An extra honey polyphenols-rich diet ameliorates the high-fat diet induced chronic kidney disease via modulating gut microbiota in C57BL/6 mice.

Honey is not equivalent to sugar and possess a worldwide health promoting effects such as antioxidant, antibacterial, anti-inflammatory, and hepatoprotective activities. Nevertheless, the potential impacts of honey on high-fat diet induced chronic kidney disease (CKD) and gut microbiota remain to be explored. Herein a high-fat diet was used to induce a mouse CKD model, and analysis was conducted on liver, kidney, spleen indices, tissue morphology, biochemical parameters, CKD related genes, and gut microbial diversity. The results indicated that significant inhibitory effects on renal damage caused by a high-fat diet in mice and improvement in disease symptoms were observed upon honey treatment. Significant changes were also found in serum TC, TG, UA, and BUN as well as the inflammation-related protein TNF-α and IL-6 levels in renal tissues. Gene expression analysis revealed that honey intake closely relates to gut microbiota diversity, which can regulate the composition of gut microbiota, increase microbial diversity, especially Bifidobacteriales and S24_7 and promote the synthesis of short chain fatty acids (SCFAs). In summary, this study suggests that honey has both preventive and therapeutic effects on CKD, which may be associated with its ability to improve microbial composition, increase microbial diversity, and regulate SCFAs levels.

Alternative to Sugar, Honey Does Not Provoke Insulin Resistance in Rats Based on Lipid Profiles, Inflammation, and IRS/PI3K/AKT Signaling Pathways Modulation.

Insulin resistance (IR) is the central link to metabolic syndrome (MS), and IR prevention has become the key to overcoming this worldwide public health problem. A diet rich in simple sugars is an important pathogenic factor in IR development. To investigate the effect of honey on IR compared to the sugar-water diet, we analyzed phenolics and oligosaccharides in jujube honey and rape honey based on LC-MS and silane derivatization/GC-MS. The effects of different diets on glucose and lipid profile, histopathology and IR-related mechanism pathways were analyzed and compared by equal sugar levels intervention of fructose, fructose + glucose and two kinds of unifloral honey (high-/low-dose) in rats. The results suggested that sugar-equivalent honey, which differs from sugar solution, especially 17.1 g/kg BW jujube honey rich in phenolics (1.971 mg/100 g of isoquercitrin) and oligosaccharides (2.18 g/100 g of turanose), suppressed IR via maintaining glucose (OGTT and ITT) and lipid (TC, TG, LDL-C, HDL-C, and NEFA) homeostasis, improving histological structural abnormalities of the liver, adipose and skeletal muscle, reducing oxidative stress (GSH-Px and MDA) and inflammation (IL-6 and TNF-α), modulating the NF-κB (NF-κB gene expression was down-regulated to 0.94) and IRS/PI3K/AKT signaling pathways (e.g., AKT and GLUT2 expression in liver increased by 4.56 and 13.37 times, respectively) as well as reshaping the gut microbiota. These revealed a potential nutritional contribution of substituting honey for simple sugar in the diet, providing a theoretical basis for controlling IR development via dietary modification and supplementation.

Protective Mechanism of Fagopyrum esculentum Moench. Bee Pollen EtOH Extract Against Type II Diabetes in a High-Fat Diet/Streptozocin-Induced C57BL/6J Mice.

Bee pollen is known as a natural nutrient storehouse and plays a key role in many biological processes. Based on the preliminary separation, identification, and characterization of the main active components of Fagopyrum esculentum Moench. bee pollen (FBP), the protective effects of F. esculentum bee pollen extract (FBPE) on high-fat-diet (HFD) and streptozocin (STZ) induced type II diabetes mellitus (T2DM) was evaluated in this study. The results revealed that FBPE contains 10 active compounds mainly including luteolin (9.46 g/kg), resveratrol (5.25 g/kg), kaemferol (3.67 g/kg), etc. The animal experiment results showed that FBPE could improve HFD-STZ induced T2DM mice. Moreover, the underlying mechanism of the above results could be: (i) FBPE could reduce the inflammation related to phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway, and (ii) the gut microbiota remodeling. The results of correlation analysis showed Candidatus Arthromitus and SMB53 indicated positive correlations to tumor necrosis factor-α (TNF-α); Coprococcus, Ruminocossus, and Odoribacteraceae reported negative correlations to transforming growth factor-ß (TGF-ß). That FBPE has an outstanding ability to improve T2DM and could be used as a kind of potential functional food for the prevention of T2DM.

Impact of Camellia japonica Bee Pollen Polyphenols on Hyperuricemia and Gut Microbiota in Potassium Oxonate-Induced Mice.

Camellia japonica bee pollen is one of the major types of bee pollen in China and exhibits antioxidant and anti-inflammatory activities. The aims of our study were to evaluate the effects and the possible mechanism of Camellia japonica bee pollen polyphenols on the treatment of hyperuricemia induced by potassium oxonate (PO). The results showed that Camellia japonica bee pollen ethyl acetate extract (CPE-E) owned abundant phenolic compounds and strong antioxidant capabilities. Administration with CPE-E for two weeks greatly reduced serum uric acid and improved renal function. It inhibited liver xanthine oxidase (XOD) activity and regulated the expression of urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), organic anion transporter 1 (OAT1), organic cation transporter 1 (OCT1) and ATP-binding cassette superfamily gmember 2 (ABCG2) in kidneys. Moreover, CPE-E suppressed the activation of the toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB (TLR4/MyD88/NF-κB) signaling pathway and nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome in PO-treated mice, and related inflammatory cytokines were reduced. CPE-E also modulated gut microbiota structure, showing that the abundance of Lactobacillus and Clostridiaceae increased in hyperuicemic mice. This study was conducted to explore the protective effect of CPE-E on hyperuricemia and provide new thoughts for the exploitation of Camellia japonica bee pollen.

A Novel Chinese Honey from Amorpha fruticosa L.: Nutritional Composition and Antioxidant Capacity In Vitro.

False indigo (Amorpha fruticosa L., A. fruticosa) is the preferred tree indigenous for windbreak and sand control in Northwest China, while information on nutritional and bioactive characteristics of its honey is rare. Herein, 12 honey of Amorpha fruticosa L. (AFH) were sampled in Northwest China and the nutritional composition was determined. Sixteen mineral element and ten dominant polyphenols content were identified and quantified by ICP-MS (Inductively coupled plasma mass spectrometry) and HPLC-QTOF-MS (High performance liquid chromatography-Quadrupole time-of-flight mass spectrometry), respectively. Moreover, AFH demonstrated high levels of DPPH (1,1-Diphenyl-2-picrylhydrazyl) radical scavenging activity (IC50 100.41 ± 15.35 mg/mL), ferric reducing antioxidant power (2.04 ± 0.29 µmol FeSO4·7H2O/g), and ferrous ion-chelating activity (82.56 ± 16.01 mg Na2EDTA/kg), which were significantly associated with total phenolic contents (270.07 ± 27.15 mg GA/kg) and ascorbic acid contents (213.69 ± 27.87 mg/kg). The cell model verified that AFH exhibited dose-dependent preventive effects on pBR322 plasmid DNA and mouse lymphocyte DNA damage in response to oxidative stress. Taken together, our findings provide evidence for the future application of AFH as a potential antioxidant dietary in food industry.

Anti-Obesity and Gut Microbiota Modulation Effect of Secoiridoid-Enriched Extract from Fraxinus mandshurica Seeds on High-Fat Diet-Fed Mice.

Previously we conducted a phytochemical study on the seeds of Fraxinus excelsior and isolated nine secoiridoid compounds with adipocyte differentiation inhibitory activity and peroxisome proliferator activated receptor alpha (PPARα) activation effects. However, the bioactive constituents and functions of Fraxinus mandshurica seeds have not been studied. In the present study, we investigated the secoiridoid compounds in F. mandshurica seed extract (FM) using column chromatography, 1H-NMR, 13C-NMR and HPLC-DAD methods. The pancreatic lipase inhibitory activities of isolated compounds were evaluated in vitro. Additionally, the anti-obesity and gut microbiota modulation effect of FM on high-fat diet-induced obesity in C57BL/6 mice were also studied in vivo. The results showed that 19 secoiridoids were isolated from FM and identified. The total content of secoiridoids in FM reached 181.35 mg/g and the highest content was nuzhenide (88.21 mg/g). All these secoiridoid compounds exhibited good pancreatic lipase inhibitory activity with inhibition rate ranged from 33.77% to 70.25% at the concentration of 100 µM. After obese mice were administrated with FM at 400 mg/kg.bw for 8 weeks, body weight was decreased by 15.81%. Moreover, FM could attenuate the lipid accumulation in serum and liver, relieve the damage in liver and kidney, and extenuate oxidative stress injury and inflammation caused by obesity in mice. FM could also modulate the structural alteration of gut microbiota in obese mice, increasing the proportion of anti-obesity gut microbiota (Bacteroidetes, Bacteroidia, S24-7 and Allobaculum), and reducing the proportion of obesogenic gut microbiota (Firmicutes and Dorea). This study suggests that F. mandshurica seeds or their secoiridoids may have potential for use as a dietary supplement for obesity management.

Identification and quantitation of bioactive components from honeycomb (Nidus Vespae).

Honeycomb (Nidus Vespae) as an agri-food waste in bee product industry is in soaring demand for high-value utilization. This study is dedicated to investigate the physicochemical properties, chemical composition, and nutritional value of honeycomb by determination of physicochemical parameters, total phenolic and total flavonoid contents, antioxidant capacity in vitro, and bioactive components. By using ultra high-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) method, a total of 76 bioactive components from hydro-ethanolic extracts of honeycomb (EHB) were tentatively identified, where the principal ones are polyphenols and fatty acids, which were further quantified by LC-MS and GC-MS, respectively. Moreover, antimicrobial activities test has been conducted, verifying that EHB can inhibit both Gram-negative (G-) bacteria and Gram-positive (G+) bacteria, which is beneficial for the high-value utilization of honeycomb.

Chemical characterization of the main bioactive polyphenols from the roots of Morus australis (mulberry).

Morus species, commonly known as mulberry, is widely distributed in China. The mulberry tree is a high-value plant in agriculture. Morus australis is one of the major Morus species growing in Northern China. However, the biological properties of the main constituents of M. australis roots were not well studied. In the present study, through extensive chromatographic and spectral analysis, 12 phenolic compounds were isolated and identified from the M. australis roots. Compounds 1, 2, 8, 9 and 12 were isolated from M. australis roots for the first time. Antitumor activities of these polyphenols were studied on the A549 cell line. Compounds 1, 5 and 6 exhibited cytotoxicity on A549 cells and induced apoptosis in A549 cells via the intrinsic mitochondrial pathway. They also mediated inhibition of autophagic flux contributed cell death via the PI3k/Akt/mTOR pathway. In order to explore more potential bioactivities of these isolates, α-glucosidase, acetylcholinesterase and tyrosinase inhibitory activities were studied, and the results demonstrated that the inhibitory activity of these polyphenols on enzymes was not defined by their basic structural skeletons, but by the substituted position.

Honey Polyphenols Ameliorate DSS-Induced Ulcerative Colitis via Modulating Gut Microbiota in Rats.

SCOPE: Ulcerative colitis (UC) is a multifaceted and recurrent immune disorder that requires long-term potent pharmacological treatment. Honey, as a natural food of nourishment and pharmaceutical value, has been found to defend against colitis. METHODS AND RESULTS: The effects of different constituents in honey are investigated on DSS-induced colitis in rats. Rats are given DSS, sugars, honey, polyphenols, or SASP for a week, with blood and colon samples collected for the biochemical parameters and inflammation-related gene analysis and colon contents for gut microbiota. The results show that pretreatments with honey polyphenols significantly improve SOD, GSH-Px, NO, and MPO levels and reduce DSS-induced colonic apoptosis, the colonic inflammatory cytokines IL-6, TNF-α, and TGF-ß1 accompanied by downregulation of IL-1ß, IL-6, TNF-α, and IFN-γ gene and upregulation of IκB-α gene. Furthermore, honey polyphenols and SASP show similar microbial community structure shifts and selective enrichment of key species. At the genus level, honey polyphenols significantly reduce the population of Bacteroides, Corynebacterium, and Proteus species. The correlation analysis indicates that colonic gene expression regulated by honey polyphenols is relative to the key species of gut microbiota. CONCLUSIONS: Honey polyphenols improve intestinal inflammation and oxidative stress resistance via modulating gut microbiota, which is conducive to revealing the host-microbe interactions.

Jujube honey induces apoptosis in human hepatocellular carcinoma HepG2 cell via DNA damage, p53 expression, and caspase activation.

Jujube honey, a very popular honey in China, has been shown to own numerous biological properties. However, the anticancer effect and the underlying mechanisms of jujube honey in HepG2 cells have not been investigated to date. This study was designed to evaluate jujube honey-induced apoptosis and its molecular mechanism in HepG2 and the following results were obtained. Firstly, treatment with jujube honey blocked cell cycle progression at the G0/G1 phase, reduced the mitochondrial membrane potential (Δψm), induced DNA damage, and upregulates p53 expression. Secondly, pro-apoptotic proteins Bax and Bad were upregulated and antiapoptotic proteins Bcl-2 and Bcl-xL were downregulated. Lastly, caspase activation and apoptotic death occurred in HepG2 cells. In conclusion, this study showed that jujube honey induces HepG2 cell apoptosis via DNA damage, p53 expression, and caspase activation. PRACTICAL APPLICATIONS: We demonstrate the molecular mechanism by which jujube honey triggers apoptosis in HepG2 cells. This new insight provided useful information on the use of jujube honey as a potential therapeutic and preventive agent.

Rape bee pollen alleviates dextran sulfate sodium (DSS)-induced colitis by neutralizing IL-1ß and regulating the gut microbiota in mice.

Colitis is a major chronic disease in today's society. Consumption of phenolic compounds can protect against colitis. We examined the phenolic compounds of rape bee pollen extract (RPE) and investigated its prevention of DSS-induced colitis in C57BL/6 mice. HPLC-DAD-ECD analysis showed that 7 phenolic compounds were tentatively identified in RPE, of which kaempferol had the highest content (19.87 mg/g), followed by sinapic acid and rosmarinic acid. RPE at 21.2 g/kg BW (HD - high-dose group) and 10.6 g/kg BW (LD - low-dose group) ameliorated colon shortening, spleen swelling and colon weight reduction, improved the structure of colonic villi, glandular structures and crypts, which was further confirmed by conventional histological assessment, and inhibited the activities of related inflammatory cytokines. In particular, IL-1ß expression was downregulated by approximately 90% compared with that of the model group. Additionally, treatment with RPE altered the gut microbial structure of mice with colitis, showing that the abundances of Allobaculum and Bacteroides were significantly reduced and the abundance of Lactobacillus was markedly increased. This study indicated that RPE could protect the colon from DSS-induced colitis by increasing antioxidant capacity, alleviating inflammation and regulating the gut microbiota. This paper was conducted to investigate the potent protective effects of RPE treatments on a mouse model of colitis and provided new ideas for the application of rape bee pollen.

Effects of honey-extracted polyphenols on serum antioxidant capacity and metabolic phenotype in rats.

It is generally known that honey polyphenols have antioxidant capacity and numerous biological functions. However, their metabolic phenotype after digestion has not been studied. In this study, the effects of honey-extracted polyphenols (HEPs) on serum antioxidant capacity and metabolic phenotype were revealed for the first time. Herein, sixteen male Sprague-Dawley rats were randomly divided into two groups: one group was administered HEPs (200 mg per kilogram body weight dose) and the other group was fed distilled water three times. Then, 1 h after the last gavage, the metabolic profiling of serum was analyzed by UHPLC-Orbitrap-HRMS and multivariate statistical analysis, and the following results were obtained. At first, twenty-five metabolites, including polyphenols, unsaturated fatty acids, and amino acids, were selected as potential biomarkers. Then, metabolic pathway analysis showed that several amino acid metabolism pathways, ubiquinone and other terpenoid-quinone biosynthesis, arachidonic acid metabolism, nicotinate and nicotinamide metabolism, and inositol phosphate metabolism were affected. Association analysis demonstrated that the alteration of metabolites may be responsible for the increased serum antioxidant capacity. This new insight into the effects on the metabolic phenotype after HEP intake prompted the study on the biological functions and emerging health benefits of HEPs.

Hepatoprotective Effects of the Honey of Apis cerana Fabricius on Bromobenzene-Induced Liver Damage in Mice.

Apis cerana honey (honey of Apis cerana Fabricius), widely distributed in the mountain areas of East Asia, has not been studied fully. The hepatoprotective activity of A. cerana honey was evaluated against bromobenzene-induced liver damage in mice. In high dose, A. cerana honey can significantly alleviate liver injury, as is indicated by the depressed levels of serum alanine aminotransferase (ALT) (59.13%) and aspartate aminotransferase (AST) (79.71%), the inhibited malondialdehyde (MDA) content (63.30%), the elevated activities of superoxide dismutase (SOD) (73.12%) and glutathione-Px (57.24%), and the decreased expression of Transforming growth factor ß1 (51.83%) induced by bromobenzene (P < 0.05). The quantitative analysis of twelve major constituents (1 to 12) of A. cerana honey was executed by high performance liquid chromatography-diode array detector. The results indicate that treatment with A. cerana honey can prevent bromobenzene-induced hepatic damage in mice. Polyphenols might be the bioactive substances attributed to its antioxidant properties and intervention of oxidative stress.

Antioxidant and hepatoprotective effects of A. cerana honey against acute alcohol-induced liver damage in mice.

A. cerana honey, gathered from Apis cerana Fabricius (A. cerana), has not been fully studied. Samples of honey originating from six geographical regions (mainly in the Qinling Mountains of China) were investigated to determine their antioxidant and hepatoprotective effects against acute alcohol-induced liver damage. The results showed that A. cerana honeys from the Qinling Mountains had high total phenolic contents (345.1-502.1mgGAkg-1), ascorbic acid contents (153.8-368.4mgkg-1), and strong antioxidant activities in DPPH radical scavenging activity assays (87.5-136.2IC50mgmL-1), ferric reducing antioxidant powers (191.8-317.4mgTroloxkg-1), and ferrous ion-chelating activities (27.5-35.5mgNa2EDTAkg-1). Pretreatment with A. cerana honey (Qinling Mountains) at 5, 10, or 20gkg-1 twice daily for 12weeks significantly inhibited serum lipoprotein oxidation and increased serum radical absorbance capacity (ORAC) (P<0.05). Moreover, A. cerana honey inhibited acute alcohol-induced increases in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum (P<0.05), reduced the production of hepatic malondialdehyde (MDA) (P<0.05), and promoted superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities (P<0.05). More importantly, it also remarkably inhibited the level of TGF-ß1 in the serum and liver (P<0.05). The results of this study indicate that administration of A. cerana honey prevents acute alcohol-induced liver damage likely because of its antioxidant properties and ability to prevent oxidative stress.