Protective effects of Puriton^® on acute pancreatitis

Article information

J Korean Med. 2024;45(3):143-153

Publication date (electronic) : 2024 September 1

doi : https://doi.org/10.13048/jkm.24045

Dong-Uk Kim ¹^,²^,^§

, Bitna Kweon ^§

, Kwang-Ho Kim ⁷

, Gi-Sang Bae ¹^,²^,³^,

, Kyung Song ⁴^,⁵^,⁶^,

¹Department of Pharmacology, College of Korean Medicine, Wonkwang University

²Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University

³Research center of Traditional Korean medicine, Wonkwang University

⁴Department of Pharmacy, College of Pharmacy, Wonkwang University

⁵Institute of Pharmaceutical Research and Development, Wonkwang University

⁶Quantum NS, Co., Ltd., Iksan, Jeollabuk-do, 54538, Republic of Korea

⁷Kadesh, Inc., Garden Grove, CA 92841, USA

Correspondence to: Gi-Sang Bae, Department of Pharmacology, College of Korean Medicine, Wonkwang University, 460 Iksandae-ro, Iksan, 54538 Jeonbuk, South Korea, Tel: +82-63-850-6842, E-mail: baegs888@wku.ac.kr

Correspondence to: Kyung Song, College of Pharmacy, and Institute of Pharmaceutical Research and Development, Wonkwang University, 460 Iksandae-ro, Iksan, 54538, Republic of Korea, Tel: +82-63-850-6817, Fax: +82-63-853-6821, E-mail: kyungsong@wku.ac.kr

^§

These authors equally contributed.

Received 2024 July 23; Revised 2024 August 7; Accepted 2024 August 19.

Abstract

Objectives

Puriton^® is the electrolyte enriched water consisting of 31 essential minerals from biotite, kaolinite, montmorillonite, serpentine, and clinochlore, and vermiculite. It has been reported to be bactericidal and virucidal. However, the protective effect of Puriton^® against acute pancreatitis (AP) has not yet been studied. Therefore, we aimed to evaluate the protective effect of Puriton^® against cerulein-induced AP.

Methods

AP was induced by intraperitoneal injections of cerulein (50 μg/kg) hourly for 6 times. Puriton^® (100, 300, 500, or 700 μL) was administered orally 1 hour before the first cerulein injection. Mice were sacrificed 6 hours after the last cerulein injection. Pancreas, lung, and serum samples were quickly collected for further analysis.

Results

Administration of Puriton^® did not reduce the ratio of pancreas weight to body weight. However, the increased serum amylase and lipase were decreased in the Puriton^® administration group, and histological damage to pancreas and lung tissue was suppressed in the Puriton^® 100 and 300 μL administration groups, but not in the Puriton^® 500 and 700 μL administration groups. Additionally, among pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, the mRNA level of only IL-6 was decreased by Puriton^® administration.

Conclusion

In summary, we showed that the administration of Puriton^® improved the severity of cerulein-induced AP, suggesting the possibility of being an effective drug for AP.

Keywords: Puriton^®; Acute Pancreatitis (AP); Cytokine

Fig. 1

Effect of Puriton^® on pancreas weight/body weight (P.W./B.W.) ratio during cerulein-induced acute pancreatitis (AP). Data show the mean±S.E. for 9 mice for each group. Results are representative of three experiments. ^*p<0.05 vs control group, ^†p<0.05 vs cerulein treatment group.

Fig. 2

Effect of Puriton^® on the serum digestive enzymes during cerulein-induced AP. Serum (A) amylase and (B) lipase were measured as described in materials and methods. Data show the mean±S.E. for 9 mice for each group. Results are representative of three experiments. ^*p<0.05 vs control group, ^†p<0.05 vs cerulein treatment group.

Fig. 3

Effect of Puriton^® on morphological change of pancreas during cerulein-induced AP. (A) Representative hematoxylin & eosin (H&E)-stained sections of the pancreas. Histological scores for (B) edema and (C) inflammation. Data show the mean±S.E. for 9 mice for each group. Results are representative of three experiments. ^*p<0.05 vs control group, ^†p<0.05 vs cerulein treatment group.

Fig. 4

Effect of Puriton^® on morphological change of lung during cerulein-induced AP. (A) Representative hematoxylin & eosin (H&E)-stained sections of the pancreas. Histological scores for (B) alveolar membrane thickening and (C) inflammation. Data show the mean±S.E. for 9 mice for each group. Results are representative of three experiments. ^*p<0.05 vs control group, ^†p<0.05 vs cerulein treatment group.

Fig. 5

Effect of Puriton^® on the mRNA level of pro-inflammatory cytokines during cerulein-induced AP. The pro-inflammatory cytokines were detected by real time RT-PCR as described in materials and methods. Data show the mean±S.E. for 9 mice for each group. Results are representative of three experiments. ^*p<0.05 vs control group, ^†p<0.05 vs cerulein treatment group.

References

1. Iannuzzi J. P., King J. A., Leong J. H., Quan J., Windsor J. W., Tanyingoh D., et al. 2022;Global incidence of acute pancreatitis is increasing over time: A systematic review and meta-analysis. Gastroenterology 162(1):122–134. doi: 10.1053/j.gastro.2021.09.043.

2. Zheng Z., Ding Y.-X., Qu Y.-X., Cao F., Li F.. 2021;A narrative review of acute pancreatitis and its diagnosis, pathogenetic mechanism, and management. Annals of translational medicine 9(1)doi: 10.21037/atm-20-4802.

3. Petrov M. S., Yadav DJNrG.. hepatology. 2019;Global epidemiology and holistic prevention of pancreatitis. Nature reviews Gastroenterology & hepatology 16(3):175–184. doi: 10.1038/s41575-018-0087-5.

4. Mederos M. A., Reber H. A., Girgis M. D.. 2021;Acute pancreatitis: A review. Jama 325(4):382–390. doi: 10.1001/jama.2020.20317.

5. Lee J. K.. 2015;Recent advances in management of acute pancreatitis. The Korean Journal of Gastroenterology 66(3):135–143. doi: 10.4166/kjg.2015.66.3.135.

6. Kim M.-H., Choi M.-K.. 2013;Seven dietary minerals (ca, p, mg, fe, zn, cu, and mn) and their relationship with blood pressure and blood lipids in healthy adults with self-selected diet. Biological trace element research 153(69–75)doi: 10.1007/s12011-013-9656-1.

7. Hamasaki T., Teruya K., Katakura Y.. 2024;Effect of hita tenryo water™, a natural mineral water, on allergic symptoms induced by cedar in mice. Heliyon 10(5)doi: 10.1016/j.heliyon.2024.e26915.

8. Lee C.-Y., Lee C.-L.. 2021;Comparison of the improvement effect of deep ocean water with different mineral composition on the high fat diet-induced blood lipid and nonalcoholic fatty liver disease in a mouse model. Nutrients 13(5):1732. doi: 10.3390/nu13051732.

9. Li M., Guo K., He Y., Li H., Sun W., Yuan X., et al. 2024;Natural changbai mineral water reduces obesity risk through regulating metabolism and gut microbiome in a hyperuricemia male mouse model. Frontiers in Nutrition 11doi: 10.3389/fnut.2024.1308882.

10. Jin S.-E., Lee J. I., Hwang S.-J.. 2015;Case study of pharmaceutical ingredients derived from clay minerals. Economic Environmental Geology 48(3):221–229. doi: 10.9719/EEG.2015.48.3.221.

11. Balkrishna A., Solleti S. K., Singh H., Singh R., Sharma N., Varshney A.. 2021;Biotite-calx based traditional indian medicine sahastraputi-abhrak-bhasma prophylactically mitigates allergic airway inflammation in a mouse model of asthma by amending cytokine responses. Journal of Inflammation Research :4743–4760. doi: 10.2147/JIR.S313955.

12. Guo L., Liu Y., Han J., Zhu H., Wang X.. 2017;Effects of biotite v supplementation on growth performance and the immunological responses of weaned pigs after an escherichia coli lipopolysaccharide challenge. Livestock Science 195(112–117)doi: 10.1016/j.livsci.2016.12.003.

13. Long M., Liu Q., Wang D., Wang J., Zhang Y., Tang A., et al. 2021;A new nanoclay-based bifunctional hybrid fiber membrane with hemorrhage control and wound healing for emergency self-rescue. Materials Today Advances 12(100190)doi: 10.1016/j.mtadv.2021.100190.

14. Shen M., Zhang B., Wang M., Lv B.. 2020;Mica can alleviate tnbs-induced colitis in mice by reducing angiotensin ii and il-17a and increasing angiotensin-converting enzyme 2, angiotensin 1-7, and il-10. Mediators of Inflammation 2020;doi: 10.1155/2020/3070345.

15. Hong U.-S., Park C.-H., Han Y.-H., Kim D.-W., Jun C.-Y., Park S.-K., et al. 2003;2 cases of acute pancreatitis with oriental medical treatment. The Journal of Korean Oriental Internal Medicine 24(2):365–373.

16. Bok S.-H., Kim M.-H., Lee S.-Y., Bae C.-S., Lee M.-J., Kim K.-H., et al. 2020;Bactericidal and virucidal efficacies and safety of puriton^® . Processes 8(11):1481. doi: 10.3390/pr8111481.

17. Petrov M. S., Shanbhag S., Chakraborty M., Phillips A. R., Windsor J. A.. 2010;Organ failure and infection of pancreatic necrosis as determinants of mortality in patients with acute pancreatitis. Gastroenterology 139(3):813–820. doi: 10.1053/j.gastro.2010.06.010.

18. Ali U. A., Issa Y., Hagenaars J. C., Bakker O. J., van Goor H., Nieuwenhuijs V. B., et al. 2016;Risk of recurrent pancreatitis and progression to chronic pancreatitis after a first episode of acute pancreatitis. Clinical gastroenterology hepatology 14(5):738–746. doi: 10.1016/j.cgh.2015.12.040.

19. Kirkegård J., Cronin-Fenton D., Heide-Jørgensen U., Mortensen F. V.. 2018;Acute pancreatitis and pancreatic cancer risk: A nationwide matched-cohort study in denmark. Gastroenterology 154(6):1729–1736. doi: 10.1053/j.gastro.2018.02.011.

20. Kim S. C., Yang H. R.. 2013;Clinical efficacy of gabexate mesilate for acute pancreatitis in children. European journal of pediatrics 172(1483–1490)doi: 10.1007/s00431-013-2068-6.

21. McNally P. R.. 2010. Gi/liver secrets plus e-book Elsevier Health Sciences.

22. Zhou M.-T., Chen C.-S., Chen B.-C., Zhang Q.-Y., Andersson R.. 2010;Acute lung injury and ards in acute pancreatitis: Mechanisms and potential intervention. World journal of gastroenterology: WJG 16(17):2094. doi: 10.3748/wjg.v16.i17.2094.

23. Liu D., Wen L., Wang Z., Hai Y., Yang D., Zhang Y., et al. 2022;The mechanism of lung and intestinal injury in acute pancreatitis: A review. Frontiers in medicine 9:904078. doi: 10.3389/fmed.2022.904078.

24. Glaubitz J., Asgarbeik S., Lange R., Mazloum H., Elsheikh H., Weiss F. U., et al. 2023;Immune response mechanisms in acute and chronic pancreatitis: Strategies for therapeutic intervention. Frontiers in Immunology 14(1279539)doi: 10.3389/fimmu.2023.1279539.

25. Kany S., Vollrath J. T., Relja B.. 2019;Cytokines in inflammatory disease. International journal of molecular sciences 20(23):6008. doi: 10.3390/ijms20236008.

26. Malmstrøm M. L., Hansen M. B., Andersen A. M., Ersbøll A. K., Nielsen O. H., Jørgensen L. N., et al. 2012;Cytokines and organ failure in acute pancreatitis: Inflammatory response in acute pancreatitis. Pancreas 41(2):271–277. doi: 10.1097/MPA.0b013e3182240552.

27. Dugernier T. L., Laterre P.-F., Wittebole X., Roeseler J., Latinne D., Reynaert M. S., et al. 2003;Compartmentalization of the inflammatory response during acute pancreatitis: Correlation with local and systemic complications. American journal of respiratory critical care medicine 168(2):148–157. doi: 10.1164/rccm.2204019.

28. Rao S. A., Kunte A. R.. 2017;Interleukin-6: An early predictive marker for severity of acute pancreatitis. Indian Journal of Critical Care Medicine: Peer-reviewed, Official Publication of Indian Society of Critical Care Medicine 21(7):424. doi: 10.4103/ijccm.IJCCM_478_16.

29. Li J., Chen Z., Li L., Lai T., Peng H., Gui L., et al. 2022;Interleukin-6 is better than c-reactive protein for the prediction of infected pancreatic necrosis and mortality in patients with acute pancreatitis. Frontiers in Cellular Infection Microbiology 12:933221. doi: 10.3389/fcimb.2022.933221.

30. Kang M., Park K. S., Seo J. Y., Kim H.. 2011;Lycopene inhibits il-6 expression in cerulein-stimulated pancreatic acinar cells. Genes nutrition Research Practice 6(117–123)doi: 10.1007/s12263-010-0195-5.