atractylenolide-i and Inflammation

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

Microglial activation and the resulting neuroinflammation are associated with a variety of brain diseases, such as Alzheimer's disease and Parkinson's disease. Thus, the control of microglial activation is an important factor in the development of drugs that can treat or prevent inflammation-related neurodegenerative disorders. Atractylodis Rhizoma Alba (ARA) has been reported to exhibit antioxidant, gastroprotective, and anti-inflammatory effects. However, the effects of ARA ethanolic extract (ARAE) on microglia-mediated neuroinflammation have not been fully elucidated. In this work, we explored the anti-neuroinflammatory properties and underlying molecular mechanisms of ARAE in lipopolysaccharide (LPS)-stimulated microglial BV2 cells. Our results showed that ARAE significantly attenuates the production of nitric oxide (NO) and inflammatory cytokines induced by LPS. ARAE treatment also inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 without causing cytotoxicity. ARAE markedly attenuated the transcriptional activities of nuclear factor (NF)-κB and mitogen-activated protein kinases (MAPK) phosphorylation, and induced heme oxygenase (HO)-1 expression. High-performance liquid chromatography (HPLC) analysis showed that ARAE contains three main components-atractylenolide I, atractylenolide III, and atractylodin-all compounds that significantly inhibit the production of inflammatory factors. These findings indicate that ARAE may be a potential therapeutic agent for the treatment of inflammation-related neurodegenerative diseases.

Topics: Animals; Asteraceae; Cell Line; Cyclooxygenase 2; Cytokines; Gene Expression Regulation; Heme Oxygenase-1; Inflammation; Lactones; Lipopolysaccharides; Mice; Microglia; Mitogen-Activated Protein Kinases; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; Plant Preparations; Plant Roots; Sesquiterpenes; Signal Transduction

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

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