ABSTRACT
Berberine, a quaternary ammonium protoberberine alkaloid with an isoquinoline scaffold isolated from medicinal herbs, exhibits a wide spectrum of pharmacological activities. Berberine has been used in traditional Chinese medicine and Ayurvedic medicine. However, it has poor bioavailability, which seriously limits its application and development. The chemical transformation of natural products is an effective method to improve pharmacological activities. Researches have been carried out on the modification of berberine to obtain better pharmacological properties. In this paper, the structural modifications of berberine for different biological activities and its underlying mechanisms are reviewed.
Subject(s)
Anti-Bacterial Agents/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antimalarials/pharmacology , Antineoplastic Agents/pharmacology , Berberine/pharmacology , Neuroprotective Agents/pharmacology , Alzheimer Disease/drug therapy , Anti-Bacterial Agents/chemistry , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Antimalarials/chemistry , Antineoplastic Agents/chemistry , Bacteria/drug effects , Berberine/analogs & derivatives , Berberine/chemistry , Humans , Medicine, Chinese Traditional , Molecular Structure , Neuroprotective Agents/chemistry , Plants, Medicinal/chemistryABSTRACT
In early life, the immune system plays an essential role in brain development. In our study, the immunopotentiator thymosin alpha-1 (Ta1) was peripherally administered to neonatal mice to explore whether the peripheral immunopotentiator affects neurodevelopment and cognition, and to further investigate the relevant mechanism. Compared with the control group, the Ta1 mice displayed better cognitive abilities in early life. The numbers of 5-bromodeoxyuridine (BrdU)+, nestin+, T-box transcription factor 2 (Tbr2)+, BrdU+/doublecortin (DCX)+, BrdU+/ionized calcium-binding adaptor molecule 1 (Iba1)+, and BrdU+/neuronal nuclei (NeuN)+ cells in the hippocampus were increased in the Ta1 group, accompanied by increased interleukin-4 (IL-4), interferon-gamma, brain-derived neurotrophic factor, nerve growth factor, and insulin-like growth factor-1 as well as decreased IL-6 and tumor necrosis factor-α. Furthermore, the Ta1-group showed a Th1-polarized immune response, and the neurotrophic factors were positively associated with the Th1/Th2 ratio. More importantly, administration of Ta1 blocked lipopolysaccharide-induced impairment of hippocampal neurogenesis in early life. These findings suggest that peripheral Ta1 contributes to neurogenesis and cognition probably through a systemic Th1 bias, as well as neuroprotection against LPS infection by Ta1.
Subject(s)
Adjuvants, Immunologic/pharmacology , Behavior, Animal/drug effects , Cognition/drug effects , Cytokines/metabolism , Hippocampus/drug effects , Hippocampus/metabolism , Nerve Growth Factors/metabolism , Neurogenesis/drug effects , Thymosin/analogs & derivatives , Adjuvants, Immunologic/administration & dosage , Animals , Animals, Newborn , Cytokines/blood , Doublecortin Protein , Mice , Mice, Inbred C57BL , Nerve Growth Factors/blood , Thymalfasin , Thymosin/administration & dosage , Thymosin/pharmacologyABSTRACT
An Escherichia coli-expressed peptide with a molecular weight of 28.26, derived from the complementary DNA of antiviral protein RC28 isolated from the mushroom Rozites caperata (=Cortinarius caperatus), demonstrated potent antiviral activity against herpes simplex virus-1 in Vero cells and in a herpes simplex virus-1 mouse keratitis model. Plaque assays in Vero cells showed that the peptide reduced viral yields by at least 1.2 logs; in the animal model the cloned peptide delayed the occurrence of stromal keratitis and alleviated the severity of the disease. We believe this is the first report of a cloned mushroom peptide with antiviral activity for the prevention and treatment of a viral disease.
Subject(s)
Antiviral Agents/therapeutic use , Basidiomycota/chemistry , Corneal Diseases/virology , Corneal Stroma/drug effects , Herpesvirus 1, Human/drug effects , Keratitis, Herpetic/drug therapy , Peptides/therapeutic use , Agaricales , Animals , Antiviral Agents/isolation & purification , Antiviral Agents/pharmacology , Chlorocebus aethiops , Cloning, Molecular , Corneal Stroma/virology , DNA, Complementary , Disease Models, Animal , Escherichia coli , Female , Herpesvirus 1, Human/growth & development , Keratitis, Herpetic/virology , Mice, Inbred BALB C , Peptides/isolation & purification , Peptides/pharmacology , Severity of Illness Index , Vero CellsABSTRACT
A novel protein with antitumor activity, Hailongin, was purified from the aqueous extract of the whole body of Trachyrhamphus serratus, which is commonly used in traditional Chinese medicine, by bioassay-guided fractionation. Hailongin exhibited strong inhibition of proliferation of the tested human cell lines, such as A549, HeLa, LoVo and CCRF-CEM. The IC(50) values of Hailongin ranged from 5.4 to 25.7 µ/mL. An in vivo study showed that the growth of implanted S-180 solid tumors in mice was significantly inhibited by Hailongin treatment, while the immunological function of the tumor-bearing mice was enhanced. The molecular weight and the isoelectric point of Hailongin were 57.074 kDa (by MALDI-TOF-MS) and 6.2 (by isoelectric focusing-polyacrylamide gel electrophoresis), respectively. Seventeen amino acids were identified in Hailongin. The acidic amino acids accounted for the majority of Hailongin's amino acid composition. The N-terminal amino acid sequence of Hailongin was determined to be IVPYSHNAGNKGLTQMR and showed no significant homology with known proteins.