Evaluation of Some Phenolic Acids in Diabetic Neuropathy

Abstract

Background: Streptozotocin (STZ) induced neuropathy is widely used preclinical model for diabetic neuropathy (DN). DN is majorly resulted due to nitrosative and oxidative stress induced by hyperglycemia. Phenolic acids are polyphenols with free radical scavenging anti-inflammatory and neuroprotectiveaction. Methods: In this study STZ (55mg/kg, i.p) was administered in male Wistar rats and animals with hyperglycemia (fasting blood glucose ≥ 200mg/dl) were used for further study. Behavioural changes cold allodynia, mechanical hyperalgesia, heat hyperalgesia, mechanical allodynia were assessed weekly. Motor Nerve Conduction Velocity (MNCV) was also evaluated. Reduced Glutathione and Malondialdehyde were estimated to indicate oxidative stress. C-Reactive Protein (CRP), Insulin assay, serum electrolytes (Na + , K +), TNF-α, IL-6 and INF-γ were also estimated. Isolated sciatic nerve was histopathologically studied to support the results. Results: Treatment with syringic acid (SY) 12.5, 25, 50 mg/kg and of Sinapic acid (SP) 5, 10, 20 mg/kg orally for 5 weeks has shown to reduce blood glucose level. Behavioural changes were found to be improved weekly by SY and SP in dose dependent manner. 5 weeks treatment with SY and SP was able to increase antioxidant GSH and reduce MDA level in cell. Gabapentin, SY and SP treated animals have shown decrease in TNF-α, IL-6 and INF-γ and CRP. Insulin and serum electrolytes were found to be normalised in treated groups. Histopathological study has revealed protective effect of gabapentin, SY and SP by showing reverted neuronal damage. Conclusion: In conclusion, syringic acid and sinapic acid have antihyperglycemic, antioxidant and neuroprotective effect in diabetic neuropathy.

Syringic Acid Ameliorates Cardiac, Hepatic, Renal and Neuronal Damage Induced by Chronic Hyperglycaemia in Wistar Rats: A Behavioural, Biochemical and Histological Analysis

“…The administration of SA (25 mg/kg, 50 mg/kg p.o) to nSTZ diabetic rats resulted in a significant increase in BW, indicating that muscle tissue damage caused by hyperglycaemia was prevented. The antidiabetic effects of SA in the present study are in agreement with the findings of previous research reports based on a type 1 diabetes mellitus (T1DM) animal model [ 19 , 20 , 21 ]. Furthermore, uncontrolled hyperglycaemia promotes the generation of excessive free radicals, reducing the synthesis of SOD and GSH, which exaggerate a weakened defence system and tissue injury [ 84 ].…”

“…SA’s anti-inflammatory effect via the inhibition of inflammatory kinase c-jun N-terminal kinase (JNK) and its ability to reduce demyelination and improve dyslipidaemia may explain the mechanisms behind its beneficial effect [ 100 ]. SA’s neuroprotective effect is consistent with the findings of Tokmak et al, 2015, Pawar et al, 2021, and Cao et al, 2016 [ 21 , 30 , 35 ].…”

“…Doses of SA were selected based on the therapeutic efficiencies reported in previous research reports [ 19 , 20 , 21 , 37 , 55 , 56 ] and, in addition, our previous studies suggested that the LD 50 of SA is greater than 2000 mg/kg [ 46 ], which is in concordance with the results of Pawar et al, 2021 [ 21 ].…”

“…SA ( Figure 1 ) is a phenolic acid that is found in grapes, red wine, honey, acai palms, pumpkin, a variety of dry fruits (including olives and dates), spices, and other plants [ 18 ]. SA has been reported for its antidiabetic [ 19 , 20 , 21 ], antiglycating [ 22 ], antisteatosis and anti-inflammatory [ 23 , 24 , 25 ], antioxidant and antihypertensive [ 24 , 26 , 27 ], and antibacterial and antimicrobial properties [ 28 , 29 ]. It also has neuroprotective [ 30 , 31 , 32 , 33 , 34 , 35 , 36 ] and hepatoprotective properties [ 37 , 38 ], and ameliorates diabetic cataracts by suppressing aldose reductase enzyme [ 39 ].…”

Syringic acid affords antioxidant protection in the pancreas of type 2 diabetic rats

“…Syringic acid (SA) exhibits multipharmacologic properties such as antioxidant, antisteatosis, antiinflammatory and antibacterial properties [11][12][13][14].…”