Immunostimulatory Application of a Novel Polysaccharide from Tinospora cordifolia for Treatment of Human Malignancies

Conventional drug discovery programs involve a considerable amount of time and resources, which often precludes success in many cases. We rely heavily on ethnobotany and evochemistry to identify potential drug candidates. We have isolated and characterized an α-D-glucan (RR1), comprised of (1–4) linked back bone and (1–6) linked branches with a molecular mass of 550 kDa from the medicinal plant Tinospora cordifolia. RR1 activates natural killer (331%), T -(102%) and B-cells (30%) at 100µg/ml concentration. Immune activation by RR1 in lymphocytes elicited the synthesis of cytokines and chemokines, often altering the ratio and onset of pro- and anti-inflammatory cytokines. The cytokine profile demonstrated the Th1 pathway of T-helper cell differentiation essential for cell-mediated immunity with a self-regulatory mechanism for the control of its overproduction. RR1 inhibited the phagocytosis of unopsonized zymosan A bioparticles in a dose-dependent manner in macrophages. RR1 activated NF-κB in a time- and dose-dependent manner and this modulation is associated with degradation of I-κB-α thus facilitating the translocation of NF-κB into the nucleus. RR1-induced NF-κB activity peaked at 8h with I-κB alpha degradation occurring at 1h of stimulation. RR1-induced NF-κB activation occurred through TLR6 signaling as evidenced by the synthesis of IL-8 in TLR6-transfected HEK293 cells. RR1 treatment yielded significantly improved survival in mice with Ehrlich ascites tumor grafts compared to saline control with the 10mg/kg RR1 + 2mg/kg doxorubicin group showing the maximum survival. These results indicated the potential use of RR1 as an adjuvant for cancer chemotherapy.