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Proanthocyanidins--a final frontier in flavonoid research?

Proanthocyanidins are oligomeric and polymeric end products of the flavonoid biosynthetic pathway. They are present in the fruits, bark, leaves and seeds of many plants, where they provide protection against predation. At the same time they give flavor and astringency to beverages such as wine, fruit juices and teas, and are increasingly recognized as having beneficial effects on human health. The presence of proanthocyanidins is also a major quality factor for forage crops. The past 2 years have seen important breakthroughs in our understanding of the biosynthesis of the building blocks of proanthocyanidins, the flavan-3-ols (+)-catechin and (-)-epicatechin. However, virtually nothing is known about the ways in which these units are assembled into the corresponding oligomers in vivo. Molecular genetic approaches are leading to an understanding of the regulatory genes that control proanthocyanidin biosynthesis, and this information, together with increased knowledge of the enzymes specific for the pathway, will facilitate the genetic engineering of plants for introduction of value-added nutraceutical and forage quality traits.

Antineoplastic Agents, Phytogenic↗

Hibitane in the treatment of aphthous ulceration.

In the absence of a known aetiology the management of recurrent aphthous ulceration is symptomatic with the removal of predisposing factors where possible. Since the severity and duration of ulcers may be increased by bacterial contamination, the effect of chlorhexidine gluconate in mouthwash and gel forms on the natural history of the condition has been studied. The mouthwash study employed a 0.2% chlorhexidine gluconate solution, a 0.5% astringent solution and a control mouthwash. Each mouthwash was used by all of the patients, with 5 ml of each preparation being diluted with 5 ml of water for use three times a day. The gel study employed a 1% chlorhexidine gluconate and a placebo gel with approximately a 1 inch of the gel from the tubes being placed in the mouth three times a day. Both studies were carried out in the double-blind crossover manner with each preparation used for 5 weeks with a 2-week interval between preparations. In the mouthwash trial chlorhexidine gluconate significantly reduced the incidence, duration and severity of ulcers, whereas in the gel trial chlorhexidine significantly reduced the severity and duration but not the incidence of ulceration. Since the dosage regimes for chlorhexidine in the two studies were comparable, the mode of delivery would appear to be important in the therapeutic effectiveness.

Biguanides↗

DESCRIPTIVE ANALYSIS OF DIVALENT SALTS.

Many divalent salts (e.g., calcium, iron, zinc), have important nutritional value and are used to fortify food or as dietary supplements. Sensory characterization of some divalent salts in aqueous solutions by untrained judges has been reported in the psychophysical literature, but formal sensory evaluation by trained panels is lacking. To provide this information, a trained descriptive panel evaluated the sensory characteristics of 10 divalent salts including ferrous sulfate, chloride and gluconate; calcium chloride, lactate and glycerophosphate; zinc sulfate and chloride; and magnesium sulfate and chloride. Among the compounds tested, iron compounds were highest in metallic taste; zinc compounds had higher astringency and a glutamate-like sensation; and bitterness was pronounced for magnesium and calcium salts. Bitterness was affected by the anion in ferrous and calcium salts. Results from the trained panelists were largely consistent with the psychophysical literature using untrained judges, but provided a more comprehensive set of oral sensory attributes.

Journal Article↗

Wine phenolics.

Wine contains many phenolic substances, most of which originate in the grape berry. The phenolics have a number of important functions in wine, affecting the tastes of bitterness and astringency, especially in red wine. Second, the color of red wine is caused by phenolics. Third, the phenolics are the key wine preservative and the basis of long aging. Lastly, since phenolics oxidize readily, they are the component that suffers owing to oxidation and the substance that turns brown in wine (and other foods) when exposed to air. Wine phenolics include the non-flavonoids: hydroxycinnamates, hydroxybenzoates and the stilbenes; plus the flavonoids: flavan-3-ols, the flavonols, and the anthocyanins. While polymeric condensed tannins and pigmented tannins constitute the majority of wine phenolics, their large size precludes absorption and thus they are not likely to have many health effects (except, perhaps, in the gut). The total amount of phenols found in a glass of red wine is on the order of 200 mg versus about 40 mg in a glass of white wine.

Anthocyanins↗

Role of anthocyanidin reductase, encoded by BANYULS in plant flavonoid biosynthesis.

Condensed tannins (CTs) are flavonoid oligomers, many of which have beneficial effects on animal and human health. The flavanol (-)-epicatechin is a component of many CTs and contributes to flavor and astringency in tea and wine. We show that the BANYULS (BAN) genes from Arabidopsis thaliana and Medicago truncatula encode anthocyanidin reductase, which converts anthocyanidins to their corresponding 2,3-cis-flavan-3-ols. Ectopic expression of BAN in tobacco flower petals and Arabidopsis leaves results in loss of anthocyanins and accumulation of CTs.

Amino Acid Sequence↗

Umbilical care and cord separation.

Four different treatments for the care of the umbilical cord were compared in a randomised, controlled study. Triple dye was associated with a significantly earlier separation of the cord than either 1% neomycin or 1% silver sulphadiazine ointment, and it was nearly as effective as bismuth subgallate (an astringent powder) in causing rapid sloughing. If the mother is made aware that care of the umbilical cord may delay cord separation she may be spared unnecessary concern.

Clinical Trials as Topic↗

Superoxide anion scavenge effect of Quercus glauca Thunb. in whole blood of patients with ankylosing spondylitis.

Nine phenolic compounds, catechin (1), epicatechin (2), gallocatechin (3), epigallocatechin (4), procyanidin B-4 (5), catechin-3-O-rhamnoside (6), rutin (7), querglanin (8) and isoquerglanin (9) were isolated from oak leaves (Quercus glauca Thunb. Fagaceae), and the latter two (8, 9) were identified as new compounds. Several Quercus species have been used in folk medicine as an astringent for hemorrhoids and for treatment of inflammation, jaundice, and tumor. In this study, these compounds were tested for scavenging effects of the superoxide anion in the whole blood of patients with ankylosing spondylitis by means of an ultra-sensitive chemoluminescence (CL) analyzer and lucigenin amplification. The results showed that at a concentration of 2.3 x 10(-5) M, isoquerglanin (9) displayed the strongest inhibition activity (73.55%), followed by querglanin (8) (68.81%) and then gallocatechin (3) and epigallocatechin (4) (66.97 and 60.17% inhibition, respectively). In addition, the blood chemoluminescence (CL) level of patients with ankylosing spondylitis was inhibited by superoxide dismutase (SOD) but not by catalase, suggesting that superoxide anion is the major component of reactive oxygen species (ROS) involved in this assay system.

Acridines↗

The effect of tamol on human mast cell chymase and plasmin.

Tamol is widely used in the therapy of inflammatory dermatoses. It has pronounced astringent properties and is able to inactivate the neutrophil-derived elastase. Since plasminogen activation and release of mast cell chymase may occur in acute dermatitis, we investigated the inhibitory properties of tamol for these enzymes. Tamol proved to be a potent inhibitor of plasmin and mast cell chymase in concentrations relevant for use in dermatotherapy. The inhibition of mast cell chymase and plasmin by tamol was linear and non-competitive. The inactivation of proteolytic enzymes with the capacity to degrade extracellular-matrix proteins may be one of the major clinical effects of tamol in the treatment of acute inflammatory dermatoses.

Chymases↗

Adjuncts to medical management of sinusitis.

The basic principles of sinusitis therapy are to treat any infection present, facilitate drainage, and promote drainage both during and after treatment to prevent recurrence. Adjunctive measures promoting ciliary function and drainage through the sinus ostia include the following nonpharmacologic measures: steam, astringents, inhalations, saline, and hot, dry air. Pharmacologic measures include decongestants, topical corticosteroids for chronic sinusitis, mucoevacuants, and analgesics. Antihistamines are indicated for acute sinusitis only when a patient with concomitant allergies is symptomatic during the allergy season or after infection has been ruled out as the primary cause of sinusitis. Sinusitis may be associated with asthma, and some patients do not respond optimally to asthma therapy until their sinusitis is diagnosed and treated.

Administration, Topical↗

Benzoyl peroxide in the treatment of acne vulgaris: a double-blind, multi-centre comparative study of 'Quinoderm' cream and 'Quinoderm' cream with hydrocortisone versus their base vehicle alone and a benzoyl peroxide only gel preparation.

A double-blind, multi-centre general practice study was carried out to compare the effectiveness of benzoyl peroxide/potassium hydroxyquinoline sulphate cream, with or without hydrocortisone, its aqueous astringent cream base alone, and a benzoyl peroxide alcoholic gel in the treatment of 107 patients with acne vulgaris. Patients on entry were allocated at random to one of four treatment groups and instructed to apply the medication twice daily to all affected areas for 12 weeks. Assessments of the severity of acne on the face, chest and back, and response to treatment were made at 2, 4, 8 and 12 weeks. Acceptability of the treatment, i.e. 'greasiness', was also assessed by patients. The results showed that the combination cream preparation produced a greater reduction in acne scores than did the base or benzoyl peroxide alone. The addition of 1% hydrocortisone eliminated the flare reaction to benzoyl peroxide seen in patients in the other two active treatment groups. The majority of patients found the preparations cosmetically acceptable.

Acne Vulgaris↗

Evaluation of wound healing activity of Allamanda cathartica. L. and Laurus nobilis. L. extracts on rats.

BACKGROUND: Allamanda cathartica. L. is a perennial shrub used in traditional medicine for treating malaria and jaundice. Laurus nobilis. L. is a tree and has been used for its astringent, healing and diuretic properties. The objective of this study was to investigate the aqueous extracts of Allamanda and Laurus nobilis to evaluate their wound healing activity in rats. METHODS: Excision and incision wound models were used to evaluate the wound healing activity of both the extracts on Sprague Dawley rats. In each model, animals were divided into four groups of 10 animals each. In both the model, group 1 served as control and group 2 as reference standard. In an excision wound model, group 3 animals were treated with Allamanda (150 mg kg(-1) day(-1)) and group 4 animals were treated with Laurus nobilis (200 mg kg(-1) b.w day(-1)) for 14 days respectively. In the case of incision wound model, group 3 and 4 animals were treated with the extracts of Allamanda and Laurus respectively for 10 days. The effects of vehicles on the rate of wound healing were assessed by the rate of wound closure, period of epithelialisation, tensile strength, weights of the granulation tissue, hydroxyproline content and histopathology of the granulation tissue. RESULTS: The aqueous extract of Allamanda promoted wound healing activity significantly in both the wound models studied. High rate of wound contraction (P < .001), decrease in the period of epithelialisation (10.2 +/- 0.13), high skin breaking strength (440.0 +/- 4.53), significant increase in the weight of the granulation tissue (P < .001) and hydroxyproline (P < .001) content were observed in animals treated with the aqueous extract of Allamanda. Histological studies of the granulation tissue from the Allamanda treated group showed the presence of a lesser number of inflammatory cells, and increased collagen formation than the control. In Laurus nobilis treated animals, the rate of wound contraction, weight of the granulation tissue and hydroxyproline content were moderately high (P < .05). The histological study of the granulation tissue of the Laurus nobilis treated animals showed larger number of inflammatory cells, and lesser collagen when compared with the Allamanda treated group of animals. However, it was better than the control group of animals. CONCLUSION: The data of this study indicated that the leaf extract of Allamanda possesses better wound healing activity than the Laurus nobilis and it can be used to treat different types of wounds in human beings too.

Animals↗

The effect of various substances on the suppression of the bitterness of quinine-human gustatory sensation, binding, and taste sensor studies.

The purpose of this study was to quantify the degree of suppression of the perceived bitterness of quinine by various substances and to examine the mechanism of bitterness suppression. The following compounds were tested for their ability to suppress bitterness: sucrose, a natural sweetener; aspartame, a noncaloric sweetener; sodium chloride (NaCl) as the electrolyte; phosphatidic acid, a commercial bitterness suppression agent; and tannic acid, a component of green tea. These substances were examined in a gustatory sensation test in human volunteers, a binding study, and using an artificial taste sensor. Sucrose, aspartame, and NaCl were effective in suppressing bitterness, although at comparatively high concentrations. An almost 80% inhibition of bitterness (calculated as concentration %) of a 0.1 mM quinine hydrochloride solution required 800 mM of sucrose, 8 mM of aspartame, and 300 mM NaCl. Similar levels of bitterness inhibition by phosphatidic acid and tannic acid (81.7, 61.0%, respectively) were obtained at much lower concentrations (1.0 (w/v)% for phosphatidic acid and 0.05 (w/v)% for tannic acid). The mechanism of the bitterness-depressing effect of phosphatidic acid and tannic acid was investigated in terms of adsorption and masking at the receptor site. With phosphatidic acid, 36.1% of the bitterness-depressing effect was found to be due to adsorption, while 45.6% was due to suppression at the receptor site. In the case of 0.05 (w/v)% tannic acid, the total bitterness-masking effect was 61.0%. The contribution of the adsorption effect was about 27.5% while the residual masking effect at the receptor site was almost 33%. Further addition of tannic acid (0.15 (w/v)%), however, increased the bitterness score of quinine, which probably represents an effect of the astringency of tannic acid itself. Finally, an artificial taste sensor was used to evaluate or predict the bitterness-depressing effect. The sensor output profile was shown to reflect the depressant effect at the receptor site rather well. Therefore, the taste sensor is potentially useful for predicting the effectiveness of bitterness-depressant substances.

Aspartame↗

[Metabolites produced by actinomycetes--antiviral antibiotics and enzyme inhibitors].

In 1995, we discovered new antiherpetic antibiotics, called fattiviracins. The producing organism was classified as a strain belonging to Streptomyces microflavus. The strain produced at least 13 fattiviracin derivatives (FV-1 to FV-13). Fattiviracins were obtained as a white amorphous powder, and their molecular weights are in the range of 1400 to 1500. They are readily soluble in water, methanol, pyridine, and DMSO, but insoluble in other organic solvents. Fattiviracins have macrocyclic diesters formed by the binding of two trihydroxy fatty acids and two D-glucose residues in the molecule, and they can be divided into five families according to the length of the fatty acid moiety. Fattiviracins have potent activity against enveloped DNA viruses such as the herpes family, HSV-1, and VZV and enveloped RNA viruses such as influenza A and B viruses, and three strains of HIV-1, with EC(50) values on the order of a few micrograms per milliliter. The biosynthetic pathway of fattiviracins is also becoming clearer. Using bacitracin-resistant strains, enhanced and astringent production of fattiviracin was achieved. Fattiviracin FV-13, which has the longest fatty acid chains in the molecule, was dramatically enhanced by a C(55)-isoprenyl phosphate metabolism. In addition, we have screened various inhibitors of enzymes such as alkaline protease, glucosyltransferase, glucuronidase, phospholipase, deoxyribonuclease, DNA methyltransferase, and DNA topoisomerase. All the inhibitors we discovered are briefly summarized in this paper.

Antiviral Agents↗

Bismuth subgallate-epinephrine paste in adenotonsillectomies.

OBJECTIVE: To evaluate the role of bismuth subgallate-epinephrine (BSE) paste as a hemostatic in adenotonsillectomies. DATA SOURCES: MEDLINE (January 1966-October 1999) and Current Contents (January 1997-October 1999) were searched, using bismuth subgallate, adenoidectomy, tonsillectomy, and adenotonsillectomy as search terms. A citation search was performed using Science Citation Index (January 1977-October 1999). DATA SYNTHESIS: Adenotonsillectomies are common procedures; although there are few complications, hemorrhage is a concern. Bismuth subgallate has historically been used as an astringent and hemostatic. An evaluation of studies of bismuth subgallate and BSE paste was conducted. CONCLUSIONS: There is minimal evidence to support this practice, but data suggest that epinephrine may be the active ingredient in BSE paste. BSE paste is inexpensive, poses little risk, and may decrease postoperative bleeding; therefore, it may be a reasonable hemostatic agent.

Clinical Trials as Topic↗

Have fixed-prosthodontic impressions become easier?

Excellent fixed-prosthodontic impressions are ensured with the presence of healthy soft tissue, atraumatic tooth and soft-tissue preparation, use of packing cords when indicated, routine use of astringents and taking enough time to accomplish the preimpression procedures thoroughly. Currently advertised products that supposedly eliminate the difficulty of fixed-prosthodontic impressions and the need for cords have decreased some of the frustrations of impression making, but the challenge remains. Excellent impressions require accurate and stable impression materials, time, conscientious and thorough techniques, attention to every detail, good support staff and a working knowledge of all aspects of the concepts involved.

Dental Impression Materials↗

Akt-and CREB-mediated prostate cancer cell proliferation inhibition by Nexrutine, a Phellodendron amurense extract.

Evidence from epidemiological studies suggests that plant-based diets can reduce the risk of prostate cancer. However, very little information is available concerning the use of botanicals in preventing prostate cancer. As a first step toward developing botanicals as prostate cancer preventives, we examined the effect of Nexrutine on human prostate cancer cells. Nexrutine is a herbal extract developed from Phellodendron amurense. Phellodendron extracts have been used traditionally in Chinese medicine for hundreds of years as an antidiarrheal, astringent, and anti-inflammatory agent. The present study investigated its potential antitumor effect on human prostate cancer cells. Our results suggest that it inhibits tumor cell proliferation through apoptosis induction and inhibition of cell survival signaling. The results of the present study indicate that Nexrutine treatment 1) inhibits the proliferation of both androgen-responsive and androgen-independent human prostate cancer cells through induction of apoptosis; 2) reduces levels of pAkt, phosphorylated cAMP response-binding protein (pCREB) and CREB DNA-binding activity; and 3) induces apoptosis in prostate cancer cells stably overexpressing Bcl-2. Further, Akt kinase activity was reduced in cells treated with Nexrutine, and ectopic expression of myristoylated Akt protected from Nexrutine induced inhibition of proliferation, implicating a role for Akt signaling.

Antineoplastic Agents↗

Taste and olfactory processing in the brain and its relation to the control of eating.

Taste processing in primates through the nucleus of the solitary tract and the primary taste cortex is shown to represent the identity and intensity of taste inputs. In contrast, in the secondary taste cortex in the orbitofrontal area, single neurons respond to the taste of a food only if hunger is present. The neurons here reflect the reward value of taste. They show sensory-specific satiety. In addition to neurons with best responses to sweet, salt, bitter, and sour, there are separate representations of the taste of protein ("umami") and of astringency (e.g., tannic acid). In the orbitofrontal cortex, olfactory inputs converge onto neurons with taste inputs, forming representations of flavor. Neurons in this region may also respond to the sight of food and to its texture. The olfactory representation for some neurons reflects the taste association of odors; and olfactory sensory-specific satiety is represented in this part of the brain. Rapid learning of visual-to-taste associations is also a feature of the neural processing that occurs in the orbitofrontal cortex.

Animals↗

Therapeutic constituents and actions of Rubus species.

Rubus species (family Rosaceae) have been cultivated for centuries for their fruits. These and other parts of the plants have been used traditionally for therapeutic purposes. This article highlights these and the potential they can offer. The constituents reported in the various species and those demonstrated to exhibit pharmacological properties have been reviewed. In the search for biologically active compounds, one of the most frequently documented species of the genus is the raspberry plant R. idaeus, the leaves of which have been used traditionally as a uterine relaxant and stimulant during confinement, for the treatment of diarrhoea and similar enteric disorders and as an astringent. Investigations of other Rubus species have been conducted in the last twenty-five years, and have shown possible application for a wide range of indications, including bacterial infections, anxiety, pain and inflammation.

Animals↗