JOURNAL OF MEDICINAL FOOD J Med Food 00 (0) 2014, 1–8 # Mary Ann Liebert, Inc., and Korean Society of Food Science and Nutrition DOI: 10.1089/jmf.2014.0060

REVIEW ARTICLE

Bioavailability and Hypolipidemic Effects of Peanut Skin Polyphenols Rishipal R. Bansode,1 Priscilla Randolph,1 Mohamed Ahmedna,2 Leonard L. Williams,1 and Jianmei Yu3 1

Center for Excellence in Post Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, Kannapolis, North Carolina, USA. 2 Department of Health Sciences, Qatar University, Doha, Qatar. 3 Department of Family and Consumer Sciences, North Carolina Agricultural and Technical State University, Greensboro, North Carolina, USA. ABSTRACT Peanut skin is a rich source of polyphenols, such as proanthocyanidins. Peanut skin proanthocyanidins mainly consist of a subgroup called procyanidins. Peanut-based procyanidins contain oligomers of both type A and type B procyanidins. Recent studies have shown that peanut skin extracts exert protection against hepatic steatosis induced on rats fed with a high-fat diet. Studies have shown that proanthocyanidins protect against cardiovascular diseases (CVDs). The mechanism of CVD protection and hypolipidemic effect of peanut skin procyanidins has been gradually revealed in recent years. Due to the high molecular weight of procyanidins, they are not readily absorbed through the gut barrier. It is hypothesized that procyanidins exert their effect by inhibiting the absorption of dietary lipid and chylomicron secretion by enterocytes. In this review, we aim to highlight the hypolipidemic effects of peanut skin polyphenols and discuss the various molecular mechanisms, with which the polyphenols may exert the lipid-lowering function observed by weighing the absorption characteristics as well as gene expression mechanism responsible for lipid homeostasis.

KEY WORDS:  hypolipidemia  lipid metabolism  peanut skins  proanthocyanidins

Procyanidins have been extensively studied for their health benefits and known to inhibit chemically-induced lipid peroxidation, DNA fragmentation, and apoptosis in the liver and brain of mice; inhibit biomarkers of skin tumor promotion in mouse epidermis; and reduce susceptibility to cardiac ischemia induced by iron and copper.14–16 In vitro studies have shown that procyanidins exhibited antitumor properties in B16 mouse melanoma cells through mitochondrial pathway activation of caspase-3.17

INTRODUCTION

P

eanut skin is a rich source of highly active antioxidants, including catechins and procyanidins.1 Proanthocyanidins comprise the most abundant phenolic subclasses in human diet.2 Procyanidins are a subgroup of proanthocyanidins and are oligomers of catechin and epicatechin molecules.3 Peanut skin has a pink-red color and astringent taste and is generally removed before consumption or peanut processing. They are typically removed from the seed during blanching and after dry roasting.4 They are either discarded as waste or used as an animal feed ingredient.5 Peanut skin comprises 2.6% of whole peanut seed on weight basis.6 They are known to contain some fat, salt, and 16–18% crude protein.7 They are typically limited to 5–8% of the ratio of dairy cattle feed due to their high content of procyanidins, which interfere with protein digestion/absorption in animals.4,6 There has been an increased interest in peanut skin-based procyanidins due to their antioxidant properties and potential health benefits.8–13

COMPOSITION AND CHARACTERISTICS OF PEANUT SKIN POLYPHENOLS Polyphenols in peanuts are mainly present in the skins and hulls.18 The total polyphenols in peanut skin were found to be 115–149 mg/g (gallic acid equivalent [GAE]) dry skin by Nepote et al. and between 90 and 125 mg/g dry skin by Yu et al., depending upon the solvent used for extraction.19,20 In one study, the peanut skin’s redness and hue angle was shown to have a strong correlation between the total polyphenol and antioxidant capacity.21 The investigators measured the phytochemical content and antioxidant capacities of the whole seed in 27 cultivars. The total flavonoid content expressed as cyanidin chloride equivalent (CCE) ranged from 27.6 to 139.9 mg CCE/100 g fresh peanut. The total polyphenolic content of the peanut cultivars ranged from

Manuscript received 8 April 2014. Revision accepted 14 July 2014. Address correspondence to: Rishipal R. Bansode, PhD, Center for Excellence in Post Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, Kannapolis, NC 28081, USA, E-mail: rbansode@ ncat.edu

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BANSODE ET AL.

94.4 to 228.4 mg GAE/100 g. The proanthocyanidin content range from 10.1 to 103.0 mg CCE/100 g fresh peanut with an average of 31.7 mg CCE/100 g. The antioxidant capacities of these cultivars measured as the Trolox equivalent antioxidant capacity (TEAC) ranged from 59.1 to 103.8 mM TE/100 g, with a mean value of 82.3 mM TE/100 g. This study showed that the hue angle of peanut skin might be indicative of the total polyphenol content rather than its flavonoid content. The main flavonoids in peanut skin were determined using an ultra performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-qTOF MS).8 In total, 22 flavonoids and their derivatives were identified from the peanut skin extract. The polyphenolic concentration from a direct peeled peanut skin is a rich source of procyanidin, mainly A-type dimers, trimers, and tetramers.1 Proanthocyanidins mainly consist of (epi)catechins and their galloyl derivatives.3 The A-type subunits are doubly linked by the C4-C8/C6 bond and an additional C2-O-C7 or C2-OC5 ether bond, while B-type subunits are linked by the C4C8 or C4-C6 bond (Fig. 1). The phenolic compounds from dry peanut skin were extracted with good recovery with 30% methanol.22 In addition, selective extraction of oligomeric proanthocyanidins rich in A-type dimers was further achieved with ethyl acetate and subsequent treatment with AB-8 resin. The methanol extract was concentrated by evaporation of methanol, and the phenolic extract fractionated into three fractions using the Toyopearl HW-50F column. Fraction 1 contained a major component with a retention time of 21.816 min and a minor component with a retention time of 24.636 min. Both the peaks had a common mass and fragmentation pattern suggesting a pair of isomers. The molecular ion [M-H] - at m/z spectrum of 575.4 is consistent with an A-type procyanidin dimer. Fraction 2 consisted of A-type procyanidin trimer(s) with

molecular ion [M-H] - at m/z of 863.1. Fraction 3 showed a prominent peak at 21.626 min with molecular ion at m/z 911.0, confirming a prominent A-type EGCG dimer. Inhibition of a-amylase activity In another study that focused on the separation and characterization of polyphenols from peanut seed skin, the effect of separated materials from the peanut skin on aamylase activity and carbohydrate absorption was accessed.23 a-Amylase is a key enzyme that catalyzes starch into oligosaccharides.24 It plays an important role in carbohydrate absorption. Its inhibition is effective in type II diabetes, cardiovascular diseases (CVDs), and neurological complications.25,26 In this study, the investigators measured polyphenolic contents of roasted peanut seed skin extracted with water and aqueous organic solvent (70% aqueous methanol, ethanol, acetone, or acetonitrile). The study found that aqueous acetone was the most effective solvent for total polyphenol extraction with highest a-amylase activity. The a-amylase inhibitory activities of polyphenol extracts of aqueous methanol, ethanol, acetone, and acetonitrile were 28.5, 22.4, 32.4, and 24.9 U/mg dry weights, respectively. On the contrary, extracts of nonpolar solvents such as hexane, ethyl acetate, and chloroform exhibited poor aamylase inhibitory activity. The specific a-amylase inhibitory activity of the acetone extract from peanut skin was about 6 times higher compared with almond seed skin extract and about 1.5 times lower compared with chestnut skin extract.27 The investigators also solubilized acetone extracts in 70% aqueous ethanol and fractionated using ultrafiltration. They found that all fractions contained the a-amylase inhibitory activity, of which fractions with over 200 kDa molecular size showed the highest inhibitory activity. The relative specific a-amylase inhibitory activity of this fraction was 2.3-folds higher than the 50–10 kDa and 15.1-fold higher than the under 10 kDa fractions. The high aamylase inhibitory activity associated with high-molecularweight (HMW) fractions suggests its association with high polymer substances in peanut skin. This result is in accordance with an earlier study showing a strong relationship between amylase inhibition and the degree of polymerization of procyanidins.28 The inhibition of the lipid peroxidation in liver homogenate

FIG. 1. Structure of A-type and B-type procyanidins.

One of the mechanisms by which cells and tissue generate free radical is by lipid peroxidation. In one such study using the four commonly found procyanidin dimers in peanut skin, the inhibitory effect of these dimers was investigated.22 The ranking of the lipid peroxidation inhibition potency was A-type ECG dimer > A-type EGCG dimer > A-type EC dimer > B-type EC dimer. It was suggested that the antioxidant potency of the A-type ECG dimer is much higher compared with the A-type EC dimer, possibly due to the existence of galloylation groups in the A-type ECG dimer.

LIPID-LOWERING EFFECT OF PEANUT SKIN POLYPHENOLS

EFFECTS OF PROCESSING ON PEANUT SKIN POLYPHENOLS Peanut skin contains 12% protein, 16% fat, and 72% carbohydrates and 140–150 mg/g dry skin total phenolics.29 It is a rich source of A-type procyanidins.30 Peanut skin is also a rich source of catechins, B-type procyanidin dimers, procyanidin trimers, tetramers, and oligomers with a higher degree of polymerization.31 Peanut skins are usually removed during peanut processing. Peanut skin polyphenols are sensitive to processing methods and yield different concentrations depending on the processing and extraction methods. In a study conducted using three different extraction methods (water, 80% ethanol, methanol) on skins collected by direct, blanching, and roasting peeling, the total phenolics (mg GAE/g dry skin) for water extraction were 56.7 – 0.54, 12.5 – 0.17, and 79.0 – 1.8 for direct, blanching, and roasting peeling, respectively.20 The total phenolics for 80% ethanol extractions were 89.9 – 2.20, 16.0 – 0.48, and 125 – 3.92, for direct, blanching, and roasting peeling, respectively. Whereas the total phenolics for methanol extraction were 90.1 – 4.90, 11.6 – 1.14, and 96.7 – 9.22 for direct, blanching, and roasting peeling, respectively. The results of this study indicate that roasting did not affect the total phenolic concentration and in fact increased the yield due to moisture loss. In addition, 80% ethanol showed higher recovery of total phenolics in roasted peanut skins. The effect of processing on the procyanidins also showed that the skin removal method has significant effects on the procyanidin contents of peanut skins.1 Blanching resulted in loss of 96.2% of procyanidin monomers, 90–92.5% dimers, 94.7–95.1% of trimers, 93.5% A-type tetramers, and 88.23% B-type tetramers. While roasting caused a loss of 45%, 14.7%, 35.2%, 18.1%, and 6.5% of procyanidin monomers, B-type dimers, A-type trimers, A-type tetramers, and B-type tetramers, respectively. However, A-type dimers and B-type trimers increased 38% and 158%, respectively. The increase of A-type dimers is speculated to be due to monomer polymerization or degradation of A-type trimers and tetramers through a mechanism that favors the formation of A-type dimers. In the same way, the increase in B-type trimers might be due to polymerization of monomers and B-type dimers. Due to the potential of peanut skin as a value-added food rich in polyphenolics, researchers evaluated the feasibility of incorporating peanut skins (blanched and roasted) into peanut butter. Blanched peanut skin could be incorporated to up to 3.75% levels higher than roasted peanut skin without altering the physical properties of the peanut butter.32 The potential of peanut skin polyphenols, by extracting procyanidins in a hot-water infusion and concentrating and spray drying for potential use as a food ingredient and an antioxidant-rich beverage, has also been studied.4 In this study, peanut skins were extracted with 70% ethanol. The soluble extract was evaporated and the aqueous fraction was spray dried with or without maltodextrin addition. Results showed that spray dried had the greatest amount of total phenolics (712.9 mg GAE/g), followed by the maltodextrin added spray-dried product (106.7 mg GAE/g) and soluble

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extract (25.8 mg GAE/g) on an as is basis. When converted to skin weight basis, the soluble extract had the highest total phenolics (55.6 mg GAE/g) followed by spray-dried (40.7 mg GAE/g) and maltodextrin containing spray-dried (30.5 mg GAE/g). This implies that spray drying resulted in 26.8% destruction of total phenolics, while addition of maltodextrin resulted in a degradation of 45.1% of total phenolics. The greater degradation of total phenolics in maltodextrin added spray-dried peanut skin product is in contrast with the literature showing addition of maltodextrin protected polyphenols and anthocyanins in spray-dried pomegranate extracts.33 The difference could be attributed to the phenolic composition of pomegranate, which is rich in anthocyanins, while peanut skin is rich in procyanidins.4 Evaluation of procyanidin in these products using a high performance liquid chromatography (HPLC) and a high performance liquid chromatography-electronspray ionization tandem mass spectrometery (HPLC-ESI-MS) showed that spray drying with and without maltodextrin resulted in a 2-fold increase in monomeric flavan-3-ols and 1.5-fold increase in DP2 procyanidins (m/z 575). The study suggests that spray drying resulted in a redistribution of procyanidin molecular weight while keeping the overall quantities. The increase in monomeric flavan-3-ols and dimers during spray drying is advantageous as they are absorbed better than the trimers and higher oligomers in the colon.34 This study further validates the potential use of peanut skin polyphenols as a food ingredient. BIOAVAILABILITY OF PEANUT SKIN-BASED POLYPHENOLS The bioavailability of polyphenol compounds depends on their physicochemical characteristics and is primarily dependent of their chemical structure.35 Study on rodents has revealed that bioavailability of polyphenols is < 10% on ingested dose with a range of 2–20%.36 The bioavailability of 18 major polyphenols has been identified in human studies with plasma concentrations ranging from 0 to 4 lM and the urinary excretion ranged from 0.3% to 0.43% of the 50 mg aglycone equivalent ingested dose.37 The bioavailability of procyanidins after consumption is poorly understood.38 They are weakly bioactive in vitro but have been shown to be highly effective in vivo. Studies in human subjects show that flavanols and procyanidins are stable during gastric transit.39 Flavanols are extensively glucoronidated and partially methylated in the small intestine, with the presence of negligible amounts of catechins or epicatechins in the mesenteric circulation.40–42 Animal studies conducted on the bioavailability of B-type procyanidins, the most common procyanidin in human diet, showed the presence of these unconjugated procyanidin dimers, including B1, B2, B3, B4, and B5, in various tissues, including plasma and urine, after feeding large doses of proanthocyanidin extracts or proanthocyanidin-rich seeds.43–45 Human studies have also confirmed the bioavailability of unconjugated procyanidin B1, B2, and B5 in plasma and serum within 30 min of consumption of the test material.46,47 Studies in rats showed that trimers can also be absorbed and

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were detected in urine and plasma.44,45,48 While in vivo studies showed that dimer B3 [catechin-(4a-8-catechin)] and trimer C2 [(catechin(-4a-8)-catechin-4a-8)-catechin] can also be absorbed by epithelial Caco-2 cells.49 The bioavailability of peanut skin polyphenols has not been extensively studied. A recent study evaluated the bioavailability and demonstrated limited absorption of procyanidins.8 This is in agreement with the pharmacokinetic study done by Serra et al., using a grape seed procyanidin extract in simulated gastrointestinal digestion.50 The study investigated a targeted LC/MS analysis of rat serum given a peanut skin extract gavage (250 mg/kg body weight). The results showed that A-type procyanidin, catechin, and epicatechin were detectable, while B-type procyanidin was undetectable at the dosages studied. Procyanidin reached the Cmax at 30 min and was rapidly cleared within 1 h after ingestion. Catechin and epicatechin showed similar trends as A-type procyanidin but at lower concentration ranges. In contrast, another study has shown that absorption of procyanidin A1 and A2 was shown to be only 5–10% of that of monomeric epicatechin in small intestine of rats when fed a flavonoid-enriched diet. These dimers were not conjugated or methylated thereby conserving their biological activity inside the body.3

FIG. 2.

Metabolism of procyanidins Procyanidin oligomers are cleaved into monomers and dimers in the stomach.51 They are further metabolized during their transfer across enterocytes in the small intestines resulting in metabolism of epicatechin to glucuronides, Omethyl glucuronides, and O-methyl conjugates/metabolites (Fig. 2). Epicatechin dimers are also present on the serosal side suggesting that they would enter the portal vein, they are transported to the liver where they further undergo metabolism or conjugation to glucuronides or sulfates.52 Glucuronides of flavanols can be cleaved back to the aglycones in vivo by b-glucuronide, which is present in a variety of organs.51,53,54 The kidney is the main site of metabolism of phase II metabolites of procyanidins, while brain was shown to have methyl catechin sulfate after procyanidin intake.55 HYPOCHOLESTEROLEMIC EFFECT OF PEANUT SKIN POLYPHENEOLS ON HEALTH The hypercholesterolemic effect of peanut skin polyphenols has been reported in both in vivo and in vitro studies.10,12,56 In one study, a dietary fiber-free, water-soluble fraction was fed to rats for 3 weeks.10 Feeding rats with either peanut skin or water-soluble fraction-based high-cholesterol

Metabolism and conjugation of procyanidins in vivo.

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LIPID-LOWERING EFFECT OF PEANUT SKIN POLYPHENOLS

diets resulted in a significantly lower total lipid level. Total low-density lipoprotein (LDL), high-density lipoprotein (HDL) and esterified cholesterol levels showed significant lower values in rat serum fed with peanut skin and watersoluble fraction. The decrease in lipid levels was most pronounced in LDL-cholesterol. In addition, there was an increase in the amount of total cholesterol in feces during the feeding test. No significant effect was observed in hepatic lipid in groups receiving the water-soluble fraction. The study also demonstrated that the decrease in serum cholesterol and increase in fecal cholesterol were not ascribable to the effect of peanut dietary fiber.56 Another study investigated the hypocholesterolemic effect of low-molecular-weight (LMW) or HMW fractions of peanut skin polyphenols.10 They demonstrated that when rats fed with high-cholesterol diet supplemented with either LMW or HMW, the diet containing the LMW polyphenol fraction was more effective in reducing plasma lipid levels than the control diet. The total cholesterol in plasma was reduced by 75.5% in the LMW group. This reduction in total cholesterol was mainly the decrease in LDL cholesterol. On the contrary, the HMW group showed no significant difference in the plasma lipid levels. Hepatic total cholesterols were also received in the LMW group compared to control diet. On the contrary, the HMW group had higher liver total cholesterol levels (Table 1). Procyanidin A1 and epicatechin-(4b/6)-epicatechin(2b/O/7, 4b/8)-catechin (EEC) present in peanut skin polyphenol were shown to have a cholesterol micelledegrading effect in vitro.12 In this study, the cholesterol micellar solution was incubated with water-soluble polyphenol fractions. The results showed that addition of watersoluble peanut skin polyphenols degraded the micelle in a dose-dependent manner, whereas it had no effect on the bile acids in micelle. It was further shown that procyanidin A1 dimer and EEC (a trimer) exerted micellar degradation, while catechin (a monomer) did not degrade the cholesterol micelle.

All the results suggest that feeding the LMW fraction of peanut skin polyphenols to rats that were fed with a highcholesterol diet has no significant influence on the liver/ intestine circulation of cholesterol and bile acid. Nevertheless, LMW peanut skin-based polyphenols inhibited the intestinal transport of dietary cholesterol as a result of decomposition of the bile acid emulsified micelle structure in the intestines. HYPOLIPEDEMIC EFFECTS OF PEANUT SKIN-BASED POLYPHENOLS Foods rich in polyphenols are known to exert cardiovascular protection by improving lipid homeostatsis.9 Animal studies have shown that proanthocyanidins reduce the plasma levels of atherogenic apolipoprotein B (ApoB)-triglyceriderich lipoproteins and LDL-cholesterol.57 Polyphenols from peanut skins have been recently demonstrated to show hypolipidemic effects. Polyphenol-rich extracts were supplemented to male Wistar rats receiving a Western-type diet for 10 weeks.9 Administration of a Western diet (WD) resulted in significant body weight gain in the WD group compared with the groups that received peanut skin extract (PE) oral dose of 150 or 300 mg/kg body weight. The white adipose tissues (WAT) in both PE groups were significantly lower than the WD group. Liver histology and liver accumulation analysis showed PE groups had greatly reduced intercellular vacuoles in a dose-dependent manner. The liver section stained with Oil Red-O staining verified the reduction of lipid droplets in rats that received PE supplementation (Table 1). Chemical analysis of lipids extracted from the liver revealed elevated levels of triglyceride and cholesterol contents in the WD group compared with the PE supplementation groups. On the contrary, fecal triglyceride and cholesterol levels were significantly lower in WD groups suggesting an increased excretion of fecal triglyceride and cholesterol upon supplementation with PE.

Table 1. Biochemical, Genetic, and Physiological Effects Upon Peanut Skin Polyphenol Supplementation Studied In Vivo and In Vitro Diet

Experimental model

Biochemical, genetic, and physiological effects

Literature source

High-cholesterol diet

Sprague Dawley rats

56

High-cholesterol diet

In vitro

High-cholesterol diet

Sprague Dawley rats

High-fat diet

Wistar rats

Oral gavage of oil and peanut skin emulsion High-fat diet

Wistar rats

Lower-molecular-weight polyphenols reduced plasma cholesterol. Epicatechin-(4b/6)-epicatechin-(2b/O/7, 4b8)-catechin (EEC) showed potent cholesterol micelle degrading activity. Decreased serum lipids and cholesterol levels and increased fecal lipids and cholesterol levels. Decreased body weight; decreased epididymal fat pads, reduced serum triglycerides and cholesterol levels; reduced FAS, SREBP1c, ACC, and PPARa mRNA levels in liver. Reduced plasma triglycerides and VLDL.

Wistar rats

Reduced plasma fatty acid.

12 10 9

8 8

ACC, acetyl-CoA carboxylase; FAS, fatty acid synthase; PPARa, proliferator-activated receptor alpha; SREBP1c, sterol regulatory element binding protein-1c; VLDL, very low-density lipoprotein.

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Peanut skin polyphenols reduce plasma lipids The plasma lipid levels in the above study reflected the hepatic lipid contents. Plasma triglycerides were significantly lower than the WD group. HDL levels also showed slightly reduced levels, while LDL levels were unchanged. However, very low-density lipoprotein (VLDL) levels showed significant reduction in PE-supplemented groups compared with the WD group. Plasma glucose showed a slight increase in PE groups, while the liver enzymes, alanine ALT and AST levels were lower in PE groups signifying a protective effect on high fat-induced liver damage compared with the WD group. A possible explanation to the reduced lipid levels in plasma is the inhibition of absorption of dietary lipids and diminishing chylomicron secretion by enterocytes due to procyandins in foods.58 Procyanidins can regulate ApoB and microsomal triglyceride transfer protein (MTP) and thus inhibit the efficient assembly and secretion of chylomicron.59–61 Peanut skin polyphenols involved in fatty acid synthesis and lipolysis gene regulation Gene expression analysis of rat liver tissue indicates that peanut skin extract regulates the gene responsible for fatty acid synthesis, lipid hydrolysis, lipid storage, and transportation.8 The expression of liver mRNA levels in these groups showed downregulation of fatty acid synthase (FAS), sterol regulatory element binding protein-1c (SREBP1c), acetyl-CoA carboxylase (ACC), and fat intake-related genes such as peroxisome proliferator-activated receptor gamma (PPARc), whereas peroxisome proliferator-activated receptor alpha (PPARa) was slightly upregulated in the PE group receiving 300 mg/kg body weight. These results support the role of procyanidins, a key component of the peanut skin polyphenols, downregulating SREBP1c in a farnesyl X receptor (FXR)-dependent mechanism previously suggested by Blade et al.57 CONCLUSION Peanut (Arachis hypogaea L. Fabaceae), is one of the most important economical crops owing to its wide distribution, nutritional characteristics, and widespread application in the food industry. Peanut skin and hulls are generated in large quantities as waste product during peanut seed processing. These wastes are rich in polyphenolic compounds mainly procyanidins. Recent studies have explored the role of these phenolics as antioxidant, hypocholesterolemic, and hypolipidemic bioactive compounds.1,9,10,62 Procyanidins from peanut skins have been shown to be bioavailable and effectively reach target tissues.63 Procyanidins from peanut skin affect lipid metabolism and has important consequences on CVD. Flavonoids and procyanidins and their biological action corroborate this hypothesis.57 Studies with models demonstrate that procyanidins have a positive effect on the triglyceride metabolism since they significantly reduce plasma triglyceride, especially if the concentration of triglyceride is usually elevated.8 Recent studies have indicated

that the estimated amount of polyphenols reaching the colon is very high and that microbe-derived phenolic metabolites represent the largest portion of phenolic intake.64 Polyphenols undergo catabolic activity in the colon and play an important role in regulating energy supply to the gut epithelium and host cell response.65 This indicates that the beneficial effects of procyanidins could be mainly due to the microbial catabolism leading to the formation of conjugated metabolites formed during phase II metabolism in the gut, rather than the original polymeric forms.64 So far, the biological properties of microbial-derived metabolites have not been extensively studied. Also, of importance is the understanding of how dietary polyphenols could modulate gut microbiota. This understanding will further establish proanthocyanidins as a prebiotic group of compounds potentially regulating beneficial bacteria in the gut. Furthermore, the role of proanthocyanidins from peanut skin and its metabolites in lipid homeostasis also needs to be ascertained in clinical experiments. On the other hand, researchers have investigated the feasibility of incorporating peanut skin (blanched and roasted) in peanut butter.32 Studies have also been undertaken to show the effect of processing, such as spray drying on the antioxidant capacity, total phenolics of peanut skins.4 Future studies with the oligomeric procyanidins from peanut skin extract will aid in broadening our understanding in how these compounds are metabolized. The mechanism of action of these phenolics along with new therapeutic potentials raises a very interesting possibility of using these phenolics as a nutritional supplement and as a bioactive ingredient in value-added food products. AUTHOR DISCLOSURE STATEMENT No competing financial interests exist. REFERENCES 1. Yu J, Ahmedna A, Goktepe I, Dai J: Peanut skin procyanidins: composition and antioxidant activities as affected by processing. J Food Comp Anal 2006;19:364–371. 2. Gu L, Kelm MA, Hammerstone JF, Beecher G, Holden J, Haytowitz D, Gebhardt S, Prior RL: Concentrations of proanthocyanidins in common foods and estimations of normal consumption. J Nutr 2004;134:613–617. 3. Appeldoorn MM, Vincken J-P, Gruppen H, Hollman PCH: Procyanidin dimer A1, A2, and B2 are absorbed without conjugation or methylation from the small intestine of rats. J Nutr 2009;139:1469–1473. 4. Constanza KE, White BL, Davis JP, Sanders TH, Dean LL: Value-added processing of peanut skins: antioxidant capacity, total phenolics, and procyanidin content of spray-dried extracts. J Agric Food Chem 2012;60:10776–10783. 5. Hill GM: Peanut by-products fed to cattle. Vet Clin North Am Food Anim Pract 2002;18:295–315. 6. Sobolev VS, Cole RJ: Note on utilization of peanut seed testa. J Sci Food Agric 2003;84:105–111. 7. Ahmed EM, Young CT: Composition, quality, and flavor of peanuts. In: Peanut Science and Technology (Pattee HE, Young CT, eds.). APRES, Yoakum, TX, 1982, pp. 655–688.

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