Genotoxicity, acute and sub-acute toxicity profiles of methanolic Cordyceps militaris (L.) Fr. extract in Swiss Albino Mice

Abstract

Ethnopharmacological relevanceCordyceps militaris, a traditional medicinal fungus, parasitizes the intestines of lepidopteron pupae or larvae, predominantly during the winter, and undergoes fruiting in the summer or autumn. Compounds extracted from C. militaris have demonstrated a broad spectrum of pharmacological effects, including antioxidant, anti-tumor, anti-metastatic, anti-inflammatory, antiviral, anti-diabetic, and various others. Aim of the studyHerein, our study aimed at elucidating the acute, sub-acute toxicity, and genotoxicity profiles of C. militaris methanolic extract following oral administration in Swiss albino mice, representing the inaugural comprehensive exploration of the toxicological and safety profiles of C. militaris. Materials and methodsPrior studies have predominantly focused on its biological activities rather than its toxicity. Acute oral toxicity study was conducted at 500, 1000, and 2000 mg/Kg B.W. doses of C. militaris over a 14-day period. For sub-acute toxicity study, three groups of mice were administered 100, 300, and 600 mg/Kg B.W. of C. militaris extract for 28 consecutive days; one group served as a control. Mice were monitored for their body weight and behavioural changes once daily. Hematological, serum biochemical, histopathological, histomorphometric, seminal parameters, and mutagenic investigations were performed post-treatment period. ResultsAcute oral toxicity study at 2000 mg/Kg revealed no signs of toxicity, with an LD50 value surpassing 2000 mg/Kg. No occurrences of mortality observed, and no significant changes were noted in body weight, organ weight, or behaviour. Hematological analysis illustrated a marked upsurge in RBC, Hb, HCT, PLT, MPV, and PCT, alongside minor variations in differential leucocyte count post 28-day treatment. Liver enzyme tests indicated slight elevation in ALP, while renal enzyme tests showed alterations in CRE and BUN levels. Genotoxicity profile and histopathological assessments of the liver, spleen, testis, and ovary manifested no remarkable irregularities, except for mild renal toxicity. Seminal parameters including sperm concentration, motility and testosterone levels demonstrated a noteworthy increase. ConclusionsThe study sheds light on the potential risks and safety considerations associated with C. militaris-based medicinal products. These findings establish a foundation for further investigations and the refinement of dosage optimization in the application of C. militaris, with the aim of mitigating any potential adverse effects.