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Abstract

Dragon fruit, known as Hylocereus undantus (HU), has traditionally been utilized in Banyuwangi, East Java, Indonesia, for addressing gout and rheumatism. Despite its empirical use, there is a lack of reported pharmacological research on this plant. This study aimed to explore the properties of HU extract in treating hyperuricemia, inflammation, and pain. Adenine-potassium oxonate-induced mice were employed to evaluate anti-hyperuricemia activity, measuring uric acid, blood urea nitrogen (BUN), and creatinine serum levels. Carrageenan-induced paw edema in rats was used to assess anti-inflammatory activity, while acetic acid-induced abdominal writhing and hot plate tests were conducted to investigate anti-nociceptive effects. The results revealed that administering HU extracts at 400 mg/kg notably reduced uric acid levels (p<0.01). Moreover, doses of 100, 200, and 400 mg/kg showed significant reductions in BUN and creatinine serum levels (p<0.0001). At a dose of 400 mg/kg, HU extract exhibited a significant anti-inflammatory effect two hours post-administration, manifesting a 15% and 26% reduction in paw edema for male and female mice, respectively (p<0.005, p<0.001). Additionally, doses of 200 and 400 mg/kg demonstrated anti-nociceptive effects in acetic acid-induced abdominal constriction. Furthermore, at 400 mg/kg, the extract exhibited anti-nociceptive activity (p<0.001) three hours post-administration using the hot plate method. This study underscores the potent anti-hyperuricemia, anti-inflammatory, and anti-nociceptive properties of HU. The implications of these findings contribute significantly to comprehending the therapeutic potential of HU.

References

Bakshi, J., Lathar, P., Mehra, M., Grewal, S., Dhingra, D., & Kumari, S. (2022). Evaluation of anti-inflammatory response of berberine-loaded gum nanocomplexes in carrageenan-induced acute paw edema in rats. Pharmacological Reports : PR, 74(2), 392–405.

Benn, C. L., Dua, P., Gurrell, R., Loudon, P., Pike, A., Storer, R. I., & Vangjeli, C. (2018). Physiology of hyperuricemia and urate-lowering treatments. Frontiers in Medicine, 5, 160.

Chang, Y. H., Chiang, Y. F., Chen, H. Y., Huang, Y. J., Wang, K. L., Hong, Y. H., Ali, M., Shieh, T. M., & Hsia, S. M. (2021). Anti-inflammatory and anti- hyperuricemic effects of chrysin on a high fructose corn syrup-induced hyperuricemia rat model via the amelioration of urate transporters and inhibition of NLRP3 inflammasome signaling pathway. Antioxidants (Basel, Switzerland), 10(4), 564.

Chen, Y., Li, C., Duan, S., Yuan, X., Liang, J., & Hou, S. (2019). Curcumin attenuates potassium oxonate- induced hyperuricemia and kidney inflammation in mice. Biomedicine & pharmacotherapy = Biomedecine & Pharmacotherapie, 118, 109195.

Choi E. M. (2007). Antinociceptive and antiinflammatory activities of pine (Pinus densiflora) pollen extract. Phytotherapy Research : PTR, 21(5), 471–475.

Danve, A., Sehra, S. T., & Neogi, T. (2021). Role of diet in hyperuricemia and gout. Best practice & research. Clinical Rheumatology, 35(4), 101723.

Guan, J., Huang, X. Q., Dong, J. L., Lu, H. M., Lin, Y. W., Liu, M., Yi, Z. B., Wu, L. M., Huang, Y. M., & Lan, T. (2020). A novel mouse model of hyperuricemia and gouty nephropathy. Chinese Medical Journal, 133(16), 2012–2014.

Guo, Y., Jiang, Q., Gui, D., & Wang, N. (2015). Chinese Herbal Formulas Si-Wu-Tang and Er-Miao-San Synergistically Ameliorated hyperuricemia and renal impairment in rats induced by adenine and potassium oxonate. Cellular Physiology and Biochemistry: International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, 37(4), 1491–1502.

Higgs, J., Wasowski, C., Loscalzo, L. M., & Marder, M. (2013). In vitro binding affinities of a series of flavonoids for μ-opioid receptors. Antinociceptive effect of the synthetic flavonoid 3,3-dibromoflavanone in mice. Neuropharmacology, 72, 9–19.

Joshi, M., & Prabhakar, B. (2020). Phytoconstituents and pharmaco-therapeutic benefits of pitaya: A wonder fruit. Journal of Food Biochemistry, 44(7), e13260.

Liao, W., Liu, W., Yan, Y., Li, L., Tong, J., Huang, Y., Guo, S., Jiang, W., & Fu, S. (2022). Hylocereus undatus flower extract suppresses OVA-induced allergic asthma in BALb/c mice by reducing airway inflammation and modulating gut microbiota. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 153, 113476.

Lin, Z. M., Liu, Y. T., Huang, Y. T., Yang, X. Q., Zhu, F. H., Tang, W., Zhao, W. M., He, S. J., & Zuo, J. P. (2021). Anti-nociceptive, anti-inflammatory, and anti-arthritic activities of pregnane glycosides from the root bark of Periploca sepium bunge. Journal of Ethnopharmacology, 265, 113345.

Jimenez-Garcia, S. N., Garcia-Mier, L., Ramirez- Gomez, X. S., Aguirre-Becerra, H., Escobar-Ortiz, A., Contreras-Medina, L. M., Garcia-Trejo, J. F., & Feregrino-Perez, A. A. (2022). Pitahaya peel: A by- product with great phytochemical potential, biological activity, and functional application. Molecules (Basel, Switzerland), 27(16), 5339.

Li, S., Li, L., Yan, H., Jiang, X., Hu, W., Han, N., & Wang, D. (2019). Antigouty arthritis and antihyperuricemia properties of celery seed extracts in rodent models. Molecular Medicine Reports, 20(5), 4623–4633.

Motevalian, M., Shiri, M., Shiri, S., Shiri, Z., & Shiri, H. (2017). Anti-inflammatory activity of Elaeagnus angustifolia fruit extract on rat paw edema. Journal of Basic and Clinical Physiology and Pharmacology, 28(4), 377–381.

Naz, I., Masoud, M. S., Chauhdary, Z., Shah, M. A., & Panichayupakaranant, P. (2022). Anti-inflammatory potential of berberine-rich extract via modulation of inflammation biomarkers. Journal of Food Biochemistry, 46(12), e14389.

Nemirovsky, A., Chen, L., Zelman, V., & Jurna, I. (2001). The antinociceptive effect of the combination of spinal morphine with systemic morphine or buprenorphine. Anesthesia and Analgesia, 93(1), 197–203.

Nguyen, T. D., Thuong, P. T., Hwang, I. H., Hoang, T. K., Nguyen, M. K., Nguyen, H. A., & Na, M. (2017). Anti- hyperuricemic, anti-inflammatory and analgesic effects of Siegesbeckia orientalis L. resulting from the fraction with high phenolic content. BMC Complementary and Alternative Medicine, 17(1), 191.

Orlandi, L., Vilela, F. C., Santa-Cecília, F. V., Dias, D. F., Alves-da-Silva, G., & Giusti-Paiva, A. (2011). Anti-inflammatory and antinociceptive effects of the stem bark of Byrsonima intermedia A. Juss. Journal of Ethnopharmacology, 137(3), 1469–1476.

Pang, X., Zhao, S., Zhang, M., Cai, L., Zhang, Y., & Li, X. (2021). Catechin gallate acts as a key metabolite induced by trypsin in Hylocereus undatus during storage indicated by omics. Plant Physiology and Biochemistry : PPB, 158, 497–507.

Pascual, E., Addadi, L., Andrés, M., & Sivera, F. (2015). Mechanisms of crystal formation in gout-a structural approach. Nature reviews. Rheumatology, 11(12), 725–730.

Ragab, G., Elshahaly, M., & Bardin, T. (2017). Gout: An old disease in new perspective - A review. Journal of Advanced Research, 8(5), 495–511.

Riaz, M., Al Kury, L. T., Atzaz, N., Alattar, A., Alshaman, R., Shah, F. A., & Li, S. (2022). Carvacrol alleviates hyperuricemia-induced oxidative stress and inflammation by modulating the NLRP3/NF-κB Pathwayt. Drug Design, Development and Therapy, 16, 1159–1170.

Salam, H. S., Tawfik, M. M., Elnagar, M. R., Mohammed, H. A., Zarka, M. A., & Awad, N. S. (2022). Potential apoptotic activities of Hylocereus undatus peel and pulp extracts in MCF-7 and Caco-2 cancer cell lines. Plants (Basel, Switzerland), 11(17), 2192.

Serafini, M., Peluso, I., & Raguzzini, A. (2010). Flavonoids as anti-inflammatory agents. The Proceedings of the Nutrition Society, 69(3), 273–278.

Tang, W., Li, W., Yang, Y., Lin, X., Wang, L., Li, C., & Yang, R. (2021). Phenolic compounds profile and antioxidant capacity of pitahaya fruit peel from two red- skinned species (Hylocereus polyrhizus and Hylocereus undatus). Foods (Basel, Switzerland), 10(6), 1183.

Uddin, G., Rauf, A., Siddiqui, B. S., Muhammad, N., Khan, A., & Shah, S. U. (2014). Anti-nociceptive, anti-inflammatory, and sedative activities of the extracts and chemical constituents of Diospyros lotus L. Phytomedicine: International Journal of Phytotherapy And Phytopharmacology, 21(7), 954–959.

Wu, X., Wang, Y., Huang, X. J., Fan, C. L., Wang, G. C., Zhang, X. Q., Zhang, Q. W., & Ye, W. C. (2011). Three new glycosides from Hylocereus undatus. Journal of Asian natural products research, 13(8), 728–733.

Yahfoufi, N., Alsadi, N., Jambi, M., & Matar, C. (2018). The immunomodulatory and anti-inflammatory role of polyphenols. Nutrients, 10(11), 1618.

Yanai, H., Adachi, H., Hakoshima, M., & Katsuyama, H. (2021). Molecular biological and clinical understanding of the pathophysiology and treatments of hyperuricemia and its association with metabolic syndrome, cardiovascular diseases and chronic kidney disease. International Journal of Molecular Sciences, 22(17), 9221.

Yin, C., Liu, B., Wang, P., Li, X., Li, Y., Zheng, X., Tai, Y., Wang, C., & Liu, B. (2020). Eucalyptol alleviates inflammation and pain responses in a mouse model of gout arthritis. British Journal of Pharmacology, 177(9), 2042–2057.

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