• Journal of Ginseng Research
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• v.45 no.4
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• pp.465-472
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• 2021

Background: Ginseng can help regulate brain excitability, promote learning and memory, and resist cerebral ischemia in the central nervous system. Ginsenosides are the major effective compounds of Ginseng, but their protein targets in the brain have not been determined. Methods: We screened proteins that interact with the main components of ginseng (ginsenosides) by affinity chromatography and identified the 14-3-3 ζ protein as a potential target of ginsenosides in brain tissues. Results: Biolayer interferometry (BLI) analysis showed that 20(S)-protopanaxadiol (PPD), a ginseng saponin metabolite, exhibited the highest direct interaction to the 14-3-3 ζ protein. Subsequently, BLI kinetics analysis and isothermal titration calorimetry (ITC) assay showed that PPD specifically bound to the 14-3-3 ζ protein. The cocrystal structure of the 14-3-3 ζ protein-PPD complex showed that the main interactions occurred between the residues R56, R127, and Y128 of the 14-3-3 ζ protein and a portion of PPD. Moreover, mutating any of the above residues resulted in a significant decrease of affinity between PPD and the 14-3-3 ζ protein. Conclusion: Our results indicate the 14-3-3 ζ protein is the target of PPD, a ginsenoside metabolite. Crystallographic and mutagenesis studies suggest a direct interaction between PPD and the 14-3-3 ζ protein. This finding can help in the development of small-molecular compounds that bind to the 14-3-3 ζ protein on the basis of the structure of dammarane-type triterpenoid.

• Journal of Ginseng Research
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• v.46 no.6
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• pp.750-758
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• 2022

Background: Mild cognitive impairment (MCI) is a transitional condition between normality and dementia. Ginseng is known to have effects on attenuating cognitive deficits in neurogenerative diseases. Ginsenosides are the main bioactive component of ginseng, and their protein targets have not been fully understood. Furthermore, no thorough analysis is reported in ginsenoside-related protein targets in MCI. Methods: The candidate protein targets of ginsenosides in brain tissues were identified by drug affinity responsive target stability (DARTS) coupled with label-free liquid chromatography-mass spectrometry (LC-MS) analysis. Network pharmacology approach was used to collect the therapeutic targets for MCI. Based on the above-mentioned overlapping targets, we built up a proteineprotein interaction (PPI) network in STRING database and conducted gene ontology (GO) enrichment analysis. Finally, we assessed the effects of ginseng total saponins (GTS) and different ginsenosides on mitochondrial function by measuring the activity of the mitochondrial respiratory chain complex and performing molecular docking. Results: We screened 2526 MCI-related protein targets by databases and 349 ginsenoside-related protein targets by DARTS. On the basis of these 81 overlapping genes, enrichment analysis showed the mitochondria played an important role in GTS-mediated MCI pharmacological process. Mitochondrial function analysis showed GTS, protopanaxatriol (PPT), and Rd increased the activities of complex I in a dose-dependent manner. Molecular docking also predicted the docking pockets between PPT or Rd and mitochondrial respiratory chain complex I. Conclusion: This study indicated that ginsenosides might alleviate MCI by targeting respiratory chain complex I and regulating mitochondrial function, supporting ginseng's therapeutic application in cognitive deficits.

• Journal of Ginseng Research
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• v.46 no.5
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• pp.666-674
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• 2022

Background: Ginsenosides and their metabolites have antidepressant-like effects, but the underlying mechanisms remain unclear. We previously identified 14-3-3 ζ as one of the target proteins of 20 (S)-protopanaxadiol (PPD), a fully deglycosylated ginsenoside metabolite. Methods: Corticosterone (CORT) was administered repeatedly to induce the depression model, and PPD was given concurrently. The tail suspension test (TST) and the forced swimming test (FST) were used for behavioral evaluation. All mice were sacrificed. Golgi-cox staining, GSK 3β activity assay, and Western blot analysis were performed. In vitro, the kinetic binding analysis with the Biolayer Interferometry (BLI) was used to determine the molecular interactions. Results: TST and FST both revealed that PPD reversed CORT-induced behavioral deficits. PPD also ameliorated the CORT-induced expression alterations of hippocampal Ser9 phosphorylated glycogen synthase kinase 3β (p-Ser9 GSK 3β), Ser133 phosphorylated cAMP response element-binding protein (p-Ser133 CREB), and brain-derived neurotrophic factor (BDNF). Moreover, PPD attenuated the CORT-induced increase in GSK 3β activity and decrease in dendritic spine density in the hippocampus. In vitro, 14-3-3 ζ protein specifically bound to p-Ser9 GSK 3β polypeptide. PPD promoted the binding and subsequently decreased GSK 3β activity. Conclusion: These findings demonstrated the antidepressant-like effects of PPD on the CORT-induced mouse depression model and indicated a possible target-based mechanism. The combination of PPD with the 14-3-3 ζ protein may promote the binding of 14-3-3 ζ to p-GSK 3β (Ser9) and enhance the inhibition of Ser9 phosphorylation on GSK 3β kinase activity, thereby activating the plasticity-related CREBeBDNF signaling pathway.

• The Journal of Korea Institute of Information, Electronics, and Communication Technology
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• v.9 no.1
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• pp.58-66
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• 2016

The purpose of this study is to consider of fasting cure as natural healing and holistic medicine. As a study method, this author conducted a literature review to figure out the history and meaning of fasting found in religious thoughts and studied the cases applying fasting to either mental or physical healing analytically. According to the study results, first, in terms of religious thoughts, fasting plays significant roles mentally, and the act of fasting influences mankind's mind considerably. Second, fasting as a means of humans' mental and physical healing has been playing significant roles as the medical act of natural healing that has been transmitted from a long time ago. As a result, this author has found that fasting cure has great value as holistic medicine based on natural healing. Based on the implications of this study, this researcher expects that this study will be used as fundamental material to provide the directions and grounds of fasting cure as efficient healing in the aspects of holistic medicine exerting effects on chronic disease resulted from habits or diseases caused by stress, a factor that results in many different kinds of diseases in this age.

• Journal of Ginseng Research
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• v.47 no.5
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• pp.662-671
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• 2023

Background: 20(S)-protopanaxadiol (PPD), a ginsenoside metabolite, has prominent benefits for the central nervous system, especially in improving learning and memory. However, its transcriptional targets in brain tissue remain unknown. Methods: In this study, we first used mass spectrometry-based drug affinity responsive target stability (DARTS) to identify the potential proteins of ginsenosides and intersected them with the transcription factor library. Second, the transcription factor PURA was confirmed as a target of PPD by biolayer interferometry (BLI) and molecular docking. Next, the effect of PPD on the transcriptional levels of target genes of PURA in brain tissues was determined by qRT-PCR. Finally, bioinformatics analysis was used to analyze the potential biological features of these target proteins. Results: The results showed three overlapping transcription factors between the proteomics of DARTS and transcription factor library. BLI analysis further showed that PPD had a higher direct interaction with PURA than parent ginsenosides. Subsequently, BLI kinetic analysis, molecular docking, and mutations in key amino acids of PURA indicated that PPD specifically bound to PURA. The results of qRT-PCR showed that PPD could increase the transcription levels of PURA target genes in brain. Finally, bioinformatics analysis showed that these target proteins were involved in learning and memory function. Conclusion: The above-mentioned findings indicate that PURA is a transcription target of PPD in brain, and PPD upregulate the transcription levels of target genes related to cognitive dysfunction by binding PURA, which could provide a chemical and biological basis for the study of treating cognitive impairment by targeting PURA.

• Advances in Traditional Medicine
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• v.4 no.3
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• pp.137-156
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• 2004

Altruistic virtuous caring, possibly originated from religion and/or spirituality, is indispensable for holistic health through channeling vital energy with diet, exercise and meditation. This is a participant-observed medical anthropological research of a first generation Korean elderly immigrant health professional woman living in a four generational family. She had hypertension and was concerned about possible attack of stroke. Multi-religious, spiritual, and cosmological vital energy based on holistic Nature-oriented health beliefs and practices influenced by psychosocial, cultural and economic background, education, self- discipline and self-cultivation of individual, and group or family may create health. Self-care beliefs based on confidence in self-control of one's life style for oneself and others influence individual and group health practice. The holistic alternative health beliefs and practices were proved to be efficacious and beneficial by her self-evaluation, evaluation of significant others, biomedical professionals, and laboratory tests. That may have potential application for global health.

• Journal of Physiology & Pathology in Korean Medicine
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• v.38 no.5
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• pp.196-204
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• 2024

Over the past several decades there have been many attempts to integrate the fields of Conventional and Holistic medicine. However, to date, successful integration has yet to be achieved. For the purpose of providing greater understanding and effective methods for the diagnostic and treatment of functional body disorders this review presents a plausible method for successful consolidation of the reductionism and holism concepts present at the core of modern and traditional medicine. Reconstruction of modern physiological knowledge and understanding of changes in cardiovascular function was used to provide explanations for symptoms associated with the concept of Byeon-Jeung in Korean Medicine. The symptoms correlated with the Byeon-Jeung for Liver Qi Stagnation, Spleen Qi Deficiency, and Stomach Yin Deficiency were shown to be linked to decreases in blood flow and the corresponding functional disorders associated with such. These results demonstrate how modern physiological understanding of the body can serve as an appropriate stepping stone to assist in the integration of Conventional and Holisitic medicine.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.5
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• pp.1242-1253
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• 2004

Leukemia is a blood disease that occurs in the abnormal process of leukocyte maturation. Its main medical treatment is chemical therapy and bone medical transplant. But its treatments give rise to ill effects and sequela. At present, the cause of leukemia is not fully understood. But oriental concept of curing leukemia is the holistic thinking that emphasizes the unity, wholeness, and the relationship between the human organs, including western medical concept of blood cause. So it is estimated that holistic medical treatment in oriental medicine could present new medical way of curing leukemia. I read over the diary on struggles against leukemia, survey on the leukemia patients, and, medical charts in the oriental clinics that treated in the holistic way, and I interviewed the leukemia patients. With these materials, I classified the early main attacking symptoms according to the chief complaints of one hundred leukemia patients. With these results collected, I present new alternative treatment by oriental medical diagnosis. The chief early complaints that leukemia patients give are fatigue, enervation, cold, contusion, fever, high fever, sweating at sleep, myalgia, arthralgia, and dizziness, in order of main symptoms. Fatigue occurs mainly by spleen and stomach weakness and marrow shortage. So it is estimated that It is important to treat the spleen that is responsible for supplementing the marrow. Because the leukemia patients have anemia and hemorrhage, to treat the spleen is important for hematopoiesis and controlling blood. In case of cold, it penetrates into the body when the body is weak. So its treatment is to increase body's health. But the cause of fever is difficult to classify into outer cause and inner cause. But in case of children under 14 years old, fever is the main sypmptom. I think this is because children have the body with pure vital energy. Hemorrhage is thought to be the result of yin-lack and heat-miasma of spleen and stomach channels. Contusion occurs from the qi-weakness and the not-controlling-blood. Sweating at sleep is from the yin-weakness. It is found with all weak symptoms. Dizziness is from the yin-blood impairment. Weight-loss is from the marrow shortage. Myalgia and arthralgia is mainly from inner weakness, not outer maisma. Most leukemia patients have the idea that holistic treatment of leukemia could be of assistance and give help to the low immunity. So it is expected that holistic medical treatment could contribute to knowing the cause and treatment of leukemia, and give people reliability on oriental medical treatment, through the profound diagnosis of leukemia.

• Journal of Physiology & Pathology in Korean Medicine
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• v.30 no.6
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• pp.367-369
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• 2016

The recent introduction of the systems biology or systems medicine opens a new horizon in the field of traditional oriental medicine research. Until now many recent researches of traditional medicine have been conducted based upon reductionist approach, but traditional medicine should be treated by a holistic approach. In this short review, I outlined usefulness of systems approach in medicine and proposed a potential application area of traditional medicine research.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.1
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• pp.245-256
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• 2006

This research sought to survey oriental medicine diagnosis methods currently practiced, analyze their advantages and disadvantages, and work out clinical establish direction for oriental medicine diagnosis methods. Oriental medicine diagnosis methods currently practiced in the related circles are categorized into traditional Korean diagnosis methods and holistic auxiliary diagnosis methods. The traditional Korean diagnosis method focuses on treating diseases of traditional Korean health management methods which are based on the bodily self-viability capabilities according to the Orient's viewpoint of health. Under the diagnosis method, based on the cognition of maximizing the state of the bodily self-viability capabilities together with the characteristics of diseases, symptoms, pulse, first face-to-face patient observation, physical constitution, and life principle are managed according to form, color, pulse and symptom which divide the bodily viability capacities into inherent and acquired elements amid both elements interacting.