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Aristolochia manshuriensis Kom (Aristolochiaceae) (AMK) is known for toxicity and mutagenicity. The tumorigenic role of AMK has yet to be understood. AMK extracts were extracted from root crude drug. SD (Sprague Dawley) rats underwent gavage with AMK (0.92 g/kg) every other day for 10 (AMK-10) or 20 (AMK-20) weeks. Stomach samples were gathered for histopathological evaluation, microarray and mRNA analysis. The gastric weight to body weight ratio (GW/BW) is 1.7 in the AMK-10 cohort, and 1.8 in AMK-20 cohort compared to control (CTL) cohort. Liver function was damaged in AMK-10 and AMK-20 rats compared to CTL rats. There were no significant changes of CRE (creatinine) in AMK-10 and AMK-20 rats. Histopathological analysis revealed that rats developed dysplasia in the forestomach in AMK-10 rats, and became gastric carcinoma in AMK-20 rats. Genes including Mapk13, Nme1, Gsta4, Gstm1, Jun, Mgst2, Ggt6, Gpx2, Gpx8, Calml3, Rasgrp2, Cd44, Gsr, Dgkb, Rras, and Amt were found to be critical in AMK-10 and AMK-20 rats. Pik3cb, Plcb3, Tp53, Hras, Myc, Src, Akt1, Gnai3, and Fgfr3 worked in AMK-10 rats, and PDE2a and PDE3a played a pivotal role in AMK-20 rats. AMK induced benign or malignant gastric tumours depends on the period of AMK administration. Genes including Mapk13, Nme1, Gsta4, Gstm1, Jun, Mgst2, Ggt6, Gpx2, Gpx8, Calml3, Rasgrp2, Cd44, Gsr, Dgkb, Rras, Amt, Pik3cb, Plcb3, Tp53, Hras, Myc, Src, Akt1, Gnai3, Fgfr3, PDE2a, and PDE3a were found to be critical in aristolochic acid-induced gastric tumour process. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Aristolochia manshuriensis Kom (AMK), belonging to the Aristolochia family, is traditionally used in China to remove heart fire, promote dieresis, restore menstruation, and enhance milk secretion. The active constitutes of AMK are aristolochic acids (AAs, I and II) that are reported to cause serious side effects including nephrotoxicity and carcinogenicity. Aim of the study The tumorigenic role of AMK is far to be understood. We analyzed the toxicity reactions after long-term exposure of AMK in rats. Materials and Methods Sprague–Dawley rats underwent gavage with AMK doses of 51 mg/kg (AMK-1), 253 mg/kg (AMK-2), 508 mg/kg (AMK-3), 1029 mg/kg (AMK-4) or AAs of 15 mg/kg (AAs), and then sacrificed at the 6th, 10th, 14th, 18th, 22th, 26th and 30th weeks. Endpoint measurements included clinical observations, body weights, blood biochemistry, haematology and histomorphological observations. Results Body weight decreased after AMK or AAs treatment in rats. AMK destroyed renal function, and induced anemia in rats. AMK caused kidney, stomach, bladder and subcutaneous tumors in rats. In addition, primary hepatic carcinoma was not observed in rats. Conclusions AMK had significant toxic effects in rats with regard to decreased body weight, diminished renal function, increased anemia and tumor incidence. Kidney, stomach, bladder and subcutaneous tissue are carcinogenic target organs of AMK or AAs, however liver is no- carcinogenic target organ of AMK or AAs in rats. AMK is carcinogenic in rats, and not be safe for humans. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Geniposide, the major active constituent of Fructus Gardeniae (FG), has been widely used to treat various diseases in China. Aim of the study This chronic toxicity study was conducted to investigate the safety of geniposide. Materials and methods Geniposide was administered to Sprague-Dawley (SD) rats of both sexes by oral gavage at dosages of 25, 50, or 100 mg/kg in a volume of 10 mL/kg once daily for 26 weeks. Endpoints included clinical observations, food consumption, body weights, blood biochemistry, haematology, and histomorphological observations. Results The administration of geniposide did not influence animal mortality, the general conditions of the animals, body weights or food consumption. After 4 weeks of administration, significant toxicity was not observed. However, in the 13th week of the toxicity study, a few haematological parameters and some relative organ weights of male rats in the 50 and 100 mg/kg geniposide groups were significantly increased. The percentage of reticulocytes (Retic %) was significantly increased in male and female rats administered 100 mg/kg geniposide. In addition, two female rats in the 100 mg/kg geniposide group showed slight pathological changes in hepatic and renal tissues. Furthermore, in a chronic (26 weeks) toxicity study, differences were detected in alanine aminotransferase (ALT), aspartate aminotransferase (AST), sodium (Na + ), potassium (K + ), white blood cell (WBC), red blood cell (RBC), and haemoglobin (HGB) levels and the relative weights of the liver and spleen in male rats administered 100 mg/kg geniposide. In addition, differences were detected in Retic % and the relative weights of the liver, thymus, and kidneys in female rats administered 100 mg/kg geniposide. Urinalysis results from male and female rats in the 100 mg/kg geniposide group revealed noticeable changes. The histopathological structures of hepatic and renal tissues in the high-dose geniposide group exhibited serious abnormalities and pigment deposition. Conclusion Geniposide affected serum biochemistry, urinalysis, and haematological parameters as well as relative organ weights. The treatment also caused noticeable pathological abnormalities in liver and kidney tissues. Therefore, administration of a high dose of geniposide (100 mg/kg) for 26 weeks could induced obvious liver and kidney damage. [ABSTRACT FROM AUTHOR]