PMID- 30032733
OWN - NLM
STAT- MEDLINE
DCOM- 20190807
LR  - 20190807
IS  - 1475-2697 (Electronic)
IS  - 0022-149X (Linking)
VI  - 93
IP  - 5
DP  - 2019 Sep
TI  - Antifilarial activity of azadirachtin fuelled through reactive oxygen species 
      induced apoptosis: a thorough molecular study on Setaria cervi.
PG  - 519-528
LID - 10.1017/S0022149X18000615 [doi]
AB  - Efficacious therapeutic strategies against lymphatic filariasis are always sought 
      after. However, natural products are a promising resource for developing 
      effective antifilarial agents. Azadirachtin, a significant tetranortriterpenoid 
      phytocompound found in Azadirachta indica, was evaluated in vitro for 
      antifilarial potential against the filarial parasite Setaria cervi. Dye exclusion 
      and MTT assay confirmed the antifilarial potential of azadirachtin against S. 
      cervi with a median lethal dose (LC50) of 6.28 mug/ml for microfilariae (mf), and 
      9.55 mug/ml for adult parasites. Morphological aberrations were prominent in the 
      histological sections of the azadirachtin-exposed parasites. Moreover, 
      alterations in the reactive oxygen species (ROS) parameters in treated parasites 
      were evident. Induction of apoptosis in treated parasites was confirmed by DNA 
      laddering, acridine orange (AO)/ethidium bromide (EtBr) double staining and in 
      situ DNA fragmentation. The downregulation of anti-apoptotic CED-9 and 
      upregulation of proapoptotic EGL-1, CED-4 and CED-3 at both the transcription and 
      translation levels confirmed apoptosis execution at the molecular level. Changes 
      in the gene expressions of nuc-1, cps-6 and crn-1 further clarified the molecular 
      cause of DNA degradation. Furthermore, azadirachtin was found to be non-toxic in 
      both in vitro and in vivo toxicity analyses. Therefore, the experimental evidence 
      detailed the pharmacological effectiveness of azadirachtin as a possible 
      therapeutic agent against filariasis.
FAU - Mukherjee, N
AU  - Mukherjee N
AD  - Parasitology Laboratory,Department of Zoology (Centre for Advanced 
      Studies),Visva-Bharati University,Santiniketan 731 235,West Bengal,India.
FAU - Joardar, N
AU  - Joardar N
AD  - Parasitology Laboratory,Department of Zoology (Centre for Advanced 
      Studies),Visva-Bharati University,Santiniketan 731 235,West Bengal,India.
FAU - Sinha Babu, S P
AU  - Sinha Babu SP
AUID- ORCID: 0000-0002-7441-6426
AD  - Parasitology Laboratory,Department of Zoology (Centre for Advanced 
      Studies),Visva-Bharati University,Santiniketan 731 235,West Bengal,India.
LA  - eng
PT  - Journal Article
DEP - 20180723
PL  - England
TA  - J Helminthol
JT  - Journal of helminthology
JID - 2985115R
RN  - 0 (Anthelmintics)
RN  - 0 (Helminth Proteins)
RN  - 0 (Limonins)
RN  - 0 (Plant Extracts)
RN  - 0 (Reactive Oxygen Species)
RN  - O4U1SAF85H (azadirachtin)
MH  - Animals
MH  - Anthelmintics/*pharmacology
MH  - *Apoptosis
MH  - DNA Fragmentation
MH  - Elephantiasis, Filarial/drug therapy
MH  - Female
MH  - Helminth Proteins/genetics
MH  - Lethal Dose 50
MH  - Limonins/*pharmacology
MH  - Male
MH  - Plant Extracts/*pharmacology
MH  - Reactive Oxygen Species/*metabolism
MH  - Setaria Nematode/*drug effects/genetics
OTO - NOTNLM
OT  - Setaria cervi
OT  - anthelmintic
OT  - apoptosis
OT  - azadirachtin
OT  - lymphatic filariasis
OT  - reactive oxygen species
OT  - toxicity
EDAT- 2018/07/24 06:00
MHDA- 2019/08/08 06:00
CRDT- 2018/07/24 06:00
PHST- 2018/07/24 06:00 [pubmed]
PHST- 2019/08/08 06:00 [medline]
PHST- 2018/07/24 06:00 [entrez]
AID - S0022149X18000615 [pii]
AID - 10.1017/S0022149X18000615 [doi]
PST - ppublish
SO  - J Helminthol. 2019 Sep;93(5):519-528. doi: 10.1017/S0022149X18000615. Epub 2018 
      Jul 23.