Author(s): Nandhidha. R1, Punnagai. K


DOI: 10.52711/0974-360X.2022.00747   

Address: Nandhidha. R1, Punnagai. K*
1Department of Pharmacology, Sri Ramachandra Medical College and Research Institute, Porur, Chennai, 600116, Tamil Nadu, India.
2Professor and Head, Department of Pharmacology, Sri Ramachandra Medical College and Research Institute, Porur, Chennai - 600116, Tamil Nadu, India.
*Corresponding Author

Published In:   Volume - 15,      Issue - 10,     Year - 2022

Wound healing is a very complex process involving many stages out of which inflammatory stage remains as a rate limiting phase. Most of the anti-inflammatory drugs were proven to speed up the wound healing process which is majorly achieved by migration of monocytes and neutrophils to the healing site along with leukocytes. The presence of inflammatory mediators like interleukins, TNF delay the healing process and so the drug that actively combats these mediators will prevent the prolongation of wound healing. On the other hand SGLT2 inhibitors otherwise called as Gliflozins are extensively used for their antidiabetic potential. These drugs were also proven to exhibit antihyperlipidemic, antioxidant, cardio-protective, antihypertensive activities. Considering this, Gliflozins like Canagli?ozin, Dapagli?ozin and Empagli?ozin were employed to investigate their anti-inflammatory profile and their wound healing ability in vitro on VERO cell lines. Anti-inflammatory activity was investigated in vitro using protease inhibition assay at drug concentration of 200, 400, 600, 800 and 1000 ??g/ml. This showed that the selected Gliflozins exhibited good activity compared to that of the standard drug. Invitro cytotoxicity was determined using MTT assay on VERO cell lines and Canagli?ozin showed a significant viability at 250??g/ml compared to control. Similarly wound healing activity was determined invitro using scratch assay method. Dapagliflozin showed a significant activity of over 60% wound closure compared to the standard drug Phenytoin. Overall this work opens up a new route for exploring other medications in the SGLT2 inhibitor family for the aforementioned actions, as well as creating alternatives to the medication's principal action. This also allows for the avoidance and limitation of the use of multiple drugs for various pharmacological activities.

Cite this article:
Nandhidha. R1, Punnagai. K. Evaluation of Anti-Inflammatory and Wound Healing Potential of Sodium Glucose Co-Transporter2 (SGLT2) Inhibitors. Research Journal of Pharmacy and Technology2022; 15(10):4457-2. doi: 10.52711/0974-360X.2022.00747

Nandhidha. R1, Punnagai. K. Evaluation of Anti-Inflammatory and Wound Healing Potential of Sodium Glucose Co-Transporter2 (SGLT2) Inhibitors. Research Journal of Pharmacy and Technology2022; 15(10):4457-2. doi: 10.52711/0974-360X.2022.00747   Available on:

1.    T. M. Sree Vidhya, Geetha. In Vitro Evaluation of Anti-Inflammatory Activity of Andrographis paniculata. Research J. Pharm. and Tech. 2018; 11(3): 957-958. doi: 10.5958/0974-360X.2018.00178.6
2.    Charde RM, Charde MS, Fulzele SV, Satturwar PM, Kasture AV, Joshi SB. Evaluation of Ethanolic Extract of Moringa Oleifera for Wound Healing, Anti-inflammatory and Antioxidant Activities on Rats. Research J. Pharm. and Tech. 4(2): February 2011; Page 254-258.
3.    Stenvinkel P, Ketteler M, Johnson RJ, Lindholm B, Pecoits-Filho R, Riella M, Heimburger O, Cederholm T, Girndt M. IL‑10, IL‑6, and TNF-alpha: central factors in the altered cytokine network of uremia–the good, the bad, and the ugly. Kidney Int 2005; 67: 1216–1233.
4.    Heinlin J, Schreml S, Babilas P, Landthaler M, Karrer S. Cutaneous wound healing. Therapeutic interventions. Hautarzt 2010; 61: 611–626
5.    Jay, S., Babak, B., Sarah, A. (2015). Empagliflozin in the treatment of type 2 diabetes: Evidence to date. Drug Design, Development and Therapy, 9, 5793–803. doi:10.2147/DDDT.S69926.
6.    Sriram S., Arul Amutha Elizabeth, Akila L. Cost Analysis of SGLT2 Inhibitors in patients with type 2 Diabetes in India. Research J. Pharm. and Tech. 2020; 13(12):5861-5865.
7.    Shariq, U. M., Jamal, S. T., Memon, M. M., Khan, M. S., Rawasia, W. F., Talha Ayub, M. Sreenivasan, J., Golzar, Y. (2018). Sodium-glucose co-transporter 2 inhibitors and cardiovascular outcomes: A systematic review and meta-analysis. European Journal of Preventive Cardiology, 25(5), 495–502. doi:10.1177/2047487318755531.
8.    Bonora, B. M., Avogaro, A., Fadini, G. P. (2020). Extraglycemic Effects of SGLT2 Inhibitors: A Review of the Evidence. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 13, 161–174. doi:10.2147/DMSO.S233538.
9.    Scheen, A. J. (2014). Pharmacodynamics, Efficacy and Safety of Sodium–Glucose Co-Transporter Type 2 (SGLT2) Inhibitors for the Treatment of Type 2 Diabetes Mellitus. Drugs, 75(1), 33–59.  doi:10.1007/s40265-014-0337-y.
10.    Sushil D. Patil, Shaikh Abdul Muqeet, Sanjay J. Kshirsagar. Review Study on Canagliflozin. Asian J. Research Chem. 2018; 11(5):819-823.
11.    Haas, B., Eckstein, N., Pfeifer, V., Mayer, P., Hass, M. D. S. (2014). Efficacy, safety and regulatory status of SGLT2 inhibitors: Focus on canagliflozin. Nutrition & Diabetes, 4(11), e143. doi:10.1038/nutd.2014.40.
12.    Vinutha Kommineni, K.P.R. Chowdary, S.V.U.M. Prasad. Formulation of Dapagliflozin and Saxagliptin Tablets and In vitro Evaluation by RP-HPLC Method. Asian J. Pharm. Ana. 2019; 9(2):93-98.
13.    Sayali S. More, Sandeep S. Sonawane, Santosh S. Chhajed, Sanjay J. Kshirsagar. Development and Validation of RP-HPLC Method for Simultaneous Estimation of Saxagliptin and Dapagliflozin in Tablets. Asian J. Pharm. Tech. 2018; 8 (3):145-148 .
14.    Rahul K. Godge, Ganesh S. Shinde, Shraddha Joshi. Simultaneous Estimation and Validation of Dapagliflozin and Saxagliptin in Bulk Drug and Dosage Form by RP-HPLC. Research J. Science and Tech. 2019; 11(1):59-63.
15.    Gandla. Kumara Swamy, R. Lalitha, Ch. Mounika, B. Soumya, D. Sudheer Kumar. A Validated RP-HPLC Method for Simultanious Determination of Metformin and Canagliflozin in Pharmaceutical Formulation. Asian J. Pharm. Ana. 2018; 8(2): 73-77.
16.    Vichare V S, Choudhari V P, M Venkat Reddy. Development and Validation of UV-Visible Spectroscopic Methods for Simultaneous Estimation of Canagliflozin and Metformin in Pharmaceutical Formulation. Asian J. Research Chem. 2019; 12(1): 16-20.
17.    Dave Vidhi, Paresh Patel. Method development and Validation of UV Spectrophotometric estimation of Remogliflozin Etabonate in bulk and its tablet dosage form. Research Journal of Pharmacy and Technology. 2021; 14(4):2042-4.
18.    Madaan, T., Husain, I., Akhtar, M., Najmi, A. K. (2018). Exploring novel pharmacotherapeutic applications and repurposing potential of sodium glucose Co Transporter 2 inhibitors. Clinical and Experimental Pharmacology and Physiology, 45(9), 897–907. doi:10.1111/1440-1681.12963. 
19.    García-Ropero, Á., Santos-Gallego, C. G., & Badimon, J. J. (2019). The anti-inflammatory effects of SGLT inhibitors. Aging, 11(16), 5866–5867.
20.    De Nicola L, Gabbai FB, Liberti ME, Sagliocca A, Conte G, Minutolo R. Sodium/glucose cotransporter 2 inhibitors and prevention of diabetic nephropathy: targeting the renal tubule in diabetes. Am J Kidney Dis. 2014 Jul; 64(1):16-24.
21.    Lee TM, Chang NC, Lin SZ. Dapagliflozin, a selective SGLT2 Inhibitor, attenuated cardiac fibrosis by regulating the macrophage polarization via STAT3 signaling in infarcted rat hearts. Free Radic Biol Med. 2017; 104:298–310. 10.1016/j.freeradbiomed.2017.01.035
22.    Ashrafi Jigheh Z, Ghorbani Haghjo A, Argani H, Roshangar L, Rashtchizadeh N, Sanajou D, Nazari Soltan Ahmad S, Rashedi J, Dastmalchi S, Mesgari Abbasi M. Empagliflozin alleviates renal inflammation and oxidative stress in streptozotocin-induced diabetic rats partly by repressing HMGB1-TLR4 receptor axis. Iran J Basic Med Sci. 2019; 22:384–90. 10.22038/ijbms.2019.31788.7651
23.    Secker, Philipp & Beneke, Sascha & Schlichenmaier, Nadja & Delp, Johannes & Gutbier, Simon & Leist, Marcel & Dietrich, Daniel. (2018). Canagliflozin mediated dual inhibition of mitochondrial glutamate dehydrogenase and complex I: an off-target adverse effect. Cell Death & Disease. 9. 10.1038/s41419-018-0273-y.
24.    Sakat, S., Juvekar, A. R., Gambhire, M. N. (2010). In vitro antioxidant and antiinflammatory activity of methanol extract of Oxalis corniculata Linn. Int J Pharm Pharm Sci, 2(1), 146-155.
25.    Oyedepo, O. O., Femurewas, A. J. (1995). Anti-protease and membrane stabilizing activities of extracts of Fagra santhoxiloides, Olax subscorpioides and Tetrapluera tetraptera. Ln. J Pharm, 33, 65-69.
26.    Muniandy, K., Gothai, S., Tan, W. S., Kumar, S. S., Mohd Esa, N., Chandramohan, G., Al-Numair, K. S., Arulselvan, P. (2018). In Vitro Wound Healing Potential of Stem Extract of Alternanthera sessilis. Evidence Based Complement Alternative Medicin,. 3142073. doi: 10.1155/2018/3142073.
27.    Okeleye Benjamin I., Mkwetshana Noxolo T., Ndip Roland N. Evaluation of the antibacterial and antifungal potential of Peltophorum africanum: toxicological effect on human chang liver cell line. Sci. World J. 2013;2013
28.    Ninčević V., Omanović Kolarić T., Roguljić H., Kizivat T., Smolić M., Bilić Ćurčić I. Renal Benefits of SGLT 2 Inhibitors and GLP-1 Receptor Agonists: Evidence Supporting a Paradigm Shift in the Medical Management of Type 2 Diabetes. Int. J. Mol. Sci. 2019;20:5831. doi: 10.3390/ijms20235831.
29.    Secker P.F., Beneke S., Schlichenmaier N., Delp J., Gutbier S., Leist M., Dietrich D.R. Canagliflozin mediated dual inhibition of mitochondrial glutamate dehydrogenase and complex I: An off-target adverse effect. Cell Death Dis. 2018;9:226. doi: 10.1038/s41419-018-0273-y.
30.    H. Ebaid, O. M. Ahmed, A. M. Mahmoud, and R. R. Ahmed, “Limiting prolonged inflammation during proliferation and remodeling phases of wound healing in streptozotocin-induced diabetic rats supplemented with camel undenatured whey protein,” BMC Immunology, vol. 14, no. 1, article 31, pp. 1–13, 2013.
31.    Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB. Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal. 2014 Mar 1; 20(7):1126-67.
32.    Lee WC, Chau YY, Ng HY, Chen CH, Wang PW, Liou CW, Lin TK, Chen JB. Empagliflozin Protects HK-2 Cells from High Glucose-Mediated Injuries via a Mitochondrial Mechanism. Cells. 2019 Sep 14; 8(9), 1085. doi: 10.3390/cells8091085
33.    Guo S., Dipietro L.A. Factors affecting wound healing. J. Dent. Res. 2010; 89:219–229
34.    Sk. Karishma, K. Lakshmi, D. Eswar Tony, A. Narendra Babu, Rama Rao Nadendla. Pharmacological Evaluation of Leaf Extract of Terminalia bellerica with Moringa oleifera for its Synergistic Action on Anti-diabetic Activity and Anti-inflammatory Activity in Rats. Research J. Pharm. and Tech. 2019; 12(3): 1181-1184.
35.    Liang Chun-Chi, Park Ann Y., Guan Jun-Lin. In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nat. Protoc. 2007; 2:329–333.
36.    Anusha. D, Nagaraju Kancherla, Darling Chellathai. In vitro Screening of Antioxidant, Anti-Inflammatory activity of Vitex negundo Methanolic leaf extract. Research J. Pharm. and Tech. 2019; 12(6): 2824-2827.

Recomonded Articles:

Research Journal of Pharmacy and Technology (RJPT) is an international, peer-reviewed, multidisciplinary journal.... Read more >>>

RNI: CHHENG00387/33/1/2008-TC                     
DOI: 10.5958/0974-360X 

56th percentile
Powered by  Scopus

SCImago Journal & Country Rank

Recent Articles


Not Available