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A combination of alkaloids and triterpenes of Alstonia scholaris (Linn.) R. Br. leaves enhances immunomodulatory activity in C57BL/6 mice and induces apoptosis in the A549 cell line.
Molecules. 2013 Nov 12; 18(11):13920-39.M

Abstract

Experiments were conducted to evaluate the induction of apoptosis and the immunomodulatory activities of alkaloids and triterpenes of Alstonia scholaris (Linn.) R. Br. leaves (ASL). Importantly, their possible synergistic properties were also explored in this study. Human lung adenocarcinoma cell line A549 and Lewis tumor-bearing C57BL/6 mice were used for the evaluation of their activities. A MTT assay was used to determine the proliferation inhibition in A549 cells. Annexin-V/PI double staining as well as flow cytometry was performed to detect apoptosis and cell cycle status. Enzyme-linked immunosorbent assay (ELISA) was conducted to determine the levels of inflammatory mediators interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in serum. Furthermore, western blot analysis was applied to evaluate the expressions of proteins associated with cell death. Alkaloids or triterpenes showed a high anti-proliferative activity in A549 cells, with IC50 values of 14.4 µg/mL and 9.3 µg/mL, respectively. The alkaloids and triterpenes combination could significantly inhibit tumor growth in tumor-bearing C57BL/6 mice, compared with alkaloids or triterpenes alone (7.5, 15, 30 g raw material/kg). The immune organs indexes including spleen index and thymus index were increased remarkably by the combination of alkaloids and triterpenes, whereas the levels of IL-6 and TNF-α were up-regulated significantly. Moreover, Annexin-V/PI double staining and flow cytometry showed that the combination of alkaloids and triterpenes (1, 2 and 3 mg raw material/kg) could induce apoptosis and cause S cell cycle arrest in A549 cells. Western blot analysis also showed that their combination (2 mg raw material/kg) significantly down-regulated Bcl-2 expression and pro-casp8 level, whereas it remarkably increased the level of cleaved caspase-8 leading to apoptosis in A549 cells. These observations provide preliminary evidence that both alkaloids and triterpenes possess immune regulation and induction apoptosis activities. Their combination has a stronger activity than that of either class alone. Our findings suggested that these components might be beneficial for the prevention and treatment of NSCLC through a significant synergy effect.

Authors+Show Affiliations

Key Laboratory of New Drug Delivery Systems of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing 210028, Jiangsu, China. ychen202@hotmail.com.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24225772

Citation

Feng, Liang, et al. "A Combination of Alkaloids and Triterpenes of Alstonia Scholaris (Linn.) R. Br. Leaves Enhances Immunomodulatory Activity in C57BL/6 Mice and Induces Apoptosis in the A549 Cell Line." Molecules (Basel, Switzerland), vol. 18, no. 11, 2013, pp. 13920-39.
Feng L, Chen Y, Yuan L, et al. A combination of alkaloids and triterpenes of Alstonia scholaris (Linn.) R. Br. leaves enhances immunomodulatory activity in C57BL/6 mice and induces apoptosis in the A549 cell line. Molecules. 2013;18(11):13920-39.
Feng, L., Chen, Y., Yuan, L., Liu, X., Gu, J. F., Zhang, M. H., & Wang, Y. (2013). A combination of alkaloids and triterpenes of Alstonia scholaris (Linn.) R. Br. leaves enhances immunomodulatory activity in C57BL/6 mice and induces apoptosis in the A549 cell line. Molecules (Basel, Switzerland), 18(11), 13920-39. https://doi.org/10.3390/molecules181113920
Feng L, et al. A Combination of Alkaloids and Triterpenes of Alstonia Scholaris (Linn.) R. Br. Leaves Enhances Immunomodulatory Activity in C57BL/6 Mice and Induces Apoptosis in the A549 Cell Line. Molecules. 2013 Nov 12;18(11):13920-39. PubMed PMID: 24225772.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A combination of alkaloids and triterpenes of Alstonia scholaris (Linn.) R. Br. leaves enhances immunomodulatory activity in C57BL/6 mice and induces apoptosis in the A549 cell line. AU - Feng,Liang, AU - Chen,Yan, AU - Yuan,Ling, AU - Liu,Xuan, AU - Gu,Jun-Fei, AU - Zhang,Ming-Hua, AU - Wang,Ying, Y1 - 2013/11/12/ PY - 2013/09/30/received PY - 2013/11/06/revised PY - 2013/11/06/accepted PY - 2013/11/15/entrez PY - 2013/11/15/pubmed PY - 2014/6/7/medline SP - 13920 EP - 39 JF - Molecules (Basel, Switzerland) JO - Molecules VL - 18 IS - 11 N2 - Experiments were conducted to evaluate the induction of apoptosis and the immunomodulatory activities of alkaloids and triterpenes of Alstonia scholaris (Linn.) R. Br. leaves (ASL). Importantly, their possible synergistic properties were also explored in this study. Human lung adenocarcinoma cell line A549 and Lewis tumor-bearing C57BL/6 mice were used for the evaluation of their activities. A MTT assay was used to determine the proliferation inhibition in A549 cells. Annexin-V/PI double staining as well as flow cytometry was performed to detect apoptosis and cell cycle status. Enzyme-linked immunosorbent assay (ELISA) was conducted to determine the levels of inflammatory mediators interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in serum. Furthermore, western blot analysis was applied to evaluate the expressions of proteins associated with cell death. Alkaloids or triterpenes showed a high anti-proliferative activity in A549 cells, with IC50 values of 14.4 µg/mL and 9.3 µg/mL, respectively. The alkaloids and triterpenes combination could significantly inhibit tumor growth in tumor-bearing C57BL/6 mice, compared with alkaloids or triterpenes alone (7.5, 15, 30 g raw material/kg). The immune organs indexes including spleen index and thymus index were increased remarkably by the combination of alkaloids and triterpenes, whereas the levels of IL-6 and TNF-α were up-regulated significantly. Moreover, Annexin-V/PI double staining and flow cytometry showed that the combination of alkaloids and triterpenes (1, 2 and 3 mg raw material/kg) could induce apoptosis and cause S cell cycle arrest in A549 cells. Western blot analysis also showed that their combination (2 mg raw material/kg) significantly down-regulated Bcl-2 expression and pro-casp8 level, whereas it remarkably increased the level of cleaved caspase-8 leading to apoptosis in A549 cells. These observations provide preliminary evidence that both alkaloids and triterpenes possess immune regulation and induction apoptosis activities. Their combination has a stronger activity than that of either class alone. Our findings suggested that these components might be beneficial for the prevention and treatment of NSCLC through a significant synergy effect. SN - 1420-3049 UR - https://www.unboundmedicine.com/medline/citation/24225772/A_combination_of_alkaloids_and_triterpenes_of_Alstonia_scholaris__Linn___R__Br__leaves_enhances_immunomodulatory_activity_in_C57BL/6_mice_and_induces_apoptosis_in_the_A549_cell_line_ L2 - https://www.mdpi.com/resolver?pii=molecules181113920 DB - PRIME DP - Unbound Medicine ER -