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The Effect of Two Terpenoids, Ursolic Acid and Oleanolic Acid on Epidermal Permeability Barrier and Simultaneously on Dermal Functions (우솔릭산과 올레아놀산이 피부장벽과 진피에 미치는 영향에 대한 연구)

  • Suk Won, Lim;Sung Won, Jung;Sung Ku, Ahn;Bora, Kim;In Young, Kim;Hee Chang , Ryoo;Seung Hun, Lee
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.30 no.2
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    • pp.263-278
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    • 2004
  • Ursolic acid (UA) and Oleanolic acid (ONA), known as urson, micromerol and malol, are pentacyclic triterpenoid compounds which naturally occur in a large number of vegetarian foods, medicinal herbs, and plants. They may occur in their free acid form or as aglycones for triterpenoid saponins, which are comprised of a triterpenoid aglycone, linked to one or more sugar moieties. Therefore UA and ONA are similar in pharmacological activity. Lately scientific research, which led to the identification of UA and ONA, revealed that several pharmacological effects, such as antitumor, hepato-protective, anti-inflammatory, anticarcinogenic, antimicrobial, and anti-hyperlipidemic could be attributed to UA and ONA. Here, we introduced the effect of UA and ONA on acutely barrier disrupted and normal hairless mouse skin. To evaluate the effects of UA and ONA on epidermal permeability barrier recovery, both flanks of 8-12 week-old hairless mice were topically treated with either 0.01-0.1mg/mL UA or 0.1-1mg/mL ONA after tape stripping, and TEWL (transepidermal water loss) was measured. The recovery rate increased in those UA or ONA treated groups (0.1mg/mL UA and 0.5mg/mL ONA) at 6h more than 20% compared to vehicle treated group (p < 0.05). Here, we introduced the effects of UA and ONA on acute barrier disruption and normal epidermal permeability barrier function. For verifying the effects of UA and ONA on normal epidermal barrier, hydration and TEWL were measured for 1 and 3 weeks after UA and ONA applications (2mg/mL per day). We also investigated the features of epidermis and dermis using electron microscopy (EM) and light microscopy (LM). Both samples increased hydration compared to vehicle group from 1 week without TEWL alteration (p < 0.005). EM examination using RuO4 and OsO4 fixation revealed that secretion and numbers of lamellar bodies and complete formation of lipid bilayers were most prominent (ONA=UA > vehicle). LM finding showed that thickness of stratum corneum (SC) was slightly increased and especially epidermal thickening and flattening was observed (UA > ONA > vehicle). We also observed that UA and ONA stimulate epidermal keratinocyte differentiation via PPAR Protein expression of involucrin, loricrin, and filaggrin increased at least 2 and 3 fold in HaCaT cells treated with either ONA (10${\mu}$M) or UA (10${\mu}$M) for 24 h respectively. This result suggested that the UA and ONA can improve epidermal permeability barrier function and induce the epidermal keratinocyte differentiation via PPAR Using Masson-trichrome and elastic fiber staining, we observed collagen thickening and elastic fiber elongation by UA and ONA treatments. In vitro results of collagen and elastin synthesis and elastase inhibitory activity measurements were also confirmed in vivo findings. These data suggested that the effects of UA and ONA related to not only epidermal permeability barrier functions but also dermal collagen and elastic fiber synthesis. Taken together, UA and ONA can be relevant candidates to improve epidermal and dermal functions and pertinent agents for cosmeseutical applications.

Comparison between the method of the measurement 25 Vitamin D3 (25 Vitamin D3 측정에 있어서 화학발광미세입자 측정법과 화학발광면역 측정법 간의 비교 및 고찰)

  • Kim, dae-won;Lee, jung-hee;Jung, an-na;Seo, so-yoen
    • The Korean Journal of Nuclear Medicine Technology
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    • v.19 no.2
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    • pp.112-114
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    • 2015
  • Purpose Vitamin D to Anti- Rickets both steroid compounds showing activity, By acting on bone tissue secretary and the key to maintain serum Ca homeostasis. The blood level of vitamin D is the largest in D3 that the concentration of the metabolite is reflected in the holding state of vitamin D in vivo. Sunlight to change the 7-dehydrocholesterol in the skin and through the skin to D3, In the liver in combination with the D2 and D3 D4 changes. The Radioimmunoassay(RIA) method is measuring the D 3, the sensitivity can be measured also difficult trace substance to measure the normal test because it is very sensitive, but recently, a check is possible, for the Total D3 in Chemimicroparticle immunoassay(CMIA) or Chemiluminescent immunoassay(CLIA) measuring using microparticle RIA and CMIA(Architect i2000SR) / use the CLIA(DXI-800) method to compare and evaluate the correlation between the tests in the same test items. Materials and Methods Commissioned from January 2014 to March 2015 patients were enrolled in a total of 273 people. 29 out of 273 people conducted by RIA were compared with CMIA, 244 patients were compared with CLIA. Using reagents and equipment were used RIA(Diasource), CMIA(Architect i2000SR, Abbott Diagnostics) / CLIA( Unicel DXi-800, Beckman coulter). Results Correlation of the RIA and CLIA was a R2 = 0.1844 (y = 0.7303x + 3.9005), and the correlation of RIA CMIA is R2 = 0.2762 (y = 0.8862x + 4.56) respectively. (According to statistics, during the same period RIA is Deficiency 4.31%, Insufficiency 90.53%, Sufficiency 5.16%, was Excess 0%, CLIA / CMIA is Deficiency 17.02%, Insufficiency 75.91%, Sufficiency 7.03%, indicating the distribution of 0.03 % Excess) Conclusion Serum vitamin D and parathyroid hormone that show an inverse relationship, the level above which are not parathyroid hormone and vitamin D reduced the increase. The density is different for each study, at most 20 is reported to be the maximum between 30 ng / ml. In Korea it requires a proposed standard of vitamin D deficiency, reference to the WHO lack the case more than 10ng/ml, 20ng/ml and defined by the lack of, if not more than, the IOM, but looking at 12ng/ml or less to the normal to lack, at least 20ng/ml, the reference do not match the deficit under 20ng/ml, 21-29ng/ml relative lack between, was also defined as a sufficient condition for more than 30ng/ml. Although not statistically is between RIA and CLIA two ways to vitamin D levels change according to season match, when seasonally seen in summer as commonly known (April to September), winter (October to March) relative to the increase measured than it was found. Finally, the study on the correlation between the two methods have been expected to result in a consistent and apply the same view high reference value on the graph is difficult. However, there may be differences between the test equipment and methods, and could be especially the case of RIA method using an organic solvent is difficult to compare different methods and correlated view similar trend in vitamin D deficiency and quarterly aspect ratio.

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Protective Effects of Chaenomeles sinensis Koehne Extract on Ethanol-induced Liver Damage in Rat (에탄올에 의해 유발된 간독성에 대한 모과 추출물의 보호효과)

  • Lee, Yu-Mi;Lee, Jae-Joon;Shin, Hyoung-Duck;Lee, Myung-Yul
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.35 no.10
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    • pp.1336-1342
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    • 2006
  • This study was performed to investigate the effect of ethanol extract of Chaenomeles sinensis Koehne (CS) on alcohol-induced liver damage in rats. Male Sprague-Dawley rats weighing $135{\pm}10g$ were divided into 6 groups for 4 weeks; normal group (ND), alcohol (35%, 10 mL/kg/day) treated group (ET), CS ethanol extract 200 mg/kg/day treated group (ND-CSL), CS ethanol extract 400 mg/kg/day treated group (ND-CSH), CS ethanol extract 200 mg/kg/day and alcohol treated group (ET-CSL), and CS ethanol extract 400 mg/kg/day and alcohol treated group (ET-CSH). The body weight gain and food efficiency ratio were no differences between ND and ET. There were increases in the activities of serum alanine aminotransferase (ALT), asparate aminotransferase (AST), and alkaline phosphatase (ALP) in ET. On the other hand, the administration of CS decreased ALT, AST and ALP activities in serum. It was also observed that the hepatic activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px) and xanthine oxidase (XO) increased by alcohol treatment were also markedly decreased in the CS administered groups as compared with ET. The activities of hepatic SOD, catalase, GSH-Px and XO were riot significantly different among the normal diet groups. Contents of thiobarbituric acid reactive substances (TBARS) were increased by the administration of alcohol, on the other hand, the administration of CS reduced TBARS value in the liver. In addition, the content of glutathione (GSH) in the liver was decreased by alcohol administration, however, GSH increased after administering CS. In conclusion, the administration of alcohol develops the hyperoxidation of liver lipids through tile increase in enzymes activity related to the lipid peroxiation, however, it was decreased after administring CS. Thus, CS may have a possible protective effect on ethanol-induced hepatotoxicity in rat liver.

Proanthocyanidins Suppresses Lipopolysaccharide-stimulated Inflammatory Responses via Heme Oxygenase-1 Induction in RAW264.7 Macrophages (프로안토시아니딘의 항염증효과)

  • Cheon, Hye-Jin;Park, Sun Young;Jang, Hee-Ji;Cho, Da-Young;Jung, Jiwon;Park, Gimin;Jeong, Kyeong Mi;Kim, Jin-Kyung
    • Journal of Life Science
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    • v.29 no.4
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    • pp.484-491
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    • 2019
  • Proanthocyanidins are naturally occurring polyphenolic compounds abundant in many vegetables, plant skins (rind/bark), seeds, flowers, fruits, and nuts. Numerous in vitro and in vivo studies have demonstrated myriad effects potentially beneficial to human health, such as antioxidation, immunomodulation, DNA repair, and antitumor activity. Among immune cells, macrophages are crucial players in a variety of inflammatory responses to environmental conditions. However, it has been widely reported that macrophages cause chronic inflammation and are involved in a variety of diseases, such as obesity, diabetes, metabolic syndrome, and cancer. In this study, we report the suppressive effect of proanthocyanidins via the heme oxygenase-1 (HO-1)-related system, on the immune response of the LPS-stimulated mouse macrophage cell line RAW264.7. Increased HO-1 expression at mRNA and protein levels were found in proanthocyanidins-treated RAW264.7 cells. Further, proanthocyanidins enhanced nuclear factor-erythroid 2-related factor 2 translocation into the nucleus. RAW264.7 cells were treated with lipopolysaccharide (LPS) with or without proanthocyanidins, and inflammatory mediator expression levels were assessed. Proanthocyanidins treatment resulted in the attenuation of nitric oxide production and inducible nitric oxide synthase expression in LPS-stimulated RAW264.7 cells. In addition, mRNA and protein expression of proinflammatory cytokines, such as tumor necrosis factor-${\alpha}$ and interleukin-6, was inhibited by proanthocyanidins treatment in LPS-stimulated RAW264.7 cells. These findings support proanthocyanidins as a promising anti-inflammatory agent.

Effects of Fresh and Black Garlic Hot Water Extract Powder on the Lipid Composition of Hypercholesterolemia Rats (생마늘 및 흑마늘 열수추출 분말이 고콜레스테롤 혈증 흰쥐의 체내 지질조성에 미치는 영향)

  • Kang, Min-Jung;Shin, Jeong Yeon;Lee, Soo Jung;Shin, Jung Hye
    • Journal of Life Science
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    • v.31 no.1
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    • pp.37-46
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    • 2021
  • The effects of freeze-dried powder from fresh and black garlic hot water extracts on the lipid metabolism in Sprague-Dawley rats fed a high-cholesterol diet were analyzed. The experimental group was classified into the normal group (NG), the high-fat (HF) and high-cholesterol diet group (CG), the HFC and 1% fresh garlic hot water extract powder-added diet group (FGEG), and the HFC and 1% black garlic hot water extract powder-added diet group (BGEG), respectively. The serum total lipid content was 381.52±7.30 mg/ml and 368.80±4.40 mg/ml in the FGEG and the BGEG, respectively, and was significantly lower than that of the CG. The total cholesterol and triglyceride contents of the FGEG and BGEG were also significantly lower than that of the CG. The high-density lipoprotein (HDL) cholesterol was significantly higher, and the low-density lipoprotein (LDL) and the very low-density lipoprotein (VLDL) cholesterol content was lower in the FGEG and BGEG than in the CG. The serum ALT and AST activities were significantly lower than those of the CG, and especially the BGEG was lower. The total cholesterol content and the triglyceride levels of the liver tissue were 36.0% and 14.3% lower in the BGEG than in the CG, respectively. The thiobarbituric acid reactive substance (TBARS) concentrations in the serum and the liver tissue were higher in the CG than in the FGEG and BGEG, but there was no difference between them. Based on these results, garlic extract powders significantly reduced the lipid profile and increased the antioxidant activity in rats in vivo. The black garlic hot water extract powder was more effective than raw garlic because of the total number of phenolic compounds and browning substances in the black garlic.

Study on the Safety of Firefly Luciferase in Human as a Transient Reporter Gene of Oncolytic Virotherapy (항암 바이러스 치료제의 보고유전자로써 반딧불이 루시퍼레이즈의 인체 내 안전성에 대한 연구)

  • Hong, Young Mi;Yoon, Woong Hee;Lee, You Ra;Kim, Soo Ji;Ngabire, Daniel;Narayanasamy, Badrinath;Ornella, Mefotse Saha Cyrelle;Kim, Myunghee;Cho, Euna;Lee, Bora;Hwang, Tae-Ho
    • Journal of Life Science
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    • v.31 no.11
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    • pp.1028-1036
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    • 2021
  • Firefly luciferase (FLuc) can function as an efficient marker in the gene and viral therapies. Nonetheless, its clinical translation has been unaccomplished with the concerns on its exogenous nature and the similarity with human fatty acyl-CoA synthetase. In this study, we aimed to show safety of FLuc by conducting a set of preclinical experiments and a human use. Initially, FLuc permeability across the plasma membrane was investigated by delivering the FLuc-carrying viral vector, OTS-412, or the FLuc recombinant protein. After in vitro infection of OTS-412 into different cancer cell lines, FLuc activity was detected only in the cell lysates, but not in culture media. In addition, recombinant FLuc protein further showed the impermeability against the plasma membrane. Similar result was also observed in the in vivo experiment. After being injected into the VX2 tumor-bearing rabbit, the FLuc exclusively resided within the tumor tissue without being detected in the blood plasma or other organs. Human cancer cell lines originated from various organs were lysed and treated to the FLuc, and none of the human substrates was reactive against the FLuc. As a final step, FLuc recombinant protein was intravenously injected into a human. The luciferase was degraded with the half-life of 20 to 30 minutes in blood, and was untraceable from 1.5 hr after the injection. In addition, the blood plasma was nonresponsive against the fatty acids. Hematological analysis was also comparable between the pre- and post-injection. Altogether, our study collectively demonstrates the safety of the firefly luciferase.

Protective Effect of Mixed Extract including Hovenia dulcis Thunberg against Chronic Ethanol Treatment-induced Cytotoxicity in a Brain and Liver Tissue (만성 알코올 섭취로부터 유도되는 뇌 및 간 조직 독성에 대한 지구자 혼합 추출물의 보호 효과)

  • Kim, Jong-Min;Park, Seon-Kyeong;Guoa, Tian-Jiao;Kang, Jin-Yong;Ha, Jeong-Su;Lee, Du-Sang;Kwon, O-Jun;Lee, Uk;Heo, Ho Jin
    • Journal of agriculture & life science
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    • v.50 no.2
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    • pp.125-138
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    • 2016
  • To assess the industrial possibility of mixed-extracts containing Hovenia dulcis Thunberg and 12 different botanical ingredients, a protective effect was confirmed in the chronic ethanol-induced the liver, brain, and blood injury in mouse. Blood glucose levels of the normal control group(NG) and ethanol administration group(EG) were respectively 119.43mg/dL and 305.25mg/dL, and the mixed-extracts administration group(100, 200mg/kg body weight + 25% ethanol 5g/kg body weight respectively; ME100 & ME200) were decreased to 272.76mg/dL and 234.60mg/dL. Blood ethanol contents were decreased in ME100 and ME200(3.85mg/dL, 3.08mg/dL) compared to EG(4.08mg/dL), and blood acetaldehyde contents were also decreased in ME(15.76mg/dL, 15.16mg/dL) compared to EG(18.72mg/dL). The contents of hepatotoxic indicators such as glutamine pyruvic transaminase(GPT) and glutamic oxaloacetic transaminase (GOT), nephrotoxic indicators such as blood urea nitrogen(BUN), and creatine(CRE), and total cholestero(TCHO), and triglyceride(TG) in mouse blood serum were significantly decreased in the ME compared to EG. The acetylcholinesterase(AChE) activity of ME(109.00% and 108.47%, respectively) in mouse brain tissues was decreased in ME compared to EG(116.10%). Finally, ME was remarkable in vivo antioxidant activities in the mouse liver and brain tissues by superoxide dismutase(SOD), oxidized glutathione(GSH)/total GSH ratio and the malondialdehyde (MDA) assay. Therefore, the mixed-extracts was considered to be effective a high value food with protective effect against chronic ethanol traetment-induced cytotoxicity in liver and brain tissues.

Anticarcinogenic Responses of MCF-7 Breast Cancer Cells to Conjugated Linoleic Acid (CLA) (식이성 Conjugated Linoleic Acid (CLA)가 유선암 세포(MCF-7)에서의 항암효과에 미치는 영향)

  • 문희정;이순재;박수정;장유진;이명숙
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.32 no.3
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    • pp.418-427
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    • 2003
  • Conjugated linoleic acid (CLA) is the mixture of positional and geometric isomers of linoleic acid (LA, C18:2 $\omega$6), which is found abundantly in dairy products and meats. This study was peformed to investigate the anticarcinogenic effect of CLA in MCF-7 breast cancer cells. MCF-7 cell were treated with LA and CLA at the various concentrations of 15, 30, 60, 120 UM each. After incubation for 48 and 72 hours, cell proliferation, fatty acids incorporation into cell, peroxidation and activities of antioxidant enzymes were measured. Postaglandin E$_2$ (PGE$_2$) and thromboxane $A_2$ (TXA$_2$) were measured for the eicosanoids metabolism. There was no cell growth differences in both of LA and CLA treated MCF-7 cells at 48 hr incubation. Compared to LA, cell growth was decreased by CLA treatment according to increasing concentration at longer incubation times, respectively (p<0.05). Both of LA and CLA was incorporated into the cellular lipids 22~54% higher than in control but LA incorporation was not so linear as CLA according to concentration. Arachidonic acid (C20:4, $\omega$6) was synthesized after treatment of LA but did not in CLA, respectively. The lipid peroxide concentration in LA 120 $\mu$M group increased as 1.7 times as that in CLA 120 $\mu$M treated. The activities of antioxidant enzymes such as glutathione peroxidase and glutathione reductase were increased by the supplementation with CLA 120 $\mu$M at 72 hr incubation (p<0.001) compared to LA, otherwise activity of superoxide dismutase was not different in both. PGE$_2$ and TXA$_2$ levels were lower in condition of CLA treatments according to lower levels of arachidonic acids than those in LA treated group, respectively. Overall, the dietary CLA might change the MCF-7 cell growth by the changes of cell composition, production of lipid peroxide, activities of antioxidant enzymes and eicosanoid synthesis compared to dietary LA.

Induction of Apoptosis by Piceatannol in YD-15 Human Oral Cancer Cells (피세아타놀에 의한 YD-15 구강암세포의 세포자가사멸 유도 효과)

  • Lee, Hae-Nim;Jang, Hye-Yeon;Kim, Hyeong-Jin;Shin, Seong-Ah;Choo, Gang-Sik;Park, Byung-Kwon;Kim, Byeong-Soo;Jung, Ji-Youn
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.7
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    • pp.975-982
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    • 2015
  • Piceatannol (trans-3,4,3',5'-trihydroxystilbene), a natural stilbene, is an analogue of resveratrol. In the present study, possible mechanisms by which piceatannol exerts its pro-apoptotic action in cultured human oral cancer YD-15 cells were investigated. To investigate whether or not piceatannol has effects on cancer cell viability, human oral YD-15 cells were treated with piceatannol (0, 50, and $100{\mu}M$). Piceatannol treatment ($100{\mu}M$) showed the strongest inhibition of cell proliferation and reduced cell viability in a dose-dependent manner. Chromatin condensation detected by DAPI staining significantly increased in a concentration-dependent manner, indicating apoptosis. Piceatannol treatment activated initiator Bax (pro-apoptotic) and cPARP in a concentration-dependent manner. Further, piceatannol induced down-regulation of Bcl-2 (anti-apoptotic). We also evaluated the activity of piceatannol against oral cavity cancer tumors in mice. Piceatannol-treated nude mice bearing YD-15 xenograft tumors exhibited significantly reduced tumor volume and weight due to the potent effect of piceatannol on tumor cell apoptosis, as determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. Immunohistochemistry staining showed elevated expression of cleaved-caspase-3 as well as reduced expression of Ki-67 in the piceatannol-treated group. Therefore, piceatannol can be developed as a cancer preventive medicine due to its growth inhibitory effects and induction of apoptosis in human oral cancer cells.

A prognosis discovering lethal-related genes in plants for target identification and inhibitor design (식물 치사관련 유전자를 이용하는 신규 제초제 작용점 탐색 및 조절물질 개발동향)

  • Hwang, I.T.;Lee, D.H.;Choi, J.S.;Kim, T.J.;Kim, B.T.;Park, Y.S.;Cho, K.Y.
    • The Korean Journal of Pesticide Science
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    • v.5 no.3
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    • pp.1-11
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    • 2001
  • New technologies will have a large impact on the discovery of new herbicide site of action. Genomics, combinatorial chemistry, and bioinformatics help take advantage of serendipity through tile sequencing of huge numbers of genes or the synthesis of large numbers of chemical compounds. There are approximately $10^{30}\;to\;10^{50}$ possible molecules in molecular space of which only a fraction have been synthesized. Combining this potential with having access to 50,000 plant genes in the future elevates tile probability of discovering flew herbicidal site of actions. If 0.1, 1.0 or 10% of total genes in a typical plant are valid for herbicide target, a plant with 50,000 genes would provide about 50, 500, and 5,000 targets, respectively. However, only 11 herbicide targets have been identified and commercialized. The successful design of novel herbicides depends on careful consideration of a number of factors including target enzyme selections and validations, inhibitor designs, and the metabolic fates. Biochemical information can be used to identify enzymes which produce lethal phenotypes. The identification of a lethal target site is an important step to this approach. An examination of the characteristics of known targets provides of crucial insight as to the definition of a lethal target. Recently, antisense RNA suppression of an enzyme translation has been used to determine the genes required for toxicity and offers a strategy for identifying lethal target sites. After the identification of a lethal target, detailed knowledge such as the enzyme kinetics and the protein structure may be used to design potent inhibitors. Various types of inhibitors may be designed for a given enzyme. Strategies for the selection of new enzyme targets giving the desired physiological response upon partial inhibition include identification of chemical leads, lethal mutants and the use of antisense technology. Enzyme inhibitors having agrochemical utility can be categorized into six major groups: ground-state analogues, group specific reagents, affinity labels, suicide substrates, reaction intermediate analogues, and extraneous site inhibitors. In this review, examples of each category, and their advantages and disadvantages, will be discussed. The target identification and construction of a potent inhibitor, in itself, may not lead to develop an effective herbicide. The desired in vivo activity, uptake and translocation, and metabolism of the inhibitor should be studied in detail to assess the full potential of the target. Strategies for delivery of the compound to the target enzyme and avoidance of premature detoxification may include a proherbicidal approach, especially when inhibitors are highly charged or when selective detoxification or activation can be exploited. Utilization of differences in detoxification or activation between weeds and crops may lead to enhance selectivity. Without a full appreciation of each of these facets of herbicide design, the chances for success with the target or enzyme-driven approach are reduced.

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