Absorption enhancing activity of seven herbal extracts on ciprofloxacin using everted sac method

Vedamurthy Joshi, Shivakumar Inamdar, Rajesh Kowti, Sachin A.B., Ankit Acharya


Objective: Ciprofloxacin is a broad-spectrum fluoroquinolone antibiotic with poor permeability. The present study aimed to investigate the influence of seven alcoholic herbal extracts on the in-vitro absorption of ciprofloxacin using everted sac method.

Methods: The herbal extracts include Curcuma longa (turmeric), Piper nigrum (black piper), Moringa oleifera (drum stick), Piper betle (betel leaf), Trachyspermum ammi (ajwain seeds), Murraya koenigii (curry leaves), Plumbago zeylanica. Influence of Verapamil, a known P-gp inhibitor on ciprofloxacin absorption was also studied. Drug-extract compatibility studies were carried with FTIR. Histological study was carried to detect the influence of the extract on the isolated intestine.

Results: The results indicated significant improvement in the apparent permeability coefficient (Paa) of ciprofloxacin when co-incubated with plant extracts. Amongst all herbal extracts, Piper nigrum extract showed the highest percentage of ciprofloxacin permeability i.e. Paa increases from 15.245 cm/sec to 18.012 cm/sec, which was 18.24% higher than ciprofloxacin alone as control. Paa of ciprofloxacin (3.0 mM) was found increased in the following order ranging from highest to lowest. Piper nigrum >Curcuma longa >Piper betle >Murraya koenigii >Moringa oleifera >Plumbago zeylanica >Trachyspermum ammi.

Conclusions: In conclusion, the permeability of Ciprofloxacin can be increased with the co incubation of the above extracts.


Ciprofloxacin, Everted sac method, Permeability coefficient, Bioenhancers, Piper nigrum, Moringa oleifera, Piper betle, Trachyspermum ammi, Murraya koenigii, Plumbago zeylanica

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Awortwe C, Bouic PJ, Masimirembwa CM, Rosenkranz B. Inhibition of major drug metabolizing CYPs by common herbal medicines used by HIV/AIDS patients in Africa– implications for herb-drug interactions. Drug Met Lett. 2014;7(2):83–95.

Hellum BH, Nilsen OG. In-vitro inhibition of CYP3A4 metabolism and P-glycoprotein-mediated transport by trade herbal products. Basic Clinic Pharmaco Toxico. 2007;102:466–75.

El Astal Z. Increasing Ciprofloxacin Resistance Among Prevalent Urinary Tract Bacterial Isolates in Gaza Strip, Palestine. Journal of Biomedicine and Biotechnology. 2005;3:238-41.

Park MS, Okochi H, Benet LZ. Is Ciprofloxacin a Substrate of P-glycoprotein? 2011;1–9.

Amin ML. P-glycoprotein inhibition for optimal drug delivery. Drug Target Insights. 2013;7:27–34.

Sharom FJ. The P-glycoprotein multidrug transporter. Essays Biochem. 2011;50(1):161–78.

Lin JH, Yamazaki M. Role of P-glycoprotein in pharmacokinetics: clinical implications. Clin Pharmacokinet. 2003;42(1):59-98.

Dantzig AH, Shepard RL, Cao J, Law KL, Ehlhardt WJ, Baughman TM, et al. Reversal of Pglycoprotein-mediated multidrug resistance by a potent cyclopropyl dibenzosuberane modulator, LY335979. Cancer Res. 1996;56:4171-79.

Eagling VA, Profit L, Back DJ. Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-1 protease inhibitor saquinavir by grape fruit juice components. Br J Clin Pharmacol. 1999;48(4):543-52.

Breda SA, Jimenez-Kairuz AF, Manzo RH, OliveraME. Solubility behavior and biopharmaceutical classification of novel high-solubility ciprofloxacin and norfloxacin pharmaceutical derivatives. 2009;371(2):106-13.

Wagner D, Spahn-Langguth H, HanafyA, KoggelA, Langguth P. Intestinal drug efflux: formulation and food effects. Adv Drug Deliv Rev. 2001;50(1):S13-31.

Pawar MA, Patil SS, Nagrik DM. Phytochemical and physicochemical investigation of Curcuma Linn rhizome. Int J Chem Phys Sci. 2015;4:458-64.

Kokate CK. Practical Pharmacognosy. 4th ed., New Delhi; VallabhPrakashan; 2015: 1-23.

Harbone JB, Turner BL. Plant chemosystematics. Academic press, London; 1984: 61-2.

Siddiqui AA, Ali M. Practical Pharmaceutical chemistry. 1st ed. CBS Publishers and Distributors, New Delhi; 1997: 126-131.

Dixit P, Jain DK, Dumbwani J. Standardization of an ex-vivo method for determination of intestinal permeability of drugs using everted rat intestine apparatus. J Pharmacol Toxicol. 2012;65(1):13–7.

Kaynak MS, Buyuktuncel E, Caglar H, Sahin S. Determination of regional intestinal permeability of diclofenac and metoprolol using a newly-developed and validated high performance liquid chromatographic method. Trop J Pharm Res. 2015;14(1):163-70.

Sailaja B, Venkateswarlu G. Oxidative spectrophotometric determination of drugs using KMnO4 and rhodamine-b. Acta Biomedica Scientia. 2014;1(1):1-5.

Alarfaj NA, Razeq SA, Alsehaly HM. Determination of josamycin and ciprofloxacin in their pharmaceutical dosage forms by spectrophotometry. Asian J Chem. 2011;23(8):3362.

Custodio JM, Wu C, Benet LZ. Predicting drug disposition, absorption/ elimination/ transporter interplay and the role of food on drug absorption. Adv Drug Deliv Rev. 2008;60(6):717–33.

Hunter J, Hirst BH. Intestinal secretion of drugs. The role of P-glycoprotein and related drug efflux systems in limiting oral drug absorption. Adv Drug Deliv Rev. 1997;97:129–57.

Dautrey S, Felice K, Petiet A, Lacour B, Carbon C, Farinotti R. Active intestinal elimination of ciprofloxacin in rats: Modulation by different substrates. Br J Pharmacol 1999;127:1728–34.

Cavet ME, West M, Simmons NL. Fluoroquinolone (ciprofloxacin) secretion by human intestinal epithelial (Caco-2) cells. Br J Pharmacol. 1997;121:1567–78.

Griffiths NM, Hirst BH, Simmons NL. Active secretion of the fluoroquinolone ciprofloxacin by human intestinal epithelial Caco-2 cell layers. Br J Pharmacol. 1993;108:575–6.

Moorthi C, Kathiresan K. Curcumin–Piperine/ Curcumin–Quercetin/Curcumin–Silibinin dual drug-loaded nanoparticulate combination therapy: A novel approach to target and treat multidrug-resistant cancers. J Med Hypotheses Ideas. 2013;7(1):15–20.

Oga EF, Sekine S, Shitara Y, Horie T. P-glycoprotein mediated efflux in Caco-2 cell monolayers: the influence of herbals on digoxin transport. J Ethnopharmacol. 2012;144(3):612–7.

Hou X, Takahashi KK, Tanaka K, Tougou K, Qiu F, Komatsu K, et al. Curcuma drugs and curcumin regulate the expression and function of P-gp in Caco-2 cells in completely opposite ways. 2008;358:224–9.

Ampasavate C, Sotanaphun U, Phattanawasin P, Piyapolrungroj N. Effects of Curcuma spp. on P-glycoprotein function. Phytomedicine. 2010;17(7):506–12.

Dudhatra GB, Mody SK, Awale MM, Patel HB, Modi CM, Kumar A, et al. A Comprehensive Review on Pharmaco-therapeutics of Herbal Bioenhancers. Sci World J 2012;2012:1–33.

Bansal T, Jaggi M, Khar RK, Talegaonkar S. Emerging significance of flavonoids as P-glycoprotein inhibitors in cancer chemotherapy. J Pharm Pharm Sci a Publ Can Soc Pharm Sci Société Can des Sci Pharm. 2009;12(1):46–78.

Abdallah HM, Al-Abd AM, El-Dine RS, El-Halawany AM. P-glycoprotein inhibitors of natural origin as potential tumor chemo-sensitizers: A review. Journal of Advanced Research. 2015;6(1):45-62.

Seral C, Carryn S, Tulkens PM, Van Bambeke F. Influence of P-glycoprotein and MRP effux pump inhibitors on the intracellular activity of azithromycin and ciprofloxacin in macrophages infected by Listeria monocytogenes or Staphylococcus aureus. J Antimicrob Chemother. 2003;51(5):1167–73.

Tariq M, Gore M, Aruna K. Antibacterial and synergistic activity of ethanolic ajwain (trachyspermum ammi) extract on ESBL and MBL producing uropathogens. Int J Pharm Pharm Sci. 2014;6(6):278–84.


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