Plants as Medicine: Botanical Therapeutics

Ilya Raskin 한국원예학회 2006 한국원예학회 기타간행물 Vol.- No.-

Biochemistry of Salicylic Acid and its Role in Disease Resistance

Lee, Hyung-Il,Raskin, Ilya The Korean Society of Plant Biotechnology 1997 식물생명공학회지 Vol.24 No.4

Salicylic acid (SA) is involved in the establishment of systemic acquired resistance (SAR) in many plant including tobacco. Considering the important role of SA in disease resistance, biosynthetic and metabolic pathways of SA in tobacco have been studied extensively: The initial step for biosynthetic pathway of SA is conversion of phenylalanine to trans-cinnamic acid, followed by decarboxylation of trans-cinnamic acid to benzoic acid and ie subsequent ring hydroxylation at the C-2 position to form SA. In TMV inoculated tobacco, most of the newly synthesized SA is glucosylated or methylated. Methyl salicylate has been identified as a biologically active, volatile signal. In contrast, the two glucosylated forms accumulate in the vicinity of lesions and consist of SA glucoside, a major metabolite, and SA glucose ester, a relatively minor from. Two enzymes involved in SA biosynthesis and metabolism have been purified and characterized : benzoic acid 2-hydroxylase which catalyzes conversion of benzoic acid to SA; UDP-Glucose: SA 1-O-D glucosyltransferase which converts SA to SA glucose ester. Further studies of the biosynthetic and metabolic pathways of SA will help to elucidate the SAR signal transduction pathway and provide potential tools for the manipulation of disease resistance.

The Effect of Initial Duloxetine Dosing Strategy on Nausea in Korean Patients with Major Depressive Disorder

이민수,안용민,정석훈,Richard Walton,Mun Sung Kim,Joel Raskin 대한신경정신의학회 2012 PSYCHIATRY INVESTIGATION Vol.9 No.4

Objective To assess the relative severity of nausea in patients from Korea with major depressive disorder (MDD) who were treated with duloxetine at low (30 mg) or high (60 mg) doses, with or without food, for the first week of an 8 week treatment. Methods Adult patients (n=249), with MDD and a 17-item Hamilton Rating Scale for Depression (HAMD17) score of ≥15, received openlabel once daily duloxetine. At Week 0, patients were randomized to 4 groups: 30 mg with food (n=63), 60 mg with food (n=59), 30 mg without food (n=64), and 60 mg without food (n=63). At Week 1, all patients switched to duloxetine 60 mg for 7 weeks. The primary outcome measure was item 112 (nausea) of the Association for Methodology and Documentation in Psychiatry adverse event scale. Effectiveness was assessed by change in HAMD17 total score. Results Overall, 94.4% (235/249) of patients completed Week 1 and 55.0% (137/249) of patients completed the study. For Week 1, nausea was significantly less severe for patients who received 30 mg compared with 60 mg duloxetine (p=0.003), regardless of food intake. In all groups, nausea severity was highest at Week 1 and declined throughout the study. HAMD17 score was reduced in all groups and the most common adverse event reported was nausea (145/249; 58.2%). Conclusion To minimize nausea, Korean patients with MDD who require duloxetine treatment could be given 30 mg once daily, regardless of food, for the first week followed by 60 mg once daily for the course of therapy.

(p)ppGpp, a Small Nucleotide Regulator, Directs the Metabolic Fate of Glucose in <i>Vibrio cholerae</i>

Oh, Young Taek,Lee, Kang-Mu,Bari, Wasimul,Raskin, David M.,Yoon, Sang Sun American Society for Biochemistry and Molecular Bi 2015 The Journal of biological chemistry Vol.290 No.21

<P>When <I>V. cholerae</I> encounters nutritional stress, it activates (p)ppGpp-mediated stringent response. The genes <I>relA</I> and <I>relV</I> are involved in the production of (p)ppGpp, whereas the <I>spoT</I> gene encodes an enzyme that hydrolyzes it. Herein, we show that the bacterial capability to produce (p)ppGpp plays an essential role in glucose metabolism. The <I>V. cholerae</I> mutants defective in (p)ppGpp production (<I>i.e.</I> Δ<I>relA</I>Δ<I>relV</I> and Δ<I>relA</I>Δ<I>relV</I>Δ<I>spoT</I> mutants) lost their viability because of uncontrolled production of organic acids, when grown with extra glucose. In contrast, the Δ<I>relA</I>Δ<I>spoT</I> mutant, a (p)ppGpp overproducer strain, exhibited better growth in the presence of the same glucose concentration. An RNA sequencing analysis demonstrated that transcriptions of genes consisting of an operon for acetoin biosynthesis were markedly elevated in N16961, a seventh pandemic O1 strain, but not in its (p)ppGpp<SUP>0</SUP> mutant during glucose-stimulated growth. Transposon insertion in acetoin biosynthesis gene cluster resulted in glucose-induced loss of viability of the Δ<I>relA</I>Δ<I>spoT</I> mutant, further suggesting the crucial role of acetoin production in balanced growth under glucose-rich environments. Additional deletion of the <I>aphA</I> gene, encoding a negative regulator for acetoin production, failed to rescue the (p)ppGpp<SUP>0</SUP> mutant from the defective glucose-mediated growth, suggesting that (p)ppGpp-mediated acetoin production occurs independent of the presence of AphA. Overall, our results reveal that (p)ppGpp, in addition to its well known role as a stringent response mediator, positively regulates acetoin production that contributes to the successful glucose metabolism and consequently the proliferation of <I>V. cholerae</I> cells under a glucose-rich environment, a condition that may mimic the human intestine.</P>

Cholera Toxin Production during Anaerobic Trimethylamine <i>N</i>-Oxide Respiration Is Mediated by Stringent Response in <i>Vibrio cholerae</i>

Oh, Young Taek,Park, Yongjin,Yoon, Mi Young,Bari, Wasimul,Go, Junhyeok,Min, Kyung Bae,Raskin, David M.,Lee, Kang-Mu,Yoon, Sang Sun American Society for Biochemistry and Molecular Bi 2014 The Journal of biological chemistry Vol.289 No.19

<P>As a facultative anaerobe, <I>Vibrio cholerae</I> can grow by anaerobic respiration. Production of cholera toxin (CT), a major virulence factor of <I>V. cholerae</I>, is highly promoted during anaerobic growth using trimethylamine <I>N</I>-oxide (TMAO) as an alternative electron acceptor. Here, we investigated the molecular mechanisms of TMAO-stimulated CT production and uncovered the crucial involvement of stringent response in this process. <I>V. cholerae</I> 7th pandemic strain N16961 produced a significantly elevated level of ppGpp, the bacterial stringent response alarmone, during anaerobic TMAO respiration. Bacterial viability was impaired, and DNA replication was also affected under the same growth condition, further suggesting that stringent response is induced. A Δ<I>relA</I> Δ<I>spoT</I> ppGpp overproducer strain produced an enhanced level of CT, whereas anaerobic growth via TMAO respiration was severely inhibited. In contrast, a ppGpp-null strain (Δ<I>relA</I> Δ<I>spoT</I> Δ<I>relV</I>) grew substantially better, but produced no CT, suggesting that CT production and bacterial growth are inversely regulated in response to ppGpp accumulation. Bacterial capability to produce CT was completely lost when the <I>dksA</I> gene, which encodes a protein that works cooperatively with ppGpp, was deleted. In the Δ<I>dksA</I> mutant, stringent response growth inhibition was alleviated, further supporting the inverse regulation of CT production and anaerobic growth. <I>In vivo</I> virulence of Δ<I>relA</I> Δ<I>spoT</I> Δ<I>relV</I> or Δ<I>dksA</I> mutants was significantly attenuated. The Δ<I>relA</I> Δ<I>spoT</I> mutant maintained virulence when infected with exogenous TMAO despite its defective growth. Together, our results reveal that stringent response is activated under TMAO-stimulated anaerobic growth, and it regulates CT production in a growth-dependent manner in <I>V. cholerae</I>.</P>

Challenges and Tribulations in the Commercialization of New Crops: Aromatic and Medicinal Plants

James E. Simon,Elton Jefthas,Petrus Longenhaven,Marianna Smith,Erica Renaud,Rodolfo Juliani,Mingfu Wang,Noah Zimba,Dan Acquaye,Chung-Heon Park,Ilya Raskin,Pierre Tannous 韓國藥用作物學會 2002 한국약용작물학회지 Vol.10 No.4

Challenges and Tribulations in the Commercialization of New Crops: Aromatic and Medicinal Plants

Simon, James E.,Jefthas, Elton,Longenhaven, Petrus,Smith, Marianna,Renaud, Erica,Juliani, Rodolfo,Wang, Mingfu,Zimba, Noah,Acquaye, Dan,Park, Chung-Heon,Raskin, Ilya,Tannous, Pierre The Korean Society of Medicinal Crop Science 2002 韓國藥用作物學會誌 Vol.10 No.4

Association between Painful Physical Symptoms and Clinical Outcomes in Korean Patients with Major Depressive Disorder: A Three-Month Observational Study

이민수,홍진표,윤세창,노재성,Kwang Hun Lee,Jung Ki Kim,Sang Yeol Lee,Pritibha Singh,Tamas Treuer,Victoria Reed,Joel Raskin,Sun Young Yum 대한신경정신의학회 2009 PSYCHIATRY INVESTIGATION Vol.6 No.4

Objective: This paper aims to examine the association between painful physical symptoms (PPS) and major depressive disorder (MDD) in a naturalistic clinical practice setting within a Korean population. Methods: Patients with acute MDD that joined a multicountry, observational, three-month study in six Asian countries and regions were classified as PPS+ (mean score ≥2) and PPS-(mean score <2) using the modified Somatic Symptom Inventory. In this analysis, we report the results from the Korean subset, where depression severity was assessed using the Clinical Global Impression of Severity (CGI-S) scale and 17-item Hamilton Depression Rating Scale (HAMD17). Pain severity was measured using a visual analogue scale (VAS), while the EuroQoL (EQ-5D) assessed patient well-being. Results: Of 198 patients, 45.96% (91/198) of patients were classified as PPS+, of which 78.02% (71/91) were women. PPS+ patients had significantly more severe depression at baseline {CGI-S score, mean [standard deviation (SD)], PPS+: 5.09 [0.79]; PPS-: 4.63 [0.76]; p<0.001; HAMD17 total score, mean [SD], PPS+: 24.34 [5.24]; PPS-: 20.76 [5.12]; p<0.001} and poorer quality of life [EQ-5D overall health state, mean (SD), PPS+: 39.37 (20.52); PPS-: 51.27 [20.78]; p<0.001] than PPS- patients. Both groups improved significantly (p<0.001) in depression and pain severity outcomes, as well as quality of life by endpoint, but no significant within-group baseline-to-endpoint change wase observed. Conclusion: The frequency of PPS was common in Korean patients with MDD, and was associated with more severe depression, poorer quality of life, and a trend towards poorer clinical outcome.

Targeted knockout of a chemokine-like gene increases anxiety and fear responses

Choi, Jung-Hwa,Jeong, Yun-Mi,Kim, Sujin,Lee, Boyoung,Ariyasiri, Krishan,Kim, Hyun-Taek,Jung, Seung-Hyun,Hwang, Kyu-Seok,Choi, Tae-Ik,Park, Chul O,Huh, Won-Ki,Carl, Matthias,Rosenfeld, Jill A.,Raskin, National Academy of Sciences 2018 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.115 No.5

<▼1><P><B>Significance</B></P><P>Emotion-related responses, such as fear and anxiety, are important behavioral phenomena in most animal species, as well as in humans. However, the underlying mechanisms of fear and anxiety in animals and in humans are still largely unknown, and anxiety disorders continue to represent a large unmet medical need in the human clinic. Animal models may speed up discovery of these mechanisms and may also lead to betterment of human health. Herein, we report the identification of a chemokine-like gene family, <I>samdori</I> (<I>sam</I>), and present functional characterization of <I>sam2</I>. We observed increased anxiety-related responses in both zebrafish and mouse knockout models. Taken together, these results support a crucial and evolutionarily conserved role of <I>sam2</I> in regulating anxiety-like behavior.</P></▼1><▼2><P>Emotional responses, such as fear and anxiety, are fundamentally important behavioral phenomena with strong fitness components in most animal species. Anxiety-related disorders continue to represent a major unmet medical need in our society, mostly because we still do not fully understand the mechanisms of these diseases. Animal models may speed up discovery of these mechanisms. The zebrafish is a highly promising model organism in this field. Here, we report the identification of a chemokine-like gene family, <I>samdori</I> (<I>sam</I>), and present functional characterization of one of its members, <I>sam2</I>. We show exclusive mRNA expression of s<I>am2</I> in the CNS, predominantly in the dorsal habenula, telencephalon, and hypothalamus. We found knockout (KO) zebrafish to exhibit altered anxiety-related responses in the tank, scototaxis and shoaling assays, and increased <I>crh</I> mRNA expression in their hypothalamus compared with wild-type fish. To investigate generalizability of our findings to mammals, we developed a <I>Sam2</I> KO mouse and compared it to wild-type littermates. Consistent with zebrafish findings, homozygous KO mice exhibited signs of elevated anxiety. We also found bath application of purified SAM2 protein to increase inhibitory postsynaptic transmission onto CRH neurons of the paraventricular nucleus. Finally, we identified a human homolog of <I>SAM2</I>, and were able to refine a candidate gene region encompassing <I>SAM2</I>, among 21 annotated genes, which is associated with intellectual disability and autism spectrum disorder in the 12q14.1 deletion syndrome. Taken together, these results suggest a crucial and evolutionarily conserved role of <I>sam2</I> in regulating mechanisms associated with anxiety.</P></▼2>