1. Amygdalin의 중추성 및 말초성 진통작용 규명: 살구씨에서 추출한 amygdalin의 중추성 통증과 말초성 통증에 대한 효과와 기전을 연구하여, 본 연구진이 분리한 amygdalin이 새로운 진통소염제로서의 기능성 식품 또는 천연물 신약으로 개발되는 것을 목표로 함. 본 연구진의 amygdalin과 Sigma Chemical Co.의 amygdalin의 기능적인 차이를 규명하여 본 제품이 새로운 진통제로 개발되어 고부가가치의 연구업적이 되도록 함. GLP 기관에서 amygdalin의 독성검사를 시행하였음. 2.
1. Amygdalin의 중추성 및 말초성 진통작용 규명: 살구씨에서 추출한 amygdalin의 중추성 통증과 말초성 통증에 대한 효과와 기전을 연구하여, 본 연구진이 분리한 amygdalin이 새로운 진통소염제로서의 기능성 식품 또는 천연물 신약으로 개발되는 것을 목표로 함. 본 연구진의 amygdalin과 Sigma Chemical Co.의 amygdalin의 기능적인 차이를 규명하여 본 제품이 새로운 진통제로 개발되어 고부가가치의 연구업적이 되도록 함. GLP 기관에서 amygdalin의 독성검사를 시행하였음. 2. Amigdalin의 급성 및 만성 통증에 대 한 효과 규명 : 급, 만성 통증 동물 모델을 이용하여 amygdalin 의 진통 소염 효능을 검증하고 분자 수준의 작용기전을 규명하였음. 2개의 급성 통증모델, 1개의 만성통증 모델, 그리고 1개의 신경병리성 통증 모델 제작 완료하여 amygdalin의 진통, 소염 효능의 실험적 검증하였으며 신경병리성 통증 모델을 제외한 3종의 급, 만성 통증 모델에서 진통, 소염 효능 확인 하였음. 3. Amygdalin의 추출 및 제품화에 대한 연구: Amygdalin의 물 추출물을 다량 확보하여 각 세부과제에서 사용 할 수 있도록 공급하였음. Amygdalin의 대량 생산법 개발하였고, Amygdalin의 순도를 99% 이상이 되도록 재결정법을 개발하였음.
Abstract▼
Amygdalin (D-mandelonitrile B-gentiobioside) is a cynogenic compound found in sweet and bitter almonds, Persicae semen and Armeniacae semen. Amygdalin had been used for the treatment of cancers and for the relief of the pain. We made an aqueous extraction of amygdalin from Armeniacae semen. Pain is
Amygdalin (D-mandelonitrile B-gentiobioside) is a cynogenic compound found in sweet and bitter almonds, Persicae semen and Armeniacae semen. Amygdalin had been used for the treatment of cancers and for the relief of the pain. We made an aqueous extraction of amygdalin from Armeniacae semen. Pain is the first response to injury or infection, and injury and infection activate the immune system to produce inflammatory responses. Lipopolysaccharide (LPS) initiates a number of major cellular responses thatplay vital roles in the pathogenesis of the inflammatory responses. LPS stimulates the production of inflammatory mediators such as nitric oxie (NO), tumor necrosis factor-a (TNF-α), interleukins, prostaglandins (PGE₂), and leukotrienes. Moreover, LPS enhances the pain response to various somatic stimuli. PGE₂ is a key inflammatory mediator and an increased level of PGE₂ mediates the cardinal features of inflammation such as pain, edema, and fever$^{15,16}$. PGE₂is converted from arachidonic acid by cyclooxygenase (COX). There are two isoforms of COX: COX-1 and COX-2. COX-1 is the constitutively expressed form in the normal physiologic functions, while COX-2 is expressed only in response to inflammatory signals such as cytokines and bacterial endotoxin, LPS. COX-2 produces large amount of PGE₂ and this PGE₂ induces inflammation. NO is synthesized from L-arginine by nitric oxide synthase (NOS), and NO plays an important role in the regulation of many physiological processes. There are three distinct isoforms of NOS: neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS). Of these, iNOS is an important enzyme that is involved in the regulation of inflammation. It has been reported that LPS upregulates iNOS expression in macrophages and microglial cells. In this study, we investigated the effects of amygdalin on the several types of pain and inflammation. For this study, cell study, patch clamp technique, in vivo studies using acute and chronic pain animal models were performed. In cell study, amygdalin suppressed the PGE₂ synthesis and the NO production by inhibiting the LPS-stimulated mRNA expressions of COX-2 and iNOS in the BV2 cells. In patch clamp study, amygdalin alleviated LPS-induced activation on glycine induced-ion current and LPS-induced inhibition on glutamate induced-ion current in the periaqueductal gray (PAG) neurons. The present results reveal that amygdalin activates descending pain control system in the PAG neurons. In animal studies, amygdalin exerted analgesic and anti-inflammatory effects on acetic acid-induced abdominal pain, formalin-induced pain, carrageenan-induced arthritis, colitis-induced chronic pain in rats and it also facilitated functional recovery after sciatic crushed nerve injury in rats. These results show that amygdalin exerts anti -inflammatory and analgesic effects.
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