A New Hope for the Treatment of Autoimmune Diseases: Piperine

Öz

Piper nigrum, which is mostly grown in tropical and subtropical regions and belongs to the "Piperaceae" family, is a plant considered as the "King of spices". Piperine, a natural compound responsible for the bitter taste of long pepper and black pepper, is an alkaloid found in P. nigrum. In addition to its use as a food preservative and a food ingredient, piperine is used in traditional medicine for its immunomodulatory, anticancer, antioxidant, neuroprotective and anti-inflammatory properties. Compounds derived from natural products such as P. nigrum and Piper longum have become the focus of numerous studies due to their use in the treatment of neurodegenerative, cancer, autoimmune and chronic diseases. Our aim in this review is to evaluate the therapeutic utility of piperine compound in autoimmune diseases.

Anahtar Kelimeler

• Black Pepper
• Piperine
• Alkaloid
• Autoimmunity
• Autoimmune Diseases

Otoimmün Hastalıkların Tedavisi İçin Yeni Bir Umut: Piperin

Öz

Çoğunlukla tropikal ve subtropikal bölgelerde yetiştirilen ve "Piperaceae" familyasında yer alan Piper nigrum, ‘‘Baharatların kralı’’ olarak kabul edilen bir bitkidir. Uzun biberin ve karabiberin acı tadından sorumlu olan ve doğal bir bileşik olarak tanımlanan piperin, P. nigrum’da bulunan bir alkaloiddir. Piperinin, gıda koruyucusu ve bir gıda bileşeni olarak kullanılmasının yanı sıra immünomodülatör, antikanser, antioksidan, nöroprotektif ve antienflamatuvar gibi özellikleri nedeniyle geleneksel tıpta kullanılmaktadır. P. nigrum ve Piper longum gibi doğal ürünlerden elde edilen bileşiklerin nörodejeneratif, kanser, otoimmün ve kronik hastalıkların tedavisinde kullanılması nedeniyle çok sayıda araştırmanın odak noktası haline gelmiştir. Bu derlemedeki amacımız, otoimmün hastalıklarda piperin bileşiğinin terapötik olarak kullanılabilirliğini değerlendirmektir.

Anahtar Kelimeler

• Karabiber
• Piperin
• Alkaloid
• Otoimmünite
• Otoimmün Hastalıklar

Kaynakça

1. 1. Shukla, R., Rai, N., Singhai, M., & Singhai, A. K. (2018). A magical medicinal fruit of piper Nigrum. World Journal of Pharmaceutical Research, 7(8), 418-425.
2. 2. Gurinderdeep, S. (2017). Piperine: a remarkable marker with intense biological activity. International Journal of Pharmacognosy and Chinese Medicine, 1(4), 122.
3. 3. Vargas-Uricoechea H. (2023). Molecular Mechanisms in Autoimmune Thyroid Disease. Cells, 12(6), 918. https://doi.org/10.3390/cells12060918
4. 4. Shakerian, L., Kolahdooz, H., Garousi, M., Keyvani, V., Kheder, R. K., Faraj, T. A., ... & Esmaeili, S. A. (2022). IL-33/ST2 axis in autoimmune disease. Cytokine, 158, 156015.
5. 5. Shen, P., Lin, W., Deng, X., Ba, X., Han, L., Chen, Z., Qin, K., Huang, Y., & Tu, S. (2021). Potential Implications of Quercetin in Autoimmune Diseases. Frontiers in immunology, 12, 689044. https://doi.org/10.3389/fimmu.2021.689044
6. 6. Srivastava, A. K., & Singh, V. K. (2017). Biological action of Piper nigrum-the king of spices. European Journal of biological research, 7(3), 223-233.
7. 7. Emer, Z. (2005). Tane ve Toz karabiber Üzerine Ozonun Dekontaminasyon Yöntemi Olarak Etkisi. Yüksek Lisans Tezi, Mühendislik ve Fen Bilimleri Enstitüsü, Gebze İleri teknoloji Enstitüsü, Kocaeli.
8. 8. Hirasa, K., & Takemasa, M. (1998). Spice science and technology. CRC Press.

9. 9. Siddiqui, B. S., Begum, S., Gulzar, T., & Noor, F. (1997). An amide from fruits of Piper nigrum. Phytochemistry, 45(8), 1617-1619.
10. 10. Alodeani, E. A., Arshad, M., & Izhari, M. A. (2015). Drug likeness and physicochemical properties evaluation of the alkaloids found in black pepper: piperine, piperidine, piperettine and piperanine. European Journal of Pharma and medical research, 2(6), 296-301.
11. 11. Kayamba, F., Dunnill, C., Hamnett, D. J., Rodríguez, A., Georgopoulos, N. T., & Moran, W. J. (2013). Piperolein B, isopiperolein B and piperamide C9: 1 (8E): total synthesis and cytotoxicities. RSC advances, 3(37), 16681-16685.
12. 12. Park, K. R., Leem, H. H., Cho, M., Kang, S. W., & Yun, H. M. (2020). Effects of the amide alkaloid piperyline on apoptosis, autophagy, and differentiation of pre-osteoblasts. Phytomedicine, 79, 153347.
13. 13. Vasavirama, K., & Upender, M. (2014). Piperine: a valuable alkaloid from piper species. Int J Pharm Pharm Sci, 6(4), 34-8.
14. 14. Haq, I. U., Imran, M., Nadeem, M., Tufail, T., Gondal, T. A., & Mubarak, M. S. (2021). Piperine: A review of its biological effects. Phytotherapy research, 35(2), 680-700.
15. 15. Imran, M., Samal, M., Qadir, A., Ali, A., & Mir, S. R. (2022). A critical review on the extraction and pharmacotherapeutic activity of piperine. Polymers in Medicine, 52(1), 31-36.
16. 16. Lu J-J, Bao J-L, Chen X-P, Huang M, Wang Y-T (2012) Alkaloids isolated from natural herbs as the anticancer agents. Evid Based Complement Alternat Med 2012.
17. 17. Roberts MF (2013) Alkaloids: biochemistry, ecology, and medicinal applications. Springer, New York
18. 18. Bribi N (2018) Pharmacological activity of alkaloids: a review. Asian J Bot 1. https://doi. org/10.63019/ajb.v1i2.467
19. 19. Yamada Y, Kokabu Y, Chaki K, Yoshimoto T, Ohgaki M, Yoshida SNK, Koyama T, Sato F, (2011) Isoquinoline alkaloid biosynthesis is regulated by a unique bHLH-type transcription factor in Coptis japonica, Plant Cell Physiol. 52, 1131-1141.
20. 20. Tiring, G., Satar, S. ve Özkaya, O. 2021. Sekonder Metabolitler. Bursa Uludag Üniv. Ziraat Fak. Derg., 35(1), 203- 215.
21. 21. Hussain G, Rasul A, Anwar H, Aziz N, Razzaq A, Wei W, Ali M, Li J, Li X (2018) Role of plant derived alkaloids and their mechanism in neurodegenerative disorders. Int J Biol Sci 14(3):341
22. 22. Gurinderdeep, S. (2017). Piperine: a remarkable marker with intense biological activity. International Journal of Pharmacognosy and Chinese Medicine, 1(4), 122.
23. 23. Ahmad, N., Fazal, H., Abbasi, B. H., Farooq, S., Ali, M., & Khan, M. A. (2012). Biological role of Piper nigrum L.(black pepper): A review. Asian Pacific Journal of Tropical Biomedicine, 2(3), S1945–S1953.
24. 24. Derosa, G., Maffioli, P., & Sahebkar, A. (2016). Piperine and its role in chronic diseases. Anti-inflammatory nutraceuticals and chronic diseases, 173-184.
25. 25. Quijia, C.R. and M. Chorilli, Characteristics, Biological Properties and Analytical Methods of Piperine: A Review. Critical Reviews in Analytical Chemistry, (2020). 50(1): p. 62-77.
26. 26. Parthasarathy VA., et al. “Chemistry of spices”. London: CABI (2008).
27. 27. Srinivasan, K. (2007). Black pepper and its pungent principle-piperine: a review of diverse physiological effects. Critical reviews in food science and nutrition, 47(8), 735-748.
28. 28. Surya D, Vijayakumar RS, Nalini N (2004) Antioxidant efficacy of black pepper (Piper nigrum L.) and piperine in rats with high fat diet induced oxidative stress. Redox Rep 9(2): 105-110.
29. 29. Sunila E and Kuttan G. “Immunomodulatory and antitumor activity of Piper longum Linn. and piperine”. Journal of Ethnopharmacology 90 (2004): 339-346.
30. 30. Hritcu L, Noumedem JA, Cioanca O, Hancianu M, Kuete V, et al. (2014) Methanolic extract of Piper nigrum fruits improves memory impairment by decreasing brain oxidative stress in amyloid beta(1-42) rat model of Alzheimer’s disease. See comment in PubMed Commons below Cell MolNeurobiol 34: 437- 449.
31. 31. Bolat Z B, İşlek Z, Demir B N, Yılmaz E N, Şahin F, Ucisik M H, 2020, Curcumin-and Piperine-Loaded Emulsomes as Combinational Treatment Approach Enhance the Anticancer Activity of Curcumin on HTC116 Colorectal Cancer Model, Frontiers in Bioengineering and Biotechnology, 8, 1–21.
32. 32. Yamaguchi, Y., Kasukabe, T., & Kumakura, S. (2018). Piperlongumine rapidly induces the death of human pancreatic cancer cells mainly through the induction of ferroptosis. International journal of oncology, 52(3), 1011-1022.
33. 33. İSKİN, A. E., & BUDAK, F. (2023). Enfeksiyon Hastalıklarında Ferroptozun Rolü. Uludağ Üniversitesi Tıp Fakültesi Dergisi, 49(3), 425-438.
34. 34. VURMAZ, A., BOZKURT, F., & AKBULUT, M. D. (2020). F64A TARAFINDAN ALZHEİMER BENZERİ DEMANS OLUŞTURULAN RATLARDA BETAİN ve PİPERİNİN ETKİSİ. Kocatepe Tıp Dergisi, 21(2), 183-190.
35. 35. Kim, J., Lee, K. P., Lee, D. W., & Lim, K. (2017). Piperine enhances carbohydrate/fat metabolism in skeletal muscle during acute exercise in mice. Nutrition & metabolism, 14(1), 1-8.
36. 36. Evan Prince S, Aayesha N, Mahima V, Mahaboobkhan R (2013) Analgesic, antipyretic and ulcerogenic effects of piperine: an active ingredient of pepper. J Pharm Sci Res 5(10):203–206
37. 37. Das S., Paul P., Dastidar D.G., Chakraborty P., Chatterjee S., Sarkar S., Maiti D., Tribedi P. Piperine exhibits potential antibiofilm activity against Pseudomonas aeruginosa by accumulating reactive oxygen species, affecting cell surface hydrophobicity and quorum sensing. Appl. Biochem. Biotech. 2023;195:3229–3256. doi: 10.1007/s12010-022-04280-1. [PubMed] [CrossRef] [Google Scholar] [Ref list]
38. 38. Choi S, Choi Y, Choi Y, Kim S, Jang J, Park T (2013) Piperine reverses high fat diet-induced hepatic steatosis and insulin resistance in mice. Food Chem 141(4):3627–3635
39. 39. Dong Y, Huihui Z, Li C. Piperine inhibit inflammation, alveolar bone loss and collagen fibers breakdown in a rat periodontitis model. J Periodontal Res 2015;50:758 –65. DOI: 10.1111/jre.12262.
40. 40. Sharma S, Kalia NP, Suden P, Chauhan PS, Kumar M. Protective efficacy of piperine against Mycobacterium tuberculosis. Tuberculosis (Edinb). 2014;94(4):389–396. doi:10.1016/j.tube.2014.04.007
41. 41. Aswar U, Shintre S, Chepurwar S, Aswar M. Antiallergic effect of piperine on ovalbumin - induced allergic rhinitis in mice. Pharm Biol 2015;53:1358 –66. DOI: 10.3109/13880209.2014.982299
42. 42. Doucette CD, Rodgers G, Liwski RS, Hoskin DW (2015) Piperine from black pepper inhibits activation-induced proliferation and effector function of T lymphocytes. J Cell Biochem 116(11):2577–2588
43. 43. Zhai, W. J., Zhang, Z. B., Xu, N. N., Guo, Y. F., Qiu, C., Li, C. Y., ... & Guo, M. Y. (2016). Piperine plays an anti-inflammatory role in Staphylococcus aureus endometritis by inhibiting activation of NF-κB and MAPK pathways in mice. Evidence-Based Complementary and Alternative Medicine, 2016.
44. 44. Buagaew, A., & Poomipark, N. (2020). Protective effect of piperine from Piper chaba fruits on LPS-induced inflammation in human intestinal cell line. Journal of Medicinal Plants Research, 14(9), 438-444.
45. 45. Ying X, Yu K, Chen X, et al. (2013) Piperine inhibits LPS induced expression of inflammatory mediators in RAW 264.7 cells. Cell Immunol. 285: 49-54.
46. 46. Bajad, S., Coumar, M., Khajuria, R., Suri, O. P., & Bedi, K. L. (2003). Characterization of a new rat urinary metabolite of piperine by LC/NMR/MS studies. European journal of pharmaceutical sciences, 19(5), 413-421.
47. 47. Piyachaturawat, P., Glinsukon, T., & Toskulkao, C. (1983). Acute and subacute toxicity of piperine in mice, rats and hamsters. Toxicology letters, 16(3-4), 351-359.
48. 48. Rosenblum, M. D., Remedios, K. A., & Abbas, A. K. (2015). Mechanisms of human autoimmunity. The Journal of clinical investigation, 125(6), 2228–2233. https://doi.org/10.1172/JCI78088
49. 49. Xiang, Y., Zhang, M., Jiang, D., Su, Q., & Shi, J. (2023). The role of inflammation in autoimmune disease: a therapeutic target. Frontiers in immunology, 14, 1267091. https://doi.org/10.3389/fimmu.2023.1267091
50. 50. Goswami, T. K., Singh, M., Dhawan, M., Mitra, S., Emran, T. B., Rabaan, A. A., Mutair, A. A., Alawi, Z. A., Alhumaid, S., & Dhama, K. (2022). Regulatory T cells (Tregs) and their therapeutic potential against autoimmune disorders - Advances and challenges. Human vaccines & immunotherapeutics, 18(1), 2035117. https://doi.org/10.1080/21645515.2022.2035117
51. 51. Grebinoski, S., & Vignali, D. A. (2020). Inhibitory receptor agonists: the future of autoimmune disease therapeutics?. Current opinion in immunology, 67, 1–9. https://doi.org/10.1016/j.coi.2020.06.001
52. 52. Ring, G. H., & Lakkis, F. G. (1999). Breakdown of self-tolerance and the pathogenesis of autoimmunity. Seminars in nephrology, 19(1), 25–33.
53. 53. Anaya JM, Castiblanco J, Lessard CJ. Non-HLA genes and autoimmune diseases. In: Anaya JM, Shoenfeld Y, Rojas-Villarraga A, et al., editors. Autoimmunity: From Bench to Bedside [Internet]. Bogota (Colombia): El Rosario University Press; 2013 Jul 18. Chapter 18. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459446/
54. 54. Brostof J, G, K. Scadding Male, I.M.Roith. Autoimmune diseases .A general intraduction. Clinical Immunology.Gower Med.Publishing London 1991.
55. 55. Nagafuchi, Y., Yanaoka, H., & Fujio, K. (2022). Lessons From Transcriptome Analysis of Autoimmune Diseases. Frontiers in immunology, 13, 857269. https://doi.org/10.3389/fimmu.2022.857269
56. 56. Lahita R. G. (2023). Sex and gender influence on immunity and autoimmunity. Frontiers in immunology, 14, 1142723. https://doi.org/10.3389/fimmu.2023.1142723
57. 57. Radu, A. F., & Bungau, S. G. (2021). Management of rheumatoid arthritis: an overview. Cells, 10(11), 2857.
58. 58. Bang, J. S., Oh, D. H., Choi, H. M., Sur, B. J., Lim, S. J., Kim, J. Y., ... & Kim, K. S. (2009). Anti-inflammatory and antiarthritic effects of piperine in human interleukin 1β-stimulated fibroblast-like synoviocytes and in rat arthritis models. Arthritis research & therapy, 11(2), 1-9.
59. 59. Murunikkara, V., Pragasam, S. J., Kodandaraman, G., Sabina, E. P., & Rasool, M. (2012). Anti-inflammatory effect of piperine in adjuvant-induced arthritic rats—a biochemical approach. Inflammation, 35, 1348-1356.
60. 60. Yende, S. R., Sannapuri, V. D., Vyawahare, N. S., & Harle, U. N. (2010). Antirheumatoid activity of aqueous extract of Piper longum on freunds adjuvant-induced arthritis in rats. Int J Pharm Sci Res, 1(9), 129-133.
61. 61. Bhalekar M.R., Madgulkar A.R., Desale P.S., Marium G. Formulation of piperine solid lipid nanoparticles (SLN) for treatment of rheumatoid arthritis. Drug. Dev. Ind Pharm. 2017;43(6):1003–1010. [PubMed] [Google Scholar] [Ref list]
62. 62. Umar, S., Sarwar, A. H. M. G., Umar, K., Ahmad, N., Sajad, M., Ahmad, S., ... & Khan, H. A. (2013). Piperine ameliorates oxidative stress, inflammation and histological outcome in collagen induced arthritis. Cellular Immunology, 284(1-2), 51-59.
63. 63. Baito, Q. N., Jaafar, H. M., & Mohammad, T. A. M. (2023). Piperine suppresses inflammatory fibroblast-like synoviocytes derived from rheumatoid arthritis patients Via NF-κB inhibition. Cellular Immunology, 391, 104752.
64. 64. Wootla, B., Eriguchi, M., & Rodriguez, M. (2012). Is multiple sclerosis an autoimmune disease?. Autoimmune diseases, 2012.
65. 65. Liu, Z., Hu, Q., Wang, W., Lu, S., Wu, D., Ze, S., ... & Huang, J. (2020). Natural product piperine alleviates experimental allergic encephalomyelitis in mice by targeting dihydroorotate dehydrogenase. Biochemical Pharmacology, 177, 114000.
66. 66. Roshanbakhsh, H., Salmani, M. E., Dehghan, S., Nazari, A., Javan, M., & Pourabdolhossein, F. (2020). Piperine ameliorated memory impairment and myelin damage in lysolecethin induced hippocampal demyelination. Life sciences, 253, 117671.
67. 67. Nasrnezhad, R., Halalkhor, S., Sadeghi, F., & Pourabdolhossein, F. (2021). Piperine improves experimental autoimmune encephalomyelitis (EAE) in lewis rats through its neuroprotective, anti-inflammatory, and antioxidant effects. Molecular neurobiology, 58(11), 5473-5493.
68. 68. Espinosa G, Cervera R. Lupus eritematoso sistémico In: Cervera R, Espinosa G, Ramos M, Hernández-Rodríguez J, Cid MC, eds. Enfermedades Autoinmunes Sistémicas. Diagnóstico y Tratamiento. Madrid, Spain: Editorial Médica Panamericana S.A., 2014:1–27.
69. 69. Hoover PJ, Costenbader KH. ABD'li romatologların bakış açısından lupus nefritinin epidemiyolojisi ve yönetimine ilişkin bilgiler . Böbrek İnt . 2016; 90 ( 3 ):487–92. doi: 10.1016/j.kint.2016.03.042. [ PMC ücretsiz makalesi ] [ PubMed ] [ CrossRef ] [ Google Akademik ]
70. 70. Peng, X., Yang, T., Liu, G., Liu, H., Peng, Y., & He, L. (2018). Piperine ameliorated lupus nephritis by targeting AMPK-mediated activation of NLRP3 inflammasome. International immunopharmacology, 65, 448-457.
71. 71. Pannu, N., & Bhatnagar, A. (2020). Combinatorial therapeutic effect of resveratrol and piperine on murine model of systemic lupus erythematosus. Inflammopharmacology, 28, 401-424.
72. 72. Yan, R., Liang, X., & Hu, J. (2023). miR-141-3p alleviates ulcerative colitis by targeting SUGT1 to inhibit colonic epithelial cell pyroptosis. Autoimmunity, 56(1), 2220988.
73. 73. Gupta, R. A., Motiwala, M. N., Dumore, N. G., Danao, K. R., & Ganjare, A. B. (2015). Effect of piperine on inhibition of FFA induced TLR4 mediated inflammation and amelioration of acetic acid induced ulcerative colitis in mice. Journal of ethnopharmacology, 164, 239-246.
74. 74. Li, Q., Zhai, W., Jiang, Q., Huang, R., Liu, L., Dai, J., ... & Wu, Q. (2015). Curcumin–piperine mixtures in self-microemulsifying drug delivery system for ulcerative colitis therapy. International journal of pharmaceutics, 490(1-2), 22-31.
75. 75. Guo, G., Shi, F., Zhu, J., Shao, Y., Gong, W., Zhou, G., ... & Shi, W. (2020). Piperine, a functional food alkaloid, exhibits inhibitory potential against TNBS-induced colitis via the inhibition of IκB-α/NF-κB and induces tight junction protein (claudin-1, occludin, and ZO-1) signaling pathway in experimental mice. Human & Experimental Toxicology, 39(4), 477-491.
76. 76. Parkkola, A., Laine, A. P., Karhunen, M., Härkönen, T., Ryhänen, S. J., Ilonen, J., Knip, M., & Finnish Pediatric Diabetes Register (2017). HLA and non-HLA genes and familial predisposition to autoimmune diseases in families with a child affected by type 1 diabetes. PloS one, 12(11), e0188402. https://doi.org/10.1371/journal.pone.0188402