Favourable drug-lead pharmacokinetic features for designing gallic acid-standardized Syzygium polyanthum aqueous extract-based product

  • Hassan Fahmi Ismail Institute of Marine Biotechnology, Universiti Malaysia Terengganu, 21030 Kuala Nerus, Terengganu Darul Iman, Malaysia
  • Anis Fadhlina Institute of Food Security and Sustainable Agriculture, Universiti Malaysia Kelantan, 17600 Jeli, Kelantan.
  • Siti Nurazwa Zainol Proliv Life Sciences Sdn Bhd, D-1-15, Residensi Bistaria, Jln Ulu Kelang, Taman Ukay Bistari, 68000 Ampang, Selangor Darul Ehsan, Malaysia.
  • Archan Kumar Mamillapalli Aurigene Pharmaceutical Services Limited, Bollaram Road, Miyapur, Hyderabad-500 049, Telangana, India.
  • Vijayabalaji Venkatesan Aurigene Pharmaceutical Services Limited, Bollaram Road, Miyapur, Hyderabad-500 049, Telangana, India.
  • Rajesh Eswarappa Aurigene Pharmaceutical Services Limited, Bollaram Road, Miyapur, Hyderabad-500 049, Telangana, India.
  • Renuka Pillai Aurigene Pharmaceutical Services Limited, Bollaram Road, Miyapur, Hyderabad-500 049, Telangana, India.
  • Fadzilah Adibah Abdul Majid Institute of Marine Biotechnology, Universiti Malaysia Terengganu, 21030 Kuala Nerus, Terengganu Darul Iman, Malaysia
Keywords: Gallic acid, Syzygium polyanthum, aqueous extract, pharmacokinetic

Abstract

In this study, Syzygium polyanthum was standardized against gallic acid (GA), and a complete pharmacokinetic test was conducted using in vitro and in vivo models against this phytochemical. High-performance liquid chromatography showed that GA is a major phytochemical in aqueous extract of S. polyanthum. It exhibited a low equilibrium solubility and physiochemical stability at pH 2.0 and 7.4, but it deteriorated rapidly at pH 9.2. It showed low permeability toward Caco-2 intestinal absorption with eight times slower absorption in oral than intravenous administration. GA was unstable in mouse, rat, and dog plasma sera with in vitro half-lives (t1/2) of 60, 53, and 56 min, respectively, but was relatively stable in human plasma serum (t1/2 = 185 min). Approximately 5.6% of GA (10 µM) bound to the human plasma proteins. GA was stable in mouse, rat, dog, and human microsomal extracts with in vitro microsomal intrinsic clearance values of 72, 68, 6, and 22 µL/min/mg, respectively. GA selectively inhibited or stimulated the activity of the tested CYP450 enzymes. The in vivo oral bioavailability of GA was 54%, with short elimination half-life and a high volume of distribution. Thus, the mention pharmacokinetic features of GA must be considered during the development of GA-based products to yield the optimum dosage and pharmacological effect.

References

Abdelwahed, A., Bouhlel, I., Skandrani, I., Valenti, K., Kadri, M., Guiraud, P., Steiman, R., Mariotte, A.M., Ghedira, K., Laporte, F. and Dijoux-Franca, M.G. (2007). Study of antimutagenic and antioxidant activities of Gallic acid and 1, 2, 3, 4, 6-pentagalloylglucose from Pistacia lentiscus: Confirmation by microarray expression profiling. Chemico-biological interactions, 165(1),1-13.
Ali, A.M., Mooi, L.Y., Yih, K.Y., Norhanom, A.W., Saleh, K., Lajis, N.H., Yazid, A.M., Ahmad, F.B.H. and Prasad, U. (2000). Anti-tumor promoting activity of some malaysian traditional vegetable (ulam) extracts by immunoblotting analysis of Raji cells. Natural Product Sciences, 6(3), pp.147-150.
Alias, N., Leow, T. C., Ali, M. S. M., Tajudin, A. A., Salleh, A. B., & Rnzra, R. (2017). Anti-obesity potential of selected tropical plants via pancreatic lipase inhibition. Advances in Obesity, Weight Management & Control, 6(4).
Avriliyanti, F., Suparwitri, S., & Alhasyimi, A. A. (2017). Rinsing effect of 60% bay leaf (Syzygium polyanthum wight) aqueous decoction in inhibiting the accumulation of dental plaque during fixed orthodontic treatment. Dental Journal (Majalah Kedokteran Gigi), 50(1), 1-5.
Aytac, Z., Kusku, S. I., Durgun, E., & Uyar, T. (2016). Encapsulation of gallic acid/cyclodextrin inclusion complex in electrospun polylactic acid nanofibers: Release behavior and antioxidant activity of gallic acid. Materials Science and Engineering: C, 63, 231-239.
Badhani, B., Sharma, N., & Kakkar, R. (2015). Gallic acid: a versatile antioxidant with promising therapeutic and industrial applications. RSC Adv 5: 27540–27557.
Calvo, R., Lukas, J. C., Rodriguez, M., Leal, N., & Suarez, E. (2006). The role of unbound drug in pharmacokinetics/pharmacodynamics and in therapy. Current pharmaceutical design, 12(8), 977-987.
Chen, C., Zhou, H., Guan, C., Zhang, H., Li, Y., Jiang, X., Dong, Z., Tao, Y., Du, J., Wang, S. and Zhang, T. (2020). Applicability of free drug hypothesis to drugs with good membrane permeability that are not efflux transporter substrates: A microdialysis study in rats. Pharmacology research & perspectives, 8(2), e00575.
Chuysinuan, P., Chimnoi, N., Techasakul, S., & Supaphol, P. (2009). Gallic acid‐loaded electrospun poly (L‐lactic acid) fiber mats and their release characteristic. Macromolecular Chemistry and Physics, 210(10), 814-822.
Daily, E. B., & Aquilante, C. L. (2009). Cytochrome P450 2C8 pharmacogenetics: a review of clinical studies. Pharmacogenomics, 10(9), 1489-1510.
Darusman, L. K., Wahyuni, W. T., & Alwi, F. (2013). Acetylcholinesterase inhibition and antioxidant activity of Syzygium cumini, S. aromaticum and S. polyanthum from Indonesia. Journal of Biological Sciences, 13(5), 412.
Fahmi, H., Nurazwa, S., Kumar, A., Sai, M., & Adibah, F. (2020). Favourable drug-lead pharmacokinetic features for designing Gallic acid standardized Syzygium polyanthum aqueous extract-based product. RSC Adv. 10, 34581-34594
Faralli, A., Shekarforoush, E., Mendes, A. C., & Chronakis, I. S. (2019). Enhanced transepithelial permeation of gallic acid and (−)-epigallocatechin gallate across human intestinal caco-2 cells using electrospun xanthan nanofibers. Pharmaceutics, 11(4), 155.
Fitri, K. S. A., Ramdhani, D., & Mustarichie, R. (2017). Comparative study on activities of anti-bacillary dysentery Shigella dysenteriae of Syzygium polyanthum and Dracaena angustifolia leaves ethanol extracts. Asian J Pharm Clin Res, 10(2), 348-352.
Friedman, M., & Jürgens, H. S. (2000). Effect of pH on the stability of plant phenolic compounds. Journal of agricultural and food chemistry, 48(6), 2101-2110.
Groschwitz, K. R., & Hogan, S. P. (2009). Intestinal barrier function: molecular regulation and disease pathogenesis. Journal of allergy and clinical immunology, 124(1), 3-20.
Grosvenor, P. W., Gothard, P. K., McWilliam, N. C., Supriono, A., & Gray, D. O. (1995). Medicinal plants from riau province, sumatra, Indonesia. Part 1: uses. Journal of ethnopharmacology, 45(2), 75-95.
Grosvenor, P. W., Supriono, A., & Gray, D. O. (1995). Medicinal plants from Riau Province, Sumatra, Indonesia. Part 2: antibacterial and antifungal activity. Journal of ethnopharmacology, 45(2), 97-111.
Hamad, A., Mahardika, M. G. P., Yuliani, I., & Hartanti, D. (2017). Chemical constituents and antimicrobial activities of essential oils of Syzygium polyanthum and Syzygium aromaticum. Rasayan Journal of Chemistry, 10(2), 564-569.
Har, L., & Intan, S. I. (2012). Antioxidant activity, total phenolics and total flavonoids of Syzygium polyanthum (Wight) Walp leaves. International Journal of Medicinal and Aromatic Plants, 2(2), 219-228.
Hefti, F. F. (2008). Requirements for a lead compound to become a clinical candidate. BMC neuroscience, 9(3), 1-7.
Hidayati, M. D., Ersam, T., Shimizu, K., & Fatmawati, S. (2017). Antioxidant activity of Syzygium polyanthum extracts. Indonesian Journal of Chemistry, 17(1), 49-53.
Honda, S., Ishida, R., Hidaka, K., & Masuda, T. (2019). Stability of polyphenols under alkaline conditions and the formation of a xanthine oxidase inhibitor from gallic acid in a solution at pH 7.4. Food Science and Technology Research, 25(1), 123-129.
Ismail, A., & Ahmad, W. A. N. W. (2017). Autonomic receptors and nitric-oxide involvements in mediating vasorelaxation effect induced by Syzygium polyanthum leaves extract. Pharmacognosy research, 9(Suppl 1), S9.
Ismail, A., & Ahmad, W. A. N. W. (2019). Syzygium polyanthum (Wight) Walp: a potential phytomedicine. Pharmacognosy Journal, 11(2).
Ismail, A., Mohamed, M., Sulaiman, S. A., & Wan Ahmad, W. A. N. (2013). Autonomic nervous system mediates the hypotensive effects of aqueous and residual methanolic extracts of Syzygium polyanthum (Wight) Walp. var. polyanthum leaves in anaesthetized rats. Evidence-Based Complementary and Alternative Medicine, 2013.
Ismail, A., Rahim, E. N. A. A., Omar, M. N., & Ahmad, W. A. N. W. (2020). Antihypertensive Assay-Guided Fractionation of Syzygium polyanthum Leaves and Phenolics Profile Analysis Using LCQTOF/MS. Pharmacognosy Journal, 12(6s).
Ismail, A., Ramli, N. S., Mohamed, M., & Ahmad, W. A. N. W. (2018). Acute and sub-acute antihypertensive effects of Syzygium polyanthum leaf extracts with determination of gallic acid using HPLC analysis. Pharmacognosy Journal, 10(4).
Ismail, H. F., Hashim, Z., Soon, W. T., Ab Rahman, N. S., Zainudin, A. N., & Majid, F. A. A. (2017). Comparative study of herbal plants on the phenolic and flavonoid content, antioxidant activities and toxicity on cells and zebrafish embryo. Journal of traditional and complementary medicine, 7(4), 452-465.
Jing, X., Hou, Y., Hallett, W., Sahajwalla, C. G., & Ji, P. (2019). Key physicochemical characteristics influencing adme properties of therapeutic proteins. Therapeutic Enzymes: Function and Clinical Implications, 115-129.
Karimi-Khouzani, O., Heidarian, E., & Amini, S. A. (2017). Anti-inflammatory and ameliorative effects of gallic acid on fluoxetine-induced oxidative stress and liver damage in rats. Pharmacological reports, 69(4), 830-835.
Kato, E., Nakagomi, R., Gunawan-Puteri, M. D., & Kawabata, J. (2013). Identification of hydroxychavicol and its dimers, the lipase inhibitors contained in the Indonesian spice, Eugenia polyantha. Food chemistry, 136(3-4), 1239-1242.
Khorsandi, K., Kianmehr, Z., & Hosseinzadeh, R. (2020). Anti-cancer effect of gallic acid in presence of low level laser irradiation: ROS production and induction of apoptosis and ferroptosis. Cancer cell international, 20(1), 1-14.
Kok-Yong, S., Lawrence, L. (2015). Drug distribution and drug elimination. Basic pharmacokinetic concepts and some clinical applications, 99-116.
Konishi, Y., Kobayashi, S., & Shimizu, M. (2003). Transepithelial transport of p-coumaric acid and gallic acid in Caco-2 cell monolayers. Bioscience, biotechnology, and biochemistry, 67(11), 2317-2324.
Konsoula, R., & Jung, M. (2008). In vitro plasma stability, permeability and solubility of mercaptoacetamide histone deacetylase inhibitors. International journal of pharmaceutics, 361(1-2), 19-25.
Kusuma, I. W., Kuspradini, H., Arung, E. T., Aryani, F., Min, Y. H., Kim, J. S., & Kim, Y. U. (2011). Biological activity and phytochemical analysis of three Indonesian medicinal plants, Murraya koenigii, Syzygium polyanthum and Zingiber purpurea. Journal of Acupuncture and Meridian Studies, 4(1), 75-79.
Lelono, R. A., Tachibana, S., & Itoh, K. (2009). In vitro antioxidative activities and polyphenol content of Eugenia polyantha Wight grown in Indonesia. Pakistan journal of biological sciences: PJBS, 12(24), 1564-1570.
Malik, A. (2013). Antidiarrheal Acitivity of Ethanolik Extract of Bay Leaves (Syzygium polianthum (Weight.) Walp.). International Research Journal of Pharmacy (IRJP), 4(4).
Mao, X., Wu, L.F., Zhao, H.J., Liang, W.Y., Chen, W.J., Han, S.X., Qi, Q., Cui, Y.P., Li, S., Yang, G.H. and Shao, Y.Y. (2016). Transport of corilagin, gallic acid, and ellagic acid from Fructus phyllanthi tannin fraction in Caco-2 cell monolayers. Evidence-Based Complementary and Alternative Medicine. 9205379-9205379.
Maya, S., Prakash, T., & Madhu, K. (2018). Assessment of neuroprotective effects of Gallic acid against glutamate-induced neurotoxicity in primary rat cortex neuronal culture. Neurochemistry international, 121, 50-58.
Ménard, S., Cerf-Bensussan, N., & Heyman, M. (2010). Multiple facets of intestinal permeability and epithelial handling of dietary antigens. Mucosal Immunol 3: 247–259. Link: http://bit. ly/37h4xGi.
Mohamed, S., Saka, S., El‐Sharkawy, S. H., Ali, A. M., & Muid, S. (1996). Antimycotic screening of 58 Malaysian plants against plant pathogens. Pesticide science, 47(3), 259-264.
Orveda, 2021. Visibly brightening & skin perfecting masque. (https://orveda.com/visibly-brightening-skin-perfecting-masque, accessed 22 april 2021).
Othman, A., Mukhtar, N. J., Ismail, N. S., & Chang, S. K. (2014). Phenolics, flavonoids content and antioxidant activities of 4 Malaysian herbal plants. International Food Research Journal, 21(2), 759.
Perumal, S., Mahmud, R., Piaru, S. P., Cai, L. W., & Ramanathan, S. (2012). Potential antiradical activity and cytotoxicity assessment of Ziziphus mauritiana and Syzygium polyanthum. International Journal of Pharmacology, 8(6), 535-541.
Peterson, C. T., Denniston, K., & Chopra, D. (2017). Therapeutic uses of Triphala in Ayurvedic medicine. The Journal of Alternative and Complementary Medicine, 23(8), 607-614.
Phacebioactive, 2021. (https://www.phacebioactive.com/products/illuminating-serum, accessed 22 april 2021).
Phiriyawirut, M., & Phaechamud, T. (2012). Gallic acid-loaded cellulose acetate electrospun nanofibers: thermal properties, mechanical properties, and drug release behavior.
Priscilla, D. H., & Prince, P. S. M. (2009). Cardioprotective effect of gallic acid on cardiac troponin-T, cardiac marker enzymes, lipid peroxidation products and antioxidants in experimentally induced myocardial infarction in Wistar rats. Chemico-biological interactions, 179(2-3), 118-124.
Rashidi, L., Vasheghani-Farahani, E., Soleimani, M., Atashi, A., Rostami, K., Gangi, F., Fallahpour, M. and Tahouri, M.T., 2014. A cellular uptake and cytotoxicity properties study of gallic acid-loaded mesoporous silica nanoparticles on Caco-2 cells. Journal of nanoparticle research, 16(3), pp.1-14.
Safriani, N., Arpi, N., & Erfiza, N. M. (2015). Potency of curry (Murayya koeniigi) and salam (Eugenia polyantha) leaves as natural antioxidant sources. Pakistan Journal of Nutrition, 14(3), 131.
Sang, S., Lambert, J.D., Tian, S., Hong, J., Hou, Z., Ryu, J.H., Stark, R.E., Rosen, R.T., Huang, M.T., Yang, C.S. and Ho, C.T. (2004). Enzymatic synthesis of tea theaflavin derivatives and their anti-inflammatory and cytotoxic activities. Bioorganic & medicinal chemistry, 12(2), 459-467.
Shahrzad, S., Aoyagi, K., Winter, A., Koyama, A., & Bitsch, I. (2001). Pharmacokinetics of gallic acid and its relative bioavailability from tea in healthy humans. The Journal of Nutrition, 131(4), 1207-1210.
Smith, D. A., Di, L., & Kerns, E. H. (2010). The effect of plasma protein binding on in vivo efficacy: misconceptions in drug discovery. Nature reviews Drug discovery, 9(12), 929-939.
Sorrentino, E., Succi, M., Tipaldi, L., Pannella, G., Maiuro, L., Sturchio, M., Coppola, R. and Tremonte, P. (2018). Antimicrobial activity of gallic acid against food-related Pseudomonas strains and its use as biocontrol tool to improve the shelf life of fresh black truffles. International journal of food microbiology, 266, pp.183-189.
Sulistiyani, S. Falah, W.T. Wahyuni, T. Sugahara, S. Tachibana and Syaefudin , 2014. Cellular Mechanism of the Cytotoxic Effect of Extracts from Syzygium polyanthum Leaves. American Journal of Drug Discovery and Development, 4: 90-101.
Sumono, A., & Sd, A. W. (2008). The use of bay leaf (Eugenia polyantha Wight) in dentistry. Dental Journal (Majalah Kedokteran Gigi), 41(3), 147-150.
Wang, R., Ma, L., Weng, D., Yao, J., Liu, X., & Jin, F. (2016). Gallic acid induces apoptosis and enhances the anticancer effects of cisplatin in human small cell lung cancer H446 cell line via the ROS-dependent mitochondrial apoptotic pathway. Oncology reports, 35(5), 3075-3083.
Watson, R. R., & Preedy, V. R. (Eds.). (2019). Bioactive food as dietary interventions for diabetes. Academic Press.
Widharna, R. M., Tamayanti, W. D., Hendriati, L., Hamid, I. S., & Widjajakusuma, E. C. (2015). Antidiabetic effect of the aqueous extract mixture of Andrographis paniculata and Syzygium polyanthum leaf. European Journal of Medicinal Plants, 82-91.
Widyawati, T., Purnawan, W. W., Atangwho, I. J., Yusoff, N. A., Ahmad, M., & Asmawi, M. Z. (2015a). Anti-diabetic activity of Syzygium polyanthum (Wight) leaf extract, the most commonly used herb among diabetic patients in Medan, North Sumatera, Indonesia. International Journal of Pharmaceutical Sciences and Research, 6(4), 1698.
Widyawati, T., Roslan, N. A. B., Yusoff, N. A., Asmawi, M. Z., & Ahamad, M. (2016). The evaluation of antioxidant and free radical scavenging activities of Eugenia polyantha leaves extracts. International Journal of Chemistry Technology Research, 9(9), 465-471.
Widyawati, T., Yusoff, N. A., Asmawi, M. Z., & Ahmad, M. (2015b). Antihyperglycemic effect of methanol extract of Syzygium polyanthum (Wight.) leaf in streptozotocin-induced diabetic rats. Nutrients, 7(9), 7764-7780.
Williams, J. M., Duckworth, C. A., Burkitt, M. D., Watson, A. J. M., Campbell, B. J., & Pritchard, D. M. (2015). Epithelial cell shedding and barrier function: a matter of life and death at the small intestinal villus tip. Veterinary pathology, 52(3), 445-455.
Wong, S. P., Leong, L. P., & Koh, J. H. W. (2006). Antioxidant activities of aqueous extracts of selected plants. Food chemistry, 99(4), 775-783.
Youhanna, S., & Lauschke, V. M. (2021). The past, present and future of intestinal in vitro cell systems for drug absorption studies. Journal of Pharmaceutical Sciences, 110(1), 50-65.
Zanger, U. M., & Klein, K. (2013). Pharmacogenetics of cytochrome P450 2B6 (CYP2B6): advances on polymorphisms, mechanisms, and clinical relevance. Frontiers in genetics, 4, 24.
Zanger, U. M., & Schwab, M. (2013). Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacology & therapeutics, 138(1), 103-141.
Zhou, D., Yang, Q., Tian, T., Chang, Y., Li, Y., Duan, L.R., Li, H. and Wang, S.W. (2020). Gastroprotective effect of gallic acid against ethanol-induced gastric ulcer in rats: Involvement of the Nrf2/HO-1 signaling and anti-apoptosis role. Biomedicine & Pharmacotherapy, 126, p.110075.
Zong, L., Inoue, M., Nose, M., Kojima, K., Sakaguchi, N., Isuzugawa, K., Takeda, T. And Ogihara, Y. (1999). Metabolic fate of gallic acid orally administered to rats. Biological and Pharmaceutical Bulletin, 22(3), 326-329.
Published
2022-12-20
How to Cite
Hassan Fahmi Ismail, Fadhlina, A., Siti Nurazwa Zainol, Archan Kumar Mamillapalli, Vijayabalaji Venkatesan, Rajesh Eswarappa, Renuka Pillai, & Fadzilah Adibah Abdul Majid. (2022). Favourable drug-lead pharmacokinetic features for designing gallic acid-standardized Syzygium polyanthum aqueous extract-based product. Indonesian Journal of Pharmacy, 33(4), 666–679. https://doi.org/10.22146/ijp.3639
Section
Research Article