Antidiarrheal Activity of Wood Creosote: Inhibition of Muscle Contraction and Enterotoxin-Induced Fluid Secretion in Rabbit Small Intestine

Ogata, Norio; Shibata, Takashi

doi:10.1159/000056092

Cited by 10 publications

(7 citation statements)

References 19 publications

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“…Although these two pathways are different, the ultimate effects of LT and STa are similar, i.e., activation (opening) of CFTR. Therefore, our previous finding that wood creosote inhibits both LT-and STa-induced fluid secretion of rabbit jejunum in vivo [22,23] strongly suggests that this compound inhibits Cl -secretion from enterocytes by inhibiting a CFTR function.…”

Section: Discussionmentioning

confidence: 94%

“…We previously reported its various pharmacological properties [18][19][20][21]. We also reported that intestinal fluid secretion caused by LT and STa enterotoxins of Escherichia coli was inhibited by wood creosote in vivo in rabbit jejunum [22,23]. These results suggest that some constituent of wood creosote inhibits Cl -secretion by affecting cyclic AMP-or cyclic GMP-mediated pathways of Cl -secretion through Cl -channels in intestinal epithelium [9,[24][25][26].…”

Section: Introductionmentioning

confidence: 89%

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Inhibition of Rat Intestinal Cl<sup>–</sup> Secretion by 4,5-Dimethylresorcinol

Ogata

Shibata²

2004

Pharmacology

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Wood creosote, a mixture of phenolic compounds, inhibits enterotoxin-induced intestinal fluid secretion, suggesting that one of its constituents suppresses transepithelial Cl^– secretion from the intestinal mucosa. To identify an active constituent in wood creosote that inhibits intestinal Cl^– secretion through Cl^– channels, we first examined its effect on Cl^– secretion using a cultured cell line transfected with complementary DNA encoding a Cl^–channel and a Cl^–-sensitive fluorescent dye. We next assayed chromatographic fractions of wood creosote for the inhibitory activity on Cl^– secretion using a Ussing chamber. We found that 4,5-dimethylresorcinol, identified by gas chromatography-mass spectrometry, inhibited intestinal Cl^– secretion dose-dependently when added to a serosal, but not mucosal, surface of rat jejunum, a half-inhibitory concentration being 3.8 µg/ml (28 µmol/l). It was strongly suggested that this effect was due to inhibition of Cl^– channels.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 89%

Inhibition of Rat Intestinal Cl<sup>–</sup> Secretion by 4,5-Dimethylresorcinol

Ogata

Shibata²

2004

Pharmacology

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“…The secretion inhibition was more potent following serosal application whereas in the colon it inhibited STa-induced secretion with equal potency following serosal or mucosal addition. Wood creosote suppressed STa-induced increase in Isc (short circuit current) in a concentration-dependent manner, without causing a complete inhibition [96,97]. STa-induced fluid secretion in ligated rabbit jejunum was also inhibited.…”

Section: Wood Creosotementioning

confidence: 99%

Antibacterial and Antidiarrheal Activities of Plant Products against Enterotoxinogenic Escherichia coli

Dubreuil

2013

Toxins

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Enterotoxigenic Escherichia coli (ETEC) produces two types of enterotoxins: heat-labile (LT) and heat-stable (STa and STb). These molecules are involved in the induction of secretory diarrhea in animals including humans. This condition is currently treated using a fluid replacement therapy and antibiotics. This treatment is often not available to people in developing countries, and several die from the condition provoke by ETEC. Over the years, plants and plant extracts have been use as traditional medicine to treat various gastrointestinal ailments including diarrhea. Many of these plant products have been claimed to be active against diarrhea, however few have been extensively studied. The main objective of this review was to gather the scattered information on the antidiarrheal activities reported for various plant products on ETEC. This includes two major effects: (1) The inhibitory effect on bacterial growth or viability and (2) The interference with ETEC enterotoxins activity upon the intestinal epithelium. We will focus on plant products and extracts for which we have major indications of their biological activity against ETEC and their enterotoxins. Because Vibrio cholerae toxin (CT) is structurally, antigenically and mechanistically related to LT, it will also be discussed in this review.

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“…tility, slowing intestinal transit time, inhibiting chloride ion secretion, and augmenting net fluid absorption from the intestine in many in vivo and ex vivo animal models. [4][5][6] Clinical experience in humans indicates that wood creosote suppresses intestinal hypermotility and produces an antispasmodic effect in the setting of acute diarrhea. Decreased stool volume and frequency and relief of abdominal cramping have also been observed and reported anecdotally by clinicians.…”

confidence: 99%

Multiple‐Dose Escalation, Safety, and Tolerability Study of Wood Creosote, the Principal Active Ingredient of Seirogan, an Herbal Antidiarrheal Medication, in Healthy Subjects

Kuge

Shibata

Willett³

2003

The Journal of Clinical Pharma

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Seirogan, an herbal medicine containing wood creosote (CAS 8021-39-4), a mixture of simple phenolic compounds, has been marketed for the past century in Asia for the treatment of acute diarrhea and associated symptoms, such as abdominal discomfort and cramping. The present study was designed to assess the safety and tolerability of an anticipated acute antidiarrheal dosing regimen. Sixty healthy males were randomized into five groups of 12 subjects each (9 wood creosote; 3 placebo) to receive 45-, 90-, 135-, 180-, and 225-mg tablets every 2 hours for five doses. Serial sitting and standing vital signs, ECG rhythm strips, and continuous telemetry monitoring were obtained predose and for 24 hours after the first dose. Clinical laboratory tests and 12-lead resting ECGs were obtained predose and 24 hours postdose. Of the subjects, 27% (12/45) receiving wood creosote and 27% (4/15) receiving placebo reported adverse events. The most common adverse events were altered taste and somnolence, reported more often with 180- and 225-mg doses. Wood creosote had no clinically significant effects on vital signs, ECG intervals or interpretations, or clinical laboratory tests. No clinically significant or serious dysrhythmias were reported on continuous telemetry monitoring. It was concluded that oral doses of wood creosote 45 to 225 mg every 2 hours for up to five doses were safe and well tolerated in 45 healthy subjects. Wood creosote doses ranging from 45 to 135 mg per dose, which are commonly administered antidiarrheal doses in Asia, were associated with minimal side effects.

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Antidiarrheal Activity of Wood Creosote: Inhibition of Muscle Contraction and Enterotoxin-Induced Fluid Secretion in Rabbit Small Intestine

Cited by 10 publications

References 19 publications

Inhibition of Rat Intestinal Cl<sup>–</sup> Secretion by 4,5-Dimethylresorcinol

Inhibition of Rat Intestinal Cl<sup>–</sup> Secretion by 4,5-Dimethylresorcinol

Antibacterial and Antidiarrheal Activities of Plant Products against Enterotoxinogenic Escherichia coli

Multiple‐Dose Escalation, Safety, and Tolerability Study of Wood Creosote, the Principal Active Ingredient of Seirogan, an Herbal Antidiarrheal Medication, in Healthy Subjects

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