Comprehensive toxicological profiling of Costus pictus D. Don methanolic leaf extract using in-vitro and in-vivo...

In tropical nations like India, the herb Costus pictus, belonging to the family Costaceae, is widely distributed. Because of its many therapeutic benefits, C. pictus is used extensively by different ethnic communities. In addition to its possible antibacterial, anti-inflammatory, and antioxidant qualities, C. pictus leaf powder has long been used to treat diabetes. Even though C. pictus leaves have several therapeutic uses and are widely used in traditional medicine; there is no empirical evidence of their efficacy or toxicity.

This investigation thoroughly examined the cytotoxicity, mutagenicity, acute and subacute toxicity and genotoxicity of methanolic C. pictus leaf extract (CPLE) through in-vitro and in-vivo analysis using animal models.

Salmonella typhimurium (TA100) was the bacterial strain utilized for the Ames mutagenicity test, and the human embryonic kidney 293 cell line (HEK-293) was used for in-vitro cytotoxicity. Gas Chromatography-Mass Spectrometry (GC-MS) analysis was also performed to evaluate the phytochemical components of the subjected extract. Male and female mice were administered a single oral dose of 250, 500, 1000, or 2000 mg/kg body weight of CPLE for an acute toxicity study. The mice were then monitored for any signs of toxicity for 14 days. Each mouse in the sub-acute toxicity study received oral CPLE at doses of 250, 500, or 1000 mg/kg body weight for a duration of 28 days. Body weights of the mice were recorded weekly, and their overall behaviour was routinely observed. Following the 28-day experiment, the mice were sacrificed, and various histological, haematological and serum biochemical tests were carried out. Blood samples containing different CPLE dosages were used for the genotoxicity analysis using the comet assay.

Ames mutagenicity and cell cytotoxicity studies indicated minimal levels of toxicity and mutagenicity up to a moderate dosage, and the GC-MS chromatogram also revealed several beneficial phytochemical components of the extract. The acute toxicity study conducted in Swiss albino mice demonstrated zero mortality among the animals, and the median lethal dose, popularly known as LD₅₀ value, for the leaf extract was determined to be 2000 mg/kg body weight. When leaf extract was administered at dosages of 250 and 500 mg/kg body weight, sub-acute toxicity evaluations showed no negative effects. Though the liver histology of the test mice showed some harmful effects at highest dose, notably 1000 mg/kg body weight. In the genotoxicity study, we did not find any DNA damage even at the higher dose.

Although C. pictus leaf extract is generally regarded as safe for consumption, dosages exceeding 500 mg/kg body weight may present potential safety concerns. These findings provide a foundation for the development of novel therapeutic agents with improved safety profiles and enhanced efficacy.