Effect of Ethanol Extract from Purple Eggplant Skin (Solanum melongena L) On Blood Glucose Levels and Pancreatic Β Cells Regeneration on White Rats Male Hypercholesterolemia-Diabetic

 

Joni Tandi^1*, Rama Danthy¹, Purwaningsih¹, Hadi Kuncoro²

¹Program Studi S1 Farmasi, STIFA Pelita Mas, Palu, Indonesia

²Laboratorium Penelitian dan Pengembangan Kefarmasian FARMAKA TROPIS, Faculty of Pharmacy, Universitas Mulawarman, Samarinda, Indonesia

 

ABSTRACT:

To observed secondary metabolite compounds in the purpleeggplant skin fruit ethanol extract, the effect and effective dose on blood glucose levels and regeneration of pancreatic β cells of white rats male Hypercholesterolemia-Diabetic. This research is a laboratory experiment with a Phytochemical assay using a specified reagent for the ethanol extract of purple eggplant skin. The effect and effective dose on blood glucose levels and regeneration of pancreatic β cells animal model using posttest randomized controlled-group design. A total of 30 rats were divided into six groups. Group I; normal control given standard feed: group II; negative control is given Na CMC 0.5%, high cholesterol feed and induced by streptozotocin 30 mg/kg BW; experimental groups were given extract of ethanol from purple eggplant skin each with dose 25, 50 and 100 mg/kg BW, high cholesterol feed, and streptozotocin 30 mg/kg BW. The data obtained were analyzed using one-way ANOVA test at 95% confidence level and continued with LSD Post Hoc test and description of histologic damage level of the pancreaswas analyzed by Kruskal-Wallis test followed by Mann-Whitney test for observed the difference between treatments. Extracts ethanol of purple eggplant skinaffect blood glucose levels and pancreatic β cell regeneration and an effective dose is a dose of 25 mg/kg body weight was the most effective extract.This research confirm that the ethanol extract from purple eggplant  skin (Solanum melongena L) affect blood glucose levels and pancreatic β cell regeneration.

 

 

 

INTRODUCTION:

The development of the times affects the changes in human lifestyle, because the changing lifestyle due to daily busyness that causes an unhealthy lifestyle. Starting from an unhealthy diet without attention to intake of incoming nutrients such as carbohydrates. Excessive carbohydrate intake due to unhealthy eating patterns often causes various diseases one of which is diabetes mellitus. The high intensity of eating and stress suppressing throughout the day, making blood glucose levels very difficult to control¹.

 

 

Diabetes mellitus is a syndrome of metabolic disorders characterized by high blood glucose levels resulting from a deficiency of insulin hormone secretion or when insulin resistance occurs, Cells cannot effectively use the insulin produced². Diabetes mellitus can lead to the production of excessive free radicals or usually known as Reactive Oxygen Species (ROS). ROS will trigger the occurrence of oxidative stress because free radicals in the body more than antioxidants, free radicals can diffuse into the cell membranes which subsequently react with membrane lipids produce malondialdehyde (MDA). MDA is one of the end products of lipid cell membrane peroxidation by excessive free radicals so that MDA is used as an index of measurement of free radical activity in the body. The oxidation goal of ROS in addition to lipids is DNA, in the oxidation of guanine nucleotide DNA prone to oxidative ROS reactions. The compounds produced from guanine oxidation are 8-hydroxy-deoxyguanosine (8-OHdG). Oxidizing guanine in DNA strands, resulting in DNA losing guanine nucleotides. The sustained reaction can lead to DNA damage, thus inhibiting the process of cell division in spermatogenesis and mitochondria and disrupt respiration that can interfere with cell energy^3,4.

 

Treatment of Diabetes Mellitus disease takes a long time with relatively high medical costs, as well as the side effects of synthetic drugs caused by long-term use. One of the plants commonly used as alternative medicine is purple eggplant (Solanum melongena L)⁵. Eggplants knew as sources of pharmaceuticals and nutraceuticals⁶. Previous studies have suggested that phytochemical screening results show that purple eggplant ethanol extract contains alkaloids and flavonoid compounds that are shown to have antioxidant activity⁵. The anthocyanin from purple eggplant is included in the flavonoid compound that acts as an antioxidant⁷. These antioxidant activities allow flavonoids to capture or neutralize free radicals that can improve the state of the damaged tissue in other words the inflammatory process can be inhibited⁸.

 

Based on previous research, the researchers are interested in conducting further research, whether the extract of ethanol purple eggplant seeds affects blood glucose level and regeneration of pancreas β cells in white male rats Hypercholesterolemia-Diabetes.

 

MATERIAL AND METHOD:

Materials:

Aluminum foil, 40 mesh sieving, Mixing rod, Maceration vessel, Mixer (National), Porcelain cup, Glass chute (Pyrex), Erlenmeyer (Pyrex), Chemical glass (Pyrex), Pyrex, Glucometer (ACCU-CHEK), Glass object, Glucose test strip (ACCU-CHEK), Test animal cage, Pumpkin Measuring (Pyrex), Mortar And Stamper, Micrometer, Olympus Olympus BX 51, Microtome Knife, Surgical Knife, Water-cool (Denville), micropipette (Soccorex), Rotary vacuum evaporator (Eyelet), 3 ml oral Sure (Terumo Syringe), 3 ml injection syringe (Terumo Syringe), Reaction Tubes (Pyrex), Gram Scales and Analytical Scales (Oahu’s), glass containers.

 

Aquadest, Alcohol 70% (Merck), Ammonia, Hydrochloric Acid (Merck), Sulfuric Acid (Merck), Ethanol 96% (Merck), Eater, Canada balsam, 10% formalin, pancreatic tissue, Filter paper, Chloroform, Duck egg yolk, Chloroform, FeCl₃ solution, 10% NaCl solution, Goat Fat, Pig Oil, Standard Feed, Dragendorff Reagent, Lieberman-Burchard Reagent (Merck), Meyer Reagent, Wagner Reagent, Hematoxylin Dye eosin, Magnesium P Powder, Sodium CMC, Streptozotocin (Bio world USA) and Metformin Tablets (PT Hexpharm Jaya) xylol and 30 White rats (Rattus novergicus) for pancreatic tissue.

 

Plant material:

Skin of Purple eggplant fruit (Solanummelongena L.) as plant material is obtained around the city of Palu, Central Sulawesi Province. The skin part from purple eggplantis processed into dried simplicia then powdered using sieved with a 40 mesh sieve.

 

Extraction process and phytochemical assay:

1 Kg from powder skin of purple eggplant macerated with 96% ethanol solvent for three days, during stirring occasionally stirring to speed up the dissolution process after extract is filtered using filter paper. The obtained filtrate was separated from the ethanol solvent by using a rotary evaporator at 60°C and evaporated using a water bath with a temperature of 60 ℃ to remove the remaining solvents still present in the extract until obtained by purple skin thickening extract.

 

Preparation of Streptozotocin solution:

0.3-gramStreptozotocin (STZ) dissolved into buffer citrate pH 4.5 to 100 mL, then shaken until homogeneous, resulting in STZ stock solution of 30 mg/kg BW, then induced in white mouse through intraperitoneal (ip) administration.

 

Preparation of Metformin Suspension:

216 mg Metformin tablet powder suspended in NaCl 0.5% to 100 ml.

 

Preparation animal model for Hypercholesterolemia-Diabetic:

Food containing High Fat from standard feed 80%, 15% pig oil, 5% duck egg yolk. Heat the pig oil until it melts. Eggs are boiled until cooked, then taken yellow and crushed until smooth. Standard feed mixed with pig oil and egg yolk then stirred until homogeneous.

 

Selection of Test Animal:

The test animal used was white mouse with inclusion criteria of 3-4 months old, body weight 150-200 gram, male sex, white hair color, healthy body condition (active and not deformed), while exclusion criteria were sick rat, body weight decreased to less than 150 grams and mice died during the study¹⁰.

 

Data analysis:

Data of blood glucose examination result using Glucometer Accu Check and obtained blood glucose level then analyzed using SPSS 23 software program with One Way Anova statistic test, at 95% confidence level. This test is used to determine the differences between treatment groups. If there is a significant difference, then it is done with a further test of Post Hoc LSD used to observed a significant difference between the control group and the treatment group14.

Data of histology examination result of the microscopic pancreas using Olympus BX-51 microscope with 100 μm scale and obtained as a picture scoring data of histologic damage level of the pancreatic white male cell, then analyzed using nonparametric test Kruskal Wallis and followed by Mann Whitney test to know the difference between group¹⁴.

 

RESULTS AND DISCUSSION:

This study used skin from purple eggplant fruit ethanol extract (SolanummelongenaL.) by maceration method. Maceration is a cold extraction process of soaking the powder of simplicia into the solvent. During the immersion process, the liquid penetrates the cell wall and enter into the cell cavity containing the active substance. The active substance will dissolve into solventcaused bythe difference of concentration between the active substance solutions inside the cell with the outside of the cell, the concentrated solution is pushed out. The process continues in order to obtain equilibrium concentration between the solution outside and inside the cell this method was chosen based on the characteristics of the active substance contained in simplicia to the heating process which is still unknown.96% ethanol is chosen as a solvent because it is more selective, antimicrobe activity, lower toxicity, neutral, and can be mixed with water in all comparisons, requires less heat for concentrating processes and limited soluble confounding agents.

 

Phytochemical Assay:

Table 1. Phytochemical Screening Results Extracts of eggplant ethanol

Information :

(+): Contains a class of secondary metabolites

(-): Does not contain classes of secondary metabolites

Phytochemical preliminary tests were performed to determine the type of chemical compounds contained in the skin of purple eggplant fruit ethanol extract (Solanummelongena L.). Based on phytochemical test results (Table 1), it was found that skin of purple eggplant fruit ethanol extract (Solanummelongena L.) contained secondary metabolite compounds classes alkaloids, flavonoids, saponins, tannins, and polyphenols.

 

This study used a male white rat (Rattus norvergicus) of 30 as a test animal because these animals tend to be easy to adapt, handling and maintenance more easily, high reproduction ability, hormonal male rats more stable because not occur estrus phase and pregnancy that can interfere the end result of a study, the characteristics of production and reproduction tend to be similar to other mammals as well as easy in handling at the time of test treatment⁹. The white rat was first adapted for 14 days. 30 male males divided into six groups of treatment each group consisting of 5 rats, Group 1 (normal control) only given standard feed, then five groups of other rats fed high cholesterol for four weeks. Feeding high cholesterol can increase the content of free fatty acids in the plasma cells causing a decrease in insulin sensitivity in peripheral tissues, so with high cholesterol feeding the cholesterol levels in the blood will increase high, then injected streptozotocin with low doses (30 mg / kg BB in citrate-buffered saline 4.5) a stable dose of doses increases the blood glucose levels administered intraperitonally⁹.Streptozotocin is often used as induction of diabetes mellitus in test animals because it selectively damages pancreatic beta cells. Streptozotocin is a diabetogenic agent that can trigger increased production of excessive free radicals and cause oxidative stress, then measured blood glucose levels after induction to observed elevated blood glucose levels, after which the rats are treated according to the prescribed group.

 

Table 2. Table Average Measurement of Glucose Level of Male Rats

Description: p> 0.05: Different not significant

p <0.05: Significantly different

 

Based on one way ANOVA statistical calculation, the 0th day blood glucose level in all treatment groups showed that there was no significant difference that was marked with value (p> 0.05), it showed that all test animals used were inhomogeneous condition with blood glucose level still within the normal range between 70-107 mg/dl (normal glucose levels in mice between 50-135 mg/dl).

 

After induction of high cholesterol and streptozotocin on the 31st day, blood glucose levels were measured. The results of one way ANOVA statistical calculation shows that there are significant differences marked by the value (p <0.05). All test animals were in hyperglycemia except group I (normal control) where blood glucose levels were between 213-547 mg/dl (normal glucose levels in mice ranged from 50-135 mg/dl).

 

On the 38th day, blood glucose level was measured after ethanol extract of purple eggplant extract for seven days. The measurement results show blood glucose levels between 125-295 mg/dl. One way ANOVA statistical calculation shows that there are significant differences from all treatment groups is indicated by p = 0,000 <0.05. LSD (Least Significantly Difference) posthoc test was done to observe the significant difference between treatment groups. The result of LSD (Least Significant Difference) LSD post-test showed that dose 25 mg/kg BW (group IV) was significantly different with normal control group p = 0,022 <0,05 meaning that 25 mg/kg BW did not give any significant effect in decreasing blood glucose levels. The dosage of 25 mg/kg BW (group IV) was significantly different from the negative control group p = 0.000 <0,05 meaning that 25 mg/kg BW had a significant effect in lowering blood glucose levels. When compared to positive control p = 0,332> 0,05 it means that dose 25 mg/kg BW has a significant effect in decreasing blood glucose level in the presence of active substance contained in extract of purple egg ethanol extract is proportional to metformin as a positive control. When compared with the dose of 50 mg/kg BW, p = 0,502> 0,05 means that the dose 25 mg/kg Bb is not significant with dose 50 mg/kg BW but significantly different with dose 100 mg / kg BB p = 0,013 < 0,05 meaning effect dose 25 mg/kg BB not equal to dose 100 mg / kg BB.

 

 

Table 3. Results of Pancreatic Histopathology Preparation Scoring Observations

Treatment	Histopathology Scores of Test Animal Pancreas				Average ± SD
	1	2	3	4
Normal Control	0	0	0	0	0±0
Pain Control	4	4	4	4	4±0
Positive Control	1	1	1	2	1,25±0,5
Ethanol Extract Skin Seeds Eggplant Purple Dose 25 mg / Kg BB	2	2	2	1	1,75±0,5
Ethanol Extract Skin Seeds Eggplant Purple Dose 50 mg / Kg BB	3	3	3	2	2,75±0,5
Ethanol Extract Skin Seeds Eggplant Purple Dose 100 mg / Kg BB	3	3	3	3	3±0

Information:

Pancreatic damage score:

Score 0 = Normal cell shape, and no necrosis occurs

Score 1 = Normal cell shape, no visible cell necrosis, but degeneration occurs

Score 2 = Abnormal cell shape as well as degeneration

Score 3 = Abnormal cell shape and most noticeable cell necrosis

Score 4 = Abnormal cell shape and almost all necrotic cells visible

 

Dose 50 mg/kg BW (group V) was significantly different with normal control group p = 0,005 <0,05 meaning dose 50 mg/kg BW shown non significant effect in decreasing blood glucose level. The dosage of 50 mg/kg BW (group V) was significantly different from the negative control group p = 0.000 <0,05 meaning the dose 50 mg/kg BW already had a significant effect in lowering blood glucose levels.Comparation to positive control p = 0,760> 0,05 meaning dose 50 mg / kg BW has a significant effect in lowering blood glucose level in the presence of active ingredients contained in purple eggplant skin ethanol extract is proportional to metformin as a positive control. Comparation with dosage of 25 mg / kg BW, p = 0,502> 0,05 mean dose 50 mg/kg BW is not significant with dose 25 mg / kg BW and different not significant with dose 100 mg/kg BB p = 0,056> 0,05 meaning effect of dose 50 mg / kg BW equal to dose 100 mg / kg BW.

 

The doses of 100 mg/kg BW (group VI) differed significantly from the normal control group p = 0.000 <0.05, meaning that the dose of 100 mg/kg BW did not have a significant effect in lowering blood glucose levels. Dose 100 mg/kg BW (group VI) was significantly different with negative control group p = 0,023<0,05 meaning that dose 100 mg/kg BW already gives a significant effect in decreasing blood glucose level. When compared to positive control p = 0,102> 0,05 meaning dose of 100 mg/kg BW already gives a significant effect in lowering blood glucose level with the active ingredient content contained in extract purple skin ethanol extract is proportional to metformin as positive control. When compared with dose 25 mg / kg BB p = 0,0132 <0,05 mean dose 100 mg / kg Bb is significantly different with dose 25 mg / kg BW but will not differ significantly with dose 50 mg / kg BB p = 0,056> 0,05 meaning effect dose 50 mg / kg BB not equal to dose 100 mg / kg BB. Although each doseaffects the decrease in blood glucose levels, the average blood glucose levels of test animals have not reached a normal state then continued giving the extract again for seven days until 45 days.

 

On the 45th day, blood glucose measurement was performed after 7 days of extract. The measurement results show blood glucose levels between 87-125 mg / dl. One way ANOVA statistical calculation shows that there are significant differences from all treatment groups is indicated by p = 000 <0.05. so that further post hoc LSD testing was done to see the significant differences between treatment groups. Further post-LSD assay results showed that the dose of 25 mg / kg BW (group IV) was not significant with the normal control group p = 0.993> 0.05 meaning that 25 mg / kg BW had a significant effect in lowering blood glucose levels. The dosage of 25 mg / kg BW (group IV) was significantly different from the negative control group p = 0.000 <0,05 meaning that 25 mg / kg BW had a significant effect in lowering blood glucose levels. When compared to positive control p = 0,920> 0,05 it means that dose 25 mg / kg BW has a significant effect in lowering blood glucose level with the active ingredient contained in extract purple skin ethanol extract is proportional to metformin as positive control. When compared with dosage of 50 mg / kg BW, p = 0,795> 0,05 means dose 25 mg / kg BW is not significant with dose 50 mg / kg BW and different not significant with dose 100 mg / kg BB p = 0,569 < 0,05 meaning effect dose 25 mg / kg BW equal to dose 100 mg / kg BW.

 

Dose 50 mg / kg BW (group V) was significantly different with normal control group p = 0,788> 0,05 meaning that dose 50 mg / kg BW already have a significant effect in decreasing blood glucose level. The dosage of 50 mg / kg BW (group V) was significantly different from the negative control group p = 0.000 <0,05 meaning that the dose 50 mg / kg BW already had a significant effect in lowering blood glucose levels. When compared to positive control p = 0,873> 0,05 it means that dose 50 mg / kg BW has a significant effect in lowering blood glucose level with the active ingredient contained in extract purple skin ethanol extract is proportional to metformin as positive control. When compared with dose 25 mg / kg BW, p = 0,795> 0,05 mean dose 50 mg / kg BW is not significant with dose 25 mg / kg BW and different not significant with dose 100 mg / kg BB p = 0,756> 0,05 meaning effect of dose 50 mg / kg BW equal to dose 100 mg / kg BW.

 

Dose 100 mg / kg BW (group VI) was significantly different with normal control group p = 0,563> 0,05 meaning dose 100 mg / kg BW already give effect in decreasing blood glucose level. The dose of 100 mg/kg BW (group VI) was significantly different from the negative control group p = 0.000 <0.05, meaning that the dose of 100 mg/kg BW already had a significant effect in lowering blood glucose levels. When compared to positive control p = 0,639> 0,05 meaning dose of 100 mg/kg BW has a significant effect in lowering blood glucose level with the active ingredient contained in extract purple skin ethanol extract is proportional to metformin as a positive control. When compared with dose 25 mg / kg BW, p = 0,569> 0,05 mean dose 100 mg / kg BW is not significant with dose 25 mg / kg BW and different not significant with dose 50 mg / kg BB p = 0,756> 0,05 meaning effect of dose 50 mg / kg BW equal to dose 100 mg / kg BW. From the results of measurements of blood sugar levels on the 45th day showed the three doses of purple eggplant ethanol extract (Solanummelongena L.) gave the effect of lowering blood sugar levels in mice (Rattusnovergicus) hypercholesterolemia-diabetes.

 

Figure 1: Profile of Blood Glucose Level Before Treatment (Day 0), After Induction (Day 1 to 31) And During Treatment (Day 38 s / d Day 45).

 

Based on Mann-Whitney's analysis, there were significant differences in the histopathology of pancreatic rats from each treatment group (p <0.05), ie normal control group was significantly different with all groups (p <0.05). The negative control group differed significantly with the normal control group, the positive control group, the dose treatment group 25 mg/kg BW and 50 mg/kg BW (p <0.05) but not significantly different with the treatment group of 100 mg/kg BW (p> 0.05). The positive control group differed significantly with the normal control group and the treatment group of 100 mg / kg BW (p <0.5) but differed from the treatment group dose 25 mg / kgBB and 50 mg / kg BW (p> 0.05) . The treatment group of 100 mg/kg BW was significantly different from the normal control group, the positive control group, the dosage of 25 mg/kg BW and 50 mg/kg BW (p <0,5) but not significantly different from the negative control group (p> 0.05). The treatment group with dose 25 mg/kg Bb was significantly different with the normal control group and the treatment group of 100 mg/kg BW (p <0,5) but not significantly different with the positive control group and the dose treatment group 50 mg/kg BW > 0.05). The treatment group dose 50 mg / kg BW was significantly different with the normal control and treatment group of 100 mg / kg BW (p <0,5) but not significantly different with positive control group and treatment group dose 25 mg / kg BW (p> 0 , 05).

 

Figure 2: Histopathology of white rat tissue pancreas score 0 (Normal) (400x magnification, HE staining)

 

Figure 3: Histopathology of white rat tissue pancreas scores 1 (1/4 total pancreatic cell necrosis) (400x magnification, HE staining)

 

Figure 4:Histopathology of white rat tissue pancreas scores 2 (1/2 total necrosis of pancreatic cells) (400 × magnification, HE staining).

 

Figure 5:Histopathology of white rat tissue pancreas scores 3 (3/4 total pancreatic cell necrosis) (400 × magnification, HE staining).

 

Figure 6: Histopathology of white mouse pancreatic tissue score 4 (necrosis of all pancreatic cells) (400 × magnification, HE staining).

 

Based on observations of histopathology preparations of rat pancreas and analyzes, it was proved that giving purple eggplant ethanol extract affected histopathology images of streptozotocin-induced pancreatic mice. From the extract of purple eggplant ethanol extract at 25 mg/kg BW, 50 mg/kgBW and 100 mg/kg BW already have an effect on histopathology picture of rat pancreas, but at a dose of 100 mg/kg BW the effect is not too good compared to dose 25 mg/kg BW and dose 50 mg/kg BW that have a better effect.

 

This suggests that administration ethanol extract of skin fruit purple eggplant (SolanummelongenaL.) has the effect of lowering blood glucose levels in the white rat (Rattusnovergicus). The phytochemical assay showed the class of secondary metabolite consist of alkaloids, flavonoids, saponins, tannins, and polyphenols. Alkaloids can lower gluconeogenesis so that glucose levels in the body and insulin requirements decrease. Antioxidant activity canbinding free radicals that cause improvement in pancreatic beta cells and cause improvement of tissues, there is an increase in the amount of insulin in the body so that blood glucose will enter the cells resulting in decreased blood glucose levels in the body. Flavonoids act as antioxidants in order to inhibit the formation of free radicals and can regenerate damaged pancreatic β cells so that insulin deficiency can be overcome. Saponins can lower blood glucose levels by inhibiting gastric emptying. Gastric emptying is slowing then the food absorption will be longer and blood glucose levels improve. Tanin has a hypoglycemic activity that increases glycogenesis and serves as an astringent or chelating that can shrink the intestinal epithelial membrane, thus reducing the absorption of nutrients as a result inhibiting glucose intake and the rate of glucose elevation is not too high¹⁰. Whereas polyphenols have a powerful antioxidant activity reducing oxidative stress.

 

CONCLUSION:

Skin of Purple eggplant fruit ethanol extract (Solanummelongena L.) contains secondary metabolite compounds class of flavonoids, alkaloids, polyphenols, tannins, and saponins. The extract has an effect on blood glucose levels and regeneration of pancreatic β cells of male hypercholesterolemia-diabetic white rats with effective dose 25 mg/Kg BW.

 

ACKNOWLEDGMENT:

The Author gratefully thanks to STIFA Pelita Mas Palu for Funding research and all research facilities.

 

 

REFERENCES:

1.     Trilestari Herni.. Relationship between dietary behavior and glucose levels when in type II diabetes mellitus patients in Ambarketawang Yogyakarta. Jurnal Sains dan Kesehatan. 2016

2.     International Diabetes Federation. 2015. IDF Diabetes Atlas. 7th Edition.

3.     Fajans SS, Bell GI, and Polonsky KS. Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young. New England Journal of Medicine 2001;345(13); 971-980.

4.     Tandi J, Wulandari Ayu, Asrifa. Effect of Gendola Merah Leaf Ethanol Extract (Basella alba L.) against Creatinine levels, urea and Rat Kidney tubules Histological Description White Males (Rattus norvegicus) diabetic Streptozotocin induced. Jurnal Farmasi  Galenika2017; 3(2); 93 – 102.

5.     Martiningsih NW, Sukarta IN, dan Yuniana PE. Phytochemical Screening and Antioxidant Activity Test of Ethanol Extracts of Purple Eggplant Fruit (Solanum melongena L.).  (Jurnal Kimia) Journal Of Chemistry2014; 8(2); 145-152.

6.     Gürbüz N, Uluişik S, Frary A, Frary A, Doğanlar S. Health benefits and bioactive compounds of eggplant, Food Chemistry2018; 268(1); 602-610.

7.     Aer BN, Wullur AC, Citraningtyas G. The effect of purple eggplant skin ethanol extract (Solanum melongena L.) Against Blood Sugar Levels in Male White Rat Strains Wistar (Rattus norvegicus). Jurnal Ilmiah Pharmacon 2013; 2 (4); 135-141.

8.     Suryani N. Endang HT. Aulanni’am. Effect of Methanolic Swieteniamahagoni Seed Extracts in Increasing Insulin Level, Decreasing TNF-α Expression and Repairing Pancreatic Tissue Damage on Diabetic Rat. Jurnal Kedokteran Brawijaya 2013;27(3); 137-145.

9.     Azhari DM, Yuliet Y, and Khaerati K. Powder Oyster Mushroom Activity Test (Pleurotus ostreatus (Jacq.) P. Kumm) Against Blood Glucose Levels in Animal Models of Diabetes Hypercholesterolemia. Jurnal Farmasi Galenika (Galenika Journal of Pharmacy) 2016; 2(2); 96-102.

10.   Harborne JB. Phytochemical methods: A guide to modern techniques of plant analysis. 1987.

11.   Shepherd PR, and Kahn BB. Glucose transporters and insulin action—implications for insulin resistance and diabetes mellitus. New England Journal of Medicine 1999; 341(4); 248-257.

12.   Tandi J, As’ad Suryani, Natzir R, Bukhari A. Test of Ethanol extract Red Gedi Leaves (Abelmoschus Manihot.(L.) Medik) in White Rat (Rattus Norvegicus)Type 2 Diabetes Mellitus. International Journal of Sciences: Basic and Applied Research (IJSBAR) 2016; 30(4); p. 84.

13.   Asrifa A, Yusriadi Y, and Martina A. Effect Test of Gendola Merah Leaf Ethanol Extract (Basella alba L.) Against Tubular Histological Overview of Kidney White Male Rat (Rattus Norvegicus) Streptozotocin induced. Farmakologika-Jurnal Farmasi 2017;14(02); 165-173.

14.   Tandi J, Amelia J, Ayu G, Irwan. Effect Of Ethanol Extract of Kenikir (CosmosCaudatus Kunth.) Leaves In Blood Glucose,Cholesterol And Toward Histopathology Pancreas Description In Male White Rats (RattusNorvegicus).Proceeding International Seminar and Expo on Jamu 2 2017;43-45.

15.   Tandi J, Hanifah M,  Yuliet, Yusriadi. Effectiveness of Red Gedi Leaf Extract on Blood Glucose, Malondialdehyde, 8-Hydroxy-Deoxiguanosine, and Insulin Diabetes Mice. J. Trop. Pharm. Chem2016; 3(4);265-266.

16.   Tendean I, Kenta YS, Mulyani S. Test of Taro Leaf Ethanol Extract (Colocasia Escuenta (L.) Schott.) Against Histopathology Overview of Male White Rat Pancreas (Rattus norvegicus) Diabetes hypercholesterolemia. Farmakologika - Jurnal Farmasi 2017; 14(2); 138-148,

 

 

 

 

 

 

 

Received on 17.12.2018          Modified on 21.01.2019

Accepted on 28.02.2019        © RJPT All right reserved