Study of 18β glycyrrhetinic acid for the prevention of progression of diabetes induced neuropathy in laboratory animals
Abstract
Diabetes is a metabolic disease that is associated with oxidative stress and the dysfunction of mitochondria. Long-term diabetes may cause different associated complications. One of the most common complications of diabetes mellitus is neuropathy. The present study aimed to investigate the possible neuroprotective effects of 18β glycyrrhetinic acid (GA), the metabolite of glycyrrhizic acid, which is the main active component commonly used in traditional Chinese medicine on oxidative damage and the sciatic nerve of diabetes-induced neuropathy in laboratory animals. Diabetes was induced in male Wistar rats (200–260 g) by injecting a single dose of nicotinamide (110 mg/kg, intraperitoneally) and streptozotocin (STZ) (55 mg/kg, intraperitoneally). The rats were divided into six groups. Pregabalin (10 mg/kg, p.o.) and 18β GA (50, 100, and 200 mg/kg, p.o.) were administered daily after four weeks of nicotinamide-STZ injection to the rats of groups III to VI respectively for four weeks. Various behavioral (heat and mechanical hyperalgesia, allodynia, etc.), hemodynamic and biochemical parameters were investigated, and the histological examination of the sciatic nerve was carried out. In the present study, the 18β GA (100 and 200 mg/kg) significantly (p < 0.01, p < 0.001) increased in the tail withdrawal latency and increased in paw withdrawal threshold, and increased in systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure. Furthermore, 18β GA (100 and 200 mg/kg) significantly (p < 0.01, p < 0.001) restored altered blood glucose level, total protein, antioxidant status, and histological abnormalities. Pregabalin (10 mg/kg) showed a maximum protective effect, but a low dose of 18β GA (50 mg/kg) was not enough to show the protective activity in diabetic rats. In most of the tests, non-significant differences were observed between the control and 18β GA 200 mg/kg groups. Moreover, 18β GA lowers the inflammation and demyelination in sciatic nerves. Beyond its antioxidant role possessed neuroprotective effect via modulation of endogenous enzymes in nicotinamide-STZ induced diabetic in rats.
Keywords:
Glycyrrhetinic acid, nicotinamide, STZ, hyperalgesia, neuroprotective, cardioprotectiveDOI
https://doi.org/10.25004/IJPSDR.2021.130201References
Deepthi B, Sowjanya K, Lidiya B, Bhargavi R, Babu P. A Modern Review of Diabetes Mellitus: An Annihilatory Metabolic Disorder. Journal of In Silico & In Vitro Pharmacology. 2017; 3:1-14.
Ahmed A. History of diabetes mellitus. Saudi Medical Journal. 2002; 23:373-378.
King H, Mikhail PM. World Health Organization activities in the field of diabetes Mellitus. World Health Statistics Quarterly. 1988; 41:197-199.
Kokiwar P, Gupta S, Durge P. Prevalence of diabetes in a rural area of central India. International Journal Diabetes Dev Ctries. 2007; 27(1):8-10.
Du X, Matsumura T, Edelstein D, Rossetti L, Zsengellér Z, Szabó C, Brownlee M. Inhibition of GAPDH activity by poly (ADP-ribose) polymerase activates three major pathways of hyperglycemic damage in endothelial cells. Journal of Clinical Investigation. 2003; 112(7):1049–1057.
Lotfy M, Adedhate J, Kalasz H, Singh J. Chronic complicatios of diabetes Mellitus: A mini review. Current Diabetes Review. 2007; 13(1):3-10.
Thaifa M, Roshna S, Arya U, Babu A. A review on diabetes mellitus and diabetic neuropathy: A plant based approach. Journal of Pharmacognosy and Phytochemistry 2017; 6(3):506-510.
Takeda S, Ishihara K, Wakui Y, Amagya S, Maruno M, Akao T, Kobashi K. Bioavailability study of glycyrrhetinic acid after oral administration of glycyrrhizin in rats; relevance to the intestinal bacterial hydrolysis. J Pharm Pharmacol. 1997; 48:902–905.
Doll R, Hill ID, Hut ton C, Underwood DJ. Clinical trial of a triterpenoids liquorice compound in gastric and duodenal ulcer. Lancet. 1962; 5:793–796.
Ohuchi K, Kamada Y, Levine L, Tsurufuji S. Glycyrrhizin inhibits prostaglandin E2 production by activated peritoneal macrophages from rats. Prostag Med. 1981; 7:457–463.
Ito M, Sato A, Hirabayashi K, Tanabe F, Shigeta S, Baba M, De Clercq E, Nakashima H, Yamamoto N. Mechanism of inhibitory effect of glycyrrhizin on replication of human immunodeficiency virus (HIV). Antivir Res.1988; 7:289–298.
Abe N, Ebina T, Ishida N. Interferon induction by glycyrrhizin and glycyrrhetinic acid in mice. Microbiol Immunol. 1982; 9:535– 539.
Kiso Y, Tohkin M, Hikino H, Hattori M, Sakamoto T, Namba T. Mechanism of antihepatotoxic activity of glycyrrhizin. I. Effect of free radical generation and lipid peroxidation. Planta Med. 1984; 50:298–302.
Horigome H, Hirano T, Oka K. Therapeutic effect of glycyrrhetinic acid in MRL lpr/lpr mice: implications of alteration of corticosteroid metabolism. Life Sci. 2001; 61:2429–2438.
Armanini D, De Palo CB, Mattarello MJ, Spinella P, Zaccaria M, Ermolao A, Palermo M, Fiore C, Sartorato P, Francini-Pesenti F, Karbowiak I. Effect of licorice on the reduction of body fat mass in healthy subjects. J Endocrinol Investig. 2003; 646–650.
Ko BS, Jang JS, Hong SM, Sung SR, Lee JE, Lee MY, Jeon WK, Park S. Changes in components, sitizing and insulinotropic actions. Biosci Biotechnol Biochem. 2007; 71:1452–1461.
Kalaiarasi P, Kaviarasan K, Pugalendi V. Hypolipidemic activity of 18β-glycyrrhetinic acid on streptozotocin-induced diabetic rats. European Journal of Pharmacology. 2009; 612:93-97.
Kalaiarasi P, Pugalendi V. Ant i-hyperglycemic ef fect of 18β-glycyrrhetinic acid, aglycone of glycyrrhizin, on streptozo¬tocin-diabetic rats. European Journal of Pharmacology. 2009; 606:269-273.
Negi G, Kumar A, Kaundal R, Gulati A, Sharma S. Functional and biochemical evidence indicating beneficial effect of Melatonin and Nicotinamide alone and in combination in experimental diabetic neuropathy. Neuropharmacology. 2010; 58:585-592.
Dhanshree D, Upaganlawar A, Upasani C. Neuroprotective Effects of Protocatechuic Acid in Diabetes Induced Neuropathic Pain. American Journal of Biochemistry and Molecular Biology. 2017; 111-117.
Kumar S, Tahashildar J, Kota K. Neuroprotective effect of ethanolic root extract of Boerhaavia diffusa (linn.) against streptozotocin induced diabetic neuropathy in animal model. Journal of Chemical and Pharmaceutical Research. 2016; 8(3):831-840.
Trinder P. Determination of blood glucose using an oxidase peroxidase system with a non-carcinogenic chromogen. Journal of clinical Pathology. 1969; 22:158-161.
Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001; 414.
Chan Y, Woo U. Prevention of overweight and obesity: how effective is the current public health approach. International Journal Environ Res Public Health. 2010; 7:765-783.
Necker H, Hellon. Noxious thermal input from the rat tail: modulation by descending inhibitory influences. Pain. 1978; 4(3):231-242.
Saha L, Hota D, Chakrabarti A. Pain Res. Treat. 2012; 43579.
Kannan SA, Saade NE, Haddad JJ, Abdelnoor AM, Atweh SF, Jabbur SJ, Garabelian BS. Endotoxin induced local inflammation and hyperalgesia in rats mince, a new model for inflammatory pain. Pain. 1996; 66:373-379.
Randall L, Selitto J. A method for measurement of analgesic activity on inflamed tissue. Arch Int Pharmacodyn Ther. 1957; 111:409-419.
Chaplan R , B ach W , P ogrel W , C hung J , Y aksh T . Q uantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods. 1994; 53:55-63.
Aswar M, Patil V. A systematic review on neuropathy. International Journal of Drug Development and Research. 2016; 8(2):29-34.
Muthuraman A, Singh N, Jaggi A. Protective effect of Acorus calamus L. in rat model of vincristine induced painful neuropathy: An evidence of anti-inflammatory and anti-oxidative activity. Food Chem Toxicol. 2011; 49:2557-2563.
Kumar A, Kaundal R, Iyer S, Sharma S. Effects of resveratrol on nerve functions, oxidative stress and DNA fragmentation in experimental diabetic neuropathy. Life Sciences. 2007; 80:1236-1244.
Volkan S, Bilge P, Gürkan Y, Hatice K, Huseyin A, Aslan T, Oytun E, Dilek T. Neuroprotective effects of octreotide on diabetic neuropathy in rats. Biomedicine & Pharmacotherapy. 2017; 89:468-472.
Nitya NP, Venkanna B, Madhu C, Lingaraju, Vinay Kant, Najeeb Latief, Amar SM, Dhirendra K, Dinesh K, Surendra KT. Atorvastatin attenuates neuropathic pain in rat neuropathy model by down-regulating oxidative damage at peripheral, spinal and supraspinal levels. Neurochemistry International. 2014; 68:1-9.
Amit KD, Kiran SR, Shiva K, Anuchadra RR, Asjad V, Arvindkumar EG, Pinaki G, Sachin LB, Subhash LB. Ameliorative effects quercetin against impaired motor nerve function, inflammatory mediators and apoptosis in neonatal streptozotocin-induced diabetic neuropathy in rats. Biomedicine & Aging Pathology. 2012.
Maitraie D, Chi-Feng H, Huang-Yao T, Ya-Ting L, Bai-Luh W, Shyh- Chyun Y, Jih-Pyang W, Chun-Nan L. Synthesis, anti-inflammatory, and antioxidant activities of 18 β-glycyrrhetinic acid derivatives as chemical mediators and xanthine oxidase inhibitors. Bioorganic & Medicinal Chemistry. 2009; 17:2785-2792.
Hardy M, Hendricks J, Paulson J, Faunce N. 18β-glycyrrhetinic acid inhibits rotavirus replication in culture. Virology Journal. 2012; 9:96.
Delaney A, Dunger A, Di Matteo M, Cunningham M, Green M, Green I. Biochem Pharmacol. 1995; 50:2015-2020.
Vincent A, Russell J, Low P, Feldman L. Endocrin Rev. 2014; 25:612- 28.
Kamble H, Bodhankar S. Cardioprotective effect of concomitant administration of trigonelline and sitagliptin on cardiac biomarkers, lipid levels, electrocardiographic and heamodynamic modulation on cardiomyopathy in diabetic Wistar rats. Biomedicine & Aging Pathology. 2014; 4:335-342.
Kandhare A, Raygude K, Ghosh P, Ghule A, Bodhankar S. Neuroprotective effect of naringin by modulation of endogenous biomarkers in streptozotocin induced painful diabetic neuropathy. Fitoterapia. 2012; 83:650-659.
Dobrestov M, Romanovsky D, Stimers J. Early Diabetic Neuropathy: Triggers and Mechanism. World J Gastroenterol. 2007; 13(2):175- 191.
Bierhaus A, Chevion S, Chevion M, Hofmann M, Quehenberger P, Illmer T. Advanced glycation end product-induced activation of NF-kappaB is suppressed by alpha-lipoic acid in cultured endothelial cells. Diabetes. 1997; 46(9):1481-1490.
Blickle J, Doucet T, Krummel T, Hannedouche T. Diabetic nephropathy in the elderly. Diabetes & Metabolism. 2008; 33:S40-S55.
Kim S, Lee J, Yang E, Kil I, Park J. Human sensitive to apoptosis gene protein inhibits peroxynitrite-induced DNA damage. Biochemistry Biophysical Research Communication. 2003; 301:671-674.
Halliwell B. Drug antioxidant effects. A basis for drug selection. Drugs. 1992; 42:569-605.
Cade W. Diabetes-Related Microvascular and Macrovascular Diseases in the Physical Therapy Setting. Journal of the American Physical Therapy Association. 2008; 88(11): 1322-1335.
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