Peltophorum Africanum, a Traditional South African Medicinal Plant, Contains an Anti HIV-1 Constituent, Betulinic Acid

Theo, Andros; Masebe, Tracy; Suzuki, Yasuhiro; Kikuchi, Haruhisa; Wada, Shoko; Chikwelu, Larry; Bessong, Pascal; Usuzawa, Motoki; Oshima, Yoshiteru; Hattori, Toshio

doi:10.1620/tjem.217.93

Cited by 52 publications

(32 citation statements)

References 32 publications

(35 reference statements)

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“…Normal values in this study are: a < 820 ng/ml; b < 46 pg/ml; c 2-8 pmol/L; d < 0.5 ng/ml; e < 1.0 pg/ml. Since a limitation of this study is the low numbers of patients, the involvement of immune activation-induced OPN in various side effects of HAART should be carefully investigated with appropriate controls in a large number of patients in Africa where HAART was introduced very recently and 3 million people received HAART accounting for 30% of those needing such treatment (Ford et al 2009), and many patients still take herbal medicine, which was shown by us to contain an anti-HIV compound (Theo et al 2009). It is also interesting to investigate whether anti-HIV herbal medicine could increase the OPN production or cause side effects like HAART.…”

Section: Discussionmentioning

confidence: 99%

Persistent Elevation of Plasma Osteopontin Levels in HIV Patients Despite Highly Active Antiretroviral Therapy

Chagan-Yasutan

Saitoh

Ashino

et al. 2009

Tohoku J. Exp. Med.

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Section: Discussionmentioning

confidence: 99%

Persistent Elevation of Plasma Osteopontin Levels in HIV Patients Despite Highly Active Antiretroviral Therapy

Chagan-Yasutan

Saitoh

Ashino

et al. 2009

Tohoku J. Exp. Med.

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“…Betulinic acid (BA), a natural pentacyclic triterpene isolated from birch, exhibits a variety of biological activities, including anti-HIV, anti-HBV, anti-malarial [8][9][10] and potent anti-tumor properties in melanoma [11] , leukemia [12] , colon [13] , lung [14] , gliomas [15] , prostate carcinoma [16] , gastric adenocarcinoma [17] and multiple myeloma [18,19] . Various mechanisms have been reported for the extensive anticancer activity of BA, including directly triggering mitochondrial membrane permeabilization [20] , regulating Bcl-2 family proteins [21] , downregulating Hiwi expression [17] and suppressing the activation of the STAT3 pathway through the induction of the protein tyrosine phosphatase SHP-1 [19] .…”

Section: Introductionmentioning

confidence: 99%

Betulinic acid inhibits autophagic flux and induces apoptosis in human multiple myeloma cells in vitro

Yang

Yan

et al. 2012

Acta Pharmacol Sin

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Aim: To investigate the effects of betulinic acid (BA) on apoptosis and autophagic flux in multiple myeloma cells and the relationship between the two processes. Methods: The proliferation of human multiple myeloma KM3 cells was measured with MTT assay. FITC/PI double-labeled flow cytometry (FCM) and Hoechst 33258 staining were used to analyze the cell apoptosis. Caspase 3, PARP, Beclin1, LC3-II, and P62 were detected using Western blotting. Results: Treatment of KM3 cells with BA (5−25 μg/mL) suppressed the cell proliferation in time-and dose-dependent manners. The IC 50 values at 12, 24, and 36 h were 22.29, 17.36, and 13.06 μg/mL, respectively. BA treatment dose-dependently induced apoptosis of KM3 cells, which was associated with the activation of caspase 3. However, Z-DEVD-FMK, a specific inhibitor of caspase 3, did not decrease, but rather sensitized the cells to BA-induced apoptosis, suggesting an alternative mechanism involved. On other hand, BA treatment dose-dependently increased the accumulation of LC3-II and P62 in KM3 cells, representing the inhibition of autophagic flux. Furthermore, BA treatment dose-dependently downregulated the expression of Beclin 1, an important inducer of autophagy, in KM3 cells. In the presence of BA, Z-DEVD-FMK induced autophagy and increased the amount of LC3-II in KM3 cells, which may occur via attenuating BA-induced decrease in the level of Beclin 1. Similarly, rapamycin, an autophagy inducer, increased the amount of LC3-II in KM3 cells. In the presence of BA, rapamycin caused further increase in the amount of LC3-II. Furthermore, rapamycin sensitized BA-treated KM3 cells to apoptosis. Conclusion:The results demonstrate that BA induces apoptosis and blocks autophagic flux in KM3 cells. Furthermore, in addition to activation of caspase 3, the inhibition of autophagic flux also contributes to the BA-mediated apoptosis of KM3 cells.

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“…Betulinic acid (BA), isolated from birch trees, is a natural pentacyclic triterpene which has demonstrated anti-HIV, anti-HBV and anti-malarial abilities [1][2][3] . In addition, BA is believed to play an important role in delaying or preventing carcinogenesis.…”

Section: Introductionmentioning

confidence: 99%

Effect of betulinic acid on the regulation of Hiwi and cyclin B1 in human gastric adenocarcinoma AGS cells

Yang

Chang

et al. 2009

Acta Pharmacol Sin

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Aim:To investigate the effect of betulinic acid (BA) on the proliferation, apoptosis and cell cycle of gastric adenocarcinoma cell AGS in vitro and elucidate the underlying mechanisms. Methods: The effect of BA on the proliferation of AGS cells was measured by using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium (MTT) assay. Apoptosis was analyzed by using Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) double-labeled flow cytometry (FCM) and Hoechst 33258 staining. The influence of BA on cell cycle of AGS cells was tested by PI staining. Both FCM and reverse transcription-PCR (RT-PCR) technologies were applied to detect the expression of Hiwi and Cyclin B1. Results: BA exhibited significant cell proliferation inhibition, as well as its potency of inducing apoptosis in AGS cells in vitro in a timeand dose-dependent manner. The IC 50 value for 24 h was 18.25 μg/mL (95% confidence interval: 15.16 to 27.31 μg/mL). Cells treated with BA showed increased cell population in G 2 /M phase, with decreased S phase population. The expression of Hiwi and Cyclin B1 was down-regulated in BA-treated AGS cells in a dose-dependent manner. Conclusion: BA exerted potent effect on growth inhibition, G 2 /M cell cycle arrest and induction of apoptosis in AGS cells in vitro, possibly associated with the down-regulation of Hiwi and its downstream target Cyclin B1 expression. The potent antitumor capacity of BA suggested that it could be a promising new experimental anticancer agent in human gastric adenocarcinoma treatment.

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Peltophorum Africanum, a Traditional South African Medicinal Plant, Contains an Anti HIV-1 Constituent, Betulinic Acid

Cited by 52 publications

References 32 publications

Persistent Elevation of Plasma Osteopontin Levels in HIV Patients Despite Highly Active Antiretroviral Therapy

Persistent Elevation of Plasma Osteopontin Levels in HIV Patients Despite Highly Active Antiretroviral Therapy

Betulinic acid inhibits autophagic flux and induces apoptosis in human multiple myeloma cells in vitro

Effect of betulinic acid on the regulation of Hiwi and cyclin B1 in human gastric adenocarcinoma AGS cells

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