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Liu T, Wang L, Ji L, Mu L, Wang K, Xu G, Wang S, Ma Q. Plantaginis Semen Ameliorates Hyperuricemia Induced by Potassium Oxonate. Int J Mol Sci 2024; 25:8548. [PMID: 39126116 PMCID: PMC11313179 DOI: 10.3390/ijms25158548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 07/25/2024] [Accepted: 07/27/2024] [Indexed: 08/12/2024] Open
Abstract
Plantaginis semen is the dried ripe seed of Plantago asiatica L. or Plantago depressa Willd., which has a long history in alleviating hyperuricemia (HUA) and chronic kidney diseases. While the major chemical ingredients and mechanism remained to be illustrated. Therefore, this work aimed to elucidate the chemicals and working mechanisms of PS for HUA. UPLC-QE-Orbitrap-MS was applied to identify the main components of PS in vitro and in vivo. RNA sequencing (RNA-seq) was conducted to explore the gene expression profile, and the genes involved were further confirmed by real-time quantitative PCR (RT-qPCR). A total of 39 components were identified from PS, and 13 of them were detected in the rat serum after treating the rat with PS. The kidney tissue injury and serum uric acid (UA), xanthine oxidase (XOD), and cytokine levels were reversed by PS. Meanwhile, renal urate anion transporter 1 (Urat1) and glucose transporter 9 (Glut9) levels were reversed with PS treatment. RNA-seq analysis showed that the PPAR signaling pathway; glycine, serine, and threonine metabolism signaling pathway; and fatty acid metabolism signaling pathway were significantly modified by PS treatment. Further, the gene expression of Slc7a8, Pck1, Mgll, and Bhmt were significantly elevated, and Fkbp5 was downregulated, consistent with RNA-seq results. The PPAR signaling pathway involved Pparα, Pparγ, Lpl, Plin5, Atgl, and Hsl were elevated by PS treatment. URAT1 and PPARα proteins levels were confirmed by Western blotting. In conclusion, this study elucidates the chemical profile and working mechanisms of PS for prevention and therapy of HUA and provides a promising traditional Chinese medicine agency for HUA prophylaxis.
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Affiliation(s)
| | | | | | | | | | | | - Shifeng Wang
- Key Laboratory of TCM-Information Engineer of State Administration of TCM, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China; (T.L.); (L.W.); (L.J.); (L.M.); (K.W.); (G.X.)
| | - Qun Ma
- Key Laboratory of TCM-Information Engineer of State Administration of TCM, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China; (T.L.); (L.W.); (L.J.); (L.M.); (K.W.); (G.X.)
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Saeki T, Yamamoto S, Akaki J, Tanaka T, Nakasone M, Ikeda H, Wang W, Inoue M, Manse Y, Ninomiya K, Morikawa T. Ameliorative effect of bofutsushosan (Fangfengtongshengsan) extract on the progression of aging-induced obesity. J Nat Med 2024; 78:576-589. [PMID: 38662301 PMCID: PMC11937147 DOI: 10.1007/s11418-024-01803-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Accepted: 03/06/2024] [Indexed: 04/26/2024]
Abstract
This study aimed to compare fat accumulation in young and aged mice raised on a high-fat diet and to characterize the obesity-reducing effects of a Kampo medicine, bofutsushosan (BTS; fangfengtongshengsan in Chinese). Aged mice fed a high-fat diet containing 2% BTS extract for 28 days exhibited a significant reduction in weight gain and accumulation of visceral and subcutaneous fat, which were greater degree of reduction than those of the young mice. When the treatment period was extended to two months, the serum aspartate aminotransferase and alanine aminotransferase levels and the accumulation of fat droplets in the hepatocytes decreased. The mRNA expression of mitochondrial uncoupling protein 1 (UCP1) in the brown adipose tissue was significantly reduced in the aged mice compared to the young mice but increased by 2% in the BTS-treated aged mice. Additionally, the effect of BTS extract on oleic acid-albumin-induced triglyceride accumulation in hepatoblastoma-derived HepG2 cells was significantly inhibited in a concentration-dependent manner. Evaluation of the single crude drug extracts revealed that Forsythia Fruit, Schizonepeta Spike, and Rhubarb were the active components in BTS extract. These results suggest that BTS extract is effective against visceral, subcutaneous, and ectopic fats in the liver, which tend to accumulate with aging. Thus, BTS extract is useful in preventing and ameliorating the development of obesity and metabolic syndrome.
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Affiliation(s)
- Takafumi Saeki
- Central R&D Laboratory, Kobayashi Pharmaceutical Co., Ltd, 1-30-3 Toyokawa, Ibaraki, Osaka, 567-0057, Japan.
| | - Saya Yamamoto
- Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka, 577-8502, Japan
| | - Junji Akaki
- Central R&D Laboratory, Kobayashi Pharmaceutical Co., Ltd, 1-30-3 Toyokawa, Ibaraki, Osaka, 567-0057, Japan
| | - Takahiro Tanaka
- Central R&D Laboratory, Kobayashi Pharmaceutical Co., Ltd, 1-30-3 Toyokawa, Ibaraki, Osaka, 567-0057, Japan
| | - Misaki Nakasone
- Central R&D Laboratory, Kobayashi Pharmaceutical Co., Ltd, 1-30-3 Toyokawa, Ibaraki, Osaka, 567-0057, Japan
| | - Hidemasa Ikeda
- Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka, 577-8502, Japan
| | - Wei Wang
- Laboratory of Medicinal Resources, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya, 464-8650, Japan
| | - Makoto Inoue
- Laboratory of Medicinal Resources, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya, 464-8650, Japan
| | - Yoshiaki Manse
- Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka, 577-8502, Japan
| | - Kiyofumi Ninomiya
- Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka, 577-8502, Japan
- School of Pharmacy, Shujitsu University, 1-6-1 Nishigawara, Naka-ku, Okayama, 703-8516, Japan
| | - Toshio Morikawa
- Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka, 577-8502, Japan.
- Antiaging Center, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka, 577-8502, Japan.
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Takata T, Motoo Y. Novel In Vitro Assay of the Effects of Kampo Medicines against Intra/Extracellular Advanced Glycation End-Products in Oral, Esophageal, and Gastric Epithelial Cells. Metabolites 2023; 13:878. [PMID: 37512585 PMCID: PMC10385496 DOI: 10.3390/metabo13070878] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 07/20/2023] [Accepted: 07/21/2023] [Indexed: 07/30/2023] Open
Abstract
Kampo medicines are Japanese traditional medicines developed from Chinese traditional medicines. The action mechanisms of the numerous known compounds have been studied for approximately 100 years; however, many remain unclear. While components are normally affected through digestion, absorption, and metabolism, in vitro oral, esophageal, and gastric epithelial cell models avoid these influences and, thus, represent superior assay systems for Kampo medicines. We focused on two areas of the strong performance of this assay system: intracellular and extracellular advanced glycation end-products (AGEs). AGEs are generated from glucose, fructose, and their metabolites, and promote lifestyle-related diseases such as diabetes and cancer. While current technology cannot analyze whole intracellular AGEs in cells in some organs, some AGEs can be generated for 1-2 days, and the turnover time of oral and gastric epithelial cells is 7-14 days. Therefore, we hypothesized that we could detect these rapidly generated intracellular AGEs in such cells. Extracellular AEGs (e.g., dietary or in the saliva) bind to the receptor for AGEs (RAGE) and the toll-like receptor 4 (TLR4) on the surface of the epithelial cells and can induce cytotoxicity such as inflammation. The analysis of Kampo medicine effects against intra/extracellular AGEs in vitro is a novel model.
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Affiliation(s)
- Takanobu Takata
- Division of Molecular and Genetic Biology, Department of Life Science, Medical Research Institute, Kanazawa Medical University, Uchinada 920-0293, Ishikawa, Japan
| | - Yoshiharu Motoo
- Department of Medical Oncology and Kampo Medicines, Komatsu Sophia Hospital, Komatsu 923-0861, Ishikawa, Japan
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Wong AR, Yang AWH, Li K, Gill H, Li M, Lenon GB. Chinese Herbal Medicine for Weight Management: A Systematic Review and Meta-Analyses of Randomised Controlled Trials. J Obes 2021; 2021:3250723. [PMID: 33763238 PMCID: PMC7964117 DOI: 10.1155/2021/3250723] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Revised: 11/23/2020] [Accepted: 02/09/2021] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVE This review investigated the effects and safety of Chinese herbal medicine (CHM) formulas on weight management. METHODS Eighteen databases in English, Chinese, Korean, and Japanese were searched from their inceptions to September 2019. The treatment groups included CHM formulations, and the control included placebo, Western medication (WM), and lifestyle intervention (LI), with or without cointerventions (WM and/or LI). Quality of studies was assessed using Cochrane Collaboration's risk of bias assessment tool. Body weight and body mass index (BMI) were analysed in RevMan v5.4.1 and expressed as mean differences with 95% confidence intervals (CI), while adverse events were expressed as risk ratio with 95% CI. RESULTS Thirty-nine RCTs were eligible for qualitative analysis, 34 of which were included in the meta-analyses. The majority of studies had a high or unclear risk of selection, performance, and detection bias. Twenty-five CHM studies involving cointerventions revealed that CHM had significant adjunct effects on body weight and BMI at the end of treatment compared to control. No serious adverse events were reported in the CHM groups. CONCLUSION CHM indicates a promising adjunct to facilitate WM or lifestyle change for weight management. However, methodological barriers such as lack of allocation concealment and double-blinding may have led to challenges in data synthesis. More rigorously designed RCTs involving cointerventions are warranted.
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Affiliation(s)
- Ann Rann Wong
- School of Health and Biomedical Sciences, RMIT University Bundoora, VIC, Australia
| | - Angela Wei Hong Yang
- School of Health and Biomedical Sciences, RMIT University Bundoora, VIC, Australia
| | - Kangxiao Li
- School of Health and Biomedical Sciences, RMIT University Bundoora, VIC, Australia
| | - Harsharn Gill
- School of Science, RMIT University, Melbourne VIC, Australia
| | - Mingdi Li
- School of Health and Biomedical Sciences, RMIT University Bundoora, VIC, Australia
| | - George Binh Lenon
- School of Health and Biomedical Sciences, RMIT University Bundoora, VIC, Australia
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AEBP1 is a Novel Oncogene: Mechanisms of Action and Signaling Pathways. JOURNAL OF ONCOLOGY 2020; 2020:8097872. [PMID: 32565808 PMCID: PMC7273425 DOI: 10.1155/2020/8097872] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/16/2020] [Accepted: 04/13/2020] [Indexed: 12/29/2022]
Abstract
Adipocyte enhancer-binding protein 1 (AEBP1) is a transcriptional repressor involved in the regulation of critical biological processes including adipogenesis, mammary gland development, inflammation, macrophage cholesterol homeostasis, and atherogenesis. Several years ago, we first reported the ability of AEBP1 to exert a positive control over the canonical NF-κB pathway. Indeed, AEBP1 positively regulates NF-κB activity via its direct interaction with IκBα, a key NF-κB inhibitor. AEBP1 overexpression results in uncontrollable activation of NF-κB, which may have severe pathogenic outcomes. Recently, the regulatory relationship between AEBP1 and NF-κB pathway has been of great interest to many researchers primarily due to the implication of NF-κB signaling in critical cellular processes such as inflammation and cancer. Since constitutive activation of NF-κB is widely implicated in carcinogenesis, AEBP1 overexpression is associated with tumor development and progression. Recent studies sought to explore the effects of the overexpression of AEBP1, as a potential oncogene, in different types of cancer. In this review, we analyze the effects of AEBP1 overexpression in a variety of malignancies (e.g., breast cancer, glioblastoma, bladder cancer, gastric cancer, colorectal cancer, ovarian cancer, and skin cancer), with a specific focus on the AEBP1-mediated control over the canonical NF-κB pathway. We also underscore the ability of AEBP1 to regulate crucial cancer-related events like cell proliferation and apoptosis in light of other key pathways (e.g., PI3K-Akt, sonic hedgehog (Shh), p53, parthanatos (PARP-1), and PTEN). Identifying AEBP1 as a potential biomarker for cancer prognosis may lead to a novel therapeutic target for the prevention and/or treatment of various types of cancer.
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Park HS, Wijerathne CUB, Jeong HY, Seo CS, Ha H, Kwun HJ. Gastroprotective effects of Hwanglyeonhaedok-tang against Helicobacter pylori-induced gastric cell injury. JOURNAL OF ETHNOPHARMACOLOGY 2018; 216:239-250. [PMID: 29410309 DOI: 10.1016/j.jep.2018.01.025] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/22/2017] [Revised: 01/18/2018] [Accepted: 01/19/2018] [Indexed: 06/07/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Helicobacter pylori, which is found in the stomachs of approximately half of the world's population, has been associated with the development of chronic gastritis and gastric cancer. Hwanglyeonhaedok-tang (HHT) is a popular traditional medicine for the therapies of gastric ulcers and gastritis. AIM OF THE STUDY The emerging resistance of H. pylori to antibiotics arouses requirement on alternative nonantibiotic-based therapies. In the present study, we investigated the anti-inflammatory activity and anti-microbial activity of HHT against H. pylori in vitro and in an H. pylori-infected mouse model. MATERIALS AND METHODS H. pylori were treated with various concentrations of HHT and then incubated with human gastric carcinoma AGS cells. For the in vivo study, mice were orally infected with H. pylori three times over the course of 1 week, and then subjected to daily administration of HHT (120 or 600 mg/kg) for 4 weeks or standard triple therapy for 1 week. At the scheduled termination of the experiment, all mice were killed and their stomachs were collected for histological examination, quantitative real-time PCR, and Western blot analysis. RESULTS Our in vitro studies showed that HHT treatment inhibited the adhesion of H. pylori to AGS cells and suppressed the H. pylori-induced increases of inflammatory regulators, such as interleukin (IL)-8, cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS). In the mouse model, HHT treatment significantly reduced H. pylori colonization, inflammation, and the levels of IL-1β, IL-6, C-X-C motif chemokine ligand 1 (CXCL1), tumor necrosis factor alpha (TNF-α), COX-2, and iNOS in gastric mucosa. Further investigation showed that HHT treatment reduced the H. pylori-induced phosphorylations of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK), and nuclear factor-kappa B (NF-κB). CONCLUSIONS Our findings collectively suggest that HHT has anti-inflammatory activity and antibacterial activity against H. pylori and could be an alternative to antibiotics for preventing H. pylori infection.
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Affiliation(s)
- Hee-Seon Park
- Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea..
| | - Charith U B Wijerathne
- Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea..
| | - Hye-Yun Jeong
- Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea..
| | - Chang-Seob Seo
- K-herb Research Center, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea..
| | - Hyekyung Ha
- K-herb Research Center, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea..
| | - Hyo-Jung Kwun
- Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea..
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Kim H, Kim I, Lee MC, Kim HJ, Lee GS, Kim H, Kim BJ. Effects of Hwangryunhaedok-tang on gastrointestinal motility function in mice. World J Gastroenterol 2017; 23:2705-2715. [PMID: 28487607 PMCID: PMC5403749 DOI: 10.3748/wjg.v23.i15.2705] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2016] [Revised: 02/22/2017] [Accepted: 03/20/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the effects of Hwangryunhaedok-tang (HHT) on gastrointestinal (GI) motility in mice.
METHODS The effects of a boiling water extract of HHT (HHTE) on GI motility were investigated by calculating percent intestinal transit rates (ITR%) and gastric emptying (GE) values using Evans Blue and phenol red, respectively, in normal mice and in mice with experimentally induced GI motility dysfunction (GMD). In addition, the effects of the four components of HHT, that is, Gardeniae Fructus (GF), Scutellariae Radix (SR), Coptidis Rhizoma (CR), and Phellodendri Cortex (PC), on GI motility were also investigated.
RESULTS In normal ICR mice, ITR% and GE values were significantly and dose-dependently increased by the intragastric administration of HHTE (0.1-1 g/kg). The ITR% values of GMD mice were significantly lower than those of normal mice, and these reductions were significantly and dose-dependently inhibited by HHTE (0.1-1 g/kg). Additionally, GF, CR, and PC dose-dependently increased ITR% and GE values in normal and GMD mice.
CONCLUSION These results suggest that HHT is a novel candidate for the development of a gastroprokinetic agent for the GI tract.
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Chen YY, Yan Y, Zhao Z, Shi MJ, Zhang YB. Bofutsushosan ameliorates obesity in mice through modulating PGC-1α expression in brown adipose tissues and inhibiting inflammation in white adipose tissues. Chin J Nat Med 2017; 14:449-56. [PMID: 27473963 DOI: 10.1016/s1875-5364(16)30042-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2015] [Indexed: 02/07/2023]
Abstract
The inducible co-activator PGC-1α plays a crucial role in adaptive thermogenesis and increases energy expenditure in brown adipose tissue (BAT). Meanwhile, chronic inflammation caused by infiltrated-macrophage in the white adipose tissue (WAT) is a target for the treatment of obesity. Bofutsushosan (BF), a traditional Chinese medicine composed of 17 crude drugs, has been widely used to treat obesity in China, Japan, and other Asia countries. However, the mechanism underlying anti-obesity remains to be elucidated. In the present study, we demonstrated that BF oral administration reduced the body weight of obese mice induced by high-fat diet (HFD) and alleviated the level of biochemical markers (P < 0.05), including blood glucose (Glu), total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL-C) and insulin. Our further results also indicated that oral BF administration increased the expression of PGC-1α and UCP1 in BAT. Moreover, BF also reduced the expression of inflammatory cytokines in WAT, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). These findings suggested that the mechanism of BF against obesity was at least partially through increasing gene expression of PGC-1α and UCP1 for energy consumption in BAT and inhibiting inflammation in WAT.
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Affiliation(s)
- Ying-Ying Chen
- State Key Laboratory of Natural Medicines, Department of Biochemistry, China Pharmaceutical University, Nanjing 210009, China; Shanghai Key Laboratory of Complex Prescription, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Yan Yan
- State Key Laboratory of Natural Medicines, Department of Biochemistry, China Pharmaceutical University, Nanjing 210009, China
| | - Zheng Zhao
- Department of Pharmacy, Nanjing First Hospital, Nanjing Medical University, Nanjing 210009, China
| | - Mei-Jing Shi
- State Key Laboratory of Natural Medicines, Department of Biochemistry, China Pharmaceutical University, Nanjing 210009, China
| | - Yu-Bin Zhang
- State Key Laboratory of Natural Medicines, Department of Biochemistry, China Pharmaceutical University, Nanjing 210009, China.
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DNA Microarray-Based Screening and Characterization of Traditional Chinese Medicine. MICROARRAYS 2017; 6:microarrays6010004. [PMID: 28146102 PMCID: PMC5374364 DOI: 10.3390/microarrays6010004] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/16/2016] [Accepted: 01/23/2017] [Indexed: 12/14/2022]
Abstract
The application of DNA microarray assay (DMA) has entered a new era owing to recent innovations in omics technologies. This review summarizes recent applications of DMA-based gene expression profiling by focusing on the screening and characterizationof traditional Chinese medicine. First, herbs, mushrooms, and dietary plants analyzed by DMA along with their effective components and their biological/physiological effects are summarized and discussed by examining their comprehensive list and a list of representative effective chemicals. Second, the mechanisms of action of traditional Chinese medicine are summarized by examining the genes and pathways responsible for the action, the cell functions involved in the action, and the activities found by DMA (silent estrogens). Third, applications of DMA for traditional Chinese medicine are discussed by examining reported examples and new protocols for its use in quality control. Further innovations in the signaling pathway based evaluation of beneficial effects and the assessment of potential risks of traditional Chinese medicine are expected, just as are observed in other closely related fields, such as the therapeutic, environmental, nutritional, and pharmacological fields.
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Administration of Hwang-Ryun-Haedok-tang, a Herbal Complex, for Patients With Abdominal Obesity: A Case Series. Explore (NY) 2015; 11:401-6. [DOI: 10.1016/j.explore.2015.07.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Indexed: 11/19/2022]
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Park J, Bose S, Hong SW, Lee DK, Yoo JW, Lim CY, Lee M, Kim H. Impact of GNB3-C825T, ADRB3-Trp64Arg, UCP2-3'UTR 45 bp del/ins, and PPARγ-Pro12Ala polymorphisms on Bofutsushosan response in obese subjects: a randomized, double-blind, placebo-controlled trial. J Med Food 2014; 17:558-70. [PMID: 24827746 DOI: 10.1089/jmf.2013.2836] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Obesity is known to be influenced by a number of genes, including the β3 subunit of G protein (GNB3), β3-adrenergic receptor (ADRB3), uncoupling protein 2 (UCP2), and peroxisome proliferator activated receptor gamma (PPARγ). The single nucleotide polymorphisms (SNPs) of the above genes, such as GNB3-C825T, ADRB3-Trp64Arg, UCP2-3'UTR 45 bp del/ins, and PPARγ-Pro12Ala, are associated with obesity and body mass index. The present study evaluates the impact of Bofutsushosan, a traditional Eastern Asian herbal medicine with known anti-obesity properties, on obese subjects according to the presence of the above-mentioned SNPs. Upon randomization, the volunteers were allocated to receive Bofutsushosan (n=55) or placebo (n=56) treatments for 8 weeks. Following the treatment schedule, significant reductions in total cholesterol and significant improvement in the Korean version of obesity-related quality of life scale were seen in the Bofutsushosan-treated group, but not in placebo. Bofutsushosan exerted significant anti-obesity effects on a number of parameters in the carriers of the GNB3-825T allele, but only on waist circumference in the GNB3-C/C homozygote. Significant anti-obesity impact of Bofutsushosan was also seen on a number of obesity-indices in both ADRB3-Arg64 carriers and ADRB3-Trp64 homozygotes, as well as in UCP2-D/D carriers, but not in UCP2-D/I+I/I variants. The effect of Bofutsushosan was more pronounced in PPARγ-Pro/Pro genotype compared to PPARγ-Pro/Ala variants. Thus, the results revealed differential responses of the subjects to the anti-obesity effects of Bofutsushosan treatment according to the polymorphism of the vital obesity-related genes. Our study provides new insight into individualized clinical applications of Bofutsushosan for obesity.
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Affiliation(s)
- Junghyun Park
- 1 Department of Oriental Rehabilitation, Gangnam Korean Hospital, Kyunghee University , Seoul, Korea
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Bofutsushosan, a Japanese herbal (Kampo) medicine, attenuates progression of nonalcoholic steatohepatitis in mice. J Gastroenterol 2014; 49:1065-73. [PMID: 23800945 PMCID: PMC4048468 DOI: 10.1007/s00535-013-0852-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2012] [Accepted: 06/13/2013] [Indexed: 02/04/2023]
Abstract
BACKGROUND Obesity-induced liver disease (nonalcoholic fatty liver disease, NAFLD) is now the commonest cause of chronic liver disease in affluent nations. There are presently no proven treatments for NAFLD or its more severe stage, nonalcoholic steatohepatitis (NASH). Bofutsushosan (BTS), a Japanese herbal (Kampo) medicine, long used as an anti-obesity medicine in Japan and other Asian countries, has been shown to reduce body weight and improve insulin resistance (IR) and hepatic steatosis. The precise mechanism of action of BTS, however, remains unclear. To evaluate the ability of BTS to prevent the development of NASH, and determine the mediators and pathways involved. METHODS C57BL/6 mice were injected intra-peritoneally with gold-thioglucose and fed a high-fat diet (HF) or HF diet admixed with either 2 or 5 % BTS for 12 weeks. The effectiveness of BTS in attenuating features of NASH and the mechanisms through which BTS attenuated NASH were then assayed through an assessment of the anthropometric, radiological, biochemical and histological parameters. RESULTS BTS attenuated the progression of NASH through induction of adiponectin and its receptors along with an induction of PPAR-α and PPAR-γ, decreased expression of SREBP-1c, increased hepatic fatty acid oxidation and increased hepatic export of triglycerides. BTS moreover, reduced IR through phosphorylation of the protein kinase, Akt. CONCLUSIONS BTS through induction of adiponectin signaling and Akt attenuated development of NASH. Identification of the active entity in BTS should allow development of novel treatments for NASH.
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13
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Role of Kampo medicine in integrative cancer therapy. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2013; 2013:570848. [PMID: 23997796 PMCID: PMC3723058 DOI: 10.1155/2013/570848] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/19/2013] [Accepted: 06/16/2013] [Indexed: 12/12/2022]
Abstract
Clinical trials to date demonstrate that standard cancer treatments are currently the most efficient treatments for large numbers of cancer patients. Cancer treatments will increasingly require approaches that allow patients to live with cancer, by increasing their natural healing power and tumor immunity, as well as attenuating the progression of their cancers, instead of only attacking the cancer cells directly. Complementary and alternative medicine, including Kampo medicine, compensates for the drawbacks of western medicine by increasing patients' self-defense mechanisms. In Japan, clinicians who have studied both western medicine and Kampo treat cancer patients by fusing the two medical systems into a unitary one. The goal of the system is to assist the functional maintenance and recovery of the living body complex with the physical, mental, social, and spiritual balance, rather than addressing direct antitumor effects. In this review, we describe the usefulness of Kampo medicine, especially juzentaihoto, and outline the reports on evidence, in addition to the report on an attitudinal survey about the use of Kampo medicine in cancer treatment in Japan.
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Inhibitory Effects of Hwangryunhaedok-Tang in 3T3-L1 Adipogenesis by Regulation of Raf/MEK1/ERK1/2 Pathway and PDK1/Akt Phosphorylation. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2013; 2013:413906. [PMID: 23762131 PMCID: PMC3676921 DOI: 10.1155/2013/413906] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/22/2013] [Accepted: 05/07/2013] [Indexed: 01/31/2023]
Abstract
Hwangryunhaedok-tang (HRT) has been long used as traditional medicine in Asia. However, inhibitory role of HRT is unclear in early stage of 3T3-L1 adipocyte differentiation related to signaling. In the present study, we investigated the inhibitory effects of HRT on upstream signaling of peroxisome proliferation-activity receptor-γ (PPAR-γ) and CCAAT/enhancer binding protein-β (C/EBP-β) expression in differentiation of 3T3-L1 preadipocytes. We found that HRT significantly inhibited the adipocyte differentiation by downregulating several adipocyte-specific transcription factors including PPAR-γ, C/EBP-α, and C/EBP-β in 3T3-L1 preadipocytes. Furthermore, we observed that HRT markedly inhibited the differentiation media-mediated phosphorylation of Raf/extracellular mitogen-activated protein kinase 1 (MEK1)/signal-regulated protein kinase 1/2 (ERK1/2) and phosphorylation of phosphoinositide-dependent kinase 1 (PDK1)/Akt. These results indicate that anti-adipogenesis mechanism involves the downregulation of the major transcription factors of adipogenesis including PPAR-γ and C/EBP-α through inhibition of Raf/MEK1/ERK1/2 phosphorylation and PDK1/Akt phosphorylation by HRT. Furthermore, high performance liquid chromatography (HPLC) analysis showed HRT contains active antiobesity constituents such as palmatine, berberine, geniposide, baicalin, baicalein, and wogonin. Taken together, this study suggested that anti-adipogenesis effects of HRT were accounted by downregulation of Raf/MEK1/ERK1/2 pathway and PDK1/Akt pathway during 3T3-L1 adipocyte differentiation.
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Yamakawa JI, Moriya J, Takeuchi K, Nakatou M, Motoo Y, Kobayashi J. Significance of Kampo, Japanese traditional medicine, in the treatment of obesity: basic and clinical evidence. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2013; 2013:943075. [PMID: 23662155 PMCID: PMC3639634 DOI: 10.1155/2013/943075] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/21/2012] [Revised: 02/20/2013] [Accepted: 03/03/2013] [Indexed: 11/25/2022]
Abstract
The cause of obesity includes genetic and environmental factors, including cytokines derived from adipocytes (adipo-cytokines). Although drug therapy is available for obesity, it is highly risky. Our main focus in this review is on the traditional form of Japanese medicine, Kampo, in the treated of obesity. Two Kampo formulas, that is, bofutsushosan () and boiogito (), are covered by the national health insurance in Japan for the treatment of obesity. Various issues related to their action mechanisms remain unsolved. Considering these, we described the results of basic experiments and presented clinical evidence and case reports on osteoarthritis as examples of clinical application of their two Kampo medicine. Traditional medicine is used not only for treatment but also for prevention. In clinical practice, it is of great importance to prove the efficacy of combinations of traditional medicine and Western medicine and the utility of traditional medicine in the attenuation of adverse effects of Western medicine.
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Affiliation(s)
- Jun-ichi Yamakawa
- Department of General Medicine, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku District Ishikawa 920-0293, Japan
| | - Junji Moriya
- Department of General Medicine, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku District Ishikawa 920-0293, Japan
| | - Kenji Takeuchi
- Department of Anesthesia, Fukuiken Saiseikai Hospital, Fukui, Japan
| | - Mio Nakatou
- Department of General Medicine, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku District Ishikawa 920-0293, Japan
| | - Yoshiharu Motoo
- Department of Medical Oncology, Kanazawa Medical University, Ishikawa, Japan
| | - Junji Kobayashi
- Department of General Medicine, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku District Ishikawa 920-0293, Japan
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Boqué N, de la Iglesia R, de la Garza AL, Milagro FI, Olivares M, Bañuelos Ó, Soria AC, Rodríguez-Sánchez S, Martínez JA, Campión J. Prevention of diet-induced obesity by apple polyphenols in Wistar rats through regulation of adipocyte gene expression and DNA methylation patterns. Mol Nutr Food Res 2013; 57:1473-8. [DOI: 10.1002/mnfr.201200686] [Citation(s) in RCA: 66] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2012] [Revised: 01/17/2013] [Accepted: 02/11/2013] [Indexed: 11/06/2022]
Affiliation(s)
- Noemi Boqué
- Department of Nutrition, Food Science; Physiology and Toxicology; University of Navarra; Pamplona; Spain
| | - Rocío de la Iglesia
- Department of Nutrition, Food Science; Physiology and Toxicology; University of Navarra; Pamplona; Spain
| | - Ana L. de la Garza
- Department of Nutrition, Food Science; Physiology and Toxicology; University of Navarra; Pamplona; Spain
| | | | - Mónica Olivares
- Discovery Laboratory, Health and Nutrition Department; Biosearch S.A.; Granada; Spain
| | - Óscar Bañuelos
- Discovery Laboratory, Health and Nutrition Department; Biosearch S.A.; Granada; Spain
| | - Ana Cristina Soria
- Department of Instrumental Analysis and Environmental Chemistry; Institute of General Organic Chemistry (CSIC); Madrid; Spain
| | - Sonia Rodríguez-Sánchez
- Department of Instrumental Analysis and Environmental Chemistry; Institute of General Organic Chemistry (CSIC); Madrid; Spain
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Yu Q, Takahashi T, Nomura M, Yasuda M, Obatake-Ikeda K, Kobayashi S. Effects of Single Administered Bofutsushosan-Composed Crude Drugs on Diabetic Serum Parameters in Streptozotocin-Induced Diabetic Mice. Chin Med 2013. [DOI: 10.4236/cm.2013.41005] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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18
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Murayama T, Li Y, Takahashi T, Yamada R, Matsubara K, Tuchida Y, Li Z, Sadanari H. Anti-cytomegalovirus effects of tricin are dependent on CXCL11. Microbes Infect 2012; 14:1086-92. [DOI: 10.1016/j.micinf.2012.05.017] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2012] [Revised: 05/15/2012] [Accepted: 05/26/2012] [Indexed: 11/26/2022]
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Li L, Zeng H, Shan L, Yuan X, Li Y, Liu R, Zhang W. The different inhibitory effects of Huang-Lian-Jie-Du-Tang on cyclooxygenase 2 and 5-lipoxygenase. JOURNAL OF ETHNOPHARMACOLOGY 2012; 143:732-739. [PMID: 22884869 DOI: 10.1016/j.jep.2012.07.037] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/12/2012] [Revised: 07/19/2012] [Accepted: 07/23/2012] [Indexed: 06/01/2023]
Abstract
BACKGROUND Huang-Lian-Jie-Du-Tang (HLJDT), a famous traditional Chinese prescription with wide anti-inflammatory applications, is an aqueous extract of four herbal materials: Rhizoma coptidis, Radix scutellariae, Cortex phellodendri, and Fructus gardeniae. Its effects on the cyclooxygenase (COX)-2 and 5-lipoxygenase (5-LOX) pathways are thought to be responsible for its anti-inflammatory activity. However, our previous work found that the inhibitory effects of HLJDT act on the 5-LOX pathway but not on the COX pathway. The possibility that HLJDT inhibits COX-2- or 5-LOX-catalyzed eicosanoid generation by downregulating enzyme expression requires further investigation. AIM OF THE STUDY To observe the effects of HLJDT and its four major components (baicalin, baicalein, berberine and geniposide) on COX-2- or 5-LOX-catalyzed eicosanoid generation and to distinguish the effects of HLJDT on enzyme activity from those on enzyme expression. METHODS The topical anti-inflammatory activities and inhibition of eicosanoid formation of HLJDT and its components were observed in an arachidonic acid (AA)-induced mouse ear edema model. Macrophage-based systems were established to observe the effects of the drugs on enzyme activity and enzyme expression of COX-2 and 5-LOX. Further experiments were carried out to confirm these effects at the mRNA and protein levels. RESULTS Topical treatment of HLJDT significantly inhibited AA-induced mouse ear edema and reduced PGE(2) and LTB(4) release in the edematous ears. Baicalein, geniposide, and berberine also ameliorated the symptoms and suppressed eicosanoid generation with varying efficacies. Cell-based assays showed that HLJDT and baicalein inhibited the PGE(2) levels by decreasing COX-2 enzyme expression without affecting COX-2 enzyme activity in RAW 246.7 murine macrophages. The other experiments on rat peritoneal macrophages indicated that HLJDT and baicalein exerted significant inhibition on LTB(4) production by decreasing 5-LOX enzyme activity. The real-time PCR and western blotting data demonstrated that HLJDT and baicalein reduced COX-2 expression at the mRNA and protein levels, whereas no inhibition on 5-LOX expression was observed. CONCLUSIONS HLJDT can suppress eicosanoid generation via both the COX and LOX pathways, which definitely contributes to its topical anti-inflammatory activity. We have confirmed that its dual inhibition on the COX and LOX pathways mainly result from the downregulation of COX-2 expression and direct inhibition of 5-LOX activity, respectively. Baicalein worked as a potent active component in most of the tests. These findings about the different inhibitory effects of HLJDT on COX-2 and 5-LOX help to better understand the mechanism of HLJDT and promote safer applications of drug.
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Affiliation(s)
- Li Li
- Department of Natural Product Chemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, PR China
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Gene expression profiling of Bangpungtongseong-san (Bofutsushosan) and Bangkihwangki-tang (Boiogito) administered individuals. BIOCHIP JOURNAL 2012. [DOI: 10.1007/s13206-012-6206-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
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21
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Ota N, Takano F, Muroga S, Kawabata T, Ishigaki Y, Yahagi N, Ohta T. Garlic extract and its selected organosulphur constituents promote ileal immune responses ex vivo. J Funct Foods 2012. [DOI: 10.1016/j.jff.2011.11.003] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
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22
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Murayama T, Bi C, Li Y, Ishigaki Y, Takano F, Takegami T, Ohta T, Sumino H, Ubukata K, Takahashi T. Inhibitory Effects of Statins on Cytomegalovirus Production in Human Cells: Comprehensive Analysis of Gene Expression Profiles. ACTA ACUST UNITED AC 2011. [DOI: 10.1016/j.jecm.2010.12.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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