Abstract :

Atopic dermatitis (AD) presents formidable challenges in Veterinary Dermatology due to its persistent nature and diverse clinical manifestations, including itching, redness, swelling, and skin lesions. Despite advancements in therapeutic interventions like topical corticosteroids and immunomodulatory agents, a significant portion of AD patients continue to struggle with persistent symptoms and frequent flare-ups.

This study aimed to explore the effectiveness of Curcuma longa L. (CL) and Terminalia chebula Retz. (TC) alone and in combination in alleviating AD-like symptoms. A total of 54 Swiss albino mice (6 normal; 48 DNCB-treated) were divided into nine groups. Group A served as the normal control, while Group B had AD-like symptoms induced through repeated application of 2,4-dinitrochlorobenzene (DNCB) on the ear and dorsal skin (positive control). From the 14^th day onwards, Group C received standard Dexamethasone treatment at 3mg, Group D was administered Curcuma longa L. extract at 100mg, and Group E received Terminalia chebula Retz. Extract at 100mg. Groups F through H received varying concentrations (50mg, 100mg, and 200mg) of both extracts in combination, while the vehicle Carbopol was topically applied in Group I for two weeks to assess their anti-pruritic effects.

Results indicated that both Curcuma Longa and Terminalia Chebula extracts, either individually or combined, alleviated DNCB-induced AD-like symptoms, demonstrated by improvements in body weight gain, reductions in skin lesions, dermatitis scores, ear thickness, and total leukocyte count values. Histopathological analysis revealed that the combination of Curcuma Longa and Terminalia Chebula extracts at 100mg and 200mg doses reduced inflammatory cell infiltration into DNCB-induced skin lesions. Moreover, this combination also decreased the DNCB-induced elevation of Th2 cytokines interleukin (IL)-4 and Th1 cytokines IFN-γ. These findings suggest that combining Curcuma Longa and Terminalia Chebula extracts holds promise as a therapeutic approach for managing atopic dermatitis.

---

Keywords :

Atopic dermatitis, curcuma longa, curcumin, DNCB, haritaki, mice, Terminalia chebula.

---

References :

1. Abraham Fikru Mechesso, Seung-Jin Lee, Na-Hye Park, Jin-Yoon Kim, Zi-Eum Im, Joo-Won Suh and Seung-Chun Park. Mechesso. BMC Preventive effects of a novel herbal mixture on atopic dermatitis-like skin lesions in BALB/C mice. Complementary and Alternative Medicine (2019) 19:25
2. Aziz, S. J., and Zeman-Pocrnich, C. E. (2022). Tissue processing. Immunohistochemistry and Immunocytochemistry: Methods and Protocols, 47-63.
3. Bönisch, C., Irmler, M., Brachthäuser, L., Neff, F., Bamberger, M. T., Marschall, S., and Beckers, J. (2016). Dexamethasone treatment alters insulin, leptin, and adiponectin levels in male mice as observed in DIO but does not lead to alterations of metabolic phenotypes in the offspring. Mammalian Genome, 27, 17-28.
4. Benjamin, M. M. (2001). Outline of Clinical Veterinary Pathology. USA: Colorado StateUniversity.
5. Bernard, F. X., Morel, F., Camus, M., Pedretti, N., Barrault, C., Garnier, J., and Lecron, J. C. (2012). Keratinocytes under fire of proinflammatory cytokines: bona fide innate immune cells involved in the physiopathology of chronic atopic dermatitis and psoriasis. Journal of Allergy, 2012.
6. Cardiff, R. D., Miller, C. H., & Munn, R. J. (2014). Manual hematoxylin and eosin staining of mouse tissue sections. Cold Spring Harbor Protocols, 2014(6), pdb-prot073411.
7. Cronin, J. R. (2003). Curcumin: Old spice is a new medicine. Alternative & complementary therapies, 9(1), 34-38.
8. Chandrasekaran, C. V., Sundarajan, K., Edwin, J. R., Gururaja, G. M., Mundkinajeddu, D., and Agarwal, A. (2013). Immune-stimulatory and anti-inflammatory activities of Curcuma longa extract and its polysaccharide fraction. Pharmacognosy Research, 5(2), 71.
9. Chen, L., Martinez, O., Overbergh, L., Mathieu, C., Prabhakar, B. S., and Chan, L. S. (2004). Early up-regulation of Th2 cytokines and late surge of Th1 cytokines in an Atopic Dermatitis model. Clinical & Experimental Immunology, 138(3), 375-387
10. Chen, L., Martinez, O., Overbergh, L., Mathieu, C., Prabhakar, B. S., and Chan, L. S. (2004). Early up-regulation of Th2 cytokines and late surge of Th1 cytokines in an Atopic Dermatitis model. Clinical & Experimental Immunology, 138(3), 375-387.
11. Cameron Melainie, Joel J. Gagnier, Christine V. Little, Tessa J. Parsons, Anette Blümle, Sigrun Chrubasik (2009). Evidence of Effectiveness of Herbal Medicinal Products in the Treatment of Arthritis. Phytotherapy research, 23 (12): 1647-1662.
12. Hwang, D. H., Koh, P. O., Kang, C., and Kim, E. (2021). Rosa davurica Pall. improves DNCB-induced Atopic Dermatitis in mice and regulates TNF-Alpa/IFN-gamma-induced skin inflammatory responses in HaCaT cells. Phytomedicine, 91, 153708.
13. Kam-Lun Hon, Ting Fan Leung, Ho Chung Yau, Thomas Chan (2012) Paradoxical use of oral and topical steroids in steroid-phobic patients resorting to traditional Chinese medicines, 8: 263-267.
14. Yves Henrotin, Christelle Sanchez, Marc Balligand.(2005): Pharmaceutical and nutraceutical management of canine osteoarthritis: Present and future perspectives. The Veterinary Journal, Volume 170, Issue 1, July 2005, Pages 113-123
15. John F. Innes. (2004). Nutraceuticals for osteoarthritis: what is the evidence?, The North American Veterinary Conference – 2004 Proceedings:774-775.
16. Lee, Y. S., Ryu, H. W., Yang, W. K., Park, M. H., Park, Y. C., Kim, D. Y., and Kim, S. H. (2021). A combination of Olea europaea leaf extract and Spirodela polyrhiza extract alleviates atopic dermatitis by modulating immune balance and skin barrier function in a 1-chloro-2, 4-dinitrobenzene-induced murine model. Phytomedicine, 82, 153407
17. Kim, H., Kim, J. R., Kang, H., Choi, J., Yang, H., Lee, P., and Lee, K. W. (2014). 7, 8, 4′-Trihydroxyisoflavone attenuates DNCB-induced atopic dermatitis-like symptoms in NC/Nga mice. PloS one, 9(8), e104938.
18. Kim, J., Park, S., Jeon, B. S., Jang, W. S., Lee, S. J., Son, Y., and Lee, S. S. (2016). Therapeutic effect of topical application of curcumin during treatment of radiation burns in a mini-pig model. Journal of Veterinary Science, 17(4), 435-444.
19. Kim, S. J. (2018). The Inhibitory Effect of Gooseberry on DNCB-induced Atopic Dermatitis in vivo and in vitro. Biomedical Science Letters, 24(4), 349-356.
20. Kimura, T., and Doi, K. (1999). Dorsal skin reactions of hairless dogs to topical treatment with corticosteroids. Toxicologic Pathology, 27(5), 528-535.
21. Jami, M. S. I., Sultana, Z., Ali, M. E., Begum, M. M., and Haque, M. M. (2014). Evaluation of analgesic and anti-inflammatory activities on ethanolic extract of Terminalia chebula fruits in experimental animal models. American Journal of Plant Sciences, 2014.
22. Macedo, A. G., Krug, A. L. O., Souza, L. M., Martuscelli, A. M., Constantino, P. B., Zago, A. S., and Amaral, S. L. (2016). Time-course changes of catabolic proteins following muscle atrophy induced by dexamethasone. Steroids, 107, 30-36.
23. Sharma, S., Sethi, G. S., and Naura, A. S. (2020). Curcumin ameliorates ovalbumin-induced Atopic Dermatitis and blocks the progression of atopic march in mice. Inflammation, 43, 358-369.
24. Sorg, D. A., and Buckner, B. (1964). A simple method of obtaining venous blood from small laboratory animals. Proceedings of the Society for Experimental Biology and Medicine, 115(4), 1131-1132.
25. Suryawati, N., Wardhana, M., Bakta, I. M., and Jawi, M. (2022). Moisturizing Nanoemulgel of Turmeric (Curcuma longa) Rhizome Extract Ameliorates Atopic Dermatitis-like Skin Lesions in Mice Model through Thymic Stromal Lymphopoietin, Interleukin-13, and Interleukin-17. Biomolecular and Health Science Journal, 5(2), 81-87.
26. Wang, Y., Zhang, P., Zhang, J., and Hong, T. (2022). Inhibitory Effect of Bisdemethoxycurcumin on DNCB-Induced Atopic Dermatitis in Mice. Molecules, 28(1), 293.
27. Zhang, E. Y., Chen, A. Y., and Zhu, B. T. (2009). Mechanism of dinitro chlorobenzene induced dermatitis in mice: role of specific antibodies in pathogenesis. PLoS One, 4(11), e7703
28. Zhang, R., Zhang, H., Shao, S., Shen, Y., Xiao, F., Sun, J., and Yan, M. (2022). Compound traditional Chinese medicine Dermatitis ointment ameliorates inflammatory responses and dysregulation of itch-related molecules in Atopic Dermatitis. Chinese Medicine, 17, 1-19.
29. Zhao, H., Jiang, X., and Chu, W. (2020). Shifts in the gut microbiota of mice in response to dexamethasone administration. International Microbiology, 23, 565-573.