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 (0.3-12ml/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 36ml/kg.bw. The LD50 of DCD-684 in mice was 27.5 ml/kg.bw. In hepatocytes at 36ml/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.

Toxicological assessment of Opuntia dillenii (Ker Gawl.) Haw. cladode methanol extract, fractions and its alpha pyrones: Opuntiol and opuntioside.

ETHNOPHARMACOLOGICAL RELEVANCE: The edible plant Opuntia dillenii (Ker Gawl.) Haw. commonly known as Nagphana, belongs to the Cactaceae family. It is traditionally used to treat various ailments including inflammation, gastric ulcers, diabetes, hepatitis, asthma, whooping cough and intestinal spasm. AIM OF THE STUDY: Despite its traditional use in various countries, detailed toxicological studies of O. dillenii cladode are few. Thus in the current study, toxicity of O. dillenii cladode derived methanol extract, fractions and its α-pyrones: opuntiol and opuntioside have been addressed. METHODS: The test agents were assessed using both in vitro and in vivo toxicity assays. MTT on human embryonic kidney cell line (HEK-293), tryphan blue exclusion in rat neutrophils, Cytokinesis-B block micronucleus (CBMN) in human lymphocytes and genomic DNA fragmentation using agarose gel electrophoresis were performed. In acute toxicity test, mice orally received extract (5 g/kg) for 7 days followed by measurements of relative organ weight, biochemical (blood profile, liver and kidney function test) and histological studies (liver and kidney) were carried out. Rat bone marrow micronucleus genotoxicity assay was also conducted. RESULTS: O. dillenii derived test agents were non-cytotoxic and had no effect on the integrity of DNA. Methanol extract (5 g/kg) orally administered in mice did not cause any significant change in relative organ weights, biochemical parameters and liver and kidney histology as compared to vehicle control. In parallel, extract did not stimulate micronuclei formation in rat bone marrow polychromatic erythrocytes. CONCLUSION: These results led to conclude that edible O. dillenii extract is non-toxic via the oral route and appears to be non-cyto-, hepato-, nephro- or genotoxic, thereby supporting its safe traditional use against various ailments. Therefore, opuntiol and opuntioside may serve as lead compounds in designing new drug(s) derived from edible plants.

Comparative In Vitro Assessment of the Methanol Extracts of the Leaf, Stem, and Root Barks of Cnidoscolus aconitifolius on Lung and Breast Cancer Cell Lines.

OBJECTIVES: Cnidoscolus aconitifolius Mill. I.M.Johnst. is a medicinal plant widely used in ethnomedicine for the treatment of cancer and other diseases. MATERIALS AND METHODS: The effects of methanol extracts of the leaf, stem, and root barks were evaluated on breast (MCF-7) and lung (NCI-H460) cancer cells at 1-250 µg/mL using the SRB assay and the extracts were screened for phytochemicals using the standard method. RESULTS: The stem and root extracts showed no activity at the maximum concentration, while the leaf extract at 100 µg/mL showed remarkable cell growth inhibition against breast (-14.50±0.58) and lung cancer (+53.29±4.57) in vitro. The extracts showed the presence of saponins, terpenes, cardiac glycosides, and phenolic compounds. Partitioning of the active leaf extract further enhanced its activity as the chloroform fraction exhibited GI50, LC50, and total growth inhibition (TGI) of 22.5, 68.75, and 43.75 µg/mL against breast cancer, respectively, and GI50 and TGI of 35.4 and 55.8 µg/ mL against lung cancer cells, respectively. However, the aqueous fraction showed no cytotoxicity against either cell line. CONCLUSION: These results justified the ethnomedicinal uses of the plant against tumor-related ailments. Isolation of the constituents responsible for the observed activity needs to be carried out to further support this claim.