• Journal of Ginseng Research
• /
• 제45권3호
• /
• pp.420-432
• /
• 2021

Background: Many ginsenosides have been shown to be efficacious for major depressive disorder (MDD), which is a highly recurrent disorder, through several preclinical studies. We aimed to review the literature assessing the antidepressant effects of ginsenosides on MDD animal models, to establish systematic scientific evidence in a rigorous manner. Methods: We performed a systematic review on the antidepressant effects of ginsenoside evaluated in in vivo studies. We searched for preclinical trials from inception to July 2019 in electronic databases such as Pubmed and Embase. In vivo studies examining the effect of a single ginsenoside on animal models of primary depression were included. Items of each study were evaluated by two independent reviewers. A meta-analysis was conducted to assess behavioral changes induced by ginsenoside Rg1, which was the most studied ginsenoside. Data were pooled using the random-effects models. Results: A total of 517 studies were identified, and 23 studies were included in the final analysis. They reported on many ginsenosides with different antidepressant effects and biological mechanisms of action. Of the 12 included articles assessing ginsenoside Rg1, pooled results of forced swimming test from 9 articles (mean difference (MD): 20.50, 95% CI: 16.13-24.87), and sucrose preference test from 11 articles (MD: 28.29, 95% CI: 22.90-33.69) showed significant differences compared with vehicle treatment. The risk of bias of each study was moderate, but there was significant heterogeneity across studies. Conclusion: These estimates suggest that ginsenosides, including ginsenoside Rg1, reduces symptoms of depression, modulates underlying mechanisms, and can be a promising antidepressant.

• Journal of Korean Neurosurgical Society
• /
• 제61권3호
• /
• pp.343-351
• /
• 2018

Diffuse intrinsic pontine glioma (DIPG) is a deadly paediatric brain cancer. Transient response to radiation, ineffective chemotherapeutic agents and aggressive biology result in rapid progression of symptoms and a dismal prognosis. Increased availability of tumour tissue has enabled the identification of histone gene aberrations, genetic driver mutations and methylation changes, which have resulted in molecular and phenotypic subgrouping. However, many of the underlying mechanisms of DIPG oncogenesis remain unexplained. It is hoped that more representative in vitro and preclinical models-using both xenografted material and genetically engineered mice-will enable the development of novel chemotherapeutic agents and strategies for targeted drug delivery. This review provides a clinical overview of DIPG, the barriers to progress in developing effective treatment, updates on drug development and preclinical models, and an introduction to new technologies aimed at enhancing drug delivery.

• Journal of mucopolysaccharidosis and rare diseases
• /
• 제5권1호
• /
• pp.22-28
• /
• 2021

Mucopolysaccharidosis type III (MPS III) or Sanfilippo disease is an orphan-inherited lysosomal storage disease. It is one of the most common MPS subtypes. The classical presentation is an infantile-onset neurodegenerative disease characterized by intellectual regression, behavioral and sleep disturbances, loss of ambulation, and early death. Unlike other MPS, no disease-modifying therapy has been approved. Here, we review the curative therapy developed for MPS III, from historically ineffective hematopoietic stem cell transplantation and substrate reduction therapy to the promising enzyme replacement therapy or adeno-associated/lentiviral vector-mediated gene therapy. Preclinical studies are presented with recent translational first-in-man trials. We also present experimental research with preclinical mRNA and gene-editing strategies. Lessons from animal studies and clinical trials have highlighted the importance of early therapy before extensive neuronal loss. Disease-modifying therapy for MPS III will likely mandate the development of new early diagnosis strategies.

• 생명과학회지
• /
• 제32권8호
• /
• pp.611-621
• /
• 2022

DMSO (dimethyl sulfoxide)는 친유성 화합물을 용해하는 성질과 뇌혈관장벽(Blood-brain barrier)을 투과하는 화학적 특성으로 인해 근위축성 측삭경화증(amyotrophic lateral sclerosis) 등의 퇴행성 뇌신경질환을 타겟으로 하는 전임상 연구에서 용매로 널리 활용되고 있다. 그러나 DMSO를 활용한 연구 결과에 대하여 본 물질에 대한 생화학적 효과는 간과되고 있다. 본 연구에서는 근위축성 측삭경화증의 질환동물 모델인 SOD1-G93A형질 전환 마우스에 5% DMSO를 장기간 경구 투여하여 질병 표현형에 미치는 영향을 생존기간을 포함하여 신경학적, 기능학적, 조직학적으로 분석하였다. DMSO를 투여한 SOD1-G93A 동물군에서 DMSO 비투여군 보다 생존 기간과, 로타로드와 악력 측정으로 평가한 근육 기능이 유의미하게 증가했고, neurological score 가 감소했다. 반면, DMSO 투여군에서 DMSO 비투여군 대비하여 척수 운동 신경 세포와 신경근접합부가 보존되지 않았다. DMSO 투여는 SOD1-G93A형질 전환 마우스의 운동 신경 세포의 조직학적 영향을 미치지 않았지만, 신경 증상 완화와 생존 기간 등 개선된 마우스의 quality of life을 확인하였다. 본 연구 결과, DMSO를 이용한 퇴행성 뇌 질환 전임상 연구 및 후보 약물 효능 평가 시 DMSO의 생화학적 특성에 대한 종합적인 고려가 필요한 것으로 보인다.

• Toxicological Research
• /
• 제26권1호
• /
• pp.1-8
• /
• 2010

The process of new drug development consists of several stages; after identifying potential candidate compounds, preclinical studies using animal models link the laboratory and human clinical trials. Among many steps in preclinical studies, toxicology and safety assessments contribute to identify potential adverse events and provide rationale for setting the initial doses in clinical trials. Gene modulation is one of the important tools of modern biology, and is commonly employed to examine the function of genes of interest. Advances in new drug development have been achieved by exploding information on target selection and validation using genetically modified animal models as well as those of cells. In this review, a recent trend of genetically modified methods is discussed with reference to safety assessments, and the exemplary applications of gene-modulating tools to the tests in new drug development were summarized.

• 한국식품과학회지
• /
• 제36권5호
• /
• pp.818-822
• /
• 2004

본 실험은 랫드나 마우스에서 2가지 실험적 위궤양 유발 모델과 알코올 반복 투여를 이용하여 한국 전통약주의 위 보호효과를 확인하였다. 24시간 절식시킨 랫드에 전통약주를 250-1,000mg/kg를 경구 투여하고 30분 후에 150mM HCl-60% EtOH를 투여하거나 전통약주 62.5-1,000mg/kg를 투여하고 30분 후에 무수 에탄올을 경구 투여하였을 때, 대조군에 대해 유의성 있는 위병변 억제효과를 나타내었다. 또한 마우스에서 30% 알코올을 12시간 간격으로 7일간 반복투여 하였을 때, 대조군에 대해 육안으로 관찰 가능한 위병벽 억제 효과를 확인하였다.

• 융합정보논문지
• /
• 제10권2호
• /
• pp.184-192
• /
• 2020

본 연구는 척추측만증 수술에 대한 객관적이고 정량적인 효과 평가 수단으로서 스마트 깔창을 이용한 보행분석 방법(시계열 분석 포함)을 제시한다. 실험 참가자는 척추측만증 환자이며 스마트 깔창을 착용하고 3분 보행검사를 4번(수술전, 수술 후 8일, 16일, 204일), 6분 보행검사를 1번(수술 후 204일) 받았다. 깔창에는 8개의 압력센서, 가속도 및 각속도 센서가 있고, 각각의 측정값을 저장하여 환자의 수술 전후 보행특성(운동역학 및 시공간 변수)을 비교하였다. 분석결과 수술 후 환자의 모든 보행변수가 개선된 것을 알 수 있었고, 6개월 후 추적검사에서 환자의 보행이 더욱 안정된 것을 확인할 수 있었다. 하지만 환자가 오래 걸으면 한쪽 다리의 swing 시간이 다른 쪽에 비해 미세하게 짧은 현상이 다시 나타났는데, 이는 검사를 수행하는 의사의 육안으로는 발견할 수 없는 preclinical한 문제였다. 우리는 이러한 분석 방법을 통해 환자의 개선 정도를 정량적이고 객관적으로 평가할 수 있었고, preclinical한 문제도 찾을 수 있었다. 향후 이러한 분석 방법은 특정 질병의 보행 패턴을 정의하고 감별하여 적절한 치료방법을 결정하는 연구로 이어질 것이다.

• Journal of mucopolysaccharidosis and rare diseases
• /
• 제5권1호
• /
• pp.39-41
• /
• 2021

Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder of hyperphagia leading to severe obesity, intellectual deficits, compulsivity, and other behavioral problems. PWS is caused by the inactivation of contiguous genes on chromosome 15q11-q13, which complicates the development of targeted, effective therapeutics. Various preclinical studies have been conducted by developing mouse models that exhibit phenotypes similar to PWS. Oxytocin deficiency in PWS is associated with hyperphagia with impaired satiety and, food-seeking and behavior disorders. Here, we summarize the oxytocin study of ingestion behavior tested in the PWS mouse model and published data from clinical trials that have evaluated treatment effectiveness on ingestion behavior and social dysfunction in patients with PWS.

• Journal of Korean Neurosurgical Society
• /
• 제62권1호
• /
• pp.10-26
• /
• 2019

Magnetic resonance-guided focused ultrasound (MRgFUS) is an emerging new technology with considerable potential to treat various neurological diseases. With refinement of ultrasound transducer technology and integration with magnetic resonance imaging guidance, transcranial sonication of precise cerebral targets has become a therapeutic option. Intensity is a key determinant of ultrasound effects. High-intensity focused ultrasound can produce targeted lesions via thermal ablation of tissue. MRgFUS-mediated stereotactic ablation is non-invasive, incision-free, and confers immediate therapeutic effects. Since the US Food and Drug Administration approval of MRgFUS in 2016 for unilateral thalamotomy in medication-refractory essential tremor, studies on novel indications such as Parkinson's disease, psychiatric disease, and brain tumors are underway. MRgFUS is also used in the context of blood-brain barrier (BBB) opening at low intensities, in combination with intravenously-administered microbubbles. Preclinical studies show that MRgFUS-mediated BBB opening safely enhances the delivery of targeted chemotherapeutic agents to the brain and improves tumor control as well as survival. In addition, BBB opening has been shown to activate the innate immune system in animal models of Alzheimer's disease. Amyloid plaque clearance and promotion of neurogenesis in these studies suggest that MRgFUS-mediated BBB opening may be a new paradigm for neurodegenerative disease treatment in the future. Here, we review the current status of preclinical and clinical trials of MRgFUS-mediated thermal ablation and BBB opening, described their mechanisms of action, and discuss future prospects.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
• /
• pp.109.2-110
• /
• 2002