This study was performed to elucidate in vitro and in vivo anticancer activity of lipid-soluble extract from ginseng and ginseng marc. Ginseng marc is a by-product left after ginseng is extracted with hot water in ginseng industry. The lipid-soluble extracts from ginseng and ginseng marc were prepared by n-hexane extraction. Each n-hexane extract from ginseng (HEG) and ginseng marc (HEGM) represented the anti-proliferative activity against various human cancer cell lines such as human liver, colon, lung, prostate, and leukemia cancer cells in vitro. While water-soluble extract from ginseng (WEG) possessed a low anticancer activity, HEG and HEGM showed a potent anticancer activity against various cancer cell lines. Accordingly the anticancer effect of ginseng is considered to be originated mainly from lipid-soluble rather than water-soluble components.
HEG potently inhibited the proliferation of human NCI-H460 lung cancer cells in human tumor xenograft-bearing mice in vivo without any toxicity. Oral administration with 300 mg/kg/day of HEG from the day after cancer cell inoculation inhibited tumor growth by 60.0%, whereas administration with the same amount of HEG from the day after 70.0 mm³ tumor formation resulted in 18.2% inhibition. Administration of HEG in the early stages of tumors was more effective in inhibiting cancer cell proliferation.
HEG exerted anticancer effect by cell cycle arrest and apoptosis induction in NCI-H460 cancer cells. HEG potently arrested the cell cycle progression of NCI-H460 cells in the G0/G1 phase by suppressing the expression of cyclin-dependent kinase-2, -4, -6, cyclin D3, and cyclin E. In addition, HEG induced the apoptosis of NCI-H460 cells by activating caspase-8, -9 and -3 enzymes. HEG strongly inhibited cancer cell invasion and migration by suppressing the expression of matrix metalloproteinase-2 (MMP-2) in B16F10 melanoma cancer cells. The oral administration of HEG to the mice intravenously injected with B16F10 cells inhibited lung metastasis of cancer cells.
Supercritical CO₂ extraction was used to improve the yield of lipid soluble extract from ginseng marc without using an organic solvent. Supercritical CO₂ extract from ginseng marc (SCEGM) strongly inhibited the proliferation of 12 types of human cancer cells by more than 50% at an average concentration of 33.99 μg/mL. SCEGM inhibited the growth of human MKN74 gastric cancer cells in human tumor xenograft-bearing mice in vivo without any toxicity. Oral administration with 1.0 g/kg/day of SCEGM from the day after MKN74 cells inoculation inhibited tumor growth by 28.9%.
In conclusion, HEG represented the strong anticancer effect against human cancer cells in vitro and in vivo. HEG inhibited the cancer cell proliferation by arresting the G0/G1 cells progression and inducing the caspase-mediated apoptosis. HEG inhibited the migration and the metastasis of cancer cells by suppressing MMP-2 expression. Also SCEGM as well as HEGM obtained from ginseng marc possessed the potent anticancer activity against human cancer cells. The lipid-soluble extract from ginseng and ginseng marc has potential as an anticancer substance.

Keywords: Ginseng, Ginseng marc, Lipid-soluble extract, Anticancer activity, n-Hexane extract, Supercritical CO₂ extract

Rice, the most important cereal species, is a staple food for over half of the world’s population. It is rich in carbohydrates but low in essential amino acids, micronutrients, and carotenoids as provitamin A components. To strengthen the nutritional value of rice (Oryza sativa L.), plastid-dependent metabolites could be promising targets for biofortification of rice grains. First, four carotenoid components such as β-carotene, zeaxanthin, astaxanthin, and capsanthin with diverse colors and different functionalities were independently accumulated in rice endosperm by several strategies to stack multiple pathway genes: overexpression of mono-, bi-, tri-, and quad-cistronic genes based on 2A peptide sequence with ribosomal pausing activity, RNA interference, and conventional breeding as ten rice varieties: PAC rice, stPAC rice, OsCCD4a_RNAi-stPAC rice, B-PAC rice, stBAK-PAC rice, B-PAC x Ccs rice, stBAK-PAC x B-PAC x Ccs rice, OsDXS2-stPAC rice, OsDXR-stPAC rice, OsIspH1-stPAC rice. During these processes, key elements for better performance of carotenoid production in rice endosperm have been elucidated for optimal promoter and transit peptides. Taken the use of clean vector and high-throughput systems to generate and analyze transgenic rice plants together, event candidates for functional color rice have been selected for practical uses with qualifications to enter safety assessment. Also, a new biofortified rice variety, ‘Evergreen Rice’, was recently developed by overexpression of OsMYBR22 gene encoding a CCA1-like MYB-related transcription factor. It showed the color phenotypes of stay-green in leaves and evergreen in seeds and resulted in highly improved grain quality by simultaneously accumulating multiple valuable phytonutrients, including chlorophyll (antioxidants), carotenoids (provitamin A), lysine and threonine (essential amino acids) and GABA (a dietary supplement effective at lowering blood pressure and reducing neuronal excitability). Our rice varieties have great potential to supply the highly improved nutritional and functional values for human as staple food grains.

Metabolomics is the study of metabolite profiling which involves the analysis of low-molecular-weight compounds in plant cells, tissues, and biofluids, and considering interactions within various organisms and reactions of external chemicals with those organisms. In the last decades, metabolomics has developed rapidly, being applied in a vast range of life sciences such as functional genomics, chemotaxonomy, quality control of medicinal plants, elucidate biomarkers and as a tool in the natural product analysis. Recently, metabolomics have been rapidly employed for the analysis of natural products in a more holistic way, finding multiple applications and uses. In this presentation, it is described that MS and NMR coupled with multivariate analysis technique can be used to discriminate various natural products (Panax ginseng, Acanthopanax spp etc.). In addition, the application of metabolomics to investigate the effect (hypertension etc.) of bioactive substances on metabolic profiles of biofluid samples was also introduced. The application of metabolomics should be expanded in the field of natural products in the future.

The Lab of Applied Microbiology and Biomaterials (LAMB) at Gyeongsang National University since 2015 has studied structurally complex aromatic polymers that are widespread in nature including living organisms. It has been investigated how the polymers such as humic substances, lignin, melanin, and polyflavonoids are synthesized and functionally involved in environmental and biological phenomena, but their complex structures hinder a deciphering of accurate structure-function relationships, concomitantly causing their limited applications. As a Ph. D. candidate under the supervision of Dr. Jong-Rok Jeon, I have sought to elucidate key structural features that can account for unique properties of the polymers regarding direct plant stimulation, root exudation responsiveness, and specific visible light absorbance. My trials are now being connected to the product developments relevant to cosmetics and crop fertilizers by collaborations with manufacturing companies in South Korea and Italy. In this presentation, I will introduce core research missions of the Biomaterials team of LAMB and my contributions to them.

Oxyanions such as arsenic (As) and antimony (Sb) and heavy metals such as lead (Pb) and cadmium (Cd) are highly toxic and contaminate food crops due to soil pollution in agricultural land around mines. To prevent contamination of food crops, metal(loid)s should be stabilized in soil, which can be achieved by iron phosphate because oxyanions and heavy metals are stabilized with iron and phosphate, respectively. Therefore, the objectives of this study are to evaluate simultaneous stabilization of various metal(loids) in solution and soil using vivianite [Fe₃(PO₄)₂·8H₂] and to evaluate growth of lettuce by applying iron phosphate-coated biochar in metal(loid) contaminated soil. Oxyanion and heavy metal solutions were prepared both as a single metal and mixed metal solutions. Contaminated soil was treated with 1 g/kg of vivianite and 1% iron phosphate-coated biochar and bioavailable metal concentrations were analyzed. Vivianite simultaneously immobilized As, Sb, and Pb, and metal removal rate was higher in mixed metal solution than in single metal solution. Vivianite treatment in metal(loid) contaminated soil reduced bioavailable metal(loid) concentrations. Shoot and root length, fresh and dry weight, SPAD, and Fv/Fm values of lettuce treated with iron phosphate-coated biochar were higher than those of lettuce grown without biochar. In addition, iron phosphate-coated biochar reduced metal(loid) uptake by lettuce. Therefore, iron phosphate can be used to concomitantly stabilize metal(loid)s in contaminated soil, enhance plant growth and produce safe food crops.