Indigowood root extract protects hematopoietic cells, reduces tissue damage and modulates inflammatory cytokines after total-body irradiation: does Indirubin play a role in radioprotection?

Radix of Isatis indigotica (indigowood root, IR) has been used in traditional medicine for its potential anti-inflammatory effect. The purpose of this study is to investigate the radioprotective effects of radiation caused damages in hematopoietic system and normal tissues in mice. A total of 57 BALB/c mice were randomized into six treatment groups: control, IR treatment (0.195, 0.585 and 1.170 g/kg, p.o. daily), L-glutamine (0.520 g/kg) and sham group. All mice except the sham group were irradiated and then administered for one week. The radioprotective effect on hematopoietic system, serum cytokines, and intestinal toxicity was studied. Protective effects on spleen and thymus are found in IR-treated groups. IR assisted in restoration of leukocytopenia after whole mice irradiation with significant reduction of serum TNF-alpha, IL-1beta, and IL-6. These enhancements of hematopoietic effects are due to an increase in the serum G-CSF concentration in IR treated groups. In histopathological assessment, significant improvement of intestine toxicity is observed in high-dose IR and L-glutamine group. Evidences show that IR has potentials to be a radioprotector, especially in recovery of hematopoietic system, reduction of inflammatory cytokines and intestinal toxicity. Indirubin may play a crucial role, but the underlying mechanism is not very clear and warrants further studies.

Effect of extracts from indigowood root (Isatis indigotica Fort.) on immune responses in radiation-induced mucositis.

OBJECTIVES: To evaluate the effect of indigowood root (Isatis indigotica Fort.) on acute mucositis induced by radiation. DESIGN: The objective severity of mucositis, anorexia, and swallowing difficulty were measured before and after the treatment. SETTINGS: Patients with head and neck cancer receiving radiotherapy at Tian Sheng Memorial Hospital, Taiwan were recruited for this trial. SUBJECTS: Twenty (20) patients were randomized into two groups. Group 1 served as controls with only normal saline, and group 2 as the indigowood root (IR) group. INTERVENTIONS: Prophylactic application of IR consisted of gargling and then swallowing the IR preparation on the irradiated oral mucosa. OUTCOME MEASURES: Patients' characteristic distribution of gender, age, diagnosis, and mean radiation dose between the two arms were calculated by Fisher's exact test. We compared the mean of grade 1-4 mucositis, anorexia, difficulty in swallowing, and body weight change with the Mann-Whitney U test. p values less than 0.05 indicated statistical significance. RESULTS: The clinical trial showed that application of IR can reduce the severity of radiation mucositis (p = 0.01), anorexia (p = 0.002), and swallowing difficulty (p = 0.002). Although patients' resting days did not show a significant difference (p = 0.06), complete radiotherapy was done without rest for 4 of 11 patients in the IR group versus 2 of 9 in controls. Hemoglobin level between both groups showed no significant difference. Serum interleukin-6 was significantly lower in the IR group during the first, fifth, and seventh weeks. CONCLUSIONS: We confirmed that indigowood root has anti-inflammatory ability to reduce the mucosal damage caused by radiation. We postulate that indirubin may play a pharmaceutical role in improvement of radiation mucositis, anorexia, and difficulty in swallowing in our clinical trial. However, the exact mechanisms and pathways still need further analysis.