Effect of Lupeol on the Expression of Neuro Inflammatory Signalling Molecules in Brain Tissues of High Fat Diet and Sucrose Fed Type-2 Diabetic Rats

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DOI: 10.21522/TIJPH.2013.SE.24.01.Art020

Authors : Vishnu Priya Veeraraghavan, Gayathri R, Kavitha S, J. Selvaraj, Esha Gayathri K

Abstract:

Lupeol has anti- inflammatory, antimicrobial, anti-protozoal, anti-proliferative, anti-invasion, anti-angiogenic and cholesterol-lowering properties. However, the mechanisms underlying the effect of lupeol on neuroinflammatory signalling molecules have not yet been identified. The study was designed to study the effect of lupeol on the expression of inflammatory signalling molecules in brain tissue of high-fat diet and sucrose-fed type-2 diabetic rats. Adult male albino rats of Wistar 150–180 days old with 180–200 g body weight (b.wt) were divided into four groups of six rats each. Group I: Control (vehicle-treated): Group II: High fat diet-induced type-2 diabetic rats; Group III: Type-2 diabetic rats treated with lupeol (25 mg/kg b.wt/day) orally for 30 days and Group IV: Type-2 diabetic rats treated with metformin (50 mg/kg, b.wt/day orally for 30 days. After 30 days of treatment, the animals were anaesthetized, and brain tissue was dissected and used for the assessment of mRNA expression analysis. Type-2 diabetic animals showed a significant increase (p<0.05) in TNF-α and IL-6 mRNA levels in brain tissue in high-fat diet-induced type-2 diabetic animals. However, lupeol treatment, effectively reduced (p<0.05) the neuroinflammatory signaling molecules (TNF- α and IL-6 mRNA) showing that lupeol has significant role over the control of neuroinflammatory signaling. Our present findings clearly show that lupeol has a significant role in reducing neuroinflammation via the downregulation of TNF-α and IL-6 in brain tissues and hence, lupeol can be a potential natural drug for the treatment of diabetic neuropathy.

References:

[1] Forbes, J. M., Cooper, M. E., 2013, Mechanisms of diabetic complications." Physiological Reviews, 93,1.

[2] Jayaraman, S., Krishnamoorthy, K., Prasad, M., Veeraraghavan, V.P., Krishnamoorthy, R., Alshuniaber, M.A., Gatasheh, M.K., Elrobh, M., Gunassekaran., 2023, Glyphosate potentiates insulin resistance in skeletal muscle through the modulation of IRS-1/PI3K/Akt mediated mechanisms: An in vivo and in silico analysis. International Journal of Biological Macromolecules, 242(Pt 2), 124917. https://doi.org/10.1016/j.ijbiomac.2023.124917.

[3] Selvaraj, J., Muthusamy, T., Srinivasan, C., Balasubramanian, K., 2009, Impact of excess aldosterone on glucose homeostasis in adult male rat. Clinica Chimica Acta; International Journal of Clinical Chemistry, 407(1-2), 51–57. https://doi.org/10.1016/j.cca.2009.06.030.

[4] Beilharz, J. E.,  Maniam, J., 2017, Neuroprotective effects of clinically relevant doses of N-acetylcysteine against neuroinflammation and oxidative stress in a rat model of type 2 diabetes. European Journal of Pharmacology, 809.

[5] Edwards, J. L., Vincent, A. M., Cheng, H. T., Feldman, E. L., 2008, Diabetic neuropathy: mechanisms to management. Pharmacology & therapeutics, 120(1), 1–34. https://doi.org/10.1016/j.pharmthera.2008.05.005

[6] Gan, Y., 2021, Progress in phytotherapy for diabetic neuropathy: A systematic review and meta-analysis. Journal of Ethnopharmacology, 279, 114334.

[7] Javed, S., Al-Hashmi, S., Moallem, S. A., Batiha, G. E., 2021, Role of Phytochemicals in the Treatment of Diabetic Neuropathy. Journal of Drug Metabolism & Toxicology, 12(2), 10-17.

[8] Amanat, S., Rezaei, N., Beheshti, F., 2021, Phytotherapy in the treatment of diabetic neuropathy: a review. Acta Medica Iranica, 59(11), 709-717.

[9] Kannan, R., Manickam, V., 2018, Lupeol—a novel anti-inflammatory and anti-cancer dietary triterpene. Food and Function, 9(12), 6081–6095.

[10] Salehi, B., Venditti, A., Sharifi-Rad, M., Kręgiel, D., Sharifi-Rad, J., Durazzo, A., Lucarini, M., Santini, A., Souto, E. B., & Novellino, E. 2019, The therapeutic potential of apigenin. International Journal of Molecular Sciences, 20(6), 1305.

[11] Salehi, B., Fokou, P. V. T., Sharifi-Rad, M., Zucca, P., Pezzani, R., Martins, N., Sharifi-Rad, J., & Trincone, A., 2020, The therapeutic potential of naringenin: A review of clinical trials. Pharmaceuticals, 13(1), 12.

[12] Seidell, J.C., 2000, Obesity, insulin resistance and diabetes — a worldwide epidemic [Internet]. Vol. 83, British Journal of Nutrition, p. S5–8. Available from: http://dx.doi.org/10.1017/s000711450000088x

[13] Venkatesh, S., Dayanand Reddy, G., Madhava Reddy, B.,2003, Antihyperglycemic Activity of Helicteres isora Roots in Alloxan-Induced Diabetic Rats [Internet].  Pharmaceutical Biology, 41,  p. 347–350. Available from: http://dx.doi.org/10.1076/phbi.41.5.347.15937

[14] Lakshmi, V., Mahdi, A.A., Ahmad, M.K., Agarwal, S.K., Srivastava, A.K., 2015, Antidiabetic Activity of Lupeol and Lupeol Esters in Streptozotocin- Induced Diabetic Rats [Internet].  Bangladesh. Pharmaceutical Journal,17,p.138–46.Availablefrom: http://dx.doi.org/10.3329/bpj.v17i2.22330

[15] Wu, F., Zhu, J., Li, G., Wang, J., Veeraraghavan, V.P., Krishna Mohan, S., 2019, Biologically synthesized green gold nanoparticles from Siberian ginseng induce growth-inhibitory effect on melanoma cells (B16). Artif Cells Nanomed Biotechnol, 47(1),3297–305.

[16] Chen, F., Tang, Y., Sun, Y., Veeraraghavan, V.P., Mohan, S.K., Cui, C., 2019, 6-shogaol, a active constiuents of ginger prevents UVB radiation mediated inflammation and oxidative stress through modulating NrF2 signaling in human epidermal keratinocytes (HaCaT cells). J Photochem Photobiol B, 97:111518.

[17] Li, Z., Veeraraghavan, V.P., Mohan, S.K., Bolla, S.R., Lakshmanan, H., Kumaran, S., 2020, Apoptotic induction and anti-metastatic activity of eugenol encapsulated chitosan nanopolymer on rat glioma C6 cells via alleviating the MMP signaling pathway [Internet]. Journal of Photochemistry and Photobiology B: Biology, 203,   p. 111773. Available from: http://dx.doi.org/10.1016/j.jphotobiol.2019.111773

[18] Babu, S., Jayaraman, S., 2020, An update on β-sitosterol: A potential herbal nutraceutical for diabetic management. Biomed Pharmacother, 131,110702.

[19] Malaikolundhan, H., Mookkan, G., Krishnamoorthi, G., Matheswaran., N., Alsawalha, M., Veeraraghavan, V.P.,  2020, Anticarcinogenic effect of gold nanoparticles synthesized from Albizia lebbeck on HCT-116 colon cancer cell lines. Artif Cells Nanomed Biotechnol, 48(1),1206–1213.

[20] Han, X., Jiang, X., Guo, L., Wang, Y., Veeraraghavan, V.P., Krishna Mohan, S., 2019, Anticarcinogenic potential of gold nanoparticles synthesized from Trichosanthes kirilowii in colon cancer cells through the induction of apoptotic pathway. Artif Cells Nanomed Biotechnol,47(1),3577–3584.

[21] Gothai, S., Muniandy, K., Gnanaraj, C., Ibrahim, I.A.A., Shahzad, N., Al-Ghamdi, S.S., 2018, Pharmacological insights into antioxidants against colorectal cancer: A detailed review of the possible mechanisms. Biomed Pharmacother, 107,1514–1522.

[22] Veeraraghavan, V.P., Hussain, S., Balakrishna, J.P., Dhawale, L., Kullappan, M.,2021, Ambrose JM, et al. A Comprehensive and Critical Review on Ethnopharmacological Importance of Desert Truffles: Terfezia claveryi, Terfezia boudieri, and Tirmania nivea [Internet]. Food Reviews International,1–20. Available from: http://dx.doi.org/10.1080/87559129.2021.1889581

[23] Sathya, S., Ragul, V., Veeraraghavan, V.P., Singh, L., Niyas Ahamed, M.I., 2020, An in vitro study on hexavalent chromium [Cr(VI)] remediation using iron oxide nanoparticles based beads. Environmental Nanotechnology, Monitoring & Management., 1,14,100333.

[24] Yang, Z., Pu, M., Dong, X., Ji, F., Priya Veeraraghavan, V., Yang, H., 2020 , Piperine loaded zinc oxide nanocomposite inhibits the PI3K/AKT/mTOR signaling pathway via attenuating the development of gastric carcinoma: In vitroandin vivostudies. Arabian Journal of Chemistry,1,13(5):5501–5516.

[25] Rajendran, P., Alzahrani, A.M., Rengarajan, T., Veeraraghavan, V.P., Krishna Mohan, S., 2020, Consumption of reused vegetable oil intensifies BRCA1 mutations. Crit Rev Food Sci Nutr, 27,1–8.

[26] Barma, M.D., Muthupandiyan, I., Samuel, S.R., Amaechi, B.T., 2021, Inhibition of Streptococcus mutans, antioxidant property and cytotoxicity of novel nano-zinc oxide varnish. Arch Oral Biol,126,105132.

[27] Samuel, S.R., 2021, Can 5-year-olds sensibly self-report the impact of developmental enamel defects on their quality of life? Int J Paediatr Dent,31(2),285–286.

[28] Samuel, S.R., Kuduruthullah, S., Khair, A.M.B., Shayeb, M.A., Elkaseh, A., Varma, S.R., 2021, Dental pain, parental SARS-CoV-2 fear and distress on quality of life of 2 to 6 year-old children during COVID-19. Int J Paediatr Dent, 31(3),436–441.

[29] Tang, Y., Rajendran, P., Veeraraghavan, V.P., Hussain, S., Balakrishna, J,P., Chinnathambi,A., 2021, Osteogenic differentiation and mineralization potential of zinc oxide nanoparticles from Scutellaria baicalensis on human osteoblast-like MG-63 cells [Internet].  Materials Science and Engineering, 119, C.p. 111656. Available from: http://dx.doi.org/10.1016/j.msec.2020.111656

[30] Yin, Z., Yang, Y., Guo, T., Veeraraghavan, V.P., Wang, X.,  2021, Potential chemotherapeutic effect of betalain against human non-small cell lung cancer through PI3K/Akt/mTOR signaling pathway. Environ Toxicol,36(6),1011–1020.

[31] Veeraraghavan, V.P., Periadurai, N.D., Karunakaran, T., Hussain, S., Surapaneni, K.M., Jiao, X., 2021, Green synthesis of silver nanoparticles from aqueous extract of Scutellaria barbata and coating on the cotton fabric for antimicrobial applications and wound healing activity in fibroblast cells (L929). Saudi J Biol Sci, 28(7),3633–3640.

[32] Mickymaray, S., Alfaiz, F.A., Paramasivam, A., Veeraraghavan, V.P., Periadurai, N.D., Surapaneni, K.M., 2021. Rhaponticin suppresses osteosarcoma through the inhibition of PI3K-Akt-mTOR pathway. Saudi J Biol Sci,28(7),3641–3649.

[33] Teja, K.V., Ramesh, S., 2020.Is a filled lateral canal – A sign of superiority? [Internet]. Vol. 15, Journal of Dental Sciences,562–563. Available from: http://dx.doi.org/10.1016/j.jds.2020.02.009

[34] Balaji, V., Priya, V.V., Gayathri, R., 2017, Awareness of risk factors for obesity among College students in Tamil Nadu: A Questionnaire based study. Research Journal of Pharmacy and Technology, 10, 1367–1369. https://www.i-scholar.in/index.php/rjpt/article/view/155904.

[35] Kadanakuppe, S., Hiremath, S., 2016, Social and Behavioural Factors Associated with Dental Caries Experience among Adolescent School Children in Bengaluru City, India [Internet]. Vol. 14, British Journal of Medicine and Medical Research,  1–10. Available from: http://dx.doi.org/10.9734/bjmmr/2016/24021

[36] Williams, K.V., Price, J.C., Kelley, D.E.,  2001, Interactions of impaired glucose transport and phosphorylation in skeletal muscle insulin resistance: a dose-response assessment using positron emission tomography. Diabetes,50(9),2069–2079.

[37] Bertoldo, A., Price, J., Mathis, C., Mason, S., Holt, D., Kelley, C., 2005, Quantitative assessment of glucose transport in human skeletal muscle: dynamic positron emission tomography imaging of [O-methyl-11C]3-O-methyl-D-glucose. J Clin Endocrinol Metab,90(3),1752–1759.

[38] Lee, J.Y., 2008, Pharmacodynamic and pharmacokinetic interactions between herbs andwestern drugs [Internet].  Oriental Pharmacy and Experimental Medicine, 8,207–214. Available from: http://dx.doi.org/10.3742/opem.2008.8.3.207

[39] Sahu, D., Kannan, G. M., Vijayaraghavan, R., 2014, Size-dependent effect of zinc oxide on toxicity and inflammatory potential of human monocytes. Journal of toxicology and environmental health, Part A, 77(4), 177–191. https://doi.org/10.1080/15287394.2013.853224.

[40] Jayaraman, S., Devarajan, N., Rajagopal, P., Babu, S., Ganesan, S. K., Veeraraghavan, V. P., Palanisamy, C. P., Cui, B., Periyasamy, V., Chandrasekar, K, 2021, β-Sitosterol Circumvents Obesity Induced Inflammation and Insulin Resistance by down-Regulating IKKβ/NF-κB and JNK Signaling Pathway in Adipocytes of Type 2 Diabetic Rats. Molecules (Basel, Switzerland), 26(7), 2101. https://doi.org/10.3390/molecules26072101.

[41] Mithil, Vora., V. Vishnu Priya, J. Selvaraj., Gayathri ,R., Kavitha, S.,2021, Effect of Lupeol on Pro-inflammatory Markers in Adipose Tissue of High-Fat Diet and Sucrose Induced Type-2 Diabetic Rats.Journal of Research in Medical and Dental Science, 9(10) ,  116-121.

[42] Ealla KKR, Veeraraghavan VP, Ravula NR, Durga CS, Ramani P, Sahu V, Poola PK, Patil S, Panta P (2022) Silk Hydrogel for Tissue Engineering: A Review. J Contemp Dent Pract 23:467–477

[43] Patil S, Sujatha G, Varadarajan S, Priya VV (2022) A bibliometric analysis of the published literature related to toothbrush as a source of DNA. World J Dent 13:S87–S95.

[44] Vasconcelos, J.F., Teixeira, M.M., Barbosa-Filho, J.M., A S S, J R G, de Queiroz, L.P., 2008, Corrigendum to “The triterpenoid lupeol attenuates allergic airway inflammation in a murine model.” International Immunopharmacology, 8,  1216–1221.  1714. Available from: http://dx.doi.org/10.1016/j.intimp.2008.07.008.

[45] Ganesan A, Muthukrishnan A, Veeraraghavan V (2021) Effectiveness of Salivary Glucose in Diagnosing Gestational Diabetes Mellitus. Contemp Clin Dent 12:294–300

[46] Karthik EVG, Priya V (2021) Gayathri. R, Dhanraj Ganapathy. Health Benefits Of Annona Muricata-A Review. Int J Dentistry Oral Sci 8:2965–2967

[47] Priya DV, (2020) Knowledge and awareness on HIV/AIDS among college students in A university hospital setting. Int J Dent Oral Sci 1182–1186