Anti‐diabetic effect of andrographolide from Sambiloto herbs (Andrographis paniculata (Burm.f.) Nees) through the expression of PPARγ and GLUT‐4 in adipocytes
Novia Tri Astuti(1), Putri Rachma Novitasari(2), Raymond Tjandrawinata(3), Agung Endro Nugroho(4*), Suwijiyo Pramono(5)
(1) Master Program of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia
(2) Master Program of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia
(3) Dexa Laboratories of Biomolecular Sciences (DLBS), Cikarang 17550, Indonesia
(4) Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia
(5) Department of Pharmaceutical Biology, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia
(*) Corresponding Author
Abstract
Andrographolide has been shown to have a pharmacological effect as an antidiabetic. Nevertheless, the comprehensive mechanism of action has yet to be determined. Andrographolide is a primary component of the sambiloto herb (Andrographis paniculata (Burm.f.) Nees), in which a simple isolation process can obtain high yields. This study aimed to explain the anti‐diabetic effect of andrographolide compared to pioglitazone (a positive control) on glucose uptake by measuring the expression levels of peroxisome proliferator‐activated receptor gamma (PPARγ) and glucose transporter type 4 (GLUT‐4) genes in 3T3‐LI mouse adipocytes as an in vitro model. The differentiation of mature adipocytes from 3T3‐L1 fibroblasts was induced with 3‐isobutyl‐1‐methylxanthine, dexamethasone, and insulin. Andrographolide was provided through direct isolation from A. paniculata herbs. The gene expression was detected using the reverse transcription‐polymerase chain reaction (RT‐PCR). Pioglitazone and andrographolide significantly increased glucose uptake capability. Andrographolide was able to increase the mRNA levels of PPARγ and GLUT‐4 compared to pioglitazone with the best concentration at 5.6 µM. In conclusion, andrographolide can improve glucose uptake by increasing mRNA levels of PPARγ and GLUT‐4 that encodes protein, which are key factors for glucose homeostasis. Therefore, this finding further establishes the potency of andrographolide from A. paniculata as an antidiabetic.
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Ahmadian M, Suh JM, Hah N, Liddle C, Atkins AR, Downes M, Evans RM. 2013. PPARγ signaling and metabolism: the good, the bad and the future. Nat Med. 19(5):557–566. doi:10.1038/NM.3159. [accessed 2022 Mar 31]. /pmc/articles/PMC3870016/.
Al-Goblan AS, Al-Alfi MA, Khan MZ. 2014. Mechanism linking diabetes mellitus and obesity. Diabetes, Metab Syndr Obes Targets Ther. 7:587–591. doi:10.2147/DMSO.S67400. [accessed 2021 May 22]. /pmc/articles/PMC4259868/.
Anusree SS, Priyanka A, Nisha VM, Das AA, Raghu KG. 2014. An in vitro study reveals the nutraceutical potential of punicic acid relevant to diabetes via enhanced GLUT4 expression and adiponectin secretion. Food Funct. 5(10):2590–2601. doi:10.1039/c4fo00302k. http://dx.doi.org/10.1039/C4FO00302K.
Bao S, Wu YL, Wang X, Han S, Cho SB, Ao W, Nan JX. 2020. Agriophyllum oligosaccharides ameliorate hepatic injury in type 2 diabetic db/db mice targeting INS-R/IRS-2/PI3K/AKT/PPAR-γ/Glut4 signal pathway. J Ethnopharmacol. 257:112863. doi:10.1016/j.jep.2020.112863. https://doi.org/10.1016/j.jep.2020.112863.
Basu A, Jensen MD, McCann F, Mukhopadhyay D, Joyner MJ, Rizza RA. 2006. Effects of pioglitazone versus glipizide on body fat distribution, body water content, and hemodynamics in type 2 diabetes. Diabetes Care. 29(3):510–514. doi:10.2337/DIACARE.29.03.06.DC05-2004.
Blanchard PG, Turcotte V, Côté M, Gélinas Y, Nilsson S, Olivecrona G, Deshaies Y, Festuccia WT. 2016. Peroxisome proliferator-activated receptor γ activation favours selective subcutaneous lipid deposition by coordinately regulating lipoprotein lipase modulators, fatty acid transporters and lipogenic enzymes. Acta Physiol. 217(3):227–239. doi:10.1111/APHA.12665. [accessed 2022 Apr 2]. https://onlinelibrary.wiley.com/doi/full/10.1111/apha.12665.
Cao H, Graves DJ, Anderson RA. 2010. Cinnamon extract regulates glucose transporter and insulin-signaling gene expression in mouse adipocytes. Phytomedicine. 17(13):1027–1032. doi:10.1016/J.PHYMED.2010.03.023.
Chait A, den Hartigh LJ. 2020. Adipose Tissue Distribution, Inflammation and Its Metabolic Consequences, Including Diabetes and Cardiovascular Disease. Front Cardiovasc Med. 7:22. doi:10.3389/FCVM.2020.00022. [accessed 2022 Mar 31]. /pmc/articles/PMC7052117/.
Cignarelli A, Giorgino F, Vettor R. 2013. Pharmacologic agents for type 2 diabetes therapy and regulation of adipogenesis. http://dx.doi.org/103109/138134552013796996. 119(4):139–150. doi:10.3109/13813455.2013.796996. [accessed 2022 Apr 2]. https://www.tandfonline.com/doi/abs/10.3109/13813455.2013.796996.
Fajas L. 2009. Adipogenesis: a cross-talk between cell proliferation and cell differentiation. doi:10.1080/07853890310009999. [accessed 2021 May 22]. https://www.tandfonline.com/action/journalInformation?journalCode=iann20.
Fajrin FA, Nugroho AE, Nurrochmad A, Susilowati R. 2020. Ginger extract and its compound, 6-shogaol, attenuates painful diabetic neuropathy in mice via reducing TRPV1 and NMDAR2B expressions in the spinal cord. J Ethnopharmacol. 249:112396. doi: 10.1016/j.jep.2019.112396.
Fan Y, Gan M, Tan Y, Chen L, Shen L, Niu L, Liu Y, Tang G, Jiang Y, Li X, et al. 2019. MiR-152 regulates 3T3-L1 preadipocyte proliferation and differentiation. Molecules. 24(18). doi:10.3390/molecules24183379.
Fasshauer M, Klein J, Ueki K, Kriauciunas KM, Benito M, White MF, Kahn CR. 2000. Essential role of insulin receptor substrate-2 in insulin stimulation of Glut4 translocation and glucose uptake in brown adipocytes. J Biol Chem. 275(33):25494–25501. doi:10.1074/jbc.M004046200. [accessed 2021 May 22]. https://pubmed.ncbi.nlm.nih.gov/10829031/.
Fitrawan LOM, Ariastuti R, Tjandrawinata R, Nugroho A, Pramono S. 2018. Antidiabetic effect of combination of fractionated-extracts of Andrographis paniculata and Centella asiatica: In vitro study. Asian Pac J Trop Biomed. 8(11):527–532. doi:10.4103/2221-1691.245957.
Fu Y, Luo N, Klein RL, Timothy Garvey W. 2005. Adiponectin promotes adipocyte differentiation, insulin sensitivity, and lipid accumulation. J Lipid Res. 46(7):1369–1379. doi:10.1194/jlr.M400373-JLR200. [accessed 2021 May 22]. https://pubmed.ncbi.nlm.nih.gov/15834118/.
Gandhi GR, Stalin A, Balakrishna K, Ignacimuthu S, Paulraj MG, Vishal R. 2013. Insulin sensitization via partial agonism of PPARγ and glucose uptake through translocation and activation of GLUT4 in PI3K/p-Akt signaling pathway by embelin in type 2 diabetic rats. Biochim Biophys Acta - Gen Subj. 1830(1):2243–2255. doi:10.1016/j.bbagen.2012.10.016. http://dx.doi.org/10.1016/j.bbagen.2012.10.016.
Hauner H. 2002. The mode of action of thiazolidinediones. Diabetes Metab Res Rev. 18(SUPPL. 2). doi:10.1002/dmrr.249. [accessed 2021 May 22]. https://pubmed.ncbi.nlm.nih.gov/11921433/.
Harwoko, Pramono S, Nugroho AE. 2014. Triterpenoid-rich fraction of centella asiatica leaves and in vivo antihypertensive activity. Int. Food Res. J. 21(1):149-154. http://www.ifrj.upm.edu.my/volume-21-2014.html
Horita S, Nakamura M, Satoh N, Suzuki M, Seki G. 2015. Thiazolidinediones and edema: Recent advances in the pathogenesis of Thiazolidinediones-induced renal sodium retention. PPAR Res. 2015. doi:10.1155/2015/646423.
Jin L, Fang W, Li B, Shi G, Li X, Yang Y, Yang J, Zhang Z, Ning G. 2012. Inhibitory effect of Andrographolide in 3T3-L1 adipocytes differentiation through the PPARγ pathway. Mol Cell Endocrinol. 358(1):81–87. doi:10.1016/j.mce.2012.02.025.
Jin L, Shi G, Ning G, Li X, Zhang Z. 2011. Andrographolide attenuates tumor necrosis factor-alpha-induced insulin resistance in 3T3-L1 adipocytes. Mol Cell Endocrinol. 332(1–2):134–139. doi:10.1016/j.mce.2010.10.005. http://dx.doi.org/10.1016/j.mce.2010.10.005.
Kvandová M, Majzúnová M, Dovinová I. 2016. The role of PPARγ in cardiovascular diseases. Physiol Res. 65:S343–S363. doi:10.33549/physiolres.933439.
Lefterova MI, Zhang Y, Steger DJ, Schupp M, Schug J, Cristancho A, Feng D, Zhuo D, Stoeckert CJ, Liu
XS, Lazar MA. 2008. PPARγ and C/EBP factors orchestrate adipocyte biology via adjacent binding on a genomewide scale. Genes Dev. 22(21):2941–2952. doi:10.1101/gad.1709008
Maiti K, Mukherjee K, Murugan V, Saha BP, Mukherjee PK. 2010. Enhancing bioavailability and hepatoprotective activity of andrographolide from Andrographis paniculata, a well-known medicinal food, through its herbosome. J Sci Food Agric. 90(1):43–51. doi:10.1002/jsfa.3777. [accessed 2021 May 22]. https://onlinelibrary.wiley.com/doi/full/10.1002/jsfa.3777.
Malik Z, Parveen R, Parveen B, Zahiruddin S, Aasif Khan M, Khan A, Massey S, Ahmad S, Husain SA. 2021. Anticancer potential of andrographolide from Andrographis paniculata (Burm.f.) Nees and its mechanisms of action. J Ethnopharmacol. 272:113936. doi:10.1016/j.jep.2021.113936.
Moseti D, Regassa A, Kim WK. 2016. Molecular Regulation of Adipogenesis and Potential Anti-Adipogenic Bioactive Molecules. Int J Mol Sci 2016, Vol 17, Page 124. 17(1):124. doi:10.3390/IJMS17010124. [accessed 2022 Mar 21]. https://www.mdpi.com/1422-0067/17/1/124/htm.
Novitasari PR, Astuti NT, Pramono S, Tjandrawinata R, Nugroho AE. 2020. A simple LiquidLiquid Fractionation (LLF) method for isolating deoxyandrographolide dan andrographolide from herbs of Andrographis paniculata (Burm., F) Ness and its cytotoxic activity on 3T3L1 preadipocyte cells. J. Food Pharm. Sci. 8(3):306–314. doi:10.22146/jfps.875
Nugroho AE, Anas Y, Arsito PN, Wibowo JT, Riyanto S, Sukari MA. 2011. Effects of marmin, a compound isolated from Aegle marmelos Correa, on contraction of the guinea pig-isolated trachea. Pak J Pharm Sci. 24(4):427-33. PMID: 21959801.
Nugroho AE, Andrie M, Warditiani NK, Siswanto E, Pramono S, Lukitaningsih E. 2012. Antidiabetic and antihiperlipidemic effect of Andrographis paniculata (Burm. f.) Nees and andrographolide in high-fructose-fat-fed rats. Indian J Pharmacol. 44(3):377–381. doi:10.4103/0253-7613.96343. [accessed 2021 May 22]. /pmc/articles/PMC3371463/.
Nugroho AE, Rais IR, Setiawan I, Pratiwi PY, Hadibarata T, Tegar M, Pramono S. 2013. Pancreatic effect of andrographolide isolated from Andrographis paniculata (Burm. f.) Nees. Pakistan J Biol Sci. 17(1):22–31. doi:10.3923/pjbs.2014.22.31. [accessed 2021 May 22]. https://europepmc.org/article/med/24783774.
Pereira ASP, Banegas-Luna AJ, Peña-García J, Pérez-Sánchez H, Apostolides Z. 2019. Evaluation of the Anti-Diabetic Activity of Some Common Herbs and Spices: Providing New Insights with Inverse Virtual Screening. Mol 2019, Vol 24, Page 4030. 24(22):4030. doi:10.3390/MOLECULES24224030. [accessed 2022 Apr 2]. https://www.mdpi.com/1420-3049/24/22/4030/htm.
Rafat A, Philip K, Muniandy S. 2010. Antioxidant potential and content of phenolic compounds in ethanolic extracts of selected parts of Andrographis paniculata. [accessed 2021 May 22]. http://www.academicjournals.org/JMPR.
Sarjeant K, Stephens JM. 2012. Adipogenesis. Cold Spring Harb Perspect Biol. 4(9). doi:10.1101/cshperspect.a008417. [accessed 2021 May 22]. /pmc/articles/PMC3428766/.
Shoelson SE, Lee J, Goldfine AB. 2006. Inflammation and insulin resistance. J Clin Invest. 116(7):1793–1801. doi:10.1172/JCI29069. [accessed 2021 May 22]. http://www.jci.org.
Soccio RE, Chen ER, Lazar MA. 2014. Thiazolidinediones and the Promise of Insulin Sensitization in Type 2 Diabetes. Cell Metab. 20(4):573–591. doi:10.1016/J.CMET.2014.08.005.
Sugii S, Olson P, Sears DD, Saberi M, Atkins AR, Barish GD, Hong SH, Castro GL, Yin YQ, Nelson MC, et al. 2009. PPARγ activation in adipocytes is sufficient for systemic insulin sensitization. Proc Natl Acad Sci U S A. 106(52):22504–22509. doi:10.1073/pnas.0912487106. [accessed 2021 May 22]. www.pnas.org/cgi/content/full/.
Tjandrawinata RR, Wulan DD, Nailufar F, Sinambela J, Tandrasasmita OM. 2011. Glucoselowering effect of DLBS3233 is mediated through phosphorylation of tyrosine and upregulation of PPARγ and GLUT4 expression. Int. J. Gen. Med. 4:345–357. doi:10.2147/IJGM.S16517.
Wang S, Dougherty EJ, Danner RL. 2016. PPARγ signaling and emerging opportunities for improved therapeutics. Pharmacol Res. 111:76–85. doi:10.1016/j.phrs.2016.02.028. http://dx.doi.org/10.1016/j.phrs.2016.02.028.
Widyawaruyanti A, Asrory M, Ekasari W, Setiawan D, Radjaram A, Tumewu L, Hafid AF. 2014. In vivo Antimalarial Activity of Andrographis Paniculata Tablets. Procedia Chem. 13:101–104. doi:10.1016/j.proche.2014.12.012.
Wigati D, Anwar K, Sudarsono, Nugroho AE. 2017. Hypotensive Activity of Ethanolic Extracts of Morinda citrifolia L. Leaves and Fruit in Dexamethasone-Induced Hypertensive Rat. J Evid Based Complementary Altern Med. 22(1):107-113. doi: 10.1177/2156587216653660.
Zheng Y, Ley SH, Hu FB. 2018. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol. 14(2):88–98. doi:10.1038/nrendo.2017.151. [accessed 2021 May 21]. https://pubmed.ncbi.nlm.nih.gov/29219149/.
DOI: https://doi.org/10.22146/ijbiotech.68800
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