• 생명과학회지
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• 제32권10호
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• pp.762-770
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• 2022

제 2형 당뇨병은 고혈당을 특징으로 하는 만성 대사성 질환으로 인슐린 민감성및 저항성을 개선하여 세포속으로 포도당 흡수를 촉진시킴으로서 완화될 수 있다. 본 연구는 triterpenoid 화합물인 betulinic acid가 3T3-L1 지방세포에서 인슐린 신호전달체계를 개선하여 포도당 흡수를 촉진시키는지를 조사하고 그 작용기전을 규명하였다. Betulinic acid는 3T3-L1 지방세포에서 농도의존적으로 포도당 흡수를 유의하게 증가시켰으며, 이는 PM-GLUT4의 발현 증가와 관련이 있음을 관찰하였다. Betulinic acid는 인슐린 신호전달 경로에서 PI3K의 활성화 및 IRS-1tyr, Akt의 인산화를 대조군에 비해 유의하게 증가시켰다. 또한 AMPK의 활성화를 나타내는 pAMPK와 AMPK 하위인자인 pACC의 수준을 유의하게 증가시켰다. Betulinic acid에 의한 PI3K 및 AMPK 경로의 활성화를 증명하기 위해, PI3K 억제제(Wortmannin)와 AMPK의 억제제(Compound C)를 사용하여 이들 처리에 의한 포도당 흡수능과 PM-GLUT4의 발현을 측정한 결과 이들의 발현이 유의하게 저해되었다. 본 연구에서 betulinic acid는 3T3-L1 지방세포에서 PI3K 및 AMPK 경로의 활성화를 통해 세포막으로 포도당 수송체인 GLUT4 전위를 촉진시키고 포도당 흡수를 증가시킬 수 있음을 나타내었다. 이러한 결과는 betulinic acid가 인슐린 민감성을 증진시키고 고혈당을 완화하는데 도움이 될 수 있음을 시사한다.

• 약학회지
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• 제52권1호
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• pp.37-42
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• 2008

Betulinic acid, a naturally occurring pentacyclic triterpenoid, is found in abundance in the outer bark of white birch (Betula alba). In this study, we investigated if betulinic acid affects cytokine expression from activated macrophage cells. ELISA result showed that stimulation of HL-60 cells with proinflammatory cytokine such as $TNF-{\alpha}$ resulted in MCP-1 release into culture medium. In addition, transcriptional upregulation of MCP-1 in response to $TNF-{\alpha}$ was observed by RT-PCR analysis. However, incubation of HL-60 cells with betulinic acid prior to $TNF-{\alpha}$ treatment abrogated MCP-1 expression in transcription and translational level. Consistent with a number of studies which reported requirement of ERK activation for $TNF-{\alpha}$ expression, Western blot analysis showed that $TNF-{\alpha}-induced$ ERK activation was suppressed by pretreatment of HL-60 cells with betulinic acid. Taken together, our data indicate that betulinic acid exerts its anti-inflammatory effect through inhibition of $TNF-{\alpha}-induced$ ERK activation which is required for the subsequent MCP-1 release.

• 생약학회지
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• 제39권2호
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• pp.118-122
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• 2008

This study was conducted to evaluate the inhibitory effects of betulinic acid isolated from Ziziphus jujuba on various human rotavirus, such as KU, S2 and YO. The results obtained are summarized as follows: At the concentration of betulinic acid 0.1/2%, all human rotavirus is showed a maximum effect on their growth even though it's evaluated on the in vitro test. The each inhibitory rate of MA-104 cells infected by human rotavirus KU, S2 and YO was 62.1%, 59.7% and 65.2%, respectively, at the concentration of 0.1/2%. The anti-virus activity of betulinic acid was showed as the dose-dependent manner at the used dosages except at the dose of 0.1%.

• 생물정신의학
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• 제4권1호
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• pp.54-59
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• 1997

Objects : Sanjoin, the seeds of Zizyphus vulgaris var. spinosus has been used as the most important hypnotic agent in chinese medicine to treat insomnia. This research was performed in order to examine the effect of betulinic acid and sanjoinine-A which are components of Sanjoin. Method : Sleeping time, sleep recordings of EEG, EMG, serum serotonin level, and locomotor activity were measured in rats which received betulinic acid and sanjoinine-A as sleep induction material extracted from Sanjoin. Results : 1) Groups received betulinic acid, sanjoinine-A, and lorazepam showed increased sleep time than control group with saline. 2) Groups with betulinic acid, sanjoinine-A, lorazepam and saline recorded ${\beta}$-wave in sleep recordings of EEG. In EMG, there was no significant difference among all groups. 3) No significant difference in serum serotonin level among all groups was found. 4) In autonomic activity testing, groups of betulinic acid, sanjoinine-A, and lorazepam showed significantly more decreased in activity than saline group. In comparison of groups of betulinic acid and sanjoinine-A with a group of lorazepam, there was no significant difference. Conclusion : These results suggest that betulinic acid and sanjoinine-A have the sedative effect like lorazepam rather than sleep effect.

• Biomolecules & Therapeutics
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• 제19권4호
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• pp.431-437
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• 2011

Aberrant activation of microglia has been reported to cause neuronal damages by releasing a variety of pro-inflammatory cytokines. Besides where microglia become active, damages have been also observed in remote places, which is considered due to the migration of activated microglia. Therefore, an agent that could suppress abnormal activation of microglia and their subsequent migration might be valuable in activated microglia-related brain pathologies. The objective of the present study was to evaluate anti-inflammatory effects of betulinic acid on lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Pretreatment of betulinic acid significantly attenuated LPS-induced NO production and protein expression of iNOS. Betulinic acid also significantly suppressed LPS-induced release and expression of cytokines such as TNF-${\alpha}$ and IL-$1{\beta}$. Furthermore, betulinic acid significantly uppressed LPS-induced MMP-9 expression, which has been suggested to play an important role in the migration of activated microglia. In order to understand the possible mechanism by which betulinic acid suppresses LPS-induced cytokine production and migration of microglia, the role of NF-kB, a major pro-inflammatory transcription factor, was examined. Betulinic acid significantly suppressed LPS-induced degradation of IKB, which retains NF-kB in the cytoplasm. Therefore, nuclear translocation of NF-kB upon LPS stimulation was significantly suppressed with betulinic acid. Taken together, the present study for the first time demonstrates that betulinic acid possesses anti-inflammatory activity through the suppression of nuclear translocation of NF-kB in BV2 microglial cells.

• 생명과학회지
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• 제32권8호
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• pp.589-594
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• 2022

이 연구에서 베툴린산이 STZ에 의해 유발된 고혈당 쥐에서 탄수화물 소화 효소의 활성을 억제하고 식후 고혈당을 감소시킬 수 있는지 여부를 알아보았다. 그 결과, 베툴린산이 α-글루코시다아제와 α-아밀라아제 활성에 강력한 억제 효과를 보여주었다. α-글루코시다아제와 α-아밀라아제에 대한 베툴린산의 IC₅₀는 각각 12.83± 6.81 및 18.32±3.24 μM으로, 이는 경구 혈당강하제인 acarbose의 IC₅₀ 보다 값이 낮아 베툴린산의 탄수화물 소화효소의 억제 활성이 높다는 것을 나타낸다. 당뇨쥐와 정상쥐에서 증가된 식후 혈당은 베툴린산을 투입한 고혈당군, 정상군 모두 대조군보다 유의하게 식후 혈당이 억제되었습니다. 30, 60, 120분에 각각 혈당을 측정하였을 떄, 당뇨쥐에서 베툴린산을 투여한 군의 혈당은 23.22±1.1, 24.38±1.31, and 21.05±1.36 μM 으로 대조군의 혈당인 24.64± 1.7, 27.22±1.58, and 26.36±1.40 μM 보다 유의하게 감소하였다. 당뇨쥐에서 베툴린산 투여한 군의 AUC도 대조군 쥐에 비해 유의하게 감소하였지만, acarbose를 투여한 군에 비해서는 더 많이 감소하지 않았다. 이러한 연구 결과는 베툴린산이 탄수화물 소화 효소의 강력한 억제제로의 가능성을 보여주어, 당뇨병 쥐의 식후 고혈당증을 개선할 수 있을 것이라 사료된다.

• Biomolecules & Therapeutics
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• 제23권4호
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• pp.345-349
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• 2015

Betulinic acid, a pentacyclic triterpene isolated from Jujube tree (Zizyphus jujuba Mill), has been known for a wide range of biological and medicinal properties such as antibacterial, antimalarial, anti-inflammatory, antihelmintic, antinociceptive, and anticancer activities. In the study, we investigated the antiviral activity on influenza A/PR/8 virus infected A549 human lung adenocarcinoma epithelial cell line and C57BL/6 mice. Betulinic acid showed the anti-influenza viral activity at a concentration of $50{\mu}M$ without a significant cytotoxicity in influenza A/PR/8 virus infected A549 cells. Also, betulinic acid significantly attenuated pulmonary pathology including increased necrosis, numbers of inflammatory cells and pulmonary edema induced by influenza A/PR/8 virus infection compared with vehicle- or oseltamivir-treated mice in vivo model. The down-regulation of IFN-${\gamma}$ level, which is critical for innate and adaptive immunity in viral infection, after treating of betulinic acid in mouse lung. Based on the obtained results, it is suggested that betulinic acid can be the potential therapeutic agent for virus infection via anti-inflammatory activity.

• 한국약용작물학회지
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• 제28권6호
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• pp.455-462
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• 2020

Background: The purpose of this study was to analyze the applicability of dried jujube (Zizypui Fructus) distributed by size as a functional food material and herbal medicine by evaluating its physicochemical characteristics and betulinic acid content. Methods and Results: It was shown that the carbohydrate content of in jujube fruit significantly increased with fruit size; 81.42% for large, 79.83% for medium, and 76.39% for small. Similarly, the dilute ethanol extract content of each group was 72.48% (large), 69.56% (medium), and 64.16% (small). A free sugar analysis indicated that glucose, fructose and sucrose were found in quantitieds proportional to jujube fruit size, the total free sugar values were 68.85%, 63.93%, and 57.37% for large, medium, and small fruit sizes respectively. The betulinic acid content for large, medium, and small fruit was 0.50 mg/g, 0.54 mg/g, and 0.58 mg/g respectively, indicating that smaller jujube contained a higher amount of betulinic acid. Conclusions: It is considered that betulinic acid content could be used as a criteria for jujube fruit quality control.

• 약학회지
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• 제40권5호
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• pp.558-562
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• 1996

Betulinic acid and alphitolic acid, the triterpenoids of Zyziphi Fructus, were isolated with silica gel column chromatography and used as the standard substances for the analysis. The compounds were determined with HPLC and HPTLC. They were separated on reversed phase column (Nova-Pak C18) with 0.05M Na2HPO4-methanol (19:81) in HPLC and detected at 210nm. Separation on HPTLC precoated silica gel F254 plates was carried out with chloroform-methanol (6:1) and the separated compounds were reacted with p-anisaldehyde and detected at 540nm. The contents of betulinic acid and alphitolic acid in Zyziphi Fructus from four different regions in Korea were in the range of 2.9~3.8% and 3.2~3.9%, respectively.

• 생약학회지
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• 제22권3호
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• pp.162-165
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• 1991

Four triterpenoids were isolated from the leaves and stems of Lycopus lucidus and identified as betulinic acid, oleanolic acid, 3-epimaslinic acid and euscapic acid by spectroscopic methods.