In vitro and in vivo antileishmanial effects of aloe-emodin on Leishmania major

10.1016/j.jtcme.2014.11.004

Abdolhossein Dalimi；Mahdi Delavari；Fatemeh Ghaffarifar；Javid Sadraei

aloe-emodin ； apoptosis ； flow cytometry ； in vitro ； in vivo ； Leishmania major

Journal of Traditional and Complementary Medicine

5卷2期（2015 / 04 / 01）

96 - 99

英文

Cutaneous leishmaniasis is a common parasitic disease that is endemic in some parts of Iran. The drugs of choice used for leishmaniasis therapy are associated with a risk of recurrence and serious adverse effects. Therefore, finding a safe and effective treatment is of great importance. In the present study, the effect of aloe-emodin on the growth of Leishmania major amastigotes was evaluated under in vitro conditions. In addition, the efficacy of a topical of aloe-emodin ointment was investigated in BALB/c mice with cutaneous leishmanial ulcers. Different concentrations (40 μg/mL, 80 μg/mL, 120 μg/mL, and 160 μg/mL) of aloe-emodin were tested on Leishmania amastigotes twice: 24 hours and 48 hours. The induced apoptosis and necrotic effects of two concentrations (40 μg/mL and 120 μg/mL) of aloe-emodin on promastigotes were investigated by flow cytometry. Under the in vivo condition, aloe-emodin ointment efficacy was evaluated at two concentrations (i.e., 0.1% and 1%). Serum indicator factors of the test and control groups were tested to evaluate the toxic effects of this compound on the liver and kidney. Results showed that aloe-emodin inhibited the growth of Leishmania amastigotes and induced apoptosis in promastigotes. Topical application of aloe-emodin ointment likewise reduced the ulcer size. No significant differences in biochemical analysis were observed between the control and treated groups. In conclusion, aloe-emodin showed antileishmanial effects under in vitro and in vivo conditions and may be used in clinical trials.

1. Acevedo-Duncan, M,Russell, C,Patel, S,Patel, R(2004).Aloe-emodin modulates PKC isozymes, inhibits proliferation, and induces apoptosis in U-373MG glioma cells.Int Immunopharmacol,4,1775-1784.
2. Alavi-Naini, R,Fazaeli, A,O'Dempsey, T(2012).Topical treatment modalities for Old World cutaneous leishmaniasis: a review.Prague Med Rep,113,105-118.
3. Alvar, J,Velez, ID,Bern, C(2012).Leishmaniasis worldwide and global estimates of its incidence.PLoS One.,7(5),e35671.
4. Balasegaram, M,Ritmeijer, K,Lima, MA(2012).Liposomal amphotericin B as a treatment for human leishmaniasis.Expert Opin Emerging Drugs,17,493-510.
5. Ben Salah, A,Ben Messaoud, N,Guedri, E(2013).Topical paromomycin with or without gentamicin for cutaneous leishmaniasis.N Engl J Med.,368,524-532.
6. Chen, HC,Hsieh, WT,Chang, WC,Chung, JC(2004).Aloe-emodin induced in vitro G2/M arrest of cell cycle in human promyelocytic leukemia HL-60 cells.Food Chem Toxicol,42,1251-1257.
7. Chen, SH,Lin, KY,Chang, CC,Fang, CL,Lin, CP(2007).Aloe-emodin-induced apoptosis in human gastric carcinoma cells.Food Chem Toxicol,45,2296-230.
8. Croft, SL,Seifert, K,Yardley, V(2006).Current scenario of drug development for leish-maniasis.Indian J Med Res.,123,399-410.
9. Dutta, A,Bandyopadhyay, S,Mandal, C,Chatterjee, M(2007).Aloe vera leaf exudate induces a caspase-independent cell death in Leishmania donovani promastigotes.J Med Microbiol.,56,629-636.
10. Dutta, A,Mandal, G,Mandal, C,Chatterjee, M(2007).In vitro antileishmanial activity of Aloe vera leaf exudate: a potential herbal therapy in leishmaniasis.Glycoconj J.,24,81-86.
11. Dutta, A,Sarkar, D,Gurib-Fakim, A,Mandal, C,Chatterjee, M(2008).In vitro and in vivo activity of aloe vera leaf exudate in experimental visceral leishmaniasis.Parasitol Res,102,1235-1242.
12. Garnier, T,Croft, SL(2002).Topical treatment for cutaneous leishmaniasis.Curr Opin Invest Drugs,3(4)
13. Kuo, P,Lin, T,Lin, C(2002).The antiproliferative activity of aloeeemodin is through p53 dependent and p21-dependent apoptotic pathway in human hepatoma cell lines.Life Sci.,71,1879-1892.
14. Li, J,Chen, J,Zhang, XL,Lu, CH,Yang, HH(2010).A novel sensitive detection platform for antitumor herbal drug aloe-emodin based on the graphene modified electrode.Talanta,83,553-558.
15. Lin, CW,Wu, CF,Hsiao, NW(2008).Aloe-emodin is an interferon-inducing agent with antiviral activity against Japanese encephalitis virus and entero virus 71.Int J Antimicrob Agents,32,355-359.
16. Love, DC,Esko, JD,Mosser, DM(1993).A heparin-binding activity on Leishmania amastigote which mediates adhesion to cellular proteoglycans.J Cell Biol,123,759-766.
17. Mandrioli, R,Mercolini, L,Ferranti, A,Augusta Raggi, M(2011).Determination of aloe emodin in aloe vera extracts and commercial formulations by HPLC with tandem UV absorption and fluorescence detection.Food Chem,126,387-393.
18. Mohammadzadeha, M,Behnaz, F,Golshan, Z(2013).Efficacy of glucantime for treatment of cutaneous leishmaniasis in Central Iran.J Infect Public Health,6,120-124.
19. Radovic, J,Maksimovic-Ivanic, D,Timotijevic, G,Popadic, S,Ramic, Z,Trajkovic, V(2012).Cell-type dependent response of melanoma cells to aloe emodin.Food Chem Toxicol,50,3181-3189.
20. Romero, GA,Vinitius De Farias, GM,Gomes, PM,de Oliveira, M(2001).Comparison of cutaneous leishmaniasis due to Leishmania (Viannia) braziliensis and L (V) guyanensis in Brazil: clinical findings and diagnostic approach.Clin Infect Dis.,32,1304-1312.
21. Shia, DH,Huang, W,Lia, C,Wang, LT,Wang, SF(2013).Synthesis, biological evaluation and molecular modeling of aloe-emodin derivatives as new acetylcholines-terase inhibitors.Bioorg Med Chem,21,1064-1073.
22. Tabolacci, C,Lentini, A,Mattioli, P(2010).Antitumor properties of aloe-emodin and induction of transglutaminase 2 activity in B16-F10 melanoma cells.Lif Sci.,87,316-324.
23. Tian, B,Hua, Y(2005).Concentration-dependence of prooxidant and antioxidant effects of aloin and aloe-emodin on DNA.Food Chem,91,413-418.
24. William, HM,Makhoul, K(2004).Cutaneous leishmaniasis: recognition and treatment.Am Fam Physician,69,455-460.