Preclinical Safety and Anti-inflammatory Activity of a Standardized Justicia pectoralis Jacq. Extract in Experimental Models of Respiratory Inflammation.
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.
To develop a standardised extract (TI-138) and evaluate its stability, pharmacokinetics, efficacy, safety, and molecular mechanism of action.
The extract was standardised 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.
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.
The standardised 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.
To develop a standardised extract (TI-138) and evaluate its stability, pharmacokinetics, efficacy, safety, and molecular mechanism of action.
The extract was standardised 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.
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.
The standardised 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.
Authors
Tolouei Tolouei, Macedo Júnior Macedo Júnior, Potrich Potrich, de Andrade de Andrade, Dos Santos Dos Santos, Freitas Freitas, Heller Heller, Vilela Vilela, Rocha Rocha, Zimath Zimath, Fadanni Fadanni, Marques Marques, de Mesquita de Mesquita, Pereira Pereira, Correia Correia, Marcon Marcon, Siqueira Júnior Siqueira Júnior, Calixto Calixto
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