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Research regarding the anti-diarrhea activity of Hydrastis canadensis (goldenseal) and/or its active compounds berberine and hydrastine
This information has been complied in order to facilitate the research efforts of health care professionals and others. These statements have not been evaluated by the Food and Drug Administration and are not intended diagnose, treat, cure, prevent, mitigate, or prevent any disease. Nor are they intended to make specific claims regarding our products. The information is presented with the latest publications first. This is an ongoing work so check back often as we will update these pages as more information becomes available. Last Updated : 08/25/2008
The Effect of Berberine Chloride on Experimental Colitis in Rats In Vivo and In Vitro
Haiyan Zhou and Satoru Mineshita
Jour. Pharm. And Exp. Ther. Vol. 294, Issue 3, 822-829, September 2000
Berberine is an isoquinoline alkaloid with
multiple pharmacological actions, including anti-inflammatory activity. The
aims of this study were to examine the effect of berberine on the
mucosal healing process and to investigate whether berberine can
inhibit the increased production of interleukin-8 in
trinitrobenzene sulfonic acid-induced colitis in rats. Berberine
was administered orally for 3 days or 1 week at a dosage of
7.5 or 15 mg/kg/day. Tissue damage scores, body weight, colon wet
weight, and colon wall thickness were measured, and
myeloperoxidase activity in colon tissue was also examined.
Histological lesions, morphological damage, and myeloperoxidase
activity were reduced after 1 week of treatment with berberine at
a dosage of 15 mg/kg/day. Furthermore, 1 week after
trinitrobenzene sulfonic acid treatment, the production of
interleukin-8 by cultured rectal mucosa or cardiac blood mononuclear
cells with or without stimulation of lipopolysaccharide for 24 h
was also analyzed by enzyme-linked immunosorbent assay. Cardiac
blood mononuclear cells and rectal mucosa of normal rats produced
substantial amounts of interleukin-8, which increased strikingly
with the stimulation of lipopolysaccharide. Cardiac blood mononuclear
cells and rectal mucosa of trinitrobenzene sulfonic acid-treated
rats secreted more interleukin-8 than those of normal rats. The
addition of berberine with a concentration of 10
5
M to the culture media resulted in an inhibition of interleukin-8
production of rectal mucosa.
Berberine inhibits ion transport in human colonic epithelia.
Taylor CT, Winter DC, Skelly MM, O'Donoghue DP, O'Sullivan GC, Harvey BJ, Baird AW.
Eur J Pharmacol. 1999 Feb 26;368(1):111-8.
The effects of berberine on ion transport in both human colonic mucosal epithelia and an intestinal epithelial cell line (T84) were examined. Berberine (concentration range 0-500 microM) reduced both basal and stimulated ion transport responses in human colonic mucosae in a manner which was non-specific for Ca2+ -or cAMP-mediated signals. Similarly, in cultured intestinal epithelial monolayers, berberine inhibited Ca2+ -and cAMP-mediated responses indicating an inhibitory activity directly at the level of the epithelium rather than an indirect effect through other mucosal element(s). Berberine did not alter the rate of generation of cAMP by adenylyl cyclase or the activity of protein kinase A, the effector enzyme of the cAMP pathway. Berberine inhibited carbachol-stimulated 86Rb+ efflux from T84 monolayers. Berberine also inhibited K+ conductance in apically-permeabilised re-sected mucosae. These results indicate i) that berberine exerts an anti-secretory action directly upon epithelial cells and ii) the mechanism of action may be at the level of blockade of K+ channels.
Mechanism and treatment of diarrhoea due to Vibrio cholerae and Escherichia coli: roles of drugs and prostaglandins.
Rabbani GH.
Dan Med Bull. 1996 Apr;43(2):173-85.
The primary objectives of these studies were to determine the clinical efficacy and safety of the potential antisecretory and antimicrobial drugs in the treatment of diarrhoea due to Vibrio cholerae and enterotoxigenic Escherichia coli (ETEC). The drugs evaluated were chlorpromazine (CPZ), nicotinic acid, berberine, indomethacin, chloroquine, tetracycline, furazolidone, and bioflorin. Additionally, the role of prostaglandins (PGs) in the pathogenesis of cholera diarrhoea has been studied. The drug studies were carried out as placebo-controlled, randomized clinical trials in patients with active diarrhoea due to vibrio cholerae and ETEC. All patients received intravenous (i.v.) or oral rehydration solutions (ORS), but no other medications except the study drugs. Results indicate that CPZ (1 mg/kg or 4 mg/kg), berberine (200 mg), and nicotinic acid (2 g) all reduced stool volumes from 30% to more than 50% in diarrhoeal patients without significant side effects. It appeared that berberine was more effective in ETEC diarrhoea than in cholera. However, chloroquine, indomethacin, clonidine, and bioflorin had no clinically useful effects. Among the antimicrobial agents, a single dose of tetracycline was found to be effective in cholera, because the drug significantly (p < 0.05) reduced the total stool volume from 20.9 +/- 15.9 to 10.5 +/- 8.6 (liters in 6-days, mean +/- SD) compared to furazolidone. Drugs other than antimicrobial and antisecretory agents were also evaluated in the treatment of cholera. It has been shown that treatment with bioflorin, which is a bacterial preparation of lyophilized Streptococcus faecium, did not significantly (p > 0.05) reduce fluid-loss in cholera. Additional studies in animals indicated that treatment with short chain glucose polymers, alone or in combination with a chloride blocking agent, anthracene-9-carboxylic acid (A9C), significantly reduced intestinal secretion in a rat model of secretory diarrhoea. For the first time it was demonstrated that jejunal prostaglandin (PG) E2 concentrations were significantly increased during acute cholera and correlated with the volumes of stool and duration of diarrhoea. Furthermore, it was shown that treatment with indomethacin, a potent inhibitor of PG synthesis, significantly reduced jejunal PGE2 output in adults with acute cholera, in addition to net secretion of water and electrolytes. In summarizing the results, it is concluded that: (1) CPZ, berberine, and nicotinic acid are potential antidiarrhoeal agents, (2) PGs are involved in the pathogenesis of cholera, (3) tetracycline and furazolidone are effective antimicrobial agents in cholera, (4) and glucose short-chain polymers (used with the chloride blocking agent, anthracene-9-carboxylic acid) are better sources of carbohydrates in oral rehydration solutions.
Pharmacological studies on antidiarrheal
effects of berberine.
Takase H, Yamamoto K, Ito K, Yumioka E.
Nippon Yakurigaku Zasshi. 1993 Aug;102(2):101-12.
We studied the effects of berberine and Geranii Herba extract (GH) on different diarrheal models of mice, on the contractions of the isolated guinea pig intestinal smooth muscle and on the peristalsis in the rat intestine, comparing these effects with those of atropine (ATR) and papaverine (PAP). 1) Berberine significantly inhibited both the diarrhea induced by castor oil and that induced by BaCl2 at doses higher than 25 mg/kg, p.o., but did not inhibit diarrhea induced by pilocarpine or serotonin even at 250 mg/kg, p.o. GH exhibited a significant inhibition of BaCl2 induced diarrhea. ATR prevented pilocarpine-induced diarrhea most strongly in diarrheal models. PAP significantly inhibited castor oil-, BaCl2- and pilocarpine-induced diarrhea, but not the serotonin-induced one. 2) Berberine inhibited ACh- or Ba(2+)-induced contractions of the ileum and colon at a concentration of about 10(-5) g/ml, and PAP did so at about 10(-6) g/ml, but GH (10(-3) g/ml) failed to inhibit them. ATR prevented the ACh-induced contraction of the ileum and colon at concentrations 1/1000 of those needed to prevent the Ba(2+)-induced one. On the other hand, berberine as well as PAP exhibited a noncompetitive inhibition of the contractile response induced by ACh, whereas ATR showed a competitive inhibition. 3) Berberine, GH, ATR and PAP showed significantly inhibited the spontaneous peristalsis in the intestine. These results suggest that berberine and GH have antidiarrheal action and that the mechanism of action of berberine may be somewhat differ from that of GH.
[Antidiarrheal and anti-inflammatory effects of berberine]
Zhang MF, Shen YQ.
Zhongguo Yao Li Xue Bao. 1989
Mar;10(2):174-6.
Berberine sulfate (Ber) 40 and 80 mg/kg ig reduced the purging effects of
castor oil or Cassia angustifolia leaf in mice, but did not affect the
gastrointestinal transport function of Chinese ink in normal mice. Ber 60
mg/kg ig significantly inhibited the increased vascular permeability induced
by ip 0.7% acetic acid in mice. Ber 20 and 50 mg/kg sc markedly inhibited
the increased vascular permeability induced by histamine 100 micrograms/0.1
ml ic in rats. Ber 4 and 8 mg/kg sc produced obvious inhibition in the
xylene-induced swelling of mouse ear. The anti-inflammatory effects were
enhanced in a dose-dependent manner. It is suggested that the
antidiarrheal effect of Ber is relative to its restriction against exudative
inflammation to a certain extent.
Randomized controlled trial of berberine sulfate therapy for diarrhea due to enterotoxigenic Escherichia coli and Vibrio cholerae.
Rabbani GH, Butler T, Knight J, Sanyal SC, Alam K.
J Infect Dis. 1987 May;155(5):979-84.
To evaluate the antisecretory activity of berberine sulfate (BS), we studied 165 adult patients with acute diarrhea due to enterotoxigenic Escherichia coli (ETEC) and Vibrio cholerae in randomized controlled trials. In patients with ETEC diarrhea who received 400 mg of BS in a single oral dose, the mean stool volumes were significantly less than those of the controls during three consecutive 8-hr periods after treatment (P less than .05). At 24 hr after treatment, significantly more patients who were treated with BS and had ETEC diarrhea stopped having diarrhea as compared with the controls (42% vs 20%, P less than .05). In patients with cholera who received 400 mg of BS, the mean 8-hr stool volume during the second 8-hr period after treatment declined to 2.22 liters, which was significantly less than the 2.79 liters found in the controls (P less than .05). However, patients with cholera who received 1200 mg of BS plus tetracycline did not have significant reduction in stool output compared with patients who received tetracycline alone. No side effects of BS were noted. These results indicated that BS is an effective and safe antisecretory drug for ETEC diarrhea.
Antisecretory effects of berberine with morphine, clonidine, L-phenylephrine, yohimbine or neostigmine in pig jejunum.
Zhu B, Ahrens F.
Eur J Pharmacol. 1983 Dec 9;96(1-2):11-9.
The effects of berberine alone or in combination with morphine, clonidine, L-phenylephrine or yohimbine were compared in Escherichia coli heat-stable enterotoxin (ST)-exposed ligated jejunal loops in 2 week old pigs. In addition, net water and electrolyte fluxes in normal jejunal loops were measured in the presence of neostigmine, morphine, clonidine, L-phenylephrine or yohimbine alone or in combination with berberine. Berberine, morphine, clonidine and L-phenylephrine each reduced the net secretion of water and electrolytes induced by ST (P less than 0.05). A significant enhancement of antisecretory effect was observed only with the combination of berberine and L-phenylephrine. Yohimbine or neostigmine augmented the net loss of water and electrolytes produced by ST. Yohimbine did not block the antisecretory action of berberine. In normal jejunum, there was no significant difference in water and ion absorption between adrenergic or opiate agonists alone and their combination with berberine. Neostigmine reversed absorption to net secretion in normal jejunum and this effect was significantly reduced by berberine. The anti-secretory action of berberine appears similar to that of alpha 2-adrenergic agonists, opiates, and anticholinergic agents.
Effect of berberine on intestinal secretion mediated by Escherichia coli heat-stable enterotoxin in jejunum of pigs.
Zhu B, Ahrens FA.
Am J Vet Res. 1982 Sep;43(9):1594-8.
Intraluminal perfusion with Escherichia coli heat-stable enterotoxin (ST) reversed water and electrolyte movements from net absorption to net secretion in porcine jejunal segments. Addition of berberine hydrochloride (3.2 X 10(-5) M) to the perfusate reduced the jejunal secretory response of water, sodium, potassium, and chloride to ST and enhanced water and electrolyte absorption in control segments. At lower concentrations (1.1 X 10(-5) M), berberine reduced the secretory response in ST-exposed segments, but only the decrease of sodium flux was significant. In the presence of berberine, the mucosal enzyme activities of adenosine triphosphatase and disaccharidases were not significantly different between control and ST-exposed segments. Doses of 1, 2, 3, 4, 5, and 10 mg of berberine were injected into ligated loops of proximal part of the jejunum with 1 ml of ST filtrate. At doses of 2 or more mg/loop, berberine was effective in reducing water and electrolyte secretions induced by ST; the effect was dose-dependent. These findings indicate that berberine may be an effective antidiarrheal agent in E coli heat-stable enterotoxin mediated secretory diarrhea and provide a basis for the frequent empirical use of berberine alkaloid and berberine-containing plants in gastroenteritis and infectious diarrhea in Asian and other countries.
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