Modulations of cytochrome P450 expression in diabetic mice by berberine.

Berberine, an isoquinoline alkaloid isolated from medicinal plants such as Berberis aristata, Coptis chinesis, Coptis japonica, Coscinium fenestatun, and Hydrastis Canadensis, is widely used in Asian countries for the treatment of diabetes, hypertension, and hypercholesterolemia. Interaction between berberine and the cytochrome P450 enzymes (CYPs) has been extensively reported, but there are only a few reports of this interaction in the diabetic state. In this study, the effect of berberine on the mRNA of the CYPs in primary mouse hepatocytes and in streptozotocin (STZ)-induced diabetic mice was investigated. In primary mouse hepatocytes, berberine suppressed the induction of Cyp1a1, Cyp1a2, Cyp2e1, Cyp3a11, Cyp4a10, and Cyp4a14 mRNA expression by their prototypical inducers in a concentration-dependent fashion. However, berberine treatment alone increased the expression of Cyp2b9 and Cyp2b10 mRNA. In vivo, berberine showed the same hypoglycemic activity as metformin, an established hypoglycemic drug. The hepatic mRNA levels of Cyp1a1, Cyp2b9, Cyp2b10, Cyp3a11, Cyp4a10, and Cyp4a14 were increased in STZ-induced diabetic mice. Interestingly, berberine itself suppressed the expression of Cyp2e1, an adverse hepatic event-associated enzyme, while the expression of Cyp3a11, Cyp4a10, and Cyp4a14 were restored to normal levels by berberine. In conclusion, berberine has the potential to modify the expression of CYPs by either suppression or enhancement of CYPs' levels. Consumption of berberine as an anti-hyperglycemic compound by diabetic patients might provide an extra benefit due to its potential to restore the expression of Cyp2e1, Cyp3a, and Cyp4a to normal levels. However, an herb-drug interaction might be of concern since any berberine-containing product would definitely cause pronounced interactions based on CYP3A4 inhibition.

Modified expression of aryl hydrocarbon receptor-related genes by deoxymiroestrol, a phytoestrogen, in mouse hepatocytes in primary culture.

ETHNOPHARMACOLOGICAL RELEVANCE: Deoxymiroestrol (DM), a strong phytoestrogen from Pueraria candollei Wall. ex Benth. var. mirifica (family Leguminosae). This plant has long been used in traditional medicine for rejuvenation. MATERIALS AND METHODS: The expression of aryl hydrocarbon receptor-related genes in mouse hepatocytes in primary culture was quantified by real-time RT-PCR and hepatic microsomal P450 activity was assessed by using ethoxyresorufin O-dealkylation. RESULTS: The mRNA expression of the aryl hydrocarbon receptor (AhR), AhR nuclear translocator, and CYP1A1 was suppressed, whereas that of CYP1B1, estrogen receptor α (ERα), CYP2B9, and glutathione-S-transferase a2 (GSTa2) was increased. The effects of DM on the gene expression depended on treatment period and concentrations, and were similar to those of ß-estradiol (E2). DM and E2 at pharmacological concentrations had a marked synergistic effect on CYP1A1 expression after combined treatment with a typical CYP1 inducer, ß-naphthoflavone (ßNF), at the level of both transcription and enzymatic activity. DM enhanced the inducible mRNA expression of CYP1A1 and CYP1B1 similar to E2. Meanwhile, the expression of ERα mRNA was not affected by ßNF, which, on the contrary, completely eliminated the DM-induced mRNA expression of ERα, CYP2B9, and GSTa2. CONCLUSION: The findings that DM modified the expression of several metabolism-related genes suggest the need for caution when using health supplements having phytoestrogenic activity.

Gender-associated modulation of inducible CYP1A1 expression by andrographolide in mouse liver.

We previously observed a strong synergistic effect on polycyclic aromatic hydrocarbon (PAH)-induced CYP1A1 expression by andrographolide, a major constituent of an herbal medicine derived from the plant Andrographis paniculata, in mouse hepatocytes in primary culture. The present paper describes confirmation of an enhancing effect of andrographolide on the CYP1 family in vivo in the PAH-responsive C57BL/6 mouse. Andrographolide did not alter CYP1 expression in the PAH-nonresponsive DBA/2 mouse. The enhanced expression induced by andrographolide was observed in male C57BL/6 mice, but not in intact or ovariectomized females, or in orchiectomized male mice. However, treatment with testosterone restored the effect in both orchiectomized males and ovariectomized females. These observations indicate a male hormone-related system to be a crucial mediator of the modulation of CYP1 expression by andrographolide. Precautions should be taken regarding the use of A. paniculata as an alternative medication or health promotion, according to its distinctive characterization on sexually dimorphic modulation of CYP1A1 expression.

[A case of intussusception caused by descending colon cancer in a very elderly patient, lacking in abdominal symptoms].

A 90-year-old woman was admitted to our hospital because of dizziness, without any remarkable abdominal symptoms. Severe anemia was found and thus gastrointestinal investigations were performed. CT and ultrasonography showed the specific multiplex layer configuration at the anal side of the descending colon. Colonoscopy showed a round tumor occupying the lumen and a consecutive gastrografin enema showed a crab-claw-like area without filling in the descending colon. Intussusception of the colon was diagnosed and partial resection of the descending colon was performed, but without relief of intussusception. The tumor was histologically diagnosed as mucinous adenocarcinoma. By various factors, incomplete fixation between the retroperitoneum and the descending colon might result in the present condition.