RIBES NIGRUM AND ITS PROPERTIES
Drugs

Author: riccardo marsengo
Date: 08/02/2013

Description

INTRODUCTION:
The blackcurrant originated from Northern Asia and Central and Eastern Europe is widely cultivated in most countries of Europe. This small perennial shrub grows 1–2 meters tall with palmately lobed leaves with serrated margins . The plant produces purple-black, sweet, aromatic, edible and seed-containing berries of up to 12 mm in diameter. The berry fruit has a glossy skin with a persistent apical calyx. The blackcurrant fruit was first domesticated between 400–500 years ago, making it a relatively new addition to the agricultural arsenal. Blackcurrant fruits and leaves find use in both Asian and European traditional medicine for the treatment of a variety of ailments. Blackcurrants are also popularly used to prepare ‘‘cassis liqueur,’’ a traditional alcoholic beverage in France. Apart from its colorful background, the blackcurrant has many therapeutic applications that have tremendous potential for further exploration.

PHYTOCHEMICAL CONSTITUENTS:
Biochemical profiling of blackcurrants has revealed a myriad of constituents:
1) Flavonoids:
(a) Anthocyanins: Blackcurrants are an important source of anthocyanins with concentrations up to four-fold greater than other common fruits. Studies in various genotypes of blackcurrants reveal a varied anthocyanin content of 80–280 mg per 100 g of fruit with maximum levels observed up to 300 mg per 100 g of fruit. The aglycones (anthocyanidins) are salt derivatives of the 2-phenylchromenylium (flavylium) cation. Its positive charge differentiates anthocyanidins from other flavonoids. Anthocyanins are sugar derivatives of anthocyanidins.Four major anthocyanins have been identified in the blackcurrant: delphinidin-3-O-glucoside, delphinidin-3-O-rutinoside, cyanidin- 3-O-glucoside, and cyanidin-3-O-rutinoside . Cyanidin possesses a hydrogen atom at the 5 position, while delphinidin possesses a hydroxyl group at the 5 position. Proanthocyanidins are oligomer or polymer chains of flavonoids, such as catechins (flavan-3-ols), and are also known as procyanidins, or condensed tannins.
(b) Flavonols: it’s a class of compound which possess a 3- hydroxyflavone backbone. The principal flavonols found in blackcurrants are quercetin, myricetin, kaempferol and their glycosides.
2) polyunsaturated fatty acids(PUFA):
γ-linolenic acid (GLA) is an essential polyunsaturated fatty acid found in blackcurrants. GLA has been isolated from the blackcurrant seed oil. Stearidonic acid , an ω-3 fatty acid, has also been isolated from the blackcurrant seed oil. Production of stearidonic acid requires the precursor a-linolenic acid along with a Δ6-desaturase enzyme, similar to GLA.
3) structural and nonstructural carbohydrates
4) non-volatile organic acids:
L-ascorbic acid , also known as vitamin C, is an essential non-volatile organic acid and a potent antioxidant and free radical scavenger. Several studies have evaluated the ascorbic acid content in blackcurrants, which was found to vary between 70–280 mg per 100 g of fresh fruit. Thus blackcurrants are a major source of this vital vitamin, which in turn provides blackcurrants with its powerful antioxidant effects.
5) tannins and stilbenoids:
Ellagitannins, a type of hydrolyzable tannins, are a diverse class of polyphenols composed of ellagic acids linked to hydroxyl groups of a polyol carbohydrate compound, such as glucose. Gallotannins are another class of hydrolyzable tannins. Both of these compounds have been isolated from blackcurrant juices and contribute significantly towards some of its healing properties. Different types of hydroxylated phenolic acids are also present in blackcurrant fruit both in non-glycosylated and glycosylated forms. The most important compounds are gallic acid, phydroxy- benzoic acid and hydroxycinnamic acid derivatives. Stilbenoids have been isolated from blackcurrants too.
Biochemical properties of the fresh and frozen black currants and juices.-2013-
Isolation and characterization of flavonols from blackcurrant by high-performance counter-current chromatography and electrospray ionization tandem mass spectrometry.-2012-

BIOLOGICAL EFFECT OF BLACKCURRANTS:
Anti-inflammatory and immuno-modulatory responses:
The heart of the inflammatory response is mediated by a cascade of eicosanoids, signalling molecules made from the oxidation of twenty carbon essential fatty acids (EFA). There are three main EFA precursors that have been identified in synthesis–eicosapentanoic acid (EPA), dihomo-γ-linolenic acid (DGLA), and arachidonic acid (AA). Eicosanoids synthesized by AA are the most effective in eliciting an immune response.
• Blackcurrant seed oil is rich in GLA (a precursor to DGLA), alpha linolenic acid, and stearidonic acid, which are precursors to EPA. In addition to the eicosanoids, contributions to the progression of the immune response are executed by many other signaling molecules: tumor necrosis factor-a TNF-a, interleukins (IL) 1–6, nitric oxide NO and nuclear factor-kB NF-kB.
• Studies involving an in vitro administration of blackcurrant extract revealed a suppressive effect against TNF-a in the presence of lipopolysaccharide (LPS), an immunogenic bacterial product known to provoke a systemic inflammatory response syndrome and to cause septic shock. Molecules downstream of this pathway, specifically NF-kB and IL-6 were also downregulated, which further indicated acute phase cytokine inhibition.
• Another study was conducted in a rat model involving the administration of carrageenan (CGN), a family of linear sulfated polysaccharides with known immunogenic effect. CGN induces inflammation through activation of the kininkallikrein system, which in turn results in the accumulation of leukocytes and the production of acute phase cytokines and eicosanoids. Proanthocyanidin (PAC), isolated from blackcurrant leaves, was administered to mitigate the effects of CGN. PAC has an ability to scavenge free radicals and thus PAC can absorb and negate the effect of NO. However, given that both NO concentration and leukocyte migration were simultaneously reduced, it suggests that PAC may have a direct activity on the transmigration of leukocytes, although the direct mechanism of how this occurs has yet to be explored.
Inhibitory effects of proanthocyanidins from, Ribes nigrum leaves on carrageenin acute inflammatory reactions induced in rats.-2004-
Effects of prodelphinidins isolated from Ribes ,nigrum on chondrocyte metabolism and COX activity.-2002-

Antioxidant properties:
States of increased oxidative stress can be seen in disease, smoking activity and physical exercise in unconditioned individuals. Multiple accounts show empirical support regarding the antioxidant ability of blackcurrants. Data from additional studies demonstrates the neutralization of hydrogen peroxide (H2O2) and NO, as well as impeding the propagation of lipid and protein peroxidation. Antioxidant enzymes, such as glutathione (GSH) peroxidase and superoxide dismutase, were also shown to increase significantly by the blackcurrant components through an unknown mechanism. The specific antioxidant capacities of the blackcurrant fruit as a whole are mostly bequeathed to its phenolic and anthocyan content. Although the phenolic content is considered to contribute a more potent antioxidant activity than natural vitamins, high levels of vitamin C confers the additional inherent antioxidant properties to blackcurrants .Free radical scavenging activity was noted to attain maximum levels at a pH between 6.0 and 7.0, slightly more acidic than human serum. This suggests that the anthocyanin antioxidant activity potentially varies depending on its location in the human body.
Antioxidant activity of black currant (Ribes nigrum L.) extract and its inhibitory effect on lipid and protein oxidation of pork patties during chilled storage.-2012-

Antimicrobial mechanisms:
• Acidic, high molecular weight galactans found in blackcurrant seed extracts were shown to have anti-adhesive effects against Helicobacter pylori in sections of the human gastric mucosa, thus carrying antidotal prospects for virtually all duodenal ulcers. Although unknown, it has been postulated that the mechanism of action may involve blocking the interactions between the mucosal epithelial cells and the surface receptors of the organism. With regards to the microbial effects on the composition of the particular constituents of the blackcurrants, microbial enzymes were found to deconjugate glycosylated compounds, such as anthocyanins. Specifically, gram-positive organisms were found to be more proficient at this glycosylation reaction when compared to gram-negative organisms.
Anthocyanins and blackcurrant extract have been shown to inhibit peridontopathogenic proteinases, specifically those of Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola, which allow these organisms to extract usable nutrients from their environments. They have also been shown to inhibit matrix metalloproteinases 1 and 9, which break down collagen fibrils into smaller peptides and amino acids, which can serve as a nutrient source for periodontopathogens and facilitate bacterial growth in the oral cavity.
• Blackcurrants were shown to inhibit the herpes simplex virus type 1 attachment onto the cell membrane, as well as the plaque formation of herpes simplex virus types 1 and 2 and the Varicella-Zoster virus via the inhibition of protein synthesis in the early stages of infection. Results indicated that the anti-herpesvirus components of blackcurrants are several soluble molecules, which is characteristic of phenolic compounds.
• Anthocyanins extracted from blackcurrants were shown to have potent activity against influenza viruses A and B. Extracts were shown to directly inactivate both viruses, as well as prevent spread. Specifically, delphinidin was shown to inhibit virus adsorption as well as release.
Anti-herpesvirus activity of an extract of Ribes nigrum L.-2003-.
Anti-viral and anti-bacterial activities of an extract of blackcurrants (Ribes nigrum L.)-2012-
Activity of anthocyanins from fruit extract of Ribes nigrum L. against influenza A and B viruses.-2001-

IN VIVO PHARMACOLOGICAL EFFECTS OF BLACKCURRANTS:
Cardiovascular system: The ingestion of blackcurrants results in several beneficial health consequences, demonstrated in vivo, and one is evident in the cardiovascular system. Multiple studies have been conducted in animal models, demonstrating its efficacy in mitigating various cardiovascular ailments:
• A study examining rats with spontaneous hypertension were administered GLA from the oils of blackcurrants, and other agents containing oils enriched in GLA, for 7 weeks to demonstrate a notable decline in blood pressure levels.
• Blackcurrant oil, in conjunction with fish and olive oil, was shown to reduce serum levels of thromboxane B2, an inactive metabolite of thromboxane A2, a pro-thrombotic factor released by activated platelets. By decreasing thromboxane A2, there is a reduction in the risk of thrombus-formation, which leads to the development of cerebrovascular and cardiovascular incidents.
• Specific studies involving cyanidin-3-O glucoside suggested that anthocyanins had little effect on liver and plasma cholesterol levels and decreased the relative amount of hepatic saturated fatty acids. It was also shown to increase plasma tocopherol levels, suggesting a possible synergistic effect with vitamin E to maximize antioxidant activity. Blackcurrant concentrate has been shown to induce vasorelaxation through endothelial histamine H1 receptors, indirectly increasing NO levels.
Comparative study of diets enriched with evening primrose, black currant, borage or fungal oils on blood pressure and pressor responses in spontaneously hypertensive rats.-1993-
Effects of dietary anthocyanins on tocopherols and lipids in rats.-2002-

Nervous system: Studies involving rat models validate that the modulatory effect of GLA (found in blackcurrants and other natural sources of fatty acids) on thromboxane A2 aids in diabetes-associated reduced sensory and motor nerve conduction velocity.
Effectiveness of natural oils as sources of gamma-linolenic acid to correct peripheral nerve conduction velocity abnormalities in diabetic rats: modulation by thromboxane A2 inhibition.-1996-

Ocular system: In artificially induced myopia through negative lenses in the chick animal model, blackcurrant extract was demonstrated to inhibit the enlargement of globe component dimensions, which would normally occur as an adjustment to the myopia.
Skeletal system: Blackcurrant seed oil was demonstrated to impede the formation of monosodium urate crystals during acute inflammation in vivo. By inhibiting the formation of monosodium urate crystals, it should be noted that the primary factor that precipitates the disease state of gout is thus inhibited.
Suppression of monosodium urate crystal-induced inflammation by black currant seed oil.-1995-

Tumors: There are only three in vivo studies which document the antitumor effects of blackcurrant products in transplanted tumor models.
• Blackcurrant seed oil containing GLA was administered through the diet and suppressed the metastatic breast tumor in the lungs of rats.
• In another study, oral feeding of blackcurrant juice to Ehrlich carcinoma-bearing mice significantly abrogated solid tumor growth.
• Another one is the chemopreventive effect of phytoconstituents, derived from blackcurrant skin, against diethylnitrosamine (DENA)-induced hepatocellular carcinogenesis in rats. Dietary administration of the blackcurrant fraction exhibited a striking inhibition of incidence, multiplicity, size and volume of hepatocyte nodules, precursors of HCC, through suppression of abnormal cellular proliferation and induction of Apoptosis. The study demonstrated that blackcurrant phytoconstituents suppressed the DENA induced inflammatory cascade via interference with NF-kB signaling. Based on our recent investigation, blackcurrant bioactive phytochemicals diminished DENA-inflicted oxidative insult through nuclear factor E2-related factor 2 (Nrf2)-mediated induction of antioxidants and phase 2 xenobiotic-metabolizing enzymes during rat hepatocarcinogenesis.
Anthocyanin-rich black currant (Ribes nigrum L.) extract affords chemoprevention against diethylnitrosamine-induced hepatocellular carcinogenesis in rats.-2011-
Anthocyanin-rich black currant extract suppresses the growth of human hepatocellular carcinoma cells.-2010-

CLINICAL EFFECTS OF BLACKCURRANTS IN CLINICAL STUDIES:
Cardiovascular system: It has been shown that blackcurrant seed oil acts as a platelet inhibitor due to its polyunsaturated fatty acid constituents, such as GLA, and potentiates an anti-coagulant effect by inhibiting fibrin formation.
• A clinical study of blackcurrant anthocyanins involving 20 healthy male volunteers showed an improved blood flow to the shoulder muscles during typing work as well as at rest, suggesting that it may improve shoulder stiffness and reduce muscle fatigue. Blackcurrant seeds contain high levels of PUFAs as well as polyphenolic and tocopherol content, which help inhibit the oxidative damage to DNA, lipids and proteins seen in coronary heart disease, particularly concerning the generation of atherosclerotic plaques.
• Additional studies have demonstrated that administration of a blackcurrant soft oil capsule increases serum HDL-C protein while lowering triglyceride levels and total cholesterol in hyperlipidemic patients with a low body mass index, thus increasing a favorable lipid profile.
Resting blood pressure and cardiovascular reactivity to mental arithmetic in mild hypertensive males supplemented with blackcurrant seed oil.-1996-

Nervous system: The antioxidant properties of several of the chemicals found in blackcurrants have proven to have potential neuro-protective effects. Blackcurrant seed oil was demonstrated to improve serum fatty acid composition in patients afflicted by a stroke. Improving the serum fatty acid composition mitigates the poor lipid profile, which often causes or is associated with conditions such as stroke.
Composition of phospholipid fatty acids in red blood cell membranes of patients in intensive care units: effects of different intakes of soybean oil, medium-chain triglycerides, and black-currant seed oil.-1992-

Ocular system: Multiple studies have established that cyanidin has been shown to improve rhodopsin regeneration and dark adaptations. This has the effect of improving visual discernment by the eye. In addition, anthocyanins cause vasorelaxation, which can increase blood flow to the eye and reduce fatigue to improve eye function.
Stimulatory effect of cyanidin 3-glycosides on the regeneration of rhodopsin.-2003-

Skeletal system: Blackcurrant seed oil has been shown to reduce morning stiffness in rheumatoid arthritis in studies, which suggests a drop in IL-13, IL-1, TNF-a and other mediators of the inflammatory response. It did not, however, have any effect on grip or pain-score. Prodelphinidins in blackcurrant extract have shown promising results against the degenerative processes of osteoarthritis.
Treatment of rheumatoid arthritis with blackcurrant seed oil.-1994-

Renal system: Patients with gout experience painful inflammatory reactions to the formation of monosodium urate crystals. In addition to the painful joint depositions of these crystals, patients with gout also often experience urate stone formation in their kidneys, which is treated by alkalinizing the urine. Berry juice has been used to modulate urinary pH for the treatment of ailments such as kidney stones.
Suppression of monosodium urate crystal-induced inflammation by black currant seed oil.-1994-.

CONCLUSION AND FUTURE DIRECTIONS:. From a nutraceutical view point, the bioactive properties of plants are best found in fresh, intact whole fruits and active constituents of medical herbs usually have synergistic action as well as additive effects. Based on emerging evidence obtained from pre-clinical and clinical studies, blackcurrants have demonstrated significant therapeutic potential in a myriad of disease states. We detected a relatively high cytotoxic effect in ribes n. in vitro, but no toxicity has been reported in popular foods. This indicates that the cytotoxic contents of blackcurrants might be not adsorbed through the intestines.

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2013-02-18T19:04:43 - riccardo marsengo
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