Lunasin As a Promising Health-Beneficial Peptide

Eur opean Rev iew for Med ical and Pharmacol ogical Sci ences 2014; 18: 2070-2075 Lunasin as a promising health-beneficial peptide J. LIU 1, S.-H. JIA 1, M. KIRBERGER 2, N. CHEN 1 1College of Health Science, Wuhan Sports University, Wuhan, China 2Department of Natural Sciences, Clayton State University, Morrow, GA, USA Jun Liu and Shaohui Jia contributed equally to this work Abstract. – Lunasin, a 43 amino acid characterized as a small polypeptide with poly- polypeptide originally isolated from soybean, is known to produce multiple health benefits, in - Asp (D) residues located at the carboxyl termi - cluding anti-hypertension, antioxidant activity, nus , and was subsequently found in other beans, cancer prevention or therapy, anti-inflamma - grains and herbal plants , including wheat, barley, tion, hypocholesterolemic activity, anti-obesity rye, sunberry, wonderberry, bladder-cherry , jim - and immunomodulation. These effects are be - son weed , Solanum nigrum L ., amaranth and trit - lieved to be due to its unique structure that in - icale , at concentrations ranging from 0.013 to cludes a putative helical region, an Arg-Gly-Asp 4 (RGD) motif and an Asp-rich carboxyl terminus. 70.5 mg protein lunasin/g of protein (Table I ) . The focus of this article is to summarize the Since then, lunasin has been the subject of sever - discovery, characterization and biological activ - al investigations, including a very important ities of lunasin, which will provide a reference study on the cloning of the soybean lunasin gene for the future development and utilization of lu - and subsequent transfection into mammalian nasin, and a basis for exploring the underlying mechanisms of these health-beneficial func - cells, at the California University at Berkeley tions. (USA), which led to the discovery that the lu - nasin gene can disrupt mitosis and induce chro - Key Words: mosome breakage , ultimately leading to cell Lunasin, Anticancer, Anti-inflammation, Soybean apoptosis 5. peptide. Characterization of Lunasin Discovery and Resources of Lunasin Structural Characteristics There is a growing body of research suggest - Lunasin is a unique peptide composed of 43 ing that the consumption of soybean products can amino acid residues (sequence SKWQHQQD - reduce the incidence of osteoporosis and some SCRKQKQGVNLTPCEKHIMEKIQ - chronic diseases, especially cardiovascular dis - GRGDDDDDDDDD ) ( Figure 1 ) with a molecu - eases and cancers 1. Consumption of soybean lar weight of 5.5 kDa. This peptide contains 8 products is also associated with lower mortality negatively-charged Asp (D) residues at the car - rates from prostate, breast, colon, and endometri - boxyl terminus, thus providing a histone -binding al cancers 2. Therefore, the modification of nutri - property that allows it to act as a potent inhibitor tional habits (e.g., soybean consumption) is be - of positively-charged H3 and H4 histone acetyla - coming increasingly interesting as a means of tion 6. The poly-D chain is immediately preceded disease prevention and modulatory therapy. Pre - in the sequence by a cell adhesion motif Arg- vious studies have revealed that soybean contains Gly-Asp (RGD) that is responsible for the attach - a variety of phytochemicals including protease ment of lunasin to the extracellular matrix , and a inhibitors, inositol hexaphosphate (phytic acid), putative helical region (EKHIMEIQG ) which is b-sitosterol, saponins, and isoflavones 3. structurally homologous to a conserved region Lunasin was first isolated in 1987 at Niigata found in chromatin-binding proteins 7, suggesting University School of Medicine in Japan, during that the helical region may target lunasin to core the screening of protease inhibitors from soybean histones 8. This putative helical region may func - seeds , and was subsequently identified as a tion to enhance binding capability to the core his - promising anticancer candidate. It was initially tone. The RGD motif can also facilitate internal - 2070 Corresponding Author: Ning Chen, Ph.D; e-mail: [email protected] Lunasin as a promising health-beneficial peptide Figure 1. Amino acid sequences and functions of peptide fragments from lu - nasin. The function of the fragment spanning residues 1 -22 remains to be defined; the fragment spanning residues 23 -31 is responsible for chro - matin-targeting; the Arg-Gly-Asp motif (amino acid residues 32 -34) is respon - sible for peptide internalization into the cell nucleus; the polyaspartyl end (amino acid residues 35 -43) is respon - sible for its direct binding to chromatin. ization of lunasin into mammalian cells within Physiological Characteristics several minutes , followed by localization in the Since lunasin is a peptide, it is important to nucleus within a few hours 8. According to recent understand the degradation, absorption, translo - studies, the cell adhesion function of the RGD cation and distribution of lunasin in target tissues motif may be cell-line specific, with adhesion or organs subsequent to oral administration. observed in C3H cells, but not in NIH3T3 cells . Therefore, the bioavailability of lunasin has been The RGD motif can induce cell apoptosis in dif - explored in both in vitro and in vivo studies. Pre - ferent cell lines via a caspase-dependent mecha - liminary studies regarding bioavailability of lu - nism 9. In addition, lunasin may also be involved nasin in mice and rats supplied with lunasin-en - in cellular growth and proliferation, cellular riched soybean protein have revealed that 35% of function maintenance , and cell -cell signaling and ingested lunasin is distributed to the target tissues interactions 10 . Based on our current knowledge, and organs in an intact and active form 11,12 . Simi - the major functions of lunasin appear to reside in larly, a study on the bioavailability of lunasin in a the poly-D chain, RGD motif and putative helical sample from adult human males indicated that region structures, while functions associated with 4.5% of the ingested lunasin was distributed in the other amino acid residues or structures in lu - the plasma in the intact or active form of the soy - nasin remain undefined . Further research will be bean protein 13 . The high capacity of lunasin to required to determine whether smaller peptides avoid degradation by gastrointestinal and serum that include these functional domains from lu - proteinases or peptidases, and retain its bioactive nasin will be capable of similar health-promoting form during the translocation process to blood or therapeutic functions. and other organs , makes lunasin a promising can - Table I. Lunasin content in soybean, grains and medicinal plants. Plant (Latin name) Plant (General name) Lunasin content Lunasin content (mg/g protein) (mg/g seed) Triticum aestivum Wheat 0.2-0.3 Hordeum vugare L. Barley 5.9-8.7 0.01-0.02 Glycine max 5 Soybean 4.4-70.5 0.5-8.1 Amaranthus hypochondriacus Amaranth 9.5-12.1 Physalis alkekengi var. francheti Bladder-cherry 17.0 0.1 Solanum lyratum Hyyodori-jogo 22.3 0.4 Solanum nigrum L. Sunberry 36.4 1.8 Datura starmonium Jimson weed 10.3 0.3 2071 J. Liu, S.-H. Jia, M. Kirberger, N. Chen didate for the preventive treatment of cancers in mination of the inhibitory activity of linoleic acid vivo 14 . In addition, circular dichroism analysis re - oxidation and scavenging capacity of ABTS + free veals that lunasin exhibits high thermostability radicals . Lunasin appears to exhibit potent ABTS within the temperature range 25-100° C with no scavenging activity, with TEAC values of 1.41 17 apparent change in either its secondary structure and 1.90 µM, respectively . or its bioavailability 15 . Anti-inflammation Lunasin also appears to inhibit the release of Preparation of Lunasin pro-inflammatory cytokines such as tumor necro - sis factor- α (TNF- α) and interleukin -6 ( IL-6) in Current methods for the preparation of lunasin LPS-stimulated RAW264.7 cells, without im - include isolation and purification from natural pacting cell viability 17 . Its corresponding action products, prokaryotic expression and chemical mechanisms are strongly correlated with reduced synthesis. Jeong et al 12 isolated lunasin from inflammation in LPS-stimulated RAW 264.7 wheat seeds at different growth stages by extrac - macrophages , induced by lunasin through inhibi - tion using MPBS buffer supplemented with fresh tion of the nuclear factor kappa B (NF-kB) path - protease inhibitor and partial purification, and way 18 . Similarly, the treatment of RAW 264.7 identified the product using mass peptide map - macrophage with 100 µM lunasin apparently re - ping. The isolated lunasin is evaluated by de - duces the production of NO and prostaglandin terming the bioactivity of the various purified frac - E2 (PGE2 ), as well as reducing the expression of tions and intact protein. Vermont et al 26 applied a inducible nitric oxide synthase (iNOS ) and cy - method that utilized the sequential application of clooxygenase-2 (COX-2 ). anion-exchange chromatography, ultrafiltration, and reversed-phase chromatography 15 . Anticancer The lunasin gene can be synthesized by over - Lunasin, as a novel chemopreventive peptide lapping extension polymerase chain reaction derived from soybean, also functions to suppress (PCR) and expression in E. coli BL21 (DE3) chemical carcinogens and viral oncogene-in - with the use of vector pET29a. The recombinant duced transformation of mammalian cells , and to lunasin containing His-tag at the C-terminus can inhibit carcinogen-induced skin tumorigenesis in be expressed in

Load more