€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****BIOLOGY OF THE NEONATE***** Yeung CY Lee FT Wong HN Effect of a popular Chinese herb on neonatal bilirubin protein binding. In: Biol Neonate (1990) 58(2):98-103 ISSN: 0006-3126 A study on the effects of a popular Chinese herb commonly given to newborn infants was undertaken. 'Chuen-Lin', Coptis chinensus/japonicum, which is consumed by 28-51% of Chinese infants, was found to have a significant effect in displacing bilirubin from its serum protein binding as assessed by the peroxidase oxidation method. Taking this herbal tea may thus increase the risk of brain damage by free bilirubin in jaundiced infants. As neonatal hyperbilirubinaemia is highly prevalent among Southern Chinese, the use of Chuen-Lin in the perinatal period must be strongly discouraged. Registry Numbers: 635-65-4 (Bilirubin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Chan E Displacement of bilirubin from albumin by berberine. In: Biol Neonate (1993) 63(4):201-8 ISSN: 0006-3126 A study was made of the effect of berberine, the major ingredient of the Chinese herb huanglian (coptis chinensis) reported to pose some risk for kernicterus among jaundiced newborn Chinese infants, on the protein binding of bilirubin, using the peroxidase kinetic method. Berberine was found in vitro, as to its displacing effect on a molar basis, to be about tenfold superior to phenylbutazone, a known potent displacer of bilirubin, and about hundredfold to papaverine, a berberine-type alkaloid. The chronic intraperitoneal administration of berberine (10 and 20 micrograms/g) daily for 1 week to adult rats (mixed breed of Wistar and Sprague-Dawley) resulted in a significant decrease in mean bilirubin serum protein binding, due to an in vivo displacement effect and a persistent elevation in steady-state serum concentrations of unbound and total bilirubin, possibly due to inhibition of metabolism. The use of the herb and other traditional Chinese medicines containing a high proportion of berberine is best avoided in jaundiced neonates and pregnant women. Registry Numbers: 2086-83-1 (Berberine) 635-65-4 (Bilirubin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ ***CHUNG HSI I CHIEH HO TSA CHIH CHINESE JOURNAL OF MODERN DEVELOPMENTS*** Wang GD Zhang YM Xiong XY [Clinical and experimental study of burns treated locally with Chinese herbs] In: Chung Hsi I Chieh Ho Tsa Chih (1991 Dec) 11(12):727-9, 709 ISSN: 0254-9034 (Published in Chinese) According to the multiple pharmacological functions of Chinese herbs for treating burns, the authors selected some traditional herbs to cure the burning wound, which had not only the function of improving the local microcirculation of the burned surface and their bactericidal action, but also the function of changing the bacterial growth milieu action. Coptis chinensis 40%, Herba Taraxaci 40%, Fructus Mume 10% and Salvia miltiorrhizae 10% were boiled, infiltrated and disinfected. The mixture thus made was called as Burn II, which were applied on the burned surface daily, 97.1% of 103 patients were cured. Through the experiment of 60 rabbits burned by irons, which were divided into 6 groups (n = 10 in each group) and each 2 groups infected respectively with Bacillus pyocyaneus, Bacillus Coli and Staphylococcus Aureus, took one of each infected group as control group. After 14 days, the infected burned surfaces which were applied with Burn II daily. The results showed that the effect of Burn II was not only significant, but also its usage was not highly restricted by the medical condition. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****CHUNG-KUO CHUNG HSI I CHIEH HO TSA CHIH***** Chen Q Chen NJ Wang SC [Experimental study of R plasmid eliminating action of Coptis chinensis on E. coli] In: Chung Kuo Chung Hsi I Chieh Ho Tsa Chih (1996 Jan) 16(1):37-8 ISSN: 1003-5370 (Published in Chinese) The R plasmid curing experiment was performed in vitro with E. coli strain E. 102 bearing R plasmid as target bacteria and Coptis chinensis as elimination agent. The influence of different time on R plasmid elimination was also observed. Results showed that when the acting time was 24 hours, the cure rate of R plasmid was 2.42% and when the acting time increased to 48 hours, the cure rate elevated to 22.57%. The Missing patterns of R plasmid might be occurred in disappearence of either multiple or single resistance. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Huang WM Yan J Xu J [Clinical and experimental study on inhibitory effect of sanhuang mixture on platelet aggregation] In: Chung Kuo Chung Hsi I Chieh Ho Tsa Chih (1995 Aug) 15(8):465-7 ISSN: 1003-5370 (Published in Chinese) Sanhuang mixture (Xinmai capsule) is composed of Astragalus membranaceus, Coptis chinensis and Scutellaria baicalensis. It could inhibit platelet aggregation (PAG) induced by ADP in rats or by ADP and ADR in vivo. Patients with high PAG took Xinmai capsule for 4 weeks, the effective rate was 88.7%, which was same as the efficacy of aspirin 50 mg/day. In Syndrome Differentiation of TCM, the effective rate was the highest (92.3%) in the Syndrome of Qi Deficiency-Blood Stasis, and the lowest (72.7%) in the Syndrome of Stasis Phlegm and combined together. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Gao XS [Absorptive capacity of upper gastrointestinal tract with Chinese herbal medicine] In: Chung Kuo Chung Hsi I Chieh Ho Tsa Chih (1993 Jul) 13(7):433-5, 390 ISSN: 1003-5370 (Published in Chinese) 285 reports on the intoxication of Chinese herbal medicine per os were reviewed. The toxic symptoms occurred after oral administration for less than 10 min in about 110 reports. Some components of these herbal medicines might be absorbed and then reach effective level more rapidly. By segmental ligation of GI tract, experiments in rabbits, cats, rats or mice were conducted, in which principal ingredients of Rheum palmatum, Coptis chinensis, Veratrum nigrum, and aconitine were absorbed in esophagus or stomach within short period of time was observed. It suggested that the absorptive capacity of upper GI tract might have universal significance. The treatment of acute diseases by oral administration of Chinese herbal medicines is feasible. Registry Numbers: 302-27-2 (Aconitine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Zhang L Yang LW Yang LJ [Relation between Helicobacter pylori and pathogenesis of chronic atrophic gastritis and the research of its prevention and treatment] In: Chung Kuo Chung Hsi I Chieh Ho Tsa Chih (1992 Sep) 12(9):521-3, 515-6 ISSN: 1003-5370 (Published in Chinese) The total detectable rate of Helicobacter pylori (HP) of 485 patients suffering from gastric diseases was 59.6%. The HP in gastric mucosa of chronic atrophic gastritis (CAG) patients was separated from the cell culture in vitro and transferred successively. The mice were perfused with exciccate alum, and the rabbits with aspirin to injure their gastric mucosa, then HP was perfused. Result showed that the change of experimental animals was identical with that of CAG patients by means of bacteriological and pathological examination. It revealed that HP was in agreement with Robert Koch's three principles about pathogenic bacteria. According to the bacterial infectious hypothesis of CAG, 53 Chinese medicinal herbs and prescriptions were investigated with bacteriostatic test. Panax notogenseng and Magnolia officinalis were discovered to be sensitive, Prunus mume and Corydalis yanhusuo were moderate sensitive, and Coptis chinensis and Rheum palmatum highly sensitive to HP. Decoction of Clearing up the Heat and Relieving the Blood Stasis and No.2 recipe of Huowei were used to treat 70 CAG patients with Stomach Heat Syndrome. The effective rate of gastroscopic examination was 85.7%, that of pathological study was 80%. In comparing with the group of Shanjiu Weitai, there was significant difference between the traditional Chinese medicine treated group and Shanjiu Weitai control group, the former being markedly better. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Song LC Chen KZ Zhu JY [The effect of Coptis chinensis on lipid peroxidation and antioxidases activity in rats] In: Chung Kuo Chung Hsi I Chieh Ho Tsa Chih (1992 Jul) 12(7):421-3, 390 ISSN: 1003-5370 (Published in Chinese) In order to make a systematic study of the effect of Coptis chinensis on free radicals, the authors used the method that the drug and the brain homogenate of rat were mixed and incubated to investigate the effect of Coptis on lipid peroxidation. The result showed that the malondialdehyde (MDA) product of rat brain homogenate inhibited by 5% Coptis was significantly different from control (P < 0.001). On the basis of the above-mentioned results, the effect of Coptis on lipid peroxidation and diabetes of rats induced by alloxan was investigated. The result showed: (1) The MDA product of both pancreas and liver homogenate in Coptis group was significantly less than that in control and alloxan group (P < 0.01, P < 0.05). (2) Superoxide dismutases (SODs) in erythrocytes activity was the same for all groups (P > 0.50). (3) The blood catalase (CAT) activity in alloxan group markedly decreased compared with control group (P < 0.05), but no significant change between Coptis and alloxan group (P > 0.05). (4) The value of serum glucose in alloxan group was significantly increased in comparing with control group (P < 0.05). There was a trend to decrease the value of serum glucose in Coptis group compared with alloxan group, but no significant difference between two groups (P > 0.05). The experiment indicated that there was very strong inhibitory effect of Coptis to the lipid peroxidation in vitro and in vivo. Coptis could protect rat from diabetes inducing by alloxan and that probably was due to the fact that Coptis was able to inhibit alloxan inducing free radicals. Registry Numbers: EC 1.11.1.6 (Catalase) EC 1.15.1.1 (Superoxide Dismutase) 542-78-9 (Malondialdehyde) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ **CHUNG-KUO CHUNG YAO TSA CHIH CHINA JOURNAL OF CHINESE MATERIA MEDICA* Zhang H Wang T Fang X Shuai H Xie C [plants of Coptis from Tibet and Yunnan] In: Chung Kuo Chung Yao Tsa Chih (1990 Jun) 15(6):326-8, 382 ISSN: 1001-5302 (Published in Chinese) In this paper the relationship of Tibetan Huanglian and Yunnan Huanglian with Coptis teeta has been studied. The distribution and taxonomic features of Tibetan Huanglian are just the same as Coptis teeta, but quite different from Yunnan Huanglian. The results reveal that Tibetan Huanglian and Yunnan Huanglian are different in botanical origin. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Lin L [Application of equal value derivative spectrophotometry to the determination of coptis alkali in wanshi niuhuang qingxin pills] In: Chung Kuo Chung Yao Tsa Chih (1990 Jan) 15(1):32-4, 63 ISSN: 1001-5302 (Published in Chinese) The total coptis alkaloids Wanshi Niuhang Qingxin Pills were determined by equal value derivative spectrophotometry in this paper. Quantitative analysis of six mixtures of medicinal herbs can be done easily on the extract. The average recovery of berberine.HCl is 98.55 +/- 1.90% (CV). The method features good reproducibility, favorable stability and high sensitivity. Registry Numbers: 2086-83-1 (Berberine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Fang XP Wang TZ Zhang H Shuai H Li D Xie CK [Quantitative determination of 5 alkaloids in plants of Coptis from China] In: Chung Kuo Chung Yao Tsa Chih (1989 Feb) 14(2):33-5, 63 ISSN: 1001-5302 (Published in Chinese) Quantitative determination of berberine, coptisine, palmatine, jatrorrhizine and epiberberine in Coptis chinensis, C. deltoidea, C. teetoides, C. omeiensis, C. chinensis var. brevisepala, C. linearisepala, C. gulinensis, C. chinensis var. unguiculata, C. teeta and 5 different samples of C. chinensis was made by thin layer chromatography-densitometry. Registry Numbers: 2086-83-1 (Berberine) 3486-66-6 (coptisine) 3486-67-7 (palmatine) 3621-38-3 (jatrorrhizine) 6466-94-0 (bauerenol) 6873-09-2 (epiberberine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Fan J Yi S Zhang A Zhao P Lou Z Xiao X Li Z [Restricting effects of geologic background system on genuine crude drugs in Sichuan] In: Chung Kuo Chung Yao Tsa Chih (1996 Jan) 21(1):12-4, 62 ISSN: 1001-5302 (Published in Chinese) The distribution, growth, output and quality of genuine crude drugs are restricted by geologic background system (GBS), whose extensional vector system "rock-->soil-->medicinal plants" accomplishes the unity of geological grand cycle and biological pulmonary circulation. This article describes how genuine crude drugs in Sichuan, such as Coptis chinensis, etc. for example, are restricted by GBS. Registry Numbers: 2086-83-1 (Berberine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Guo X Zhang F Lin S Chen Z Qin X [Effect of ultrasonic extraction on extraction rate of berberine] In: Chung Kuo Chung Yao Tsa Chih (1995 Nov) 20(11):673-5, 703 ISSN: 1001-5302 (Published in Chinese) The parameters are proposed which can be used in extracting berberine from the rhizoma of Coptis chinensis with ultrasound. Compared with traditional immersing method, ultrasonic extraction is time saving and of higher extraction rate. Registry Numbers: 2086-83-1 (Berberine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****EUROPEAN JOURNAL OF BIOCHEMISTRY***** Sato F Tsujita T Katagiri Y Yoshida S Yamada Y Purification and characterization of S-adenosyl-L-methionine: norcoclaurine 6-O-methyltransferase from cultured Coptis japonica cells. In: Eur J Biochem (1994 Oct 1) 225(1):125-31 ISSN: 0014-2956 S-adenosyl-L-methionine:norcoclaurine 6-O-methyltransferase (norcoclaurine 6-O-methyltransferase), which catalyzes the transfer of the S-methyl group of S-adenosyl-L-methionine to the 6-hydroxyl group of 1,2,3,4-tetrahydro-1-[(4-hydroxyphenyl)methyl]-6,7- isoquinolinediol (norcoclaurine), was purified from cultured Coptis japonica cells and its enzymic properties were characterized. Purified norcoclaurine 6-O-methyltransferase had apparent pI 4.7, a native molecular mass of 95 kDa (determined by gel filtration) and subunit molecular mass of 40 kDa (SDS/PAGE). The enzyme did not require a divalent cation for activity, and the addition of Fe2+, Cu2+, Co2+, Zn2+, Mn2+, or Ni2+ at 5 mM severely inhibited enzyme activity. Neither p-chloromercuribenzoate, N-methylmaleimide nor iodoacetamide inhibited enzyme activity at 1 mM. 5,6-Dihydro-9,10- dimethoxybenzo[g]-1,3-benzodioxolo[5,6-a]qu inolizinium (berberine, the end-product of the biosynthetic pathway in which norcoclurine 6-O- methyltransferase catalyzes an intermediate step) also inhibited the activity by 50% at 10 mM. Norcoclaurine 6-O-methyltransferase methylated both (S)-norcoclaurine and (R)-norcoclaurine and (R,S)- norlaudanosoline. Further characterization of substrate-saturation kinetics and product inhibition of the purified enzyme indicated that norcoclaurine 6-O-methyltransferase follows a bi-bi ping-pong mechanism with Km values of 2.23 mM and 3.95 mM for (R,S)- norlaudanosoline and S-adenosyl-L-methionine, respectively, while Ki values for S-adenosylhomocysteine versus S-adenosyl-L-methionine and (R,S)-norlaudanosoline were 2.1 mM and 0.18 mM, respectively. Registry Numbers: EC 2.1.1. (Methyltransferases) EC 2.1.1.- (S-adenosyl-L-methionine-norcoclaurine 6-O-methyltransferase) 1306-06-5 (Durapatite) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ ****HUA-HSI I KO TA HSUEH HSUEH PAO [JOURNAL OF WEST CHINA UNIVERSITY OF*** Guo P Li Z Hong Z Liu S Wu T [Determination of berberine hydrochloride in traditional Chinese medicines containing Coptis chinensis Franch by reversed phase high performance liquid chromatography] In: Hua Hsi I Ko Ta Hsueh Hsueh Pao (1991 Mar) 22(1):90-2 ISSN: 0257-7712 (Published in Chinese) This paper reports a reversed phase high performance liquid chromatography method to determine berberine hydrochloride in Coptis chinensis Franch and in the traditional Chinese medicine containing Coptis chinensis Franch. The result shows that the mobile phase of 0.4mol/L ammonium nitratemethanol (52:48) can give a satisfactory separation. The extraction of sample with 1% H2SO4 solution using the ultrasonic vibration method is simple and easy to operate. Registry Numbers: 2086-83-1 (Berberine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF ETHNOPHARMACOLOGY***** Yang LQ Singh M Yap EH Ng GC Xu HX Sim KY In vitro response of Blastocystis hominis against traditional Chinese medicine. In: J Ethnopharmacol (1996 Dec) 55(1):35-42 ISSN: 0378-8741 This is the first inn vitro study on the activity of 20 kinds of crude extracts of traditional Chinese medicine (TCM) on the intestinal parasite, Blastocystis hominis using the criteria of living cell count (LCC) and living cell rate (LCR). LCC and LCR were applied as observation indicators, the former as a fixed-quantity and the latter as a fixed-quality method. LCR calculated percentage rate of living cells using eosin-brilliant cresyl blue staining which could differentiate between living cells and dying or dead cells. There were five extracts with no inhibitory activity, thirteen with moderate inhibition and two with high inhibition. The crude extracts of Coptis chinensis (CC) and Brucea javanica (BJ) were found to be most active against B. hominis. The active concentration of CC was 100 micrograms/ml. The active concentration of BJ was 500 micrograms/ml. The active concentration of metronidazole (MD) was 10 micrograms/ml and this was taken as an active standard drug for B. hominis. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Umeda M Amagaya S Ogihara Y Effects of certain herbal medicines on the biotransformation of arachidonic acid: a new pharmacological testing method using serum. In: J Ethnopharmacol (1988 May-Jun) 23(1):91-8 ISSN: 0378-8741 Two in vitro experimental systems were compared to evaluate the pharmacological effects of some herbal medicines on the biotransformation of arachidonic acid (AA) using the microsomal fraction of sheep vesicular glands as an enzyme source. The first system involved the addition of serum obtained from rats treated orally with the herbal medicines, while the second system involved the direct addition of herbal medicine extracts to the enzyme medium. Both systems were performed in parallel. Indomethacin, used as a reference drug, inhibited AA biotransformation in a dose-dependent manner in both experimental systems. The serum of rats orally pretreated for 1 h with Coptis japonica rhizome and Paeonia lactiflora root also inhibited AA biotransformation. Direct addition of hot water extracts of Rheum officinale rhizome, Scutellaria baicalensis root, Paeonia moutan bark and Zingiber officinale rhizome also inhibited AA biotransformation, while the extracts of Coptis japonica rhizome and Paeonia lactiflora root showed no effects. Registry Numbers: 506-32-1 (Arachidonic Acid) 53-86-1 (Indomethacin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****LIFE SCIENCES***** Chi CW Chang YF Chao TW Chiang SH P'eng FK Lui WY Liu TY Flowcytometric analysis of the effect of berberine on the expression of glucocorticoid receptors in human hepatoma HepG2 cells. In: Life Sci (1994) 54(26):2099-107 ISSN: 0024-3205 Berberine is an alkaloid found in many plants, including the Coptis chinensis and Arcangelisia flava. Berberine has been reported to have cytostatic effect on tumor growth. Previously, we have found that the level of glucocorticoid receptors (GR) was significantly higher in hepatoma than in adjacent liver tissues. Using human HepG2 hepatoma cells, we have found that GR were expressed not only in G0-G1 phases, but also in S and G2+M phases. The objective of the present study was to examine the effect of berberine on the expression of GR and its relation to cell cycle progression of HepG2 cells. Continuous exposure of HepG2 cells to various concentrations (1-50 microM) of berberine resulted in growth inhibition in a dose dependent manner. The viability of berberine-treated HepG2 cells was greater than 90% in all treatment groups. Flowcytometric analysis of berberine-treated HepG2 cells showed that the S phase fraction was significantly reduced. GR levels were higher in berberine-treated HepG2 cells than in vehicle (DMSO)-treated cells. In addition, the secretion of alpha- fetoprotein by HepG2 cells was inhibited by berberine. Finally, the berberine induced cell growth arrest was partially reversible in HepG2 cells. Registry Numbers: 2086-83-1 (Berberine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PLANT AND CELL PHYSIOLOGY***** Takeshita N Fujiwara H Mimura H Fitchen JH Yamada Y Sato F Molecular cloning and characterization of S-adenosyl-L- methionine:scoulerine-9-O-methyltransferase from cultured cells of Coptis japonica. In: Plant Cell Physiol (1995 Jan) 36(1):29-36 ISSN: 0032-0781 S-Adenosyl-L-methionine:scoulerine-9-O-methyltransferase (SMT) catalyzes the transfer of the S-methyl group of S-adenosyl-L- methionine to the 9-hydroxyl group of scoulerine during the biosynthesis of berberine. We have isolated functionally active cDNA clones (pCJSMTs) from a cDNA library prepared from cultured cells of Coptis japonica. The longest cDNA insert (pCJSMT1) had an open reading frame that encoded 351 amino acids, but the calculated molecular mass (38,364 Da) of the deduced product was slightly lower than the experimentally determined molecular mass of purified SMT. Rapid amplification of the 5' end of the cDNA indicated that the full- length cDNA of SMT consisted of 1,458 nucleotides that encoded 381 amino acids. When the full-length cDNA was expressed in E. coli, the molecular mass of the expressed SMT was greater than that of native SMT in Coptis cells. This result suggests that SMT might be produced in a pre-mature form and processed post-translationally. SMT was also found to exhibit sequence homology to other O-methyltransferases from plants and N-terminal region of the SMT polypeptide appeared to be necessary for enzymatic activity. Registry Numbers: EC 2.1.1. (Methyltransferases) EC 2.1.1.- (S-adenosyl-L-methionine - scoulerine-9-O-methyltransferase) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PLANTA MEDICA***** Lee GI Ha JY Min KR Nakagawa H Tsurufuji S Chang IM Kim Y Inhibitory effects of Oriental herbal medicines on IL-8 induction in lipopolysaccharide-activated rat macrophages. In: Planta Med (1995 Feb) 61(1):26-30 ISSN: 0032-0943 Cytokine-induced neutrophil chemoattractant (CINC), a rat interleukin- 8 (IL-8), was quantitated by using a sensitive ELISA. The CINC was induced up to 20 ng/ml from basal 1-2 ng/ml in lipopolysaccharide (LPS)-activated peritoneal macrophages. This CINC induction was significantly inhibited by steroidal anti-inflammatory drugs including dexamethasone, but not by non-steroidal drugs including indomethacin at all. Nine out of 59 herbal medicines which are frequently used in Korean traditional prescriptions for inflammatory diseases exhibited more than 50% of inhibition on the CINC induction by their total methanol extracts with 0.1 mg/ml as a final concentration. The active 9 total extracts were prepared from radix of Aralia continentalis, rhizoma of Cnidium officinale, rhizoma of Coptis chinensis, tuber of Fritillaria verticillata, radix of Saussurea lappa, tuber of Sparganium stoloniferum, flower of Syzygium aromaticum, semen of Trichosanthes kirilowii, and herba of Tripterygium regelii. These total extracts were sequentially fractionated with dichloromethane, ethyl acetate, butanol, and water. Among the solvent-fractionated extracts with 0.05 mg/ml as a final concentration, more than 50% of inhibition on the CINC induction was exhibited by the dichloromethane fraction of Aralia continentalis; the water fraction of Fritillaria verticillata; the dichloromethane fraction of Saussurea lappa; the dichloromethane, ethyl acetate, and butanol fractions of Syzygium aromaticum; the dichloromethane, ethyl acetate, and water fractions of Trichosanthes kirilowii; and the dichloromethane and ethyl acetate fractions of Tripterygium regelii. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Lee MK Kim HS Inhibitory effects of protoberberine alkaloids from the roots of Coptis japonica on catecholamine biosynthesis in PC12 cells. In: Planta Med (1996 Feb) 62(1):31-4 ISSN: 0032-0943 The effects of protoberberine alkaloids from Coptis japonica Makino (COPT) on catecholamine content and tyrosine hydroxylase (TH) activity in PC12 cells were investigated. The butanol (BuOH) fraction from COPT at a concentration of 40 micrograms/ml medium inhibited catecholamine biosynthesis. The BuOH fraction was further fractionated into separate bioactive fractions (Fr. I-IV) by silica gel column chromatography, and Fr. II and III, which contain protoberberine alkaloids such as berberine and palmatine, were isolated. Fr. III at 40 micrograms/ml medium showed 77% inhibition on dopamine content in PC12 cells (IC50; 19.5 micrograms/ml medium). TH activity was reduced by the treatment of Fr. III. Berberine and palmatine also showed an inhibitory activity on dopamine biosynthesis in PC12 cells. The IC50 values of berberine and palmatine were 9.5 and 7.7 micrograms/ml medium, respectively. This suggests that the protoberberine alkaloids from COPT have an inhibitory effect on catecholamine biosynthesis by reducing TH activity in PC12 cells. Registry Numbers: EC 1.14.16.2 (Tyrosine 3-Monooxygenase) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Kobayashi Y Yamashita Y Fujii N Takaboshi K Kawakami T Kawamura M Mizukami T Nakano H Inhibitors of DNA topoisomerase I and II isolated from the Coptis rhizomes. In: Planta Med (1995 Oct) 61(5):414-8 ISSN: 0032-0943 A water extract of Coptis chinensis was found to have the ability to stabilize the cleavable complex with mammalian DNA topoisomerase I. As the result of bioassay-guided fractionation, two protoberberine alkaloids, epiberberine and groenlandicine, were identified as active principles with topoisomerase I-mediated DNA cleavage activity in vitro. These two alkaloids did not induce topoisomerase II-mediated DNA cleavage. During further examination of the structurally related protoberberine alkaloids, berberrubine which is produced during the processing of Coptis rhizome as traditional medicine, was identified as a specific inducer of topoisomerase II-mediated DNA cleavage in vitro. These results indicated that protoberberine alkaloids are a chemical family which can induce cleavable complexes with topoisomerases I and II. Registry Numbers: EC 5.99.1.2 (DNA Topoisomerase) EC 5.99.1.3 (DNA Topoisomerase (ATP-Hydrolysing)) 19716-69-9 (protoberberine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PROCEEDINGS / ANNUAL MEETING OF THE AMERICAN ASSOCIATION FOR***** Yamashita Y Fujii N Nakano H Identification of novel topoisomerase I inhibitors (Meeting abstract). In: Proc Annu Meet Am Assoc Cancer Res (1994) 35:707 ISSN: 0197-016X DNA topoisomerase I has been shown to be the principal target for the antitumor plant alkaloid camptothecin. The extensive studies on camptothecin derivatives demonstrated that antitumor activity is correlated with their ability to stabilize a key reaction intermediate of topoisomerase I, termed cleavable complex. Recent clinical trial of camptothecin derivatives CPT-11 and topotecan have shown that these drugs have promising activities in a broad spectrum of tumors. This has led to a search for new agents which induce cleavable complex with topoisomerase I. Structurally related novel anthraquinone antibiotics have been shown to induce topoisomerase I mediated DNA cleavage: saintopin and UCE1022, produced by Paecilomyces sp, and UCE6, from actinomycetes. The cleavable complex with topoisomerase I induced by these drugs has characteristics similar to that of camptothecin with respect to their potency and the reversal at high temperature (65 C). DNA cleavage pattern produced by saintopin, UCE6 and UCE1022 were nearly identical, but strictly different from that of camptothecin. Among these new topoisomerase I inhibitors, saintopin has unique property in its mechanism of action because saintopin can also induce topoisomerase II-mediated DNA cleavage. Semisynthetic antitumor drugs with indolocarbazole structure (KT6006, KT6528 and ED-110) have been shown to have topoisomerase I-mediated DNA cleavage activities comparable to that of camptothecin. In contrast to nonintercalator camptothecin, these drugs showed DNA intercalation activity on DNA unwinding assay. Evaluation of their antitumor activity in comparison with structurally related inactive derivatives showed a correlation between antitumor activity and topoisomerase I-mediated DNA cleavage activity, indicating that the cleavable complex formation with topoisomerase I could be responsible for the antitumor activity of these indolocarbazole compounds. Bulgarein, a benzofluoranthene compound originally isolated as fungal pigment, has been identified as topoisomerase I-active compound. Topoisomerase I-mediated DNA cleavage activity of bulgarein is comparable to that of camptothecin but suppressed at higher drug concentrations. DNA unwinding assay showed that bulgarein induced the DNA winding like that of AT- specific DNA minor groove binder netropsin. DNA minor groove binding ligands, Hoechst dye 33342 and 33258, have been reported to induce topoisomerase I-mediated DNA cleavage. Although these drugs share a mechanism of action similar to camptothecin in stabilizing cleavable complex with topoisomerase I, the major DNA cleavage sites have been shown to be highly AT-rich, which is distinctly different from those induced by camptothecin. Benzophenanthridine alkaloids--nitidine isolated from Zanthoxylum nitidum and fagaronine from Fagara xanthoxylum--have been shown to induce topoisomerase I-mediated DNA cleavage. In addition, berberine type alkaloids, epiberberine and gloenlandicine isolated from Coptis chinensis, have been found to induce topoisomerase I-mediated DNA cleavage in the course of our plant extract screening. In the 1980s, only camptothecin and its derivatives were known as topoisomerase I inhibitors in contrast to the variation of topoisomerase II inhibitors. Recent success in identifying several novel topoisomerase I inhibitors shows that topoisomerase I is an important target for the screening of new antitumor agents. (9 Refs) Registry Numbers: 9007-49-2 (DNA) EC 5.99.1.2 (DNA Topoisomerase) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ ****PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES*** Okada N Koizumi N Tanaka T Ohkubo H Nakanishi S Yamada Y Isolation, sequence, and bacterial expression of a cDNA for (S)- tetrahydroberberine oxidase from cultured berberine-producing Coptis japonica cells [published erratum appears in Proc Natl Acad Sci U S A 1990 Sep;87(17):6928] In: Proc Natl Acad Sci U S A (1989 Jan) 86(2):534-8 ISSN: 0027-8424 cDNA clones for the (S)-tetrahydroberberine (H4Ber) oxidase of cultured berberine-producing Coptis japonica cells were isolated by screening a C. japonica cDNA library with synthetic nucleotides that can encode the NH2-terminal sequence of this enzyme. Analyses of the nucleotide sequences of the cloned cDNA inserts revealed a 759-base- pair open reading frame that encoded a 253-amino acid polypeptide with a Mr of 27,089 and NH2-terminal and internal sequences identical with those of the (S)-H4Ber oxidase, as determined by microsequencing methods. Escherichia coli were transformed with an expression vector carrying (S)-H4Ber oxidase cDNA. The transformed bacteria were induced to overproduce a 28-kDa protein that reacted with Coptis (S)- H4Ber oxidase-specific antibody. A comparison of the derived amino acid sequence of (S)-H4Ber oxidase with sequences in the protein data base of the Protein Research Foundation showed a marked similarity between (S)-H4Ber oxidase and the NH2-terminal portion of mouse P1- 450, which is encoded by a single exon of the mouse P1-450 gene. The availability of cloned cDNA for (S)-H4Ber oxidase allows use of the methods of molecular biology to study the regulation of (S)-H4Ber oxidase gene expression in cultured C. japonica cells in relation to berberine biosynthesis. Registry Numbers: EC 1. (Oxidoreductases) EC 1.3.3.- (tetrahydroprotoberberine oxidase) 2086-83-1 (Berberine) 63231-63-0 (RNA) 9007-49-2 (DNA) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****TOKAI JOURNAL OF EXPERIMENTAL AND CLINICAL MEDICINE***** Kaneda Y Tanaka T Saw T Effects of berberine, a plant alkaloid, on the growth of anaerobic protozoa in axenic culture. In: Tokai J Exp Clin Med (1990 Nov) 15(6):417-23 ISSN: 0385-0005 Extracts obtained by organic solvents from the root of Coptis teeta in Myanmar (Burma), were tested for growth inhibitory activity against Giardia lamblia, Trichomonas vaginalis and Entamoeba histolytica in axenic culture. All extracts had anti-protozoal activity with the methanol extract, in particular, being effective against all 3 parasites. By chromatographic analysis, the extracts were shown to contain berberine compounds and other alkaloids. Comparing the inhibitory effects of the methanol extract with berberine sulfate, a berberine salt previously shown to possess inhibitory activity, it was observed that the crude extract was more effective than the salt. This suggests that the greater inhibitory activity of the crude extract may be due to the cumulative contributions of its contained berberines and alkaloids. Based on these findings, it appears that the berberine compounds may be useful as chemotherapeutic agents against the 3 parasites tested. Registry Numbers: 2086-83-1 (Berberine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****YAKUGAKU ZASSHI. JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN***** Ozaki Y Suga C Yoshioka T Morimoto T Harada M [Evaluation on equivalence of pharmacological properties between natural crude drugs and their cultured cells based on their components. Accelerative effect of lithospermi radix and inhibitory effect of coptidis rhizoma on proliferation of granulation tissue] In: Yakugaku Zasshi (1990 Apr) 110(4):268-72 ISSN: 0031-6903 (Published in Japanese) The present study was carried out to evaluate an equivalence of pharmacological properties between natural crude drugs and their cultured cells. The effects of ether extract of Lithospermi Radix and cultured cells of Lithospermum erythrorhizon Sieb. et Zucc. and aqueous extract of Coptidis Rizoma and cultured cells of Coptis japonica Makino var. dissecta Nakai on proliferation of granulation tissue in rats were compared. The ether extracts of Lithospermi Radix and the cultured cells enhanced proliferation of granulation tissue by the cotton pellet method. The potency of both extract was about the same, if results were compared with the corresponding doses which contained the same quantity of shikonin derivatives. On the other hand, the aqueous extracts of Coptidis Rhizoma and the cultured cells inhibited it. The potency of both extract was about the same, if results were compared with the corresponding doses which contained the same quantity of berberine-type alkaloids. From these results, to evaluate an equivalence of pharmacological properties between natural crude drugs and their cultured cells, it is concluded that their qualities and quantities are not so different each other and the almost same pharmacological effect expected on the basis of their uses is required. Registry Numbers: 54952-43-1 (shikonin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Namba T Sekiya K Toshinal A Kadota S Hatanaka T Katayama K Koizumi T [Study on baths with crude drug. II.: the effects of coptidis rhizoma extracts as skin permeation enhancer] In: Yakugaku Zasshi (1995 Aug) 115(8):618-25 ISSN: 0031-6903 (Published in Japanese) Skin permeation and its enhancing activity of Coptidis Rhizoma (Coptis japonica Makino) were studied in regard to its application as a bath agent. As a result, methanol extracts and three alkaloids (berberine, coptisine, and palmatine isolated from Coptidis Rhizoma) enhanced effectively the skin permeation of 5-fluorouracil, which is taken as a hydrophilic permeant. Furthermore, it was observed that diffusion coefficient is almost constant on the skin permeation of 5- fluorouracil and was also observed that these three kinds of alkaloids did not penetrate through the skin, but adsorbed into the skin. These results suggest that these three protoberberine type alkaloids increase the concentration of polar drugs in the skin and enhance the skin permeation similarly to surfactants. Registry Numbers: 2086-83-1 (Berberine) 3486-66-6 (coptisine) 3486-67-7 (palmatine) 51-21-8 (Fluorouracil) 7732-18-5 (Water) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Ozaki Y Suzuki H Satake M [Comparative studies on concentration of berberine in plasma after oral administration of coptidis rhizoma extract, its cultured cells extract, and combined use of these extracts and glycyrrhizae radix extract in rats] In: Yakugaku Zasshi (1993 Jan) 113(1):63-9 ISSN: 0031-6903 (Published in Japanese) The present study was carried out to evaluate the bioequivalence between Coptidis Rhizoma and the cultured cells of Coptis japonica Makino var. dissecta Nakai to compare the concentration of berberine in the rat plasma after oral administration of both aqueous extracts. The concentration of berberine in the plasma after oral administration of both extracts was determined by HPLC. It was found that the values of time required for the maximum concentration (Tmax), the maximum concentration (Cmax) and the area under the plasma-time curve (AUC24h) of berberine in the rat plasma after oral administration of both extracts were about the same. It was also found that the values of Tmax, Cmax and AUC24h of berberine after oral administration of both extracts and an aqueous extract of Glycyrrhizae Radix were about the same as that of individual administration of both extracts. From these results, to evaluate the bioequivalence between Coptidis Rhizoma and cultured cells, it is important that the values of Tmax, Cmax and AUC24h of berberine after oral administration of both extracts are not different, and about the same values of berberine by the combined use of both extracts and the aqueous extract of other crude drugs are required. Registry Numbers: 2086-83-1 (Berberine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****YAO HSUEH HSUEH PAO [ACTA PHARMACEUTICA SINICA]***** Liu WZ Peng WB Yang CH [Berberine-electrochemical detector for the determination of berberine-type alkaloids in various Chinese patent medicines by flow injection analysis] In: Yao Hsueh Hsueh Pao (1991) 26(4):315-9 ISSN: 0513-4870 (Published in Chinese) A description is given for the preparation of flow through sensor and of the incorporation of the sensor into a flow injection analysis system. The parameters affecting the measurement are discussed. An accurate, convenient and rapid method is proposed for the determination of berberine-type alkaloids in various Chinese patent medicines (Coptis chinensis Franch., Phellodendron chinesis Schneid., xianglian wan, zuojin wan, ermiao wan and sanmiao wan). The slope is 54-60 mV/decade over the concentration range of 10(-3)-3 x 10(-6) mol/L berberine at pH 2-9.5. Direct potentiometry determination of berberine in various samples showed an average recovery of 99.5- 103.5% and a relative standard deviation of 1.3-3.5% at a sampling rate of 120/h. Registry Numbers: 2086-83-1 (Berberine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€