A novel role of Tinospora cordifolia in amelioration of cancer-induced systemic deterioration by taming neutrophil infiltration and hyperactivation

Abstract

BackgroundCancer has emerged as a systemic disease which targets various organs thus challenging the overall physiology of the host. Recently, we have shown that hyperactive neutrophils infiltrate various organs of tumor bearing host and contribute to gradual systemic deterioration. Therefore, taming neutrophils via potent immunomodulators could be an appropriate therapeutic approach in regulating systemic damage. Tinospora cordifolia (TC), an Ayurvedic panacea, is known for its immense medicinal values in traditional literature and recent reports have also documented its immunomodulatory potential. However, whether TC can regulate neutrophils to exert its therapeutic effectiveness has not been deciphered so far. MethodsFor the in vivo study, we utilized murine model of Dalton's Lymphoma (DL). T. cordifolia extract (TCE) treatment was scheduled at early, mid and advanced stages of tumor growth at a dose of 400 mg/kg b.w for 30 consecutive days. Effect of TCE on neutrophil infiltration was examined by immunostaining. Neutrophil elastase (NE) level in serum, ascitic fluid and various tissues was monitored by ELISA. Further, qPCR was performed to assess transcripts levels of NE, myeloperoxidase (MPO), metalloproteinases (MMP-8, MMP-9) and cathepsin G (CSTG) in various tissues. ROS level in tissue was assessed by DHE staining and organ function was assessed by histology post TCE treatment. ResultsOur findings showed that TC treatment significantly reduced neutrophil count in peripheral blood and their infiltration in vital organs of tumor-bearing host. Further, it ameliorated neutrophil hyperactivation by down regulating the expression of its key cargoes including NE, MPO, MMP-8, MMP-9 and CSTG at early and mid stage of tumor growth. In addition, TC treatment prevented histopathological alterations and restored the normal serum enzyme levels at different stages of tumor growth. Importantly, TC treatment also showed significant reduction in tumor burden which was accompanied by a remarkable increase in survival of the tumor-bearing mice. ConclusionsWe conclude that T. cordifolia could limit systemic damage via regulating neutrophil infiltration and hyperactivation which can further lead to cancer control at both prophylactic and therapeutic level.