Antidiabetic Activity of Red Marine Algae In Vitro: A Review
1–3Department of Pharmacology, Mahatma Gandhi Medical College and Research Institute, Puducherry, India
Corresponding Author: JV Sabarianandh, Department of Pharmacology, Mahatma Gandhi Medical College and Research Institute, Puducherry, India, Phone: +91 9489018018, e-mail: email@example.com
How to cite this article Sabarianandh JV, Subha V, Manimekalai K. Antidiabetic Activity of Red Marine Algae In Vitro: A Review. Ann SBV 2020;9(1):22–26.
Source of support: Nil
Conflict of interest: None
The marine ecosystem is a prosperous source of biological and chemical diversity which has been explored in the finding of unique chemicals having potential for industrial improvement as pharmaceuticals, cosmetics, nutritional supplements. Marine organisms consist of important number of novel secondary metabolites with potent pharmacological properties have been discovered. Most of the macroalgae have rich source of carotenoids, proteins, oligosaccharides, fatty acids, antioxidants, vitamins, and minerals, which are useful for medical and pharmaceutical industries. Especially, red algae are involved in photosynthesis and it also contains carrageenan, which is used for food and medicinal products. Hence, this review article is a concise of the antidiabetic effect of red algae and its bioactive components assessed in vivo and in vitro studies.
Keywords: Antidiabetic activity, Marine macroalgae, Red algae.
Natural products are established the best possible library with the maximum available diversity of chemical structural types. With the arrival of modern tools, they have been extremely screened. Based on traditional use (or) modern studies, natural products contribute 85% of the treatment regimens of 80% of the population in the world. The chemical intricacy of the complex natural products till now thought to be a disadvantage for drug discovery can be considered as an advantage for the drug development. Although research on marine native products started about 50 years ago, marine organisms have been used in folk medicine much before that exists.1 Seaweeds (or) marine macroalgae are ecologically profitable marine resources, which belong to Thallophyta plant kingdom. Marine macroalgae are classified into four groups based on the presence of pigments and morphological and anatomical characters, namely Chlorophyta (green algae), Phaeophyta (brown algae), Rhodophyta (red algae), and Cyanophyta (blue-green algae).2 Seaweeds are the groups of non-flowering marine plants commonly known as marine macroalgae having increased demand as cosmestic, pharmaceutical, and food additives.3,4 They are photosynthesizing organisms in marine environment and produce basic biomass in the intertidal zone and have a rich source of bioactive compounds such as carotenoids, proteins, oligosaccharides, essential fatty acids, antioxidants, vitamins, and minerals, which are useful in medical and pharmaceutical industries.5–7 Red algae are the most abundant and commercially valuable. They are found on the rocky shores from intertidal to subtidal zones. Red pigment phycoerythrin is involved in photosynthesis. Phycoerythrin masks the green pigment chlorophyll, which is also present in red algae. Many of the red species are thin and delicate. These red algae are harvested for using as a food item. It also contains a chemical called carrageenan, which is used as a binding agent in ice cream, puddings, and toothpaste. Other soft red algae supply a chemical agar, which is also used to make food and medicinal products, and prepare growth medium for bacteria growth.8
Diabetes mellitus (DM) is one of the metabolic disorders, which is characterized by hyperglycemia, resulting from defects in insulin secretion, action, or both.9 Insulin is a peptide hormone produced by beta cells of the pancreatic islets.10 It has two essential functions, without which the body ceases to function: insulin stimulates glucose uptake and lipid synthesis; insulin inhibits the breakdown of lipids, proteins, and glycogens and also causes gluconeogenesis.11–13 According to the International Diabetes Federation (IDF), it was estimated that in 2017, there were 451 million (age 18–99 years) people with diabetes worldwide. These figures were expected to increase to 693 million by 2025. Many people affected by diabetes will eventually have a series of diabetic complications such as nephropathy, neuropathy, retinopathy, diabetic foot, ketoacidosis, and even increased risk of cardiovascular disease.14 Complications continue to be a major medical problem. Many indigenous Indian medicinal plants including seaweeds (lower plants) have been found to be useful for successfully managing diabetes. One of the great advantages of medicinal plants is that these are readily available and have very low side effects.15 This review gives a comprehensive knowledge of the red marine algae in vitro antidiabetic activity and its bioactive compounds with their target site of action to help the researchers to explore its in vivo activity in the future (Table 1).
RED ALGAE HAVING ANTIDIABETIC ACTIVITY IN DIFFERENT MODES OF ACTIONS
α-Amylase Inhibitory Activity
Vinoth et al. (Champia parvula): The crude extract of C. Parvula was carried out for α-amylase inhibitory activity at different concentrations (100 to 900 μg/mL), and it showed the inhibitory activity at the dose of 173 μg/mL for α-amylase activity.16
|S. no.||Species||Compound name||Site on action||IC50 values||Ref.|
|1||Champia parvula||NA||α-Amylase inhibition||173 μg/mL||16|
|α-Glucosidase inhibition||81 μg/mL|
|2||Laurencia dendroidea||NA||α-Glucosidase inhibition||3.71 μg/mL||27|
|PTP1B inhibitors||1.15 μg/mL|
|3||Actinotrichia fragilis||NA||α-Glucosidase inhibition||1.3 μg/mL||19|
|4||Polysiphonia urceolata||3-Bromo-4(3 bromo-4,5-dihydroxyphenyl methyl)-5-(hydroxymethyl)1,2-benzenediol||PTP1B inhibitors||4.9 μg/mL||32|
|5||Symphocladia latiuscula||Bis-(2,3,6-tribromo-4,5-dihyroxyphenyl) methane||PTP1B inhibitors||4.3 μmol/L||28|
|Bromophenols||Aldose reductase inhibitors||0.11 to 1.15 μg/mL||26|
|2,3,6-Tribromo-4,5-dihydroxybenzyl methyl ether||PTP1B inhibitors||3.9 μmol/L||28|
|1,2-Bis–(2,3,6-tribromo-4,5-dihydroxyphenyl)-ethane||PTP1B inhibitors||3.5 μmol/L||28|
|6||Gracilaria Opuntia||NA||Increase in the levels of insulin and C-peptide due to increased insulin secretion from pancreatic β-cells||125 and 175 mg/kg BW||33|
|7||Portieria hornemannii||NA||α-Amylase inhibitory||430 μg/mL||17|
|α-Glucosidase inhibition||60 μg/mL|
|8||Spyridia fusiformis||NA||α-Amylase inhibition||175 μg/mL||17|
|α-Glucosidase inhibition||57 μg/mL|
|9||Halymenia durvilae||NA||α-Glucosidase inhibition||0.32 μg/mL||20|
|10||Rhodomela confervoides||2,2′,3,3′-Tetrabromo-4,4′5,5′ tetra hydroxy diphenyl methane||PTP1B inhibitors||2.4 μM||29|
|3-Bromo-4,5-bis (2,3′-dibromo-4,5-dibromobenzyl) pyrocatechol||PTP1B inhibitors||1.7 μM||29|
|3,4-Dibromo-5-(methoxymethyl)benzene-1,2-diol||PTP1B inhibitors||3.4 μM||29,30|
|3-(2,3-Dibromo-4,5-dihydroxyphenyl)-2-methylpropanal||PTP1B inhibitors||4.5 μM||29,30|
|3,4-Dibromo-5-(2-bromo-3,4-dihydroxy-6-(isobutoxymethyl)benzyl)benzene-1,2-diol||PTP1B inhibitors||0.8 μM||29,30|
|11||Laurencia similis||1,2,5-Tribromo-3-bromoamino-7-bromomethylnaphthalene||PTP1B inhibitors||102 μg/mL||31|
|3′,5′6′6-Tetrabromo-2,4 dimethyl diphenyl ether||PTP1B inhibitors||3.0 μg/mL||31|
|2′,5′,6′5,6,-Pentabromo-3′,4′,3,4-tetramethoxybenzo-phenone||PTP1B inhibitors||2.7 μg/mL||31|
|12||Grateloupia elliptica||2,4,6-Tribromo phenol||α-Glucosidase inhibition||60.3 μM||21|
|2,4-Dibromo phenol||110.4 μM|
|13||Odonthalia corymbifera||2,3-Dibromo-4,5 dihydroxybenzyl||α-Glucosidase inhibition||0.4 mM.||24|
|14||Polyopes lancifolia||2,3-Dibromo-4,5 dihydroxybenzyl||α-Glucosidase inhibition||0.098 μM||23|
|15||Polysiphonia morrowii||3-Bromo-4,5-dihydroxy benzyl alcohol||α-Glucosidase inhibition||3.6 μg/mL||22|
|3-Bromo-4,5-dihydroxybenzyl methyl ether||α-Glucosidase inhibition||4.8 μg/mL||22|
|16||Palmaria sp.||NA||α-Amylase inhibition||∼0.1 μg/mL||18|
|17||Laurencia papillosa||NA||α-Glucosidase inhibition||>1000 μg/mL||19|
|18||Palmaria palmata||Protein hydrolysates||Dipeptidyl peptidase IV inhibition||1.65 ± 0.12 mg/mL||25|
Murugesan et al. (Portieria horemannii and Spyridia fusiformis): The crude extracts of P. horemannii and S. fusiformis were assessed at the concentration of 900 μg/mL exhibited α-amylase inhibitory activity with IC50 values 430 and 175 μg/mL, respectively.17
Nwosu et al. (Palmaria sp.): The phenolic extract showed minimal α-amylase inhibitory activity with IC50 value estimated at ∼0.1 μg/mL.18
α-Glucosidase Inhibitory Activity
Vinoth et al. (Champia Parvula): The crude extract of C. Parvula was carried out for α-glucosidase inhibitory activity at different concentrations (100 to 900 μg/mL), and it showed the inhibitory activity at the dose of 81 μg/mL for α-glucosidase activity.16
Osman et.al.: The crude extracts of Actinotrichia fragilis and Laurencia papillosa exhibit α-glucosidase inhibitory activity. It was carried out by using 96-well plate. About 100 μL of enzyme solution and 20 μL of crude were mixed at different concentrations (200, 500, and 1000 mg/mL), and the results showed the higher IC50 values 1.3 μg/mL and >1000 μg/mL, respectively.19
Murugesan et al. (Portieria horemannii and Spyridia fusiformis): The crude extracts of P. horemannii and S. fusiformis were assessed at the concentration of 900 μg/mL exhibited α-glucosidase inhibitory activity with IC50 values 60 and 57 μg/mL, respectively.17
Sanger et al. (Halymenia durvilae): α-Glucosidase inhibition of crude extract of H. durvilae showed that all the test concentrations (0.156, 0.312, 0.625, 1.25, 2.5 and 5 mg/mL) have highest α-glucosidase inhibitory activity at IC50 values 0.32 μg/mL.20
Kim et al. (Grateloupia elliptica): Two bromophenols, 2,4,6-tribromophenol and 2,4-dibromophenol, were purified from the red alga Grateloupia elliptica. IC50 values of 2,4,6-tribromophenol and 2,4-dibromophenol were 60.3 and 110.4 μM against Saccharomyces cerevisiae a-glucosidase, and 130.3 and 230.3 lM against Bacillus stearothermophilus a-glucosidase, respectively. In addition, both minimally inhibited rat-intestinal sucrase (IC50 of 4.2 and3.6 mM) and rat-intestinal maltase (IC50 of 5.0 and 4.8 mM). Therefore, bromophenols of G. elliptica have potential as natural nutraceuticals to prevent DM because of their high α-glucosidase inhibitory activity.21
Kurihara et al. (Polysiphonia morrowii): The crude extract of P. morrowii was carried out α-glucosidase inhibitory activity by using rat-intestinal maltase and sucrase assays. Bromophenol compounds 3-bromo-4,5-dihydroxy benzyl alcohol and 3-bromo-4,5-dihydroxybenzyl methyl ether showed IC50 3.6 and 4.8 mM.22
Kim, Kurihara and Kim et al. (Polyopes lancifolia): P. lancifolia bromophenol compound, 3-dibromo-4,5 dihydroxybenzyl, was purified and identified from the P. lancifolia alga and the compound exhibited strongly competitive inhibition against S. cerevisiae α–glucosidase.23
Kurihara et al. (Odanthalia corymbifera): Bromophenol compounds were isolated from O. corymbifera. The novel bromophenols were determined as 4-bromo-2,3-dihydroxy-6-hydroxymethylphenyl, 2,5-dibromo-6-hydroxy-3-hydroxymethylphenyl ether, bis (2,3-dibromo-4,5-dihydroxy benzyl) ether, and 2,3-dibromo-4,5-dihydroxybenzyl alcohol. Among these bromophenols, 2,3-dibromo-4,5-dihydroxybenzyl alcohol strongly exhibits α-glucosidase of IC50 values 0.4 mM.24
Dipeptidyl Peptidase IV Inhibitory Activity
Harnedy et al. (Palmaria palmata): P. palmata protein hydrolysates generated with Alcalase and corolase P. palmata showed highest DPP IV inhibitory activity with aqueous protein hydrolysates, control protein sample, and the protein hydrolysate generated with flavor zyme had IC50 values >5 mg/mL and showed a significant increase in DPP IV of IC50 values 1.65 ± 0.12 mg/mL.25
Aldose Reductase Inhibitory Activity
Okuyama et al. (Symphyocladia latiuscula): S. latiuscula containing high concentrations of bromophenols which were isolated like 2,2,3,6,6-penta bromo 3′,4,4′,5′-tetrahydroxy dibenzyl ether, bis (2,3,6-tribromo-4,5-dihydroxyphenyl) methane, 2,2′,3,5′,6′-pentabromo-3′,4,4′,5 tetrahydroxydiphenylmethene, 2,3,6,tribromo-4,5-dihydroxy methylbenzene, and 2,3,6-tribromo-4,5-diydroxy-benzaldehyde inhibited aldose reductase activity of IC50 values 0.40, 0.40, 1.15, and 0.25 μg/mL, respectively.26
Protein Tyrosine Phosphatase 1B Inhibitor Activity
Nguyen et al. (L. dendroidea): Inhibition of mammalian α-glucosidases and PTP1B of the ethyl acetate fraction was evaluated and compared with acarbose and ursolic acid as the positive controls. The fraction inhibited strongly all tested enzymes, with IC50 values of 3.71, 14.17, 23.31, and 1.15 μg/mL against yeast α-glucosidase, rat intestinal sucrase, rat intestinal maltase, and PTP1B, respectively.27
Liu et al. (Symphyocladia latiuscula): S. latiuscula was identified and structurally characterized by eight known bromophenols and then evaluated for inhibitory effects on protein tyrosine phosphatase 1B (PTP1B), a potential therapeutic drug target in the treatment of type 2 DM by using an in vitro assay. Bromophenol compounds such as 2,3,6-tribromo-4,5-dihydroxybenyl methyl ether, bis (2,3,6-tribromo-4,5-dihydroxy phenyl) methane, 1,2-bis (2,3,6-tribromo-4,5-dihydroxyphenyl ethane) showed strong inhibitory activity at the concentrations of 3.9, 4.3, and 3.5 μmol/L, respectively.28
Shi Da Yong et al. isolated bromophenol compounds such as 2,2’,3,3’-tetrabromo-4,4’5,5’ tetra hydroxy diphenyl methane, 3-bromo-4,5-Bis (2,3’-dibromo-4,5-dibromobenzyl) pyrocatechol, 3,4-dibromo-5-(methoxymethyl)benzene-1,2-diol, 3-(2,3-dibromo-4,5-dihydroxyphenyl)-2-methylpropanal, 3,4-dibromo-5-(2-bromo-3,4-dihydroxy-6-(isobutoxymethyl)benzyl)benzene-1,2-diol from Rhodomeda confervoides which showed potent in vitro PTP1B inhibitory effects, with IC50 values at 2.4, 1.7, 3.4, 4.5 and 0.8 µM respectively.29,30
Qin et al. (Laurencia similis): Bromophenol compounds of L. similis, 1,2,5-tribromo-3-bromoamino-7-bromomethylnaphthalene, 3′,5′6′6-tetrabromo-2,4 dimethyl diphenyl ether, and 2′,5′,6′5,6,-pentabromo-3′,4′,3,4-tetramethoxybenzo-phenone, showed PTP1B IC50 values at 102, 3.0, and 2.7 μg/mL.31
Liu et al.: Polysiphonia urceolata (red alga) contains five bromophenol compounds such as as 3-bromo-4-[3-bromo-4,5-dihydroxyphenyl]methyl-5-(hydroxymethyl)-1,2-benzenediol, 3-bromo-4,5-dihydroxy-α-ethoxy-toluol, 3-bromo-4,5-dihydroxybenzyl alcohol, 3-bromo-4,5-dihydroxybenzaldehyde, 3,5-dibromo-4-hydroxybenzyl alcohol and 3,5-dibromo-4-hydroxybenzaldehyde, were isolated from the red alga Polysiphonia urceolata were elucidated by chemical and spectroscopic methods including 2D NMR techniques and revealed the potent effect in 3-bromo-4-[3-bromo-4, 5-dihydroxyphenyl] methyl-5-(hydroxymethyl)-1,2-benzenediol potent inhibition against PTP1B enzyme with IC50 = 4.9 μg/mL.32
In Vivo Study
Nguyen et al. : The crude extract of L. dendroidea showed strongly inhibitory α-glucosidase and PTP1B activity with IC50 values of 3.71, 14.17, 23.31 and 1.15 µg/mL against yeast α-glucosidase. Rat intestinal sucrase, maltase and PTP1B respectively showed significantly lower than positive controls.27
Rayapu et al. (Gracilaria opuntia): G. opuntia was extracted in different solvents like aqueous, methanolic, and ethanolic extracts, and it was given at different doses (50, 100, 125, 150, and 200 mg/kg body) in STZ-induced diabetic rats. It showed 125 and 175 mg/kg concentrations of G. opuntia to treat the STZ-induced diabetic rats and also reduced the blood glucose, and HbA1c levels of G. opuntia showed a significant increase in the levels of insulin due to increased secretion of insulin from pancreatic β-cells.33
Diabetes and other metabolic disorders are major problems that the world is facing nowadays. Most of these diseases are due to improper nutritional habits and go along with the increased production of free radicals and/or insufficient antioxidant defense system.34 Seaweeds are proved to stand as a good source of natural bioactive compounds with many therapeutic activities.35 Preventing and treating diabetes with medications attempt these problems. They can reduce postprandial hyperglycemia by inhibiting various enzymes such as α-amylase, α-glucosidase,36 aldose reductase, PTP1B, dipeptidyl peptidase IV found to be an effective strategy related to their activity of pancreatic β-cells (synthesis or release) or the insulin-like activity of seaweeds. All of these actions may be responsible for the reduction of diabetic complication.37 Moreover, the cost of the drugs is high, and also, they cause adverse effects.38 Most of the seaweeds have pharmacologically bioactive compounds such as bromophenols, alginate, carrageen, and agar as phycocolloids have been obtained from seaweeds to be used as a medicine and pharmacy.39 Since there is increasing demand in the use of natural products with antidiabetic activity due to the side effects associated with insulin and oral hypoglycemic agents, the marine algae could be of better choice in this condition.40
The present review revealed comprehensive details of red marine algae and its use for the treatment of DM. Some of the marine algae are more potent and cost-effective for the management of diabetes. Since the allopathic drugs showed severe adverse effect for long-term usage, the natural sources such as herbal and marine algae are used as antidiabetic, dietary, and nutritional supplements. However, many other active compounds obtained from marine algae have not been well characterized. These marine red algae are useful to the health professionals, scientists, and scholars working in the field of pharmacology and therapeutics to develop antidiabetic drugs.
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