| Kinase Assay: |
| Food Chem Toxicol. 2014 Jun;68:38-43. | | Betulinic acid isolated from Vitis amurensis root inhibits 3-isobutyl-1-methylxanthine induced melanogenesis via the regulation of MEK/ERK and PI3K/Akt pathways in B16F10 cells.[Pubmed: 24632067] | Previously, Betulinic acid was identified as one of the main compounds responsible for the anti-melanogenic effect in Vitis amurensis root.
METHODS AND RESULTS:
In this study, we investigated the precise mechanism underlying the anti-melanogenic activity of Betulinic acid in B16F10 cells. Betulinic acid significantly attenuated 3-isobutyl-1-methylxanthine (IBMX)-induced melanin production by inhibiting tyrosinase, tyrosinase related protein (TRP)-1, and TRP-2 expression through the modulation of their corresponding transcription factors, microphthalamia associated transcription factor (MITF) and cAMP response element binding protein (CREB), in B16F10 cells. In addition, phosphorylation of mitogen-activated protein kinase kinase (MEK)/extracellular regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K)/Akt, involved in the melanogenic processes, were ameliorated by Betulinic acid treatment. Role of MEK/ERK and PI3K/Akt signaling pathway in the melanogenesis was confirmed by using specific inhibitors, PD98059 (for MEK/ERK) and LY294002 (for PI3K/Akt), respectively. As a result, Betulinic acid inhibited melanin production by tyrosinase, TRP-1, and TRP-2 inhibition through the regulation of CREB and MITF, which was accompanied with MEK/ERK and PI3K/Akt inactivation in IBMX-stimulated B16F10 cells.
CONCLUSIONS:
Consequently, these results demonstrate a novel molecular function of Betulinic acid derived from V. amurensis root in melanogenesis, which in turn enhances our understanding on the application of cosmetic therapy for reducing skin hyperpigmentation. | | J Immunol. 2003 Sep 15;171(6):3278-86. | | Betulinic acid suppresses carcinogen-induced NF-kappa B activation through inhibition of I kappa B alpha kinase and p65 phosphorylation: abrogation of cyclooxygenase-2 and matrix metalloprotease-9.[Pubmed: 12960358] | Betulinic acid (BA), a pentacyclic triterpene isolated from the bark of the white birch tree, has been reported to be a selective inducer of apoptosis in tumor cells. It also exhibits anti-inflammatory and immunomodulatory properties. How BA mediates these effects is not known. Because of the critical role of the transcription factor NF-kappaB in growth modulatory, inflammatory, and immune responses, we postulated that BA modulates the activity of this factor.
METHODS AND RESULTS:
In this study we investigated the effect of BA on NF-kappaB and NF-kappaB-regulated gene expression activated by a variety of inflammatory and carcinogenic agents. BA suppressed NF-kappaB activation induced by TNF, PMA, cigarette smoke, okadaic acid, IL-1, and H(2)O(2). The suppression of NF-kappaB activation was not cell-type specific. BA suppressed the activation of IkappaBalpha kinase, thus abrogating the phosphorylation and degradation of IkappaBalpha. We found that BA inhibited NF-kappaB activated by TNFR 1, TNFR-associated death domain, TNFR-associated factor 2, NF-kappaB-inducing kinase, and IkappaBalpha kinase. Treatment of cells with this triterpinoid also suppressed NF-kappaB-dependent reporter gene expression and the production of NF-kappaB-regulated gene products such as cyclooxygenase-2 and matrix metaloproteinase-9 induced by inflammatory stimuli. Furthermore, BA enhanced TNF-induced apoptosis.
CONCLUSIONS:
Overall, our results indicated that BA inhibits activation of NF-kappaB and NF-kappaB-regulated gene expression induced by carcinogens and inflammatory stimuli. This may provide a molecular basis for the ability of BA to mediate apoptosis, suppress inflammation, and modulate the immune response. |
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| Animal Research: |
| Zhongguo Zhong Yao Za Zhi. 2014 Mar;39(6):1097-100. | | Research on HBV DNA inhibition of plasmid acute infection mouse with betulinic acid[Pubmed: 24956858] | Betulinic acid is a naturally occurring pentacyclic triterpenoid, which has antiretroviral, antimalarial, and anti-inflammatory properties. The purpose of this study is to investigate the HBV DNA replication inhibition in the mouse model with Betulinic acid.
METHODS AND RESULTS:
Hydrodynamic injection method via the tail vein with the Paywl. 3 plasmid was used to establish the animal mode (n = 15), and the mice were randomly divided into the PBS control group (n = 5), Betulinic acid treatment group (n = 5) and lamivudine control group (n = 5). The day after successful modeling , the mice would have taken Betulinic acid (100 mg x kg(-1)), lamivudine (50 mg x kg(-1)), PBS drugs orally, once daily for 7 days, blood samples were acquired from the orbital venous blood at 3, 5, 7 days after the administering, HBsAg and HBeAg in serum concentration were measured by ELISA and the mice were sacrificed after 7 days, HBV DNA southern detections were used with part of mice livers. The results showed that Betulinic acid significantly inhibited the expression of HbsAg in the mice model at the fifth day compared with the control group, and there was no significant differences between the effects of lamivudine and the PBS control group; both the Betulinic acid and lamivudine groups had no significant inhibition for the HBeAg expression; the HBV DNA expressions of the liver tissue from the Betulinic acid and lamivudine groups were inhibited compared with the control group.
CONCLUSIONS:
Taken together, these results reveal Betulinic acid can inhibit the HBsAg expression and replication of the liver HBV DNA in the mouse model. |
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