Background <p><i>Tylophora</i> species produce phenanthroindolizidine alkaloids (PIAs) and are traditionally used for treating allergic disorders. However, the antiallergic potential of individual PIAs and the mechanisms involved are not known. This study aimed to explore the antiasthmatic potential of <i>Tylophora</i> PIAs through network pharmacology. It also compared in vivo antiallergic potential of <i>Tylophora</i> species containing (<i>T. indica</i>) or deficient in (<i>T. pauciflora</i>) the key PIA, tylophorine.</p> Methods <p>Network pharmacology predicted bioactive PIAs, potential targets and molecular mechanisms, whereas molecular docking evaluated interactions between PIAs and targets. Various extracts of <i>T. indica</i> [aqueous (TiAq), hydroalcoholic (TiHA), ethanolic (TiEt)] and <i>T. pauciflora</i> [aqueous (TpAq), hydroalcoholic (TpHA), ethanolic (TpEt)] were assessed for efficacy against C48/80-induced anaphylaxis in mice at 200&#xa0;mg/kg BW oral dose. Promising extracts were evaluated against ovalbumin (OVA)-induced asthma in mice.</p> Results <p>Twelve PIAs were assessed in silico for antiallergic potential. TiHA and TpHA (both 200&#xa0;mg/kg BW) were most effective regarding inhibition of mortality and histamine level with the former performing better. In OVA-induced asthma, both extracts reduced inflammatory cell count in blood and bronchoalveolar lavage fluid. OVA-specific IgE and cytokines IL-4, IL-5, IL-13, and TGF-β were reduced, whereas IFN-γ was enhanced by extracts. Also, transcript abundance of IL-4, IL-5, IL-13, and TGF-β decreased and of IFN-γ increased in lungs and lung inflammatory score reduced significantly. TiHA and TpHA were safe up to 2000&#xa0;mg/kg BW.</p> Conclusion <p>TiHA and TpHA (both 200&#xa0;mg/kg BW) possess significant antiallergic potential, possibly due to the holistic effect of phytomolecules. However, tylophorine itself may not be responsible for the antiallergic effect of <i>Tylophora</i> species.</p> Graphical abstract <p></p>

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Comparison of Tylophora indica with Tylophora pauciflora coupled with network pharmacology of phenanthroindolizidine alkaloids sheds light on its antiallergic potential

  • Pratibha,
  • Amit Kaushik,
  • Aqib Sarfraz,
  • Saumya Shah,
  • Mridula Sahu,
  • Feroz Khan,
  • Velusamy Sundaresan,
  • Puja Khare,
  • Karuna Shanker,
  • Daya N. Mani,
  • Ashutosh K. Shukla

摘要

Background

Tylophora species produce phenanthroindolizidine alkaloids (PIAs) and are traditionally used for treating allergic disorders. However, the antiallergic potential of individual PIAs and the mechanisms involved are not known. This study aimed to explore the antiasthmatic potential of Tylophora PIAs through network pharmacology. It also compared in vivo antiallergic potential of Tylophora species containing (T. indica) or deficient in (T. pauciflora) the key PIA, tylophorine.

Methods

Network pharmacology predicted bioactive PIAs, potential targets and molecular mechanisms, whereas molecular docking evaluated interactions between PIAs and targets. Various extracts of T. indica [aqueous (TiAq), hydroalcoholic (TiHA), ethanolic (TiEt)] and T. pauciflora [aqueous (TpAq), hydroalcoholic (TpHA), ethanolic (TpEt)] were assessed for efficacy against C48/80-induced anaphylaxis in mice at 200 mg/kg BW oral dose. Promising extracts were evaluated against ovalbumin (OVA)-induced asthma in mice.

Results

Twelve PIAs were assessed in silico for antiallergic potential. TiHA and TpHA (both 200 mg/kg BW) were most effective regarding inhibition of mortality and histamine level with the former performing better. In OVA-induced asthma, both extracts reduced inflammatory cell count in blood and bronchoalveolar lavage fluid. OVA-specific IgE and cytokines IL-4, IL-5, IL-13, and TGF-β were reduced, whereas IFN-γ was enhanced by extracts. Also, transcript abundance of IL-4, IL-5, IL-13, and TGF-β decreased and of IFN-γ increased in lungs and lung inflammatory score reduced significantly. TiHA and TpHA were safe up to 2000 mg/kg BW.

Conclusion

TiHA and TpHA (both 200 mg/kg BW) possess significant antiallergic potential, possibly due to the holistic effect of phytomolecules. However, tylophorine itself may not be responsible for the antiallergic effect of Tylophora species.

Graphical abstract