Preclinical safety and anti-inflammatory activity of a standardized Justicia pectoralis Jacq. extract in experimental models of respiratory inflammation.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Justicia pectoralis Jacq. (Acanthaceae), known as chambá, is traditionally used in Latin America for respiratory ailments as an expectorant with bronchodilatory and anti-inflammatory properties. However, scientific validation of its efficacy and safety is limited. AIM OF THE STUDY: To develop a standardized extract (TI-138) and evaluate its stability, pharmacokinetics, efficacy, safety, and molecular mechanism of action. METHODS: The extract was standardized and characterised by LC-MS/MS. Pharmacokinetics and CYP3A4 interaction were studied in rats. Efficacy was assessed in three respiratory models. Mechanistic insights were obtained via PCR array, RT-qPCR, and ELISA. Safety was assessed through genotoxicity assays, acute and long-term toxicity studies, and CNS, cardiovascular, and respiratory safety pharmacology conducted under GLP conditions. RESULTS: TI-138 showed a stable phytochemical profile for over two years and four months and good oral absorption. In rats, pharmacokinetics showed rapid absorption (0.25 h) with peak plasma levels of ∼1.5 μg/mL (coumarin) and 2.0 μg/mL (o-coumaric acid). Orally administered TI-138 had expectorant and antitussive effects, reduced airway inflammation and remodelling in asthma, and modulated inflammatory and immune-related gene expression. Safety studies showed no genotoxicity and acceptable toxicity at therapeutic doses. Notably, TI-138 suppressed the expression of several important genes involved in pro-inflammatory and immune-regulatory pathways, including Cd19, Ctla4, Cyp7a1, H2-Eb1, Il2, Il4, Il10, Il13, Il17a, and Tnf, and reduced the expression of Ccl19, Ccl5, Ccr4, Cd28, and Cd4 to levels below those observed in animals challenged with saline alone (saline + vehicle). Also of relevance, TI-138 significantly reduced pulmonary levels of pro-inflammatory cytokines-including IL-5, IL-13, and TNF-α-as well as IgE production. CONCLUSIONS: The standardized Justicia pectoralis extract (TI-138) demonstrated efficacy in preclinical models of respiratory inflammation and cough, with no genotoxicity and a favourable safety profile. Its activity appears to involve the modulation of relevant genes associated with airway inflammation, supporting further clinical studies to develop a new, approved phytomedicine for clinical use.