Author(s): Karan Wadhwa, A.C. Rana, Payal Mittal, Sahil Banwala, Shivkant Sharma


DOI: 10.52711/0974-360X.2023.00164   

Address: Karan Wadhwa1*, A.C. Rana2, Payal Mittal3, Sahil Banwala4, Shivkant Sharma5
1Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, Haryana, 124001, India.
2Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, Haryana, 136119, India.
3University Institute of Pharma Sciences, Chandigarh University, Gharuan, Mohali, Punjab 140413, India.
4SDM College of Pharmacy, Rajound, Kaithal, Haryana, 136044, India.
5R.K.S.D College of Pharmacy Kaithal, Haryana, 136027, India.
*Corresponding Author

Published In:   Volume - 16,      Issue - 2,     Year - 2023

The poor bioavailability of various drugs is the utmost obstacle in oral drug delivery. The use of natural bioenhancer as supplements with the primary therapeutic agent has gained wider acceptance and has been emerged as a potential method to increase the bioavailability of various drugs. Gallic acid is one of the chief phenolic natural compounds extensively distributed in plants and fruit. Despite its broad spectrum pharmacological effects, gallic acid significantly augments the bioavailability of diverse classes of drugs at low doses by impeding liver metabolism and altering gastrointestinal permeability. In this context, this review aims to summarise the promising bioavailability enhancing activity of gallic acid on different therapeutic agents. Furthermore, current evidence confirms that the intervention with gallic acid leads to enhance the bioavailability of various drugs; however, extensive research is need of the hour so that it could be utilized in drug formulations in the future for clinical use.

Cite this article:
Karan Wadhwa, A.C. Rana, Payal Mittal, Sahil Banwala, Shivkant Sharma. Insights on prospective role of Gallic acid as a Bioavailability Enhancer. Research Journal of Pharmacy and Technology 2023; 16(2):983-8. doi: 10.52711/0974-360X.2023.00164

Karan Wadhwa, A.C. Rana, Payal Mittal, Sahil Banwala, Shivkant Sharma. Insights on prospective role of Gallic acid as a Bioavailability Enhancer. Research Journal of Pharmacy and Technology 2023; 16(2):983-8. doi: 10.52711/0974-360X.2023.00164   Available on:

1.    Dudhatra GB, Mody SK, Awale MM, et al. A comprehensive review on pharmacotherapeutics of herbal bioenhancers. Sci World J. 2012;2012:1-33. doi:10.1100/2012/637953
2.    Atal N, Bedi KL. Bioenhancers: Revolutionary concept to market. J Ayurveda Integr Med. 2010;1(2):96-99. doi:10.4103/0975-9476.65073
3.    Qazi G, Bedi KL, Johri RK, Kapahi BK. Bioavailability/bioefficacy enhancing activity of Cuminum cyminum and extracts and fractions thereof. 2009.
4.    Kesarwani K, Gupta R. Bioavailability enhancers of herbal origin: An overview. Asian Pac J Trop Biomed. 2013;3(4):253-266. doi:10.1016/S2221-1691(13)60060-X
5.    Johri RK, Zutshi U. An Ayurvedic formulation “Trikatu” and its constituents. J Ethnopharmacol. 1992;37(2):85-91. doi:10.1016/0378-8741(92)90067-2
6.    Peterson B, Weyers M, Steenekamp JH, Steyn JD, Gouws C, Hamman JH. Drug bioavailability enhancing agents of natural origin (bioenhancers) that modulate drug membrane permeation and pre-systemic metabolism. Pharmaceutics. 2019;11(33):1-46. doi:10.3390/pharmaceutics11010033
7.    Khanuja SPS, Arya JS, Ranganathan T, Kumar S, Kumar S. Antibiotic pharmaceutical composition with lysergol as bio-enhancer and method of treatment. 2007.
8.    Atal CK, Zutshi U, Rao PG. Scientific evidence on the role of Ayurvedic herbals on bioavailability of drugs. J Ethnopharmacol. 1981;4(2):229-232. doi:10.1016/0378-8741(81)90037-4
9.    K. G. Bose. Pharmacopoeia India. Bose Laboratories, Calcutta, India; 1929.
10.    Atal CK. A breakthrough in drug bioavailability-a clue from age old wisdom of Ayurveda. IDMA Bull. 1979;10:483-484.
11.    Bhimanwar R, Kothapalli L, Khawshi A. Quercetin as natural bioavailability modulator: An overview. Res J Pharm Technol. 2020;13(4):2043-2050. doi:10.5958/0974-360X.2020.00368.6
12.    Breedveld P, Beijnen JH, Schellens JHM. Use of P-glycoprotein and BCRP inhibitors to improve oral bioavailability and CNS penetration of anticancer drugs. Trends Pharmacol Sci. 2006;27(1):17-24. doi:10.1016/
13.    Kang MJ, Cho JY, Shim BH, Kim DK, Lee J. Bioavailability enhancing activities of natural compounds from medicinal plants. J Med Plants Res. 2009;3(13):1204-1211.
14.    Patil PR, Vakhariya RR, Magdum CS. Solubility as well as Bioavailability Enhancement Techniques. Res J Pharm Dos Forms Technol. 2019;11(2):105. doi:10.5958/0975-4377.2019.00016.8
15.    Vitthal HP. Bioenhancers-A Review. Res J Pharm Dos Forms Technol. 2015;7(4):274. doi:10.5958/0975-4377.2015.00039.7
16.    Jain G, Patil UK. Strategies for enhancement of bioavailability of medicinal agents. Int J Pharm Sci Res. 2015;6(12):5315-5324. doi:10.13040/IJPSR.0975-8232.6(12). 5315-24
17.    Atal CK, Dubey RK, Singh J. Biochemical basis of enhanced drug bioavailability by piperine: evidence that piperine is a potent inhibitor of drug metabolism. J Pharmacol Exp Ther. 1985;232(1):258-262.
18.    Reen RK, Jamwal DS, Taneja SC, et al. Impairment of UDP-glucose dehydrogenase and glucuronidation activities in liver and small intestine of rat and guinea pig in vitro by piperine. Biochem Pharmacol. 1993;46(2):229-238. doi:10.1016/0006-2952(93)90408-O
19.    Bhardwaj RK, Glaeser H, Becquemont L, Klotz U, Gupta SK, Fromm MF. Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4. J Pharmacol Exp Ther. 2002;302(2):645-650. doi:10.1124/jpet.102.034728
20.    Shamsi S, Tran H, Tan RSJ, Tan ZJ, Lim LY. Curcumin, piperine, and capsaicin: A comparative study of spice-mediated inhibition of human cytochrome P450 isozyme activities. Drug Metab Dispos. 2017;45(1):49-55. doi:10.1124/dmd.116.073213
21.    Khajuria A, Thusu N, Zutshi U. Piperine modulates permeability characteristics of intestine by inducing alterations in membrane dynamics: Influence on brush border membrane fluidity, ultrastructure and enzyme kinetics. Phytomedicine. 2002;9(3):224-231. doi:10.1078/0944-7113-00114
22.    Han Y, Chin Tan TM, Lim LY. In vitro and in vivo evaluation of the effects of piperine on P-gp function and expression. Toxicol Appl Pharmacol. 2008;230(3):283-289. doi:10.1016/j.taap.2008.02.026
23.    Singh DV, Godbole MM, Misra K. A plausible explanation for enhanced bioavailability of P-gp substrates in presence of piperine: Simulation for next generation of P-gp inhibitors. J Mol Model. 2013;19(1):227-238. doi:10.1007/s00894-012-1535-8
24.    Annamalai AR, Manavalan R. Effect of “Trikatu” and its individual components and piperine on gastrointestinal tracts. Indian Drugs. 1990;27(12):595-604.
25.    Bajad S, Bedi KL, Singla AK, Johri RK. Piperine inhibits gastric emptying and gastrointestinal transit in rats and mice. Planta Med. 2001;67(2):176-179. doi:10.1055/s-2001-11505
26.    Johri RK, Thusu N, Khajuria A, Zutshi U. Piperine-mediated changes in the permeability of rat intestinal epithelial cells. Biochem Pharmacol. 1992;43(7):1401-1407. doi:10.1016/0006-2952(92)90195-o
27.    Reanmongkol W, Janthasoot W, Wattanatorn W, Dhumma-Upakorn P, Chudapongse P. Effects of piperine on bioenergetic functions of isolated rat liver mitochondria. Biochem Pharmacol. 1988;37(4):753-757. doi:10.1016/0006-2952(88)90151-7
28.    Jamwal DS, Singh J. Effects of piperine on enzyme activities and bioenergetic functions in isolated rat liver mitochondria and hepatocytes. J Biochem Toxicol. 1993;8(4):167-174. doi:10.1002/jbt.2570080402
29.    Majeed M, Badmaev V, Rajendran R. Use of piperine to increase the bioavailability of nutritional compounds. 1996.
30.    Can ÖD, Turan N, Demir Özkay Ü, Öztürk Y. Antidepressant-like effect of gallic acid in mice: Dual involvement of serotonergic and catecholaminergic systems. Life Sci. 2017;190:110-117. doi:10.1016/j.lfs.2017.09.023
31.    Ali R, Mathew M, Elizabeth Reji S, Issac A. Comparative Studies on Total Polyphenols, Flavanoids and Antioxidant Potential of some Marketed brands of packed Green Tea. Res J Pharm Tech. 2020;13(7). doi:10.5958/0974-360X.2020.00562.4
32.    Alegbe EO, Teralı K, Olofinsan KA, Surgun S, Ogbaga CC, Ajiboye TO. Antidiabetic activity-guided isolation of gallic and protocatechuic acids from Hibiscus sabdariffa calyxes. J Food Biochem. 2019;43(7):1-12. doi:10.1111/jfbc.12927
33.    Variya BC, Bakrania AK, Patel SS. Antidiabetic potential of gallic acid from Emblica officinalis: Improved glucose transporters and insulin sensitivity through PPAR-γ and Akt signaling. Phytomedicine. 2019:152906. doi:10.1016/j.phymed.2019.152906
34.    Bak EJ, Kim J, Jang S, et al. Gallic acid improves glucose tolerance and triglyceride concentration in diet-induced obesity mice. Scand J Clin Lab Invest. 2013;73(8):607-614. doi:10.3109/00365513.2013.831470
35.    Gandhi GR, Jothi G, Antony PJ, et al. Gallic acid attenuates high-fat diet fed-streptozotocin-induced insulin resistance via partial agonism of PPARγ in experimental type 2 diabetic rats and enhances glucose uptake through translocation and activation of GLUT4 in PI3K/p-Akt signaling pathway. Eur J Pharmacol. 2014;745:201-216. doi:10.1016/j.ejphar.2014.10.044
36.    Punithavathi VR, Prince PSM, Kumar R, Selvakumari J. Antihyperglycaemic, antilipid peroxidative and antioxidant effects of gallic acid on streptozotocin induced diabetic Wistar rats. Eur J Pharmacol. 2011;650(1):465-471. doi:10.1016/j.ejphar.2010.08.059
37.    Hsu CL, Yen GC. Effect of gallic acid on high fat diet-induced dyslipidaemia, hepatosteatosis and oxidative stress in rats. Br J Nutr. 2007;98(4):727-735. doi:10.1017/S000711450774686X
38.    Jang A, Srinivasan P, Lee NY, et al. Comparison of hypolipidemic activity of synthetic gallic acid-linoleic acid ester with mixture of gallic acid and linoleic acid, gallic acid, and linoleic acid on high-fat diet induced obesity in C57BL/6 Cr Slc mice. Chem Biol Interact. 2008;174(2):109-117. doi:10.1016/j.cbi.2008.05.018
39.    Umadevi S, Gopi V, Elangovan V. Regulatory mechanism of gallic acid against advanced glycation end products induced cardiac remodeling in experimental rats. Chem Biol Interact. 2014;208(1):28-36. doi:10.1016/j.cbi.2013.11.013
40.    Jin L, Lin MQ, Piao ZH, et al. Gallic acid attenuates hypertension, cardiac remodeling, and fibrosis in mice with N G -nitro- l -arginine methyl ester-induced hypertension via regulation of histone deacetylase 1 or histone deacetylase 2. J Hypertens. 2017;35(7):1502-1512. doi:10.1097/HJH.0000000000001327 Journal
41.    Zhang T, Ma L, Wu P, et al. Gallic acid has anticancer activity and enhances the anticancer effects of cisplatin in non‑small cell lung cancer A549 cells via the JAK/STAT3 signaling pathway. Oncol Rep. 2019;41(3):1779-1788. doi:10.3892/or.2019.6976
42.    Giftson JS, Jayanthi S, Nalini N. Chemopreventive efficacy of gallic acid, an antioxidant and anticarcinogenic polyphenol, against 1,2-dimethyl hydrazine induced rat colon carcinogenesis. Invest New Drugs. 2010;28(3):251-259. doi:10.1007/s10637-009-9241-9
43.    Maruszewska A, Tarasiuk J. Antitumour effects of selected plant polyphenols, gallic acid and ellagic acid, on sensitive and multidrug-resistant leukaemia HL60 cells. Phyther Res. 2019;33(4):1208-1221. doi:10.1002/ptr.6317
44.    Tawfeeq TA, Jasim GA, A. Nasser A, Al-Sudani BT. Isolation of Lupeol and Gallic acid with cytotoxic activity of two different extracts from the leaves of Iraqi Conocarpus erectus L. Res J Pharm Technol. 2021;14(7):3495-3503. doi:10.52711/0974-360x.2021.00606
45.    Kaur S, Muthuraman A. Ameliorative effect of gallic acid in paclitaxel-induced neuropathic pain in mice. Toxicol Reports. 2019;6:505-513. doi:10.1016/j.toxrep.2019.06.001
46.    Mansouri MT, Farbood Y, Sameri MJ, Sarkaki A, Naghizadeh B, Rafeirad M. Neuroprotective effects of oral gallic acid against oxidative stress induced by 6-hydroxydopamine in rats. Food Chem. 2013;138(2-3):1028-1033. doi:10.1016/j.foodchem.2012.11.022
47.    Samad N, Jabeen S, Imran I, Zulfiqar I, Bilal K. Protective effect of gallic acid against arsenic-induced anxiety−/depression- like behaviors and memory impairment in male rats. Metab Brain Dis. 2019;34(4):1091-1102. doi:10.1007/s11011-019-00432-1
48.    Bayramoglu G, Kurt H, Bayramoglu A, Gunes HV, Degirmenci İ, Colak S. Preventive role of gallic acid on hepatic ischemia and reperfusion injury in rats. Cytotechnology. 2015;67(5):845-849. doi:10.1007/s10616-014-9724-1
49.    Rasool MK, Sabina EP, Ramya SR, et al. Hepatoprotective and antioxidant effects of gallic acid in paracetamol-induced liver damage in mice. J Pharm Pharmacol. 2010;62(5):638-643. doi:10.1211/jpp.62.05.0012
50.    Safaei F, Mehrzadi S, Khadem Haghighian H, et al. Protective effects of gallic acid against methotrexate-induced toxicity in rats. Acta Chir Belg. 2018;118(3):152-160. doi:10.1080/00015458.2017.1394672
51.    Kuamwat RS, Mruthunjaya K, Gupta MK. Hepatoprotective effect of gallic acid and gallic acid phytosome against carbon tetrachloride induced damage in albino rats. Res J Pharm Technol. 2012;5(5):677-681.
52.    Hajipour S, Sarkaki A, Farbood Y, Eidi A, Mortazavi P, Valizadeh Z. Effect of gallic acid on dementia type of Alzheimer disease in rats: Electrophysiological and histological studies. Basic Clin Neurosci. 2016;7(2):97-106. doi:10.15412/
53.    Liu KYP, Hu S, Chan BCL, et al. Anti-inflammatory and anti-allergic activities of pentaherb formula, moutan cortex (Danpi) and gallic acid. Molecules. 2013;18(3):2483-2500. doi:10.3390/molecules18032483
54.    Pandurangan AK, Mohebali N, Esa NM, Looi CY, Ismail S, Saadatdoust Z. Gallic acid suppresses inflammation in dextran sodium sulfate-induced colitis in mice: Possible mechanisms. Int Immunopharmacol. 2015;28(2):1034-1043. doi:10.1016/j.intimp.2015.08.019
55.    Peng CC, Hsieh CL, Wang HE, Chung JY, Chen KC, Peng RY. Ferulic acid is nephrodamaging while gallic acid is renal protective in long term treatment of chronic kidney disease. Clin Nutr. 2012;31(3):405-414. doi:10.1016/j.clnu.2011.11.003
56.    Borges A, Ferreira C, Saavedra MJ, Simões M. Antibacterial activity and mode of action of ferulic and gallic acids against pathogenic bacteria. Microb Drug Resist. 2013;19(4):256-265. doi:10.1089/mdr.2012.0244
57.    Lima VN, Oliveira-Tintino CDM, Santos ES, et al. Antimicrobial and enhancement of the antibiotic activity by phenolic compounds: Gallic acid, caffeic acid and pyrogallol. Microb Pathog. 2016;99:56-61. doi:10.1016/j.micpath.2016.08.004
58.    Lee JH, Oh M, Seok JH, et al. Antiviral effects of black raspberry (Rubus coreanus) seed and its gallic acid against influenza virus infection. Viruses. 2016;8(6):1-12. doi:10.3390/v8060157
59.    Govea-Salas M, Rivas-Estilla AM, Rodríguez-Herrera R, et al. Gallic acid decreases hepatitis C virus expression through its antioxidant capacity. Exp Ther Med. 2016;11(2):619-624. doi:10.3892/etm.2015.2923
60.    Li ZJ, Liu M, Dawuti G, et al. Antifungal Activity of Gallic Acid In Vitro and In Vivo. Phyther Res. 2017;31(7):1039-1045. doi:10.1002/ptr.5823
61.    Zanwar AA, Badole SL, Shende PS, Hegde M V., Bodhankar SL. Role of Gallic Acid in Cardiovascular Disorders. In: Polyphenols in Human Health and Disease. Vol 2. Elsevier Inc.; 2013:1045-1047. doi:10.1016/B978-0-12-398456-2.00080-3
62.    Goldberg I, Rokem JS. Organic and Fatty Acid Production, Microbial. In: Encyclopedia of Microbiology. 3rd ed. Elsevier Inc.; 2009:421-442. doi:10.1016/B978-012373944-5.00156-5
63.    Choubey S, Varughese LR ache., Kumar V, Beniwal V. Medicinal importance of gallic acid and its ester derivatives: a patent review. Pharm Pat Anal. 2015;4(4):305-315. doi:10.4155/ppa.15.14
64.    Kitagawa S, Nabekura T, Kamiyama S, et al. Effects of alkyl gallates on P-glycoprotein function. Biochem Pharmacol. 2005;70(8):1262-1266. doi:10.1016/j.bcp.2005.07.013
65.    Ow Y-Y, Stupans I. Gallic Acid and Gallic Acid Derivatives: Effects on Drug Metabolizing Enzymes. Curr Drug Metab. 2005;4(3):241-248. doi:10.2174/1389200033489479
66.    Pu QH, Shi L, Yu C. Time-dependent inhibition of CYP3A4 by gallic acid in human liver microsomes and recombinant systems. Xenobiotica. 2015;45(3):213-217. doi:10.3109/00498254.2014.973470
67.    Shaik M, Vanapatla SR. Enhanced oral bioavailability of linagliptin by the influence of gallic acid and ellagic acid in male wistar albino rats: Involvement of p-glycoprotein inhibition. Drug Metab Pers Ther. 2019;34(2):1-7. doi:10.1515/dmpt-2018-0020
68.    Athukuri BL, Neerati P. Enhanced oral bioavailability of diltiazem by the influence of gallic acid and ellagic acid in male wistar rats: Involvement of CYP3A and P-gp inhibition. Phyther Res. 2017;31(9):1441-1448. doi:10.1002/ptr.5873
69.    Athukuri BL, Neerati P. Enhanced oral bioavailability of metoprolol with gallic acid and ellagic acid in male wistar rats: Involvement of CYP2D6 inhibition. Drug Metab Pers Ther. 2016;31(4):229-234. doi:10.1515/dmpt-2016-0029
70.    Basu S, Jana S, Patel VB, Patel H. Effects of piperine, cinnamic acid and gallic acid on rosuvastatin pharmacokinetics in rats. Phyther Res. 2013;27(10):1548-1556. doi:10.1002/ptr.4894
71.    Basu S, Patel VB. Comparative pharmacokinetics of rosuvastatin in male C57BL / 6 mice following single intravenous and oral administration co-administered with herbal bioenhancers. J Pharm Res. 2012;5(8):4119-4124.
72.    Basu S, Rastogi H, Patel VB, Patel H. Effect of herbal bioenhancers on saquinavir in human Caco-2 cell monolayers and pharmacokinetics in rats. Int J Med Pharm Sci. 2012;2(2):27-41.
73.    Kotwal P, Dogra A, Sharma A, et al. Effect of natural phenolics on pharmacokinetic modulation of bedaquiline in rat to assess the likelihood of potential food–drug interaction. J Agric Food Chem. 2020;68(5):1257-1265. doi:10.1021/acs.jafc.9b06529

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