In vivo assessment of safety and mechanisms underlying in vitro relaxation induced by Mikania laevigata Schultz Bip. ex Baker in the rat trachea

• Published in: Journal of ethnopharmacology Vol. 112; no. 3; pp. 430 - 439
• Main Authors: Graça, Carlos, Baggio, Cristiane Hatsuko, Freitas, Cristina Setim, Rattmann, Yanna Dantas, de Souza, Lauro Mera, Cipriani, Thales Ricardo, Sassaki, Guilherme Lanzi, Rieck, Lia, Pontarolo, Roberto, da Silva-Santos, José Eduardo, Marques, Maria Consuelo Andrade
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 25-07-2007; Elsevier
• Subjects: 4-Aminopyridine - pharmacology; Acetylcholine - pharmacology; Animals; Asteraceae; bioassays; Biological and medical sciences; Brazil; chemical constituents of plants; Coumarins - chemistry; Coumarins - isolation & purification; Coumarins - pharmacology; Dose-Response Relationship, Drug; ethnobotany; Female; Gas Chromatography-Mass Spectrometry; General pharmacology; Glyburide - pharmacology; Guaco syrup; herbal medicines; human health and safety; In Vitro Techniques; Male; Medical sciences; medicinal plants; medicinal properties; Mice; Mikania; Mikania - chemistry; Mikania laevigata; muscle relaxants; Muscle Relaxation - drug effects; Muscle, Smooth - drug effects; Muscle, Smooth - physiology; NG-Nitroarginine Methyl Ester - pharmacology; Oxadiazoles - pharmacology; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; plant extracts; Plant Extracts - chemistry; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Potassium Channel Blockers - pharmacology; Quinoxalines - pharmacology; Rats; Rats, Wistar; Relaxation; safety testing; Tetraethylammonium - pharmacology; Toxicity; Toxicity Tests, Acute - methods; Toxicity Tests, Chronic - methods; trachea (vertebrates); Trachea - drug effects; Trachea - physiology; traditional medicine; Brazil; Relaxation; Mikania laevigata; Guaco syrup; Toxicity; Asteraceae; Evaluation; Rat; Pharmacognosy; Rodentia; Compositae; Respiratory system; In vitro; Medicinal plant; Respiratory tract; In vivo; Vertebrata; Mammalia; Dicotyledones; Animal; Angiospermae; Plant origin; Spermatophyta; Mechanism of action; Trachea
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2007.03.026

Mikania laevigata, popularly known in Brazil as “guaco”, is largely used in folk medicine against respiratory diseases. However, neither the assessment of the toxicity of “guaco” syrup (GS, used by humans) nor its efficacy or mechanisms of action has been properly investigated. Using
in vitro procedures, we showed that the hydroalcoholic extract (HE) from
Mikania laevigata induces a concentration-dependent relaxation of rat trachea which does not depend on epithelium-derived substances but involves changes in the cellular mobilization of calcium, perhaps due to a direct effect on membrane potassium channels. In addition, we assessed both oral and intraperitoneal acute toxicity, as well as the oral subchronic and chronic toxicity of GS containing controlled amounts of coumarin, the main biological marker of
Mikania laevigata preparations used in humans. The calculated LD
50 of GS after intraperitoneal administration was 0.904
g/kg in mice (both sexes) and 0.967 and 0.548
g/kg in male and female rats, respectively. However, the LD
50 values of GS by the oral route were calculated to be up to 10
g/kg, in both male and female mice and rats. Repeated dose 28- or 90-day oral treatment with GS (75, 150 and 300
mg/kg) did not produce any disturbances in the hematological or biochemical parameters of either male or female rats, nor did it provide evidence of toxicity in the hepatic, renal or pancreatic systems. Besides the mechanistic findings, our results provide evidence of the safety of
Mikania laevigata in rodents, even after subchronic and chronic administration, at least in relation to the evaluated parameters.