Hyperoside Research Articles

From Fresh to Dried Lavender Flower: Changes in Phytochemical Profile According to Drying Method

Lavandula angustifolia Mill. is a part of the Lamiaceae family, which includes aromatic plants used in perfumery, manufactory, food, ornamental, and medicinal sectors. Both fresh and dried lavender flowers can be exploited in different ways; however, post-harvest treatments such as drying processes can help maintain the flowers’ properties for a longer period. This study analyzed fresh (F) and dried lavender flower ultrasound-assisted extracts, comparing two different drying methods, i.e., heat-pump drying (HP) and hot-air drying (HA), to assess potential differences in their effect on the phytochemical composition (total phenolic content, total anthocyanin content, and phenolic profile) and antioxidant activity (FRAP, DPPH, and ABTS assays) of flowers, focusing on three lavender selections from north-western Alps (i.e., Susa, Stura, and Tanaro). Results showed that HP-dried flowers are to be preferred over HA-dried flowers, as they contain +66.73% of phenolics and +62.2% of anthocyanins, and they have higher antioxidant activity (from 60.32% to 284.3% more according to the assay). HP-dried flowers, particularly those from the Tanaro selection, showed also higher values in the relative antioxidant capacity index (RACI) and the global antioxidant score (GAS), ranking together with the fresh flowers. Nine bioactive compounds out of thirteen were detected by means of HPLC, seven in F (caffeic acid, hyperoside, quercetin, ellagic acid, catechin, epicatechin, and dehydroascorbic acid), four in HA (ferulic acid, hyperoside, quercitrin, and epicatechin), and two in HP (caffeic acid and hyperoside). The higher temperatures used in HA probably promoted oxidative and biochemical reactions that led to the presence and increase in these compounds. However, many other phenolic compounds may contribute to the antioxidant power of lavender extracts. Overall, HP resulted in an effective and sustainable method for drying lavender flowers and may have interesting applications to obtain final products richer in bioactive compounds and antioxidant activity to be used in the functional food industry.

Apple polyphenol biotransformation using probiotics in vitro and dynamic simulated digestion by bionic rats.

The present study investigated the effects of fermentation by Lactobacillus rhamnosus zrx01 (LR-zrx01), Lactobacillus acidophilus zrx02 (LA-zrx02), and Lactobacillus plantarum zrx03 (LP-zrx03), as well as dynamic simulated digestion by bionic rats, on the biotransformation and antioxidant potential of apple polyphenols. Polyphenols were determined by ultra-high-performance liquid chromatography-mass spectrometry, the dynamic simulated digestion of fermented apple pulp was determined by bionic rats, and the antibacterial and antioxidant activities were analyzed. The polyphenol content of apple pulp fermented using the three strains was respectively 1.41, 1.38, and 1.36 times that of non-fermented pulp. The antibacterial activity of apple pulp improved dramatically after fermentation. Moreover, the antioxidant potential of apple pulp increased after fermentation and digestion. After dynamic simulated digestion by bionic rats, the polyphenol content in unfermented and the three fermented groups increased significantly by 1.19, 1.23, 1.20, and 1.19 times compared to that before digestion, respectively. The major polyphenols in each group with obvious changes were epicatechin, rutin, kaempferol, quercetin-3 galactoside, p-coumaric acid, and two unknown substances, 1 and 2. Fermented and digested apple polyphenols showed better biotransformation effects and mostly existed in the form of small molecules, which was conducive to the improvement of polyphenol bioavailability and beneficial to the absorption of active substances by the human body. These findings build a foundation for the development of functional food beverages. © 2023 Society of Chemical Industry.

Metabolomic profiling of different clones of vitis vinifera L. cv. “Glera” and “Glera lunga” grapes by high-resolution mass spectrometry

Prosecco wine production has been strongly extended in the last decade and several new clones have been introduced. "Glera" (minimum 85%) and "Glera lunga" are grape varieties of great economic impact used to produce Prosecco wines. Study of grape berry secondary metabolites is effective in the classification of vine varieties and clones. High-resolution mass spectrometry provides complete panorama of these metabolites in single analysis and coupling to statistical multivariate analysis is successfully applied in vine chemotaxonomy. update and deepen the knowledge on the "Glera" and "Glera lunga" berry grapes chemotaxonomy and investigate some of the most produced and marketed clones by using the modern analytical and statistical tools. five clones of "Glera" and two of "Glera lunga" grown in the same vineyard with same agronomical practices were studied for three vintages. Grape berry metabolomics was characterized by UHPLC/QTOF and multivariate statistical analysis was performed on the signals of main metabolites of oenological interest. "Glera" and "Glera lunga" showed different monoterpene profiles ("Glera" is richer in glycosidic linalool and nerol) and differences in polyphenols (catechin, epicatechin and procyanidins, trans-feruloyltartaric acid, E-ε-viniferin, isorhamnetin-glucoside, quercetin galactoside). Vintage affected the accumulation of these metabolites in berry. No statistical differentiation among the clones of each variety, was found. Coupling HRMS metabolomics/statistical multivariate analysis enabled clear differentiation between the two varieties. The examined clones of same variety showed similar metabolomic profiles and enological characteristics, but vineyard planting using different clones can result in more consistent final wines reducing the vintage variability linked to genotype × environment interaction.

Quercetin 3-O-Galactoside Isolated from Limonium tetragonum Inhibits Melanogenesis by Regulating PKA/MITF Signaling and ERK Activation.

Quercetin 3-O-galactoside (Q3G) is a common dietary flavanol that has been shown to possess several bioactivities, including anti-melanogenesis. However, how Q3G exerts its anti-melanogenic effect has not been studied. The current study, therefore aimed to investigate the anti-melanogenesis potential of Q3G and elucidate the underlying action mechanism in α-melanocyte-stimulating hormone (α-MSH)-induced hyperpigmentation model of B16F10 murine melanoma cells. Results showed that α-MSH stimulation significantly increased tyrosinase (TYR) and melanin production, which were significantly downregulated by Q3G treatment. The treatment with Q3G suppressed the transcriptional and protein expressions of melanogenesis-related enzymes TYR, tyrosinase related protein-1 (TRP-1), and TRP-2, along with the melanogenic transcription factor microphthalmia-associated transcription factor (MITF) in B16F10 cells. It was shown that Q3G downregulated MITF expression and suppressed its transcriptional activity by inhibiting the cAMP-dependent protein kinase A (PKA)-mediated activation of CREB and GSK3β. In addition, MAPK-regulated MITF activation signaling was also involved in the inhibition of melanin production by Q3G. The results suggest that the anti-melanogenic properties of Q3G rationalize further studies in vivo to confirm its action mechanism and consequent utilization as a cosmetic ingredient against hyperpigmentation.

Hyperoside attenuates Cd-induced kidney injury via inhibiting NLRP3 inflammasome activation and ROS/MAPK/NF-κB signaling pathway in vivo and in vitro.

Cadmium accumulates in the kidney and causes inflammation. The NLRP3 inflammasome has been linked to the pathogenesis of inflammation. Hyperoside (HYP) possesses potent nephroprotective properties against of kidney injury. This study aimed to research the effects and related mechanism of HYP on Cd-induced kidney damage. Wide-type and NLRP3-/- mice were used to determine the role of NLRP3 inflammasome in Cd-induced renal dysfunction. Female C57BL/6 were treated with Cd (50m,g/L) and HYP (25, 50mg/kg) for 12 weeks. In vitro experiments, the human renal proximal-tubule epithelial cells (RPTEC/TERT1) were pretreated with HYP (50-200μM) before exposure to Cd. NLRP3 deficiency attenuated Cd-induced NLRP3 activation, inflammation and kidney injury in mice. HYP treatment significantly alleviated Cd-induced kidney injury by decreasing indexes of kidney function, reducing pro-inflammatory cytokines release, decreasing ROS production and suppressing NLRP3 inflammasome activation. Moreover, treatment with siRNA targeting NLRP3 blocked the anti-inflammatory protective effect of HYP in Cd-treated cells. Additionally, HYP markedly inhibited Cd-induced MAPK/NF-κB pathway stimulation in vitro and in vivo. The findings indicated HYP conferred protection against Cd-induced kidney inflammation via suppression of NLRP3 inflammasome mediated by ROS/MAPK/NF-κB signaling. Our results thus support the notion of developing HYP as promising therapeutic candidate for Cd-induced kidney injury.

Exploring the binding effects and inhibiting mechanism of hyperoside to lipase using multi-spectroscopic approaches, isothermal titration calorimetry, inhibition kinetics and molecular dynamics.

Hyperoside (HYP) is a flavonoid with various physiological activities. The present study examined the interaction mechanism between HYP and lipase using multi-spectrum and computer-aided techniques. Results demonstrated that the force type of HYP on lipase was mainly hydrogen bond, hydrophobic interaction force, and van der Waals force, and HYP had an excellent binding affinity with lipase at 1.576 × 105 M-1. HYP dose-dependently inhibited lipase in the inhibition experiment, and its IC50 value was 1.92 × 10-3 M. Moreover, the results suggested that HYP could inhibit the activity by binding to essential groups. Conformational studies indicated that the conformation and microenvironment of lipase were slightly changed after the addition of HYP. Computational simulations further confirmed the structural relationships of HYP to lipase. The interaction between HYP and lipase can provide ideas for the development of functional foods related to weight loss. The results of this study help comprehend the pathological significance of HYP in biological systems, as well as its mechanism.

Chemical constituents and antifungal potential of Attalea geraensis Barb. Rodr. (Arecaceae) palm leaves, a species native to the Cerrado of Brazil.

Fungal diseases, especially those that affect the root systems of plants, caused by Rhizoctonia and Macrophomina are limiting factors for achieving high crop yields. Alternatives to controlling fungi with chemical products drive the search for new options for bioactive compounds from plants. Attalea geraensis, a palm tree from the Brazilian Cerrado, is rich in flavonoids with antifungal actions. The objective of this work is to identify the chemical classes present in the ethanolic extract of green leaves of A. geraensis and determine the antifungal potential of the extract against isolates of Macrophomina phaseolina (Tassi) Goid. and Rhizoctonia solani JG Kühn. Phytochemical prospection, flavonoid dereplication, and antifungal activity were carried out of the ethanolic extract of the green leaves of A. geraensis harvested in the Cerrado area of Brazil. Steroids, triterpenes, saponins, and anthraquinones are described here for the first time for the leaves of A. geraensis. The flavonoids quercetin, isorhamnetin, 3,7-dimethylquercetin, quercetin 3-galactoside, 5,7-dihydroxy-2-(4-hydroxy-3-methoxyphenyl)-3-{[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-4H-chromen-4-one, rhamnazin 3-galactoside, keioside, and rhamnazin 3-rutinoside were identified. Of these, only quercetin and isorhamnetin had already been identified in the leaves of A. geraensis. The results show a fungistatic potential for the species. The diversity of flavonoids present in the leaves of A. geraensis may be the result of a synergistic action between fungus and plant or there could be an antagonistic effect between flavonoids and the other identified chemical classes.

Neuroprotective effect of hyperoside in MPP+/MPTP -induced dopaminergic neurodegeneration.

Parkinson's disease (PD) is a neurodegenerative disease characterized by the pathological loss of nigrostriatal dopaminergic neurons, which causes an insufficient release of dopamine (DA) and then induces motor and nonmotor symptoms. Hyperoside (HYP) is a lignan component with anti-inflammatory, antioxidant, and neuroprotective effects. In this study, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its active neurotoxic metabolite 1-methyl-4-phenylpyridinium ion (MPP+) were used to induce dopaminergic neurodegeneration. The results showed that HYP (100µg/mL) reduced MPTP-mediated cytotoxicity of SH-SY5Y cells in vitro, and HYP [25mg/(kg d)] alleviated MPTP-induced motor symptoms in vivo. HYP treatment reduced the contents of nitric oxide (NO), H2O2, and malondialdehyde (MDA), as well as the mitochondrial damage of dopaminergic neurons, both in vitro and in vivo. Meanwhile, HYP treatment elevated the levels of neurotrophic factors such as glial cell line-derived neurotrophic factor, brain-derived neurotrophic factor, and recombinant cerebral dopamine neurotrophic factor in vivo, but not in vitro. Finally, Akt signaling was activated after the administration of HYP in MPP+/MPTP-induced dopaminergic neurodegeneration. However, the blockage of the Akt pathway with Akt inhibitor did not abolish the neuroprotective effect of HYP on DA neurons. These results showed that HYP protected the dopaminergic neurons from the MPP+- and MPTP-induced injuries, which did not rely on the Akt pathway.

Proteomic and metabolomic analyses reveal stage- and tissue- specific flavonoid accumulation in Ginkgo biloba

Ginkgo biloba L. is rich in bioactive ingredients and thus has great economic and medicinal value. Efficient extraction and rational utilization of key flavonoid components from appropriate tissues has important practical significance, and specific strategies should be developed to improve their effective utilization. Herein, quantitative proteomics and metabolomics were deployed for the identification of protein and metabolite profiles in the leaf (collected in June and September, JL and SL, respectively), kernel and exotesta (collected in September, SK and SE, respectively). In total, 8130 known metabolites were identified, and cluster analysis proved the close relationship between the leaf groups. Venn diagrams revealed 67 differentially expressed proteins (DEPs) distributed among the different groups with SL as the control. The regulatory relationship between DEPs and differentially expressed metabolites (DEMs) of the flavonoid biosynthesis pathway in the SE vs. SL and SE vs. JL comparisons was revealed by KGML network analysis. In addition, kaempferol, kaempferol-3-O-glucoside, luteolin, quercetin, ginkgolide C, isoquercitrin, quercetin 3-galactoside, quercitrin, catechin and rutin were differentially expressed between most pairs of groups and related to the flavonoid biosynthesis pathway. Therefore, these compounds can be used as effective references when selecting appropriate plant tissues from which to extract certain bioactive components.

Copigmentation effect of flavonols on anthocyanins in black mulberry juice and their interaction mechanism investigation

Copigmentation effect of flavonoids on black mulberry juice and its main anthocyanin, cyanidin-3-O-glucoside (C3G), was evaluated. Results showed that the hyperchromic effect of flavonols, such as kaempferol (KAE), hyperoside (HYP), rutin (RUT), quercetin (QTI) and isoquercitrin (IQT), was better than that of quercitrin (QTR) and catechin (CAT). The degradation rate constant (k) of C3G decreased by 8.6 %∼50.0 % when KAE, HYP, RUT, QTI and IQT were added, whilst half-life (t1/2), activation energy (Ea) and hydration reaction equilibrium constant (pKh) increased by 7.4 %∼99.0 %, 60.0 %∼95.7 % and 8.3 %∼37.8 % respectively. Meanwhile, the maximum absorption wavelength of the mixture displayed bathochromic shift. Molecular simulation indicated that the interaction energy with C3G was KAE > HYP > RUT > QTI > IQT > QTR > CAT. The main driving force forming C3G-flavonol complex were hydrogen bond and Van der Waals interaction. These results will provide theoretical reference to enhance color stability of food rich in anthocyanins.

Investigation of adsorption and corrosion inhibition property of Hyperoside as a novel corrosion inhibitor for Q235 steel in HaCl medium

Plant extracts have been widely reported as promising green metal corrosion inhibitors in recent years. Due to abundant sources, low cost and no pollution to the environment, plant extracts are good raw materials for preparing corrosion inhibitors. However, they have not been successfully applied in the corrosion industry owing to their unknown composition and large dosage. To further explore the effective corrosion inhibitors in plant extracts, Hyperoside (HYP) is firstly isolated from Uncaria laevigata in this work. Here, we assume that HYP shows good corrosion inhibition performance for Q235 steel in acidic medium. Then, the corrosion inhibition performance of HYP on Q235 steel in 1 M HCl solution at different temperature and corrosion time was explored by experiments and theoretical calculations. Electrochemical experiments showed that the corrosion inhibition efficiency of 300 mg/L HYP on Q235 steel in 1 M HCl was 92.34 % at 25 °C for 24 h. Excitedly, HYP (300 mg/L) still revealed a high corrosion inhibition efficiency of 80.49 % at 85 °C. Surface analysis showed that HYP formed a protective film on the steel surface. Additionally, quantum chemical calculation and molecular dynamics simulation evaluated the corrosion inhibition mechanism of HYP at the molecular level. The outstanding advantages of HYP over some plant extracts include low dosage, clear structure and sustained protection. Therefore, it can be used as a green corrosion inhibitor and shows great application prospect in oil well acidification with high temperature. Meanwhile, this work will provide some ideas for exploring the monomer or compound components that really exert inhibition effect in plant extracts.

Hyperoside suppresses osteoclasts differentiation and function through downregulating TRAF6/p38 MAPK signaling pathway

Hyperoside (HP), as a natural product, can promote proliferation and differentiation of osteoblasts and presents a protective effect on ovariectomized (OVX) mice. However, the inhibitory effect of HP on osteoclasts (OCs) and the potential mechanism remain to be elucidated. In this study, it was found that HP could effectively inhibit the differentiation and bone resorption of OCs, and its intrinsic molecular mechanism was related to the inhibition of TRAF6/p38 MAPK signaling pathway. Therefore, HP could be a promising natural compound for lytic bone diseases.

Delivery of hyperoside by using a soybean protein isolated-soy soluble polysaccharide nanocomplex: Fabrication, characterization, and in vitro release properties

Nanoparticles made from natural proteins and polysaccharides are green, biodegradable, and sustainable. In this study, soybean protein isolate (SPI) and soybean soluble polysaccharide (SSPS) were employed as delivery vehicles for hyperoside (HYP) to explore the mechanism of the formation of complexes and evaluate the performance of this mechanism at different pH values. The structures of SPI-SSPS-HYP complexes were studied by Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM) and atomic force microscopy (AFM), and the stability was evaluated based on free radical scavenging ability, loading rate, and simulated release. The results showed that nanoparticles were subjected to non-covalent electrostatic complexation, which was affected mainly by electrostatic, hydrogen bond, and hydrophobic interactions, and the optimal encapsulation efficiency was 85.56% at pH 3.5. Encapsulated HYP retained its high antioxidant capacity. This study provides a new strategy for developing a biodegradable nanocarrier with superior encapsulation properties, enhancing the application range of HYP.

A Comparison of Bioactive Metabolites, Antinutrients, and Bioactivities of African Pumpkin Leaves (Momordica balsamina L.) Cooked by Different Culinary Techniques.

Prior to consumption, African pumpkin leaves (Momordica balsamina L.) are generally cooked. In this study, the effects of common household cooking methods (boiling, steaming, microwaving, stir-frying) on bioactive metabolites, carotenoids, antioxidant activity, antinutrients and inhibitory effects on α-glucosidase and α-amylase activities were examined. A set of 14 bioactive metabolites were identified in raw and cooked African leaves using UPLC-QTOF/MS. The results showed that the four different types of household cooking methods had different effects on the bioactive metabolomics profile of African pumpkin leaves. In comparison to raw leaves and leaves cooked in other methods, the concentrations of six phenolic compounds, rutin, cryptochlorogenic acid (4-caffeoylquinic acid), pseudolaroside A, isorhamnetin 3-O-robinoside, quercetin 3-galactoside, and trans-4-feruloylquinic acid, were highest in stir-fried leaves. Of all household cooking methods tested, stir-frying increased the content of lutein, β-carotene, and zeaxanthin by 60.00%, 146.15%, and 123.51%, respectively. Moreover, stir-frying African pumpkin leaves increased the antioxidant activity (DPPH and ABTS) and the inhibition of α-glucosidase and α-amylase. Compared to all four methods of household cooking, stir-frying reduced the antinutritive compounds compared to raw leaves. This work provides useful information to the consumers on the selection of suitable cooking methods for African pumpkin leaves.

Inhibition of Human UDP-Glucuronosyltransferases1A1-Mediated Bilirubin Glucuronidation by the Popular Flavonoids Baicalein, Baicalin, and Hyperoside Is Responsible for Herb (Shuang-Huang-Lian)-Induced Jaundice.

Bilirubin-related adverse drug reactions (ADRs) or malady (e.g., jaundice) induced by some herbs rich in certain flavonoids have been widely reported. However, the causes and mechanisms of the ADRs are not well understood. The aim of this paper was to explore the mechanism of Shuang-huang-lian (SHL) injections and its major constituents-induced jaundice via inhibiting human UDP-glucuronosyltransferases1A1 (hUGT1A1)-mediated bilirubin glucuronidation. The inhibitory effects of SHL and its major constituents in the herbal medicine, including baicalein (BAI), baicalin (BA), and hyperoside (HYP), on bilirubin glucuroBBREVInidation were investigated. This study indicated that the average formation rates of bilirubin glucuronides [i.e., mono-glucuronide 1 (BMG1), BMG2, and bilirubin diglucuronide] displayed significant differences (P < 0.05). Specifically, the formation of BMGs was favored regardless of whether an inhibitor was absent or present. SHL, BAI, BA, and HYP dose-dependently inhibit bilirubin glucuronidation, showing the IC50 values against total bilirubin glucuronidation were in the range of (7.69 ± 0.94)-(37.09 ± 2.03) μg/ml, (4.51 ± 0.27)-(20.84 ± 1.99) μM, (22.36 ± 5.74)-(41.35 ± 2.40) μM, and (15.16 ± 1.12)-(42.80 ± 2.63) μM for SHL, BAI, BA, and HYP, respectively. Both inhibition kinetics assays and molecular docking simulations suggested that SHL, BAI, BA, and HYP significantly inhibited hUGT1A1-mediated bilirubin glucuronidation via a mixed-type inhibition. Collectively, some naturally occurring flavonoids (BAI, BA, and HYP) in SHL have been identified as the inhibitors against hUGT1A1-mediated bilirubin glucuronidation, which well explains the bilirubin-related ADRs or malady triggered by SHL in clinical settings. SIGNIFICANCE STATEMENT: Herbal products and their components (e.g., flavonoids), which been widely used across the entire world, may cause liver injury. As a commonly used herbal products rich in flavonoids, SHL injections easily lead to symptoms of liver injury (e.g., jaundice) owing to significant inhibition of hUGT1A1-mediated bilirubin glucuronidation by its flavonoid components (i.e., baicalein, baicalin, and hyperoside). Herb-induced bilirubin-related ADRs and the associated clinical significance should be seriously considered.

Metabolomic and chemometric profiles of ten southern African indigenous fruits

Using UPLC-QTOF/MS, metabolites were identified in 10 indigenous fruits from South Africa. Metabolomic-chemometric analysis showed chlorogenic acid scored highest for the discrimination of three different fruit clusters. Heat maps showed patterns and groupings based on the metabolite concentrations. The highest concentrations of quercetin 3-O-α-l-arabinopyranoside (401.09 mg/kg), delphinidin 3-galactoside (57.80 mg/kg), procyanidin B-type dimer (527.07 mg/kg) and epicatechin (1349.46 mg/kg), was in Englerophytum magalismontanum (Transvaal milkplum). Syzygium cordatum (Water berry) had the highest concentrations of quercetin 3-galactoside and methyl gallate 3-O-beta-d-glucopyranoside, Ficus capensis (Cape fig) the most 3-CQA and 5-CQA, and Parinari curatellifolia (Mobola plum) had the highest FRAP (9.5 mmol TEAC/g) and DPPH (14.2 IC50 µg/mL) scavenging activities. When compared to eight other indigenous fruits, Ximenia caffra (Sour plum), and Landolphia kirkii (Sand apricot vine), showed the highest inhibition of carbohydrate hydrolysing enzymes. Correlation analysis identified candidates responsible for each biological activity in these fruits, proving their utility as functional ingredients.

Hyperoside inhibits lipopolysaccharide-induced mastitis in mice by inactivating the NLRP3 inflammasome

IntroductionThe impact of bovine mastitis on animal husbandry is great huge. It is anincurable an incurable disease mainly characterized by milk and pathological changes in milk and the mammary gland, which causescause reduced yield and quality of milk, but. Unfortunately, the use of antibiotics to combat mastitis affects the production of milk, so it is urgent to find additional therapeutic molecules for mastitis treatment.Material and methodsIn this study, we analyzed the protection provided by hyperoside (HYP) in a model of mastitis in vivo and explored its functional mechanism in mouse mammary epithelial cells (mMECs) by overexpression of NOD-, LRR- and pyrin domain-containing 3 (NLRP3).ResultsOur results showed that HYP at 12.5, 25 and 50 mg/kg prevented the inflammatory response induced in lipopolysaccharide (LPS)-stimulated micemouse mammary glands as well as inflammatory cytokine production, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β and IL-8. The protection provided by HYP was also correlated with the reduction of NLRP3 signaling pathway protein levels in vivo. However, overexpression of NLRP3 reversed the effects of HYP on the NLRP3 inflammasome, cell viability and inflammatory factor levels in LPS-stimulated mMECs.ConclusionsIn summary, this study showed that HYP inhibited LPS-stimulated symptoms of breast inflammation by regulating expression of inflammatory cytokines and inhibiting the NLRP3 signaling pathway.

Hyperoside Ameliorates DSS-Induced Colitis through MKRN1-Mediated Regulation of PPARγ Signaling and Th17/Treg Balance.

Hyperoside (HYP), a naturally occurring flavonoid compound, exerts multiple biological functions including myocardial protection, antiredox, and anti-inflammatory activities. However, the role of HYP on inflammatory bowel disease (IBD) and the underlying mechanism need to be further established. Here, we show that HYP treatment profoundly alleviated dextran sulfate sodium-induced ulcerative colitis in mice, characterized by reduced pathological scores, preserved tissue integrity, suppressed colonic inflammation, and balanced Th17/Treg response. Mechanistically, HYP was shown to restrain the expression of the E3 ubiquitin ligase, makorin ring finger protein 1 (MKRN1), which in turn promoted the ubiquitination and proteasomal degradation of peroxisome proliferator-activated receptor gamma (PPARγ), an essential regulator of Th17 and Treg differentiation. Consequently, HYP treatment enhanced PPARγ signaling and hence promoted Treg differentiation while suppressing Th17 cell development during colitis. Thus, our data indicate that HYP acts through the MKRN1/PPARγ axis to modulate the Th17/Treg axis and thereby confers protection against experimental colitis. The findings extend our understanding about HYP action and may provide a potential therapeutic target for IBD.

Hyperoside Suppresses Renal Inflammation by Regulating Macrophage Polarization in Mice With Type 2 Diabetes Mellitus.

Accumulating evidence reveals that both inflammation and lymphocyte dysfunction play a vital role in the development of diabetic nephropathy (DN). Hyperoside (HPS) or quercetin-3-O-galactoside is an active flavonoid glycoside mainly found in the Chinese herbal medicine Tu-Si-Zi. Although HPS has a variety of pharmacological effects, including anti-oxidative and anti-apoptotic activities as well as podocyte-protective effects, its underlying anti-inflammatory mechanisms remain unclear. Herein, we investigated the therapeutic effects of HPS on murine DN and the potential mechanisms responsible for its efficacy. We used C57BLKS/6J Lep db/db mice and a high glucose (HG)-induced bone marrow-derived macrophage (BMDM) polarization system to investigate the potentially protective effects of HPS on DN. Our results showed that HPS markedly reduced diabetes-induced albuminuria and glomerular mesangial matrix expansion, accompanied with a significant improvement of fasting blood glucose level, hyperlipidaemia and body weight. Mechanistically, pretreatment with HPS effectively regulated macrophage polarization by shifting proinflammatory M1 macrophages (F4/80+CD11b+CD86+) to anti-inflammatory M2 ones (F4/80+CD11b+CD206+) in vivo and in bone marrow-derived macrophages (BMDMs) in vitro, resulting in the inhibition of renal proinflammatory macrophage infiltration and the reduction in expression of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor (TNF-α) and inducible nitric oxide synthase (iNOS) while increasing expression of anti-inflammatory cytokine Arg-1 and CD163/CD206 surface molecules. Unexpectedly, pretreatment with HPS suppressed CD4+ T cell proliferation in a coculture model of IL-4-induced M2 macrophages and splenic CD4+ T cells while promoting their differentiation into CD4+IL-4+ Th2 and CD4+Foxp3+ Treg cells. Taken together, we demonstrate that HPS ameliorates murine DN via promoting macrophage polarization from an M1 to M2 phenotype and CD4+ T cell differentiation into Th2 and Treg populations. Our findings may be implicated for the treatment of DN in clinic.

Effects of temperatures on growth, physiological, and antioxidant characteristics in Houttuynia cordata

Houttuynia cordata Thunb. (HC) is a traditional medicinal plant with a variety of pharmaceutical activities. The objective of this study was to investigate the growth, photosynthetic parameters, and antioxidant properties of HC plants in response to various temperatures. Pots of HC plants were maintained in day/night temperatures of 15/10 °C, 20/15 °C, 25/20 °C (control), 30/25 °C, and 35/30 °C for two months in each of five growth chambers having a 13.5 h photoperiod at 396, 432, 474, 449, and 619 µmol·m-2·s-1 radiation, respectively. Eight plants for each temperature were randomly placed in a growth chamber. HC plants survived at 30/25 °C and 35/30 °C treatments and had significantly higher plant heights, leaf numbers, and soil-plant analysis development (SPAD) and normalized difference vegetation index (NDVI) values compared to other treatments. However, long-term 35/30 °C treatment caused reductions in leaf length and width, significantly decreasing shoot and leaf fresh weight (FW) and dry weight (DW) compared to 30/25 °C treatment and controls. These results indicate that HC leaf development was affected during the 35/30 °C treatment, and that both SPAD and NDVI can help in advancing our understanding of the photosynthesis process in HC. Moreover, all plants subjected to 15/10 °C suffered more severely in all traits and parameters than other treatments. Therefore, HC plants tended to be heat-tolerant and exhibited adaptive morphologic plasticity to 30/25 °C conditions. Positive and significant correlations were observed among temperatures and total phenolics (TP), total flavonoids (TF), chlorogenic acid (CGA), and hyperoside (HO) content, and all bioactive contents increased as temperature increased, except that both CGA and HO content were remarkably decreased after 30/25 °C treatment. Thus, 30/25 °C treatment would be more beneficial for high marketability resulting from increased leaf number, DW, and all secondary metabolites compared to other treatments, and for use as a health food and for medicinal purposes. In addition, leaf growth, physiological parameters, and secondary metabolite accumulations in HC plants can be optimized for commercial production via temperature control technologies. This approach may also be applicable to leafy vegetables to produce stable industrial supplies having high leaf yields and metabolite content.