Preparation of Clinically Useful Sennoside-reduced Rhubarb.

OBJECTIVE: The aim of this study was to develop a method of removing sennoside to reduce the cathartic effect of rhubarb while conserving its other pharmacological activities. METHODS: Rhubarb powder was steam autoclaved at 121°C and 0.14 MPa for 20, 60, or 120 minutes, and HPLC analysis was conducted to determine levels of rhubarb components. Mice were fed non-autoclaved or 20-minute-autoclaved rhubarb extracts. Feces were collected and weighed over a 24-hour period. India ink was orally administered to determine the distance of fecal migration through the intestinal tract. RESULTS: Autoclaving 20, 60, and 120 minutes decreased sennoside A and B to trace levels but only autoclaving 20 minutes conserved most of the (+)-catechin, (-)-epicatechin, and (-)-epicatechin gallate contents (i.e., 69%, 90%, 88%, respectively). Therefore only rhubarb autoclaved for 20 minutes was used in subsequent experiments. Fecal output (in g) in mice treated with water (control), autoclaved rhubarb, and non-autoclaved rhubarb was 2.78 ± 0.07, 3.30 ± 0.13 (p = 0.348), and 3.81 ± 0.07 (p = 0.005). India ink migration was far less in mice treated with autoclaved rhubarb vs non-autoclaved rhubarb. CONCLUSION: Steam autoclaving the rhubarb for 20 minutes reduces sennoside levels and its cathartic activity while conserving its other pharmacological activities.

[Filtration of active fractions with function of expelling water retention with drastic purgative from Kansui Radix stir-baked with vinegar].

To study the function of expelling water retention with drastic purgative of different polarities of Kansui Radix stir-baked with vinegar on the cancerous ascites model rats, the furosemide was taken as positive control drug, and the cancerous ascites model rats were respectively orally administered with different polarities of Kansui Radix stir-baked with vinegar for 7 d. The amount of urine and ascites, the level of urinary sodium, potassium, chloride ion and pH, and the content of PRL1, AII, ALD in serum were investigated. Compared with model groups, ethyl acetate extract group showed a decreasing trend in ascites; the amount of urine of showed a significant increase (P < 0.05); the level of urinary sodium, potassium, chloride ion (P < 0.05, P < 0.01), pH (P < 0.05), and the content of PRL1, AII, ALD in serum all showed a significant decrease (P < 0.01). The effects of petroleum ether extract and n-butanol extract were weaker than that of ethyl acetate extract. The water exact was the weakest. The results showed that ethyl acetate extract is the active part of Kansui Radix stir-baked with vinegar on the function of expelling water retention with drastic purgative on the cancerous ascites model rats, alleviating the water-electrolyte disorder and body fluid acid-base imbalance, regulating the renin angiotensin aldosterone system.

The influence of rhein 8-O-ß-D-glucopyranoside on the purgative action of sennoside A from rhubarb in mice.

Rhubarb is one of the most well-known herbal medicines that constitute daiokanzoto (DKT), which is clinically effective for constipation. Sennoside A is transformed into an active metabolite, rheinanthrone, by intestinal bacteria. Sennoside A in rhubarb showed significantly accelerated metabolic activity in intestinal bacteria in comparison with sennoside A alone. In this study, we investigated the influence of rhubarb constituents on the metabolism and purgative activity of sennoside A. The 20% MeOH-eluted fraction separated by MCI-gel CHP-20P column chromatography from the water extract of rhubarb showed sennoside A metabolic activity similar to that of rhubarb extract. The 20% MeOH elute was further purified and rhein 8-O-ß-D-glucopyranoside (RG) was isolated. The metabolic activity of sennoside A was significantly accelerated by increasing the level of RG. Moreover, rhein, emodin and aloe-emodin also accelerated sennoside A metabolism. The purgative activity of sennoside A was significantly accelerated when RG or rhein was concomitantly given with sennoside A in a dose-dependent manner. These results suggest that anthraquinones contribute to the purgative action of sennoside A in rhubarb. Therefore, it is assumed that the influence of anthraquinones on the fate of rheinanthrone transformed from sennoside A may promote the purgative action of sennoside A.

Anthraquinones of Cissus populnea Guill & Perr (Amplidaceae).

Cissus populnea has been used locally to treat many ailments such as venereal, stomach and skin infections; and also used as laxative or purgative. Economically it has been used as binder in food and in lining dye pits. This work aims at determining the type of anthraquinones from the stem bark of C. populnea which might be a potential source of drugs (laxative/cathartic) using thin layer chramatograpy (TLC) and senna leaf as reference. The analysis showed the stem bark anthroquinone extract to contain physcion and chrysophanol.

[Novel exploration of cathartic pharmacology induced by rhubarb].

Rhubarb is well-known for its cathartic effect, and this cathartic effect, which is closely correlated with "whter" of traditional Chinese medicine (TCM), is brought into play in colon. Recent researches about the relation between formation and effects have identified that the anthraquinone glycosides with 1,8-dio-hydroxy and without hydroxyl in the 2, 3, 6, 7 location, such as emodin, rhein, chrysophanol, et al, can bring about fairly obvious effects of "Watery Diarrhea". Aquaporins (AQPs) are expressed abundantly in colonic epithelial cells, and the abnormal expression of AQPs can lead to the less absorption of water in colon and/or the more secretion of intestinal juice, which suggest that AQPs might be one kind of the effector molecules, which some drugs playing pharmacologic actions in colon depend on. This assumption provides a novel field of vision. Is this "Watery Diarrhea" effect induced by rhubarb concerned with the location alteration or the expression change of AQPs. We deduce that the regulative effects of AQPs by rhubarb in colon might provide a new pharmacologic explation about the cathartic effect through the exploration of TCM and Chinese herbal drugs, with TCM theory and the analysis of data about efficiency and pharmacologic researches of rhubarb and the researches of AQPs. This deduction might be used to reveal why rhubarb can bring about multi-efficiency.

Development and validation of three stability-indicating methods for determination of bisacodyl in pure form and pharmaceutical preparations.

Three new, simple, sensitive, and accurate stability-indicating methods were developed for quantitative determination of bisacodyl in the presence of its degradation products, monoacetyl bisacodyl (I) and desacetyl bisacodyl (II), in enteric coated tablets, suppositories, and raw material. The first is a spectrodensitometric method in which the drug is separated from I and II on silica gel plates using chloroform-acetone (9 + 1, v/v) as the mobile phase with ultraviolet detection of the separated bands at 223 nm over a concentration range of 0.2-1.4 microg/band for bisacodyl with mean recovery 100.35 +/- 1.923%. The second method is fourth derivative D4 spectrophotometry, which allows determination of bisacodyl in the presence of its degradation products in raw material at 223 nm using acetonitrile as the solvent with adherence to Beer's law over the concentration range 2-18 microg/mL with mean recovery 99.77+/-1.056%. In the third method, the spectrophotometric data of bisacodyl, I, and II using absolute ethanol as solvent were processed by 3 chemometric techniques: classical least-squares, principal component regression, and partial least-squares. A training set consisting of 15 mixtures containing different ratios of bisacodyl, I, and II was used for construction of the 3 models. A validation set consisting of 6 mixtures was used to validate the prediction ability of the suggested models. The 3 chemometric methods were applicable over a concentration range between 2-14microg/mL for bisacodyl with mean recovery of 99.97+/-0.865, 100.01 +/- 0.749, and 99.97 +/- 0.616% for the 3 models, respectively. The proposed methods were checked using laboratory-prepared mixtures and were successfully applied to the analysis of raw material and pharmaceutical formulations containing bisacodyl, except for the second method that applies only for raw material. The validity of the suggested procedures was further assessed by applying the standard addition technique; the recoveries obtained were in accordance with those given by the reference method.

Profiling of the resin glycoside content of Mexican jalap roots with purgative activity.

Mexican Jalap roots, a prehispanic medicinal plant complex still considered to be a useful laxative, can be found as an ingredient in some over-the-counter products sold by herbalists in contemporary Mexico. The drug is prepared from the dried roots of several morning glories, all of which have been identified as members of the genus Ipomoea. Analysis of several commercial samples was assessed by generating HPLC and 13C NMR spectroscopic profiles of the glycosidic acids obtained through saponification of the resin glycoside contents. These profiles distinguish the three Mexican jalaps currently in frequent use and can serve as analytical tools for the authentication and quality control of these purgative herbal drugs. Ipomoea purga, the authentic "jalap root", yielded two new hexasaccharides of convolvulinic and jalapinolic acids, purgic acids A (1) and B (2), respectively. Scammonic acid A (3), a tetrasaccharide, was produced from Ipomoea orizabensis, the Mexican scammony or false jalap. Operculinic acid B (4), a pentasaccharide, was identified in Ipomoea stans. Semipreparative HPLC was performed to obtain pure samples of new compounds 1 and 2 in sufficient quantity to elucidate their structure by high-field NMR spectroscopy. Purgic acid A (1) was identified as (11S)-hydroxytetradecanoic acid 11-O-beta-D-quinovopyranosyl-(1-->2)-O-beta-D-glucopyranosyl-(1-->3)-O-[beta-D-fucopyranosyl-(1-->4)]-O-alpha-L-rhamnopyranosyl-(1-->2)-O-beta-D-glucopyranosyl-(1-->2)-O-beta-D-quinovopyranoside, while purgic acid B (2) was characterized with (11S)-hydroxyhexadecanoic acid as its aglycon but having the same glycosidation sequence in the oligosaccharide core.

[Comparative studies on purgative potency among three spieces of certified rhubarb].

OBJECTIVE: To investigate the difference and causes of purgative activity in three species of certified rhubarb, so as to lay steady foundations of further research on assessing purgative activity impersonally by using measurable indexes. METHOD: The potencies of three species were comparied with purgative ED, of mice as quantitative index which were calculated, and activities of Na+ K + -ATP ase in mouse colonic epithelial cell membrane were also investigated . The related purgative contents (conjunct and free rhein, chrysophanol, chrysophanic acid, sennoside A) were detected by HPLC and contents (total anthraquinones, anthraglucosennin; conjunct and free anthraquinones) were detected by UV. RESULT: There were different purgative activities among three spieces of certified rhubarb. Each purgative ED, of mice was Rheum tanguticum ( ED50 = 0. 37 g x kg (-1)) , R. officinale ( ED50 = 0. 99 g x kg(-1) ) and R. palrnatum from Gansu (ED50 = 1. 83 g x kg(-1)) , the ratio of potency of those was 4. 94: 1. 85: 1. In the meanwhile, the difference of the inhibitory effect on Na+ -K + -ATP ase in mouse colonic epithelial cell membrane and relative purgative components also existed in the three species of certified rhubarb. CONCLUSION: It disclosed that there was notable diference of purgative activity and components among three spieces of certified Rhubarb, which probably resulted in the ultimate diference in clinical prescription and the production of Chinese patent medicines.

[Opinion of colon-targeting delivery about rhubarb extract as a purgative].

OBJECTIVE: To elucidate that rhubarb extract as a purgative should be delivered to colon from a pharmaceutical point of view. METHOD: Effects of anthranoids and free anthraquinones as purgatives on the colon motility and transit time, the absorption in vivo, and the loss in the processes of extraction, concentration and dryness were reviewed, based on the recent 60 years pharmacological, pharmaceutical and clinical experimental studies at home and abroad. RESULT AND CONCLUSION: Free anthraquinones in rhubarb extract should be regarded as purgative principles. Close attention should be paid to the loss of free anthraquinones not only in the processes of extraction, concentration and dryness, but also in the process of transit in the upper gastrointestinal tract. Colon-targeting delivery of rhubarb extract, as a purgative, may prevent absorption of free anthraquinones in the upper gastrointestinal tract, thus improving clinical effects and lowering dosage.

Isolation and structure analysis of a glucomannan from the seeds of Libyan dates.

Polysaccharides extracted from seeds of Libyan dates with hot ethanol 80% (FI) and 0.1 M phosphate solution (FII) were fractionated and purified by ion-exchange and gel-filtration chromatography. According to methylation and hydrolysis analysis, the main chains of FI and FII consisted of (1-->4)-linked glucomannan; only traces of branched sugar residues were detected. This is the first report on the isolation of glucomannan from date seeds.

Studies of aloe. VI. Cathartic effect of isobarbaloin.

The cathartic effect of isobarbaloin, a stereoisomer of barbaloin (compound principally responsible for the cathartic activity of Aloe), was examined in male rats by oral administration. Individual differences in sensitivity in the laxative activity of isobarbaloin and barbaloin was not found. The cathartic activity (ED50) of isobarbaloin in barbaloin positive rats was 19.2 mg/kg, nearly equal to that of barbaloin (19.5 mg/kg). Also, isobarbaloin administered orally was demonstrated to decompose to aloe-emodin-9-anthrone (active metabolite of barbaloin) as well as to barbaloin. Therefore, it is considered that the mechanism underlying the cathartic effect of isobarbaloin is the same as that of barbaloin.

Purgative activity and principals of the fruits of Rosa multiflora and R. wichuraiana.

Pseudocarps or seeds of Rosa multiflora, crude drug "Eijitsu" have been used as purgative in Japanese traditional medicine. R. wichuraiana was generally thought to be able to substitute for the plant. The n-butanol fractions of both plant seeds were tested on purgative activities with mice, and the values of the 50% effective dose (ED50) were 5.6 g/kg as the seed weight for R. multiflora and 57 g/kg as the seed weight for R. wichuraiana. From pseudocarps of R. multiflora, a new purgative compound, multinoside A acetate, was isolated, and its ED50 value was tested to be 150 mg/kg (77-291 mg/kg, 95% confidence limit). The other isolated compounds were three known quercetin glycosides, quercetin 3-O-xyloside, isoquercitrin and hyperin. From pseudocarps of R. wichuraiana, three quercetin glycosides, isoquercitrin, hyperin and quercetin 3-O-beta-D-glucuronide were isolated similarly, but no purgative components of R. multiflora were detected.

Bicascarosides in fluid extracts of cascara.

Bianthraquinone glycosides are formed during the preparation and conservation of fluid extracts of cascara. Analysis of these preparations has shown that up to 20% of total amount of anthracene glycosides can be dimerized. These dimers are devoid of laxative activity. They are absorbed in the intestine and very slowly excreted.

Ispaghula sensitization in workers manufacturing a bulk laxative.

Exposure to ispaghula dust in a pharmaceutical factory resulted in chest tightness/wheeze, nasal, and ocular or skin symptoms in 48 of 92 exposed workers. Whilst symptoms were not incapacitating in the majority (44) of these, one worker required antihistamines and three others experienced severe respiratory symptoms when exposed to the dust. These three were atopic, had a positive RAST and skin test to ispaghula; a combination unique to them. There was a significant relationship between work-related symptoms and atopic status, however, smoking did not influence symptoms, total serum IgE and specific anti-ispaghula IgE. We conclude that handling ispaghula produces an irritant effect in most exposed people, however, sensitization to the dust can occur with severe respiratory symptoms.

The extraction, isolation and identification of the purgative component of Croton penduliflorus seed oil.

The purgative principles in Croton penduliflorus seed oil were isolated as white crystals by a bioassay-guided chromatographic separation process. The crystals were recovered in 7% w/w yield and identified (IR, 1H-NMR, GC-MS) as a mixture of palmitic, stearic and arachidic acids in approximately equimolar concentration.