Renal toxicity caused by oral use of medicinal plants: the yacon example.
OBJECTIVE
Yacon [Smallanthus sonchifolius (Poepp. & Endl.) H. Robinson, Asteraceae] is an Andean species that has traditionally been used as an anti-diabetic herb in several countries around the world, including Brazil. Its hypoglycaemic action has recently been demonstrated in normal and diabetic rats. However, studies about the safety of prolonged oral consumption of yacon leaf extracts are lacking. Thus, this work was undertaken to evaluate the repeated-dose toxicity of three extracts from yacon leaves: the aqueous extract (AE) prepared as a tea infusion; the leaf-rinse extract (LRE), which is rich in sesquiterpene lactones (STLs); and a polar extract from leaves without trichomes, or polar extract (PE), which lacks STLs but is rich in chlorogenic acids (CGAs).


METHODS
The major classes of the compounds were confirmed in each extract by IR spectra and HPLC-UV-DAD profiling as well as comparison to standard compounds. The toxicity of each extract was evaluated in a repeated-dose toxicity study in Wistar rats for 90 days.


RESULTS
The PE was rich in CGAs, but we did not detect any STLs. The AE and LRE showed the presence of STLs. The polar extract caused alterations in some biochemical parameters, but the animals did not show signs of behavioural toxicity or serious lesions in organs. Alterations of specific biochemical parameters in the blood (creatinine 7.0 mg/dL, glucose 212.0 mg/dL, albumin 2.8 g/dL) of rats treated with AE (10, 50 and 100 mg/kg) and LRE (10 and 100 mg/kg) pointed to renal damage, which was confirmed by histological analysis of the kidneys.


CONCLUSIONS
The renal damage was associated with increased blood glucose levels after prolonged oral administration of the AE. This observation suggested that the hypoglycaemic effect observed after treatment for 30 days in an earlier study is reversible and was likely the result of renal injury caused by the toxicity of yacon. Because STLs were detected in both AE and LRE, there is strong evidence that these terpenoids are the main toxic compounds in the leaves of the yacon. Based on our results, we do not recommend the oral use of yacon leaves to treat diabetes.
Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café s/n, 14040-903 Ribeirão Preto, SP, Brazil.
Rejane Barbosa
RB
de Oliveira
Daniela Aparecida Chagas
DA
de Paula
Bruno Alves
BA
Rocha
João José
JJ
Franco
Leonardo
L
Gobbo-Neto
Sérgio Akira
SA
Uyemura
Wagner Ferreira
WF
dos Santos
Fernando Batista
FB
Da Costa
D000284:Administration, Oral; D000818:Animals; D019659:Asteraceae / Q000737:chemistry / Q000633:toxicity*; D001786:Blood Glucose / Q000378:metabolism; D001938:Brazil; D002726:Chlorogenic Acid / Q000008:administration & dosage / Q000633:toxicity; D020834:Ethnopharmacology; D005260:Female; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000633:toxicity; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D007783:Lactones / Q000008:administration & dosage / Q000633:toxicity; D008297:Male; D008519:Medicine, Traditional; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000633:toxicity; D018515:Plant Leaves / Q000737:chemistry / Q000633:toxicity; D010946:Plants, Medicinal / Q000737:chemistry / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000633:toxicity
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007783:Lactones; D010936:Plant Extracts; D012717:Sesquiterpenes; C535244:yacon syrup; D002726:Chlorogenic Acid