**Therapeutic Potential of Seaweed Polysaccharides for Diabetes Mellitus**

Amir Husni

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.76570

#### **Abstract**

Seaweed has attracted a great deal of interest as excellent sources of nutrients. Seaweeds contain polysaccharides, proteins, amino acids, lipids, peptides, minerals, and some vitamins. Polyphenols of seaweed was used ascosmetics and pharmacological asantioxidants,protection from radiation, anti-inflammatory, hypoallergenic, antibacterial, and antidiabetic. Besides that seaweed also has a high content of antioxidant that can be used to ward off free radicals that increase due to the condition of hyperglycemia in a patient with diabetes mellitus. Hence, a great deal of attention has been directed at isolation and characterization of seaweed polysaccharides because of their numerous health benefits, especially for diabetes mellitus. This paperis expected to provide information on the effect of alginate from two seaweeds on blood glucose and lipid profiles of diabetic rats.-

**Keywords:** *Sargassum crassifolium*, *Turbinaria ornata*, diabetes mellitus, seaweed, alginate-

#### **1. Introduction**

 Diabetes mellitus (DM) is a disease caused by hyperglycemia due to a relative or absolute insulin insufficiency. Chronic hyperglycemia can cause complications such as neuropathy, retinopathy, nephropathy, and cardiovascular disease [1]. Hyperglycemia can also cause impaired balance metabolism of carbohydrates, fats, and proteins [2]. International Diabetes Federation (IDF) estimates that in 2013 there were 382-×-106 people with diabetes and 316-×-10<sup>6</sup> people suffer from impaired glucose tolerance and increased risk of diabetes. These results are expected to increase to 471-×-106 in 2035 and predicted less than 25years; there would be 592-×-10<sup>6</sup> people have diabetes without quick and precise prevention [3].-

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

 Seaweeds are the most abundant resources in the ocean. Seaweeds contain polysaccharides, proteins, amino acids, lipids, peptides, minerals, and some vitamins. Polyphenols of seaweed was usedas cosmetics and pharmacological as antioxidants, protection from radiation, antibiotics, anti-inflammatory, hypoallergenic, antibacterial, and antidiabetic [4]. Polyphenol extracts from seaweed, for example, *Alaria*, *Ascophyllum*, *Padina*, and *Palmaria*, are able to inhibit the activity of α-amylase and α-glucosidase that can lower blood glucose levels [5, 6]. On the other hand, seaweed also has a high content of antioxidants that can have beneficial value for diabetes mellitus patient [7]. Research on the use of Na alginate from *Turbinaria ornata* and *Sargassum crassifolium* on invivo studies in diabetic rats was limited. This paper is expected to provide information about the effect of Na alginate from *T. ornata* and *S. crassifolium* on the blood glucose and lipid profiles of drug-induced diabetic rats.-

#### **2. Extraction of polysaccharides from marine algae**

 Na alginate from *T. ornata* and *S. crassifolium* was extracted as explained by Husni etal. [8, 9]. Dried samples were weighted and were soaked in distilled water with the addition of 0.1-N HCl to pH-4 for about 24h 1:15 (w/v). The seaweed was washed with distilled water until pH-7. The filtrate was added with 0.5-N Na<sup>2</sup> CO3-(pH-11) 1:10 (w/v) and then heated at 60°C for 2h. The viscous mixture was added with distilled water 1:10 (w/v) and separated from its residue by centrifuge (3500rpm, 5min, 4°C) (1rpm-=-1/60-Hz). The Na alginate extract was added with 5-N H<sup>2</sup> O2 1:4 (v/v), stirred for 30min before left for two h. The mixture was added with 0.5-M CaCl2 and stirred for 30min followed by adding 0.5-N HCl until pH-2. The mixture was stirred and left for 30min at room temperature. Insoluble material (alginic acid) was separated from the supernatant by centrifuge. Alginic acid was weighed, was added with distilled water and 0.5-N Na<sup>2</sup> CO3-2:2:3 (w/v/v), and was stirred for one h at room temperature to obtain a solid form of Na alginate. Na alginate was precipitated with EtOH slowly 1:1 (v/v) and stirred for 30min, after being centrifuged, followed by drying at 60°C, and the yield of alginate was determined.-

#### **3. Alginate characterizations (structural and physical properties)**

 FTIR spectroscopy was used to identifythepolysaccharide structures. A pellet of sodium- alginate was prepared with KBr. FTIR spectrum was recorded on Shimadzu-FTIR Prestige- 21 with a resolution of 4cm−1in the 4000–400cm−1region, with a scan speed of 0.20cms−1. The FTIR spectrum of sodium Na alginateof *T. ornata* showed similar bands to that Na- alginate standard in 3500–1300cm−1region, while the fingerprint region has two bands at- 948.98cm−1and 871.82cm−1 (**Figure 1**). Sodium alginate of *T. ornata* showed eight characteristic bands which also could be found in sodium alginate standard (**Table 1**). According- to literature, the band at 3400cm−1assigned to the hydrogen bonded O-H stretching vibrations and the weak signal at 2931.80cm−1due to C-H stretching vibrations [10] and the- asymmetric stretching of carboxylate O-C-O vibration at 1627.92cm−1 [10, 11]. The band at-

**Figure 1.** Infrared spectra of Na alginate standard (red) and Na alginate of *T. ornata* (black).-


**Table 1.** FTIR spectrum of Na alginate from *T. ornata* and standard.-

1427.32cm−1is assigned to C-O-H deformation vibration with the contribution of O-C-O- symmetric stretching vibration of carboxylate group [10, 12]. The band 1087.85cm−1might- be assigned to C-O and C-C stretching vibrations of pyranose ring [10–12], and the band- at 1033.85cm−1might also be due to C-O stretching vibrations [10]. The anomeric regionof the fingerprint (950–750cm−1) showed two characteristic absorption bands. The band at- 948.98cm−1was assigned to the C-O stretching vibration of uronic acid residues, and the- one at 871.82cm−1was assigned to the C1-H deformation vibration of *β*-mannuronic acid- residues [10, 12].-

 The peak infrared spectrum of standard alginate and *S. crassifolium* can be seen in **Table 2**. Based on the FTIR test conducted on alginate extract of *S. crassifolium* and alginate standard (**Figure 2**) on the first band of alginate extract spectra, the vibration frequency of- 779.24cm−1shows the residue of guluronic acid. The second band, standard alginate spectra and alginate extracts, contained the same vibration frequency at 948.98cm−1showing- the suspected vibration of C-O stretching as uronic acid. The third band detected vibrations from C-O stretching, wavelengths 1033.85cm−1at standard alginate, and 1026.13cm−1- on alginate extract. The fourth band in the standard alginate detected vibrations at wavelengths of 1095.57 and 1087.85cm−1in the extra alginate indicating the presence of OCO- rings. Symmetrical and asymmetrical C-O vibrations were detected in the standard alginate- of the fifth and sixth bands indicating the presence of carboxylic groups at 1303.88 and- 1419.61cm−1wavelengths, but this vibration was not detected in the alginate extract. The- seventh band contained a vibration of 2931.8cm−1in standard alginates and alginate extracts- indicating the presence of C-H stretching. O-H is stretching vibration indicating the presence of H atomic bonds detected in both alginates, 3425.58cm−1in standard alginate and- 3471.87cm−1 in alginate extract.-


**Table 2.** FTIR spectrum of Na alginate from *S. crassifolium* and standard.-

**Figure 2.** Infrared spectra of Na alginate standard (red) and Na alginate of *S. crassifolium* (black).-

#### **4. Biological activity of polysaccharides from marine algae**

#### **4.1. Effect of Na alginate of** *T. ornata* **on body weight of rats**

Alloxan-induced diabetic rats did not show a significant decrease in body weight after the injection of alloxan. Five groups of diabetic rats had decreased in body weight on 15days treatment, and there were significant differences between the groups of rats. There was no significant difference between diabetic control (negative control) compared to positive control, and the positive control was not significantly different compared to alloxan diabetic rats treated with Na alginate 200mg/kg. Alloxan-induced diabetic rats treated with Na alginate(s) (200, 400, 600mg/kg) did not show significant difference between each other. Administration of Na alginate(s) (400, 600mg/kg) showed a significant difference compared to negative control. The body weight of alloxan-induced diabetic rats treated with Na alginate 600mg/kg was not significantly different compared to normal control.-

The lowering of rats' body weight treated with alginate from *T. ornata* showed lower than a study conducted by Wikanta etal. [16] using κ-carrageenan and ί-carrageenan. In those researches, κ-carrageenan increased the weight by 34.1g, and ί-carrageenan increased the weight by 30.1g from the body weight on alloxan-induced diabetic rats after 15days of treatment. The significant reduction in total body weight could be attributed to the loss of fat from adipose tissue and catabolism of amino acids in the muscle tissue [17].-

#### **4.2. Effect of Na alginate of** *S. crassifolium* **on body weight of rats**

 Diabetic mice showed weight loss in all treatment groups except the normal control group. Normal control group gained weight of 24.1g. The negative control group had a very significant weight loss of 51.6g. The positive control group had a weight loss of 47.2g. The treatment group of extract 200mg/kghad a weight loss of 58.8g. The treatment group of 400mg/- kg extract had a weight loss of 45.3g. Meanwhile, the treatment group giving 600mg/kg extract experienced a decrease in body weight by 43.1g. Streptozotocin (STZ)-induced diabetic rats are one of the animal models of type 1 diabetes mellitus. It is well known for its selective pancreatic islet beta-cell cytotoxicity and has been extensively used to induce type 1 diabetes in an experimental rat model. Glibenclamide is often used as a standard antidiabetic drug in STZ-induced diabetes to compare the efficacy of a variety of hypoglycemic drugs [18].-

Throughout the experiments, all the rats were monitored daily and/or weekly for the symptoms of type 1 diabetes mellitus, including polydipsia, polyuria, polyphagia, hyperglycemia,- and muscle wasting leading to weight loss and insulin deficiency. **Figure 1** shows the observations of body weight of treated rats during the whole period of experiments. The body weight- was continuously increased in the normal group and decreased in all diabetes groups. A severe- loss of body weight characterizes STZ-induced diabetes. Due to absolute or relative deficiency- of insulin and decrease of the production of ATP, protein synthesis decreases in all tissues.-

#### **5. Effect of Na alginate on blood glucose-**

Alloxan is a urea derivative which causes selective necrosis of the pancreatic islet β-cells [19]. Alloxan and its reduction product dialuric acid establish a redox cycle with the formation of superoxide radicals [20]. Preprandial blood glucose levels were determinedas fasting blood glucose. Fasting is defined as no calorie intake for at least 8h [1]. Diabetes is diagnosed when the fasting plasma glucose concentration is consistently ≥7mmol/L (126mg/dL) or when the 2h plasma glucose concentration (after drinking a 75g glucose load) is consistently ≥11.1mmol/L (200mg/dL) [21].-

Administration of alloxan led to a significant increase of preprandial blood glucose levels- in rats after 3days. Administration of Na alginate(s) (200, 400, 400mg/kg) significantly- reduced the blood glucose level compared to diabetic control. The dose of 200 and 400mg/- kg of Na alginate did not show a significant difference compared to normal control and- positive control (**Table 3**). The result was supported by previous studies using fiber to- decrease preprandial blood glucose. Nelson etal. [22] used high indigestible fiber and low- indigestible fiber diet to decrease preprandial blood glucose in diabetic dogs for 8months- which resulted in high indigestible fiber significantly that reduces preprandial blood glucose better than low indigestible fiber. Nelson etal. [23] used similar treatment in diabetic- cats for 24weeks and showed high indigestible fiber which gave a better effect on decreasing preprandial blood glucose than low indigestible fiber. Chandalia etal. [12] compared- the amount of fiber that was given to diabetic patients according to the American Diet-


\*Values are means ± SD. Values followed by the different superscript symbol(s) in each column were significantly different (*P*<0.05).-

**Table 3.** Effect of Na alginate of *T. ornata* and *S. crassifolium* on preprandial blood glucose in alloxan-induced diabetic rats.-

Association (8g digestible fiber and 16 indigestible fiber) and fiber-rich diet (25g digestible- fiber and 25 indigestible fiber) for 6weeks. Fiber-rich diet decreased 13% preprandial blood- glucose lower than ADA diet.-

 Normal postprandial blood glucose level is <180mg/dL [1]. In the normal state, the postprandial blood glucose level increases less than 50mg/dL from the preprandial blood glucose level after carbohydrate intake [24]. Alloxan-induced diabetic rats' postprandial blood glucose level surpassed 200mg/dL after 3days of injection. After 15days of treatment, the result was the administration of Na alginate(s) (200, 400, 600mg/kg) which significantly reduces postprandial blood glucose levels on rats compared to diabetic control (P-<-0.05). However, it failed to restore the level to that of normal control group and positive control group (P-<-0.05). The positive control group could restore the postprandial blood glucose level at the same level as a normal control group (**Table 4**).-

 Wolf etal. [25] used 1.5g sodium alginate to show its effect on postprandial glucose peak and glucose uptake reduction after 3h which resulted in line 32.80-±-3.40 and 1429-±-276mg/dL.- Sodium alginate had a reduction effect better than 1.2g gum arabic and 0.3g gum guar with postprandial glucose peak 40.40-±-3.30mg/dL and glucose uptake 1717-±-433mg/dL.-A study on the effect of a meal containing alginate compared to testing a meal without alginate by Torsdottir etal. [26] showed that postprandial blood glucose levels by meal containing alginate decrease 31% lower than a meal without alginate.-

 Preprandial glucose levels for all treatment groups of alginate from *S. crassifolium* were classified into normal levels ranging from 69.311 to 88.029mg/dL and no significant difference. The streptozotocin-induced treatment group experienced very high preprandial glucose levels exceeding 200mg/dL and can be categorized as DM.-The same is also shown in Moree etal. [27]. In this study, male Wistar rats induced by streptozotocin dose 60mg/kg increased blood glucose levels <200mg/dL.-The use of 60mg/kg of streptozotocin in mice can trigger an autoimmune process that can produce damage to the Langerhans island beta cells [28]. Also,


\*Values are means ± SD. Values followed by the different superscript symbol(s) in each column were significantly different (*P*<0.05).-

**Table 4.** Effect of Na alginate of *T. ornata* and *S. crassifolium* on postprandial blood glucose in alloxan-induced diabetic rats.-

STZ is also capable of generating reactive oxygen that has a high role in the destruction of pancreatic β-cells and eventually occurs inhibition of insulin secretion and synthesis resulting in hyperglycemia [29].-

All treatment groups of extracts of *S. crassifolium* did not differ significantly with the positive control (**Table 3**). It can be concluded that all three doses of administration of the extract of *S. crassifolium* had the same effect as the positive control group in lowering blood glucose levels in mice suffering from DM.-The opposite is shown in the negative control treatment group that has a prepreg glucose level that increases from day to day due to accumulated glucose buried in the blood without treatment efforts.-

In general, the viscosity of dietary fiber can reduce the rise in blood glucose levels and reduce food intake by slowing the empty stomach and slowing the absorption of nutrients in the small intestine. Based on these two mechanisms, it is still not clear what mechanisms apply to sodium alginate, perhaps one or both [30]. Different doses of alginate will affect the viscosity of the given test preparation. So, it will lead to differences in the viscosity of the fluid in the gastrointestinal tract and ultimately result in differences in the rate of glucose absorption from the gastrointestinal tract into the blood vessels [31].-

#### **6. Total cholesterol**

 Diabetes is associated with major abnormalities in fatty acid metabolism. The resulting disturbance results in an abnormal lipoprotein cascade from the large chylomicron through to the small HDL particle [31, 32]. Total cholesterol in the serum of negative control was not significantly different compared to positive control, Na alginate 200 and 400mg/kg treatment, and normal control. Na alginate 600mg/kg of *T. ornata* was a significant difference compared to negative control (P-<-0.05). The alginate dose of 200 and 600mg/kg of *T. ornata* did not show the difference (P->-0.05) (**Table 5**) significantly.-

Several previous studies supported the result. Suzuki etal. [33] evaluated the effect of alginate-rich guluronic and mannuronic on cholesterol levels in rats fed with diets containing- both alginates and cholesterol which resulted from reductions in liver cholesterol in rats fed- with each alginate and significantly low cholesterol accumulation in mannuronic acid-rich- alginate. Ren etal. [34] screened 26 species of seaweeds and six polysaccharides from algae- to study their effect on lipid in rats fed with basal diet for 28days of treatment. The six- polysaccharides were sulfated glucuronoxylomannan (0.5%),fucoidin (1%), sodium alginate- (1%),funorin (2.5%), porphyrin (2.5%),and agar (2.5%). Reduction effect of each polysaccharide was 64, 65, 68, 77, 88, and 95%, respectively, compared to control group. At the end- of the study, the polysaccharides could restore the cholesterol level to the same level as the- control group.-

Total cholesterol levels of the normal control group, positive control, and alginate 600mg/kg of *S. crassifolium* had a significant difference compared to the negative control group (**Table 5**). The three treatment groups had lower cholesterol levels than the negative control group. An extract at a dose of 600mg/kg of *S. crassifolium* can lower total cholesterol levels as well as positive controls (glibenclamide). The opposite is shown by the treatment group giving the extract dose of 200 and 400mg/kg of *S. crassifolium*. Both the doses are less effective in lowering total cholesterol levels in mice suffering from diabetes compared to glibenclamide and alginate 600mg/kg of *S. crassifolium*.-

Wikanta etal. [35] reported that sodium alginate could lower total cholesterol in mice with hypercholesterolemia. Administration of sodium alginate with a viscosity of 450 cps significantly reduced total cholesterol levels compared to sodium alginate with lower viscosity. Because, sodiumalginate is a water-soluble fiber compound, forming a viscous solution. The stomach fluid cannot digest this compound in the gastrointestinal tract. When dissolved in water, the sodium alginate fibers form a mesh-like grid that strongly binds many water molecules in a well-defended solute. Its properties as emulgator increasingly enhance the binding ability. A similar mechanism occurs against lipid molecules in bile acids in the gastrointestinal tract. The binding or bonding of lipids by the alginate makes lipid and cholesterol unable


\*Values are means ± SD. Values followed by the different superscript symbol(s) in each column were significantly different (*P*<0.05).-

**Table 5.** Effect of Na alginate of *T. ornata* and *S. crassifolium* on the total cholesterol in alloxan-induced diabetic rats.-

to absorb the body through the small intestine so that it eventually comes out with the stool. Suzuki et al. [33] also reported thatalginate with various mannuronic acid and guluronic acid compositions can decrease total blood cholesterol levels.-

#### **7. HDL-c**

 Administration of Na alginate to alloxan-induced diabetic rats for 200mg/kg alginate of *T. ornata* did not show significant differences compared to negative control and positive control (P->-0.05) (**Table 6**). The alginate of *T. ornata* at a dose of 200 and 400mg/kg was not significantly different between each other. All of the various doses of alginate were significantly different compared to normal control (P-<-0.05). HDL-c management on type 2 diabetes is targeting for >40mg/dL (>50mg/dL on female) [1]. HDL particles seem to have antioxidant properties, inhibiting the oxidation of LDL cholesterol and the expression of cellular adhesion molecules and monocyte recruitment. The HDL may also reduce the risk of thrombosis by inhibiting platelet activation and aggregation [33]. Ren etal. [34] reported that three algal species showed the ability to increase HDL-c levels in blood serum of rats. Fucoidan could increase HDL-c levels up to 47% compared to the control group. Five other polysaccharides, sulfated glucuronoxylorhamman, sodium alginate, funoran, porphyran, and agar, found increased HDL-c by 31.97, 28.93, 9.14, 3.55, and 26.90%, respectively.-

According to Rohman [36] HDL is a protective lipoprotein, in addition to functioning to bring fat to the liver; HDL proved to inhibit the oxidation of LDL and adhesion molecules. HDL-c levels throughout the treatment group did not have a significant difference. The same is also shown in the study of Suzuki etal. [33] that there was no statistically significant difference in HDL-c levels in mice suffering from hypercholesterolemia treated with sodium alginate in comparison with different glucuronic acid and mannuronic acids.-


\*Values are means ± SD. Values followed by the different superscript symbol(s) in each column were significantly different (*P*<0.05).-

**Table 6.** Effect of Na alginate of *T. ornata* and *S. crassifolium* on HDL-c in alloxan-induced diabetic rats.-

#### **8. LDL-c**

LDL-c after administration of alginate(s) from *T. ornata* (200, 400, 600mg/kg) was not- significantly different between each other. Alginate of *T. ornata* 600mg/kg showed a- significant difference compared to negative control, positive control, and normal control- group (**Table 7**). Ren etal. [34] studied the effect of polysaccharide extracts from algae- on LDL-c in blood serums of rats given with basal diet for 28days. The six polysaccharides used in the study decreased LDL-c levels in blood serum. Sodium alginate (1%)- decreased 34.04% of LDL-c. Five other polysaccharides, sulfated glucuronoxylorhamman, sodium alginate, funoran, porphyran, and agar, decreased the LDL-c in line with- 36.42, 37.66, 24.33, 36, and 14%, respectively, compared to normal control. LDL is not- usually increased in diabetes. In part, this may represent a balance of factors that affect- LDL production and catabolism. A necessary step in LDL production is hydrolysis of its- precursor VLDL by LpL.-A reduction can happen in this step because LpL deficiency or- excess surface apoproteins (C1, C3, or possibly E) decreases LDL synthesis. Conversely,- increases in this lipolytic step that accompany weight loss, fibric acid drug therapy, and- treatment of diabetes may increase LDL levels. In diabetes, a reduction in LDL production may be counterbalanced by decreases in LDL receptors and/or the affinity of LDL- for those receptors [37].-

Administration of sodium alginate from *S. crassifolium* most effective in lowering LDL-c levels near the control group was 600mg/kg followed by 200mg/kg and 400mg/kg. The negative control group had a very significant difference with all the other treatment groups (**Table 7**). The negative control group had higher LDL-c levels when compared to the other treatment groups. Meanwhile, the positive control group had lower LDL-c levels than the other


\*Values are means ± SD. Values followed by the different superscript symbol(s) in each column were significantly different (*P*<0.05).-

**Table 7.** Effect of Na alginate of *T. ornata* and *S. crassifolium* on LDL-c in alloxan-induced diabetic rats.-

treatment groups. Levels of LDL-c in this study are still within normal limits, i.e., <130mg/- dL, and Rachmat and Rasyid [38] reported that mice were given 50 and 250g of alginates of *S. crassifolium* which also did not affect LDL-c levels.-

#### **9. Triglyceride**

Triglyceride management on type 2 diabetes is targeting for <150mg/dL [1]. When the glucose levels excess in the blood, glucose will be converted to triglycerides in which triacylglycerol synthesis process is known as lipogenesis. Carbohydrate-rich meal can lead to increase- the process of lipogenesis in the liver and adipose tissue. However, the occurrence of insulin resistance inhibits lipogenesis process making glucose and free fatty acid levels in blood- plasma increased. In the liver, triglyceride accumulation can cause malfunctioning of the- liver (fatty liver) or liver cirrhosis in the long term [39]. Triglyceride of alloxan-induced diabetic rats did not show a significant difference between the groups of treatment using alginate of *T. ornata*. The triglyceride levels remained at normal levels through the given time of- the study (**Table 8**).-

Paxman et al. [40] reported that a drinkcontaining alginate in the obese patienthad no effect- on tryglyceride level.-Triglyceride levels did not show a significant difference between alginate treatment group and control group. Ren etal. [34] used six polysaccharides from algal- species as a treatment for rats given with basal diet for 28days. All of the polysaccharides- used in this research could reduce triglyceride levels as good as their ability reducing LDL-c- in blood serum. Funoran and sulfated glucuronoxylorhamman reduced triglyceride levels- between 46 and 64% compared to the control group. Sodium alginate could decrease the-


\*Values are means ± SD. Values followed by the different superscript symbol(s) in each column were significantly different (*P*<0.05).-

**Table 8.** Effect of Na alginate of *T. ornata* and *S. crassifolium* on the triglyceride in alloxan-induced diabetic rats.-

triglyceride level to 29% compared to the control group. Fucoidan can reduce the triglyceride- levels to 12–20% [34].-

The levels of triglycerides during the experiment using alginate of *S. crassifolium* were decreased. The negative control treatment group had a significant difference when compared to all treatment groups (**Table 8**). This suggests that the three doses of alginate from *S. crassifolium* can lower triglyceride levels equally well with the positive control group that is close to the triglyceride levels of the normal control group.-

 All groups treated with DM except for the normal control group showed elevated triglyceride levels. Levels of triglycerides increased up to 574.867mg/dL.-The condition of hypertriglyceridemia can be diagnosed if the triglyceride level->150mg/dL [41]. According to Pujar- etal. [42], this can be due to direct damage from the pancreatic tissue by high free fatty acids.- The concentration of high free fatty acid will decrease the pH and may activate trypsinogen.- Also, high triglyceride levels can also be caused by the destruction of chylomicron which- is a triglyceride carrier. This changes the acinar function and opens the pancreatic tissue to- triglycerides.-

#### **10. Necrosis of pancreas**

Necrosis is defined as the type of cell death caused by changing the morphology of the nucleus, including chromatin condensation and fragmentation, minor changes in cytoplasmic organelles, and overall causes of cell shrinkage (apoptosis) and autophagic accumulation of two vacuole membranes in the cytoplasm [43]. In type I diabetes mellitus, patients found changes in the pancreas in the form of the reduced size of the pancreas, atrophy in the exocrine pancreas, and atrophy of the acinar cells around the degenerated Langerhans island. On the other hand,in type II diabetes mellitus, an imbalance of exocrine secretion of the pancreas and impaired control of blood glucose occur [44].-

Normal controls show normal cell conditions (**Figure 3**). Negative controls show some damage to the cell. The positive control treatment group also shows the same. The treatment- group of sodium alginate extract is entirely damaged in cells (necrosis). The treatment group- of *S. crassifolium* dose of alginate at 200 and 400mg/kg had more damage than the treatment- group of 600mg/kg alginate. The results of the histological analysis showed that all treatment groups experienced cell damage (necrosis) except the normal control group. According- to Holemans etal. [45], streptozotocin prevents DNA synthesis in mammals and bacterial- cells. In bacterial cells, it provides a special reaction with the cytosine group that causes- degeneration and destruction of DNA.-This biochemical reaction in mammals causes cell- death. Damage to cells in the islets of Langerhans island cells caused by streptozotocin is- irreversible. Similar results were also shown in a study conducted by Elias etal. [46] and- Ikebukuro etal. [47].-

**Figure 3.** Histological studies of STZ diabetic rat pancreas. Normal control: pancreatic section showed the normal size of islets, and destruction was absent (Grade -). Negative control: pancreatic section showed (green arrow) occasional islets, and (orange arrow) destruction was severe (Grade ++++). Positive control (diabetic rats +5mg glibenclamide/kg b.w.): pancreatic section showed moderate islet architecture (green arrow), and destruction (orange arrow) was moderate (Grade +++). Diabetic rats +200mg alginate/kg b.w., and diabetic rats 400mg alginate/kg b.w.: pancreatic section showed (green arrow) occasional islets, and (orange arrow) destruction was severe (Grade ++++). Diabetic rats +600mg alginate/kg b.w.: pancreatic section showed (green arrow) additive improvement in the mass of islets as compared to other alginate treatments, and (orange arrow) destructions was mild (Grade ++). Grade −, normal; Grade ++++, severe destruction; Grade +++, moderate destruction; Grade ++, mild injury.-

#### **11. Conclusion**

Administration of alginate from *T. ornata* in alloxan-induced diabetic rats decreased the preprandial and postprandial blood glucose, lowered total cholesterol, increased HDL-c, and lowered LDL-c in dependent dose manner. However, sodium alginate of *T. ornata* did not show anyeffect on triglyceride. This result can be valuable information to discover alternative therapy- to achieve and/or maintain glycemic control and lipid profile management on diabetes patient.- Nevertheless, the possibility warrants further confirmation. On the other hand, the present- study shows that the alginate *S. crassifolium* has potential antidiabetic action in STZ-induced- diabetic rats and the effect was found to be more similar to the reference drug glibenclamide.-

#### **Acknowledgements**

Research Grants Flagship Universitas Gadjah Mada supported this research through DIPA UGM 2014 number LPPM-UGM/478/LIT/2014.-

#### **Conflict of interest-**

The authors declare no conflict of interest.-

### **Author details**

Amir-Husni-

Address all correspondence to: a-husni@ugm.ac.id-

Department of Fisheries, Faculty of Agriculture Universitas Gadjah Mada, Yogyakarta, Indonesia-

#### **References**


**Chapter 4**

**Provisional chapter**

**Tilapia (***Oreochromis aureus***) Collagen for Medical**

**Tilapia (***Oreochromis aureus***) Collagen for Medical** 

DOI: 10.5772/intechopen.77051

Collagen is a natural polymer widely used in pharmaceutical products and nutritional supplement due to its biocompatibility and biodegradability. Collagen is a fibrous protein that supports various tissues, and its primary structure is formed by repeated units of glycineproline-hydroxyproline. Traditional sources of collagen, such as bovine and pig skins or chicken waste, limit their use due to the dangers of animal-borne diseases. Thus, marine animals are an alternative for the extraction of collagen. The common name of *Oreochromis aureus* is tilapia, widely cultivated for sale as frozen fillets. During its processing, a large amount of collagen-rich wastes are generated. Therefore, the objective of this book chapter is to prove the potential of tilapia skin as an alternative source of collagen for the elaboration of biomaterials. Additionally to the literature review, experimental results of the extraction and characterization of tilapia skin collagen for use in medical dressings are presented.

**Keywords:** acid soluble collagen, marine byproducts, fish skin, valorization, biomimetic

Collagen is widely used in the manufacture of medical materials due to its availability, versatility, compatibility, and degradability in advantage with other biomimetic biomaterials [1]. Traditionally, most of the collagen is extracted from the skins of cattle and pigs or chicken waste. However, these sources limit their applications due to the religious beliefs of some consumers and because of the risk of diseases such as bovine spongiform encephalopathy and aphthous fever disease [2]. During the production of commercial fish products, byproducts

such as skin, bones, and scales rich in collagen are generated [3].

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

distribution, and reproduction in any medium, provided the original work is properly cited.

**Biomaterials**

**Abstract**

materials

**1. Introduction**

**Biomaterials**

David R. Valenzuela-Rojo, Jaime López-Cervantes and Dalia I. Sánchez-Machado

and Dalia I. Sánchez-Machado

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

David R. Valenzuela-Rojo, Jaime López-Cervantes

http://dx.doi.org/10.5772/intechopen.77051
