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Airways Relaxant and Antiasthmatic Activity of Aconitum heterophyllum Wall ex Royle. Roots: A Mechanistic Insight

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Abstract

Aconitum heterophyllum Wall ex Royle. (Ranunculaceae) is a traditional medicinal herb that has shown extensive pharmacological potential to treat cough, diarrhea, and infectious diseases but no scientific evidence is available to validate its antiasthmatic potential. In this study, we have investigated the tracheal relaxation and antiasthmatic activity of the selected bioactive fraction of A. heterophyllum. Chemical profiling of the most effective fraction obtained via bioassay-guided fractionation was done using LC-MS (Liquid chromatography-mass spectrometry, a technique utilized in the identification, separation, and quantification of known and unknown compounds). Molecular docking analysis of characterized constituents was performed to recognize the binding receptors, followed by an evaluation of the tracheal relaxation ability of active fraction. An acute oral toxicity study of the most effective fraction was done using OECD guidelines 423. Further, the therapeutic efficacy of the fraction was validated in asthma using a guinea pig model of ovalbumin (OVA) induced allergic asthma. The bio-guided activity revealed that hydro-methanolic extract of A. heterophyllum roots (F-1) was the most active fraction. LC-MS analysis of F-1 showed the presence of six major bioactive compounds in F-1. Molecular docking studies revealed strong binding affinities of identified constituents with histaminic receptor (H1) and muscarinic receptor (M3). The ex vivo study demonstrated smooth muscle relaxant activity of F-1 via dysregulating diverse signal transduction pathways viz. histaminic and muscarinic receptors antagonism (non-competitive), stimulation of β2-adrenergic receptor pathway, and soluble guanylyl cyclase activation. The findings of acute oral toxicity studies revealed that F-1 had no toxicity up to the dose of 2000 mg/Kg. The anti-asthmatic therapeutic efficacy of F-1 was further confirmed by the amelioration of respiratory hyperresponsiveness in asthmatic guinea pigs. This is the first evidence-based study showing the antiasthmatic therapeutic potential of the traditionally used herb A. heterophyllum through, computational and animal studies.

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Abbreviations

Ach:

acetylcholine

A. heterophyllum :

Aconitum heterophyllum

Cdyn:

dynamic compliance

CRC:

concentration-response curve

COX:

cyclooxygenase

CPCSEA:

committee for the purpose of control and supervision of experiments on animals

DAG:

1,2-diacylglycerol

EC50 :

half maximal inhibitory concentration

F-1:

chloroform fraction of hydro-methanolic extract of A. heterophyylum roots

His:

histamine

IAEC:

Institutional Animal Ethical Committee

IgE:

immunoglobulin E

IL-4:

interleukin-4

IL-13:

interleukin-13

IP3:

1,4,5-trisphosphate

L-NAME:

Nω-nitro-L-arginine methyl ester

NOS:

nitric oxide synthase

ODQ:

1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one

OPA:

O-phthalaldehyde

OVA:

ovalbumin

ROCK:

Rho-associated kinase

sRaw:

specific resistance

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Acknowledgements

We are thankful to the late Prof. Aditya Shastri, Vice-Chancellor, Banasthali Vidyapith, Rajasthan, India for granting all the financial and institutional support required for the successful accomplishment of this research work.

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Authors and Affiliations

  1. Department of Pharmacy, Banasthali Vidyapith, Banasthali, Rajasthan, India

    Ritika Gururani, Akansha Bisht, Kajal Kumari, Sarvesh Paliwal & Swapnil Sharma

  2. Department of Pharmacology, Saveetha College of Pharmacy, Saveetha Institute of Medical and Technical Sciences, Chennai, India

    Saraswati Patel

  3. Department of Pharmacy, Central University of Rajasthan, Ajmer, India

    Smita Jain

  4. Department of Chemistry, Banasthali Vidyapith, Banasthali, Rajasthan, India

    Jaya Dwivedi

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  1. Ritika Gururani
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Contributions

R.G: Investigation and draft writing, S.P: Statistical analysis, A.B: Data curation, SJ: Contributed to draft writing, SaP Conceptualization and editing, JD: Visualization and supervision Swapnil Sharma: Conceptualization, supervision, and visualization.

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Correspondence to Sarvesh Paliwal or Swapnil Sharma.

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Gururani, R., Patel, S., Bisht, A. et al. Airways Relaxant and Antiasthmatic Activity of Aconitum heterophyllum Wall ex Royle. Roots: A Mechanistic Insight. Cell Biochem Biophys (2024). https://doi.org/10.1007/s12013-024-01374-x

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