## 3 Bioactive Compounds in Peanut Skins
### Effects in Animal Models  
Animal models have been used to determine the effectiveness of the polyphenols in peanut skins to influence blood chemistry. Studies on rats for lowering cholesterol used the water-soluble portion incorporated into a high-fat diet [88; 89; 90]. Filtration was used to partition the extracts into a high molecular weight (MW) fraction and a low MW fraction. The findings were that the lower MW fraction was more effective in slowing the transport of cholesterol from the diet into the intestinal transport system. Further study showed that the trimer was more effective than the dimer [90]. This was attributed to the low MW fraction being better able to disrupt the micelles involved. In another study using the rat model, plasma, and liver triglyceride (TG) and cholesterol (TC) levels were significantly reduced, while fecal secretion of TG and TC was greatly increased upon peanut skin extract administration [91]. The effect of the extracts from peanut skins on the blood chemistry of the rat subjects using a water-only extraction scheme is described by an earlier publication [92]. The plasma of rats fed the peanut skin extracts as part of high fat or \"Western\" diet was monitored [90]. Total blood lipids were reduced by the peanut skin fortified diet. The bioavailability of procyanidin A2 was considered to be greater. Peanut skins extracted with 70% ethanol in water were used to evaluate the effectiveness of peanut skin extract to mitigate the effects of an atherogenic diet in a mouse model system [93]. The addition of 0.78% peanut skin extract to a high-fat diet produced some lowering of hepatic cholesterol and glycogen levels in the test subjects. Extracts of peanut skins prepared using 40% ethanol in water followed by elution from HP-20 resin with ethanol were used in a mouse model study [94]. The dried extract was added to the animal diet at 4, 80, and 160 mg/kg of the body weight. At the two highest dosages, reduced body weights, food intake, adipose tissue, and expression of leptin protein were reported. Extracts of peanut skins were made with either pure water or methanol to determine the protective effects of extracts against liver damage induced by chloroform (CCl\({}_{4}\)) in mice [95]. The animal subjects were fed either 50 or 100 mg/kg of extract. One group was fed prior to injection of CCl\({}_{4}\) and another group was fed after injection. Ingestion of CCl\({}_{4}\) is known to both cause peroxidation of the liver membranes and to interfere with Ca\({}^{2+}\) homeostasis, which leads to liver cell damage. By monitoring levels of certain liver enzymes in the blood of the experimental animals and examination of the liver tissues by microscopy, the study showed that the methanolic extract was better able to decrease the levels of the plasma enzymes indicating less damage than the aqueous extracts. The action of the superoxide dismutase, a protective enzyme against oxidation, was increased. The physical examination of the liver cells also showed fewer fat cells and inflammatory damage when the methanol extracts were fed. This indicated that the antioxidant-rich methanolic extracts from peanut skins had a protective effect on the liver of the test animals. Extraction of peanut skins has become commercialized to provide material for further studies. Aqueous ethanol without further definition was described as the solvent for the extraction of peanut skins for a study of the effect of the material on the formation of blood platelets in an animal model [96]. The goal of the study was to elucidate the mechanism of the observed action on hemorrhage described by traditional Chinese medical practice. The action of the anthocyanins from black peanut skins against UV-induced skin cell damage was reported [97]. After extraction with acidified water followed by a partition into ethyl acetate as previously described [29], the anthocyanins were isolated and used to treat human keratinocyte cells (HaCaT cells) as well as the dorsal skin of live mice.