Reversion of Asthmatic Complications and Mast Cell Signalling Pathways in BALB/c Mice Model Using Quercetin Nanocrystals.
The tranquillizing effects of quercetin on allergic asthma are promising, but its poor water solubility and bioavailability is still a bottleneck. In this study, an ovalbumin (OVA) sensitized BALB/c mice asthma model was used to investigate the potential of quercetin nanocrystals (nQ) on relieving asthma aggravation. The water soluble nQ was prepared by the homogenization using the high energy sonication method. X-ray diffraction data showed the formation of nQ (10-30 nm) which was in agreement with transmission electron microscopy. The nQ was found to be more stable and soluble in PBS, and sera of BALB/c mice compared to bulk quercetin. Dose dependent experiments with nQ on OVA sensitized asthma mice exhibited significant anti-asthmatic potential of nQ at much lower dose (1 mg/kg body weight) compared to bulk quercetin. The treatment of nQ remarkably resulted in reduced OVA specific immunoglobulin E (sIgE) production, anaphylaxis signs and type 1 skin test. The nQ also significantly modulated the expression of Th2 cytokines like IL-4 and IL-5, which are responsible for IgE class switching and suppressed the degranulation/secretion of different chemical mediators (PGD2, mMCPT-1 Cys-L and TSLP) from activated mast cells. The levels of FcεR1, Syk, c-Yes, PI-3, p-PI-3, PLC-γ2, and p-PLC-γ2 were found to be reduced in the OVA sensitized BALB/c mice treated with nQ compared to those treated with OVA only. The results indicate that nQ alleviate pulmonary inflammation and airway hyporesponsiveness in allergic asthma at much lower dose compared to bulk quercetin and may be considered as a potential drug for the treatment of asthmatic patients.
Kriti
K
Gupta
Sandeep
S
Kumar
Rinkesh Kumar
RK
Gupta
Akanksha
A
Sharma
Alok K
AK
Verma
K
K
Stalin
Bhushan P
BP
Chaudhari
Mukul
M
Das
Surinder P
SP
Singh
Premendra D
PD
Dwivedi
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000737:chemistry; D000975:Antioxidants / Q000008:administration & dosage / Q000737:chemistry; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D011794:Quercetin / Q000008:administration & dosage* / Q000737:chemistry; D012074:Remission Induction / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D016896:Treatment Outcome
D018927:Anti-Asthmatic Agents; D000975:Antioxidants; D016207:Cytokines; D053769:Nanocapsules; D011794:Quercetin