1.Pharmacokinetics and anti-inflammatory activity of cannabidiol/ γ-polyglutamic acid-g-cholesterol nanomicelles.
Rui LI ; Li-Yan LU ; Chu XU ; Rui HAO ; Xiao YU ; Rui GUO ; Jue CHEN ; Wen-Hui RUAN ; Ying-Li WANG
China Journal of Chinese Materia Medica 2025;50(2):534-541
In this study, the pharmacokinetic characteristics and tissue distribution of cannabidiol(CBD)/γ-polyglutamic acid-g-cholesterol(γ-PGA-g-CHOL) nanomicelles [CBD/(γ-PGA-g-CHOL)NMs] were investigated by pharmacokinetic experiments, and the effect of CBD/(γ-PGA-g-CHOL)NMs on the lipopolysaccharide(LPS)-induced inflammatory damage of cells was evaluated by cell experiments. CBD/(γ-PGA-g-CHOL)NMs were prepared by dialysis. The CBD concentrations in the plasma samples of male SD rats treated with CBD and CBD/(γ-PGA-g-CHOL)NMs were investigated, and the pharmacokinetic parameters were calculated and compared. UPLC-MS/MS was employed to determine the concentration of CBD in tissue samples. The heart, liver, spleen, lung, kidney, and muscle samples were collected at different time points to explore the tissue distribution of CBD and CBD/(γ-PGA-g-CHOL)NMs. The Caco-2 cell model of LPS-induced inflammation was established, and the cell viability, transepithelial electrical resistance(TEER), and secretion levels of inflammatory cytokines were determined to compare the anti-inflammatory activity between the two groups. The results showed that CBD/(γ-PGA-g-CHOL)NMs had the average particle size of(163.1±2.3)nm, drug loading of 8.78%±0.28%, and encapsulation rate of 84.46%±0.35%. Compared with CBD, CBD/(γ-PGA-g-CHOL)NMs showed increased peak concentration(C_(max)) and prolonged peak time(t_(max)) and mean residence time(MRT_(0-t)). Within 24 h, the tissue distribution concentration of CBD/(γ-PGA-g-CHOL)NMs was higher than that of CBD. In addition, both CBD and CBD/(γ-PGA-g-CHOL)NMs significantly enhanced Caco-2 cell viability and TEER, lowered the secretion levels of inflammatory cytokines, and alleviated inflammation. Moreover, CBD/(γ-PGA-g-CHOL)NMs demonstrated stronger anti-inflammatory effect. It can be inferred that γ-PGA-g-CHOL blank nanomicelles are good carriers of CBD, being capable of prolonging the circulation time of CBD in the blood, improving the bioavailability and tissue distribution concentration of CBD, and protecting against LPS-induced inflammatory injury. The findings can provide an experimental basis for the development and clinical application of oral CBD preparations.
Animals
;
Cannabidiol/administration & dosage*
;
Polyglutamic Acid/analogs & derivatives*
;
Humans
;
Male
;
Rats
;
Rats, Sprague-Dawley
;
Anti-Inflammatory Agents/administration & dosage*
;
Micelles
;
Caco-2 Cells
;
Cholesterol/pharmacokinetics*
;
Tissue Distribution
;
Nanoparticles/chemistry*
2.Fresh Rehmanniae Radix regulates cholesterol metabolism disorder in mice fed with high-fat and high-cholesterol diet via FXR-mediated bile acid reabsorption.
Xin-Yu MENG ; Yan CHEN ; Li-Qin ZHAO ; Qing-Pu LIU ; Yong-Huan JIN ; Wei-Sheng FENG ; Xiao-Ke ZHENG
China Journal of Chinese Materia Medica 2025;50(6):1670-1679
This study aims to investigate the potential effect of the water extract of fresh Rehmanniae Radix on hypercholesterolemia in mice that was induced by a high-fat and high-cholesterol diet and explore its possible mechanism from bile acid reabsorption. Male C57BL/6 mice were randomly assigned into the following groups: control, model, low-and high-dose(4 and 8 g·kg~(-1), respectively) fresh Rehmanniae Radix, and positive drug(simvastatin, 0.05 g·kg~(-1)). Other groups except the control group were fed with a high-fat and high-cholesterol diet for 6 consecutive weeks to induce hypercholesterolemia. From the 6th week, mice were administrated with corresponding drugs daily via gavage for additional 6 weeks, while continuing to be fed with a high-fat and high-cholesterol diet. Serum levels of total cholesterol(TC), triglycerides(TG), low density lipoprotein-cholesterol(LDL-c), high density lipoprotein-cholesterol(HDL-c), and total bile acid(TBA), as well as liver TC and TG levels and fecal TBA level, were determined by commercial assay kits. Hematoxylin-eosin(HE) staining, oil red O staining, and transmission electron microscopy were performed to observe the pathological changes in the liver. Three livers samples were randomly selected from each of the control, model, and high-dose fresh Rehmanniae Radix groups for high-throughput transcriptome sequencing. Differentially expressed genes were mined and KEGG pathway enrichment analysis was performed to predict the key pathways and target genes of the water extract of fresh Rehmanniae Radix in the treatment of hypercholesterolemia. RT-qPCR was employed to measure the mRNA levels of cholesterol 7α-hydroxylase(CYP7A1) and cholesterol 27α-hydroxylase(CYP27A1) in the liver. Western blot was employed to determine the protein levels of CYP7A1 and CYP27A1 in the liver as well as farnesoid X receptor(FXR), apical sodium-dependent bile acid transporter(ASBT), and ileum bile acid-binding protein(I-BABP) in the ileum. The results showed that the water extract of fresh Rehmanniae Radix significantly lowered the levels of TC and TG in the serum and liver, as well as the level of LDL-c in the serum. Conversely, it elevated the level of HDL-c in the serum and TBA in feces. No significant difference was observed in the level of TBA in the serum among groups. HE staining, oil red O staining, and transmission electron microscopy showed that the water extract reduced the accumulation of lipid droplets in the liver. Further mechanism studies revealed that the water extract of fresh Rehmanniae Radix significantly down-regulated the protein levels of FXR and bile acid reabsorption-related proteins ASBT and I-BABP. Additionally, it enhanced CYP7A1 and CYP27A1, the key enzymes involved in bile acid synthesis. Therefore, it is hypothesized that the water extract of fresh Rehmanniae Radix may exert an anti-hypercholesterolemic effect by regulating FXR/ASBT/I-BABP signaling, inhibiting bile acid reabsorption, and increasing bile acid excretion, thus facilitating the conversion of cholesterol to bile acids.
Animals
;
Male
;
Bile Acids and Salts/metabolism*
;
Mice, Inbred C57BL
;
Mice
;
Diet, High-Fat/adverse effects*
;
Cholesterol/metabolism*
;
Drugs, Chinese Herbal/administration & dosage*
;
Hypercholesterolemia/genetics*
;
Receptors, Cytoplasmic and Nuclear/genetics*
;
Rehmannia/chemistry*
;
Liver/drug effects*
;
Humans
;
Cholesterol 7-alpha-Hydroxylase/genetics*
;
Plant Extracts
3.Hot aqueous leaf extract of Lasianthera africana (Icacinaceae) attenuates rifampicin-isoniazid-induced hepatotoxicity.
Lucky Legbosi NWIDU ; Raphael Ellis TEME
Journal of Integrative Medicine 2018;16(4):263-272
OBJECTIVESThe aim of this study is to evaluate the hepatoprotective effect of Lasianthera africana (Icacinaceae) against isoniazid (INH) and rifampicin (RIF)-induced liver damage in rats.
METHODSThe hepatoprotective effects of hot aqueous L. africana (HALA) leaf extract (0.1-1 g/kg) and silymarin (50 mg/kg) were assessed in a model of oxidative liver damage induced by RIF and INH (100 mg/kg each) in Wistar rats for 28 days. Biochemical markers of hepatic damage such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were assessed. The antioxidant statuses of plasma glutathione peroxidase (GSPx), glutathione reductase (GSH), catalase (CAT) and superoxide dismutase (SOD) and lipid peroxidation were evaluated.
RESULTSThe pretreatment of INH and RIF decreased hematological indices and the antioxidant levels (P < 0.001) and increased the levels of liver marker enzymes (P < 0.001). However, pretreatment with HALA extract and silymarin provoked significant elevation of hematological indices. The levels of AST, ALT, and ALP were depressed (P < 0.001). Total triglycerides, total cholesterol, total bilirubin and low-density lipoprotein were decreased (P < 0.001). However, high-density lipoprotein, bicarbonate, and electrolytes like chloride and potassium were elevated (P < 0.001), but sodium was depressed (P < 0.05). Additionally, GSH, GSPx, SOD and CAT were elevated (P < 0.01) and malondialdehyde was depressed (P < 0.001) when compared to the RIF-INH-treated rats. Histopathological evaluations support hepatoprotective activity.
CONCLUSIONThis study demonstrated that HALA leaf extract attenuated RIF-INH-induced hepatotoxicity. L. africana could be exploited in management of RIF-INH-induced hepatitis.
Alanine Transaminase ; metabolism ; Animals ; Antibiotics, Antitubercular ; toxicity ; Aspartate Aminotransferases ; metabolism ; Chemical and Drug Induced Liver Injury ; drug therapy ; etiology ; metabolism ; Cholesterol ; metabolism ; Female ; Glutathione ; metabolism ; Humans ; Isoniazid ; toxicity ; Liver ; drug effects ; enzymology ; Magnoliopsida ; chemistry ; Male ; Malondialdehyde ; metabolism ; Plant Extracts ; administration & dosage ; Plant Leaves ; chemistry ; Rats, Wistar ; Rifampin ; toxicity ; Superoxide Dismutase ; metabolism
4.Phytochemical characterization of polyphenolic compounds with HPLC-DAD-ESI-MS and evaluation of lipid-lowering capacity of aqueous extracts from Saharan plant Anabasis aretioides (Coss & Moq.) in normal and streptozotocin-induced diabetic rats.
Omar FARID ; Farid KHALLOUKI ; Morad AKDAD ; Andrea BREUER ; Robert Wyn OWEN ; Mohamed EDDOUKS
Journal of Integrative Medicine 2018;16(3):185-191
OBJECTIVEAnabasis aretioides (Coss & Moq.), a Saharan plant belonging to Chenopodiaceae family, is widely distributed in semi-desert areas from the Tafilalet region of Morocco. This plant is extensively used by local population against diabetes and cardiovascular disorders. The purpose of the study was to investigate the effect of the aqueous A. aretioides extract on lipid metabolism in normal and streptozotocin (STZ)-induced diabetic rats and to identify the polyphenolic compounds present. In addition, the in vitro antioxidant activity of the aqueous A. aretioides extract was also evaluated.
METHODSThe effect of an aerial part aqueous extract (APAE) of A. aretioides (5 mg/kg of lyophilized A. aretioides APAE) on plasma lipid profile was investigated in normal and STZ-induced diabetic rats (n = 6) after once daily oral administration for 15 days. The aqueous extract was tested for its 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity. Polyphenolic compounds in the extracts were definitively characterized by high-performance liquid chromatography-diode array detection-electrospray ionization-mass spectrometry.
RESULTSIn diabetic rats, oral administration of A. aretioides APAE provoked a significant decrease in both plasma cholesterol and triglyceride levels from the first to the second week (P < 0.01). A significant decrease on plasma triglyceride levels was also observed in normal rats (P < 0.01), where the reduction was 53%. In addition, the phytochemical analysis revealed the presence of 12 polyphenolic compounds. Moreover, according to the DPPH radical-scavenging activity, the aqueous extract showed an in vitro antioxidant activity.
CONCLUSIONAqueous A. aretioides APAE exhibits lipid-lowering and in vitro antioxidant activities. Many polyphenols were present in this extract and these phytoconstituents may be involved in the pharmacological activity of this plant.
Animals ; Antioxidants ; administration & dosage ; Chenopodiaceae ; chemistry ; Cholesterol ; blood ; Chromatography, High Pressure Liquid ; Diabetes Mellitus, Experimental ; blood ; drug therapy ; Humans ; Hypolipidemic Agents ; administration & dosage ; chemistry ; Male ; Phytochemicals ; administration & dosage ; chemistry ; Plant Extracts ; administration & dosage ; chemistry ; Polyphenols ; administration & dosage ; chemistry ; Rats ; Rats, Wistar ; Streptozocin ; Tandem Mass Spectrometry ; Triglycerides ; blood
5.Hypolipidemic effect of SIPI-7623, a derivative of an extract from oriental wormwood, through farnesoid X receptor antagonism.
Yi-Fang DENG ; Xiao-Ling HUANG ; Mei SU ; Peng-Xia YU ; Zhen ZHANG ; Quan-Hai LIU ; Guo-Ping WANG ; Min-Yu LIU
Chinese Journal of Natural Medicines (English Ed.) 2018;16(8):572-579
Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily of ligand-activated transcription factors. As a metabolic regulator, FXR plays key roles in bile acid and cholesterol metabolism and lipid and glucose homeostasis. Therefore, FXR is a potential drug target for several metabolic syndromes, especially those related to lipidemia disorders. In the present study, we identified small molecule SIPI-7623, a derivative of an extract from Oriental wormwood (Artemisia capillaris), and found that it specifically upregulated the expression of cholesterol-7-alpha-hydroxylase (CYP7A1), downregulated the expression of sterol-regulatory element-binding protein 1c (SREBP-1c) in the liver, and inhibited the expression of ileal bile acid binding-protein (IBABP) in the ileum of rats. We found that inhibition of FXR by SIPI-7623 decreased the level of cholesterol and triglyceride. SIPI-7623 reduced the levels of cholesterol and triglyceride in in vitro HepG2 cell models, ameliorated diet-induced atherosclerosis, and decreased the serum lipid content on rats and rabbits model of atherosclerosis in vivo. Furthermore, SIPI-7623 decreased the extent of atherosclerotic lesions. Our resutls demonstrated that antagonism of the FXR pathway can be employed as a therapeutic strategy to treat metabolic diseases such as hyperlipidemia and atherosclerosis. In conclusion, SIPI-7623 could be a promising lead compound for development of drugs to treat hyperlipidemia and atherosclerosis.
Animals
;
Artemisia
;
chemistry
;
Atherosclerosis
;
drug therapy
;
genetics
;
metabolism
;
Cholesterol
;
metabolism
;
Cholesterol 7-alpha-Hydroxylase
;
genetics
;
metabolism
;
Drugs, Chinese Herbal
;
administration & dosage
;
Humans
;
Hyperlipidemias
;
drug therapy
;
genetics
;
metabolism
;
Hypolipidemic Agents
;
administration & dosage
;
Liver
;
drug effects
;
metabolism
;
Male
;
Rabbits
;
Rats
;
Rats, Sprague-Dawley
;
Receptors, Cytoplasmic and Nuclear
;
antagonists & inhibitors
;
genetics
;
metabolism
;
Sterol Regulatory Element Binding Protein 1
;
genetics
;
metabolism
;
Triglycerides
;
metabolism
6.Kimchi attenuates fatty streak formation in the aorta of low-density lipoprotein receptor knockout mice via inhibition of endoplasmic reticulum stress and apoptosis.
Minji WOO ; Mijeong KIM ; Jeong Sook NOH ; Chan Hum PARK ; Yeong Ok SONG
Nutrition Research and Practice 2017;11(6):445-451
BACKGROUND/OBJECTIVES: Endoplasmic reticulum (ER) stress is positively associated with atherosclerosis via elevating macrophage cell death and plaque formation, in which oxidative stress plays a pivotal role. Antioxidative, lipid-lowering, and anti-atherogenic effects of kimchi, a Korean fermented vegetable, have been established, wherein capsaicin, ascorbic acid, quercetin, 3-(4'-hydroxyl-3',5'-dimethoxyphenyl)propionic acid, and lactic acids were identified. In this study, mechanisms of action of kimchi methanol extracts (KME) on fatty streak formation via suppression of ER stress and apoptosis in aorta were examined in low-density lipoprotein receptor knockout mice. MATERIALS AND METHODS: Mice fed a high cholesterol diet with an oral administration of KME (KME group, 200 mg·kg-bw⁻¹·day⁻¹) or distilled water (control group) for 8 weeks (n = 20 for group). Plasma lipid and oxidative stress levels were evaluated. Protein expression was measured by western blot assay. Fatty streak lesion size and the degree of apoptosis were examined in the aorta. RESULTS: Compared to the control group, in the KME group, plasma lipids levels were decreased and oxidative stress was alleviated (P < 0.05). Protein expression levels of nuclear factor (erythroid-derived 2)-like 2-mediated antioxidants in aorta were increased whereas those for ER stress markers, glucose regulated protein 78, phospho-protein kinase RNA-like ER kinase, phospho-eukaryotic initiation factor 2 subunit α, X-box binding protein 1, and C/EBP homologous protein were decreased in the KME group (P < 0.05). Moreover, apoptosis was suppressed via downregulation of phospho-c-Jun N-terminal kinase, bcl-2-associated X protein, caspases-9, and -3 with a concomitant upregulation of anti-apoptotic protein, B-cell lymphoma 2 (P < 0.05). Fatty streak lesion size was reduced and the degree of apoptosis was less severe in the KME group (P < 0.05). CONCLUSIONS: In conclusion, antioxidant activity of KME might prevent fatty streak formation through, in part, inhibition of ER stress and apoptosis in aortic sinus where macrophages are harbored.
Administration, Oral
;
Animals
;
Antioxidants
;
Aorta*
;
Apoptosis*
;
Ascorbic Acid
;
Atherosclerosis
;
bcl-2-Associated X Protein
;
Blotting, Western
;
Capsaicin
;
Carrier Proteins
;
Cell Death
;
Cholesterol
;
Diet
;
Down-Regulation
;
Endoplasmic Reticulum Stress*
;
Endoplasmic Reticulum*
;
Glucose
;
Hypercholesterolemia
;
Lactic Acid
;
Lipoproteins*
;
Lymphoma, B-Cell
;
Macrophages
;
Methanol
;
Mice
;
Mice, Knockout*
;
Oxidative Stress
;
Phosphotransferases
;
Plasma
;
Prokaryotic Initiation Factor-2
;
Quercetin
;
Receptors, Lipoprotein*
;
Sinus of Valsalva
;
Up-Regulation
;
Vegetables
;
Water
7.Restoration of Declined Immune Responses and Hyperlipidemia by Rubus occidenalis in Diet-Induced Obese Mice.
Youngjoo LEE ; Jiyeon KIM ; Jinho AN ; Sungwon LEE ; Heetae LEE ; Hyunseok KONG ; Youngcheon SONG ; Hye Ran CHOI ; Ji Wung KWON ; Daekeun SHIN ; Chong Kil LEE ; Kyungjae KIM
Biomolecules & Therapeutics 2017;25(2):140-148
Hyperlipidemia, which is closely associated with a fatty diet and aging, is commonly observed in the western and aged society. Therefore, a novel therapeutic approach for this disease is critical, and an immunological view has been suggested as a novel strategy, because hyperlipidemia is closely associated with inflammation and immune dysfunction. In this study, the effects of an aqueous extract of Rubus occidentalis (RO) in obese mice were investigated using immunological indexes. The mice were fed a high-fat diet (HFD) to induce hyperlipidemia, which was confirmed by biochemical analysis and examination of the mouse physiology. Two different doses of RO and rosuvastatin, a cholesterol synthesis inhibitor used as a control, were orally administered. Disturbances in immune cellularity as well as lymphocyte proliferation and cytokine production were significantly normalized by oral administration of RO, which also decreased the elevated serum tumor necrosis factor (TNF)-α level and total cholesterol. The specific immune-related actions of RO comprised considerable improvement in cytotoxic T cell killing functions and regulation of antibody production to within the normal range. The immunological evidence confirms the significant cholesterol-lowering effect of RO, suggesting its potential as a novel therapeutic agent for hyperlipidemia and associated immune decline.
Administration, Oral
;
Aging
;
Animals
;
Antibody Formation
;
Cholesterol
;
Diet
;
Diet, High-Fat
;
Homicide
;
Hyperlipidemias*
;
Inflammation
;
Lymphocytes
;
Mice
;
Mice, Obese*
;
Physiology
;
Reference Values
;
Rosuvastatin Calcium
;
Rubus*
;
Tumor Necrosis Factor-alpha
8.Effects of Rapamycin on Clinical Manifestations and Blood Lipid Parameters in Different Preeclampsia-like Mouse Models.
Yan-Hong YI ; Zi YANG ; Yi-Wei HAN ; Jing HUAI
Chinese Medical Journal 2017;130(9):1033-1041
BACKGROUNDThe pathogenesis of some types of preeclampsia is related to fatty acid oxidation disorders. Rapamycin can regulate fatty acid metabolism. This study aimed to investigate the effects of rapamycin on the clinical manifestations and blood lipid parameters in different preeclampsia-like mouse models.
METHODSTwo preeclampsia-like mouse models and a control group were established: L-NA (injected with Nω-nitro-L-arginine methyl ester), LPS (injected with lipopolysaccharide), and the control group with normal saline (NS). The mouse models were established at preimplantation (PI), early- and late-pregnancy (EP, LP) according to the time of pregnancy. The administration of rapamycin (RA; L-NA+RA, LPS+RA, and NS+RA) or vehicle as controls (C; L-NA+C, LPS+C, NS+C) were followed on the 2nd day after the mouse models' establishment. Each subgroup consisted of eight pregnant mice. The mean arterial pressure (MAP), 24-h urinary protein, blood lipid, fetus, and placental weight were measured. The histopathological changes and lipid deposition of the liver and placenta were observed. Student's t-test was used for comparing two groups. Repeated measures analysis of variance was used for blood pressure analysis. Qualitative data were compared by Chi-square test.
RESULTSThe MAP and 24-h urinary protein in the PI, EP, and LP subgroups of the L-NA+C and LPS+C groups were significantly higher compared with the respective variables in the NS+C group (P < 0.05). The preeclampsia-like mouse models were established successfully. There was no significant difference in the MAP between the PI, EP, and LP subgroups of the L-NA+RA and L-NA+C groups and the LPS+RA and LPS+C groups. The 24-h urine protein levels in the PI and EP subgroups of the L-NA+RA group were significantly lower compared with the respective levels in the L-NA+C groups (1037 ± 63 vs. 2127 ± 593 μg; 976 ± 42 vs. 1238 ± 72 μg; bothP < 0.05), also this effect appeared similar in the PI and EP subgroups of the LPS+RA and LPS+C groups (1022 ± 246 vs. 2141 ± 432 μg; 951 ± 41 vs. 1308 ± 30 μg; bothP < 0.05). The levels of serum-free fatty acid (FFA) in the PI and EP subgroups of the L-NA+RA groups were significantly lower compared with the respective levels in the L-NA+C group (2.49 ± 0.44 vs. 3.30 ± 0.18 mEq/L; 2.23 ± 0.29 vs. 2.84 ± 0.14 mEq/L; bothP < 0.05). The levels of triglycerides (TG) and total cholesterol in the PI subgroup of the L-NA+RA group were significantly lower compared with the respective levels in the L-NA+C (1.51 ± 0.16 vs. 2.41 ± 0.37 mmol/L; 2.11 ± 0.17 vs. 2.47 ± 0.26 mmol/L; bothP < 0.05), whereas high-density lipoprotein serum concentration was significantly higher (1.22 ± 0.19 vs. 0.87 ± 0.15 mmol/L;P < 0.05) and low-density lipoprotein serum concentration did not exhibit a significant difference. There were no significant differences in the FFA of the PI, EP, and LP subgroups between the LPS+RA and the LPS+C groups. The levels of TG in the PI subgroup of the LPS+RA group were significantly lower compared with the respective levels in the LPS+C group (0.97 ± 0.05 vs. 1.22 ± 0.08 mmol/L;P < 0.05).
CONCLUSIONRapamycin can improve clinical manifestations and blood lipid profile in part of the preeclampsia-like mouse models.
Animals ; Blood Pressure ; drug effects ; Chi-Square Distribution ; Cholesterol ; blood ; Disease Models, Animal ; Female ; Lipid Metabolism ; drug effects ; Lipids ; blood ; Lipoproteins, HDL ; blood ; Lipoproteins, LDL ; blood ; Mice ; Mice, Inbred C57BL ; Placenta ; drug effects ; metabolism ; Pre-Eclampsia ; blood ; drug therapy ; Pregnancy ; Pregnancy Outcome ; Sirolimus ; therapeutic use ; Triglycerides ; administration & dosage ; blood
9.Corn silk extract improves cholesterol metabolism in C57BL/6J mouse fed high-fat diets.
Jae Hoon CHA ; Sun Rim KIM ; Hyun Joong KANG ; Myung Hwan KIM ; Ae Wha HA ; Woo Kyoung KIM
Nutrition Research and Practice 2016;10(5):501-506
BACKGROUND/OBJECTIVES: Corn silk (CS) extract contains large amounts of maysin, which is a major flavonoid in CS. However, studies regarding the effect of CS extract on cholesterol metabolism is limited. Therefore, the purpose of this study was to determine the effect of CS extract on cholesterol metabolism in C57BL/6J mouse fed high-fat diets. MATERIALS/METHODS: Normal-fat group fed 7% fat diet, high-fat (HF) group fed 25% fat diet, and high-fat with corn silk (HFCS) group were orally administered CS extract (100 mg/kg body weight) daily. Serum and hepatic levels of total lipids, triglycerides, and total cholesterol as well as serum free fatty acid, glucose, and insulin levels were determined. The mRNA expression levels of acyl-CoA: cholesterol acyltransferase (ACAT), cholesterol 7-alpha hydroxylase (CYP7A1), farnesoid X receptor (FXR), lecithin cholesterol acyltransferase (LCAT), low-density lipoprotein receptor, 3-hyroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), adiponectin, leptin, and tumor necrosis factor α were determined. RESULTS: Oral administration of CS extract with HF improved serum glucose and insulin levels as well as attenuated HF-induced fatty liver. CS extracts significantly elevated mRNA expression levels of adipocytokines and reduced mRNA expression levels of HMG-CoA reductase, ACAT, and FXR. The mRNA expression levels of CYP7A1 and LCAT between the HF group and HFCS group were not statistically different. CONCLUSIONS: CS extract supplementation with a high-fat diet improves levels of adipocytokine secretion and glucose homeostasis. CS extract is also effective in decreasing the regulatory pool of hepatic cholesterol, in line with decreased blood and hepatic levels of cholesterol though modulation of mRNA expression levels of HMG-CoA reductase, ACAT, and FXR.
Adipokines
;
Adiponectin
;
Administration, Oral
;
Animals
;
Blood Glucose
;
Cholesterol*
;
Diet
;
Diet, High-Fat*
;
Fatty Liver
;
Glucose
;
Homeostasis
;
Insulin
;
Leptin
;
Metabolism*
;
Mice*
;
Oxidoreductases
;
Phosphatidylcholine-Sterol O-Acyltransferase
;
Receptors, Lipoprotein
;
RNA, Messenger
;
Silk*
;
Sterol O-Acyltransferase
;
Triglycerides
;
Tumor Necrosis Factor-alpha
;
Zea mays*
10.High maysin corn silk extract reduces body weight and fat deposition in C57BL/6J mice fed high-fat diets.
Eun Young LEE ; Sun Lim KIM ; Hyeon Jung KANG ; Myung Hwan KIM ; Ae Wha HA ; Woo Kyoung KIM
Nutrition Research and Practice 2016;10(6):575-582
BACKGROUNG/OBJECTIVES: The study was performed to investigate the effects and mechanisms of action of high maysin corn silk extract on body weight and fat deposition in experimental animals. MATERIALS/METHODS: A total of 30 male C57BL/6J mice, 4-weeks-old, were purchased and divided into three groups by weight using a randomized block design. The normal-fat (NF) group received 7% fat (diet weight basis), the high-fat (HF) group received 25% fat and 0.5% cholesterol, and the high-fat corn silk (HFCS) group received high-fat diet and high maysin corn silk extract at 100 mg/kg body weight through daily oral administration. Body weight and body fat were measured, and mRNA expression levels of proteins involved in adipocyte differentiation, fat accumulation, fat synthesis, lipolysis, and fat oxidation in adipose tissue and the liver were measured. RESULTS: After experimental diet intake for 8 weeks, body weight was significantly lower in the HFCS group compared to the HF group (P < 0.05), and kidney fat and epididymal fat pad weights were significantly lower in the HFCS group compared to the HF group (P < 0.05). In the HFCS group, CCAAT/enhancer binding protein-β, peroxisome proliferator-activated receptor-γ1 (PPAR-γ1), and PPAR-γ2 mRNA expression levels were significantly reduced (P < 0.05) in the epididymal fat pad, whereas cluster of differentiation 36, lipoprotein lipase, acetyl-CoA carboxylase-1, sterol regulatory element binding protein-1c, pyruvate dehydrogenase kinase, isozyme-4, glucose-6-phosphate dehydrogenase, and stearoyl-CoA desaturase-1 mRNA expression levels were significantly decreased in liver and adipose tissues (P < 0.05). In the HFCS group, mRNA expression levels of AMP-activated protein kinase, hormone-sensitive lipase, and carnitine palmitoyltransferase-1 were elevated (P < 0.05). CONCLUSIONS: It can be concluded that high maysin corn silk extract inhibits expression of genes involved in adipocyte differentiation, fat accumulation, and fat synthesis as well as promotes expression of genes involved in lipolysis and fat oxidation, further inhibiting body fat accumulation and body weight elevation in experimental animals.
Acetyl Coenzyme A
;
Adipocytes
;
Adipose Tissue
;
Administration, Oral
;
AMP-Activated Protein Kinases
;
Animals
;
Body Weight*
;
Carnitine
;
Cholesterol
;
Diet
;
Diet, High-Fat*
;
Glucosephosphate Dehydrogenase
;
Humans
;
Kidney
;
Lipolysis
;
Lipoprotein Lipase
;
Liver
;
Male
;
Mice*
;
Oxidoreductases
;
Peroxisomes
;
Phosphotransferases
;
Pyruvic Acid
;
RNA, Messenger
;
Silk*
;
Sterol Esterase
;
Weights and Measures
;
Zea mays*

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