The in Vitro Antischistosomal Activity and Genotoxicity of the Active Ingredients of Allium sativum (allicin) and Curcuma longa (curcumin)
-
Hadeer Abd El-Hak RASHED
,
Ali Hussein ABU ALMAATY
,
Maha Farid Mohamed SOLIMAN
,
Nahla Soliman EL-SHENAWY
Abstract
Background: In this study, we assessed the in vitro antischistosomal activity of the active ingredients of Allium sativum (allicin) and Curcuma longa (curcumin) on Schistosoma mansoni.
Methods: This study was conducted in Faculty of Science, Port said University, Egypt (2018). Adult worms were exposed to a range of concentrations of AL or CU, and worm survival was assessed 24 h post-exposure to calculate the lethal concentration of the compounds. Scanning electron microscopy was used to assess ultrastructural changes in the surface of AL- or CU- treated worms. The genotoxicities of AL and CU on S. mansoni were determined by DNA fragmentation analysis.
Results: We determined the concentrations of AL and CU required to kill 50% of S. mansoni (LC50). The LC50 of AL was 8.66 µL/mL, whereas 100% mortality of S. mansoni was achieved by AL at concentrations of 50 µL/mL. The LC50 of CU was 87.25 µL/mL, with the highest mortality of 91.3% seen after 24 h exposure to 100 µg/mL CU. Ultrastructural studies revealed that exposure to either AL or CU led to mild or severe surface damage to S. mansion, respectively. The degree of damage in the worms was sex-dependent. Interestingly, while CU exposure resulted in DNA fragmentation in S. mansoni worms, we observed no genotoxic effects of AL.
Conclusion: Both AL and CU exhibit antischistosomal activity; the study provided evidence suggesting that these compounds act through distinct mechanisms. These promising results encourage further investigation into these compounds as potential antischistosomal agents, either alone or as complementary treatments to praziquantel.
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2. Deribew K, Tekeste Z, Petros B, et al. Urinary schistosomiasis and malaria associated anemia in Ethiopia. Asian Pac J Trop Biomed. 2013;3(4):307-10.
3. Coltart C, Whitty CJ. Schistosomiasis in non-endemic countries. Clin Med (lond). 2015;15(1):67-9.
4. World Health Organization (WHO). Report of the WHO informal consultation on schistosomiasis control. WHO/CDS/CPC/SIP/99, 2. Geneva: WHO; 1999.
5. Melman SD, Steinauer ML, Cunningham C, et al. Reduced susceptibility to praziquantel among naturally occurring Kenyan isolates of Schistosoma mansoni. PLoS Negl Trop Dis. 2009;3(8):e504.
6. Wang W, Dai JR, Li HJ, et al. Is there reduced susceptibility to praziquantel in Schistosoma japonicum? Evidence from Chin. Parasitology. 2010;137(13):1905–12.
7. Crellen T, Walker M, Lamberton PH, et al. Reduced efficacy of praziquantel against Schistosoma mansoni is associated with multiple rounds of mass drug administration. Clin Infect Dis. 2016;63(9):1151–9.
8. EL Shenawy NS, Soliman MFM, Reyad SI. The effect of antioxidant properties of aqueous garlic extract and Nigella sativa as anti-schistosomiasis agents in mice. Rev Inst Med Trop Sao Paulo. 2008;50(1):29–36.
9. Soliman FM. Evaluation of avocado/soybean unsaponifiable alone or concurrently with praziquantel in murine schistosomiasis. Acta Trop. 2012;122(3):261-6.
10. Ali SA, El-Regal NS, Saeed SM. The antischistosomal activity of two active constituents isolated from the leaves of Egyptian medicinal plants. Infect Dis (Auckl). 2015;8:5-16.
11. Selem R, Rashed S, Younis M, et al. A novel green approach for treatment of immature Schis-tosomiasis mansoni infection in mice; Arabic gum (Acacia Senegal) antischistosomal properties. Afr J Pharm Pharmacol. 2018;12(29):436-45.
12. Abdullah TH, Kandil O, Elkadi A, et al. Garlic revisited: therapeutic for the major diseases of our times. J Natl Med Assoc. 1988;80(4):439–45.
13. Patya M, Zahalka MA, Vanichkin A, et al. Allicin stimulates lymphocytes and elicits an antitumor effect: a possible role of p21ras. Int Immunol. 2004;16(2):275-81.
14. Huang L, Song Y, Lian J, et al. Allicin inhibits the invasion of lung adenocarcinoma cells by altering tissue inhibitor of metalloproteinase/matrix metalloproteinase balance via reducing the activity of phosphoinositide 3-kinase/AKT signaling. Oncol Lett. 2017;14(1):468–74.
15. Metwally DM, Al-Olayan EM, Alanazi M, et al. Antischistosomal and anti-inflammatory activity of garlic and allicin compared with that of praziquantel in vivo. BMC Complement Altern Med. 2018;18(1):135.
16. Sunita K, Singh DK. Fascioliasis control: in vivo and in vitro phytotherapy of vector snail to kill Fasciola larva. J Parasitol Res. 2011;2011:240807.
17. Metwalley KM. Assessment of the antischisto-somal activity of some plant extracts against Schis-tosoma mansoni infection. World J Med Sci. 2015;12(2):162–9.
18. Sadrefozalayi S, Aslanipour B, Alan M, et al. De-termination and comparison of in vitro radical scavenging activity of both garlic oil and aqueous garlic extracts and their in vivo antioxidant effect on schistosomiasis disease in mice. Tur J Agric Food Sci Technol (TURJAF). 2018;6(7):820–7.
19. Lima CMBL, Freitas FIS, de Morais LCSL, et al. Ultrastructural study on the morphological changes to male worms of Schistosoma mansoni af-ter in vitro exposure to allicin. Rev Soc Bras Med Trop. 2011;44(3):327–30.
20. Buescher R, Yang L. Turmeric. In: Lauro GJ, Francis FJ, editors. Natural food colorants. New York: Marcel Dekker; 2000. p. 205–26.
21. Wang X, Hang Y, Liu J, et al. Anticancer effect of curcumin inhibits cell growth through miR-21/PTEN/Akt pathway in breast cancer cell. Oncol Lett. 2017;13(6):4825–31.
22. Venkatesan N. Curcumin attenuation of acute adriamycin myocardial toxicity in rats. Br J Pharmacol. 1998;124(3):425–7.
23. Aggarwal BB, Harikumar KB. Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol. 2009;41(1):40–59.
24. Tu C-T, Han B, Liu HC, et al. Curcumin protects mice against concanavalin A-induced hepatitis by inhibiting intrahepatic intercellular adhesion molecule-1(ICAM-1) and CXCL10 expression. Mol Cell Biochem. 2011;358(1-2):53–60.
25. Allam G. Immunomodulatory effects of curcu-min treatment on murine schistosomiasis mansoni. Immunobiology. 2009;214(8):712–27.
26. Mahmoud EA, Elbessoumy AA. Hematological and Biochemical Effects of Curcumin in Schisto-soma Mansoni Infested Mice. Assiut Vet Med J. 2014;60(142):184–95.
27. Hussein A, Rashed S, El hayawan I, et al. Evalua-tion of the anti-schistosomal effects of turmeric (Curcuma longa) versus praziquantel in Schistosoma mansoni infected mice. Iran J Parasitol. 2017;12(4):587-96.
28. Morais ER, Oliveira KC, Magalhães LG, et al. Ef-fects of curcumin on the parasite Schistosoma man-soni: A transcriptomic approach. Mol Biochem Parasitol. 2013;187:91–7.
29. De Aguiar DP, Moscardini MBM, Morais ER, et al. Curcumin generates oxidative stress and in-duces apoptosis in adult Schistosoma mansoni worms. PLoS One. 2016;11(11):e0167135.
30. Abdel-Zaher M, Abed GH, Abdel-Hakeem SS. Ultrastructural changes of Schistosoma mansoni worms associated with the administration of its polyvalent vaccine. JZOS. 2016;3(6):9-20.
31. Hassan EA, Abdel-Rahman MA, Ibrahim MM, et al. In vitro antischistosomal activity of venom from the Egyptian snake Cerastes cerastes. Rev Soc Bras Med Trop. 2016;49(6):752–7.
32. De Oliveira RN, Ferreira PM, Calado M, et al. Sesquiterpenes effects on DNA of Schistosoma mansoni after in vivo treatment. Gene Rep. 2018;11:205-12.
33. Sabah AA, Fletcher C, Webbe G, et al. Schistosoma mansoni: chemotherapy of infections of different ages. Exp Parasitol. 1986;61(3):294–303.
34. Mohamed AM, Metwally NM, Mahmoud SS. Sativa seeds against Schistosoma mansoni different stages. Mem Inst Oswaldo Cruz. 2005;100(2):205–11.
35. de Moraes J, Nascimento C, Yamaguchi LF, et al. Schistosoma mansoni: In vitro schistosomicidal activi-ty and tegumental alterations induced by piplartine on schistosomula. Exp Parasitol. 2012;132(2):222–7.
36. El-Faham MH, Eissa MM, Igetei JE, et al. Treatment of Schistosoma mansoni with miltefosine in vitro enhances serological recognition of defined worm surface antigens. PLoS Negl Trop Dis. 2017;11(8):e0005853.
37. World Health Organization (WHO). Molluscicide screening and evaluation. Bull World Health Organ. 1965;33(4):567-81.
38. Tchounwou PB, Englande AJ, Malek EA, et al. The effects of Bayluscide and Malathion on miracidial survival in schistosomiasis control. J Environ Sci Health B. 1991;26(1):69-82.
39. Ritchie LS, Lopez VA, Cola JM. Prolonged application of an organation against Biomphalaria glabrata and Schistosoma mansoni. In: Tomas C, editor. Molluscicides in Schistosomiasis Control. New York, London: Academic Press; 1974. p. 77-88.
40. Olivier L, Stirewalt MA. An efficient method for exposure of mice to cercariae of Schistosoma mansoni. J Parasitol. 1952;38(1):19-23.
41. Smithers SE, Terry RJ. The infection of laboratory hosts with cercariae of Schistosoma mansoni and the recovery of the adult worms. Parasitology. 1965;55(4):695–700.
42. Holtfreter MC, Loebermann MCM, Klammt S, et al. Schistosoma mansoni: schistosomicidal effect of mefloquine and primaquine in vitro. Exp Parasitol. 2011;127(1):270-6.
43. 43. El Bardicy S, El Sayed I, Yousif F, et al. Schistosomicidal and molluscicidal activities of amino alkylamino substituted neo- and norneocryptolepine derivatives. Pharm Biol. 2012;50(2):134–40.
44. Sambrook J, Russel DW. Molecular cloning: a laboratory manual. 3rd ed. Cold Spring: Harbour Laboratory Press; 2001.
45. Mantawy MM, Aly HF, Zayed N, et al. Antioxidant and schistosomicidal effect of Allium sativum and Allium cepa against Schistosoma mansoni different stages. Eur Rev Med Pharmacol Sci. 2012;3:69-80.
46. Shoheib ZS, El-Nouby KA, Deyab FA, et al. Potential effect of Curcuma longa extract on infectivity and pathogenicity of Schistosoma mansoni cercariae. J Egypt Soc Parasitol. 2008;38(1):141-59.
47. Magalhães LG, Machado CB, Morais ER, et al. In vitro schistosomicidal activity of curcumin against Schistosoma mansoni adult worms. Parasitol Res. 2009;104(5):1197–201.
48. Abou-Shady OM, Mohammed SS, Attia SS, et al. In vitro effect of mefloquine on adult Schistosoma mansoni. Res J Parasitol. 2015;10(3):111-9.
49. Hoffmann KF, Strand M. Molecular identification of a Schistosoma mansoni tegumental protein with similarity to cytoplasmic dynein light chains. J Biol Chem. 1996;271(42):26117-23.
50. Shuhua X, Binggui S, Utzinger J, et al. Ultrastructural alterations in adult Schistosoma mansoni caused by artemether. Mem Inst Oswaldo Cruz. 2002;97(5):717-24.
2. Deribew K, Tekeste Z, Petros B, et al. Urinary schistosomiasis and malaria associated anemia in Ethiopia. Asian Pac J Trop Biomed. 2013;3(4):307-10.
3. Coltart C, Whitty CJ. Schistosomiasis in non-endemic countries. Clin Med (lond). 2015;15(1):67-9.
4. World Health Organization (WHO). Report of the WHO informal consultation on schistosomiasis control. WHO/CDS/CPC/SIP/99, 2. Geneva: WHO; 1999.
5. Melman SD, Steinauer ML, Cunningham C, et al. Reduced susceptibility to praziquantel among naturally occurring Kenyan isolates of Schistosoma mansoni. PLoS Negl Trop Dis. 2009;3(8):e504.
6. Wang W, Dai JR, Li HJ, et al. Is there reduced susceptibility to praziquantel in Schistosoma japonicum? Evidence from Chin. Parasitology. 2010;137(13):1905–12.
7. Crellen T, Walker M, Lamberton PH, et al. Reduced efficacy of praziquantel against Schistosoma mansoni is associated with multiple rounds of mass drug administration. Clin Infect Dis. 2016;63(9):1151–9.
8. EL Shenawy NS, Soliman MFM, Reyad SI. The effect of antioxidant properties of aqueous garlic extract and Nigella sativa as anti-schistosomiasis agents in mice. Rev Inst Med Trop Sao Paulo. 2008;50(1):29–36.
9. Soliman FM. Evaluation of avocado/soybean unsaponifiable alone or concurrently with praziquantel in murine schistosomiasis. Acta Trop. 2012;122(3):261-6.
10. Ali SA, El-Regal NS, Saeed SM. The antischistosomal activity of two active constituents isolated from the leaves of Egyptian medicinal plants. Infect Dis (Auckl). 2015;8:5-16.
11. Selem R, Rashed S, Younis M, et al. A novel green approach for treatment of immature Schis-tosomiasis mansoni infection in mice; Arabic gum (Acacia Senegal) antischistosomal properties. Afr J Pharm Pharmacol. 2018;12(29):436-45.
12. Abdullah TH, Kandil O, Elkadi A, et al. Garlic revisited: therapeutic for the major diseases of our times. J Natl Med Assoc. 1988;80(4):439–45.
13. Patya M, Zahalka MA, Vanichkin A, et al. Allicin stimulates lymphocytes and elicits an antitumor effect: a possible role of p21ras. Int Immunol. 2004;16(2):275-81.
14. Huang L, Song Y, Lian J, et al. Allicin inhibits the invasion of lung adenocarcinoma cells by altering tissue inhibitor of metalloproteinase/matrix metalloproteinase balance via reducing the activity of phosphoinositide 3-kinase/AKT signaling. Oncol Lett. 2017;14(1):468–74.
15. Metwally DM, Al-Olayan EM, Alanazi M, et al. Antischistosomal and anti-inflammatory activity of garlic and allicin compared with that of praziquantel in vivo. BMC Complement Altern Med. 2018;18(1):135.
16. Sunita K, Singh DK. Fascioliasis control: in vivo and in vitro phytotherapy of vector snail to kill Fasciola larva. J Parasitol Res. 2011;2011:240807.
17. Metwalley KM. Assessment of the antischisto-somal activity of some plant extracts against Schis-tosoma mansoni infection. World J Med Sci. 2015;12(2):162–9.
18. Sadrefozalayi S, Aslanipour B, Alan M, et al. De-termination and comparison of in vitro radical scavenging activity of both garlic oil and aqueous garlic extracts and their in vivo antioxidant effect on schistosomiasis disease in mice. Tur J Agric Food Sci Technol (TURJAF). 2018;6(7):820–7.
19. Lima CMBL, Freitas FIS, de Morais LCSL, et al. Ultrastructural study on the morphological changes to male worms of Schistosoma mansoni af-ter in vitro exposure to allicin. Rev Soc Bras Med Trop. 2011;44(3):327–30.
20. Buescher R, Yang L. Turmeric. In: Lauro GJ, Francis FJ, editors. Natural food colorants. New York: Marcel Dekker; 2000. p. 205–26.
21. Wang X, Hang Y, Liu J, et al. Anticancer effect of curcumin inhibits cell growth through miR-21/PTEN/Akt pathway in breast cancer cell. Oncol Lett. 2017;13(6):4825–31.
22. Venkatesan N. Curcumin attenuation of acute adriamycin myocardial toxicity in rats. Br J Pharmacol. 1998;124(3):425–7.
23. Aggarwal BB, Harikumar KB. Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol. 2009;41(1):40–59.
24. Tu C-T, Han B, Liu HC, et al. Curcumin protects mice against concanavalin A-induced hepatitis by inhibiting intrahepatic intercellular adhesion molecule-1(ICAM-1) and CXCL10 expression. Mol Cell Biochem. 2011;358(1-2):53–60.
25. Allam G. Immunomodulatory effects of curcu-min treatment on murine schistosomiasis mansoni. Immunobiology. 2009;214(8):712–27.
26. Mahmoud EA, Elbessoumy AA. Hematological and Biochemical Effects of Curcumin in Schisto-soma Mansoni Infested Mice. Assiut Vet Med J. 2014;60(142):184–95.
27. Hussein A, Rashed S, El hayawan I, et al. Evalua-tion of the anti-schistosomal effects of turmeric (Curcuma longa) versus praziquantel in Schistosoma mansoni infected mice. Iran J Parasitol. 2017;12(4):587-96.
28. Morais ER, Oliveira KC, Magalhães LG, et al. Ef-fects of curcumin on the parasite Schistosoma man-soni: A transcriptomic approach. Mol Biochem Parasitol. 2013;187:91–7.
29. De Aguiar DP, Moscardini MBM, Morais ER, et al. Curcumin generates oxidative stress and in-duces apoptosis in adult Schistosoma mansoni worms. PLoS One. 2016;11(11):e0167135.
30. Abdel-Zaher M, Abed GH, Abdel-Hakeem SS. Ultrastructural changes of Schistosoma mansoni worms associated with the administration of its polyvalent vaccine. JZOS. 2016;3(6):9-20.
31. Hassan EA, Abdel-Rahman MA, Ibrahim MM, et al. In vitro antischistosomal activity of venom from the Egyptian snake Cerastes cerastes. Rev Soc Bras Med Trop. 2016;49(6):752–7.
32. De Oliveira RN, Ferreira PM, Calado M, et al. Sesquiterpenes effects on DNA of Schistosoma mansoni after in vivo treatment. Gene Rep. 2018;11:205-12.
33. Sabah AA, Fletcher C, Webbe G, et al. Schistosoma mansoni: chemotherapy of infections of different ages. Exp Parasitol. 1986;61(3):294–303.
34. Mohamed AM, Metwally NM, Mahmoud SS. Sativa seeds against Schistosoma mansoni different stages. Mem Inst Oswaldo Cruz. 2005;100(2):205–11.
35. de Moraes J, Nascimento C, Yamaguchi LF, et al. Schistosoma mansoni: In vitro schistosomicidal activi-ty and tegumental alterations induced by piplartine on schistosomula. Exp Parasitol. 2012;132(2):222–7.
36. El-Faham MH, Eissa MM, Igetei JE, et al. Treatment of Schistosoma mansoni with miltefosine in vitro enhances serological recognition of defined worm surface antigens. PLoS Negl Trop Dis. 2017;11(8):e0005853.
37. World Health Organization (WHO). Molluscicide screening and evaluation. Bull World Health Organ. 1965;33(4):567-81.
38. Tchounwou PB, Englande AJ, Malek EA, et al. The effects of Bayluscide and Malathion on miracidial survival in schistosomiasis control. J Environ Sci Health B. 1991;26(1):69-82.
39. Ritchie LS, Lopez VA, Cola JM. Prolonged application of an organation against Biomphalaria glabrata and Schistosoma mansoni. In: Tomas C, editor. Molluscicides in Schistosomiasis Control. New York, London: Academic Press; 1974. p. 77-88.
40. Olivier L, Stirewalt MA. An efficient method for exposure of mice to cercariae of Schistosoma mansoni. J Parasitol. 1952;38(1):19-23.
41. Smithers SE, Terry RJ. The infection of laboratory hosts with cercariae of Schistosoma mansoni and the recovery of the adult worms. Parasitology. 1965;55(4):695–700.
42. Holtfreter MC, Loebermann MCM, Klammt S, et al. Schistosoma mansoni: schistosomicidal effect of mefloquine and primaquine in vitro. Exp Parasitol. 2011;127(1):270-6.
43. 43. El Bardicy S, El Sayed I, Yousif F, et al. Schistosomicidal and molluscicidal activities of amino alkylamino substituted neo- and norneocryptolepine derivatives. Pharm Biol. 2012;50(2):134–40.
44. Sambrook J, Russel DW. Molecular cloning: a laboratory manual. 3rd ed. Cold Spring: Harbour Laboratory Press; 2001.
45. Mantawy MM, Aly HF, Zayed N, et al. Antioxidant and schistosomicidal effect of Allium sativum and Allium cepa against Schistosoma mansoni different stages. Eur Rev Med Pharmacol Sci. 2012;3:69-80.
46. Shoheib ZS, El-Nouby KA, Deyab FA, et al. Potential effect of Curcuma longa extract on infectivity and pathogenicity of Schistosoma mansoni cercariae. J Egypt Soc Parasitol. 2008;38(1):141-59.
47. Magalhães LG, Machado CB, Morais ER, et al. In vitro schistosomicidal activity of curcumin against Schistosoma mansoni adult worms. Parasitol Res. 2009;104(5):1197–201.
48. Abou-Shady OM, Mohammed SS, Attia SS, et al. In vitro effect of mefloquine on adult Schistosoma mansoni. Res J Parasitol. 2015;10(3):111-9.
49. Hoffmann KF, Strand M. Molecular identification of a Schistosoma mansoni tegumental protein with similarity to cytoplasmic dynein light chains. J Biol Chem. 1996;271(42):26117-23.
50. Shuhua X, Binggui S, Utzinger J, et al. Ultrastructural alterations in adult Schistosoma mansoni caused by artemether. Mem Inst Oswaldo Cruz. 2002;97(5):717-24.
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| Issue | Vol 16 No 1 (2021) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijpa.v16i1.5540 | |
| Keywords | ||
| Schistosoma mansoni Allicin Curcumin Ultrastructural DNA | ||
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How to Cite
1.
El-Hak RASHED H, ABU ALMAATY A, SOLIMAN M, EL-SHENAWY N. The in Vitro Antischistosomal Activity and Genotoxicity of the Active Ingredients of Allium sativum (allicin) and Curcuma longa (curcumin). Iran J Parasitol. 2021;16(1):101-110.
