ABSTRACT
BACKGROUND: Deoxypodophyllotoxin, isolated from the Traditional Chinese Medicine Anthriscus sylvestris, is well-known because of its significant anti-tumor activity with strong toxicity in vitro and in vivo. OBJECTIVE: In this article, a series of deoxypodophyllotoxin derivatives were synthesized and their anti-tumor effectiveness was evaluated. METHODS: The anti-tumor activity of deoxypodophyllotoxin derivatives was investigated by the MTT assay method. Apoptosis percentage was measured by flow cytometer analysis using Annexin-V-FITC. RESULTS: The derivatives revealed obvious cytotoxicity in the MTT assay by decreasing the number of late cancer cells. The decrease of Bcl-2/Bax could be observed in MCF-7, HepG2, HT-29, and MG-63 using Annexin V-FITC. The ratio of Bcl-2/Bax in the administration group was decreased, which was determined by the ELISA kit. CONCLUSION: The derivatives of deoxypodophyllotoxin could induce apoptosis in tumor cell lines by influencing Bcl-2/Bax.
Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Drugs, Chinese Herbal/pharmacology , Podophyllotoxin/analogs & derivatives , Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors , bcl-2-Associated X Protein/antagonists & inhibitors , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Drugs, Chinese Herbal/chemical synthesis , Drugs, Chinese Herbal/chemistry , Humans , Molecular Structure , Podophyllotoxin/chemical synthesis , Podophyllotoxin/chemistry , Podophyllotoxin/pharmacology , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Structure-Activity Relationship , Tumor Cells, Cultured , bcl-2-Associated X Protein/genetics , bcl-2-Associated X Protein/metabolismABSTRACT
Valeriana jatamansi Jones (V. jatamansi) has been widely used for treating anxiety and its mechanism involves many aspects including GABA level. This study aimed to evaluate the anxiolytic potency of an iridoid fraction extracted from the radix and rhizomes of V. jatamansi. The iridoid fraction was extracted by using D101 resin; its major components were analysed preliminarily by thin layer chromatography, ultraviolet spectrophotometry and high-performance liquid chromatography; and its anxiolytic effects at 6 mg/kg (low-dose), 9 mg/kg (medium-dose) and 12 mg/kg (high-dose) were evaluated using the elevated plus maze test, the light-dark box test, the Vogel's drinking conflict test, and the open field drink test. Its action mechanism was investigated using the ELISA. This study provided evidence on the anxiolytic potency of the iridoid fraction from V. jatamansi and revealed its action mechanism of regulating the GABA level.
Subject(s)
Anti-Anxiety Agents/pharmacology , Iridoids/pharmacology , Valerian/chemistry , Animals , Anti-Anxiety Agents/isolation & purification , Anxiety/drug therapy , Behavior, Animal/drug effects , Chromatography, High Pressure Liquid , Chromatography, Thin Layer , Iridoids/isolation & purification , Mice , Plant Roots/chemistry , Rhizome/chemistryABSTRACT
Context Fatty acid synthase (FAS) is the only mammalian enzyme to catalyse the synthesis of fatty acid. The expression level of FAS is related to cancer progression, aggressiveness and metastasis. In recent years, research on natural FAS inhibitors with significant bioactivities and low side effects has increasingly become a new trend. Herein, we present recent research progress on natural fatty acid synthase inhibitors as potent therapeutic agents. Objective This paper is a mini overview of the typical natural FAS inhibitors and their possible mechanism of action in the past 10 years (2004-2014). Method The information was collected and compiled through major databases including Web of Science, PubMed, and CNKI. Results Many natural products induce cancer cells apoptosis by inhibiting FAS expression, with fewer side effects than synthetic inhibitors. Conclusion Natural FAS inhibitors are widely distributed in plants (especially in herbs and foods). Some natural products (mainly phenolics) possessing potent biological activities and stable structures are available as lead compounds to synthesise promising FAS inhibitors.
Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Fatty Acid Synthases/antagonists & inhibitors , Fatty Acid Synthesis Inhibitors/therapeutic use , Neoplasms/drug therapy , Animals , Antineoplastic Agents, Phytogenic/adverse effects , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Apoptosis/drug effects , Fatty Acid Synthases/chemistry , Fatty Acid Synthases/metabolism , Fatty Acid Synthesis Inhibitors/adverse effects , Fatty Acid Synthesis Inhibitors/chemistry , Fatty Acid Synthesis Inhibitors/isolation & purification , Humans , Neoplasms/enzymology , Neoplasms/pathology , Phytotherapy , Plants, Medicinal , Protein Conformation , Structure-Activity RelationshipABSTRACT
Bioassay-guided chemical investigation of the roots of Anthriscus sylvestris (L.) Hoffm. resulted in the isolation of nine compounds, whose structures were determined by spectroscopic methods. Compound 1 was isolated from this plant for the first time and compounds 3 and 9 were first found from this genus. Different polar fractions of A. sylvestris extract and compounds 1, 6-8 and 9 were evaluated for antitumor activities against HepG2 (human hepatocellular carcinoma), MG-63 (human osteosarcoma cells), B16 (melanoma cells) and HeLa (human cervical carcinoma cells) lines by the MTT method. The petroleum ether fraction of A. sylvestris extract exhibited excellent inhibitory activity with an IC50 value of 18.3 µg/ml. Among the isolates from the petroleum ether fraction, compound 7 showed significant inhibition against the growth of the four tumor cells with IC50 values ranging from 12.2-43.3 µg/ml.