atractylenolide-i and Disease-Models--Animal

Atractylodes macrocephala Koidz is a widely used as a traditional Chinese medicine. Atractylenolides (-I, -II, and -III) are a class of lactone compounds derived from Atractylodes macrocephala Koidz. Research into atractylenolides over the past two decades has shown that atractylenolides have anti-cancer, anti-inflammatory, anti-platelet, anti-osteoporosis, and antibacterial activity; protect the nervous system; and regulate blood glucose and lipids. Because of structural differences, both atractylenolide-I and atractylenolide-II have remarkable anti-cancer activities, and atractylenolide-I and atractylenolide-III have remarkable anti-inflammatory and neuroprotective activities. We therefore recommend further clinical research on the anti-cancer, anti-inflammatory and neuroprotective effects of atractylenolides, determine their therapeutic effects, alone or in combination. To investigate their ability to regulate blood glucose and lipid, as well as their anti-platelet, anti-osteoporosis, and antibacterial activities, both in vitro and in vivo studies are necessary. Atractylenolides are rapidly absorbed but slowly metabolized; thus, solubilization studies may not be necessary. However, due to the inhibitory effects of atractylenolides on metabolic enzymes, it is necessary to pay attention to the possible side effects of combining atractylenolides with other drugs, in clinical application. In short, atractylenolides have considerable medicinal value and warrant further study.

Topics: Animals; Atractylodes; Disease Models, Animal; Humans; Inflammation; Lactones; Medicine, Chinese Traditional; Mice; Neoplasms; Nervous System Diseases; Rhizome; Sesquiterpenes

Cancer cachexia is a multifactorial metabolic syndrome that affects ∼50%-80% of cancer patients, and no effective therapy for cancer cachexia is presently available. In traditional Chinese medicine, a large portion of patients with cancer cachexia was diagnosed as spleen deficiency syndrome and treated with tonifying TCMs that produce clinic benefits. In this study we established a new animal model of spleen deficiency and cancer cachexia in mice and evaluated the therapeutic effects of atractylenolide I, an active component of tonifying TCM BaiZhu, in the mouse model. Cancer cachexia was induced in male BALB/c mice by inoculation of mouse C26 colon adenocarcinoma cells, whereas spleen deficiency syndrome was induced by treating the mice with spleen deficiency-inducing factors, including limited feeding, fatigue, and purging. The mouse model was characterized by both cachexia and spleen deficiency characteristics, including significant body weight loss, cancer growth, muscle atrophy, fat lipolysis, spleen, and thymus atrophy as compared with healthy control mice, cancer cachexia mice, and spleen deficiency mice. Oral administration of atractylenolide I (20 mg· kg

Topics: Adenocarcinoma; Animals; Cachexia; Colonic Neoplasms; Disease Models, Animal; Lactones; Male; Mice; Mice, Inbred BALB C; Sesquiterpenes; Spleen; Splenic Diseases; Syndrome

Parkinson's disease (PD) is an age-related neurological disorder characterized by a loss of dopaminergic neurons within the midbrain. Neuroinflammation has been nominated as one of the key pathogenic features of PD. Recently, the inadequate pharmacotherapy and adverse effects of conventional drugs have spurred the development of unconventional medications in the treatment of PD. The purpose of this study is to investigate the anti-neuroinflammatory mechanisms of Atractylenolide-I (ATR-I) in in vivo and in vitro models of PD. Nitrite assay was measured via Griess reaction in lipopolysaccharide (LPS) stimulated BV-2 cells. mRNA and protein levels were determined by a reverse transcription-polymerase chain reaction (RT-PCR) and immunoblot analysis, respectively. Further, flow cytometry, immunocytochemistry, and immunohistochemistry were employed in BV-2 cells and MPTP-intoxicated C57BL6/J mice. Pre-treatment with ATR-I attenuated the inflammatory response in BV-2 cells by abating the nuclear translocation of nuclear factor-κB (NF-κB) and by inducing heme oxygenase-1 (HO-1). The intraperitoneal administration of ATR-I reversed MPTP-induced behavioral deficits, decreased microglial activation, and conferred protection to dopaminergic neurons in the mouse model of PD. Our experimental reports establish the involvement of multiple benevolent molecular events by ATR-I in MPTP-induced toxicity, which may aid in the development of ATR-I as a new therapeutic agent for the treatment of PD.

Topics: Animals; Cell Line; Cytokines; Disease Models, Animal; Heme Oxygenase-1; Injections, Intraperitoneal; Lactones; Lipopolysaccharides; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; Microglia; Neuroprotective Agents; NF-kappa B; Nitric Oxide Synthase Type II; Parkinson Disease; Reactive Oxygen Species; Sesquiterpenes

Atractylenolide I (AT-I), an active compound isolated from Atractylodes macrocephala Koidz (Compositae), shows several pharmacological activities.. Our present study is designed to investigate the protective effect of AT-I on systemic inflammation in the mouse model of sepsis created by cecal ligation and puncture (CLP), and explore the possible mechanism.. Sepsis mouse model was established by CLP, and the tested dosages of AT-I were 10, 20, and 40 mg/kg (ip). Pro-inflammatory cytokines in serum (TNF-α, IL-1β and IL-6) were determined by the ELISA method; serum lipopolysaccharide (LPS) level was measured by the Limulus Amebocyte Lysate (LAL) test; white blood cells (WBC) were counted by Blood cell analyzer; contents of alanine transaminase (ALT), aspartate transarninase (AST), creatinine (Cre), and blood urea nitrogen (BUN) in serum were determined by automatic biochemistry analyzer. For survival rate tests, CLP mice were observed within 7 days, and body temperature was measured at 0, 4, 8, 12, 24, 48 and 72 h after surgery.. Our results indicated that AT-I significantly increased the survival rate of mice with sepsis (p < 0.05), whereas the WBCs and levels of LPS, pro-inflammatory cytokines (TNF-α, IL-1β and IL-6), ALT, AST, Cre, and BUN decreased significantly after treatment with AT-I (p < 0.05).. In conclusion, the AT-I ameliorates sepsis syndrome by reduction of pro-inflammatory cytokines and LPS, and provides an improvement in liver and kidney functions.

Topics: Alanine Transaminase; Animals; Anti-Inflammatory Agents; Aspartate Aminotransferases; Biomarkers; Blood Urea Nitrogen; Cecum; Creatinine; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Inflammation; Inflammation Mediators; Kidney; Lactones; Ligation; Lipopolysaccharides; Liver; Mice; Punctures; Sepsis; Sesquiterpenes; Time Factors

Xiaoyaosan (XYS), a well-known formula for relieving depression, was originated from the book of "Taiping Huimin Heji Jufang" in Song Dynasty (960-1127 AD), composed of Radix Bupleuri, Radix Angelicae Sinensis, Radix Paeoniae Alba, Rhizoma Atractylodis Macrocephalae, Poria, Herba Menthae, Rhizoma Zingiberis Recens and Radix Glycyrrhizae with dose proportion of 6:6:6:6:6:3:2:2. It is commonly used for the treatment of depression-related syndromes in China. In the formula, Radix Bupleuri usually serves as the principal drug, Radix Angelicae Sinensis and Radix Paeoniae Alba serve as the ministerial drugs, Rhizoma Atractylodis Macrocephalae, Poria, Herba Menthae and Rhizoma Zingiberis Recens serve as adjunctive drugs, Radix Glycyrrhizae serves as messenger drug, they coordinate with each other and enhance the effect of the formula. In our previous experiments, the antidepressant effect of XYS was revealed. However, the antidepressant part (or component) of this prescription was still obscure.. An experimental despair animal model: the mice tail suspension test (TST) was used to evaluate the antidepressant activity of XYS and its fractions. GC-MS method was developed to identify the volatile components and determine 4 major volatile components in active fraction.. In the TST test, the effect of a low polar fraction (XY-EA) was superior to other fractions of XYS. 13 volatile compounds in the XY-EA were identified on the basis of standards, isolation and structural determination in our laboratory, NIST 05 database and literature data. The content of 4 major volatile compounds in XY-EA which is 6.703%.. The petroleum ether fraction (XY-EA) appears to be the active fraction of XYS. 4 major components Z-ligustilide, palmitic acid, atractylenolide I, and atractylenolide II may be the antidepressant active compounds.

Topics: 4-Butyrolactone; Animals; Antidepressive Agents; Behavior, Animal; Depression; Disease Models, Animal; Drugs, Chinese Herbal; Gas Chromatography-Mass Spectrometry; Lactones; Male; Mice; Mice, Inbred ICR; Molecular Structure; Motor Activity; Palmitic Acid; Phytotherapy; Plants, Medicinal; Sesquiterpenes; Volatilization

Although some anti-allergic activities of the rhizome of Atractylodes japonica have been previously reported, the active principle(s) for anti-allergic action is not fully elucidated and the effect of this plant material on atopic dermatitis (AD) is not known. In this study, the 70% ethanol extract of the rhizome of A. japonica was found to significantly inhibit 5-lipoxygenase (5-LOX)-catalyzed leukotrienes (LT) production from rat basophilic leukemia (RBL)-1 cells. From the extract of A. japonica, three major sesquiterpene derivatives including atractylenolide I, atractylenolide III and eudesma-4,7-dien-8-one were successfully isolated. Among these compounds, only atractylenolide I was shown to strongly inhibit 5-LOX from RBL-1 cells (IC(50) = 18.6 μM). To evaluate the effects of experimental AD, the ethanol extract of A. japonica (200 mg/day) was administered orally to hapten-treated NC/Nga mice which is an animal model of AD. It was firstly found that the extract significantly inhibited AD-like symptoms in mice, as judged by severity score and scratching behavior. Taken together, it is concluded that A. japonica possesses the inhibitory activity on 5-LOX and an animal model of AD, and atractylenolide I may contribute, at least in part, to these anti-allergic actions of A. japonica.

Topics: Animals; Anti-Allergic Agents; Arachidonate 5-Lipoxygenase; Atractylodes; Cell Line, Tumor; Dermatitis, Atopic; Disease Models, Animal; Inhibitory Concentration 50; Lactones; Leukemia, Basophilic, Acute; Leukotrienes; Lipoxygenase Inhibitors; Male; Mice; Plant Extracts; Rats; Rhizome; Sesquiterpenes; Severity of Illness Index

The roots of Cyathula officinalis Kuan are widely used in Chinese medicine for the treatment of inflammatory disorders. Here, the ability of C. officinalis Kuan to downregulate matrix metalloproteinase (MMP)-13 was examined since MMP-13 is an important enzyme for the degradation of the cartilage collagen matrix, especially under arthritic conditions. The ethanol extract of C. officinalis Kuan as well as the N-hexane and chloroform soluble fractions were found to potently inhibit MMP-13 induction in IL-1 β-treated SW1353 cells, a human chondrosarcoma cell line, at 50-200 µg/mL. Activity-guided separation led to the isolation of six compounds, palmitic acid (1), β-sitosterol (2), α-spinasterol (3), atractylenolide I (4), 1,3-diacetoxy-tetradeca-6E,12E-dien-8,10-dyn (5), and N-trans-feruloyl-3-methyldopamine (6). Among these, 4 and 5 exhibited MMP-13 downregulating activity in IL-1 β-treated SW1353 cells. And 4 also showed anti-oedematous activity against λ-carageenan-induced paw edema in mice at 20-200 mg/kg, p. o. The results of this study provide information that can help elucidate the action mechanism of C. officinalis Kuan. In addition, the results presented here suggest that C. officinalis Kuan and its constituents may have the potential for chondroprotection against cartilage degrading disorders.

Topics: Acetates; Alkynes; Amaranthaceae; Animals; Carrageenan; Cartilage; Cell Line, Tumor; Chondrocytes; Chondrosarcoma; Disease Models, Animal; Dopamine; Down-Regulation; Edema; Humans; Hypolipidemic Agents; Interleukin-1beta; Lactones; Male; Matrix Metalloproteinase 13; Medicine, Chinese Traditional; Mice; Mice, Inbred ICR; Phytotherapy; Plant Extracts; Plant Roots; Sesquiterpenes; Sitosterols; Stigmasterol

Angiogenesis is involved in the pathology of chronic inflammatory diseases. Application of anti-angiogenic strategies is beneficial in the treatment of inflammatory disorders. Atractylenolide I is an anti-inflammation agent. To further investigate the anti-angiogenesis mechanism of atractylenolide I in cell and mice based on inflammation model, the vascular index and microvessel outgrowth were measured by using the Freunds complete adjuvant (FCA) induced mouse air pouch model as well as the mice aortic ring co-cultured with peritoneal macrophages model. The ID(50) values of atractylenolide I were 15.15 mg/kg and 3.89 microg/ml for inhibiting the vascular index in vivo and microvessel outgrowth in vitro, respectively. Atractylenolide I could dose-dependently inhibit the production of nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF) activity in the flute of mouse air pouch and the peritoneal macrophages stimulated by lipopolysaccharide (LPS). Atractylenolide I displayed a potent inhibitory effect on angiogenesis by a set of down-regulatory actions of NO, TNF-alpha, IL-1beta, IL-6, VEGF and PlGF in chronic inflammation.

Topics: Angiogenesis Inhibitors; Animals; Anti-Inflammatory Agents; Aorta; Chronic Disease; Coculture Techniques; Disease Models, Animal; Dose-Response Relationship, Drug; Endothelial Cells; Endothelium, Vascular; Female; Inflammation; Inhibitory Concentration 50; Interleukin-1beta; Interleukin-6; Lactones; Macrophages, Peritoneal; Male; Mice; Mice, Inbred BALB C; Microvessels; Molecular Structure; Neovascularization, Pathologic; Nitric Oxide; Nitric Oxide Synthase Type II; Placenta Growth Factor; Pregnancy Proteins; Sesquiterpenes; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

The petroleum ether-ether (1 : 1) extract of Atractylodis macrocephalae was screened by cell membrane chromatography (CMC) and subsequently separated by column chromatography (CC) and high performance liquid chromatography (HPLC). Five components were isolated and identified as atractylenolide III 1, atractylenolide I 2, 14-acetoxy-12-senecioyloxytetradeca-2E,8E,10E-trien-4,6-diyn-1-ol 3, 14-acetoxy-12-alpha-methylbutyl-2E,8E,10E-trien-4,6-diyn-1-ol 4 and 14-acetoxy-12-beta-methylbutyl-2E,8E,10E-trien-4,6-diyn-1-ol 5 by routine spectrometric methods. The data of 5 and (13)C-NMR data of 3 and 4 were reported for the first time. Further in vivo experiments showed that the five components exhibited significant inhibiting effects both on the ear edema induced by xylene and on the peritoneal capillary permeability induced by acetic acid in mice.

Topics: Alkynes; Animals; Anti-Inflammatory Agents, Non-Steroidal; Atractylodes; Disease Models, Animal; Drugs, Chinese Herbal; Ear; Edema; Lactones; Mice; Molecular Structure; Plants, Medicinal; Sesquiterpenes; Xylenes