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PubMed2005

[Butcher's Broom, in the treatment of venous insufficiency].

Numerous extracts of the plants, natural compounds and their derivatives, acting on the venous system, including horse-chestnut seed extracts aescin, rutin, troxerutin, diosmin and hesperidine. They have a long tradition in herbal medicine for their venotonic and anti-oedematous properties. This review is concerning Rusci aculeati rhizoma, which recently taken in Poland on the symptoms of chronic venous insufficiency and hemorrhoids.

Chronic Disease↗
PubMed2006

Toxicological aspects of flavonoid interaction with biomacromolecules.

OBJECTIVES: Flavonoids are widely accepted as health promoting phytochemicals, however, some flavonoids show ability of direct interaction with DNA and/or enhance carcinogen activation into DNA modifying agents. Thus, their potential harmful effect on the human body should be examined in detail. METHODS: Direct interaction of flavonoids (quercetin, rutin) with DNA was examined using square wave voltammetry on carbon paste electrode. Induction effect of selected flavonoids on content of cytochrome P450 1A1, carcinogens activating enzyme, in colon and liver microsomal samples of animals exposed to flavonoids was determined by Western blotting, using anti-cytochrome P450 1A1 specific antibody. RESULTS: Of the natural flavonoids tested, induction of CYP1A1 was elicited by the typical citrus flavonoid naringenin in the colon, as well as by flavone in the liver. Moreover, synthetic beta-naphthoflavone and naturally occurring chrysin, quercetin and diosmin induced CYP1A1 in both tissues. The oxidation signals of guanine and adenine in the DNA molecule were decreased in the presence of flavonoids. CONCLUSIONS: Although flavonoids are often considered to be safe because of their "plant origin", ingestion of flavonoids should be taken with caution. Enhanced expression of CYP1A1 in colon tissue might be responsible for increasing incidence of colorectal carcinoma in humans. Electrochemistry can be used to study the interactions of flavonoids and DNA.

Adenine↗
PubMed1991

Effect of benzopyrone derivatives on simultaneously induced croton oil ear oedema and carrageenin paw oedema in rats.

Carrageenin paw oedema and croton oil ear oedema induced simultaneously in rats are inhibited in a dose-dependent manner and to statistically significant degrees by lipoxygenase- and cyclooxygenase-blocker flavonoids (diosmin, fisetin, quercetin, myricetin, galangin, sophoricoside, hesperidin-methylchalcone, oligomeric procyanidin, anthocyanidins (delphinidin, pelargonidin], and the prostaglandin antagonist polyphloretin phosphate and di-4-phloretin phosphate. Outstanding anti-inflammatory effects are displayed by myricetin and delphinidin, which contain vicinal hydroxy groups in ring B. The results confirm the importance of hydroxy group substitution in ring B. The most effective of the examined substances proved to be the prostaglandin antagonist di-4-phloretin phosphate.

Animals↗
PubMed1990

Preliminary screening of some Egyptian weeds for antimicrobial activity.

Eleven Egyptian weeds collected from the Menoufeya district were screened for phytochemical compounds effective against several representatives of bacteria and yeasts. It was found that Soxhlet benzene extracts, especially those of Capsella bursa-pastoris (L.) Medik., were the most effective. Alkaloids and flavonoids of Capsella gave the highest antibiotic potencies and had the broadest antimicrobial spectra. It is suggested that these alkaloids might consist of yohimbine and ergocristine and the flavonoids included the flavone diosmin.

Alkaloids↗
PubMed1989

[Edematous syndromes caused by capillary hyperpermeability. Diffuse angioedema].

Edema due to increased capillary permeability (ICP) may be diffuse or localized. Local edemas (Quincke edema, angioneurotic edema) are most often allergic or very rarely due to a defect in C1-inhibitor. Generalized edemas due to ICP share the following clinical features: Fluid retention (subcutaneous edema and diffused swelling) is predominant in lower limbs; it is worsened by orthostatism and warmth and alleviated by decubitus and cold, with important weight variations between morning and evening. It is associated with enhanced thirst, hypotension, oliguria, headaches and blood volume reduction; secondary hyperaldosteronism is the main mechanism. These troubles are due to ICP, associated with lymphatic drainage abnormalities; ICP is measured by the isotopic Landis Test. This abnormality is present in several diseases. Idiopathic orthostatic edema (IOE) is frequent and often unrecognized, occurring mainly in women, often associated with luteal insufficiency. Iatrogenic complications (diuretic and laxative abuses) are frequently superimposed. ICP may be corrected by vitamins P (rutin, anthocyanosides, diosmin, Ginkgo biloba extracts...) Cyclic shock due to ICP is rare. It is characterized by cyclic edema and shock with hypovolemia, hypoproteinemia; the mechanism of shock is a severe loss of fluid and protein from the vascular bed. It is often associated with monoclonal gammapathy and complement activation. In our personal case, the trouble in CP was present all along the disease with permanent edema and low blood pressure (especially in orthostatism). Vit "P" and Ginkgo biloba extracts were able to partially improve CP and the clinical troubles. However, in spite of this treatment a fatal shock occurred after ten years follow-up. Episodic angioedema associated with eosinophilia was first described by Gleich.(ABSTRACT TRUNCATED AT 250 WORDS)

Capillary Permeability↗
PubMed1989

Protective effect of a purified flavonoid fraction against reactive oxygen radicals. In vivo and in vitro study.

S 5682 is a purified flavonoid fraction containing 90% diosmin (flavone derivative) and 10% hesperidin (flavanone derivative). In this study the scavenging properties of S 5682 on active oxygen radicals were demonstrated in vivo and in vitro. The activity of intravenous S 5682 was evaluated in the rat by measuring the degree of hyperglycemia provoked by an intravenous injection of alloxan, the metabolism of which produces active oxygen radicals which are toxic to B cells of the pancreas. S 5682 produced a decrease in the hyperglycemia in a dose-dependent manner (25 mg/kg and 50 mg/kg). The production in vitro of active oxygen radicals during phagocytosis by polymorphonuclear cells and macrophages is accompanied by emission of photons which can be amplified in the presence of luminol. Measurement of this chemiluminescence is a way of determining the quantity of active oxygen radicals generated in the medium, this may be reduced either by a decrease in production or by an increase in neutralisation through a reducing effect. Results demonstrated that S 5682 had a scavenging effect on active oxygen radicals for concentrations between 2 x 10(-8) mol/l and 2 x 10(-4) mol/l. The concentration of S 5682 reducing the chemiluminescence by 50% was 1.6 x 10(-5) mol/l. These scavenging properties imply that S 5682 has a pharmacological action on capillary hyperpermeability as well as an anti-inflammatory and anti-oedematous action.

Animals↗
PubMed1987

Effect of chronic treatment with a purified flavonoid fraction on inflammatory granuloma in the rat. Study of prostaglandin E2 and F2 alpha and thromboxane B2 release and histological changes.

S-5682 (Daflon-500 mg), a purified flavonoid fraction, consisting of 90% diosmin (a flavone derivative) and 10% hesperidin (a flavanone derivative), was administered to rats by intubation in the daily dose of 100 mg/d. 15 days after the start of treatment, polyurethane sponges were implanted in the subcutaneous connective tissue in the dorsolumbar region under rapid ether anaesthesia. Similar fragments of sponge were implanted in a group of control animals who received the vehicle (saccharose syrup) only, also by the oral route. The rats were sacrificed in fractions of 7 animals drawn from each of the two groups (control and treated) after 4, 8, 16 and 30 days (only 5 animals from each group on day 30) after implantation of the polyurethane sponges. The granulomas formed were removed, weighed and their prostaglandin (PG)E2, PGF2 alpha and thromboxane (Tx)B2 contents were determined. In addition a full cell count (polymorphs, lymphocytes, macrophages, plasmocytes and giant cells) was performed and the animals were histologically examined. The results show that treatment of the animals with S-5682 had the following effects: 1. A significant fall in the mean weight of the granulomas formed after 4 and 8 days was observed, reflecting inhibition of oedema formation during the early phase of the inflammatory reaction. 2. The synthesis of PGE2 (78.5% inhibition on day 4) and PGF2 alpha (45.2% on day 16) was inhibited. 3. There was very early inhibition of TxB2 synthesis (59.5% inhibition on day 4). 4. A later reduction in cell migration towards the inflammatory focus occurred which was statistically significant on day 16 (49.6% reduction in the total number of migrant cells). 5. Multiple histological aspects of the acute inflammatory reaction (diapedesis of polymorphs, lymphocytes, histiocytes and macrophages) and features of the chronic inflammatory reaction (newly formed microvascularisation of the granuloma tissue, perivascular oedema, presence of collagen fibres) were improved.

Animals↗
PubMed1996

Effects of a purified micronized flavonoid fraction on capillary filtration in diabetic patients.

The objective of the present study was to investigate the effects of a purified micronized flavonoid fraction (Daflon 500 mg) on the increased capillary filtration of albumin (CFA) which is an early change in the microcirculation of patients with diabetes. A placebo controlled trial lasting 30 to 42 days including two equal groups of 20 patients, following a 15-day initial placebo run-in phase. The CFA test employed consisted of injecting albumin labelled with technetium (99mTc) intravenously, applying a venous tourniquet to one arm, and counting the radioactivity on the ipselateral forearm using an external gamma camera. The disappearance of radioactivity was analysed by means of two parameters after the tourniquet had been released, i.e. albumin retention (AR) and the LF/HF index which indicates lymphatic function in interstitial protein clearance. All patients included exhibited an increase in these two indices before the initial placebo run-in phase and at the end of the run-in period. At the end of the treatment phase, AR had significantly decreased in the group treated by the flavonoid fraction (FF) by comparison with the placebo group, and had normalized in 65% of patients in the FF group, compared with 25% of patients in the placebo group (p = 0.010). The LF/HF index normalized in 55% of cases in the FF group, compared with no patients on placebo (p = 0.00001). This study suggests that the flavonoid fraction tested here can improve and even normalize capillary filtration of albumin in diabetic patients.

Adult↗
PubMed2004

Benzo-pyrones for reducing and controlling lymphoedema of the limbs.

BACKGROUND: Lymphoedema is the accumulation of excess fluid in the body caused by obstruction of the lymphatic drainage mechanisms. It can be caused by a number of factors, including congenital predisposition, parasitic infection or surgery. Lymphoedema is chronic and progressive and affects a significant proportion of the population. The standard treatment regimes include compression hosiery, skin care and exercise. The use of drugs in treatment, particularly benzo-pyrones, has gained favour over the last ten years. Benzo-pyrones, originally developed for use in vascular medicine, are prescribed to reduce vascular permeability and thus the amount of fluid forming in the subcutaneous tissues. Advocates for this treatment method believe that, as a result of reducing filtration, the drugs have some beneficial effect on pain and discomfort in the swollen areas. Proponents also claim that these drugs increase macrophage activity, encouraging the lysis of protein, which in turn reduces the formation of fibrotic tissue in the lymphoedematous limb. OBJECTIVES: To assess the effectiveness of benzo-pyrones compared to placebo or to different benzo-pyrones in reducing limb volume, pain and discomfort in lymphoedematous limbs. To assess the effect of benzo-pyrones on the quality of affected tissues and on the patient's quality of life and, finally, to establish the incidence of adverse effects SEARCH STRATEGY: We searched the Cochrane Breast Cancer Group register (September 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4,2003), MEDLINE, EMBASE, CINAHL, UnCover, PASCAL, SIGLE, reference lists produced by The British Lymphology Society, the National Research Register (NRR) and The International Society of Lymphology congress proceedings. SELECTION CRITERIA: Types of studies considered for review were randomised controlled trials testing Paroven, coumarin, Venastat, Cyclo 3 Fort or Daflon versus placebo (with both groups having or not having standard physical treatment DATA COLLECTION AND ANALYSIS: Eligibility for inclusion was confirmed by two blinded reviewers who screened the papers independently using a checklist of criteria relating to the randomisation and blinding of the trial. Both reviewers extracted data from the eligible studies using a data extraction form. MAIN RESULTS: Overall, 15 trials were included that evaluated the role of benzo-pyrones. Three trials of oxerutin were found. Each tested the drug over 6 months using the same dose of drug against placebo. Two were crossover trials and one a parallel group trial with a total number of 127 participants and data available for only 81 of them. There were insufficient data provided in any of the trials to calculate the per cent reduction or increase in baseline excess limb volume. Standard deviations or confidence intervals and the numbers in the groups at the different stages of the trial were missing for all the data in two of the reports and for much of the data in the third, making any attempt at meta-analysis impossible. One trial testing Cyclo 3 Fort (approved name) over 3 months was found and involved 57 patients but provided insufficient data to allow a proper analysis of its findings. A single trial of Daflon (approved name) was found, lasting 6 months and involving 104 participants; once again there was insufficient information provided in the report to reach a conclusion about the effectiveness of the drug. Three trials of coumarin combined with troxerutin were found and tested two different doses of the drug against each other with no placebo, however, numbers of participants in the trial groups and baseline data were not provided. Eight trials of coumarin were identified. Two of the reports were confirmed as reporting the same trial and a further trial potentially also referred to the same trial but this was unconfirmed. A further two papers appeared to refer to the same trial but this was not confirmed. Three trials involved the same researcher. Five studies were conducted in India or China and they added anti-filarial dia or China and they added anti-filarial drugs to the interventions tested. The numbers of participants withdrawn and the numbers included in the analyses in all these trials were not extractable; the reporting of outcome measures in most of the trials was not clear. Loprinzi's 1999 trial in the USA reported the conduct of the trial and its findings with more detail, however, its conclusions were very much at odds with the findings of the other trials, finding that no difference was observed between those on the active preparation (coumarin) and placebo in any of the outcomes under investigation. This trial also reported a case of hepato-toxicity in a patient receiving the active preparation. REVIEWERS' CONCLUSIONS: Meta-analysis was not performed due to the poor quality of the trials. It is not possible to draw conclusions about the effectiveness of Benzopyrones in reducing limb volume, pain, or discomfort in lymphoedematous limbs from these trials.

Anticoagulants↗
PubMed2005

Determination of flavonoids in citrus juices by micro-HPLC-ESI/MS.

Flavonoids are a large class of naturally occurring aromatic secondary plant metabolites. They constitute one of the most characteristic classes found in nature and more than 4000 flavonoids have been identified and divided into several subclasses. Flavonoids have several effects on human health, mainly related to their antioxidant activity. As a result of the increased interest in the biologically active compounds in food, many research studies have investigated the detection and quantification of antioxidants. Citrus plants are of great interest since they accumulate large amounts of flavonoids and fruit and juices of these species are consumed in large quantities. Despite the extensive research performed on Citrus flavonoids, many compounds still remain unidentified. In this work, flavonoids of five citrus juices: lemon, grapefruit, bergamot, orange, and mandarin were analyzed by microHPLC coupled on-line with an MS detector equipped with an ESI source operating in negative mode. The use of microcolumn HPLC greatly enhanced detection performance. In total, 20 flavonoids of two different subclasses (flavanone and flavone glycosides) were identified with the help of retention data and MS spectral information.

Beverages↗
PubMed2000

Micronized purified flavonidic fraction compared favorably with rubber band ligation and fiber alone in the management of bleeding hemorrhoids: randomized controlled trial.

PURPOSE: The aim of this study was to assess the role of micronized purified flavonidic fraction in the management of bleeding nonprolapsed hemorrhoids. METHODS: Patients were randomly assigned to receive ispaghula husk alone, rubber band ligation plus ispaghula husk, or micronized purified flavonidic fraction plus ispaghula husk. Other colorectal diseases were excluded by colonoscopy. Blinded observers noted the time for bleeding to stop completely, recurrences, and treatment complications. RESULTS: A total of 162 patients were randomly assigned with no significant differences in the age and gender distributions among the groups. Hemorrhoidal bleeding was relieved most expediently in the micronized purified flavonidic fraction plus ispaghula husk group (ispaghula husk alone n = 66, mean (standard error of the mean) 10.6 (2.3) days; rubber band ligation plus ispaghula husk n = 57, 5.6 (1.1) days; micronized purified flavonidic fraction plus ispaghula husk n = 39, 3.9 (1.2) days; P = 0.03). However, there were no significant differences in the recurrences at six months of follow-up (ispaghula husk alone n = 8 (12 percent); rubber band ligation plus ispaghula husk n = 12 (21 percent); micronized purified flavonidic fraction plus ispaghula husk n = 2 (5.1 percent); P = 0.075). No complications or side-effects were noted. CONCLUSIONS: micronized purified flavonidic fraction used with fiber supplements rapidly and safely relieved bleeding from nonprolapsed hemorrhoids.

Adult↗
PubMed1996

Low-molecular-weight heparins and Daflon for prevention of postoperative thromboembolism.

The efficacy of low-molecular-weight heparins (LMWH) alone versus a combination of Daflon 500 mg with LMWH in preventing postoperative symptomatic thromboembolism was investigated. A total of 1372 patients aged 40 years or older undergoing major abdominal, pelvic, or abdominal wall surgery were randomized into four groups. Group A (n = 591) received enoxoparin 20 mg or fraxiparin 0.3 ml. Group B (n = 595) received the regimens of group A plus Daflon 500 mg. Group C (n = 93) received enoxoparin 40 mg or fraxiparin 0.6 ml. Group D (n = 93) received the regimens of group C plus Daflon 500 mg. Each LMWH was given subcutaneously once a day during the hospitalization and continued in groups C and D for 15 days after discharge (high risk patients). Daflon 500 mg was given as two tablets every 8 hours during the day before surgery, two tablets 6 hours before surgery, and two tablets once a day on postoperative days 4 to 15. Daily clinical examination was performed; and phlebography or perfusion lung scanning (or both) were used in symptomatic patients to confirm deep vein thrombosis (DVT) or pulmonary embolism (PE). The wound was examined on a daily basis for hematomas. The diagnosis of PE was established in two patients of group A and in three patients of group C; symptomatic DVT was established in one patient in group A and three patients of group C. Neither DVT nor PE were established in Daflon 500 mg groups. These data suggest that the combination of Daflon 500 mg and LMWH is more effective than LMWH alone for preventing symptomatic thromboembolism.

Adult↗
PubMed2005

Flavonoids to reduce bleeding and pain after stapled hemorrhoidopexy: a randomized controlled trial.

INTRODUCTION: Control of postoperative symptoms is of paramount importance in ambulatory surgery. This trial was conducted to evaluate whether a micronized purified flavonoid fraction (MPFF) (Detralex((R))) reduces postoperative bleeding, pain and consumption of analgesics after ambulatory stapled hemorrhoidopexy, as reported in trials after classic hemorrhoidectomy. Phlebotropic activity, protective effect on the capillaries and anti-inflammatory properties of this drug have been reported in several studies. METHODS: Sixty-three patients with third-degree hemorrhoids had ambulatory stapled hemorrhoidopexy under spinal anesthesia in the period of one year. The patients were randomized, with 30 receiving Detralex 500 mg (2 tablets 3 times daily for 5 days after the operation) and 33 forming the control group. The patients were asked to daily self-assess the presence of blood on defecation, degree of pain and consumption of analgesics for the first week after the operation. RESULTS: There was no significant difference between the two groups in duration of presence of blood, degree of pain or analgesics requirement. No major complications, such as bleeding requiring transfusion or hospitalization, sepsis, anal stenosis or urgent defecation, were noted in the follow-up period. There were no side effects from Detralex treatment. DISCUSSION: In our study we could not demonstrate any positive effect of prescribing flavonoids after stapler hemorrhoidopexy. This procedure may not be sufficiently aggressive and is associated with too few postoperative complications to show any protective influence of flavonoids.

Analgesics↗
PubMed2006

The effect of purified micronized flavonoid fraction on the healing of anastomoses in the colon in rats.

PURPOSE: Anastomotic leakage of colonic and rectal anastomoses is a major complication after large intestine surgery. Many factors influence the healing of colon anastomoses. Flavonoids have been recognized for centuries as physiologically active constituents that are used to treat human diseases. We studied the effects of a clinically used, micronized, purified flavonoid fraction on the healing of colonic anastomosis in rats. METHODS: Male Sprague-Dawley rats were used. The flavonoid group of rats received 100 mg/kg per day of Daflon for 14 days until surgery. Thereafter, a resection and anastomosis were performed. The bursting pressure of the anastomoses and the hydroxyproline levels of the perianastomotic tissue were determined to evaluate the healing on the third and seventh days of surgery for both flavonoid and control groups. RESULTS: The bursting pressure of the flavonoid group was higher on the seventh day. The hydroxyproline levels of the flavonoid group were significantly higher than in the control group on both the third and seventh days after surgery. CONCLUSIONS: Although the micronized purified flavonoid fraction has some inhibitory properties on the healing of the anastomosis, its net effect was to obtain a better anastomotic healing of the colon in rats.

Anastomosis, Surgical↗
PubMed2005

Venous leg ulcer: a meta-analysis of adjunctive therapy with micronized purified flavonoid fraction.

OBJECTIVE: To assess the effect of oral treatment with micronized purified flavonoid fraction (MPFF) on leg ulcer healing. DESIGN: Meta-analysis of randomised prospective studies using MPFF in addition to conventional treatment. MATERIALS AND METHODS: Five prospective, randomised, controlled studies in which 723 patients with venous ulcers were treated between 1996 and 2001 were identified. Conventional treatment (compression and local care) in addition to MPFF was compared to conventional treatment plus placebo in two studies (N = 309), or with conventional treatment alone in three studies (N = 414). The primary end point was complete ulcer healing at 6 months. RESULTS: At 6 months, the chance of healing ulcer was 32% better in patients treated with adjunctive MPFF than in those managed by conventional therapy alone (RRR: 32%; CI, 3-70%). This difference was present from month 2 (RRR: 44%; CI, 7-94%), and was associated with a shorter time to healing (16 versus 21 weeks; P = 0.0034). The main benefit of MPFF was present in the subgroup of ulcers between 5 and 10 cm2 in area (RRR: 40%; CI, 6-87%), and those present for 6-12 months duration (RRR: 44%; CI, 6-97%). CONCLUSION: These results confirm that venous ulcer healing is accelerated by MPFF treatment. MPFF might be a useful adjunct to conventional therapy in large and long standing ulcers.

Administration, Oral↗
PubMed2003

A new flavonoid derivative, dosmalfate, attenuates the development of dextran sulphate sodium-induced colitis in mice.

In this study, we have evaluated the efficacy of dosmalfate, a new flavonoid derivative compound, for the prevention and treatment of experimental colitis. To induce colitis, BALB/c mice received 5% dextran sulphate sodium (DSS) in their drinking water continuously for 7 days. Colitis was quantified by a clinical damage score, colon length, weight loss, stool consistency and rectal bleeding. Inflammatory response was assessed by neutrophil infiltration, determined by histology and myeloperoxidase (MPO) activity. Interleukin (IL)-1 beta, prostaglandins (PG)E(2) and (PG)D(2) concentrations in colonic tissue, histological and histochemical analysis of the lesions were also measured. Dosmalfate (400-800 mg/kg body weight, p.o.) ameliorated severe colitis reduced the degree of inflammation through reduction of neutrophil infiltration and IL-1 beta levels. (PG)E(2) and (PG)D(2) synthesis were significantly reduced in colitis control group and treatment with dosmalfate abolished the decrease in PG synthesis in colon mucosa. We conclude that dosmalfate is protective in acute DSS-induced colitis. The beneficial effects seem to be related to a decrease of neutrophil infiltration, absence of up-regulation of IL-1 beta and increase of PG production in colon mucosa.

Administration, Oral↗