• 약학회지
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• 제49권5호
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• pp.386-391
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• 2005

The discovery of drugs for the treatment of mast cell-mediated allergic disease is a very important subject in human health. The Amomum xanthiodes (Zingiberaceae) has been used for centuries as a traditional medicine in Korea and is known to have an anti-inflammatory effect. However, its specific mechanism of action is still unknown. In this report, we investigated the effect of hot water extract from Amomum xanthiodes (EAX) on the mast cell-mediated allergic reaction and studied its possible mechanisms of action. EAX inhibited compound 48/80-induced systemic anaphylaxis and serum his­tamine release in mice. EAX decreased the passive cutaneous anaphylaxis reaction activated by anti-dinitrophenyl (DNP) IgE antibody. EAX dose-dependently reduced histamine release from rat peritoneal mast cells activated by compound 48/80 or anti-DNP IgE. EAX increased cAMP and decreased compound 48/80-induced intracellular $Ca^{2+}$ levels. Our findings provide evidence that EAX inhibits mast cell-derived allergic reactions, and also demonstrate the involvement of cAMP and intracellular $Ca^{2+}$ in these effects.

• BMB Reports
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• 제56권10호
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• pp.527-536
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• 2023

Serotonin receptors, also known as 5-HT receptors, belong to the G protein-coupled receptors (GPCRs) superfamily. They mediate the effects of serotonin, a neurotransmitter that plays a key role in a wide range of functions including mood regulation, cognition and appetite. The functions of serotonin are mediated by a family of 5-HT receptors including 12 GPCRs belonging to six major families: 5-HT₁, 5-HT₂, 5-HT₄, 5-HT₅, 5-HT₆ and 5-HT₇. Despite their distinct characteristics and functions, these receptors' subtypes share common structural features and signaling mechanisms. Understanding the structure, functions and pharmacology of the serotonin receptor family is essential for unraveling the complexities of serotonin signaling and developing targeted therapeutics for neuropsychiatric disorders. However, developing drugs that selectively target specific receptor subtypes is challenging due to the structural similarities in their orthosteric binding sites. This review focuses on the recent advancements in the structural studies of 5-HT receptors, highlighting the key structural features of each subtype and shedding light on their potential as targets for mental health and neurological disorders (such as depression, anxiety, schizophrenia, and migraine) drugs.

• 사상체질의학회지
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• 제24권4호
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• pp.84-91
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• 2012

Objectives : The purpose of this study is to investigate the inhibitory or inductive potentials of Yuldahanso-tang (YDT) and Chungsimyonja-tang (CST), herbal formulas for Taeeumin, on cytochrome P450 (CYP450) drug metabolizing enzyme. The mechanisms for the herbal formula-drug interaction has not been well reported in spite of the chance for co-administration with conventional drugs. Methods : To evaluate the interaction potential of YDT-drug or CST-drug, the fluorescence-based enzyme assays on CYP450 isozymes including CYP3A4, CYP2C19, CYP2D6 and CYP2E1 were established in vitro. The inhibitory effects of herbal formulas were characterized with $IC_{50}$ values. Results : YDT showed inhibitory effects on CYP2D6 and CYP2E1-mediated metabolism, while it exhibited week inhibition on CYP3A4 and CYP2C19 relatively. CST exerted relatively weak inhibitory effects on the four CYP450 isozymes compared to that of YDT. Conclusions : These results suggest that the herbal formula-drug interaction could be occur when YDT are co-administered with drugs mediated by CYP2D6 or CYP2E1.

• BMB Reports
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• 제55권9호
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• pp.417-428
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• 2022

Herbal medicine, a multi-component treatment, has been extensively practiced for treating various symptoms and diseases. However, its molecular mechanism of action on the human body is unknown, which impedes the development and application of herbal medicine. To address this, recent studies are increasingly adopting systems pharmacology, which interprets pharmacological effects of drugs from consequences of the interaction networks that drugs might have. Most conventional network-based approaches collect associations of herb-compound, compound-target, and target-disease from individual databases, respectively, and construct an integrated network of herb-compound-target-disease to study the complex mechanisms underlying herbal treatment. More recently, rapid advances in high-throughput omics technology have led numerous studies to exploring gene expression profiles induced by herbal treatments to elicit information on direct associations between herbs and genes at the genome-wide scale. In this review, we summarize key databases and computational methods utilized in systems pharmacology for studying herbal medicine. We also highlight recent studies that identify modes of action or novel indications of herbal medicine by harnessing drug-induced transcriptome data.

• Korean Circulation Journal
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• 제52권3호
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• pp.173-197
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• 2022

Treatment options for patients with heart failure (HF) with reduced ejection fraction (HFrEF) have expanded considerably over the past few decades. Whereas neurohormonal modulation remains central to the management of patients with HFrEF, other pathways have been targeted with drugs that have novel mechanisms of action. The angiotensin receptor-neprilysin inhibitors (ARNIs) which enhance levels of compensatory molecules such as the natriuretic peptides while simultaneously providing angiotensin receptor blockade have emerged as the preferred strategy for inhibiting the renin angiotensin system. Sodium glucose cotransporter 2 (SGLT2) inhibitors which were developed as hypoglycemic agents have been shown to improve outcomes in patients with HF regardless of their diabetic status. These agents along with beta blockers and mineralocorticoid receptor antagonists are the core medical therapies for patients with HFrEF. Additional approaches using ivabradine to slow heart rate in patients with sinus rhythm, the hydralazine/isosorbide dinitrate combination to unload the heart, digoxin to provide inotropic support and vericiguat to augment cyclic guanosine monophosphate production have been shown in well-designed trials to have beneficial effects in the HFrEF population and are used as adjuncts to the core therapies in selected patients. This review provides an overview of the medical management of patients with HFrEF with focus on the major developments that have taken place in the field. It offers prospective of how these drugs should be employed in clinical practice and also a glimpse into some strategies that may prove to be useful in the future.

• 생명과학회지
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• 제31권12호
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• pp.1120-1127
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• 2021

우울증은 높은 유병률과 자살률 증가로 인해 사회적 기능에 부정적인 영향을 미치며, 경제적 부담 또한 높은 질환이다. 우울증은 신경염증, 시냅스 기능장애, 인지 결손과 같은 뇌에서 다양한 현상과 관련이 있다. 임상에서 사용되는 항우울제들은 치료효과가 낮아 빠른 효능을 보이는 항우울제 개발이 시급하다. 현재까지 우울증과 관련된 다양한 유전자, 단백질, 그리고 신호전달계에 대한 많은 연구가 수행되었지만, 우울증의 발생기전은 명확하게 밝혀지지 않았다. Sirtuin 1은 nicotinamide-adenine dinucleotid- (NAD⁺-) dependent histone deacetylases로써 세포 분화, 세포 사멸, 발생, 자가소화작용, 암 대사에 관여하는 것으로 알려져 있다. 최근의 유전연구들은 Sirtuin 1이 우울증의 잠재적 타겟 유전자라고 제안하고 있다. 또한 전임상 연구에서는 Sirtuin 1의 신호전달기전이 우울행동에 영향을 미친다고 보고 하였다. 본 종설에서는 우울증과 Sirtuin 1에 대한 최신 지식을 제시하였다. 소교세포의 활성, 일주기 생체 리듬, 신경세포 생성, 및 인지기능의 조절에 관여하는 Sirtuin 1이 우울증에 미치는 다양한 영향을 설명하였다. 아울러 Sirtuin 1이 우울증 핵심 기전중의 하나인 신경가소성의 손상에 미치는 영향과 그 기전에 대해서 논의하였다.

• 대한약침학회지
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• 제18권3호
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• pp.11-18
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• 2015

Objectives: Systems biology is a novel subject in the field of life science that aims at a systems' level understanding of biological systems. Because of the significant progress in high-throughput technologies and molecular biology, systems biology occupies an important place in research during the post-genome era. Methods: The characteristics of systems biology and its applicability to traditional medicine research have been discussed from three points of view: data and databases, network analysis and inference, and modeling and systems prediction. Results: The existing databases are mostly associated with medicinal herbs and their activities, but new databases reflecting clinical situations and platforms to extract, visualize and analyze data easily need to be constructed. Network pharmacology is a key element of systems biology, so addressing the multi-component, multi-target aspect of pharmacology is important. Studies of network pharmacology highlight the drug target network and network target. Mathematical modeling and simulation are just in their infancy, but mathematical modeling of dynamic biological processes is a central aspect of systems biology. Computational simulations allow structured systems and their functional properties to be understood and the effects of herbal medicines in clinical situations to be predicted. Conclusion: Systems biology based on a holistic approach is a pivotal research methodology for understanding the mechanisms of traditional medicine. If systems biology is to be incorporated into traditional medicine, computational technologies and holistic insights need to be integrated.

• BMB Reports
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• 제49권3호
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• pp.139-148
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• 2016

In the past decade, the incidence of type 2 diabetes (T2D) has rapidly increased, along with the associated cardiovascular complications. Therefore, understanding the pathophysiology underlying T2D, the associated complications and the impact of therapeutics on the T2D development has critical importance for current and future therapeutics. The prevailing feature of T2D is hyperglycemia due to excessive hepatic glucose production, insulin resistance, and insufficient secretion of insulin by the pancreas. These contribute to increased fatty acid influx into the liver and muscle causing accumulation of lipid metabolites. These lipid metabolites cause dyslipidemia and non-alcoholic fatty liver disease, which ultimately contributes to the increased cardiovascular risk in T2D. Therefore, understanding the mechanisms of hepatic insulin resistance and the specific role of liver lipids is critical in selecting and designing the most effective therapeutics for T2D and the associated co-morbidities, including dyslipidemia and cardiovascular disease. Herein, we review the effects and molecular mechanisms of conventional anti-hyperglycemic and lipid-lowering drugs on glucose and lipid metabolism.

• 대한한방내과학회지
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• 제28권2호
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• pp.377-384
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• 2007

Objective : Immune potentiation including activation of T cells, B cells, macrophages, and dendritic cells is known to play a key role in prevention and treatment of patients with cancer. In this study, we investigated the effects of Acanthopanax sessiliflorus (AR) on the immune system, especially on thymocytes, splenocytes, and macrophages. Methods : We investigated the effects of AR on proliferation of splenocytes in normal mice, and the effects on proliferation of splenocytes and thymocytes in tumor-bearing mice. In addition, the effect of AR on NO production using macrophages was investigated. Results : Treatment with AR accelerated proliferation of splenocytes in vitro. AR also accelerated thymocyte proliferation, but did not affect splenocytes proliferation in normal mice. In contrast, AR accelerated proliferation of splenocytes and thymocytes significantly in tumor bearing mice. In addition, NO production level from macrophages was elevated by treatment with AR. Conclusion : These results demonstrate that AR has anti-cancer activities and related mechanisms are involved in immune potentiation such as acceleration of immune cell proliferation and elevation of NO production level in macrophages. In addition, we also demonstrate the possibilities of AR as complementary and alternative medicine to standard anti-cancer drugs.

• The Korean Journal of Physiology and Pharmacology
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• 제26권3호
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• pp.157-164
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• 2022

Disulfiram (DSF) is an aldehyde dehydrogenase inhibitor. DSF has potent anti-cancer activity for solid and hematological malignancies. Although the effects on cancer cells have been proven, there have been few studies on DSF toxicity in bone marrow cells (BMs). DSF reduces the metabolic activity and the mitochondrial membrane potential of BMs. In subset analyses, we confirmed that DSF does not affect the proportion of BMs. In addition, DSF significantly impaired the metabolic activity and differentiation of BMs treated with granulocyte macrophage-colony stimulating factor, an essential growth and differentiation factor for BMs. To measure DSF toxicity in BMs in vivo, mice were injected with 50 mg/kg, a dose used for anti-cancer effects. DSF did not significantly induce BM toxicity in mice and may be tolerated by antioxidant defense mechanisms. This is the first study on the effects of DSF on BMs in vitro and in vivo. DSF has been widely studied as an anti-cancer drug candidate, and many anti-cancer drugs lead to myelosuppression. In this regard, this study can provide useful information to basic science and clinical researchers.