ABSTRACT
Epigallocatechin-3-gallate (EGCG) is the most abundant and biologically active catechin in green tea, and it exerts multiple effects in humans through mechanisms that remain to be clarified. The present study used bioinformatics to identify possible mechanisms by which EGCG reduces the risk of ovarian cancer. Possible human protein targets of EGCG were identified in the PubChem database, possible human gene targets were identified in the National Center for Biotechnology Information database, and then both sets of targets were analyzed using Ingenuity Pathway Analysis (IPA). The results suggest that signaling proteins affected by EGCG in ovarian cancer, which include JUN, FADD, NFKB1, Bcl-2, HIF1α, and MMP, are involved primarily in cell cycle, cellular assembly and organization, DNA replication, etc. These results identify several specific proteins and pathways that may be affected by EGCG in ovarian cancer, and they illustrate the power of integrative informatics and chemical fragment analysis for focusing mechanistic studies.
Subject(s)
Catechin/analogs & derivatives , Computational Biology , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Tea/chemistry , Catechin/pharmacology , Catechin/therapeutic use , Female , Gene Regulatory Networks/drug effects , Humans , Ovarian Neoplasms/pathology , Protein Interaction Maps/drug effects , Signal Transduction/drug effects , Signal Transduction/geneticsABSTRACT
Systemic lupus erythematosus (SLE) is an autoimmune disease of uncertain etiology that affects multiple tissues and organs. Arsenic trioxide (ATO) has been used in lupus-prone mice with a regulatory effect on immune abnormality. Tetra-arsenic tetra-sulfide (As4S4), a traditional Chinese medicine, is effective on acute promyelocytic leukemia with mild side effects than ATO. In this study, a pilot study was performed to investigate the effects and the mechanism of As4S4 on the lupus-prone BXSB mice. Improvement of monocytosis (p<0.05) in spleen and decreased serum interleukin-6 (IL-6) (p=0.0277) were observed with As4S4 treatment. As4S4-treated mice exhibited amelioration of skin, liver and renal disease with mild side effects. Histological analysis revealed that As4S4 suppressed immune complex deposition, mesangial proliferation and inflammatory cell infiltration in kidney and liver. Our study support that As4S4 selectively suppresses cutaneous lupus and nephritis in BXSB mice and might be a potential treatment for SLE.
Subject(s)
Arsenicals/therapeutic use , Lupus Erythematosus, Systemic/drug therapy , Sulfides/therapeutic use , Animals , Antibodies, Antinuclear/blood , Arsenic/blood , Arsenicals/pharmacology , Hair/chemistry , Lupus Erythematosus, Systemic/immunology , Male , Medicine, Chinese Traditional , Mice , Mice, Inbred C57BL , Pilot Projects , Spleen/drug effects , Spleen/immunology , Splenomegaly/drug therapy , Splenomegaly/immunology , Sulfides/pharmacologyABSTRACT
To induce arthritis, the adjuvant with heat-killed Mycobacterium tuberculosis was injected into the ankle joint in rats. Local redness, swelling, hotness, pain, and motor dysfunction of the inflamed joint (as well as mental dullness) were observed 48 h after inoculation. At this time, the maximal binding capacity (Bmax) of muscarinic receptors in limbic system was increased, while the dissociation constant (Kd) was unchanged. Injection of morphine (5 mg.kg-1) 3 times within 48 h after the inoculation resulted in a decrease of Bmax and an increase of Kd of M-receptors, together with diminution of pain and disappearance of dullness.