Identification of anti-inflammatory constituents in Phellodendri Cortex and Coptidis Rhizoma by monitoring the suppression of nitric oxide production

Abstract

Phellodendri Cortex (Obaku in Japanese) and Coptidis Rhizoma (Oren), both of which contain berberine, have been used to prepare the kampo formula orengedokuto to treat inflammatory diseases, including dermatitis, gastric ulcers, and gastritis. These drugs are blended differently in other formulas, such as the use of Phellodendri Cortex in shichimotsukokato to treat hypertension and Coptidis Rhizoma in hangeshashinto to treat diarrhea and stomatitis. However, the differences in their medicinal properties are not well characterized. We prepared extracts from Phellodendron amurense bark (PAB) and Coptis chinensis rhizome (CCR) and separated them into alkaloid and non-alkaloid fractions. Anti-inflammatory effects were examined by monitoring the production of nitric oxide (NO), which is a pro-inflammatory mediator. A non-alkaloid fraction of the PAB extract suppressed NO production in hepatocytes more efficiently than that of the CCR extract. When each non-alkaloid fraction of the PAB and CCR extracts was administered to mice, the fractions of both extracts decreased the levels of mRNAs encoding inducible NO synthase and molecules in the interleukin-1β signaling pathway. Limonin and obakunone identified in the PAB non-alkaloid fraction suppressed NO production, exhibiting IC values of 16 and 2.6 μM, respectively, whereas berberine and coptisine displayed IC values of 12 and 14 μM, respectively. Limonin and obakunone reduced the expression of the iNOS gene, probably through the transcription factor nuclear factor-κB. Therefore, both limonoids and alkaloids may be responsible for the anti-inflammatory effects of the PAB extract, whereas alkaloids may be primarily responsible for those of the CCR extract. The different composition of the constituents may modulate the anti-inflammatory effects of Phellodendri Cortex and Coptidis Rhizoma.

Antimalarial activity of traditional Kampo medicine Coptis Rhizome extract and its major active compounds

“…Coptis Rhizome is one of the components of a formula, Orengedokuto, which has been used to treat in ammatory disease [43], and berberine is strongly suggested to be responsible for its anti-in ammatory effect [44,45]. In our study, we have con rmed the in vivo anti-malarial activity of Coptis Rhizome, but the Orengedokuto, whose 33.3% content [36] is Coptis Rhizome did not show a comparable effect on the reduction of parasitemia.…”

Bitter melon fruit extract has a hypoglycemic effect and reduces hepatic lipid accumulation in ob/ob mice

“…Specific pathogen‐free, male Wistar rats (Charles River Laboratories Japan Inc., Yokohama, Japan) were housed at 21–23°C under a 12‐hr light–dark cycle with a γ‐ray‐irradiated CRF‐1 diet (Charles River Laboratories Japan Inc.) and water available ad libitum and acclimated for at least a week. Hepatocytes were prepared from the liver of rats (6‐ to 8‐week‐old, 250–300 g of body weight), according to the previously published method (Fujii et al, ; Kanemaki, Kitade, Hiramatsu, Kamiyama, & Okumura, ). Briefly, the anesthetic combination of medetomidine hydrochloride (0.40 mg/kg body weight; Nippon Zenyaku Kogyo Co., Ltd., Koriyama, Fukushima, Japan), midazolam (2.0 mg/kg body weight; Astellas Pharma Inc., Tokyo, Japan), and butorphanol tartrate (3.5 mg/kg body weight; Meiji Seika Pharma Co. Ltd., Tokyo, Japan) was administered intraperitoneally to a rat, and the liver was perfused with collagenase (FUJIFILM Wako Pure Chemical Corporation, Osaka, Japan) from the portal vein.…”

“…Specific pathogen‐free, male 7‐week‐old Lep ob/ob ( ob/ob ) and Lep +/+ (wild‐type) mice (Japan SLC, Inc., Hamamatsu, Japan) were housed at 21–23°C under a 12‐hr light–dark cycle with a γ‐ray‐irradiated CRF‐1 diet and water available ad libitum and acclimated for 1 week. Then each type of the mice (eight mice per type) was randomly assigned into two groups (four mice per group) on Day 0 and fed a γ‐ray‐irradiated CRF‐1 diet with/without 1% EtOAc‐soluble fraction for 7 days with water available ad libitum, according to the previously published method to administer a fraction of herbal medicine to mice (Fujii et al, ). Blood was drawn by a small incision in the tail to measure glucose levels using a Glucocard® PlusCare GT‐1820 Monitoring System (Arkray, Inc., Kyoto, Japan).…”

Role of limonin in anticancer effects of Evodia rutaecarpa on ovarian cancer cells

“…Limonin, one of the compounds found in ER [13,14], is the major limonoid and a bitter compound, mainly found in seeds. Several studies have indicated that limonin shows biological activities, including antioxidant, antiinflammatory, and antiviral effects [15][16][17]. Validation studies have demonstrated the anticancer effects of limonin in various cancer cell lines [18][19][20][21][22][23].…”