ABSTRACT
Livergol (LG), which is the extract of Silybum marianum and commonly known as milk thistle possess hepatoprotective effect and have got licensed for sale in Iran and other countries. LG was evaluated for its capacity to counteract the toxic effects of bromobenzene (BB) on mouse liver. The bioactive component of this plant is known to reinforce naturally occurring liver function through antioxidant activity, the stimulation of bile production and regeneration by the liver organ, resulting in enhanced protection against toxicants, hepatitis, and cirrhosis. The major bioactive components of this product are the flavonolignan ssilibinin, silidianin, silicristin, and isosilibinin. Mice were treated for 10 days with daily gavage of microemulsions (MEs), into which 0-400 mg/kg LG was dispersed. 0.36 ml/kg BB was injected intraperitoneally (ip) to each animal on day 10, followed by sacrifice on day 11, and histological evaluation of hematoxylin-eosin (HE)-stained liver tissue samples, afterwards followed by evaluation liver enzymes level, aminotransferase (AST), alanine aminotransaminase (ALT) and alkaline phosphatase (ALP) activities. Significant suppression of BB-mediated damage to liver tissue, and increased in AST, ALT, and ALP level was observed to occur dose-responsively with LG administration, suggesting a use for LG as a chemoprotectant for persons chronically exposed to industrial solvents.
ABSTRACT
The most important components of Plantago lanceolata L. leaves are catalpol, aucubin, and acteoside (=verbascoside). These bioactive compounds possess different pharmacological effects: anti-inflammatory, antioxidant, antineoplastic, and hepatoprotective. The aim of this study was to protect Plantago lanceolata extract from hydrolysis and to improve its antioxidant effect using self-nano-emulsifying drug delivery systems (SNEDDS). Eight SNEDDS compositions were prepared, and their physical properties, in vitro cytotoxicity, and in vivo AST/ALT values were investigated. MTT cell viability assay was performed on Caco-2 cells. The well-diluted samples (200 to 1000-fold dilutions) proved to be non-cytotoxic. The acute administration of PL-SNEDDS compositions resulted in minor changes in hepatic markers (AST, ALT), except for compositions 4 and 8 due to their high Transcutol contents (80%). The non-toxic compositions showed a significant increase in free radical scavenger activity measured by the DPPH test compared to the blank SNEDDS. An indirect dissolution test was performed, based on the result of the DPPH antioxidant assay; the dissolution profiles of Plantago lancolata extract were statistically different from each SNEDDS. The anti-inflammatory effect of PL-SNEDDS compositions was confirmed by the ear inflammation test. For the complete examination period, all compositions decreased ear edema as compared to the positive (untreated) control. It can be concluded that PL-SNEDDS compositions could be used to deliver active natural compounds in a stable, efficient, and safe manner.
Subject(s)
Anti-Inflammatory Agents/administration & dosage , Antioxidants/administration & dosage , Ear Diseases/drug therapy , Edema/drug therapy , Plant Extracts/administration & dosage , Plantago/chemistry , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Antioxidants/chemistry , Antioxidants/pharmacology , Caco-2 Cells , Cell Survival/drug effects , Ear Diseases/chemically induced , Edema/chemically induced , Emulsions , Humans , Hydrolysis , Nanoparticles/chemistry , Particle Size , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Leaves/chemistry , Xylenes/adverse effectsABSTRACT
The aim of this study was to develop topical self-microemulsifying drug delivery systems (SMEDDS) containing antitumor agents (bleomycin, cisplatin and ifosfamide) and to investigate their inhibitory potential in SMEDDS on human cervical cancer HeLa cells. The physicochemical properties of cytostatic drug loaded SMEDDS were characterized. The cytotoxicity of main components of SMEDDS was also investigated. Their IC50 values were determined. HeLa cells were treated by different concentrations of cisplatin, bleomycin and ifosfamide alone and in various SMEDDS. The inhibitory effect on cell growth was analyzed by MTT cell viability assay. Inflammation is a driving force that accelerates cancer development. The inhibitory effect of these antitumor agents has also been tested on HeLa cells in the presence of inflammatory mediators (IL-1-ß, TNF-α) as an in vitro model of inflamed human cervix. Significant differences in the cytotoxicity of cytostatic drugs alone and in SMEDDS have been found in a concentration-dependent manner. The self-micro emulsifying system may potentiate the effectiveness of bleomycin, cisplatin and ifosfamide topically. The effect of SMEDDS containing antitumor agents was decreased significantly in the presence of inflammatory mediators. According to our experiments, the optimal SMEDDS formulation is 1:1:2:6:2 ratios of Isopropyl myristate, Capryol 90, Kolliphor RH 40, Cremophor RH40, Transcutol HP and Labrasol. It can be concluded that SMEDDS may increase the inhibitory effect of bleomycin, ifosfamide and cisplatin on human cervical cancer HeLa cells. Inflammation on HeLa cells hinders the effectiveness of SMEDDS containing antitumor agents. Our results might ensure useful data for development of optimal antitumor formulations.
