• Journal of Life Science
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• v.32 no.10
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• pp.762-770
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• 2022

Hyperglycemia in type 2 diabetes can be alleviated by promoting cellular glucose uptake. Betulinic acid (3β,-3-hydroxy-lup-20(29)-en-28-oic acid) is a pentacyclic lupane-type triterpenoid compound. Although there have been studies on the antidiabetic activity of betulinic acid, studies on cellular glucose uptake are lacking. We investigated the effects of betulinic acid on glucose uptake and its mechanism of action in 3T3-L1 adipocytes. Betulinic acid significantly stimulated glucose uptake in 3T3-L1 adipocytes by increasing the phosphorylation of the insulin receptor substrate 1-tyrosine (IRS-1tyr) in the insulin signaling pathway, which in turn stimulated the activation of phosphoinositide 3-kinase (PI3K) and the phosphorylation of protein kinase B (Akt). The activation of PI3K and Akt by betulinic acid translocated glucose transporter 4 to the plasma membrane (PM-GLUT4), thereby increasing the expression of PM-GLUT4 and thus stimulating cellular glucose uptake. Betulinic acid also significantly increased the phosphorylation/activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase. The activation of PI3K and AMPK by betulinic acid was confirmed using the PI3K inhibitor wortmannin and the AMPK inhibitor compound C. The increase in glucose uptake induced by betulinic acid was significantly decreased by wortmannin and compound C in the 3T3-L1 adipocytes. These results suggest that betulinic acid stimulates glucose uptake by activating PI3K and AMPK in 3T3-L1 adipocytes.

• YAKHAK HOEJI
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• v.52 no.1
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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.

• Korean Journal of Pharmacognosy
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• v.39 no.2
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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%.

• Korean Journal of Biological Psychiatry
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• v.4 no.1
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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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• v.19 no.4
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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.

• Journal of Life Science
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• v.32 no.8
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• pp.589-594
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• 2022

The objective of this study was to investigate whether betulinic acid can inhibit the activities of carbohydrate-digesting enzymes and reduce postprandial hyperglycemia in mice with streptozotocin-induced diabetes. Our results revealed that betulinic acid has potent inhibitory effects on α-glucosidase and α-amylase activities. The half-maximal inhibitory concentrations (IC₅₀) of betulinic acid were 12.83±6.81 and 18.32±3.24 μM for α-glucosidase and α-amylase, respectively. This result indicates lower IC₅₀ values and higher inhibitory activities than those of acarbose, an oral hypoglycemic drug. The increase in postprandial blood glucose levels was significantly suppressed in the betulinic acid group than in the control group of diabetic and normal mice. Postprandial blood glucose levels were 23.22±1.1, 24.38±1.31, and 21.05±1.36 μM in the betulinic acid group compared to 24.64±1.7, 27.22±1.58, and 26.36±1.40 μM in the control group of diabetic mice at 30, 60 and 120 min, respectively. The area under the curve also significantly decreased with the administration of betulinic acid in diabetic mice, however, it did not decrease more than that after acarbose administration. Our results showed that betulinic acid may be a potent inhibitor of carbohydrate-digesting enzymes and ameliorate postprandial hyperglycemia in diabetic mice.

• Biomolecules & Therapeutics
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• v.23 no.4
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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.

• Korean Journal of Medicinal Crop Science
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• v.28 no.6
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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.

• YAKHAK HOEJI
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• v.40 no.5
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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.

• Korean Journal of Pharmacognosy
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• v.22 no.3
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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.