PHARMACOLOGICAL POTENTIALS OF BETALAINS
Shivangi Dubey, Dr. Ginpreet Kaur*
Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM’s NMIMS
Vile Parle (West), Mumbai, India
Corresponding author’s* Email id: ginpreet.aneja@gmail.com
Abstract
Betalains are water soluble plant pigments of the order caryophyllales, that are widely used as a colorant. Betalains also possess desirable range of biological activities, including antioxidants, anti-inflammatory, hepatoprotective, anticancer, antidiabetes, antilipidemic, anti-microbial activity. It derived from sources such as red beetroot, amaranth, prickly pear, red pitahaya, etc. Betalains are divided into 2 groups based on the color and the confer either the betacyanins (purple reddish) or betaxanthins (yellowish orange). The purpose of this review is to focus on betalains potential activity with regards to it in treating and preventing many diseases.
Keywords: Betalains, anti-inflammatory, hepatoprotective, anti-cancer, anti-diabetic, anti-lipidemics, antimicrobial, betacyanins, betaxanthins.
Introduction
Betalains are water soluble phytoconstituent which is stable in a pH range 3-7 and possess ionizable carboxyl groups and a positive charge on the nitrogen molecule because of which they can be classified as zwitterions like trimethylglycine. Betalains consist of red-violet betacyanins and yellow betaxanthins, are characteristics water- soluble, nitrogen containing pigments which accumulates in plants, fruits and few vegetative tissues of the plant order with the caryophyllales. The Caryophyllales accumulating the betalains is one of the most prominent examples of the chemotaxonomic relevance of plant secondary products. Other than this betalains was also found in some fungi e.g. Amanita muscaria. [1]
Fig No.1: Chemical structure of Betalains
Recent interest created in betalains has driven by the discovery that the sources of nitrate may have important implications for managing or treating cardiovascular diseases. Nitrate itself do not have any physiological functions, rather its effects are seen due to in vivo reduction to Nitric oxide (NO). When it is ingested it is 1st absorbed by the upper part of small intestine into the systemic circulation. Nearly 25% of nitrate enters the entero-salivary cycle where bacterial species are located which converts nitrate to nitrite. Moreover, salivary nitrite is reabsorbed into circulation by stomach where it is metabolized into nitric oxide and other nitrogen oxides by a variety of reductase enzymes [2]. A number of researches have reported showing betalains antioxidant, antiinflammatory, anti-diabetic, anti-lipidemic, anti-microbial and hepatoprotective activity. Betacyanins are the class of compounds which possess radical scavenging activity and a have antioxidant property. [3,4,5]. Studies show that they prevent oxidative processes which are responsible for generating many diseases in humans. Since it has a good bioavailability it provides protection against certain oxidative stress related disorders. [5]
Extraction of the betalains from any plants or cell culture is normally done with methanol, but addition of the Ascorbic acid to the extraction media is required. [6]. It ultimately leads to the slightly acidic pH and also inhibits possible oxidation. Conventional anion exchange chromatography using a gradient of the formic acid is used for the purification of betacyanin extract. [7] But, this may also leads to complete degradation of the betacyanin conjugates which is in unstable form found in the isolation of betacyanins. [8] In such cases gel filtration can be alternative, despites its separation performance and low capacity. Recently according to the research countercurrent chromatography is used to isolate betalains from red beet root extract. [9] Fourier transform ion cyclotron resonance mass spectroscopy gives ultrahigh resolution and is very helpful in structure elucidation of betalains. [10] Betalains work by assisting the body in a total transformation by neutralizing the toxins and by supporting cell’s natural detoxification process. [11] Nopalea Cactus juice has proven to show relief in pain and inflammation, main reason behind this is the presence of antioxidant betalains. [12]
BIOAVAILIBILITY
For any compound to be beneficial for health it must be bioavailable in vivo. The active compounds are absorbed through gastro intestinal tract (GIT) and made available in the circulation, in the sufficient quantities to be utilized by the cells. [13,14] Past studies shows the bioavailability of betalains by measuring their presence in human urine, betalains are also absorbed through a functioning intestinal barrier, indicating its bioavailability. [15,16] Preclinical studies was done on 6 healthy humans by providing them with 500ml of beet root juice, result shows betacyanins is present in their urine at concentration equivalent to ~0.3% of taken dose over a period of 24 hrs, use of urinary excretion is used as a indicator for the bioavailability because it does not account of the circulatory and biliary clearance of the compounds. [17]
[Table I]
Related Mechanisms Uses
Activation of Nuclear Factor-Kappa B Inflammation
Lowering of blood glucose level. Diabetes
Electron donating capacity and the ability to defuse Oxidative stress
highly reactive radicals targeting cell membranes
Inhibition of oxidation of LDL Cardiovascular Health
Interaction with peroxynitrate responsible DNA damage
for DNA damage
Decreasing acetyl cholinesterase and oxidative Cognitive impairment
stress responsible for damage of hippocampus and cortex
INFLAMMATION
Betalains has emerged as one of the potent anti-inflammatory agent. Anti-inflammatory effect seems to be effective by interfering with pro inflammatory signaling cascade. The most promising is Nuclear Factor-Kappa B, as it directly activates and transcribes most gene targets that help in regulating and amplifying the inflammatory response (i.e., cytokines, chemokines, apoptotic and phagocytic cells). [18] Preclinical studies was done on nephrotoxic rats by giving them beet root extract 250 mg or 500 mg.kg./bm for 28 days shows attenuation in NF –κB DNA binding activity. Another study shows that betanin treatment with 25 mg and 100 mg. kg/bm for 5 days inhibits NF –κB DNA binding activity in the rats induced with acute renal damage. [19,20]
OXIDATIVE STRESS
Betalains metabolites (betanin and betanidin) are shown to reduce linoleate damage induced by cytochrome C oxidase and the lipid membrane oxidation induced by H2O2-activated metmyoglobin and free iron (AA-Fe). [16] Betanin’s high antioxidant activity appears from its exceptional electron donating capacity and ability to defuse the highly reactive radicals targeting cell membranes. Preclinical studies was done on rats by giving them beet root juice 8 ml.kg.bm/day for 28 days, the results shows decrease in lipid peroxidation, protein oxidation and the DNA damage following xenobiotic inducing liver injury. [21,22] According to recent studies on this it shows that the effect of beet root was 80% because of betanin present in beet root extract.
ANTIOXIDANT AND DNA DAMAGE
Betanin and Betanidin able to inhibit lipid peroxidation. The antioxidant property of betalains appears to bleach the molecule. Betalains are reports to interact with peroxynitrate in vitro and due to peroxynitrate which is the most potent nitrosylative oxidant damage to DNA occur, incubation with betalains reduces the damage having potency more than Vitamin C and almost equal the potency to Blueberry anthocyanins. [23,16] In this process carboxyl group of the cyclo-dopa group becomes nitrosylated and deattaching itself from the betalamic acid. Preclinical studies shows that betalain 300-600 mg/kg was most potent inhibitor of lipid peroxidation showing high anti-oxidant activity by its electron donating capacity and its ability to defuse the highly reactive radical targeting the cell membranes. [24,25]
COGNITIVE IMPAIRMENT
There are certain mechanisms responsible for cognition impairment in diabetes, like oxidative stress plays a major role in neurons damage, increased oxidative stress in diabetes produces damage to hippocampus and cortex which leads to morphological abnormalities and the memory impairments (Alzimer). Increase in acetyl cholinesterase, causes alteration in cholinergic transmission. Increase in free radical damages the cellular proteins, lipids and nucleic acid, causing cellular cell necrosis indirectly which affects cellular signaling pathways and the gene regulation to induce neuronal apoptosis and contributing neuropathy associated with diabetes. [26,27,28,29] Betalains work by decreasing acetyl cholinesterase and oxidative stress. Clinical study was done on beet root extract on 65 years old with type 2 diabetes, 250ml for 14 days, results shown significant improvement in cognition impairment,[30,31] but the study does not proves that it is because of betalain present in it, further more studies are going on it. [32]
DIABETES
Betalains shows potent activity in case of diabetes. Diabetes is a metabolic disorders characterized by ¬elevated sugar levels in blood, which is caused by defects in insulin secretion and further signaling cascades, diet which plays a major role in the maintenance of the blood sugar level, in the hyperglycosylation of biomolecules associated with the diverse metabolisms, and in the prevention of the pathologies associated with that [33] Betalains due to their water-soluble nature, nitrogen content, intactness during assimilation, and stability in the circulatory system helps in lowing blood glucose level. Study shows that after the intake of 1396 mg of betalains shows reduced glucose level after 3 mins and reduced insulin response in over 60 mins. Many more studies was done on betalains showing its potential effect I treating diabetes. [34]
CARDIOVASCULAR HEALTH
Cardiovascular health issues are major problem these days. Consumption of betalains reduces oxidative damage and the hemolysis of red blood cells. Betalains also helps in atherosclerosis by binding it with the LDL, which leads to the inhibition of oxidation of LDL appears by both the betanidin and the betanin which is more potent than Vitamin E. [35,36]
Conclusion
Based on the available data betalains appears to show effective results in treating diabetes, inflammation, hepatotoxicity, lipidemia, also shows potent antioxidant property. All of these pharmacological properties are said to be associated directly or indirectly with free radical-scavenging abilities of bioactive molecules, which are abundant in red beet. Furthermore, apart from this the scope of this review several studies are still going on to show more effective uses of betalains. [37,38]
FUTURE DIRECTION
As such there is no evidence available showing that betalain is used to prevent cognitive impairment. But, due to its oxidative property it can be used to treat cognition. Studies are going on to show its effect on cognition. In future it may also be used to treat many more diseases due to wide functionality and also due to its availability. [39,40]