Assessment of acute, sub-acute, chronic and genotoxicity of polyherbal formulation DCD-684 in mice

Digas colic drops (DCD-684) a polyherbal formulation containing Carum carvi, Foeniculum vulgare, Mentha arvensis, Mentha piperita and Zingiber officinale is widely used in Pakistan against gastrointestinal ailments including infantile colic. The DCD-684 (0.03-3ml/kg.bw) administered orally in acute (7-days) and sub-acute toxicity (14-days) tests, displayed neither mortality nor toxicological changes in physical, behavioral, biochemical and histopathological parameters. In chronic study (90-days), DCD-684 (0.3-12 ml/kg.bw) also revealed no changes. However, at 18 and 36 ml/kg.bw, liver demonstrated mild inflammation correlating with raised aspartate transaminase (AST), alkaline phosphatase (ALP) and alpha fetoprotein (AFP) levels. Increased levels of urea and inflamed renal parenchyma indicated mild nephro-toxicity with high alanine aminotransferase (ALT) at 36 ml/kg.bw. The LD50 of DCD-684 in mice was 27.5 ml/kg.bw. In hepatocytes at 36 ml/kg.bw, elevated mRNA expression of pro-inflammatory chemokines and cytokines were evident. DCD-684 neither damaged DNA nor induced cytotoxicity in micronucleus assay. In conclusion, polyherbal DCD-684 caused neither hepatic, renal, genotoxicity nor any undesirable effect in mice. Higher doses administered for 90 days showed mild toxic effects with no sign of necrosis, fibrosis or genotoxicity. Thus, in mice DCD-684 demonstrated a wide margin of safety to be used for the relief of infantile colic.

Automated summary

Digas colic drops (DCD-684), a polyherbal formulation used for gastrointestinal ailments including infantile colic in Pakistan, showed no toxicity in acute and sub-acute tests. In chronic study, higher doses of DCD-684 demonstrated mild toxic effects on liver and kidney parameters, but no signs of necrosis, fibrosis, or genotoxicity were observed. Overall, DCD-684 displayed a wide margin of safety in mice for the relief of infantile colic.