Evaluation of therapeutic and toxic levels of Conium maculatum L. extract in gestation and foetal development of adult albino rats.

BACKGROUND: Conium maculatum L. (C.M) is a poisonous plant species particularly for animals including mainly cattle. Even though it is known for its toxicity, clinically has significance due to sedative, antispasmodic and anti-inflammatory properties. For the first time present this study designed to investigate the therapeutic and fatal doses of C.M extract in gestated albino Wistar rats. OBJECTIVE: To evaluate the therapeutic and toxic levels of different concentrations of C.M extract in gestation and foetal development of adult albino Wistar rats. MATERIALS AND METHODS: C.M extract at different doses of 10 mg/kg, 20 mg/kg, 30 mg/kg, 40 mg/kg and 50 mg/kg was orally administered to rats in the entire gestation period. The changes in morphology of mother and siblings, foetal formation, pups birth rate, pups survival rate and AchE levels, MAO levels, and Dopamine levels were measured to ensure the nonlethal dose of the extract. RESULTS: In the treated mother rat group, 50 mg/kg concentration caused death and 20 mg/kg concentration of extract showed good therapeutic values. Birth rate, survival rate, dopamine, MAO levels, SOD, AchE and protein levels decreased upon increasing concentration, whereas LPO and MAO levels increased in mother and sibling rats. Histopathological studies showed that 20 mg/kg concentration of extract showed no damage in neuron cells with maximum increase in number. CONCLUSION: Our findings suggests that C.M 50 mg/kg dose is a toxic concentration in the mother group whereas 40 mg/kg dose in sibling rats by increasing the levels free radicals, decreasing AchE neurotransmitters level, and increasing MAO levels.

Structure prediction, molecular simulations of RmlD from Mycobacterium tuberculosis, and interaction studies of Rhodanine derivatives for anti-tuberculosis activity.

Tuberculosis is the most dangerous disease causing maximum deaths than any other, caused by single infectious agent. Due to multidrug resistant of Mycobacterium tuberculosis strains, there is a need of new drugs and drug targets. In this work, we have selected RmlD (α-dTDP-6-deoxy-lyxo-4-hexulose reductase) in the dTDP Rhamnose pathway as drug target to control tuberculosis using Rhodanine analogues. In order to study interaction of RmlD with Rhodanine analogues, a three-dimensional model based on crystal structures such as 1VLO from Clostridium, 1KBZ from Salmonella typhimurium, and 2GGS from Sulfolobus was generated using Modeller 9v7. The modeled structure reliability has been checked using programs such as Procheck, What if, Prosa, Verify 3D, and Errat. In an attempt to find new inhibitors for RmlD enzyme, docking studies were done with a series of Rhodanine and its analogues. Detailed analysis of enzyme-inhibitor interactions identified specific key residues, SER5, VAL9, ILE51, HIS54, and GLY55 which were important in forming hydrogen bonds in binding affinity. Homology modeling and docking studies on RmlD model provided valuable insight information for designing better inhibitors as novel anti-tuberculosis drugs by rational method.