PMID- 35980291
OWN - NLM
STAT- MEDLINE
DCOM- 20220908
LR  - 20220913
IS  - 1543-8392 (Electronic)
IS  - 1543-8384 (Linking)
VI  - 19
IP  - 9
DP  - 2022 Sep 5
TI  - Therapeutic Potential of Quercetin-Loaded Nanoemulsion against Experimental 
      Visceral Leishmaniasis: In Vitro/Ex Vivo Studies and Mechanistic Insights.
PG  - 3367-3384
LID - 10.1021/acs.molpharmaceut.2c00492 [doi]
AB  - Visceral leishmaniasis (VL) is one of the most fatal and neglected tropical 
      diseases caused by Leishmania donovani (L. donovani). The applications of 
      currently available chemotherapy (amphotericin B, miltefosine, and others) in VL 
      treatment have been limited due to their poor bioavailability, unfavorable 
      toxicity profile, and prolonged parenteral dosing. Quercetin (QT), a potent 
      natural antioxidant, is a prominent target when conducting investigations on 
      alternative therapies against L. donovani infections. However, the therapeutic 
      applications of QT have been restricted due to its low solubility and 
      bioavailability. In the present study, we developed and evaluated the 
      antileishmanial activity (ALA) of quercetin-loaded nanoemulsion (QTNE) against L. 
      donovani clinical strains. In vitro anti-promastigote assay results demonstrated 
      that QTNE (IC(50) 6.6 muM, 48 h) significantly inhibited the growth of parasites 
      more efficiently than the pure QT suspension in a dose- and time-dependent 
      manner. Results of the anti-amastigote assay revealed that the infected 
      macrophages (%) of QTNE were significantly more than those of the pure QT 
      suspension at all concentrations (6.6, 26.4, and 52.8 muM; p < 0.05, p < 0.01 
      compared to the control). Moreover, the results of in vitro and ex vivo studies 
      assisted in determining the mechanistic insights associated with the ALA of QTNE. 
      The overall findings suggested that QTNE exhibited potential ALA by enhancing the 
      intracellular ROS and nitric oxide levels, inducing distortion of membrane 
      integrity and phosphatidylserine release (AV/PI), rupturing the parasite DNA 
      (late apoptosis/necrosis process), and upregulating the immunomodulatory effects 
      (IFN-gamma and IL-10 levels). Additionally, QTNE showed superior biocompatibility 
      against all of the treated healthy cells (PBMCs, PECs, and BMCs) as compared to 
      the control. In conclusion, QTNE acts as a potential antileishmanial agent 
      targeting both promastigote and intracellular amastigote forms of L. donovani, 
      which thus opens a new avenue for the use of QTNE in VL therapy.
FAU - Das, Sabya Sachi
AU  - Das SS
AUID- ORCID: 0000-0002-4042-8525
AD  - Department of Pharmaceutical Sciences and Technology, Birla Institute of 
      Technology, Mesra, Ranchi 835215, Jharkhand, India.
FAU - Dubey, Amit Kumar
AU  - Dubey AK
AD  - Department of Biotechnology, National Institute of Pharmaceutical Education and 
      Research (NIPER) Hajipur, Vaishali 844102, Bihar, India.
AD  - Parasite Immunology Lab, Division of Microbiology, Indian Council of Medical 
      Research (ICMR)-Rajendra Memorial Research Institute of Medical Sciences 
      (RMRIMS), Patna 800007, Bihar, India.
FAU - Verma, Priya Ranjan Prasad
AU  - Verma PRP
AD  - Department of Pharmaceutical Sciences and Technology, Birla Institute of 
      Technology, Mesra, Ranchi 835215, Jharkhand, India.
FAU - Singh, Shubhankar Kumar
AU  - Singh SK
AD  - Parasite Immunology Lab, Division of Microbiology, Indian Council of Medical 
      Research (ICMR)-Rajendra Memorial Research Institute of Medical Sciences 
      (RMRIMS), Patna 800007, Bihar, India.
FAU - Singh, Sandeep Kumar
AU  - Singh SK
AUID- ORCID: 0000-0001-5702-4554
AD  - Department of Pharmaceutical Sciences and Technology, Birla Institute of 
      Technology, Mesra, Ranchi 835215, Jharkhand, India.
LA  - eng
PT  - Journal Article
DEP - 20220818
PL  - United States
TA  - Mol Pharm
JT  - Molecular pharmaceutics
JID - 101197791
RN  - 0 (Antiprotozoal Agents)
RN  - 9IKM0I5T1E (Quercetin)
SB  - IM
MH  - Animals
MH  - *Antiprotozoal Agents/pharmacology/therapeutic use
MH  - Humans
MH  - *Leishmania donovani
MH  - *Leishmaniasis, Visceral/drug therapy/parasitology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Quercetin/pharmacology/therapeutic use
OTO - NOTNLM
OT  - QTNE
OT  - antileishmanial activity
OT  - cell death
OT  - immunomodulatory effects
OT  - targeted drug delivery
OT  - visceral leishmaniasis
EDAT- 2022/08/19 06:00
MHDA- 2022/09/09 06:00
CRDT- 2022/08/18 10:05
PHST- 2022/08/19 06:00 [pubmed]
PHST- 2022/09/09 06:00 [medline]
PHST- 2022/08/18 10:05 [entrez]
AID - 10.1021/acs.molpharmaceut.2c00492 [doi]
PST - ppublish
SO  - Mol Pharm. 2022 Sep 5;19(9):3367-3384. doi: 10.1021/acs.molpharmaceut.2c00492. 
      Epub 2022 Aug 18.