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1.
J Ethnopharmacol ; 329: 118156, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38583729

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Throughout Chinese history, Hydrangea paniculata Siebold has been utilized as a traditional medicinal herb to treat a variety of ailments associated to inflammation. In a number of immune-mediated kidney disorders, total coumarins extracted from Hydrangea paniculata (HP) have demonstrated a renal protective effect. AIM OF THE STUDY: To investigate renal beneficial effect of HP on experimental Adriamycin nephropathy (AN), and further clarify whether reversing lipid metabolism abnormalities by HP contributes to its renoprotective effect and find out the underlying critical pathways. MATERIALS AND METHODS: After establishment of rat AN model, HP was orally administrated for 6 weeks. Biochemical indicators related to kidney injury were determined. mRNAs sequencing using kidney tissues were performed to clarify the underlying mechanism. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis, western blot, molecular docking, and drug affinity responsive target stability (DARTS) assay was carried out to further explore and confirm pivotal molecular pathways and possible target by which HP and 7-hydroxylcoumarin (7-HC) played their renal protection effect via modulating lipid metabolism. RESULTS: HP could significantly improve renal function, and restore renal tubular abnormal lipid metabolism and interstitial fibrosis in AN. In vitro study demonstrated that HP and its main metabolite 7-HC could reduce ADR-induced intracellular lipid deposition and fibrosis characteristics in renal tubular cells. Mechanically, HP and 7-HC can activate AMP-activated protein kinase (AMPK) via direct interaction, which contributes to its lipid metabolism modulation effect. Moreover, HP and 7-HC can inhibit fibrosis by inhibiting CCAAT/enhancer binding protein beta (C/EBPß) expression in renal tubular cells. Normalization of lipid metabolism by HP and 7-HC further provided protection of mitochondrial structure integrity and inhibited the nuclear factor kappa-B (NF-κB) pathway. Long-term toxicity using beagle dogs proved the safety of HP after one-month administration. CONCLUSION: Coumarin derivates from HP alleviate adriamycin-induced lipotoxicity and fibrosis in kidney through activating AMPK and inhibiting C/EBPß.


Subject(s)
AMP-Activated Protein Kinases , CCAAT-Enhancer-Binding Protein-beta , Coumarins , Doxorubicin , Hydrangea , Animals , Doxorubicin/toxicity , Coumarins/pharmacology , Coumarins/isolation & purification , Male , CCAAT-Enhancer-Binding Protein-beta/metabolism , AMP-Activated Protein Kinases/metabolism , Rats , Hydrangea/chemistry , Kidney/drug effects , Kidney/metabolism , Kidney/pathology , Rats, Sprague-Dawley , Kidney Diseases/chemically induced , Kidney Diseases/drug therapy , Kidney Diseases/metabolism , Kidney Diseases/prevention & control , Molecular Docking Simulation , Lipid Metabolism/drug effects , Cell Line , Plant Extracts/pharmacology , Plant Extracts/chemistry , Umbelliferones
2.
J Nat Med ; 77(4): 978-985, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37517070

ABSTRACT

The dried and fermented leaves of Hydrangea macrophylla var. thunbergii are currently used as crude drugs (Sweet Hydrangea Leaf) with a sweet taste for patients with diabetes. In recent years, cases of food poisoning with symptoms of vomiting etc. have been reported after drinking a decoction of this crude drug. Cyanogenic glycosides have been suggested as potential causative agents. However, cyanogenic glycosides from H. macrophylla var. thunbergii was ambiguous. In the present study, we found that the leaves contained the cyanogenic glycoside taxiphillin (1). Next, the content of 1 in leaves of different sizes, colors, parts, and growth periods was quantified. In addition, we prepared the leaves of plants grown in five types of soils with different pH values (pH 5.0-7.5). The content of 1 in the leaves of the plants grown in these soils was quantified. The content of 1 varied greatly, with more than a three-fold difference, depending on when the leaves were collected from the plants. Furthermore, we compared the content of 1 in the crude drug obtained under different processing conditions for H. macrophylla var. thunbergii. The results showed that 1 was mostly hydrolyzed during plant processing. It has been suggested that cyanogenic glycosides are not the causative constituents of food poisoning.


Subject(s)
Hydrangea , Humans , Hydrangea/chemistry , Glycosides/chemistry , Plant Leaves/chemistry
3.
Biosci Biotechnol Biochem ; 87(9): 1045-1055, 2023 Aug 23.
Article in English | MEDLINE | ID: mdl-37296229

ABSTRACT

Binding of the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to the cognate angiotensin-converting enzyme 2 (ACE2) receptor is the initial step in the viral infection process. In this study, we screened an in-house extract library to identify food materials with inhibitory activity against this binding using enzyme-linked immunosorbent assays and attempted to ascertain their active constituents. Hydrangea macrophylla var. thunbergia leaves were identified as candidate materials. Its active compounds were purified using conventional chromatographic methods and identified as naringenin, dihydroisocoumarins, hydrangenol, and phyllodulcin, which have affinities for the ACE2 receptor and inhibit ACE2 receptor-spike S1 binding. Given that boiled water extracts of H. macrophylla leaves are commonly consumed as sweet tea in Japan, we speculated that this tea could be used as a potential natural resource to reduce the risk of SARS-CoV-2 infection.


Subject(s)
COVID-19 , Coumarins , Hydrangea , Humans , Angiotensin-Converting Enzyme 2/metabolism , Hydrangea/chemistry , Protein Binding , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Tea , Coumarins/pharmacology
4.
Nutrients ; 14(1)2022 Jan 03.
Article in English | MEDLINE | ID: mdl-35011083

ABSTRACT

Obesity is a major health problem that is caused by body fat accumulation and that can lead to metabolic diseases. Owing to several side effects of the currently used antiobesity drugs, natural plants have risen as safe and potential candidates to alleviate obesity. We have previously reported the antiobesity effect of Hydrangea serrata (Thunb.) Ser. leaves extract (WHS) and its underlying mechanisms. As an extension of our preclinical studies, this study aimed to investigate the effect of WHS on body weight and body fat reduction in overweight or obese humans. A total of 93 healthy overweight or obese males and females, aged 19-65 years, with body mass indexes (BMIs) ≥ 25 and <32 kg/m2, were recruited and received either an oral administration of 600 mg of WHS, or placebo tablets for 12 weeks. Daily supplementation with WHS decreased body weights, body fat masses, and BMIs compared with the placebo-treated group. The hip circumferences, visceral fat areas, abdominal fat areas, and visceral-to-subcutaneous ratios decreased after WHS supplementation. No significant side effects were observed during or after the 12 weeks of WHS intake. In conclusion, WHS, which has beneficial effects on body weight and body fat reduction, could be a promising antiobesity supplement that does not produce any side effects.


Subject(s)
Adipose Tissue/drug effects , Body Weight/drug effects , Hydrangea/chemistry , Overweight/drug therapy , Plant Extracts/administration & dosage , Plant Leaves/chemistry , Abdominal Fat/drug effects , Adult , Aged , Anti-Obesity Agents , Body Composition/drug effects , Body Mass Index , Double-Blind Method , Humans , Intra-Abdominal Fat/drug effects , Male , Middle Aged , Obesity/drug therapy , Obesity/physiopathology , Overweight/physiopathology , Placebos
5.
J Ethnopharmacol ; 288: 115004, 2022 Apr 24.
Article in English | MEDLINE | ID: mdl-35051603

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Esculetin is a bioactive compound of medicinal herb Hydrangea paniculata, and has showed anti-oxidation and anti-inflammation bioactivities. Renal local oxidative stress and inflammation are import contributors for progression of lupus nephritis (LN). AIM OF THE STUDY: In the present study, the renal protective effect of esculetin against LN was evaluated using MRL/lpr mice. MATERIALS AND METHODS: MRL/lpr mice were orally administrated with esculetin (20 mg/kg and 40 mg/kg) from 10 to 20 weeks and then renal function and kidney pathology were analyzed. RESULTS: Esculetin significantly attenuated renal impairment in MRL/lpr mice by reducing blood urea nitrogen (BUN), serum creatinine (Scr) and albuminuria, and ameliorated the glomerular hypertrophy, tubular interstitial fibrosis and mononuclear cell infiltration into interstitium. mRNA microarray suggested that esculetin could significantly down-regulate complement cascade, inflammation and fibrosis pathway, and up-regulate Nrf2-related anti-oxidation genes. Most surprising finding in the current study was that esculetin could inhibit the complement activation both in classical and alternative pathway using in vitro hemolysis assay, further enzyme assay suggested that esculetin blocked the C3 convertase (C4b2a) to exert this inhibitory capability. Molecular docking predicted that esculetin had four conventional hydrogen bonds interacting with C4b2a, and CDOCKER energy is relatively lower. Luciferase reporter gene demonstrated that esculetin could activate Nrf2 signaling pathway, and further flow cytometry confirmed that anti-oxidation bioactivity of esculetin was dependent on Nrf2 activation. On the other hand, esculetin could inhibit NFκB nuclear translocation and TGFß-smad3 profibrosis pathway. CONCLUSION: Esculetin shows beneficial effect on LN progression, and it may be a good natural leading compound for design of chemical compounds to treat LN.


Subject(s)
Complement Activation/drug effects , Inflammation/drug therapy , Lupus Nephritis/drug therapy , Umbelliferones/pharmacology , Animals , Blood Urea Nitrogen , Creatinine/blood , Disease Progression , Dose-Response Relationship, Drug , Female , Hydrangea/chemistry , Inflammation/pathology , Mice , Mice, Inbred MRL lpr , Molecular Docking Simulation , NF-E2-Related Factor 2/metabolism , NF-kappa B/metabolism , Signal Transduction/drug effects , Umbelliferones/administration & dosage , Umbelliferones/isolation & purification
6.
Nutrients ; 13(10)2021 Oct 16.
Article in English | MEDLINE | ID: mdl-34684625

ABSTRACT

We previously reported the potential anti-obesity effects of the water extract of Hydrangea serrata (Thunb.) Ser. leaves (WHS) in high-fat diet-induced obese mice. As an extension of our previous study, we investigated the anti-adipogenic and anti-obesity effects of WHS and its underlying molecular mechanisms in 3T3-L1 preadipocytes and genetically obese db/db mice. WHS attenuated the gene expression of adipogenic transcription factors, CCAAT/enhancer binding protein (C/EBP)α, peroxisome proliferator-activated receptor (PPAR)γ, and sterol regulatory element binding protein (SREBP)-1. Moreover, WHS inhibited the mitotic clonal expansion of preadipocytes by inducing G1 cell cycle arrest. Oral administration of WHS alleviated body weight gain and body fat accumulation in vivo. In addition, adipocyte hypertrophy and liver steatosis were ameliorated by WHS treatment. WHS reduced C/EBPα, PPARγ, and SREBP-1 expression and activated AMPKα phosphorylation in both white adipose tissue (WAT) and liver tissue. WHS also mildly upregulated the expression of thermogenic proteins, including uncoupling protein-1, PPARs, PPARγ coactivator-1α, and sirtuin-1, in brown adipose tissue (BAT). Furthermore, WHS altered the gut microbiota composition to resemble that of wild-type mice. Taken together, our findings suggest that WHS could alleviate adiposity by inhibiting adipogenesis in WAT and the liver and modulating the gut microbiota.


Subject(s)
Anti-Obesity Agents/pharmacology , Hydrangea/chemistry , Obesity/drug therapy , Plant Extracts/pharmacology , 3T3-L1 Cells , Adipocytes/drug effects , Adipogenesis/drug effects , Adipose Tissue, Brown/metabolism , Adipose Tissue, White/metabolism , Adiposity/drug effects , Animals , CCAAT-Enhancer-Binding Protein-alpha/genetics , CCAAT-Enhancer-Binding Protein-alpha/metabolism , Diet, High-Fat/adverse effects , Gastrointestinal Microbiome/drug effects , Male , Mice , Mice, Inbred C57BL , Mice, Obese , Obesity/genetics , Obesity/metabolism , PPAR gamma/genetics , PPAR gamma/metabolism , Sterol Regulatory Element Binding Protein 1/genetics , Sterol Regulatory Element Binding Protein 1/metabolism , Thermogenesis/drug effects , Weight Gain/drug effects
7.
J Sep Sci ; 44(10): 2153-2159, 2021 May.
Article in English | MEDLINE | ID: mdl-33811736

ABSTRACT

Two antimalaria alkaloids, febrifugine and isofebrifugine, were successfully separated from total alkaloids of Dichroa febrifuga roots by one-step preparative countercurrent chromatography with a selected biphasic solvent system. The selected biphasic solvent system was composed of chloroform: methanol: water (2:1:1, v/v) according to partition performance of the two target components. Selection of biphasic solvent system was conducted by high performance liquid chromatography combined with high performance thin layer chromatography, which greatly assisted the screening procedure for biphasic solvent system. Totally, 50 mg of total alkaloid was separated by one-step preparative countercurrent chromatography, yielding 12 mg of febrifugine and 9 mg of isofebrifugine with more than 98.0% purity, respectively.


Subject(s)
Alkaloids/isolation & purification , Countercurrent Distribution/methods , Hydrangea/chemistry , Piperidines/isolation & purification , Plant Extracts/isolation & purification , Quinazolines/isolation & purification , Alkaloids/chemistry , Piperidines/chemistry , Plant Extracts/chemistry , Plant Roots/chemistry , Quinazolines/chemistry
8.
Food Funct ; 12(6): 2672-2685, 2021 Mar 21.
Article in English | MEDLINE | ID: mdl-33656018

ABSTRACT

Obesity is an increasing health problem worldwide as it is the major risk factor for metabolic diseases. In the present study, we investigated the anti-obesity effects of WHS by examining its effects on high fat diet (HFD)-induced obese mice. Male C57BL/6 mice were fed either a normal diet (ND) or a high fat diet (HFD) with or without WHS. At the end of the experiment, we observed the changes in their body weight and white adipose tissue (WAT) weight and lipid profiles in plasma. We performed western blot and histological analyses of WAT and liver to elucidate the molecular mechanisms of action. We also conducted fecal 16S rRNA analysis for investigating the gut microbiota. Our results indicated that pre- and post-oral administration of WHS significantly prevented body weight gain and reduced body fat weight in HFD-induced obese mice. In addition, WHS was found to improve adipocyte hypertrophy and liver fat accumulation by regulating the AMPK and AKT/mTOR pathways. WHS ameliorated hyperlipidemia by reducing total cholesterol and low-density lipoprotein (LDL) and decreased the energy metabolism-related hormones, leptin and insulin, in mouse plasma. Furthermore, we found that WHS modulated gut dysbiosis by normalizing HFD-induced changes. Taken together, our in vivo data implicate that WHS can be considered as a potential dietary supplement for alleviating obesity.


Subject(s)
AMP-Activated Protein Kinases/metabolism , Gastrointestinal Microbiome/drug effects , Hydrangea/chemistry , Obesity/metabolism , Plant Extracts/pharmacology , Animals , Body Weight/drug effects , Diet, High-Fat , Lipids/blood , Mice , Mice, Obese , Plant Leaves/chemistry , Signal Transduction/drug effects
9.
Nutrients ; 13(1)2021 Jan 17.
Article in English | MEDLINE | ID: mdl-33477276

ABSTRACT

Alzheimer's disease (AD) is a neurodegenerative disease conceptualized as a clinical-biological neurodegenerative construct where amyloid-beta pathophysiology is supposed to play a role. The loss of cognitive functions is mostly characterized by the rapid hydrolysis of acetylcholine by cholinesterases including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Moreover, both enzymes are responsible for non-catalytic actions such as interacting with amyloid ß peptide (Aß) which further leads to promote senile plaque formation. In searching for a natural cholinesterase inhibitor, the present study focused on two isocoumarines from hydrangea, thunberginol C (TC) and hydrangenol 8-O-glucoside pentaacetate (HGP). Hydrangea-derived compounds were demonstrated to act as dual inhibitors of both AChE and BChE. Furthermore, the compounds exerted selective and non-competitive mode of inhibition via hydrophobic interaction with peripheral anionic site (PAS) of the enzymes. Overall results demonstrated that these natural hydrangea-derived compounds acted as selective dual inhibitors of AChE and BChE, which provides the possibility of potential source of new type of anti-cholinesterases with non-competitive binding property with PAS.


Subject(s)
Cholinesterase Inhibitors/pharmacology , Hydrangea/chemistry , Acetylcholinesterase/metabolism , Alzheimer Disease/enzymology , Amyloid beta-Peptides/metabolism , Binding Sites , Butyrylcholinesterase/metabolism , Cholinesterase Inhibitors/chemistry , Humans , Hydrophobic and Hydrophilic Interactions , Isocoumarins , Kinetics , Molecular Docking Simulation , Plant Extracts/chemistry , Structure-Activity Relationship
10.
Nutrients ; 12(6)2020 May 28.
Article in English | MEDLINE | ID: mdl-32481760

ABSTRACT

Previously, we reported that the hot water extract of Hydrangea serrata leaves (WHS) and its active component, hydrangenol, possess in vitro and in vivo effects on skin wrinkles and moisturization. We conducted a randomized, double-blind, placebo-controlled trial to clinically evaluate the effect of WHS on human skin. Participants (n = 151) were randomly assigned to receive either WHS 300 mg, WHS 600 mg, or placebo, once daily for 12 weeks. Skin wrinkle, hydration, elasticity, texture, and roughness parameters were assessed at baseline and after 4, 8, and 12 weeks. Compared to the placebo, skin wrinkles were significantly reduced in both WHS groups after 8 and 12 weeks. In both WHS groups, five parameters (R1-R5) of skin wrinkles significantly improved and skin hydration was significantly enhanced when compared to the placebo group after 12 weeks. Compared with the placebo, three parameters of skin elasticity, including overall elasticity (R2), net elasticity (R5), and ratio of elastic recovery to total deformation (R7), improved after 12 weeks of oral WHS (600 mg) administration. Changes in skin texture and roughness were significantly reduced in both WHS groups. No WHS-related adverse reactions were reported. Hence, WHS could be used as a health supplement for skin anti-aging.


Subject(s)
Cutis Laxa/drug therapy , Dietary Supplements , Elasticity/drug effects , Hydrangea/chemistry , Organism Hydration Status/drug effects , Phytotherapy , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Plant Leaves/chemistry , Skin Aging/drug effects , Skin/drug effects , Administration, Oral , Adult , Cutis Laxa/prevention & control , Double-Blind Method , Female , Humans , Male , Middle Aged , Plant Extracts/administration & dosage , Plant Extracts/isolation & purification
11.
Chin J Integr Med ; 26(2): 130-137, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31872368

ABSTRACT

OBJECTIVE: To determine the effects of Hydrangeae Dulcis Folium (EHDF) on physical stress, changes in the whole-body cortisol level and behaviour in zebrafish (Danio rerio). METHODS: One hundred and seventy-four fish were randomly divided into 4 [adrenocorticotropin hormone (ACTH) challenge test: 4 fish per group] or 6 groups (behavioural test: 10-12 fish per group, whole-body cortisol: 4 fish per group). Net handling stress (NHS) was used to induce physical stress. Fish were treated with vehicle or EHDF (5-20 mg/L) for 6 min before they were exposed to stress. And then, fish were sacrificed for collecting body fluid from whole-body or conducted behavioural tests, including novel tank test and open field test, and were evaluated to observe anxiety-like behaviours and locomotion. In addition, to elucidate the mode of action of the anti-stress effects of EHDF, ACTH (0.2 IU/g, i.p.) challenge test was performed. RESULTS: The increased anxiety-like behaviours in novel tank test and open field test under stress were prevented by treatment with EHDF at 5-20 mg/L (P <0.05). Moreover, compared with the unstressed group, which was not treated with NHS, the whole-body cortisol level was significantly increased by treatment with NHS (P <0.05). Compared with the NHS-treated stressed control group, pre-treatment with EHDF at concentrations of 5-20 mg/L for 6 min significantly prevented the NHS-increased whole-body cortisol level (<0.05). In addition, ACTH challenge test showed that EHDF completely blocked the effects of ACTH on cortisol secretion (P <0.05). CONCLUSION: EHDF may be a good antistress candidate and its mechanism of action may be related to its positive effects on cortisol release.


Subject(s)
Adrenocorticotropic Hormone/pharmacology , Hydrangea/chemistry , Hydrocortisone/metabolism , Plant Extracts/pharmacology , Stress, Physiological/drug effects , Animals , Chromatography, Liquid , Flowers/chemistry , Zebrafish
12.
Nutrients ; 11(10)2019 Oct 02.
Article in English | MEDLINE | ID: mdl-31581754

ABSTRACT

Our previous study showed that hydrangenol isolated from Hydrangea serrata leaves exerts antiphotoaging activity in vitro. In this study, we determined its antiphotoaging effect in UVB-irradiated HR-1 hairless mice. We evaluated wrinkle formation, skin thickness, histological characteristics, and mRNA and protein expression using qRT-PCR and Western blot analysis in dorsal skins. Hydrangenol mitigated wrinkle formation, dorsal thickness, dehydration, and collagen degradation. Hydrangenol increased the expression of involucrin, filaggrin, and aquaporin-3 (AQP3) as well as hyaluronic acid (HA) production via hyaluronidase (HYAL)-1/-2 downregulation. Consistent with the recovery of collagen composition, the expression of Pro-COL1A1 was increased by hydrangenol. Matrix metalloproteinase (MMP)-1/-3, cyclooxygenase-2 (COX-2), and interleukin-6 (IL-6) expression was reduced by hydrangenol. Hydrangenol attenuated the phosphorylation of mitogen-activated protein kinases (MAPKs) including ERK and p38, activator protein 1 (AP-1) subunit, and signal transduction and activation of transcription 1 (STAT1). Hydrangenol upregulated the expression of nuclear factor-E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO-1), glutamate cysteine ligase modifier subunit (GCLM), and glutamate cysteine ligase catalysis subunit (GCLC). Taken together, our data suggest that hydrangenol can prevent wrinkle formation by reducing MMP and inflammatory cytokine levels and increasing the expression of moisturizing factors and antioxidant genes.


Subject(s)
Dermatologic Agents/pharmacology , Hydrangea/chemistry , Isocoumarins/pharmacology , Plant Extracts/pharmacology , Plant Leaves/chemistry , Skin Aging/drug effects , Skin/drug effects , Ultraviolet Rays/adverse effects , Water/metabolism , Animals , Antioxidants/metabolism , Collagen Type I/metabolism , Collagen Type I, alpha 1 Chain , Cytokines/metabolism , Dermatologic Agents/isolation & purification , Inflammation Mediators/metabolism , Isocoumarins/isolation & purification , Male , Matrix Metalloproteinase 13/metabolism , Matrix Metalloproteinase 3/metabolism , Mice, Hairless , Plant Extracts/isolation & purification , Proteolysis , Signal Transduction , Skin/metabolism , Skin/pathology , Skin/radiation effects , Skin Aging/radiation effects
13.
Zhongguo Zhong Yao Za Zhi ; 44(9): 1829-1835, 2019 May.
Article in Chinese | MEDLINE | ID: mdl-31342709

ABSTRACT

The chemical constituents from methanol extract of Dichroa hirsuta were separated by silica gel and Sephadex LH-20 column chromatography,high pressure preparative liquid chromatography( HPLC) and recrystallization. Their structures were elucidated by NMR and MS. Nine compounds were obtained and their structures were identified as 3ß,21α-O-diacetyl-lup-9( 11)-en-7ß-ol( 1),( Z)-methyl p-hydroxycinnamate( 2),cis-p-coumaric acid ethyl ester( 3),( E)-methyl p-hydroxycinnamate( 4),trans-p-coumaric acid ethyl ester( 5),4( 3 H)-quinazolinone( 6),7-hydroxycoumarin( 7),hydrangenol( 8) and thunberginol C( 9). Compound 1 is a new lupane-type triterpenoid,and compounds 1-5,8-9 were firstly isolated from this plant. Dual reporter assay results showed that compounds 2-5 could activate the Nrf2-ARE signaling pathway.


Subject(s)
Drugs, Chinese Herbal , Hydrangea/chemistry , Triterpenes/pharmacology , Chromatography, High Pressure Liquid , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Triterpenes/isolation & purification
14.
Phytomedicine ; 57: 385-395, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30849675

ABSTRACT

BACKGROUND: Water extract of Hydrangea paniculata (HP) stem, rich in coumarin glycosides, has been demonstrated to have renal protective effect in several experimental kidney injury animal models. Currently, it is under pre-clinical development as a class 5 herbal drug against membranous nephropathy. However, whether it also benefits diabetic nephropathy (DN) is not clear. PURPOSE: This study was performed to investigate the protective effect of HP on streptozotocin-induced experimental DN, and further understand its molecular mechanisms. METHODS: In the present study, type 1 diabetes rat model was established by the intraperitoneal injection of streptozotocin. HP was orally administered every day for three months. Biochemical analysis and histopathological staining were conducted to evaluate the renal functions. In vivo pharmacokinetic study was conducted to analyse the metabolites of HP with high blood drug concentration. In vitro assay using these metabolites was performed to analyse their ability to reduce reactive oxygen species (ROS) production induced under high glucose (HG) condition by flow cytometry. Reverse transcription-polymerase chain reaction was conducted to analyse the mRNA level of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and IL6 and western blot was performed to analyse the phosphorylation status of smad 2/3 in HK2 cells under TGFß1 stimulation. RESULTS: The treatment with HP significantly reduced the blood urea nitrogen and serum creatinine content, and urine albumin excretion in diabetic rats, and increased the creatinine clearance rate. Periodic acid-schiff and methenamine staining and immunohistochemistry revealed that HP also ameliorated glomerulosclerosis and tubular vacuolar degeneration, as well as the deposition of fibronectin and collagen IV in the glomeruli. Pharmacokinetic study results revealed that the major coumarin compounds from HP were metabolised into umbelliferone and esculetin. By in vitro assay, umbelliferone and esculetin were found to significantly decrease ROS production induced by HG content, as well as increase the mRNA level of Nrf2. HP and its metabolites also can down-regulate fibronectin secretion in HK2 cells stimulated by TGFß1 and inhibit smad2/3 phosphorylation. CONCLUSION: HP has beneficial effect on DN by increasing Nrf2 expression and inhibiting TGF-smad signal activation. Further, it can be a novel herbal drug against DN.


Subject(s)
Coumarins/pharmacology , Diabetic Nephropathies/drug therapy , Hydrangea/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Animals , Coumarins/chemistry , Diabetes Mellitus, Experimental/complications , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/pathology , Fibrosis/drug therapy , Fibrosis/pathology , Glycosides/chemistry , Glycosides/pharmacology , Kidney/drug effects , Kidney/metabolism , Kidney/physiology , Molecular Targeted Therapy/methods , NF-E2-Related Factor 2/metabolism , Plant Extracts/pharmacokinetics , Rats , Rats, Wistar , Smad2 Protein/metabolism , Smad3 Protein/metabolism , Streptozocin , Umbelliferones/pharmacokinetics
15.
Molecules ; 23(6)2018 Jun 12.
Article in English | MEDLINE | ID: mdl-29895788

ABSTRACT

The blue sepal color of hydrangea is due to a metal complex anthocyanin composed of 3-O-glucosyldelphinidin (1) and an aluminum ion with the co-pigments 5-O-caffeoylquinic acid (2) and/or 5-O-p-coumaroylquinic acid (3). The three components, namely anthocyanin, Al3+ and 5-O-acylquinic acids, are essential for blue color development, but the complex is unstable and only exists in an aqueous solution. Furthermore, the complex did not give analyzable NMR spectra or crystals. Therefore, many trials to determine the detailed chemical structure of the hydrangea-blue complex have not been successful to date. Instead, via experiments mixing 1, Al3+ and 2 or 3 in a buffered solution at pH 4.0, we obtained the same blue solution derived from the sepals. However, the ratio was not stoichiometric but fluctuated. To determine the composition of the complex, we tried direct observation of the molecular ion of the complex using electrospray-ionization mass spectrometry. In a very low-concentration buffer solution (2.0 mM) at pH 4.0, we reproduced the hydrangea-blue color by mixing 1, 2 and Al3+ in ratios of 1:1:1, 1:2:1 and 1:3:1. All solution gave the same molecular ion peak at m/z = 843, indicating that the blue solution has a ratio of 1:1:1 for the complex. By using 3, the observed mass number was m/z = 827 and the ratio of 1, 3 and Al3+ was also 1:1:1. A mixture of 1, 3-O-caffeoylquinic acid (4) and Al3+ did not give any blue color but instead was purple, and the intensity of the molecular ion peak at m/z = 843 was very low. These results strongly indicate that the hydrangea blue-complex is composed of a ratio of 1:1:1 for 1, Al3+ and 2 or 3.


Subject(s)
Aluminum/isolation & purification , Anthocyanins/isolation & purification , Chlorogenic Acid/analogs & derivatives , Coumarins/isolation & purification , Glucosides/isolation & purification , Hydrangea/chemistry , Quinic Acid/analogs & derivatives , Aluminum/chemistry , Anthocyanins/chemistry , Chlorogenic Acid/chemistry , Chlorogenic Acid/isolation & purification , Coumarins/chemistry , Flowers/chemistry , Glucosides/chemistry , Hydrogen-Ion Concentration , Molecular Structure , Plant Extracts/chemistry , Quinic Acid/chemistry , Quinic Acid/isolation & purification , Spectrometry, Mass, Electrospray Ionization
16.
Zhongguo Zhong Yao Za Zhi ; 42(9): 1711-1716, 2017 May.
Article in Chinese | MEDLINE | ID: mdl-29082694

ABSTRACT

To develop the HPLC method for simultaneous determination of febrifugine and isofebrifugine in Dichroa febrifuga root, and on the basis of this, the feasibility of quantitative analysis of multi-component by a single-marker (QAMS) model for the determination of the two alkaloids was investigated. The chromatographic separation was performed on an octadecyl bonded silica gel column with mixed solvent consisting of acetonitrile-water-glacial acetic acid-triethylamine (9∶91∶0.36∶0.745) as mobile phase at a flow rate of 1.0 mL•min⁻¹. The detection wavelength was set at 225 nm, and the column temperature was set at 30 ℃. The linear range of febrifugine and isofebrifugine were 10.7-426 ng and 10.6-424 ng, respectively. Their average recovery were 98.33% (RSD 2.7%) and 100.4% (RSD 1.8%), respectively. On the basis of this established method, febrifugine was used as the internal reference substance to calculate the relative correction factors (RCF) and the relative retention values (RRV) of isofebrifugine to febrifugine. Through a series of methodology evaluations, the two alkaloids were simultaneously assayed only by quantitative determination of febrifugine. This result played the part of demonstration role for the application of QAMS model in the determination of isomers.


Subject(s)
Hydrangea/chemistry , Piperidines/isolation & purification , Plant Roots/chemistry , Quinazolines/isolation & purification , Chromatography, High Pressure Liquid
17.
Int J Mol Sci ; 18(7)2017 Jul 10.
Article in English | MEDLINE | ID: mdl-28698525

ABSTRACT

Sodium arsenite (NaAsO2) has been recognized as a worldwide health concern. Hydrangea macrophylla (HM) is used as traditional Chinese medicine possessing antioxidant activities. The study was performed to investigate the therapeutic role and underlying molecular mechanism of HM on NaAsO2-induced toxicity in human liver cancer (HepG2) cells and liver in mice. The hepatoprotective role of HM in HepG2 cells was assessed by using 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT), reactive oxygen species (ROS), and lactate dehydrogenase (LDH) assays. Histopathology, lipid peroxidation, serum biochemistry, quantitative real-time polymerase chain reaction (qPCR) and Western blot analyses were performed to determine the protective role of HM against NaAsO2 intoxication in liver tissue. In this study, we found that co-treatment with HM significantly attenuated the NaAsO2-induced cell viability loss, intracellular ROS, and LDH release in HepG2 cells in a dose-dependent manner. Hepatic histopathology, lipid peroxidation, and the serum biochemical parameters alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were notably improved by HM. HM effectively downregulated the both gene and protein expression level of the mitogen-activated protein kinase (MAPK) cascade. Moreover, HM well-regulated the Bcl-2-associated X protein (Bax)/B-cell lymphoma-2 (Bcl-2) ratio, remarkably suppressed the release of cytochrome c, and blocked the expression of the post-apoptotic transcription factor caspase-3. Therefore, our study provides new insights into the hepatoprotective role of HM through its reduction in apoptosis, which likely involves in the modulation of MAPK/caspase-3 signaling pathways.


Subject(s)
Arsenites/toxicity , Caspase 3/metabolism , Drugs, Chinese Herbal/pharmacology , Hydrangea/chemistry , Mitogen-Activated Protein Kinases/metabolism , Sodium Compounds/toxicity , Alanine Transaminase/metabolism , Apoptosis/drug effects , Aspartate Aminotransferases/metabolism , Hep G2 Cells , Humans , Mitochondria/drug effects , Mitochondria/metabolism , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , bcl-2-Associated X Protein/metabolism
18.
Biol Pharm Bull ; 37(6): 884-91, 2014.
Article in English | MEDLINE | ID: mdl-24882400

ABSTRACT

Potent ligands of peroxisome proliferator-activated receptor γ (PPARγ) such as thiazolidinediones (pioglitazone, troglitazone, etc.) improve insulin sensitivity by increasing the levels of adiponectin, an important adipocytokine associated with insulin sensitivity in adipose tissue. Several constituents from medicinal plants were recently reported to show PPARγ agonist-like activity in 3T3-L1 cells, but did not show agonistic activity at the receptor site different from thiazolidinediones. Our recent studies on PPARγ agonist-like constituents, such as hydrangenol and hydrangeic acid from the processed leaves of Hydrangea macrophylla var. thunbergii, piperlonguminine and retrofractamide A from the fruit of Piper chaba, and tetramethylkaempferol and pentamethylquercetin from the rhizomes of Kaempferia parviflora, are reviewed.


Subject(s)
Hydrangea/chemistry , Hypoglycemic Agents/therapeutic use , PPAR gamma/agonists , Piper/chemistry , Plant Preparations/therapeutic use , Zingiberaceae/chemistry , Adiponectin/blood , Animals , Blood Glucose/metabolism , Dose-Response Relationship, Drug , Drug Discovery , Humans , Hypoglycemic Agents/isolation & purification , Hypoglycemic Agents/pharmacology , Insulin Resistance , Molecular Structure , Plant Preparations/isolation & purification , Plant Preparations/pharmacology
19.
Fitoterapia ; 96: 138-45, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24811324

ABSTRACT

Three new coumarin glucosides (1, 3, 4), and a new secoiridoid glucoside (2), together with one known secoiridoid glucoside (5), were isolated from the stems of Hydrangea paniculata. Their structures were elucidated on the basis of spectroscopic methods, including extensive NMR, MS and CD spectra. At 10 µM, compounds 1-5 showed hepatoprotective activities against DL-galactosamine-induced toxicity in HL-7702 cells.


Subject(s)
Coumarins/pharmacology , Glucosides/pharmacology , Hydrangea/chemistry , Iridoids/pharmacology , Cell Line , Cell Survival/drug effects , Coumarins/chemistry , Coumarins/isolation & purification , Galactosamine/toxicity , Glucosides/chemistry , Glucosides/isolation & purification , Humans , Hydrolysis , Iridoids/chemistry , Iridoids/isolation & purification , Liver/drug effects , Magnetic Resonance Spectroscopy , Molecular Structure , Plant Stems/chemistry
20.
Zhongguo Zhong Yao Za Zhi ; 38(5): 709-13, 2013 Mar.
Article in Chinese | MEDLINE | ID: mdl-23724681

ABSTRACT

OBJECTIVE: To investigate chemical constituents from Chinese herbal medicine Hydrangea macrophylla. METHOD: The compounds were separated and purified by column chromatography over silica gel, ODS, and preparative HPLC. Their structures were identified by spectral methods including 1H, 13C-NMR and MS. RESULT: Eleven compounds were isolated and identified as zeorin, hopane-6, 22-diol (1), botulin (2), betulinic acid (3), 2-ethyl-3-methyl-maleimide-N-beta-D-glucopyranoside (4), uridine (5), thymidine (6), adenosine (7), nicotinamide (8), methyl pyroglutamate (9), hydrangenol (10) and hydrangenol-4'-O-beta-D-glucopyranoside (11), respectively. CONCLUSION: Compounds 14 and 7-9 were obtained from the genus Hydrangea for the first time.


Subject(s)
Drugs, Chinese Herbal/analysis , Drugs, Chinese Herbal/isolation & purification , Hydrangea/chemistry , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal/chemistry , Flowers/chemistry
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