Inhibitory Effect of Coptidis Rhizoma and Scutellariae Radix on Azoxymethane-Induced Aberrant Crypt Foci Formation in Rat Colon.

Abstract

This study was conducted to obtain effective cancer chemopreventive agents with low toxicity from medicinal herbs. The effect of aqueous extracts from 9 medicinal herbs with antiinflammatory effect were examined on the formation of azoxymethane (AOM)-induced aberrant crypt foci (ACF), putative preneoplastic lesions of the colon. Male F344 rats were treated with 15 mg/kg body weight of AOM once a week for two weeks. Herbal extract consisting of 2% of the diet was administered from 1 d prior to the first carcinogen treatment. The number of AOM-induced ACF per colon was counted at 4 week. Extracts of Coptidis Rhizoma and Scutellariae Radix significantly inhibited AOM-induced ACF formation. The number of ACF was decreased to 54% and 78% of that of the control by 2% Coptidis Rhizoma and Scutellariae Radix extract in the diet, respectively. Berberine and Baicalin, major ingredients of Coptidis Rhizoma and Scutellariae Radix, inhibited ACF formation at a dose equivalent to the amount in each herbal extract. Therefore, to investigate the mechanisms of action of berberine and baicalein which is the active substances of orally administered baicalin, their effects on cyclooxygenase 1 and 2 activities were studied. Berberine was found to inhibit cyclooxygenase 2 activity without inhibition of cyclooxygenase 1 activity, and baicalein inhibited cyclooxygenase 1 activity. Thus, Coptidis Rhizoma and Scutellariae Radix suppressed experimental colon carcinogenesis, and their chemopreventive effects were explained from the inhibition of berberine on cyclooxygenase 2 activity and baicalein on cyclooxygenase 1 activity.

Anticachectic effects of the natural herb Coptidis rhizoma and berberine on mice bearing colon 26/clone 20 adenocarcinoma

“…Studies from our laboratory and others have shown that C. rhizoma, a berberine-rich herb obtained from the root of various Coptis plants, possesses antitumor and cancer-preventive properties. 9,12,18 Previously, we found that oral administration of C. rhizoma significantly prevented weight loss in nude mice bearing (n ϭ 9) (n ϭ 9) (n ϭ 9) (n ϭ 6) (n ϭ 6)…”

“…Interestingly, muscle wasting induced by PIF may be associated with elevation of prostaglandin E 2 (PGE 2 ), 23 and it is known that C. rhizoma inhibits cyclooxygenase-2 activity. 12 This herb might exert anticachectic action via direct interaction with PIF and PGE 2 -generating pathways. We also found that CR supplementation significantly prevented hypoglycemia in tumor-bearing mice compared to the normal diet.…”

“…rhizoma powder was made from Coptis japonica Makino by boiling in water and spray drying at Tsumura (Tokyo, Japan). 9,10,12 Berberine, a major component of C. rhizoma, was purchased from Wako (Osaka, Japan). Since herbal remedies in human beings are generally administered on the free demand of patients, we designed a mouse diet containing the herb or berberine that permitted daily free intake.…”

“…It is present in the extract powder of C. rhizoma at a concentration of approximately 20%. 12,16 We therefore chose to use C. rhizoma extract powder at final concentrations of 1% and 2% of the diet (CR supplement). Unfortunately, 2% CR supplementation markedly decreased food intake in mice, resulting in loss of body weight even in the tumor-free state (data not shown).…”

Berberine inhibits the proliferation of colon cancer cells by inactivating Wnt/β-catenin signaling

“…Wnt/β-catenin has been shown to be one of the important targets for colon cancer chemoprevention. Berberine can inhibit carcinogen-induced formation of ACFs in the rat colon, which are usually considered to be preneoplastic lesions of colon mucosa (30). DMH-induced colon cancers are characterized by activating β-catenin mutations that are functionally equivalent to inactivating APC mutations (31,32).…”