Chinese chestnut shell polyphenol extract regulates the JAK2/STAT3 pathway to alleviate high-fat diet-induced, leptin-resistant obesity in mice.

Chinese chestnut shell is a by-product of chestnut food processing and is rich in polyphenols. This study sought to investigate the effect of chestnut shell polyphenol extract (CSP) on weight loss and lipid reduction in a 12-week high-fat diet (HFD)-induced murine obesity model. CSP (300 mg per kg body weight) was administered intragastrically daily. AG490, a JAK2 protein tyrosine kinase inhibitor, was also intraperitoneally injected. The results showed that an HFD induced leptin resistance (LR). Compared to corresponding values in the HFD group, CSP treatment improved blood lipid levels, weight, and leptin levels in obese mice (p < 0.01). Additionally, CSP treatment enhanced enzyme activity by improving total antioxidant capacity, attenuating oxidative stress, and reducing fat droplet accumulation and inflammation in the liver, epididymal, and retroperitoneal adipose tissue. CSP also activated the LEPR-JAK2/STAT3-PTP1B-SOCS-3 signal transduction pathway in hypothalamus tissue and improved LR while regulating the expression of proteins related to lipid metabolism (PPARγ, FAS, and LPL) in white adipose tissue in the retroperitoneal cavity. However, the amelioration of lipid metabolism by CSP was dependent on JAK2. Molecular docking simulation further demonstrated the strong binding affinity of procyanidin C1 (-10.3983297 kcal mol-1) and procyanidin B1 (-9.12686729 kcal mol-1) to the crystal structure of JAK2. These results suggest that CSP may be used to reduce HFD-induced obesity with potential application as a functional food additive.

Hawthorn fruit extract ameliorates H2O2-induced oxidative damage in neuronal PC12 cells and prolongs the lifespan of Caenorhabditis elegans via the IIS signaling pathway.

Hawthorn (Crataegus pinnatifida) fruit has a long history of use as traditional Chinese medicine and is shown to have many health benefits including antioxidant and anti-aging. In this study, the anti-aging mechanism of hawthorn fruit extract (HFE) is predicted by network pharmacology and further verified in H2O2-induced PC12 cells and Caenorhabditis elegans. Network pharmacology predicted that the antiaging mechanism of HFE is mainly involved in phosphoinositide 3-kinase (PI3K)/AKT and the insulin/insulin-like growth factor-1 (IIS) signaling pathway. HFE significantly improved cell viability, increased superoxide dismutase, catalase, and glutathione peroxidase activity, decreased lactate dehydrogenase release, the level of reactive oxygen species (ROS), and malondialdehyde content in H2O2-induced PC12 cells (p < 0.05). HFE significantly increased the mean lifespan of C. elegans by 28.43% (100 µg mL-1) and enhanced the stress resistance to H2O2, paraquat, juglone, ultraviolet radiation, and heat shock. HFE also suppressed the accumulation of aging pigments, improved the body bending ability, increased antioxidant enzyme activities, and reduced the contents of ROS and malondialdehyde. In addition, relevant gene expression, lifespan experiments with mutant strains, and molecular docking studies supported the results that HFE might extend lifespan through the IIS signal pathway.

Blue honeysuckle extracts retarded starch digestion by inhibiting glycosidases and changing the starch structure.

Blue honeysuckle rich in anthocyanins can inhibit starch-digesting enzyme activity. This study evaluated the inhibitory effect and mechanism of blue honeysuckle extract (BHE) on glycosidases (α-amylase and α-glucosidase). BHE was a mixed glycosidase inhibitor with an IC50 of 2.36 ± 0.14 and 0.06 ± 0.01 for α-amylase and α-glucosidase, respectively. Fourier transform infrared (FTIR) spectroscopy, multi-fluorescence spectroscopy, and isothermal titration calorimetry (ITC) confirmed that BHE caused the secondary structure change and static fluorescence quenching of glycosidases, and the interaction was an enthalpy-driven exothermic reaction. Molecular docking proved that the main anthocyanin monomers in BHE interacted with glycosidases through hydrogen bonds and van der Waals forces. Moreover, BHE changed the starch structure and prevented starch from being digested by glycosidases. In vivo, BHE and starch-BHE complexes effectively slowed postprandial hyperglycemia. This research provided a theoretical basis for BHE in antidiabetic healthy food research and development.

Lonicera caerulea Berry Polyphenols Extract Alleviates Exercise Fatigue in Mice by Reducing Oxidative Stress, Inflammation, Skeletal Muscle Cell Apoptosis, and by Increasing Cell Proliferation.

Exercise fatigue can exert deleterious effects on the body. This study evaluated the effects and mechanisms by which Lonicera caerulea berry polyphenols extract (LCBP) improved the treadmill endurance of mice. Comparison was performed between the effects at 25°C and low temperatures (-5°C). Energy storage, product metabolism, and other biochemical indices were determined using vitamin C (VC) as a positive control. Co-immunoprecipitation was performed to detect the interaction between different proteins. Dietary supplementation with LCBP significantly prolonged the exhaustion time during treadmill exercise by 20.4% (25 °C) and 27.4% (-5 °C). LCBP significantly regulated the expression of antioxidant and inflammatory proteins, Bcl-2 /Bax apoptosis proteins, and the PKCα -NOx2 / Nox4 pathway proteins, and activated the expression of AMPK-PGC1α -NRF1-TFAM proteins in skeletal muscle mitochondria. The gene and protein expression of miRNA-133a/IGF-1/PI3K/Akt/mTOR in skeletal muscle cells was also activated. Molecular docking confirmed that the main components of LCBP such as cyanidin-3-glucoside, catechin, and chlorogenic acid, have strong binding affinity toward AMPKα. LCBP alleviates exercise fatigue in mice by reducing oxidative stress, inflammation, and apoptosis of skeletal muscle cells, enhances mitochondrial biosynthesis and cell proliferation, reduces fatigue, and enhances performance. These effects are also significant in a low-temperature environment (Graphical Abstract). Consequently, these results provide novel insights into the anti- fatigue roles of LCBP in exercise fatigue.

Regulatory effects of hawthorn polyphenols on hyperglycemic, inflammatory, insulin resistance responses, and alleviation of aortic injury in type 2 diabetic rats.

Hawthorn polyphenol extract (HPE) is beneficial for patients with type 2 diabetes (T2D). However, the mechanism underlying its beneficial effects remains unclear. We investigated the inhibitory effects and mechanisms of HPE on insulin resistance, inflammation, and aortic injury in T2D rats, using metformin (MF) as a positive control. High-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) was used to determine the primary polyphenols in HPE. Hematoxylin & Eosin (H&E) staining was used to evaluate pathological conditions of the skeletal muscle, liver, and aorta vessels in each group. The levels of serum and intestinal tissue oxidative stress, tumor necrosis factor α (TNF-α), and inflammatory interleukin-6 (IL-6) were also assessed. Western blotting was used to evaluate protein expression levels in the associated molecular pathway. Volatile organic compounds (VOCs) from colon contents were determined using headspace-gas chromatography-ion mobility chromatography. Our results showed that supplementation with 300 mg HPE/kg body weight over four weeks significantly improved total cholesterol (TC), total triglyceride (TG), insulin, and lipopolysaccharide (LPS) levels in diabetic rats (p < 0.01). The lesions of skeletal muscle, liver, and aorta in diabetic rats were significantly improved. HPE supplementation also significantly downregulated the inflammatory factors (IL-6, TNF-α, and MCP-1) in the liver of diabetic rats via the SIRT1/AMPK/NF-κB signaling pathway. Furthermore, HPE significantly reduced insulin resistance in T2D rats by upregulating the phosphorylation of glucose absorption protein (GLUT4) and insulin resistance-associated proteins, p-IRS1, p-AKT, and p-PI3K, in the rat liver (p < 0.01). The findings show that HPE could also alleviate aortic injury by activating SIRT1 and regulating the NF-κB and Wnt2/ß-catenin signaling pathways. Overall, the results of this study suggest that both HPE and MF have similar inhibitory effects on T2D in rats and that HPE could be used as a functional food component in the adjuvant treatment of T2D.

Cerasus humilis Cherry Polyphenol Reduces High-Fat Diet-Induced Obesity in C57BL/6 Mice by Mitigating Fat Deposition, Inflammation, and Oxidation.

This study aimed to determine the anti-obesity effects and mechanisms of Cerasus humilis polyphenol (CHP) in C57BL/6 obese mice and 3T3-L1 cells. High-performance liquid chromatography-electrospray ionization-tandem mass spectrometry was used for the qualitative and quantitative identification of CHP components. The obese mice, induced by feeding high-fat diet (HFD), were treated with CHP (250 mg/kg/day) by gavage for 12 weeks. Orlistat was gavaged at 15.6 mg/kg bw/day, as a positive control group. The analysis revealed that the main components of CHP were procyanidin B2, cyanidin-3-glucoside, and pelargonidin-3-glucoside. CHP dietary supplementation significantly reduced body weight and improved blood lipid measurements in HFD-fed mice (p < 0.01). Moreover, it inhibited mRNA expression of miR-122, Srebp-1c, and Cpt1a (p < 0.01) and reduced hepatic lipid deposition, as seen by hematoxylin and eosin staining. CHP downregulated the protein expression of PPARγ and C/EBPα in HFD-induced obese mice and inhibited adipocyte differentiation (p < 0.01). Compared with the HFD group, CHP supplementation had an obvious anti-inflammatory effect (decreased protein expression, such as TNF-α, IL-6, and MCP1), reducing leptin levels and TNF-α secretion in serum and cells (p < 0.01). CHP significantly inhibited the expression of miR-27a/b (53.3 and 29.9%, p < 0.01) in mice retroperitoneal white adipocytes, enhancing the expression of the target gene Prdm16 and significantly upregulating Sirt1 (105.5%, p < 0.01) compared with the HFD group. Moreover, CHP supplementation effectively improved oxidative stress (ROS, T-AOC, SOD, CAT, and GSH-Px) induced by HFD in obese mice (p < 0.01). Thus, CHP mitigates adipocyte differentiation, browning of white adipocytes, and reduction of inflammation and antioxidant activity to reduce obesity. Consequently, these results provide novel insights into the anti-obesity roles of CHP in HFD-induced obesity.

Protective effects of hawthorn (Crataegus pinnatifida) polyphenol extract against UVB-induced skin damage by modulating the p53 mitochondrial pathway in vitro and in vivo.

This study investigated the effect of a hawthorn polyphenol extract (HPE) on ultraviolet B (UVB)-induced damage in HaCaT cells and mice. High-performance liquid chromatography/electrospray ionization tandem mass spectrometry was used to analyze the phenolic composition of HPE. The protective effects of HPE and its main components were compared in HaCaT cells. An enzyme-linked immunosorbent assay was used to detect DNA damage (8-hydroxydeoxyguanosine levels). Flow cytometry and western blotting were used to measure the extent of apoptosis and the levels of apoptosis-related proteins, respectively. Treatment with HPE or its polyphenol components inhibited the UVB-induced damage by removing an excess of reactive oxygen species (ROS), reducing DNA damage and p53 activation, regulating the protein expression of B-cell lymphoma 2 family members toward antiapoptotic ratios, and reducing caspase activation. Similar effects were observed in a UVB-irradiated mouse skin, as detected using terminal deoxynucleotidyl transferase dUTP nick-end labeling, immunohistochemistry, and western blotting assays. These results suggest that HPE can be used as a natural dietary supplement for the prevention and treatment of UVB radiation-induced skin damage. PRACTICAL APPLICATIONS: Hawthorn (Crataegus pinnatifida) shows antioxidant, anti-inflammatory, and lipid-lowering effects. As natural, healthy, and effective additives, HPEs have been widely used in food and health products. The results of this study reveal the molecular mechanisms underlying HPE effects, showing that HPE reverses the effects of UVB irradiation via removal of an excess of ROS and reduction of DNA damage and p53 expression in vitro and in vivo. Consequently, HPE upregulates the expression of antiapoptotic BCL-2 and downregulates that of proapoptotic BAX, thereby reducing the activation of caspase-3/9 and inhibiting apoptosis. These findings suggest that HPE can be used as the base ingredient for antiphotoaging food products. This study provides both theoretical and experimental background for hawthorn deep processing and utilization.

Hawthorn Polyphenol Extract Inhibits UVB-Induced Skin Photoaging by Regulating MMP Expression and Type I Procollagen Production in Mice.

Ultraviolet (UV) B radiation can cause skin aging by increasing matrix metalloproteinase (MMP) production and collagen degradation, leading to the formation of wrinkles. This study investigated whether hawthorn polyphenol extract (HPE) protects against UVB-induced skin photoaging using HaCaT human keratinocytes, normal human dermal fibroblasts (HDFs), and mice. Analysis of the phenol composition of HPE by high-performance liquid chromatography-mass spectrometry showed that chlorogenic acid (13.5%), procyanidin B2 (19.2%), and epicatechin (18.8%) collectively accounted for 51.4% of total phenol content and represent the active ingredients of hawthorn fruit. A cell viability assay revealed that HPE treatment promoted cell proliferation in HaCaT cells and HDFs. On the other hand, MMP-1 and type I procollagen production was decreased and increased, respectively, in UVB-exposed cells treated with HPE as compared with those without treatment, as determined by enzyme-linked immunosorbent assay. Hematoxylin and eosin and Weigert staining of dermal tissue specimens from mice demonstrated that HPE also reversed UVB-induced epidermal thickening and dermal damage. The increase in production of reactive oxygen species and decrease in antioxidant enzyme activity as well as the increase in nuclear factor-κB activation and mitogen-activated protein kinase phosphorylation induced by UVB irradiation were reversed by HPE (100 or 300 mg/kg body weight), which also suppressed MMP expression and stimulated the production of type I procollagen in the dorsal skin of UVB-irradiated mice. These results suggest that HPE is a natural product that can prevent UVB radiation-induced skin photoaging.

Wild Lonicera caerulea berry polyphenol extract reduces cholesterol accumulation and enhances antioxidant capacity in vitro and in vivo.

The hypocholesterolemic effect of Lonicera caerulea berry extract rich in polyphenols (LCBP) on high cholesterol-induced hypercholesterolemia and lipoprotein metabolite changes was examined in Caco-2 cells and rats. Cyanidin-3-glucoside, catechin, and chlorogenic acid are the major phenolic components of LCBP. The cholesterol-reducing effect and antioxidant capacity of these components were compared in Caco-2 cells. LCBP (80 µg/mL) and cyanidin-3-glucoside, catechin, and chlorogenic acid (50 µM) were found to be effective (p < 0.05). Rats were fed a high cholesterol diet (HCD) with or without LCBP supplementation (75, 150, and 300 mg/kg body weight intragastrically once daily) for 12 weeks. Compared with the HCD control group, LCBP supplementation at 150 and 300 mg/kg decreased the levels of TC, TG, and LDL-C, but increased that of HDL-C. LCBP treatment promoted greater neutral and acidic sterol excretion (p < 0.05) and improved the antioxidant capacity of the colon tissue, colon contents, and blood. Moreover, trimethylamine N-oxide (TMAO) levels were decreased in serum (p < 0.05). NPC1L1, ACAT2, and MTP mRNA and protein expression were reduced and ABCG5/8 expression was increased (p < 0.05) after LCBP treatment. Our results suggest that LCBP could be used as a functional food for the prevention and treatment of diseases related to excessive cholesterol accumulation.

Chicory inulin ameliorates type 2 diabetes mellitus and suppresses JNK and MAPK pathways in vivo and in vitro.

SCOPE: Chicory inulin is a naturally occurring fructan that is conducive to glucose and lipid metabolism in patients with diabetes mellitus. This study aims to investigate the mechanism by which chicory inulin improves glucolipid metabolism in diabetic conditions. METHODS AND RESULTS: Rats were injected with streptozotocin and fed with high fat diet to induce diabetes, and then administrated with different doses of chicory inulin for 8 weeks. The glycometabolism and lipid metabolism parameters were determined, the activity of insulin receptor substrate (IRS) and mitogen-activated protein kinase (MAPK) pathways were examined by western blot. The effect of chicory inulin on glucose uptake of myoblast and hepatocyte were also measured in vitro. Data were analyzed by student's t-test or one-way analysis of variance followed by the Bonferroni post-hoc testing. The results showed that chicory inulin improved glucolipid metabolism, and it activated IRS but suppressed the MAPK pathways in vivo and in vitro. CONCLUSION: Our study demonstrates that chicory inulin, as a nutritional supplement, may be beneficial for the patients with type 2 diabetes mellitus, and the metabolism-modulatory effect seems to be related with the inhibition of JNK and P38 MAPK pathways.

Effects of pretreatments on anthocyanin composition, phenolics contents and antioxidant capacities during fermentation of hawthorn (Crataegus pinnatifida) drink.

The effect of microwave and heat pretreatment on the content and composition of anthocyanins, phenolics, and the antioxidant capacity of hawthorn drink were studied. Nine anthocyanins were isolated by chromatographic separation from the Zirou hawthorn source and their structure identified using HPLC-DAD-ESI/MS analysis. Heat and microwave pretreatments had a significant impact on the relative contents of hawthorn anthocyanins, such as cyanidin-3-galactoside (82.9% and 76.9%, respectively) and cyanidin-3-glucoside (9.2% and 11.5%, respectively). Pretreatment had no significant effect on pH, total soluble solid or total acid. More anthocyanins remained after heat treatment than after microwaving (0.745mg/100mL), and were 52.4% higher than the control group after storage for 7days. The colour density of the heat treated group was higher than the control group (24.5%) after 12days of fermentation. The main antioxidant capacities of the hawthorn drinks came from total polyphenolics rather than total anthocyanins or total flavonoids.

Comparison of polyphenol, anthocyanin and antioxidant capacity in four varieties of Lonicera caerulea berry extracts.

Four varieties of Lonicera caerulea berries--'Wild', 'Beilei', 'No. 1', and 'No. 2'--were compared with respect to extraction yield, fruit weight, total soluble solids, polyphenol and anthocyanin contents, oxygen radical absorbance capacity (ORAC), and anthocyanin composition. Sixteen individual anthocyanins were identified in the selected varieties. Acylated anthocyanins, cyanidin 3-acetylhexoside and peonidin 3-acetylhexoside, were identified in L. caerulea berries for the first time. Cyanidin-3-glucoside was the most prominent anthocyanin in all four tested varieties. Wild type of L. caerulea fruit ('Wild'), with the highest polyphenol content, contained 14 anthocyanins and the highest ORAC value. Eleven anthocyanins were found in 'Beilei' berries, which had a higher ORAC value than 'No. 1' and 'No. 2'. The highest total soluble solid content and extraction yield were found in 'No. 2' and 'Wild' berries, respectively.

[Clinical study of feiyanqing rectum condensed liquid in treating 36 cases of children syncytial viral pneumonia].

OBJECTIVE: To evaluate the clinical efficacy and mechanism of Feiyangqin Rectum Condensed Liquid (FRCL) in treating children syncytial viral pneumonia. Methods Seventy-two patients were randomly divided into two groups, the 36 patients in the treated group were treated with FRCL, and the other 36 patients in the control group simply treated with Western medicine. Efficacy of treatment on clinical condition and some immune function (IgA, IgG, CD3, CD4) were observed. RESULTS: In the treated group, 28 patients were cured (77.8%), treatment was markedly effective in 4 patients (11.1%), effective in 2 (5.5%) and ineffective in 2 (5.6%), with the total effective rate of 94.4%. The corresponding number in the control group was 20 (55.6%), 7 (19.4%), 6 (16.7%), 3 (8.3%) and 91.7%, respectively. The cure rate in the treated group was obviously superior to that in the control group (P < 0.05). FRCL could improve serum IgA, IgG, CD3, CD4, and CD4/CD8, lower serum IgE, these indexes in the treated group were significantly different to those in the control group (P < 0.05). CONCLUSION: FRCL had the action in treating children syncytial viral pneumonia without any adverse reaction, one of its mechanisms might be related to its regulation on immune function.

Establishing the rDNA IGS structure of Cannabis sativa.

The rDNA intergenic spacer (IGS) structure of Cannabis sativa was established and can be used for classification and identification of this species. In this study, DNA fragments of rDNA IGS were amplified by PCR from Cannabis sativa plant extracts and a 1387 bp fragment was obtained. DNA sequence analysis revealed six different repeat motifs. In the middle of the IGS sequence, there were three sequence motifs, and the same three sections of DNA were then repeated with minor variation in sequence. The terminal region of the IGS was composed of another three different repeat units; multiple copies of these terminal repeat motifs were present in no discernible order. Within six repeat motifs, point variations were observed in five. The DNA sequence of the locus was compared with all the plant sequences registered in GenBank by the Fasta program of GCG software with the result that this DNA fragment was significantly different from any other DNA sequence recorded to date. The most similar sequence was that of Hops (Humulus lupulus), but with a similarity of only 88.9% over 579 bp. These specific and complex variations of IGS may be related to the species and geographic distributions.