Artichoke and silymarin versus functional gallbladder and sphincter of Oddi disorders: feasibility and applicability

The main pathogenetic links in the occurrence of functional gallbladder (GB) and sphincter of Oddi (SO) disorders are considered to be a disorder of the brain-gastrointestinal tract axis, impaired GB and biliary motility, changes in the physicochemical properties of bile, and visceral hypersensitivity. The current Rome IV criteria (2016) do not provide for active pharmacotherapy of biliary and gastrointestinal disorders, preferring endoscopic interventions. Opinions are expressed about the need and feasibility of additional use of agents that can affect the main pathogenetic links of this functional pathology. The current evidence base confirms the effectiveness of artichoke and silybinin in enhancing choleresis, reducing biliary tract muscle spasm and visceral hypersensitivity, modifying the composition of bile acids, and reducing the activity of inflammatory liver damage. When prescribing Afosil nutraceutical, one can expect to see the improvement of lipid metabolism in patients with functional disorders of the gastrointestinal tract and SO. Mild weight loss along with mild hypotensive, hypoglycaemic and antidepressant effects of Afosil can be considered as an additional benefit of the drug, which is important in the management of patients with functional and metabolic pathology.

References

1. Li J., Jin X., Ren J. et al. Global burden of gallbladder and biliary diseases: A systematic analysis for the Global Burden of Disease Study 2019. J. Gastroenterol. Hepatol. 2022; 37(7): 1389–1399. doi: 10.1111/jgh.15859.
2. Cotton P.B., Elta G.H., Carter C. et al. Rome IV. Gallbladder and Sphincter of Oddi Disorders. Gastroenterol. 2016; S0016-5085(16)00224-9.
3. Zeng H.Z., Yi H., He S. et al. Current treatment of biliary Sphincter of Oddi Dysfunction. Front. Med. (Lausanne). 2024; 11: 1380640. doi: 10.3389/fmed.2024.1380640.
4. FAOSTAT (2021) http://www.fao.org/statistics/en/.
5. Służały P., Paśko P., Galanty A. Natural Products as Hepatoprotective Agents-A Comprehensive Review of Clinical Trials. Plants (Basel). 2024; 13(14): 1985.
6. Direito R., Barbalho S.M., Sepodes B. et al. Plant-Derived Bioactive Compounds: Exploring Neuroprotective, Metabolic, and Hepatoprotective Effects for Health Promotion and Disease Prevention. Pharmaceutics. 2024; 16(5): 577.
7. Porro C., Benameur T., Cianciulli A. et al. Functional and Therapeutic Potential of Cynara scolymus in Health Benefits. Nutrients. 2024; 16(6): 872.
8. Feiden T., Valduga E., Zeni J. et al. Bioactive Compounds from Artichoke and Application Potential. Food Technol. Biotechnol. 2023; 61(3): 312–327.
9. Saénz Rodriguez T., García Giménez D., de la Puerta Vázquez R. Choleretic activity and biliary elimination of lipids and bile acids induced by an artichoke leaf extract in rats. Phytomedicine. 2002; 9(8):687–693.
10. Kirchhoff R., Beckers C., Kirchhoff G.M. et al. Increase in choleresis by means of artichoke extract. Phytomedicine. 1994; 1(2): 107–115.
11. Marakis G., Walker A.F., Middleton R.W. et al. Artichoke leaf extract reduces mild dyspepsia in an open study. Phytomedicine. 2002; 9(8): 694–699.
12. Holtmann G., Adam B., Haag S. et al. Efficacy of artichoke leaf extract in the treatment of patients with functional dyspepsia: a six-week placebo-controlled, double-blind, multicentre trial. Aliment. Pharmacol. Ther. 2003; 18(11–12): 1099–1105.
13. Bundy R., Walker A.F., Middleton R.W. et al. Artichoke leaf extract reduces symptoms of irritable bowel syndrome and improves quality of life in otherwise healthy volunteers suffering from concomitant dyspepsia: a subset analysis. J. Altern. Complement. Med. 2004; 10(4): 667–669. doi: 10.1089/acm.2004.10.667.
14. Báez G., Vargas C., Arancibia M. et al. Non-Chinese herbal medicines for functional dyspepsia. Cochrane Database Syst. Rev. 2023; 6(6): CD013323.
15. Liu S., Yi M., Qin J. et al. The increasing incidence and high body mass index-related burden of gallbladder and biliary diseases-A results from global burden of disease study 2019. Front. Med. (Lausanne). 2022; 9: 1002325.
16. Panahi Y., Kianpour P., Mohtashami R. et al. Efficacy of artichoke leaf extract in non-alcoholic fatty liver disease: A pilot double-blind randomized controlled trial. Phytother. Res. 2018; 32(7): 1382–1387. doi: 10.1002/ptr.6073.
17. Liu H., Li Y., Jin Y. et al. Effects of different natural products in patients with non-alcoholic fatty liver disease — A network meta-analysis of randomized controlled trials. Phytother. Res. 2024; 38(7): 3801–3824. doi: 10.1002/ptr.8182.
18. Kamel A.M., Farag M.A. Therapeutic Potential of Artichoke in the Treatment of Fatty Liver: A Systematic Review and Meta-Analysis. J. Med. Food. 2022; 25(10): 931–942.
19. Shahinfar H., Bazshahi E., Amini M. et al. Effects of artichoke leaf extract supplementation or artichoke juice consumption on lipid profile: A systematic review and dose-response meta-analysis of randomized controlled trials. Phytother. Res. 2021; 35(12): 6607–6623.
20. Osadnik T., Goławski M., Lewandowski P. et al. A network meta-analysis on the comparative effect of nutraceuticals on lipid profile in adults. Pharmacol. Res. 2022; 183: 106402.
21. Amini M.R., Sheikhhossein F., Alvani M. et al. Anti-hypertensive Effects of Artichoke Supplementation in Adults: A Systematic Review and Dose-response Meta-analysis of Randomized Controlled Trials. Clin. Nutr. Res. 2022; 11(3): 214–227.
22. Jaffar H.M., Al-Asmari F., Khan F. et al. Silymarin: Unveiling its pharmacological spectrum and therapeutic potential in liver diseases-A comprehensive narrative review. Food Sci. Nutr. 2024; 12(5): 3097–3111. doi: 10.1002/fsn3.4010.
23. Wang X., Zhang Z., Wu S.C. Health Benefits of Silybum marianum: Phytochemistry, Pharmacology, and Applications. J. Agric. Food Chem. 2020; 68(42): 11644–11664.
24. Bahmani M., Shirzad H., Rafieian S. et al. Silybum marianum: Beyond Hepatoprotection. J. Evid. Based Complementary Altern. Med. 2015; 20(4): 292–301.
25. Bai Y., Zhang J., Li J. et al. Silibinin, a commonly used therapeutic agent for non-alcohol fatty liver disease, functions through upregulating intestinal expression of fibroblast growth factor 15/19. Br. J. Pharmacol. 2024; 181(19): 3663–3684.
26. Yi M., Manzoor M., Yang M. et al. Silymarin targets the FXR protein through microbial metabolite 7-keto-deoxycholic acid to treat MASLD in obese mice. Phytomedicine. 2024; 133: 155947. doi: 10.1016/j.phymed.2024.155947.
27. Dhande D., Dhok A., Anjankar A. et al. Silymarin as an Antioxidant Therapy in Chronic Liver Diseases: A Comprehensive Review. Cureus. 2024; 16(8): e67083.
28. Li D., Zhang J., Jin Y. et al. Silibinin inhibits PM2.5-induced liver triglyceride accumulation through enhancing the function of mitochondrial Complexes I and II. Front. Pharmacol. 2024; 15: 1435230. doi: 10.3389/fphar.2024.1435230.
29. Dagli Gul A.S., Boyuk Ozcan G., Arihan O. Silibinin as a promising treatment for diabetes: Insights into behavioral and metabolic changes in an animal model. Food Sci. Nutr. 2024; 12(5): 3336–3345. doi: 10.1002/fsn3.3999.
30. Yan B., Zheng X., Chen X. et al. Silibinin Targeting Heat Shock Protein 90 Represents a Novel Approach to Alleviate Nonalcoholic Fatty Liver Disease by Simultaneously Lowering Hepatic Lipotoxicity and Enhancing Gut Barrier Function. ACS Pharmacology & Translational Science. 2024; 7(7): 2110–2124 .
31. Zhang X., Jiang Z., Jin X. et al. Efficacy of traditional Chinese medicine combined with Silibinin on nonalcoholic fatty liver disease: A meta-analysis and systematic review. Medicine (Baltimore). 2024; 103(5): e37052.
32. Li Z., Wu J., Zhao Y. et al. Natural products and dietary interventions on liver enzymes: an umbrella review and evidence map. Front. Nutr. 2024; 11:1300860.
33. Saller R., Brignoli R., Melzer J. et al. An updated systematic review with meta-analysis for the clinical evidence of silymarin. Forsch Kompl. 2008; 15(1): 9–20.
34. Wah Kheong C., Nik Mustapha N.R., Mahadeva S. A Randomized Trial of Silymarin for the Treatment of Nonalcoholic Steatohepatitis. Clin. Gastroenterol. Hepatol. 2017; 15(12): 1940–1949.e8. doi: 10.1016/j.cgh.2017.04.016.
35. Rostamian S., Heidari-Soureshjani S., Sherwin C. The Therapeutic Effect of Silymarin and Silibinin on Depression and Anxiety Disorders and Possible Mechanism in the Brain: A Systematic Review. Cent. Nerv. Syst. Agents Med. Chem. 2023; 23(2): 86–94.
36. Афосил®. compendium.com.ua.
37. Méndez-Sánchez N., Dibildox-Martinez M., Sosa-Noguera J. et al. Superior silybin bioavailability of silybin-phosphatidylcholine complex in oily-medium soft-gel capsules versus conventional silymarin tablets in healthy volunteers. BMC Pharmacol. Toxicol. 2019; 20(1): 5.
38. Abenavoli L., Greco M., Nazionale I. et al. Effects of Mediterranean diet supplemented with silybin-vitamin E-phospholipid complex in overweight patients with non-alcoholic fatty liver disease. Expert. Rev. Gastroenterol. Hepatol. 2015; 4: 519–527.
39. Loguercio C., Andreone P., Brisc C. et al. Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: a randomized controlled trial. Free Radic. Biol. Med. 2012; 52(9): 1658–1665.