title: Strychnine inhibits inflammatory angiogenesis in mice via down regulation of VEGF, TNF-α and TGF-β.
abstract: Strychnine is known to possess anti-inflammatory and antitumour activity, but its roles in tumour angiogenesis, the key step involved in tumour growth and metastasis, and the involved molecular mechanism are still unknown. We aimed to investigate the effects of strychnine on key components of inflammatory angiogenesis in the murine cannulated sponge implant angiogenesis model. Polyester-polyurethane sponges, used as a framework for fibrovascular tissue growth, were implanted in Swiss albino mice and strychnine (0.25, and 0.5 mg/kg/day) was given through installed cannulas for 9 days. The implants collected at day 9 postimplantation were processed for the assessment of haemoglobin (Hb), myeloperoxidase (MPO), N-acetylglucosaminidase (NAG) and collagen used as indexes for angiogenesis, neutrophil and macrophage accumulation and extracellular matrix deposition, respectively. Relevant inflammatory, angiogenic and fibrogenic cytokines were also determined. Strychnine treatment attenuated the main components of the fibrovascular tissue, wet weight, vascularization (Hb content), macrophage recruitment (NAG activity), collagen deposition and the levels of vascular endothelial growth factor (VEGF), tumour necrosis factor (TNF)-α and transforming growth factor (TGF-β). A regulatory function of strychnine on multiple parameters of main components of inflammatory angiogenesis has been revealed giving insight into the potential therapeutic underlying the actions of strychnine.
authors: Genome Research Laboratory, Delhi Institute of Pharmaceutical Sciences and Research, New Delhi, India. saritasaraswati@gmail.com
authors: Sarita
authors: S
authors: Saraswati
authors: S S
authors: SS
authors: Agarwal
mesh_terms: D000118:Acetylglucosaminidase / Q000378:metabolism; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D007249:Inflammation / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009389:Neovascularization, Pathologic; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011091:Polyesters; D011140:Polyurethanes; D013331:Strychnine / Q000494:pharmacology*; D015503:Surgical Sponges; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D006454:Hemoglobins; D018836:Inflammation Mediators; D011091:Polyesters; D011140:Polyurethanes; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D003094:Collagen; D009195:Peroxidase; D000118:Acetylglucosaminidase; D013331:Strychnine