|Year : 2018 | Volume
| Issue : 3 | Page : 237-242
Antioxidant and antidiabetic activities of methanolic extract of Cinnamomum cassia
Jasvin Singh1, Subramani Parasuraman2, Sathasivam Kathiresan1
1 Department of Biotechnology, Faculty of Applied Sciences, AIMST University, Kedah, Malaysia
2 Unit of Pharmacology, AIMST University, Kedah, Malaysia
|Date of Web Publication||3-Jul-2018|
Dr. Subramani Parasuraman
Unit of Pharmacology, AIMST University, Kedah
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Cinnamomum cassia or Chinese cinnamon is one of the fundamental herbs in traditional Chinese medicine. C. cassia is used as astringent, antiseptic, and used for the treatment of metabolic disorders. The antioxidant and antidiabetic effects of its extracts are unclear. Hence, the present study is planned to investigate the antioxidant and antidiabetic effects of methanolic extracts barks of C. cassia. Materials and Methods: Bark of C. cassia was extracted with methanol, ethanol, and acetone and its antioxidant activity was studied using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) free radical scavenging assays. Acute toxic effect of methanolic extract of C. cassia (MECC) carried out as Organisation for Economic Co-operation and Development guidelines. MECC was studied for its antidiabetic effect using streptozotocin (STZ)-induced diabetic rats. Results: In both DPPH and ABTS free radical scavenging assay, methanolic and ethanolic extracts exhibited free radical scavenging activity. In acute toxicity testing, MECC did not show any significant toxic signs up to 2000 mg/kg, hence the antidiabetic activity of MECC was carried out at the dose levels of 125, 250, and 500 mg/kg. MECC showed antidiabetic activity from 2nd week of the experiment onward. At the end of the study, diabetic animals showed significant increases in the levels of total cholesterol (TC), very-low-density lipoprotein, and TC/high-density lipoprotein radio compare with that of normal control and MECC prevented the STZ-induced hyperlipidemia. In the histopathological analysis, sections from the liver, pancreas, and kidney of the diabetic animals and the animals treated with MECC 500 mg/kg showed mid-to-moderate toxic effects. Conclusion: The MECC exhibited significant antioxidant and antidiabetic activities.
Abbreviation Used: ABTS: 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid, ALP: Alkaline phosphatase, ANOVA: Analysis of variance, AUHAEC: AIMST University Human and Animal Ethics Committee, BW: Body weight, CKD: Chronic kidney disease, CMC: Carboxymethyl cellulose, DPPH: 2,2-diphenyl-1-picrylhydrazyl, GLP1: Glucagon-Like Peptide-1, HDL: High-density lipoprotein, MECC: Methanolic extract of C. cassia, OECD: Organisation for Economic Co-operation and Development, SD: Sprague-Dawley rats, S-GLUT1: Sodium glucose co-transporter 1, SGOT: Serum glutamic oxaloacetic transaminase, SGPT: Serum glutamic-pyruvic transaminase, STZ: Streptozotocin, TC: Total cholesterol, VLDL: Very-low-density lipoprotein, WHO: World Health Organization.
Keywords: Cinnamomum cassia, diabetes, streptozotocin, Sprague-Dawley rats
|How to cite this article:|
Singh J, Parasuraman S, Kathiresan S. Antioxidant and antidiabetic activities of methanolic extract of Cinnamomum cassia. Phcog Res 2018;10:237-42
|How to cite this URL:|
Singh J, Parasuraman S, Kathiresan S. Antioxidant and antidiabetic activities of methanolic extract of Cinnamomum cassia. Phcog Res [serial online] 2018 [cited 2018 Dec 19];10:237-42. Available from: http://www.phcogres.com/text.asp?2018/10/3/237/235820
- Globally, the prevalence rate of diabetes is increasing, and diabetes mellitus is the ninth major cause of death. Diabetes mellitus also increase the risk of macro- and microvascular complications. In traditional medicinal system, herbs are used to managing diabetes mellitus and its complications. In traditional Chinese medicine, Cinnamomum Cassia (Lauraceae) is used for the treatment of diabetes mellitus. In this present study, the antioxidant and antidiabetic activities of methanolic extract of C. Cassia is evaluated.
| Introduction|| |
Diabetes is a serious and chronic disease that occurs when the body does not produce sufficient insulin to regulate normal blood glucose levels and it is a common effect of uncontrolled diabetes. According to the World Health Organization global report on diabetes 2016, >400 million people live with diabetes. The prevalence of diabetes is increasing dramatically in both developed and developing countries due to urbanization, population growth, aging, and increasing prevalence of obesity and physical inactivity. The International Diabetes Federation forecasts 334 million people will have diabetes in 2025 and major prevalence will be in India (79.4 million), China (42.3 million), and United States (30.3 million). Globally, the public health burden and the human economic cost are increasing with diabetes, hence the search for an alternative for the treatment of diabetes is essential in the current era.
Traditional medicine, especially plant-based drugs are said to be an important alternative in the health-care system. Historically, natural products have been used for the treatment of many diseases and illnesses since ancient times. Two-thirds of the world's population relied on plant-derived drugs. It is estimated that 1% of all flowering plants including Cinnamomum cassia have gained recognition by modern scientist although local communities have used about 10%–12% of it to treat various infections.
C. cassia (Lauraceae) also known Chinese cassia or Chinese cinnamon, is considered one of the fundamental herbs in traditional Chinese medicine. Medicinal use of cinnamon dates back approximately 5000 years, and it is traditionally used as astringent, antiseptic, and used to treat nausea, flatulence, and diarrhea., Kamble and Rambhimaiah studied the antidiabetic effect of aqueous extract of C. cassia (60 mg/kg) alone and supplemented with glibenclamide (5 mg/kg) in alloxan-induced diabetic rats, and the aqueous extract of C. cassia exert antidiabetic activity. Khan et al. also studied the effect of cinnamon on glucose and lipids levels of people with type 2 diabetes and suggested that addition of 1, 3, or 6 g of cinnamon to the diet led to significant decreases in serum glucose levels after 40 days. Cinnamon is suggested to have antifungal, antiulcer, chemopreventive, antispasmodic, and hypolipidemic  activities. The relationship between antioxidant properties and antidiabetic effect of various solvent extract of C. cassia remains unclear. Hence, the present study is planned to study the antioxidant properties and antidiabetic effect of various solvent extracts of C. cassia.
| Materials and Methods|| |
Collection and identification of barks of Cinnamomum cassia
The bark of cinnamon was collected from the local market at Bedong and its authenticity was confirmed by Dr. Deivanai Subramanian. The bark was cleaned and dried in an oven for 24 h at 40°C. The dried bark was then powdered using a blender and the power was stored in an airtight container.
Extraction of barks of Cinnamomum cassia
The powdered barks of C. cassia was packed in thimble and placed in a Soxhlet apparatus. The back powder was extracted with methanolic, ethanolic, and acetone. The extraction was carried out for 24 h at about 55°C–80°C; the extract was filtered through muslin cloth. The filtrate was concentrated to a dry mass by evaporation under reduced pressure. The yield of methanolic, ethanolic, and acetone extract of barks of C. cassia was found to be 22.57, 17, and 15.3% w/v, respectively. The extracts of barks of C. cassia were stored in a desiccator at room temperature until further analysis.
Qualitative phytochemical analysis of methanol, ethanol, and acetone extracts of C. cassia were carried out to test for the presence of constituents such as alkaloids, flavonoids, terpenoids, saponins, tannins, and glycoside. Total flavonoid content and total phenolic content of methanolic, ethanolic, and acetone extracts of C. cassia determined by the method described by elsewhere., Total flavonoid content and total phenolic content of various extracts of C. cassia compared with gallic acid and quercetin, respectively. All tests were done in triplicates.
Antioxidant activity of methanolic, ethanolic, and acetone of C. cassia was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging methods using method described by elsewhere.,,
2,2-diphenyl-1-picrylhydrazyl free radical scavenging assay
Briefly, a 0.1 mM DPPH solution was freshly prepared in methanol/ ethanol/ acetone and 1 ml of this solution was vigorously mixed with of 50 μL of various concentrations (50–1000 μg/ml) of methanolic/ethanolic/acetone extract of C. cassia, respectively, of each extract. After 30 min incubation in the dark at room temperature, and absorbance was measured at 517 nm against a blank using a ultraviolet (UV)/visible spectrometer. All analysis was performed in triplicate. The DPPH free radical scavenging properties of various extract of C. cassia compared with ascorbic acid.,
2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid free radical scavenging assay
ABTS was prepared by the mixing of 7 mM ABTS with 2.45 mM potassium persulfate and allowed the mixture to stand in the dark at room temperature for 12 h. Before assay, the ABTS working reagent was diluted with deionized water to reach an absorbance of 0.68–0.72 at 734 nm. The assay was assessed by mixing 500 μL of ABTS radical solution with 500 μL of various dilutions of each extract, and this mixture was allowed stand for 8 min, and then the absorbance was measured at 734 nm against a blank using a UV/visible spectrometer. The ABTS free radical scavenging properties of various extract of C. cassia compared with trolox (a water-soluble analog of Vitamin E). All analysis was performed in triplicate.,
Healthy, adult, either gender of Sprague-Dawley (SD) rats (200 ± 10 g body weight [BW]) were obtained from Shafazz Enterprise, Malaysia. The animals were housed in large, spacious, polyacrylic cages at an ambient room temperature with 12 h-light/12 h-dark cycle. Rats had free access to water and rodent pellets diet. The study was approved by the Human and Animal Ethics Committee (AUHAEC/FAS/2016/03) of AIMST University and the study was conducted according to Animal Research Review Panel guidelines.
Acute toxicity testing
Methanolic extract of C. cassia (MECC) was used for pharmacological screening because it has more total phenolic and total flavanoid content and showed better antioxidant activity in ABTS free radical scavenging assay. Acute oral toxicity of the MECC was carried as per the guidelines set by the Organization for Economic Co-operation and Development (OECD), revised draft guidelines 423. Healthy, adult female SD rats weighing 200 ± 10 g (3 animals/dose) were used for the experiment. Overnight fasted rats were orally fed with MECC at the dose levels of 5, 50, 300, and 2000 mg/kg BW. The rats were then closely monitored for change in their behavioral, neurological, and autonomic profiles continuously for 24 h after dosing. After 24 h, the animals were observed (at least two times a day) for a period of 14 days to evaluate the changes on behavioral, neurological, autonomic profiles, and mortality.
Antidiabetic activity of methanolic extract of
Healthy, adult male SD rats weighing 200 ± 10 g was used for the experiment. Overnight-fasted rats were administered intraperitoneally with freshly prepared 55 mg/kg streptozotocin (STZ) in 0.1 M citrate buffer (pH 4.5) to induce diabetes mellitus. After 24 h of diabetes induction, the rats were fed with 5% of the glucose solution (2 ml/kg BW) to prevent hypoglycemic mortality. Diabetes mellitus was confirmed after 48 h of diabetes induction by measuring the fasting blood glucose level using the blood sample obtained from the tail vein. Rats with fasting glucose of > 200 mg/dl were confirmed as diabetic rats and they were used for further experiment. Diabetic animals were randomly divided into five groups (Group II–VI) each group of 6 rats as follows:
- Group I: Normal control rats
- Group II: Diabetic control rats
- Group III: Diabetic animals treated with glibenclamide 10 mg/kg
- Group IV: Diabetic animals treated with MECC125 mg/kg
- Group V: Diabetic animals treated with MECC 250 mg/kg
- Group VI: Diabetic animals treated with MECC 500 mg/kg
Animals in Group I (normal control) and Group II (diabetic control) animals were received 0.5% w/v carboxymethylcellulose (CMC). Animals in Group III were treated with 10 mg/kg BW of glibenclamide and animals in Group IV–VI were treated with MECC at dose levels of 125, 250, and 500 mg/kg BW. The dose of MECC for antidiabetic study was selected from the results of acute toxicity study. The standard and test drugs were suspended with 0.5% w/v CMC and were administered once daily through oral gavage for 21 consecutive days.,
Throughout the study, changes in animal BW were measured at regular intervals. On 7th and 14th day of the experiment, few drops of venous blood was collected from all the animals through tail vein and immediately blood glucose levels were measured using a glucometer (Accu-Chek Aviva meter, Roche Diagnostics (M) Sdn. Bhd., Selangor). At the end of the study (i.e., 21st day), blood sample was collected from all the experimental animals through retro-orbital plexus puncture under diethyl ether anesthesia for biochemical analysis. Later, all the experiential animals were euthanized by cervical dislocation and the organs such as lung, heart, liver and kidney were collected and relative weight was measured. A part of liver, pancreas and kidney tissues were preserved in10% v/v neutral formalin for histopathological examination.
During the study, the few drops of blood sample were collected through rat tail vein and blood glucose was estimated immediately using glucometer. At the end of the experiment, few milliliter of the blood sample was collected in plain glass tube through retro-orbital plexus and the serum separated by centrifuging at 3000 RPM for 20 min. The serum sample was used for the estimation of biochemical parameters such as serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP), total serum cholesterol, serum triglyceride, high-density lipoprotein (HDL) cholesterol, creatinine, urea, total protein, albumin, total bilirubin, insulin, sodium, and chloride. The samples were tested using biochemical analyzer (Cobas 6000 biochemical analyzer, Roche Diagnostics) and the level of insulin was estimated using electrochemiluminescence method in Clinipath Malaysia Sdn Bhd laboratory, Malaysia.
Low-density lipoprotein (LDL) cholesterol, very LDL (VLDL), and HDL ratio were calculated mathematically. The LDL cholesterol levels was calculated using Iranian formula (LDL = TC/1.19 + TG/1.9 − HDL/1.1–38 [mg/dL]); VLDL was calculated utilizing formula LDL/5 and HDL ratio was calculated using formula ([HDL-cholesterol/TC − HDL-cholesterol] ×100 [%]).,
Organs such as liver, pancreas, and kidney were collected from normal control, diabetic control, glibenclamide, and MECC 500 mg/kg and they were preserved in 10% neutral formalin for histopathological analysis. The liver, pancreas, and kidney samples were embedded in paraffin after being dehydrated in alcohol and subsequently cleared with xylene. Five-micrometer thickness of liver, pancreas, and kidney section was prepared from paraffin blocks and stained with hematoxylin and eosin and mounted in neutral DPX medium, and the sections were examined under a light microscope.
The results of free redial scavenging assay were expressed mean ± standard deviation and the antidiabetic activity of MECC was expressed as mean ± standard error of the mean. Statistical differences between the groups were determined using repeated measure analysis of variance, followed by Tukey's post hoc test. P <0.05 is considered statistically significant.
| Results|| |
The methanolic, ethanolic, and acetone extracts of C. cassia showed the presence of alkaloids, flavonoids, terpenoids, saponins, tannins, and glycoside. MECC exhibits more phenolic content (675.33 mg GAE/g) followed by acetone extract (345.67 mg GAE/g) and ethanolic extract (85.33 mg GAE/g) of C. cassia. In total flavonoid content analysis also, MECC recorded the highest flavonoid content (5096.83 mg QE/g) which was followed by ethanolic (4974.17 mg QE/g) and acetone extract (4561.17 mg QE/g) of C. cassia.
In DPPH free radical scavenging assay, ethanolic extract exhibited the highest scavenging activity when compared against other extracts, recording an activity of 88.26% ±0.09% at concentrations of 1000 μg/ml and the results were comparable with the same concentration of ascorbic acid (87.66% ±0.52%). The methanolic and acetone extracts had the 63.08% ±0.16% and 70.79% ±0.20% scavenging activity at concentration of 1000 μg/ml, respectively.
In acute toxicity testing, MECC did not showed any significant toxic effects up to 2000 mg/kg, hence the antidiabetic activity of MECC was carried out at the dose levels of 125, 250, and 500 mg/kg. In ABTS free radical scavenging assay, methanolic extract exhibited the highest scavenging activity when compared against other extracts, recording an activity of 65.40% ±0.42% at concentrations of 1000 μg/ml and the results were comparable with the same concentration of trolox (64.60% ±0.34%) at the same concentration. The ethanolic and acetone extracts had the 63.00% ±0.08% and 62.50% ±0.32% scavenging activity at concentration of 1000 μg/ml, respectively.
In antidiabetic study, the animals were injected with STZ to induce diabetes mellitus. After STZ injection, 80% animals were developed diabetes and 10% animals were died due to STZ induced hypoglycemia.
Throughout the study, diabetic animals showed significant increases in water intake (data not presented). Diabetic animals showed inhibition of regular BW gain when compared with control animals. However, the diabetes mellitus-induced BW reduction was inhibited by the glibenclamide and MECC [Figure 1]. Throughout the experiment, diabetic control animals showed significant increases in blood glucose levels compare with control animals and MECC showed significant reduction in STZ-induced hyperglycemia from 2nd week onward [Table 1].
|Figure 1: Effect of methanolic extract of Cinnamomum cassia on body weight of Sprague-Dawley rat. Values are expressed as mean ± standard error of the mean (n = 6)|
Click here to view
|Table 1: Effect of methanolic extract of Cinnamomum cassia on blood glucose (mmol/L)|
Click here to view
In biochemical parameter analysis, diabetic animals showed significant increased levels of serum creatinine levels (P< 0.05) and MECC at 125 mg/kg showed significant increase level of ALP (P< 0.001) when compared with normal control. Biochemical parameters and mineral (sodium, potassium, and chloride) levels are found to be with in normal rage in the animals treated with MECC 250 and 500 mg/kg [Table 2] and [Table 3]. MECC-treated animals showed significant depletion in the levels of insulin when compared with control animals [Table 3]. At the end of the study, diabetic animals showed significant increases in the levels of total cholesterol (TC) (P< 0.001), VLDL (P< 0.001), and TC/HDL (P< 0.001) radio compare with normal control. Glibenclamide also significantly increased the levels of TC (P< 0.01), triglyceride (P< 0.05), and VLDL (P< 0.05) and MECC prevented the STZ-induced hyperlipidemia in rats [Table 4]. Organ weight analysis did not showed any significant variations in the absolute and relative weights of liver and kidney. In histopathological analysis, sections from liver, pancreas, and kidney of diabetic control, glibenclamide and MECC 500 mg/kg-treated animals showed mid-to-moderate toxic effects [Figure 2].
|Figure 2: Photomicrograph of a section of organs of diabetic animals and animals treated with glibenclamide and methanolic extract of Cinnamomum cassia 500 mg/kg (H and E, ×400). (a) Liver of diabetic rat showing normal configuration of liver lobules with patchy feathery degeneration of hepatocytes and mild sinusoidal congestion; (b) pancreas of diabetic rat showing permanent vesicular nuclei with well-defined nucleoli and indicative of focal toxic changes; (c) kidney of diabetic rat showing congested glomeruli, regenerative tubules, and granular degeneration of the tubular epithelial cells; (d) liver of glibenclamide-treated rat showing mottled and speckled appearance of individual hepatocytes; (e) pancreas of glibenclamide-treated rat showing acute congestion vacuolated cytoplasmic appearance; (f) kidney of glibenclamide-treated rat showing mild vacuolar degeneration of tubules; (g) liver of methanolic extract of Cinnamomum cassia 500 mg/kg-treated rat showing mild kupffer cell hyperplasia and foci sinusoidal congestion; (h) pancreas of methanolic extract of Cinnamomum cassia 500 mg/kg-treated rat showing no apparent degeneration changes of pancreatic acini and small well-delineated lymph nodes; and (i) kidney of methanolic extract of Cinnamomum cassia 500 mg/kg-treated rat showing congested glomeruli and focal areas of toxic changes within the renal tubules exhibiting vasculation|
Click here to view
|Table 2: Effect of methanolic extract of Cinnamomum cassia on biochemical parameters|
Click here to view
|Table 3: Effect of methanolic extract of Cinnamomum cassia on minerals and insulin hormone|
Click here to view
|Table 4: Effect of methanolic extract of Cinnamomum cassia on lipid profile|
Click here to view
| Discussion|| |
MECC has rich total phenolic and total flavanoid content and showed the presence of antioxidant activity in both DPPH and ABTS free radical scavenging assays. Hence, MECC was used for the pharmacological studies. The phenolic substances and flavonoids are most important bioactive constituents of plants and which may have vast potential to being an important source of phytomedicine.
Natural antioxidants can be classified accordingly by its different mechanism of action. In the present study, the various solvent extracts of C. cassia were tested for their free radical scavenging capacity and concentration-dependent radical scavenging activity was observed in DPPH and ABTS methods. The phenolic and flavonoid compounds also responsible for the antioxidant activity of plants. The antioxidant properties of the different extracts of C. cassia may be influenced by solubility, pH, and radical quenching by antioxidants.,
STZ is toxic glycoside obtained from Streptomyces achromogenes, a Gram-positive bacterium and it is toxic to the insulin-producing beta cells of the pancreas in mammals. The alkylating properties of the STZ modify the biological macromolecules, fragment DNA, and destroy the β-cells. In the diabetic control group, reduction in BW was observed, which may be due to severe muscle degeneration, increased muscle wasting, and loss of tissue proteins., The protective mechanism of the plant fraction on BW of diabetic rats may be due to its capacity to lower and regulate hyperglycemia. MECC exhibited significant antidiabetic activity against STZ-induced diabetes in rats at the end of 2nd week of the experiment onward, and the results were comparable with that of glibenclamide. This finding suggested that C. cassia has a beneficial effect on maintaining BW of diabetic rats. The flavonoids present in the plant may contribute for its antidiabetic activity. The antidiabetic effect of flavonoids and polyphenolic compounds are may be due to regeneration of damaged beta cells of pancreases and inhibition of glucose transport by inhibiting the sodium-glucose cotransporter 1 (S-GLUT1) in the intestine, respectively.
Diabetic animals showed significant increase of serum creatinine level and which can lead to the development of chronic kidney disease (CKD) and kidney failure. Lower serum creatinine independently increased the risk of diabetes and the reason is unclear. Harita et al. hypothesized that the lower serum creatinine might reflect a lower volume of skeletal muscle. Skeletal muscles are major target tissue of insulin and lower volume of skeletal muscle may have increase chances of development of insulin resistance, which may cause diabetes., In the present study, increase in the level of serum creatinine level was observed in diabetic rats.
Significant increases of ALP level was found in glibenclamide-treated group which may be due to drug effect or diseases. Glibenclamide has antioxidant properties and has hepatoprotective effect through upregulating the intracellular reactive oxygen species and subsequently activating Akt-NF-κB pathway. Hence, we hypothesis that impairment of liver enzyme in glibenclamide may be due to STZ-induced diabetes. In both, diabetic control and MECC-treated groups, significant reduction in the levels of insulin were observed, whereas glibenclamide improved the insulin secretions in diabetic animals. Li et al. also reported the effect of glibenclamide on insulin and this effect is due to increases in insulin sensitivity index level, moderately enlarged the islets and significantly reduced the scores of the injuries of the pancreas by glibenclamide. STZ also induced hyperlipidemia and this may be due to exogenous fat loading, abnormal increase in the small intestinal acyl-coenzyme A: Cholesterol acyltransferase activity and enhancement of intestinal CoA-dependent esterification. The animals treated with MECC reversed the STZ-induced hyperlipidemia.
Histopathology of the pancreas, liver, and kidney of STZ diabetic animals showed moderate-to-severe toxic effects, and this may be due to hypertrophy of hepatocytes by an increase in the intracytoplasmic eosinophilic granules in hepatic cells, tubular atrophy and necrosis in renal cells, and increased level of general oxidative stress., The animals treated with glibenclamide and MECC reversed the STZ-induced cellular damage.
C. cassia is known to have many pharmacological properties, and it is commonly used as astringent. In acute and repeated dose toxicity testing (data not presented), MECC did not showed any marked toxic effects. In a preclinical studies, hydroalcoholic extract of C. cassia showed antidiabetic activity in alloxan-induced diabetes. In a clinical study, daily intake of 6 g of C. cassia over 40 days did not any significant adverse effect and which indicates that the C. cassia is well tolerable in human. In another study, 1 g cinnamon from C. cassia did reduced blood glucose of type II diabetes patients. Mang et al., also studied the effect of cinnamon on type 2 diabetes mellitus and concluded that the cinnamon extract has moderate effect on reducing fasting plasma glucose levels with poor glycemic control. The antioxidant and antidiabetic activity of MECC is may be due to the presence of flavonoids and polyphenols. Flavonoids present in the plant regenerate the damaged beta cells of pancrease; polyphenols, a secondary metabolite of plant, increase glucagon-like peptide-1 (GLP-1) secretion, inhibit dipeptidyl peptidase-4, and exert an indirect effect on insulin secretion by modulation of gut microbiota.,
| Conclusion|| |
The MECC exerts antioxidant activity against DPPH and ABTS free radical, and antidiabetic activity against STZ-induced diabetes mellitus in rats. The MECC also did not showed any toxicity or toxic signs in acute toxicity testing. Further, it also observed that MECC inhibits STZ-induced hyperlipidemia, which may help to prevent the complications associated with diabetes mellitus such as hyperlipidemia and hypercholesterolemia.
This study was funded by FRGS grant (Grant Number: FRGS/2/2013/SG05/AIMST/02/1). The authors express our profound gratitude to Prof. Deivanai Subramanian, Department of Biotechnology, AIMST University, for identification of the plant samples.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: Estimates for the year 2000 and projections for 2030. Diabetes Care 2004;27:1047-53.
Dias DA, Urban S, Roessner U. A historical overview of natural products in drug discovery. Metabolites 2012;2:303-36.
Beutler JA. Natural products as a foundation for drug discovery. Curr Protoc Pharmacol 2009;46:9.11.1-9.11.21.
Khan R, Islam B, Akram M, Shakil S, Ahmad A, Ali SM, et al.
Antimicrobial activity of five herbal extracts against multi drug resistant (MDR) strains of bacteria and fungus of clinical origin. Molecules 2009;14:586-97.
Cai Y, Luo Q, Sun M, Corke H. Antioxidant activity and phenolic compounds of 112 traditional Chinese medicinal plants associated with anticancer. Life Sci 2004;74:2157-84.
Hoehn AN, Stockert AL. The effects of Cinnamomum cassia
on blood glucose values are greater than those of dietary changes alone. Nutr Metab Insights 2012;5:77-83.
Kamble S, Rambhimaiah S. Antidiabetic activity of aqueous extract of Cinnamomum cassia
in alloxan-induced diabetic rats. Biomed Pharmacol J 2013;6:83-8.
Khan A, Safdar M, Ali Khan MM, Khattak KN, Anderson RA. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care 2003;26:3215-8.
Goel N, Rohilla H, Singh G, Punia P. Antifungal activity of cinnamon oil and olive oil against Candida
spp. Isolated from blood stream infections. J Clin Diagn Res 2016;10:DC09-11.
Vimala G, Gricilda Shoba F. A review on antiulcer activity of few Indian medicinal plants. Int J Microbiol 2014;2014:519590.
Al-Attar AM. Chemopreventive effect of cinnamon extract on carbon tetrachloride-induced physiological changes in the frog, Rana ridibunda
. J Appl Sci 2007;7:79-90.
Jaafarpour M, Hatefi M, Najafi F, Khajavikhan J, Khani A. The effect of cinnamon on menstrual bleeding and systemic symptoms with primary dysmenorrhea. Iran Red Crescent Med J 2015;17:e27032.
Rahman S, Begum H, Rahman Z, Ara F, Iqbal MJ, Yousuf AK. Effect of cinnamon (Cinnamomum cassia
) as a lipid lowering agent on hypercholesterolemic rats. J Enam Med Coll 2013;3:94-8.
Pochapski MT, Fosquiera EC, Esmerino LA, Dos Santos EB, Farago PV, Santos FA, et al
. Phytochemical screening, antioxidant, and antimicrobial activities of the crude leaves' extract from Ipomoea batatas
(L.) Lam. Pharmacogn Mag 2011;7:165-70.
Sen S, De B, Devanna N, Chakraborty R. Total phenolic, total flavonoid content, and antioxidant capacity of the leaves of Meyna spinosa
Roxb. an Indian medicinal plant. Chin J Nat Med 2013;11:149-57.
Olugbami JO, Gbadegesin MA, Odunola OA. In vitro
free radical scavenging and antioxidant properties of ethanol extract of Terminalia glaucescens. Pharmacognosy Res 2015;7:49-56.
Loganayaki N, Siddhuraju P, Manian S. Antioxidant activity and free radical scavenging capacity of phenolic extracts from Helicteres isora L. and Ceiba pentandra L. J Food Sci Technol 2013;50:687-95.
Dechayont B, Ruamdee P, Poonnaimuang S, Mokmued K, Chunthorng-Orn J. Antioxidant and antimicrobial activities of Pogostemon cablin
(Blanco) Benth. J Bot 2017;2017:8310275.
Petchi RR, Parasuraman S, Vijaya C. Antidiabetic and antihyperlipidemic effects of an ethanolic extract of the whole plant of Tridax procumbens (Linn.) in streptozotocin-induced diabetic rats. J Basic Clin Pharm 2013;4:88-92.
Lay MM, Karsani SA, Mohajer S, Abd Malek SN. Phytochemical constituents, nutritional values, phenolics, flavonols, flavonoids, antioxidant and cytotoxicity studies on Phaleria macrocarpa
(Scheff.) Boerl fruits. BMC Complement Altern Med 2014;14:152.
Parasuraman S, Balamurugan S, Christapher PV, Petchi RR, Yeng WY, Sujithra J, et al.
Evaluation of antidiabetic and antihyperlipidemic effects of hydroalcoholic extract of leaves of Ocimum tenuiflorum (Lamiaceae) and prediction of biological activity of its phytoconstituents. Pharmacognosy Res 2015;7:156-65.
Barros Mariutti LR, Pizarro de Mattos Barreto G, Bragagnolo N, Mercadante AZ. Free radical scavenging activity of ethanolic extracts from herbs and spices commercialized in Brazil. Braz Arch Biol Technol 2008;51:1225-32.
Prior RL, Wu X, Schaich K. Standardized methods for the determination of antioxidant capacity and phenolics in foods and dietary supplements. J Agric Food Chem 2005;53:4290-302.
Mathew S, Abraham TE. In vitro
antioxidant activity and scavenging effects of Cinnamomum verum leaf extract assayed by different methodologies. Food Chem Toxicol 2006;44:198-206.
Petchi RR, Vijaya C, Parasuraman S. Antidiabetic activity of polyherbal formulation in streptozotocin-nicotinamide induced diabetic wistar rats. J Tradit Complement Med 2014;4:108-17.
] [Full text]
Baynes JW, Thorpe SR. Role of oxidative stress in diabetic complications: A new perspective on an old paradigm. Diabetes 1999;48:1-9.
Chitra J, Padma K, Archana S, Alka J. In vitro
comparisons of anti-diabetic activity of flavonoids and crude extracts of Azadiracta indica A Juss. Int J Drug Dev Res 2013;5:47-54.
Patel S, Santani D, Shah M, Patel V. Anti-hyperglycemic and anti-hyperlipidemic effects of Bryonia laciniosa seed extract and its saponin fraction in streptozotocin-induced diabetes in rats. J Young Pharm 2012;4:171-6.
Dabla PK. Renal function in diabetic nephropathy. World J Diabetes 2010;1:48-56.
Harita N, Hayashi T, Sato KK, Nakamura Y, Yoneda T, Endo G, et al.
Lower serum creatinine is a new risk factor of type 2 diabetes: The Kansai healthcare study. Diabetes Care 2009;32:424-6.
Liu H, Wang S, Wu Z, Huang Z, Chen WY, Yang Y, et al.
Glibenclamide, a diabetic drug, prevents acute radiation induced liver injury of mice via up-regulating intracellular ROS and subsequently activating Akt-NF-κB pathway. Oncotarget 2017;8:40568-82.
Li Y, Yan H, Zhang Z, Zhang G, Sun Y, Yu P, et al.
Andrographolide derivative AL-1 improves insulin resistance through down-regulation of NF-κB signalling pathway. Br J Pharmacol 2015;172:3151-8.
Honjo K, Doi K, Doi C, Mitsuoka T. Histopathology of streptozotocin-induced diabetic DBA/2N and CD-1 mice. Lab Anim 1986;20:298-303.
Otunola GA, Afolayan AJ. Antidiabetic effect of combined spices of Allium sativum, Zingiber officinale and Capsicum frutescens in alloxan-induced diabetic rats. Front Life Sci 2015;8:314-23.
Bugudare US, Divakar K, Krishnaveni Bai R, Ashfaq M. Influence of hydroalcoholic extract of Cinnamomum cassia on antidiabetic effect of glibenclamide, metformin alone and their combination. Pharmacologyonline 2011;2:798-807.
Dugoua JJ, Seely D, Perri D, Cooley K, Forelli T, Mills E, et al.
From type 2 diabetes to antioxidant activity: A systematic review of the safety and efficacy of common and Cassia cinnamon
bark. Can J Physiol Pharmacol 2007;85:837-47.
Hasanzade F, Toliat M, Emami SA, Emamimoghaadam Z. The effect of cinnamon on glucose of type II diabetes patients. J Tradit Complement Med 2013;3:171-4.
] [Full text]
Mang B, Wolters M, Schmitt B, Kelb K, Lichtinghagen R, Stichtenoth DO, et al.
Effects of a cinnamon extract on plasma glucose, HbA, and serum lipids in diabetes mellitus type 2. Eur J Clin Invest 2006;36:340-4.
Domínguez Avila JA, Rodrigo García J, González Aguilar GA, de la Rosa LA. The antidiabetic mechanisms of polyphenols related to increased glucagon-like peptide-1 (GLP1) and insulin signaling. Molecules 2017;22. pii:E903.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]