD3+CD4+ T-cells from peripheral blood and splenic lymphocytes were isolated and Th1/Th2 ratio were determined. Mouse naive CD4+ T cell were isolated and Th1/Th2 ratio, IL-4Rα expression, and IL5/IL13 secretion were determined. IL-4Rα-JAK2-STAT3 pathway change in AR mice were performed by western blot. RESULTS: Ovalbumin induced AR, nasal symptoms, pathological performance, IgE, and cytokine production. ALA treated mice showed reduced nasal symptoms, nasal inflammation, nasal septum thickening, goblet cell hyperplasia, and eosinophil infiltration. In serum and nasal fluid of ovalbumin challenged mice, ALA decreased IgE, IL-4 levels, and the increase of Th2-cells. ALA prevented the disruption of the epithelial cell barrier in ovalbumin-challenged AR mice. Simultaneously, ALA prevents IL-4 induced barrier disruption. ALA treatment of AR by affecting the differentiation stage of CD4+T cells and block IL-4Rα-JAK2-STAT3 pathway. CONCLUSION: This study suggests that ALA has the potential therapeutic effect to ovalbumin-induced AR. ALA can affect the differentiation stage of CD4+T cells and improve epithelial barrier functions through IL-4Rα-JAK2-STAT3 pathways. CLINICAL IMPLICATION: ALA might be considered as drug candidate for improving epithelial barrier function through Th1/Th2 ratio recovery in AR.

Silibinin attenuated pseudo-allergic reactions and mast cell degranulation via PLCγ and PI3K/Akt signaling pathway.

Anaphylaxis is a type of potentially fatal hypersensitivity reaction resulting from the activation of mast cells. Many endogenous or exogenous factors could cause this reaction. Silibinin is the main chemical component of silymarin and has been reported to have pharmacological activities. However, the anti-allergic reaction effect of silibinin has not yet been investigated. This study aimed to evaluate the effect of silibinin to attenuate pseudo-allergic reactions in vivo and to investigate the underlying mechanism in vitro. In this study, calcium imaging was used to assess Ca2+ mobilization. The levels of cytokines and chemokines, released by stimulated mast cells, were measured using enzyme immunoassay kits. The activity of silibinin was evaluated in a mouse model of passive cutaneous anaphylaxis (PCA). Western blotting was used to explore the related molecular signaling pathways. In results, silibinin markedly inhibited mast cell degranulation, calcium mobilization, and preventing the release of cytokines and chemokines in a dose-dependent manner via the PLCγ and PI3K/Akt signaling pathway. Silibinin also attenuated PCA in a dose-dependent manner. In summary, silibinin has an anti-pseudo-allergic pharmacological activity, which makes it a potential candidate for the development of a novel agent to arrest pseudo-allergic reactions.

Progress of research on the role of active ingredients of Citri Reticulatae Pericarpium in liver injury.

BACKGROUND: Liver is a vital organ responsible for metabolizing and detoxifying both endogenous and exogenous substances in the body. However, it is susceptible to damage from chemical and natural toxins. The high incidence and mortality rates of liver disease and its associated complications impose a significant economic burden and survival pressure on patients and their families. Various liver diseases exist, including cholestasis, viral and non-viral hepatitis, fatty liver disease, drug-induced liver injury, alcoholic liver injury, and severe end-stage liver diseases such as cirrhosis, hepatocellular carcinoma (HCC), and cholangiocellular carcinoma (CCA). Recent research has shown that flavonoids found in Citri Reticulatae Pericarpium (CRP) have the potential to normalize blood glucose, cholesterol levels, and liver lipid levels. Additionally, these flavonoids exhibit anti-inflammatory properties, prevent oxidation and lipid peroxidation, and reduce liver toxicity, thereby preventing liver injury. Given these promising findings, it is essential to explore the potential of active components in CRP for developing new drugs to treat liver diseases. OBJECTIVE: Recent studies have revealed that flavonoids, including hesperidin (HD), hesperetin (HT), naringenin (NIN), nobiletin (NOB), naringin (NRG), tangerine (TN), and erodcyol (ED), are the primary bioactive components in CRP. These flavonoids exhibit various therapeutic effects on liver injury, including anti-oxidative stress, anti-cytotoxicity, anti-inflammatory, anti-fibrosis, and anti-tumor mechanisms. In this review, we have summarized the research progress on the hepatoprotective effects of HD, HT, NIN, NOB, NRG, TN, ED and limonene (LIM), highlighting their underlying molecular mechanisms. Despite their promising effects, the current clinical application of these active ingredients in CRP has some limitations. Therefore, further studies are needed to explore the full potential of these flavonoids and develop new therapeutic strategies for liver diseases. METHODS: For this review, we conducted a systematic search of three databases (ScienceNet, PubMed, and Science Direct) up to July 2022, using the search terms "CRP active ingredient," "liver injury," and "flavonoids." The search data followed the PRISMA standard. RESULTS: Our findings indicate that flavonoids found in CRP can effectively reduce drug-induced liver injury, alcoholic liver injury, and non-alcoholic liver injury. These therapeutic effects are mainly attributed to the ability of flavonoids to improve liver resistance to oxidative stress and inflammation while normalizing cholesterol and liver lipid levels by exhibiting anti-free radical and anti-lipid peroxidation properties. CONCLUSION: Our review provides new insights into the potential of active components in CRP for preventing and treating liver injury by regulating various molecular targets within different cell signaling pathways. This information can aid in the development of novel therapeutic strategies for liver disease.

Resveratrol-loaded selenium/chitosan nano-flowers alleviate glucolipid metabolism disorder-associated cognitive impairment in Alzheimer's disease.

Resveratrol (Res) is a common natural polyphenol that inhibits inflammation and oxidative stress in Alzheimer's disease (AD). However, the absorption efficiency and in vivo bioactivity of Res are poor. High fat diet-induced metabolic disorders, including obesity and insulin resistance, can promote AD-related ß-amyloid (Aß) aggregation, Tau protein phosphorylation and neurotoxicity. Gut microbiota play a role in modulating metabolic syndrome and cognitive impairment. Herein, flower-like Res-loaded selenium nanoparticles/chitosan nanoparticles (Res@SeNPs@Res-CS-NPs) with higher loading capacity (64 %) were prepared to regulate gut microbiota in cases of AD with metabolic disorder. The nano-flowers could restore gut microbiota homeostasis to reduce lipopolysaccharide (LPS) formation and LPS-induced neuroinflammation. Additionally, Res@SeNPs@Res-CS-NPs can prevent lipid deposition and insulin resistance by decreasing Firmicutes levels and increasing Bacteroidetes levels in the gut, further inhibiting Aß aggregation and Tau protein phosphorylation through the JNK/AKT/GSK3ß signaling pathway. Moreover, Res@SeNPs@Res-CS-NPs treatment was able to regulate the relative levels of gut microbiota associated with oxidative stress, inflammation and lipid deposition, including Entercoccus, Colidextribacter, Rikenella, Ruminococcus, Candidatus_Saccharimonas, Alloprevotella and Lachnospiraceae_UCG-006. Overall, Res@SeNPs@Res-CS-NPs significantly enhances cognitive ability in AD mice with metabolic disorder, highlighting their potential for preventing cognitive impairments in AD.

Identification of the Constituents of Ethyl Acetate Fraction from Smilax china L. and Determination of Xanthine Oxidase Inhibitory Properties.

The aim of this work was to investigate the xanthine oxidase (XO)-inhibitory activity of ethanol extracts from Smilax china L. and to identify the active compounds in the ethyl acetate (EtOAc) fraction. Extraction of ethanol extracts from Smilax china L. and then ethanol extracts were concentrated, and the polyphenolic compounds were extracted with petroleum ether (PE), chloroform, EtOAc, n-butanol (n-BuOH), and residual ethanol fractions. Their effects on XO activity were then compared separately. The polyphenolic components of the EtOAc fraction were identified by HPLC and HPLC-mass spectrometry (HPLC-MS) analysis. Kinetic analysis demonstrated that all these extracts showed XO-inhibitory properties, and among them the EtOAc fraction had the strongest inhibitory effect (IC50 = 101.04 µg/mL). The inhibitory constant (Ki) of the EtOAc fraction on XO activity was 65.20 µg/mL, showing excellent inhibition on XO in the competitive mode. Sixteen compounds were identified from the EtOAc fraction. The study demonstrates that the EtOAc fraction of Smilax china L. may be a potential functional food to inhibit XO activity.

Baicalin inhibits pressure overload-induced cardiac hypertrophy by regulating the SIRT3-dependent signaling pathway.

BACKGROUND: The conserved sirtuin protein sirtuin 3 (SIRT3) is a vital protective protein for cardiac hypertrophy. Inhibition of SIRT3 accelerated the development of heart hypertrophy. On the other hand, myocardial hypertrophy was prevented by overexpressing SIRT3. SIRT3 has been proposed as a potential therapeutic target for managing or averting heart hypertrophy. Baicalin, a flavonoid extracted from the Scutellaria baicalensis plant, has anti-cardiovascular properties, including protection against cardiac hypertrophy. However, the molecular mechanism of the anti-hypertrophic effect of baicalin is not well known. PURPOSE: In this study, we aim to investigate the effect of baicalin on cardiac hypertrophy and explored its underlying molecular mechanisms. STUDY-DESIGN/METHODS: Abdominal aortic constriction (AAC)-induced mouse cardiac hypertrophy and angiotensin II (Ang II)-induced cardiomyocyte hypertrophy models were established. After baicalin treatment, cardiac hypertrophy was monitored by detecting the expression of hypertrophic genes and cell surface area. Echocardiogram was performed to check the heart function in vivo. Moreover, the protein expression of the SIRT3-dependent pathway was detected by Western blotting. RESULTS: In this work, we demonstrated that baicalin might suppress the cell surface area and the expression of the Ang II -induced myosin heavy chain ß (ß-MHC), brain natriuretic polypeptide (BNP), and atrial natriuretic factor (ANF). Additionally, it reduced the AAC rats' hypertrophic impact. We also found that baicalin prevents cardiac hypertrophy by regulating SIRT3/LKB1/AMPK signaling pathway. Moreover, we showed that baicalin upregulated the SIRT3 protein expression by inhibiting proteasome and by the activation of 20 S proteasome subunit beta type-5 (PSMB5). CONCLUSION: These results offer the first proof that baicalin inhibits cardiac hypertrophy due to its effect on the SIRT3-dependent signaling pathway, indicating its potential for treating cardiac hypertrophy and heart failure. The present study provides a preliminary experimental basis for the clinical application of baicalin and baicalin-like compounds.

Smilax china L. Polyphenols Improves Insulin Resistance and Obesity in High-fat Diet-induced Mice Through IRS/AKT-AMPK and NF-κB Signaling Pathways.

Smilax china L. is an important herb used in traditional Chinese medicine. In this study, the mechanism of Smilax china L. polyphenols (SCP) on insulin resistance and anti-obesity in mice induced by a high-fat diet (HFD) was investigated. Fifty female mice were randomly divided into five groups: control, HFD and low, medium, and high doses of SCP for 70 d. SCP significantly decreased intraperitoneal adipose tissue index, body weight gain, liver lipids, and serum inflammatory factor levels. Blood glucose and insulin concentrations, as well as insulin resistance index in SCP, were significantly lower than those in HFD. In addition, SCP markedly up-regulated the gene expression of glucose transporter 4 (GLUT4), insulin receptor substrate 1 (IRS1), insulin receptor substrate 2 (IRS2), serine-threonine kinase (AKT), Acyl-CoA oxidase (ACO), and protein kinase A (PKA), and down-regulated the expression of mammalian target of rapamycin complex 1 (mTORC1), sterol-responsive element-binding protein-1c (SREBP1c), fatty acid synthase (FAS), 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR), and forkhead box protein O1 (FOXO1). SCP significantly increased the protein expression of AKT, GLUT4, AMP-activated protein kinase (AMPK), phosphorylated-AMPK (p-AMPK), phosphorylated-AKT (p-AKT), and uncoupling protein 1 (UCP-1), and decreased the expression of SREBP1c, FAS, HMGCR, phosphorylation of IKBα (p-IKBα), and nuclear factor kappa B subunit p65 (P65) in the liver. Overall, SCP effectively reduced HFD-induced insulin resistance and obesity in mice, partly through NF-κB and IRS/AKT-AMPK signaling pathways to regulate inflammatory factors. Therefore, SCP may improve lifestyle diseases.

Kazinol B protects H9c2 cardiomyocytes from hypoxia/reoxygenation-induced cardiac injury by modulating the AKT/AMPK/Nrf2 signalling pathway.

CONTEXT: Kazinol B (KB), an isoprenylated flavan derived from Broussonetia kazinoki Sieb. (Moraceae) root, has long been used in folk medicine. OBJECTIVE: This study examines the protective effects of KB and its underlying mechanisms in hypoxia and reoxygenation (H/R)-induced cardiac injury in H9c2 rat cardiac myoblasts. MATERIALS AND METHODS: H9c2 cells were incubated with various concentrations of KB (0, 0.3, 1, 3, 10 and 30 µM) for 2 h and then subjected to H/R insults. The protective effects of KB and its underlying mechanisms were explored. RESULTS: KB significantly elevated cell viability (1 µM, 1.21-fold; 3 µM, 1.36-fold, and 10 µM, 1.47-fold) and suppressed LDH release (1 µM, 0.77-fold; 3 µM, 0.68-fold, and 10 µM, 0.59-fold) in H/R-induced H9c2 cells. Further, 10 µM KB blocked apoptotic cascades, as shown by the Annexin-V/PI (0.41-fold), DNA fragmentation (0.51-fold), caspase-3 (0.52-fold), PARP activation (0.27-fold) and Bax/Bcl-2 expression (0.28-fold) assays. KB (10 µM) downregulated reactive oxygen species production (0.51-fold) and lipid peroxidation (0.48-fold); it upregulated the activities of GSH-Px (2.08-fold) and SOD (1.72-fold). KB (10 µM) induced Nrf2 nuclear accumulation (1.94-fold) and increased ARE promoter activity (2.15-fold), HO-1 expression (3.07-fold), AKT (3.07-fold) and AMPK (3.07-fold) phosphorylation. Nrf2 knockdown via using Nrf2 siRNA abrogated KB-mediated protective effects against H/R insults. Moreover, pharmacological inhibitors of AKT and AMPK also abrogated KB-induced Nrf2 activation and its protective function. DISCUSSION AND CONCLUSIONS: KB prevented H/R-induced cardiomyocyte injury via modulating the AKT and AMPK-mediated Nrf2 induction. KB might be a promising drug candidate for managing ischemic cardiac disorders.

A Flower-like Brain Targeted Selenium Nanocluster Lowers the Chlorogenic Acid Dose for Ameliorating Cognitive Impairment in APP/PS1 Mice.

Aß aggregation-related neuroinflammation and imbalance of brain glucose homeostasis play important roles in the pathological process of Alzheimer's disease (AD). Chlorogenic acid (CGA) is one of the most common dietary polyphenols with neuroprotective effects. However, due to the low bioavailability of CGA, its application dose is usually high in vivo. In our previous study, the spherical selenium nanoparticles act as drug carriers to improve the bioactivity of resveratrol. Here, the brain-targeting peptide (TGN peptide) and CGA were used to prepare a new flowerlike selenium nanocluster (TGN-CGA@SeNCs) for enhancing the bioavailability of CGA. After decoration on selenium nanoclusters, the solubility and stability of CGA was obviously increased. Oral administration of a low dose of CGA (80 mg/kg/body weight) only slightly inhibited Aß aggregate-related neuroinflammation and glucose homeostasis disorder in the brain. Moreover, CGA showed less effect on increasing the diversity and richness of gut microbiota. At the same concentration, the CGA-modified selenium nanocluster (CGA@SeNCs) and TGN-CGA@SeNCs showed better function in ameliorating the gut microbiota disorder. Especially, TGN-CGA@SeNCs significantly increased the relative abundance of Turicibacter, Colidextribacter, Ruminococcus, Alloprevotella, and Alistipes against oxidative stress, inflammation, and glucose homeostasis imbalance. Notably, only TGN-CGA@SeNCs can transport through the blood-brain barrier (BBB), and TGN-CGA@SeNCs showed better effects than CGA@SeNCs in regulating Aß aggregation and improving brain glucose homeostasis. These results broadened the application of TGN-CGA@SeNCs, effectively improving the bioactivity of CGA, which also lowers the CGA dose for preventing AD progression.

Myricetin alleviated immunologic contact urticaria and mast cell degranulation via the PI3K/Akt/NF-κB pathway.

Immunologic contact urticaria (ICU) is characterized by the wheal and flare reaction from direct contact with a chemical or protein agent, which involves a type I hypersensitivity mediated by allergen-specific immunoglobulin E (sIgE). Myricetin (Myr), a bioactive flavonoid, exhibits antiinflammatory activities. Our results showed that treatment with Myr could alleviate ICU symptoms, including a decrease in the number of wheals and scratching, and inhibit ear swelling in the IgE/DNFB-induced mice. The serum level of IgE, histamine, interleukin (IL)-4, TNF-α, and MCP-1 were reduced in Myr-treated mice. Myr also attenuated mast cells (MCs) degranulation and H-PGDS, TSLP, IL-33, PI3K, Akt, and NF-κB mRNA levels in ICU model. The IgE-mediated anaphylaxis mouse models demonstrated anti-allergic effects of Myr. In vitro analysis showed that Myr reduced IgE-induced calcium (Ca2+ ) influx, suppressed degranulation, and chemokine release in LAD2 cells (human primary mast cells). Myr can significantly inhibited PLCγ1, Akt, NF-κB, and p38 phosphorylation. In conclusion, the study demonstrated that Myr alleviate ICU symptoms and inhibit mast cell activation via PI3K/Akt/NF-κB signal pathway.

Smilax china Polyphenols Stimulate Browning via [Formula: see text]3-Adrenergic Receptor/AMP-Activated Protein Kinase [Formula: see text] Signaling Pathway in 3T3-L1 Adipocytes.

The aim of this study is to investigate the molecular mechanism of Smilax china L. polyphenols (SCLPs) in enhancing lipid metabolism and stimulating browning to reduce lipid accumulation in 3T3-L1 adipocytes. SCLP treatment obviously decreased lipid content in a dose-dependent manner (10-40 µg/mL) in adipocytes. SCLP treatment cooperated with noradrenalin to increase lipolysis. SCLPs reduced the gene expressions of C/EBP[Formula: see text] and Ap2 and enhanced the expressions of ACO, CPT, pHSL/HSL, ATGL, and PKA in adipocytes. Furthermore, SCLPs increased mRNA and protein expressions of brown adipocyte-specific factors (UCP-1, PRDM16, PGC-1α, and PPARγ) and mRNA expressions of beige adipocyte-specific markers (CD137, Tbx1, and Tmem26) in 3T3-L1 adipocytes, as well as mitochondrial biogenesis genes (Nrf1 and Tfam). In addition, according to the immunofluorescence staining, the mitochondria number was increased by SCLP. Moreover, ß3-AR or AMPK agonist synergistic SCLPs enhanced the expressions of UCP-1, PRDM16, and PGC-1α. While ß3-AR or AMPK antagonist significantly decreased the expressions of these brown adipocyte-specific factors, SCLP treatment inhibited the effect of antagonist to improve the expression of UCP-1, PRDM16, and PGC-1α. These results indicated that SCLPs may regulate lipid metabolism and stimulate browning via the ß3-AR/AMPKα signaling pathway. Thus, SCLPs likely have potential therapeutic effects on obesity.

Multifunctional Selenium Nanoparticles with Different Surface Modifications Ameliorate Neuroinflammation through the Gut Microbiota-NLRP3 Inflammasome-Brain Axis in APP/PS1 Mice.

Neuroinflammation plays a critical role in Alzheimer's disease (AD). However, it is still unknown if neuroinflammation can be effectively treated using selenium nanoparticles (SeNPs) with different surface modifications. In this study, SeNPs were coated with dihydromyricetin (DMY), a natural polyphenol, to obtain DMY@SeNPs. Given that DMY@SeNPs are unstable under physiological conditions, they were decorated step-by-step with chitosan (CS/DMY@SeNPs) and with the blood brain barrier (BBB) targeting peptide Tg (TGNYKALHPHNG) to yield Tg-CS/DMY@SeNPs, which significantly reduced the aggregation of Aß and improved the anti-inflammatory effects of SeNPs in vitro. The mechanisms of CS/DMY@SeNPs and Tg-CS/DMY@SeNPs on regulating neuroinflammation are different. Only Tg-CS/DMY@SeNPs can cross the BBB; therefore, Tg-CS/DMY@SeNPs more successfully inhibited Aß aggregation and reduced inflammatory cytokine secretion via the NF-κB pathway in the brain of APP/PS1 mice compared to CS/DMY@SeNPs. Furthermore, both types of nanoparticles, however, were able to repair the gut barrier and regulate the population of inflammatory-related gut microbiota such as Bifidobacterium, Dubosiella, and Desulfovibrio. Of note, the relative abundance of Gordonibacter was only enhanced by Tg-CS/DMY@SeNPs, thereby downregulating the protein expression of the NLRP3 inflammasome and the concentrations of serum inflammatory factors. This demonstrates that Tg-CS/DMY@SeNPs ameliorate neuroinflammation through the gut microbiota-NLRP3 inflammasome-brain axis. Overall, our data suggest that Tg-CS/DMY@SeNPs are an ideal drug candidate for AD treatment.

Analysis of the chemical components of pomelo peels (Citrus grandis [L.] Osbeck) from different cultivars by using supercritical CO2 fluid extraction and ultra-high-performance liquid chromatography-tandem mass spectrometry.

Five pomelo cultivars (i.e., Citrus grandis cv. Shatianyou, Citrus grandis cv. Guanximiyou, Citrus grandis cv. Yuhuanyou, Citrus grandis cv. Duweiwendanyou and Citrus grandis cv. Liangpingyou) from different origins in China were selected to analyze their components by using supercritical CO2 fluid extraction coupled with ultra-high-performance liquid chromatography-tandem mass spectrometry. A total of 45 compounds were identified in the supercritical CO2 fluid extracts of the pomelo peels from the five cultivars. These compounds included eight flavonoids, 18 coumarins, four organic acids, three aldehydes, and 12 other compounds, which were identified using the obtained MS data and by comparison with commercial standards, orbitrap Chinese Traditional Medicine Library, and previous literature. Twenty-five of the identified compounds were detected for the first time in the pomelo peel extracts. Results suggested that the pomelo peels of C. grandis cv. Shatianyou contained the most natural chemical compositions. The pooled result may offer scientific evidence for further development and utilization of pomelo peels and a route for screening appropriate varieties for various demands.

Network Pharmacology-Based Strategy for Predicting Therapy Targets of Citri Reticulatae Pericarpium on Myocardial Hypertrophy.

Objective: Through a network pharmacology method, we screened the main active compounds of Citri Reticulatae Pericarpium (CRP), constructed a drug-ingredient-disease-target network, explored the molecular mechanism of its treatment of myocardial hypertrophy, and validated it by using molecular biology approach. Methods: Traditional Chinese Medicine Systems Pharmacology (TCMSP) and GeneCards were utilised to collect the effective component in CRP and the targets of CRP and myocardial hypertrophy. The STRING database constructed the protein interaction network. The drug-ingredient-disease-target network was outlined by the Cytoscape 3.9.0 software. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using the Metascape database. Real-time PCR (RT-PCR) and Western blotting were utilised to determine the mRNA and protein level of the critical targets of CRP therapy for myocardial hypertrophy. Results: We found that five practical components of CRP exerted therapeutic effects on myocardial hypertrophy by modulating 41 targets. Further analysis revealed that naringenin was the essential active compound in CRP that regulated myocardial hypertrophy. In addition, we showed that the active compounds of CRP might exert antihypertrophy effects via regulating essential target proteins such as AKT1-, MAPK3-, PPARA-, PPARG-, and ESR1-mediated signaling pathways such as cell proliferation, nuclear receptor activation, and oxidative stress. The molecular biology experiments demonstrated that naringenin inhibited the mRNA level of NPPA and NPPB induced by Ang II and regulated related targets such as AKT1, MAPK3, PPARA, PPARG, and ESR1. Conclusion: CRP could inhibit myocardial hypertrophy through multitarget and multiapproach.

Regulating the Imbalance of Gut Microbiota by Smilax china L. Polyphenols to Alleviate Dextran Sulfate Sodium-induced Inflammatory Bowel Diseases.

Smilax china L. is used not only as a kind of traditional Chinese herbal medicinal ingredients with various pharmacological properties, but also as food in certain parts of China. However, it is by far still unclear whether Smilax china L. polyphenols (SCP), as important bioactive constituents in Smilax china L., have effects on inflammatory bowel diseases (IBD). This study investigated the impact of SCP on the dextran sulfate sodium (DSS)-induced IBD and gut microbiota in mice. SCP treatments ameliorated typical symptoms of IBD as what was reflected through suppressing body weight loss, colonic shortening, intestinal barrier damage, and increasing intestinal disease activity index. SCP treatments simultaneously decreased the release of proinflammatory cytokines and oxidative stress, as well as promoted the release of anti-inflammatory factors. Furthermore, SCP ameliorated the ecological imbalance of gut microbiota and regulated the key bacteria associated with IBD (including Akkermansiaceae, Ruminococcaceae, Acidaminococcaceae, Muribaculaceae, and Anaeroplasmataceae). In general, SCP may improve DSS-induced IBD in mice by regulating inflammatory factors, inhibiting oxidative stress, reducing intestinal tissue damage, and regulating the ecological imbalance of intestinal microbiota. Thus, SCP might serve as a potential therapeutic agent against the inflammation-driven diseases.

New insights into the sorption of U(VI) on kaolinite and illite in the presence of Aspergillus niger.

The regulation effect of Aspergillus niger to the sorption behavior of U(VI) on kaolinite and illite was studied through investigating the enrichment of U(VI) on kaolinite-Aspergillus niger and illite-Aspergillus niger composites. Kaolinite- or illite-A. niger composites were prepared through co-culturation method. Results showed that U(VI) sorption on kaolinite and illite in different pH ranges could be attributed to ion exchange, outer-sphere complexes (OSCs), and inner-sphere complexes (ISCs), while only the ISCs on the bio-composites. Moreover, micro-spectroscopy tests revealed that U(VI) coordinate with phosphate, amide, and carboxyl groups on illite- and kaolinite- A. niger composites. X-ray photoelectron spectroscopy (XPS) further found that U(VI) was partly reduced to non-crystalline U(IV) by A. niger in the bio-composites, occurring as phosphate coordination polymers or biomass-associated monomers. The findings herein provide further insight into the immobilization and migration of uranium in environments.

Smilax china L. flavonoid alleviates HFHS-induced inflammation by regulating the gut-liver axis in mice.

BACKGROUND: Smilax china L., a traditional Chinese herb, has been used to treat various inflammatory disorders, particularly pelvic inflammation. The anti-inflammatory activity of the plant extract has been reported in several in vivo experimental models. However, the underlying anti-inflammatory mechanisms and the role of gut microbiota in mice on Smilax china L. flavonoid (SCF) treatment are poorly understand. PURPOSE: To investigate the role of SCF in providing the anti-inflammatory response and the role of gut microbiota in high-fat/high-sucrose (HFHS)-induced obese mice for 12 weeks. STUDY DESIGN AND METHODS: C57BL/6J mice were randomly divided into seven groups, normal chow (NC), HFHS, Orlistat, SCE, and low-, medium-, high- doses of SCF for 12 weeks. The body weight, liver weight, serum concentrations of lipopolysaccharide (LPS), and inflammatory cytokines in mice were assessed. The gene and protein expression levels of inflammation-related markers were measured by qRT-PCR and Western blot. Finally, the composition of gut microbiota was detected by analyzing 16S rDNA gene sequences. RESULTS: SCF supplement reduced body weight gain, adipose tissue and liver indexes, attenuated serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, LPS, and increased IL-10, and adiponectin. SCF significantly reduced the mRNA expression levels of TNF-α, IL-6, and increased the expression of AMPK, PPAR-γ, and IL-10 in mice's liver and adipose tissues. In addition, the TLR4, p-IκBα, NF-κB, and p65 protein expression levels were reduced after the SCF supplement. Moreover, SCF treatment ameliorated HFHS-induced gut dysbiosis, as revealed by an increased intestinal barrier protective species (Akkermansia spp). The relative abundance of Streptococcaceae, Faecalibaculum, and endotoxin-producing Desulfovibrionaceae were significantly decreased on SCF supplements. CONCLUSION: The results showed that SCF effectively inhibits HFHS-induced inflammation by suppressing the LPS-producing bacteria and pro-inflammatory bacteria group. Furthermore, the abundance of gut barrier protective species Akkermansia spp was increased to alleviate inflammatory response, inhibiting the LPS-TLR4/NF-κB signaling pathway. Thus, SCF may be a promising prophylactic for diet-induced inflammatory diseases through the gut-liver axis in mice.