Beneficial Effect of Phloroglucinol against Adverse Metabolic and Electrophysiological Alterations in Streptozotocin Induced Diabetic Rats: a possible Target for the Prevention of Diabetic Peripheral Neuropathy

Research Article

Austin Endocrinol Diabetes Case Rep. 2016; 1(1): 1001.

Beneficial Effect of Phloroglucinol against Adverse Metabolic and Electrophysiological Alterations in Streptozotocin Induced Diabetic Rats: a possible Target for the Prevention of Diabetic Peripheral Neuropathy

Bhadri N* and Razdan R

Department of Pharmacology, Al-Ameen College of Pharmacy, India

*Corresponding author: Naini Bhadri, Department of Pharmacology, Al-Ameen College of Pharmacy, Bangalore-560027, Karnataka, India

Received: May 20, 2016; Accepted: June 06, 2016; Published: June 08, 2016


Hyperlipidemia is one of the factor responsible for the advancement of DPN and can be targeted to delay the onset. Currently no approved treatment is available for DPN. Therefore in the present study, we investigated the protective effect of phloroglucinol, a natural polyphenol with antioxidant property in preventing the streptozotocin induced lipid alterations due to the progression of Diabetic Peripheral Neuropathy (DPN). Diabetes was induced by a single dose of STZ (streptozotocin) (55mg/kg i.p.) in the rats and were treated with phloroglucinol for 8 weeks. Significant elevation in serum glucose, total cholesterol, triglycerides and LDL were observed while HDL cholesterol and nerve conduction velocity were significantly reduced in diabetic rats. Interestingly, the results further indicated that the lipid abnormalities and altered nerve conduction velocity were ameliorated by phloroglucinol in diabetic rats. A significant improvement in biochemical and electrophysiological deficit was observed in phloroglucinol treated diabetic rats in dose dependent manner. Results indicate the oral administration of phloroglucinol is able to prevent hyperlipidemia caused by diabetes suggest its potential in the treatment in DPN.

Keywords: Diabetic peripheral neuropathy; Lipid alterations; Hyperlipidemia; Nerve conduction velocity


DPN: Diabetic Peripheral Neuropathy; STZ: Streptozotocin; HDL: High Density Lipoprotein; LDL: Low Density Lipoprotein; TC: Total Cholesterol; TG: Triglycerides


Diabetic Peripheral Neuropathy (DPN) is a multifaceted complication appears frequently in more than 50% patient diagnosed with type 1 or type 2 diabetes [1]. The extent of abnormalities markedly increases if the blood glucose is not controlled properly [2]. Prolonged hyperglycemia causes damage of delicate nerve fiber throughout the body by interfering with the ability of the nerves to transmit signals [3]. It also weakens small blood vessels that supply oxygen and nutrients to the different parts of the body [4]. The clinical symptoms of DPN may include numbness, sharp cramps, jabbing or burning pain, muscle weakness etc., [5]. Moreover, several other symptoms including hyperlipidemia is an important contributor to the progression of DPN and are responsible for morbidity. Excessive disturbance of carbohydrates, lipids and protein metabolism leading to an abnormal lipid profile is a major risk factor for the development of DPN [6,7]. Various clinical evidences suggested a significant association between cholesterol, fasting triglycerides and DPN [8,9]. Therefore hyperlipidemia is one of the factors responsible for the advancement of DPN and can be targeted to delay the onset.

Hyperlipidemia is associated with qualitative and quantitative abnormalities in lipoproteins include elevated levels of Total Cholesterol (TC), Triglycerides (TG), Low Density Lipoprotein (LDL) and reduced High Density Lipoprotein (HDL). Multiple etiologies are involved in damage of nerves due to hyperlipidemia associated with diabetes. Previous reports have shown the altered composition of fatty acids in diabetes [10]. Several studies have explored the role of inflammation and oxidative stress in DPN is confirming the reduction in antioxidant potential and increase in lipid peroxidation [11,12]. Systemic oxidative stress results in vascular cellular metabolism, vascular matrix molecule and circulating lipoprotein [13]. These data strengthen the basic hypothesis of the present study that hyperlipidemia is an important contributor in the progression of diabetic neuropathy.

Phloroglucinol (1,3,5- trihydroxybenzene) is a natural polyphenol found in phlorotanin component of brown algae (phaophyceae) and in some plant species [14].Recent studies have shown enormous pharmacological activities of phloroglucinol including antispasmodic, free radical scavenging and anti-inflammatory activity [15]. Polyphenols are known for the prevention of long term diabetic complications, including neuropathy [16,17]. Therefore, in this study the effect of the polyphenolic compound phloroglucinol is evaluated in preventing hyperlipidemia associated with the progression of diabetic neuropathy.

Materials and Methods

Experimental procedures were performed in accordance with the guidelines of the Institutional Animal Ethics Committee of CPCSEA, India. Adult male Wistar rats (250-300 g) were used for the present investigation. Animals were housed in individual cages and were maintained in the animal room at a temperature of 20-24ºC and a humidity 40-70%. Animals had free access to regular rat chow and water. They were acclimatized for a minimum period of one week prior to the beginning of the study.

Drugs and reagents

Phloroglucinol and Streptozotocin (STZ) were purchased from Sigma-Aldrich. Commercial diagnostic kits were obtained from Agappe Diagnostic Pvt. Ltd. All other chemicals and reagents were of analytical grade.

Preparation of drug solution

Aqueous solutions of phloroglucinol were freshly prepared every day administered to rats orally using per oral tube. STZ was dissolved in ice cold citrate buffer (pH 4.5) and used to induce diabetes by intraperitoneal injection.

Induction of diabetes

Diabetes was induced by a single intraperitoneal injection of Streptozotocin (STZ) at a dose of 55 mg/kg body weight freshly dissolved in citrate buffer. Blood samples were collected from the tail vein 72 h after STZ administration. Rats with fasting blood glucose values more than 250 mg/dl were considered diabetic.

Experimental design

After confirmation of diabetes, diabetic rats were divided into four groups (n=6): Diabetic Control (DC), diabetic + phloroglucinol (100mg/kg), diabetic + phloroglucinol (200mg/kg), diabetic + phloroglucinol (250mg/kg). Aged match rats treated with saline were used as Normal Controls (NC). Phloroglucinol was administered by oral gavage daily for eight weeks. The doses of phloroglucinol administered in the present study were decided based on the previously published studies [18]. At the end of the 8th week the animals were anesthetized (ketamine: xylazine 80:5 mg/kg i.p.) and the blood was withdrawn from the retro-orbital plexus using capillary tubes. Blood was collected in clot activator vacutainer for estimation of various biochemical parameters. Tubes were left to clot at 37°C for 10 min, then centrifuged and serum was separated. Noninvasive nerve conduction velocity studies of sciatic nerve were performed to find out the severity of neuropathy.

Estimation of biochemical parameters: Serum estimation for glucose, total cholesterol, triglyceride, HDL cholesterol and LDL cholesterol was estimated using commercial diagnostic kits.

Noninvasive nerve conduction velocity studies: Conduction velocity was measured using power lab data acquisition system [19].

Statistical analysis: All data are expressed as the mean ± Standard Error of Mean (SEM) for six rats in each group of rats. Statistical evaluation of the data was performed by Graph Pad Prism 5 using one way Analysis of Variance (ANOVA), followed by Tukey’s multiple comparison test. Values were considered statistically significant at p<0.05 (confidence level=95%).


Effect of phloroglucinol on serum glucose level

Diabetic animals exhibited significant increased serum glucose after 8 week of STZ administration. Treatment with phloroglucinol (100,200 & 250 mg/kg) for eight weeks showed a significant reduction on the elevated glucose level in the diabetic rats. All three doses of phloroglucinol have shown a significant antihyperglycemic effect (Figure 1).