Ethnopharmacological validation of Capparis spinosa L. in gastrointestinal and respiratory disorders: Evidence from in vitro, in vivo, and in silico models.

C. spinosa shows potential for reducing diarrheal episodes and fluid accumulation in animal models, supporting its traditional use for gastrointestinal issues.

Summary and findings

The study evaluated the traditional use of Capparis spinosa L. for gastrointestinal and respiratory disorders using in vitro, in vivo, and in silico methods. The hydroethanolic extract of C. spinosa L. was tested at doses of 50-200 mg/kg. Significant reductions in diarrheal episodes and fluid accumulation were observed.

Abstract

<h4>Ethnopharmacological relevance</h4>Capparis spinosa L. is traditionally used in Pakistan to treat gastrointestinal and respiratory ailments, yet its multi-target pharmacological mechanisms remain poorly understood.<h4>Aim of the study</h4>To evaluate the traditional use of Capparis spinosa L. in asthma, diarrhea, and spasm using integrated in vitro, in vivo, and in silico approaches.<h4>Methodology</h4>Hydroethanolic extract of C. spinosa L. (Cap.Cr) was analyzed by LC ESI-MS/MS. Antispasmodic and bronchodilator activities of Cap.Cr and its fractions (Ethyl acetate, n-hexane, aqueous) were assessed using isolated jejunal segments from rabbit intestine, trachea, and urinary bladder. Antidiarrheal potential was assessed in mice using castor oil-induced diarrhea, enteropooling, and intestinal transit models. Rat fecal samples were analyzed via qRT-PCR to assess the presence of Firmicutes, Lactobacillus, and V2. Molecular docking explored interactions with calcium channels and muscarinic receptors.<h4>Results</h4>LC ESI-MS/MS study identified 26 bioactive flavonoids and alkaloids. In vitro, Cap.Cr and its fractions relaxed the contractions provoked by high K⁺ and carbachol (CCh) across all tissues. The extracts shifted the Ca²⁺ and carbachol cumulative response curves (CRCs), suggesting dicyclomine-like dual Ca²⁺ antagonistic and antimuscarinic mechanism. In vivo, C. spinosa (50-200 mg/kg) significantly (p < 0.05) lessened diarrheal episodes, fluid accumulation, and intestinal transit showing efficacy comparable to loperamide and atropine. Microbiota analysis indicated an increase in Firmicutes and Lactobacillus levels by C. spinosa. In silico docking suggested high binding affinities for muscarinic receptors (M₃) and voltage-gated Ca²⁺ channels.<h4>Conclusion</h4>C. spinosa L. exerts potent antispasmodic, bronchodilator, and antidiarrheal effects and may involve Ca²⁺ channel blockade and muscarinic antagonism, demonstrating pharmacological justification for its traditional use in gut and airway dysfunctions.

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