TY - JOUR
T1 - Allicin enhances antimicrobial activity of macrophages during Mycobacterium tuberculosis infection
AU - Dwivedi, Ved Prakash
AU - Bhattacharya, Debapriya
AU - Singh, Mona
AU - Bhaskar, Ashima
AU - Kumar, Santosh
AU - Fatima, Samreen
AU - Sobia, Parveen
AU - Kaer, Luc Van
AU - Das, Gobardhan
N1 - Funding Information:
We acknowledge the support of the DBT-supported Tuberculosis Aerosol Challenge Facility at the International Centre for Genetic Engineering and Biotechnology (ICGEB, New Delhi, India) and their staff in accomplishing this work. VPD and AB and are the recipients of a DST-INSPIRE Faculty Fellowship. VPD is also the recipient of an Early Career Research Award (ECRA), Science and Engineering Research Board (SERB), Department of Science and Technology (DST), Government of India. DB is the recipient of Senior Research Associateship of the Council of Scientific and Industrial Research (CSIR), Government of India. We acknowledge financial support from the Department of Science and Technology (DST) and the Department of Biotechnology (DBT), Govt. of India. Ved Prakash Dwivedi, Debapriya Bhattacharya, Mona Singh, Ashima Bhaskar, Santosh Kumar and Parveen Sobia performed the experiments. Ved Prakash Dwivedi, Debapriya Bhattacharya, Ashima Bhaskar, Luc Van Kaer and Gobardhan Das wrote the manuscript. The authors confirm that there are no conflicts of interest.
Funding Information:
We acknowledge the support of the DBT-supported Tuberculosis Aerosol Challenge Facility at the International Centre for Genetic Engineering and Biotechnology (ICGEB, New Delhi, India) and their staff in accomplishing this work. VPD and AB and are the recipients of a DST-INSPIRE Faculty Fellowship. VPD is also the recipient of an Early Career Research Award (ECRA), Science and Engineering Research Board (SERB), Department of Science and Technology (DST), Government of India. DB is the recipient of Senior Research Associateship of the Council of Scientific and Industrial Research (CSIR), Government of India. We acknowledge financial support from the Department of Science and Technology ( DST ) and the Department of Biotechnology ( DBT ), Govt. of India.
Publisher Copyright:
© 2018
PY - 2019/10/28
Y1 - 2019/10/28
N2 - Ethnopharmacological relevance: The emergence of drug-resistant Mycobacterium tuberculosis (M.tb) strains has severely hampered global efforts towards tuberculosis (TB) eradication. The internationally accepted therapy “Directly Observed Treatment Short-course (DOTS)” is lengthy, and incorporates risks for the generation of drug-resistant M.tb variants. Multiple and extremely drug-resistant (MDR and XDR) variants of TB are now widespread throughout the globe, and totally drug-resistant (TDR) strains have appeared. Therefore, new classes of antibiotics are urgently needed to combat these deadly organisms. Historically, garlic is known to kill mycobacterial strains, and its active compound, allicin, kills various microorganisms. Here we have shown that allicin not only reduced the bacterial burden in the lungs of mice infected with Mycobacterium tuberculosis (M.tb), but also induces strong anti-tubercular immunity. Materials and methods: In the present study, the anti-mycobacterial and immunomodulatory activity of garlic extract and its pure constituent allicin were demonstrated based on several in vitro and in vivo experiments in murine model of tuberculosis. Furthermore, the validation of study was done by immunoblots showing the modulation of MAPK and SAPK/JNK signaling by allicin in macrophages. Results: Here, we report that allicin/garlic extract exhibits strong anti-mycobacterial responses in vitro and in vivo against drug-sensitive, MDR and XDR strains of TB. In addition to direct killing, allicin also induced pro-inflammatory cytokines in macrophages. Moreover, allicin/garlic extract treatment in murine models of infection resulted in induction of strong protective Th1 response, leading to drastic reduction in mycobacterial burden. These results indicated that allicin/garlic extract has both antibacterial and immunomodulatory activity. Furthermore, garlic extract reversed the immune dampening effects of frontline anti-TB drugs. Conclusion: Allicin/garlic extract alone or as an adjunct to classical antibiotics holds great promise for treatment of drug-sensitive as well as drug-resistant TB. These results warrant further study and validation of allicin for treatment of TB.
AB - Ethnopharmacological relevance: The emergence of drug-resistant Mycobacterium tuberculosis (M.tb) strains has severely hampered global efforts towards tuberculosis (TB) eradication. The internationally accepted therapy “Directly Observed Treatment Short-course (DOTS)” is lengthy, and incorporates risks for the generation of drug-resistant M.tb variants. Multiple and extremely drug-resistant (MDR and XDR) variants of TB are now widespread throughout the globe, and totally drug-resistant (TDR) strains have appeared. Therefore, new classes of antibiotics are urgently needed to combat these deadly organisms. Historically, garlic is known to kill mycobacterial strains, and its active compound, allicin, kills various microorganisms. Here we have shown that allicin not only reduced the bacterial burden in the lungs of mice infected with Mycobacterium tuberculosis (M.tb), but also induces strong anti-tubercular immunity. Materials and methods: In the present study, the anti-mycobacterial and immunomodulatory activity of garlic extract and its pure constituent allicin were demonstrated based on several in vitro and in vivo experiments in murine model of tuberculosis. Furthermore, the validation of study was done by immunoblots showing the modulation of MAPK and SAPK/JNK signaling by allicin in macrophages. Results: Here, we report that allicin/garlic extract exhibits strong anti-mycobacterial responses in vitro and in vivo against drug-sensitive, MDR and XDR strains of TB. In addition to direct killing, allicin also induced pro-inflammatory cytokines in macrophages. Moreover, allicin/garlic extract treatment in murine models of infection resulted in induction of strong protective Th1 response, leading to drastic reduction in mycobacterial burden. These results indicated that allicin/garlic extract has both antibacterial and immunomodulatory activity. Furthermore, garlic extract reversed the immune dampening effects of frontline anti-TB drugs. Conclusion: Allicin/garlic extract alone or as an adjunct to classical antibiotics holds great promise for treatment of drug-sensitive as well as drug-resistant TB. These results warrant further study and validation of allicin for treatment of TB.
KW - Adjunct therapy
KW - Allicin
KW - Garlic extract
KW - Mycobacterium tuberculosis
KW - T cells
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U2 - 10.1016/j.jep.2018.12.008
DO - 10.1016/j.jep.2018.12.008
M3 - Article
C2 - 30537531
AN - SCOPUS:85069848867
SN - 0378-8741
VL - 243
JO - Journal of Ethnopharmacology
JF - Journal of Ethnopharmacology
M1 - 111634
ER -