Methods Applied to the In Vitro Primary Toxicology Testing of Natural Products: State of the Art, Strengths, and Limits

Abstract

!The present review attempts to build up a comprehensive picture of the major primary techniques used to screen and assess the cytotoxicity of plant complex mixtures. These can be based on metabolic activity, on membrane integrity, on morphological features, on cell growth; the type of cell death can also be established from more or less specific events (e.g., apoptosis, autophagy, DNA damage detection, reactive oxygen species involvement). This review will discuss the benefits, the difficulties, and the challenges that may occur along cytotoxicity testing of raw extracts and isolated natural compounds.

The potential of silymarin for the treatment of hepatic disorders

“…Some milk thistle constituents yield a positive Ames test [26]. However, having not shown any indication of carcinogenicity in animal studies, silymarin extracts are currently considered as non-carcinogens (HMPC Genotoxicity Guideline) [24,26].…”

“…However, having not shown any indication of carcinogenicity in animal studies, silymarin extracts are currently considered as non-carcinogens (HMPC Genotoxicity Guideline) [24,26]. With silymarin, but not silibinin, the Ames test was positive in S. typhimurium strains TA98 and TA100, when testing occurred with liver S9 activation enzymes.…”

“…With silymarin, but not silibinin, the Ames test was positive in S. typhimurium strains TA98 and TA100, when testing occurred with liver S9 activation enzymes. Administration of milk thistle extract in feed for 3 months did not increase the frequencies of micro-nucleated normochromatic erythrocytes, an indication of chromosomal abnormalities, in the peripheral blood of mice [24,26].…”

1 H NMR based metabolic profiling of eleven Algerian aromatic plants and evaluation of their antioxidant and cytotoxic properties

“…After 24 h of incubation, each cell line, previously carefully washed with PBS (100 μl × 2) to remove the maximum of potentially interfering phytochemicals (Bunel, Ouedraogo, Nguyen, Stévigny, & Duez, 2014), was treated with hydroalcoholic extracts from investigated Algerian aromatic plants at four dose levels (3.125, 6.25, 12.5 and 25.0 μg/mL, final concentration levels). At 24, and 48 h of incubation, cells were treated with 150 μL of MTT (0.50 mg/mL), dissolved in the culture medium, for 1 h at 37°C in a 5% CO 2 humidified atmosphere.…”

A new approach for the assessment of the toxicity of polyphenol-rich compounds with the use of high content screening analysis

“…There are numerous conventional cytotoxicity methods which allow the in vitro effects of new drug candidates to be examined on living cells. The basic cytotoxic tests include those that measure metabolic activity of the cells, plasma membrane integrity, changes in cell number and morphology, cell growth/proliferation or the mechanisms of cell death [3]. However, one major limitation of this kind of assay is their inability to measure a wide spectrum of potential early or late pathological changes involved in drug-induced toxic injury.…”