• Journal of Ginseng Research
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• 제44권6호
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• pp.770-774
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• 2020

Background: Fermentation has been shown to improve the biological properties of plants and herbs. Specifically, fermentation causes decomposition and/or biotransformation of active metabolites into high-value products. Polyacetylenes are a class of polyketides with a pleiotropic profile of bioactivity. Methods: Column chromatography was used to isolate compounds, and extensive NMR experiments were used to determine their structures. The transformation of polyacetylene in red ginseng (RG) and the production of cazaldehyde B induced by the extract of RG were identified by TLC and HPLC analyses. Results: A new metabolite was isolated from RG fermented by Chaetomium globosum, and this new metabolite can be obtained by the biotransformation of polyacetylene in RG. Panaxytriol was found to exhibit the highest antifungal activity against C. globosum compared with other major ingredients in RG. The fungus C. globosum cultured in RG extract can metabolize panaxytriol to Metabolite A to survive, with no antifungal activity against itself. Metabolites A and B showed obvious inhibition against NO production, with ratios of 42.75 ± 1.60 and 63.95 ± 1.45% at 50 µM, respectively. A higher inhibitory rate on NO production was observed for Metabolite B than for a positive drug. Conclusion: Metabolite A is a rare example of natural polyacetylene biotransformation by microbial fermentation. This biotransformation only occurred in fermented RG. The extract of RG also stimulated the production of a new natural product, cazaldehyde B, from C. globosum. The lactone in Metabolite A can decrease the cytotoxicity, which was deemed to be the intrinsic activity of polyacetylene in ginseng.

• Journal of Pharmaceutical Investigation
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• 제38권4호
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• pp.241-247
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• 2008

Paclitaxel is a taxane diterpene amide, which was first extracted from the stem bark of the western yew, Taxus brevifolia. This natural product has proven to be useful in the treatment of a variety of human neoplastic disorders, including ovarian cancer, breast and lung cancer. Paclitaxel is a highly hydrophobic drug that is poorly soluble in water. It is mainly given by intravenous administration. Therefore, The pharmaceutical formulation of paclitaxel ($Taxol^{(R)}$; Bristol-Myers Squibb) contains 50% $Cremophor^{(R)}$ EL and 50% dehydrated ethanol. However the ethanol/Cremophor EL vehicle required to solubilize paclitaxel in $Taxol^{(R)}$ has a pharmacological and pharmaceutical problems. To overcome these problems, new formulations for paclitaxel that do not require solubilization by $Cremophor^{(R)}$ EL are currently being developed. Therefore this study utilized a supercritical fluid antisolvent (SAS) process for cremophor-free formulation. To select hydrophilic polymers that require solubilization for paclitaxel, we evaluated polymers and the ratio of paclitaxel/polymers. HP-${\beta}$-CD was used as a hydrophilic polymer in the preparation of the paclitaxel solid dispersion. Although solubility of paclitaxel by polymers was increased, physical stability of solution after paclitaxel/polymer powder soluble in saline was unstable. To overcome this problem, we investigated the use of surfactants. At 1/20/40 of paclitaxel/hydrophilic polymer/ surfactant weight ratio, about 10 mg/mL of paclitaxel can be solubilized in this system. Compared with the solubility of paclitaxel in water ($1\;{\mu}g/mL$), the paclitaxel solid dispersion prepared by SAS process increased the solubility of paclitaxel by near 10,000 folds. The physicochemical properties was also evaluated. The particle size distribution, melting point and amophorization and shape of the powder particles were fully characterized by particle size distribution analyzer, DSC, SEM and XRD. In summary, through the SAS process, uniform nano-scale paclitaxel solid dispersion powders were obtained with excellent results compared with $Taxol^{(R)}$ for the physicochemical properties, solubility and pharmacokinetic behavior.

• Natural Product Sciences
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• 제9권4호
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• pp.291-298
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• 2003

Anti-diabetic effect of various fractions of Cordyceps militaris (CM), CCCA (crude cordycepin containing adenosine), CMESS (ethanol soluble supernatant), and cordycepin were evaluated in streptozotocin (STZ) induced diabetic mice, CMESS showed potent inhibitory activity of 34.7% in starch-loaded mice (2 g/kg) while acarbose as a positive standard exhibited 37.8% of inhibition rate. After 3 days administration (50 mg/kg), cordycepin (0.2 mg/kg), and acarbose (10 mg/kg) dramatically reduced blood glucose level (inhibition ratio: 46.9%, 48.4% and 37.5% respectively). CCCA that has high contents of cordycepin (0.656 mg/4 mg) did not influence on reducing blood glucose level. The proliferation of splenocytes and peritoneal macrophages derived from STZ-induced diabetic mice administered samples were evaluated out by addition of mitogens to see the stability of the usage of these herbal medicines. Proliferation of T-lymphocyte was significantly decreased; while NO production was increased more than two fold to STZ control in the cordycepin-administered group. Changes of serum enzyme levels of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) were also evaluated. Cordycepin administered group was appeared to acarbose. We conclude that CMESS and cordycepin may be useful tools in the control of blood glucose level in diabetes and promising new drug as an anti-hyperglycemic agent without defects of immune responses and other side effects.

• Natural Product Sciences
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• 제26권2호
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• pp.136-143
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• 2020

Psoriasis is one of the most common inflammatory skin disorders, with a global prevalence of 2% - 3%. It is an autoimmune skin disorder characterized by excessive generation of plaques on the skin with typical long-lasting red, itchy, and scaly lesions. In this study, we aimed to elucidate the anti-psoriatic effect of the methanolic extract of Persicaria senticosa (PS), a bioactive edible plant extract used in traditional medicine, using a mouse model of imiquimod (IMQ)-induced psoriasis. The daily topical application of IMQ could induce human psoriasis-like lesion. The extract ameliorated IMQ-induced psoriasis. Furthermore, hematoxylin and eosin staining and the Psoriasis Area and Severity Index (PASI) scores indicated that topical application of PS led to an improvement in erythema, scaling, and thickness scores of the mouse dorsal skin and a considerable decrease in the epidermal thickness of the ear and dorsal skin in the IMQ-induced psoriatic mouse model. We also studied the effect of PS on the proliferation of keratinocytes using HaCaT cells. The extract inhibited cell proliferation and IL-6 and pSTAT3 expression induced by M5 cocktail (comprising interleukin [IL]-1α, IL-17A, IL-22, oncostatin M, and tumor necrosis factor-α) in HaCaT cells. Thus, PS might serve as a potential therapeutic agent for the treatment of psoriasis.

• 약학회지
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• 제49권3호
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• pp.237-243
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• 2005

Present study was performed for the development of a new supplementary product with gastroprotective effect. The preliminary screening were conducted for the effects of HCl-ethanol-induced gastric lesions in rats. Samples were aloe gel, active hexose correlated compound (AHCC) mentioned that have GI protective property and pulmuone healthy aloe gel (PHAG) that mixture of natural products from Pulmuone company. Aloe gel significantly inhibited HCl-ethanol-induced gastric lesions at the oral dose of 5 ml/kg. AHCC showed the strongest effectiveness at the oral dose of 1,200 mg/kg. PHAG also showed the significant effects at the oral dose of 10, 20 g/kg. In pylorus ligated rats, the treatments of aloe gel, AHCC and PHAG showed decrease in the volume of gastric secretion and acid output. And aloe gel, AHCC and PHAG significantly suppressed the aspirin-induced ulcer and chronic ulcer in pylorus ligated rats. The treatments of aloe gel and PHAG significantly reduced acetic acid-induced ulcer at the oral dose of 5 ml/kg and 10 g/kg for 12 days. In this study; we have found that PHAG had significant improvement in acute gastritis and ulcer at the dose of 20 g/kg and in chronic gastritis and ulcer at the dose of 10 g/kg. Also we evaluated the anti-bacterial activity against H. pylori treated with aloe gel, AHCC and PHAG. PHAG had a equivalent anti bacterial activity with ampicillin against H. pylori at the dose of 1 g/kg.

• Natural Product Sciences
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• 제27권3호
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• pp.201-207
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• 2021

We have previously reported that Acer tegmentosum extract, which is traditionally used in Korea to reduce alcohol-related liver injury, suppresses liver inflammation caused by excessive alcohol consumption and might improve metabolism. The active ingredient, 6-O-galloylsalidroside (GAL), was isolated from A. tegmentosum, and we hypothesized that GAL could provide desirable pharmacological benefits by ameliorating physiological conditions caused by alcohol abuse. Therefore, this study focused on whether GAL could ameliorate alcoholic fat accumulation and repair liver injury in mice. During chronic alcohol consumption plus binge feeding in mice, GAL was administered orally once per day for 11 days. Intrahepatic lipid accumulation was measured in vivo using a noninvasive method, ¹H magnetic resonance imaging, and confirmed by staining with hematoxylin and eosin and Oil Red O. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured using a Konelab system, and the triglyceride content was measured in liver homogenates using an enzymatic peroxide assay. The results suggested that GAL alleviated alcohol-induced steatosis,e as indicated by decreased hepatic and serum triglyceride levels in ethanol-fed mice. GAL treatment also correlated with a decrease in the Cd36 mRNA expression, thus potentially inhibiting the development of alcoholic steatosis via the hepatic de novo lipogenesis pathway. Furthermore, treatment with GAL inhibited the expression of cytochrome P450 2E1 and attenuated hepatocellular damage, as reflected by a reduction in ALT and AST levels. These findings suggest that GAL extracted from A. tegmentosum has the potential to serve as a bioactive agent for the treatment of alcoholic fatty liver and liver damage.

• Natural Product Sciences
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• 제27권4호
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• pp.217-227
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• 2021

This study is a record of ethnomedicinal knowledge in Begumganj province focussed on medicinal plants and their local uses for primary health care. The aim was to document and preserve the ethnomedicinal knowledge used by traditional healers of Begumganj upazila, Bangladesh, to treat human diseases and evaluate the relative efficacy of the medicinal plants. The uses of medicinal plants were documented as an ethnomedicinal data sheet using direct observation, field interview, plant interview and group interview techniques from December 2012 to January 2014 in the study area. Data were collected from 98 traditional healers through a questionnaire survey and analyzed through informant consensus factor and fidelity level. This study revealed comprehensive relationship among various diseases and families, forms and parts of plants and modes of preparation. Overall, 75 plant species under 71 genera of 47 families were documented, which are used to treat 41 diseases. Data analysis revealed that 41.33%, 14.67%, 36% and 8% of the medicinal plant species were herbs, shrubs, trees, and climbers, respectively. Leaves were the most used parts, followed by stem, root, fruit, bark, latex and rhizome. The most frequently treated diseases were dysentery, rheumatism and skin diseases. This is the first ethnobotanical survey, which recorded the importance of medicinal plants in Begumganj upazila, Bangladesh. This study can contribute to preserving the indigenous knowledge on the traditional use of medicinal plants in this region and new drug development with attracting future generations towards traditional healing practice.

• Journal of Applied Biological Chemistry
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• 제66권
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• pp.29-38
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• 2023

Recent studies have highlighted the link between diseases and inflammation across our lifespan. Our sedentary lifestyle, high-calorie diet, chronic stress, chronic infections, and exposure to pollutants and xenobiotics, collectively intensify the course and recurrence of infections and inflammation in our bodies, promoting the prevalence of chronic diseases and aging. Given such phenomena and considering additional factors such as the frequency of prescription, and easy access to over-the-counter drugs, the need for anti-inflammatory therapeutics is ever-increasing. However, the readily available anti-inflammatory treatment option comes with a greater risk of side effects or high cost (biologics). Therefore in this growing competition of discovering and developing new potent anti-inflammatory drugs, we focused on utilizing the established knowledge of traditional medicine to find lead compounds. Since lead optimization is an indispensable step toward drug development, we applied this concept for the production of potent anti-inflammatory compounds achieved by structural modification of flavonoids. The derivative obtained through acetylation of myricetin, 3,3',4',5,5',7-hexaacetate myricetin, showed a greater inhibitory effect in the production of pro-inflammatory mediators such as nitric oxide, Prostaglandin E₂, and pro-inflammatory cytokines like interleukin-6, interleukin1β, in lipopolysaccharide-stimulated RAW264.7 mouse macrophage cells compared to myricetin. The increased potency of inhibition was in conjunction with an increased inhibitory effect on inducible nitric oxide synthase and cyclooxygenase-2 proteins. Through such measures, this study supports lead optimization for well-established lead compounds from traditional medicine using a simpler and greener chemistry approach for the purpose of designing and developing potent anti-inflammatory therapeutics with possibly fewer side effects and increased bioavailability.

• 생명과학회지
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• 제26권3호
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• pp.359-363
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• 2016

한약진흥재단(NIKOM)의 640-천연물 라이브러리를 PC12세포에 10 μg/ml/day로 처리하였다. 면역강화에 관여하는 ERAP1 (Endoplasmic Reticulum AminoPeptidase 1)과 수명연장에 관여하는 FOXO1 (FOXO-family transcription factor) 유전자발현을 RT-PCR로 확인하였다. ERAP1 유전자를 1.5-2배까지 상승시킨 것은 22개, 2배 이상 발현시킨 것은 14개였다. FOXO1 유전자를 1.5-2배까지 상승시킨 것은 총 24개, 2배 이상 발현시킨 것은 4개였다. 동시에 ERAP1과 FOXO1 유전자를 2배 이상 상승시키는 것은 족도리풀(Asiasari radix)에서 분리된 (±)-Car-3-ene-2,5-dione, 두꺼비(Bufonis venenum)에서 분리된 Cinobufagin, 대국(Euphorbiae pekinensis)에서 분리된 Corilagin, 현호색(Corydalis tuber)에서 분리된 Corydaline 4종이다. 이들 4종의 천연물은 초파리를 이용한 개체의 수명연장실험에 사용될 것이다.

• Applied Biological Chemistry
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• 제48권4호
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• pp.345-351
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• 2005

난배양 미생물로부터 천연물질을 찾기 위하여 토양으로부터 직접분리 된 DNA와 cosmid vector를 이용하여 metagenomic library를 제작하고 탐색 하였다. 대장균에서 발현되는 유전자은행 초기 탐색 결과 LB배지에서 잘 자라면서 브라운 색깔을 내는 여러 개의 clone을 선발 하였다. 선발된 여러 후보 clone중 pYS85C는 돌연변이를 유도하였으며 색깔을 생산하지않는 clone 들에 대하여 염기서열을 결정 하였다. 돌연변이clone들로부터 결정된 pYS85C 염기서열 결과 아미노산이 393개이며 44.5 kDa으로 색소형성에 관여하는 4-hydroxyphenylpyruvic acid dioxygenase(HPPD) 유전자로 판명 되었다. 또한, BLAST비교 분석에서 이효소는 기존에 밝혀진 HPPD효소와 60% 정도의 identity를 보였고 C-말단에서는 많은 conserved domain이 있었다. 이러한 결과로 볼 때 천연물질을 합성 할 수 있는 유전자는 토양DNA로부터 직접 분리되어 발현될 수 있으며 이러한 기술은 새로운 물질을 찾는데 중요한 tool이 될 수 있다.