Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Phytotherapeutic Potential of Medicinal Plants for Atopic Dermatitis: Centella asiatica, Clinacanthus nutans, Senna alata, and Coccinia grandis

  • Thitiluck Swangsri (Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University) ;
  • Naowarat Saralamba (Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University)
  • Received : 2025.06.23
  • Accepted : 2026.02.12
  • Published : 2026.05.01
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Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disorder with significant global health implications, particularly in low-resource settings. In many Asian countries, traditional herbal medicine remains an integral part of healthcare and presents promising alternatives for managing AD. This review examines the therapeutic potential of four ethnomedicinal plants; Centella asiatica, Clinacanthus nutans, Senna alata, and Coccinia grandis, focusing on their anti-inflammatory, antimicrobial, and antioxidant activities. Evidence from preclinical and clinical studies highlights key bioactive compounds and underlying mechanisms, demonstrating their efficacy in alleviating AD symptoms and supporting skin barrier restoration. Comparative analysis suggests complementary and potentially synergistic effects across these species, targeting multiple aspects of AD pathophysiology. However, translation into clinical practice is constrained by inconsistent formulations, limited human trials, bioavailability challenges, and regulatory variability. Future directions include the development of standardized extracts, nanotechnology-based delivery systems, integration with conventional therapies, omics-driven precision medicine, and harmonized regulatory frameworks. Collectively, these strategies outline a therapeutic development pipeline for advancing plant-based interventions for AD from traditional use to clinical application.

Keywords

Acknowledgement

This study was supported by Mahidol University under the "New Discovery and Frontier Research Grant" (Grant No. NDFR 22/2563).

References

  1. Abo, K. A., Fred-Jaiyesimi, A. A. and Jaiyesimi, A. E. (2008) Ethnobotanical studies of medicinal plants used in the management of diabetes mellitus in South Western Nigeria. J. Ethnopharmacol. 115, 67-71. https://doi.org/10.1016/j.jep.2007.09.005
  2. Adedayo, O. A. W., Moo-Young, M., Snieckus, V., Patil, P. A. and Kolawole, D. O. (2001) Phytochemistry and antibacterial activity of Senna alata flower. Pharm. Biol. 39, 408-412. https://doi.org/10.1076/phbi.39.6.408.5880
  3. Adtani, P. N., Narasimhan, M., Punnoose, A. M. and Kambalachenu, H. R. (2017) Antifibrotic effect of Centellaasiatica Linn and asiatic acid on arecoline-induced fibrosis in human buccal fibroblasts. J. Investig. Clin. Dent. 8, e12208.
  4. Alam, A., Ferdosh, S., Ghafoor, K., Hakim, A., Juraimi, A. S., Khatib, A. and Sarker, Z. I. (2016) Clinacanthus nutans: a review of the medicinal uses, pharmacology and phytochemistry. Asian Pac. J. Trop. Med. 9, 402-409. https://doi.org/10.1016/j.apjtm.2016.03.011
  5. Albrahim, T., Alnasser, M. M., Al-Anazi, M. R., ALKahtani, M. D., Al kahtani, S. and Al-Qahtani, A. A. (2020) Potential anti-inflammatory and anti-apoptotic effect of Cocciniagrandisplant extract in LPS stimulated THP-1 cells. Environ. Sci. Pollut. Res. Int. 27, 21892-218904. https://doi.org/10.1007/s11356-020-08445-5
  6. Aliyu, A., Shaari, M. R., Ahmad Sayuti, N. S., Reduan, M. F. H., Sithambaram, S., Noordin, M. M., Shaari, K. and Hamzah, H. (2020) Subacute oral administration of Clinacanthus nutans ethanolic leaf extract induced liver and kidney toxicities in ICR mice. Molecules 25, 2631. https://doi.org/10.3390/molecules25112631
  7. Alnour, T. M. S., Ahmed-Abakur, E. H., Elssaig, E. H., Abuduhier, F. M. and Ullah, M. F. (2022) Antimicrobial synergistic effects of dietary flavonoids rutin and quercetin in combination with antibiotics gentamicin and ceftriaxone against E. coli (MDR) and P. mirabilis (XDR) strains isolated from human infections: implications for food medicine interactions. Ital. J. Food Sci. 34, 34-42. https://doi.org/10.15586/ijfs.v34i2.2196
  8. Atanu, F. O., Rotimi, D., Ilesanmi, O. B., Al Malki, J. S., Batiha, G. E. and Idakwoji, P. A. (2022) Hydroethanolic extracts of Senna alata leaves possess antimalarial effects and reverse haematological and biochemical perturbation in Plasmodium berghei-infected mice. J. Evid. Based Integr. Med. 27, 2515690X221116407.
  9. Aung, W. W., Panich, K., Watthanophas, S., Naridsirikul, S., Ponphaiboon, J., Krongrawa, W. Kulpicheswanich, P., Limmatvapirat, S. and Limmatvapirat, C. (2023) Preparation of bioactive de-chlorophyll rhein-rich Senna alata extract. Antibiotics (Basel) 12, 181. https://doi.org/10.3390/antibiotics12010181
  10. Azemi, A. K., Mokhtar, S. S., Sharif, S. E. T. and Rasool, A. H. G. (2021) Clinacanthus nutans attenuates atherosclerosis progression in rats with type 2 diabetes by reducing vascular oxidative stress and inflammation. Pharm. Biol. 59, 1432-1440.
  11. Beattie, P. E. and Lewis-Jones, M. S. (2006) A comparative study of impairment of quality of life in children with skin disease and children with other chronic childhood diseases. Br. J. Dermatol. 155, 145-151. https://doi.org/10.1111/j.1365-2133.2006.07185.x
  12. Bhattacharya, B., Pal, P., Chakraborty, S. and Samanta, A. (2010) In vitro evaluation of antifungal and antibacterial activities of the plant Cocciniagrandis (L.) J. Phytol. 2, 52-57.
  13. Bhuyar, P., Maniam, G. P. and Govindan, N. (2021) Isolation and characterization of bioactive compounds in medicinal plant Centel laasiatica and study the effects on fungal activities. J. Microbiol. Biotechnol. Food Sci. 10, 631-635. https://doi.org/10.15414/jmbfs.2021.10.4.631-635
  14. Brunner, P. M., Guttman-Yassky, E. and Leung, D. Y. (2017) The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies. J. Allergy Clin. Immunol. 139, S65-S76. https://doi.org/10.1016/j.jaci.2017.01.011
  15. Buranasudja, V., Rani, D., Malla, A., Kobtrakul, K. and Vimolmang kang, S. (2021) Insights into antioxidant activities and anti-skin aging potential of callus extract from Centellaasiatica (L.). Sci. Rep. 11, 13459.
  16. Carr, W. W. (2013) Topical calcineurin inhibitors for atopic dermatitis: review and treatment recommendations. Paediatr. Drugs 15, 303-310. https://doi.org/10.1007/s40272-013-0013-9
  17. Chia, T. Y., Gan, C. Y., Murugaiyah, V., Hashmi, S. F., Fatima, T., Ibra him, L., Abdulla, M. H., Alswailmi, F. K., Johns, E. J. and Ahmad, A. (2021) A narrative review on the phytochemistry, pharmacology and therapeutic potentials of Clinacanthus nutans (Burm. f.) Lindau leaves as an alternative source of future medicine. Molecules 27, 139. https://doi.org/10.3390/molecules27010139
  18. Chaiyamahapurk, S. and Warnnissorn, P. (2021) Prevalence and pattern of diseases of the skin and subcutaneous tissue in a primary care area in Thailand. Siriraj Med. J. 73, 357-362. https://doi.org/10.33192/Smj.2021.47
  19. Chiu, H. I., Che Mood, C. N. A., Mohamad Zain, N. N., Ramachandran, M. R., Yahaya, N., Nik Mohamed Kamal, N. N. S., Tung, W. H., Yong, Y. K., Lee, C. K. and Lim, V. (2021) Biogenic silver nanoparticles of Clinacanthus nutans as antioxidant with antimicrobial and cytotoxic effects. Bioinorg. Chem. Appl. 2021, 9920890.
  20. Choi, I. H., Kim, S., Kim, Y. and Yun, Y. (2012) The effect of TJ-15 plus TJ-17 on atopic dermatitis: a pilot study based on the principle of pattern identification. J. Altern. Complement. Med. 18, 576-582. https://doi.org/10.1089/acm.2011.0208
  21. Deshpande, S. V., Parmar, K. K., Daswadkar, S. C. and Khodade, R. B. (2011) A study of antioxidant activity of fruit extract of Coccini agrandis L. Voight. Int. J. Drug Deliv. Technol. 1, 69-72.
  22. Dinarello, C. A. (2010) Anti-inflammatory agents: present and future. Cell 140, 935-950. https://doi.org/10.1016/j.cell.2010.02.043
  23. Dong, S. H., Liu, Y. W., Wei, F., Tan, H. Z. and Han, Z. D. (2017) Asiatic acid ameliorates pulmonary fibrosis induced by bleomycin (BLM) via suppressing pro-fibrotic and inflammatory signaling path ways. Biomed. Pharmacother. 89, 1297-1309. https://doi.org/10.1016/j.biopha.2017.03.005
  24. Donkor, M. N., Donkor, A. M. and Mosobil, R. (2023) Combination therapy: synergism among three plant extracts against selected pathogens. BMC Res. Notes 16, 83.
  25. Ekor, M. (2014) The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety. Front. Pharmacol. 4, 177. https://doi.org/10.3389/fphar.2013.00177
  26. Ezemba, C. C., Okere, N. K., Kehinde, S. O., Ezemba, A. S. and Amadi, E. C. (2021) The antifungal activity of Senna alata leaf extract on dermatophytes. J. Appl. Chem. Sci. Int. 12, 61-67.
  27. Geoghegan, J. A., Irvine, A. D. and Foster, T. J. (2018) Staphylococcus aureus and atopic dermatitis: a complex and evolving relation ship. Trends Microbiol. 26, 484-497. https://doi.org/10.1016/j.tim.2017.11.008
  28. George, M., Joseph, L. and Ramaswamy. (2009) Anti-allergic, antipruritic, and anti-inflammatory activities of Centellaasiatica extracts. Afr. J. Tradit. Complement Altern. Med. 6, 554-559.
  29. Gohil, K. J., Patel, J. A. and Gajjar, A. K. (2010) Pharmacological review on Centellaasiatica: a potential herbal cure-all. Indian J. Pharm. Sci. 72, 546-556. https://doi.org/10.4103/0250-474X.78519
  30. Hajimehdipoor, H., Shahrestani, R. and Shekarchi, M. (2014) Investigating the synergistic antioxidant effects of some flavonoid and phenolic compounds. Res. J. Pharmacogn. 1, 35-40.
  31. Hao, C., Wu, B., Hou, Z., Xie, Q., Liao, T., Wang, T. and Ma, D. (2017) Asiatic acid inhibits LPS-induced inflammatory response in human gingival fibroblasts. Int. Immunopharmacol. 50, 313-318. https://doi.org/10.1016/j.intimp.2017.07.005
  32. Harnvoravongchai, P., Chankhamhaengdecha, S., Ounjai, P., Sing hakaew, S., Boonthaworn, K. and Janvilisri, T. (2018) Antimicrobial effect of asiatic acid against Clostridium difficile is associated with disruption of membrane permeability. Front. Microbiol. 9, 2125.
  33. Hashim, P. (2014) The effect of Centellaasiatica, vitamins, glycolic acid and their mixtures preparations in stimulating collagen and fibronectin synthesis in cultured human skin fibroblast. Pak. J. Pharm. Sci. 27, 233-237.
  34. Hashim, P., Sidek, H., Helan, M. H., Sabery, A., Palanisamy, U. D. and Ilham, M. (2011) Triterpene composition and bioactivities of Centel laasiatica. Molecules 16, 1310-1322. https://doi.org/10.3390/molecules16021310
  35. Hay, R. J., Johns, N. E., Williams, H. C., Bolliger, I. W., Dellavalle, R. P., Margolis, D. J., Marks, R., Naldi, L., Weinstock, M. A., Wulf, S. K., Michaud, C., Murray, C. J. L. and Naghavi, M. (2014) The global burden of skin disease in 2010: an analysis of the prevalence and impact of skin conditions. J. Invest. Dermatol. 134, 1527-1534. https://doi.org/10.1038/jid.2013.446
  36. Hennebelle, T., Weniger, B., Joseph, H., Sahpaz, S. and Bailleul, F. (2009) Senna alata. Fitoterapia 80, 385-393. https://doi.org/10.1016/j.fitote.2009.05.008
  37. Hon, K. L., Leung, T. F., Ng, P. C., Lam, M. C., Kam, W. Y., Wong, K. Y., Lee, K. C., Sung, Y. T., Cheng, K. F., Fok, T. F., Fung, K. P. and Leung, P. C. (2007) Efficacy and tolerability of a Chinese herbal medicine concoction for treatment of atopic dermatitis: a randomized, double-blind, placebo-controlled study. Br. J. Dermatol. 157, 357-363. https://doi.org/10.1111/bjd.2007.157.issue-2
  38. Igoli, J. O., Ogaji, O. G. and Tor-Anyiin, T. A. (2005) Traditional medicinal practices among the Igede people of Nigeria (part II). Afr. J. Tradit. Complement. Altern. Med. 2, 134-152.
  39. Ismail, N. Z., Md Toha, Z., Muhamad, M., Nik Mohamed Kamal, N. N. S., Mohamad Zain, N. N. and Arsad, H. (2020) Antioxidant effects, antiproliferative effects, and molecular docking of Clinacanthus nutans leaf extracts. Molecules 25, 2067. https://doi.org/10.3390/molecules25092067
  40. Jebadurai, S. G., Raj, R. E., Sreenivasan, V. S. and Binoj, J. S. (2019) Comprehensive characterization of natural cellulosic fiber from Cocciniagrandis stem. Carbohydr. Polym. 207, 675-683. https://doi.org/10.1016/j.carbpol.2018.12.027
  41. Ju Ho, P., Jun Sung, J., Ki Cheon, K. and Jin Tae, H. (2018) Anti-in flammatory effect of Centellaasiaticaphytosome in a mouse model of phthalic anhydride-induced atopic dermatitis. Phytomedicine 43, 110-119. https://doi.org/10.1016/j.phymed.2018.04.013
  42. Kanedi, M. (2016) Healing effect of leaf extract of candlebush (Cassia alata L.) on cutaneous wound infected with Trichophyton rubrum. World J. Pharm. Life Sci 2, 42-50.
  43. Kim, H. B., Zhou, H., Kim, J. H., Habre, R., Bastain, T. M. and Gilliland, F. D. (2016) Lifetime prevalence of childhood eczema and the effect of indoor environmental factors: analysis in Hispanic and non Hispanic white children. Allergy Asthma Proc. 37, 64-71. https://doi.org/10.2500/aap.2016.37.3913
  44. Kim, N. K., Lee, D. H., Seo, H. S., Sun, S. H., Oh, Y. L., Kim, J. E., Yoon, I. H., Seo, E. S., Shim, G. S. and Zaslawski, C. (2011) Hwan gryunhaedoktang in adult patients with atopic dermatitis: a ran domised, double-blind, placebo-controlled, two-centre trial—study protocol. BMC Complement. Altern. Med. 11, 68.
  45. Kondhare, D. and Lade, H. (2017) Phytochemical profile, aldose re ductase inhibitory, and antioxidant activities of Indian traditional medicinal Cocciniagrandis (L.) fruit extract. 3 Biotech 7, 378. https://doi.org/10.1007/s13205-017-1013-1
  46. Kuete, V. and Efferth, T. (2010) Cameroonian medicinal plants: phar macology and derived natural products. Front. Pharmacol. 1, 123.
  47. Langan, S. M., Silcocks, P. and Williams, H. C. (2009) What causes flares of eczema in children? Br. J. Dermatol. 161, 640-646. https://doi.org/10.1111/bjd.2009.161.issue-3
  48. Lee, H. N., Shin, S. A., Choo, G. S., Kim, H. J., Park, Y. S., Kim, B. S., Kim, S. K., Cho, S. D., Nam, J. S., Choi, C. S., Che, J. H., Park, B. K. and Jung, J. Y. (2018) Anti-inflammatory effect of quercetin and galangin in LPS-stimulated RAW264.7 macrophages and DNCB induced atopic dermatitis animal models. Int. J. Mol. Med. 41, 888-898.
  49. Lee, I. Y. and Joo, N. (2022) Identification and quantification of key phytochemicals, phytohormones, and antioxidant properties in Cocciniagrandis during fruit ripening. Antioxidants (Basel) 11, 2218. https://doi.org/10.3390/antiox11112218
  50. Lee, J. W., Park, H. A., Kwon, O. K., Jang, Y. G., Kim, J. Y., Choi, B. K., Lee, H. J., Lee, S., Paik, J. H., Oh, S. R., Ahn, K. S. and Lee, H. J. (2016) Asiatic acid inhibits pulmonary inflammation induced by cigarette smoke. Int. Immunopharmacol. 39, 208-217. https://doi.org/10.1016/j.intimp.2016.07.010
  51. Lin, C. M., Chen, H. H., Lung, C. W. and Chen, H. J. (2023) Antiviral and immunomodulatory activities of Clinacanthus nutans (Burm. f.) Lindau. Int. J. Mol. Sci. 24, 10789.
  52. Lokanathan, Y., Omar, N., Ahmad Puzi, N. N., Saim, A. and HjIdrus, R. (2016) Recent updates in neuroprotective and neuroregenerative potential of Centellaasiatica. Malays. J. Med. Sci. 23, 4-14.
  53. Maquart, F. X., Chastang, F., Simeon, A., Birembaut, P., Gillery, P. and Wegrowski, Y. (1999) Triterpenes from Centellaasiatica stimulate extracellular matrix accumulation in rat experimental wounds. Eur. J. Dermatol. 9, 289-296.
  54. Mary, B. B., Nair, P. and Diwakar, M. C. (1998) On the antipyretic, antiinflammatory, analgesic and molluscicidal properties of Polyscias fruticosa (L) harms. Anc. Sci. Life 17, 313-319.
  55. Matsuda, H., Morikawa, T., Ueda, H. and Yoshikawa, M. (2001) Medicinal foodstuffs. XXVII. Saponin constituents of gotu kola (2): structures of new ursane- and oleanane-type triterpene oligoglycosides, centellasaponins B, C, and D, from Centellaasiatica cultivated in Sri Lanka. Chem. Pharm. Bull. (Tokyo) 49, 1368-1371. https://doi.org/10.1248/cpb.49.1368
  56. Matthews, D. G., Caruso, M., Murchison, C. F., Zhu, J. Y., Wright, K. M., Harris, C. J., Gray, N. E., Quinn, J. F. and Soumyanath, A. (2019) Centellaasiatica improves memory and promotes antioxidative signaling in 5XFAD mice. Antioxidants (Basel) 8, 630. https://doi.org/10.3390/antiox8120630
  57. Meenatchi, P., Purushothaman, A. and Maneemegalai, S. (2017) Antioxidant, antiglycation and insulinotrophic properties of Cocciniagrandis (L.) in vitro: possible role in prevention of diabetic complications. J. Tradit. Complement. Med. 7, 54-64. https://doi.org/10.1016/j.jtcme.2016.01.002
  58. Midawa, S., Ali, B., Mshelia, B. and Johnson, J. (2010) Cutaneous wound healing activity of the ethanolic extracts of the leaf of Sennaalata L. (Fabaceae). J. Biol. Sci. Bioconserv. 2, 63-68.
  59. Moradi, M. T., Rafieian-Kopaei, M. and Karimi, A. (2016) A review study on the effect of Iranian herbal medicines against in vitro replication of herpes simplex virus. Avicenna J. Phytomed. 6, 506-515.
  60. Muthulakshmi, G. and Natarajan, P. (2020) Antibacterial and antifungal activity of Cocciniagrandis leaves' extracts against fish pathogens. Asian J. Biol. Life Sci. 9, 424-430. https://doi.org/10.5530/ajbls
  61. Nasution, S. L. R., Putri, M., Hulu, W., Girsang, E. and Nasution, A. N. (2019) Healing potential of Senna alata leaves extract in rats. J. Edu. Health Sport 9, 127-136.
  62. Neamsuvan, O. and Bunmee, P. (2016) A survey of herbal weeds for treating skin disorders from Southern Thailand: Songkhla and Krabi Province. J. Ethnopharmacol. 193, 574-585. https://doi.org/10.1016/j.jep.2016.09.048
  63. Odhiambo, J. A., Williams, H. C., Clayton, T. O., Robertson, C. F. and Asher, M. I.; ISAAC Phase Three Study Group (2009) Global variations in prevalence of eczema symptoms in children from ISAAC Phase Three. J. Allergy Clin. Immunol. 124, 1251-1258.e23. https://doi.org/10.1016/j.jaci.2009.10.009
  64. Oladeji, O. S., Adelowo, F. E., Oluyori, A. P. and Bankole, D. T. (2020) Ethnobotanical description and biological activities of Senna ala ta. Evid. Based Complement. Alternat. Med. 2020, 2580259.
  65. Oliveira, A. B., Ferrisse, T. M., Annunzio, S. R., Franca, M. G. A., Sil va, M. G. V., Cavalheiro, A. J., Fontana, C. R. and Brighenti, F. L. (2023) In vitro evaluation of photodynamic activity of plant extracts from Senna species against microorganisms of medical and dental interest. Pharmaceutics 15, 181. https://doi.org/10.3390/pharmaceutics15010181
  66. Ong, W. Y., Herr, D. R., Sun, G. Y. and Lin, T. N. (2022) Anti-inflam matory effects of phytochemical components of Clinacanthus nu tans. Molecules 27, 3607. https://doi.org/10.3390/molecules27113607
  67. Pamulaparthi, A. P. V. R., Banala, M. and Nanna, R. S. (2016) Total phenolic, flavonoid contents and antioxidant assays in leaf extracts of Senna alata (L.) Roxb. J. Pharm. Sci. Res. 8, 981-985.
  68. Pannangpetch, P., Laupattarakasem, P., Kukongviriyapan, V., Kukong viriyapan, U., Kongyingyoes, B. and Aromdee, C. (2007) Antioxi dant activity and protective effect against oxidative hemolysis of Clinacanthus nutans (Burm.f) Lindau. J. Sci. Technol. 29, 1-9.
  69. Paocharoen, V. (2010) The efficacy and side effects of oral Centel laasiatica extract for wound healing promotion in diabetic wound patients. J. Med. Assoc. Thai. 93, S166-S170.
  70. Patwardhan, B., Warude, D., Pushpangadan, P. and Bhatt, N. (2005) Ayurveda and traditional Chinese medicine: a comparative over view. Evid. Based Complement. Alternat. Med. 2, 465-473. https://doi.org/10.1093/ecam/neh140
  71. Peng, W. and Novak, N. (2014) Recent developments in atopic dermatitis. Review Curr. Opin. Allergy Clin. Immunol 14, 417-422. https://doi.org/10.1097/ACI.0000000000000094
  72. Peng, W. and Novak, N. (2015) Pathogenesis of atopic dermatitis. Clin. Exp. Allergy 45, 566-574. https://doi.org/10.1111/cea.2015.45.issue-3
  73. Puttarak, P. and Panichayupakaranant, P. (2012) Factors affecting the content of pentacyclic triterpenes in Centellaasiatica raw materials. Pharm. Biol. 50, 1508-1512. https://doi.org/10.3109/13880209.2012.685946
  74. Rachpirom, M., Pichayakorn, W. and Puttarak, P. (2023) Preparation, development, and scale-up of standardized pentacyclic triterpenoid-rich extract from Centellaasiatica (L.) Urb. and study of its wound healing activity. Heliyon 9, e17807.
  75. Rahmawati, F. P. N. N. and Hady, B. C. (2022) In vitro bioactivity test of Senna alata (L.) Roxb leaves extract. Int. J. Health Sci. Res. 12, 304-317. https://doi.org/10.52403/ijhsr
  76. Razali, N. N. M., Ng, C. T. and Fong, L. Y. (2019) Cardiovascular protective effects of Centellaasiatica and its triterpenes: a re view. Planta Med. 85, 1203-1215. https://doi.org/10.1055/a-1008-6138
  77. Ren, J., Li, L., Wang, Y., Zhai, J., Chen, G. and Hu, K. (2019) Gambogic acid induces heme oxygenase-1 through Nrf2 signaling path way and inhibits NF-kappaB and MAPK activation to reduce inflammation in LPS-activated RAW264.7 cells. Biomed. Pharmacother. 109, 555-562. https://doi.org/10.1016/j.biopha.2018.10.112
  78. Riaz, A., Rasul, A., Hussain, G., Zahoor, M. K., Jabeen, F., Subhani, Z., Younis, T., Ali, M., Sarfraz, I. and Selamoglu, Z. (2018) Astragalin: a bioactive phytochemical with potential therapeutic activities. Adv. Pharmacol. Sci. 2018, 9794625.
  79. Roesner, L. M., Werfel, T. and Heratizadeh, A. (2016) The adaptive immune system in atopic dermatitis and implications on therapy. Expert Rev. Clin. Immunol. 12, 787-796. https://doi.org/10.1586/1744666X.2016.1165093
  80. Russell, J. J. (2002) Topical tacrolimus: a new therapy for atopic dermatitis. Am. Fam. Physician 66, 1899-1902.
  81. Sakdarat, S., Shuyprom, A., Pientong, C., Ekalaksananan, T. and Thongchai, S. (2009) Bioactive constituents from the leaves of Clinacanthus nutans Lindau. Bioorg. Med. Chem. 17, 1857-1860. https://doi.org/10.1016/j.bmc.2009.01.059
  82. Sakharkar, P. and Chauhan, B. (2017) Antibacterial, antioxidant and cell proliferative properties of Cocciniagrandis fruits. Avicenna J. Phytomed. 7, 295-307.
  83. Saokaew, S., Suwankesawong, W., Permsuwan, U. and Chaiyaku napruk, N. (2011) Safety of herbal products in Thailand: an analysis of reports in the Thai health product vigilance center database from 2000 to 2008. Drug Saf. 34, 339-350. https://doi.org/10.2165/11586590-000000000-00000
  84. Sivaraj, A., Jenifa, B. P., Kavitha, M. S., Inbasekar, P., Senthilkumar, B. and Panneerselvam, A. (2011) Antibacterial activity of Cocciniagrandis leaf extract on selective bacterial strains. J. Appl. Pharm. Sci. 1, 120-123.
  85. Sun, B., Wu, L., Wu, Y., Zhang, C., Qin, L., Hayashi, M., Kudo, M., Gao, M. and Liu, T. (2020) Therapeutic potential of Centellaasiatica and its triterpenes: a review. Front. Pharmacol. 11, 568032.
  86. Tuntiwachwuttikul, P., Pootaeng-On, Y., Phansa, P. and Taylor, W. C. (2004) Cerebrosides and a monoacylmonogalactosylglycerol from Clinacanthus nutans. Chem. Pharm. Bull. (Tokyo) 52, 27-32. https://doi.org/10.1248/cpb.52.27
  87. Uwazie, J. N., Yakubu, M. T., Ashafa, A. O. T. and Ajiboye, T. O. (2020) Identification and characterization of anti-diabetic principle in Senna alata (Linn.) flower using alloxan-induced diabetic male Wistar rats. J. Ethnopharmacol. 261, 112997. https://doi.org/10.1016/j.jep.2020.112997
  88. Wanikiat, P., Panthong, A., Sujayanon, P., Yoosook, C., Rossi, A. G. and Reutrakul, V. (2008) The anti-inflammatory effects and the in hibition of neutrophil responsiveness by Barlerialupulina and Clinacanthus nutans extracts. J. Ethnopharmacol. 116, 234-244. https://doi.org/10.1016/j.jep.2007.11.035
  89. Weidinger, S., Beck, L. A., Bieber, T., Kabashima, K. and Irvine, A. D. (2018) Atopic dermatitis. Nat. Rev. Dis. Primers 4, 1.
  90. Williams, H. C. (2005) Clinical practice. Atopic dermatitis. N. Engl. J. Med. 352, 2314-2324. https://doi.org/10.1056/NEJMcp042803
  91. Wollenberg, A., Oranje, A., Deleuran, M., Simon, D., Szalai, Z., Kunz, B., Svensson, A., Barbarot, S., von Kobyletzki, L., Taieb, A., de Bruin-Weller, M., Werfel, T., Trzeciak, M., Vestergard, C., Ring, J. and Darsow, U.; European Task Force on Atopic Dermatitis/EADV Eczema Task Force (2016) ETFAD/EADV Eczema task force 2015 position paper on diagnosis and treatment of atopic dermatitis in adult and paediatric patients. J. Eur. Acad. Dermatol. Venereol. 30, 729-747. https://doi.org/10.1111/jdv.2016.30.issue-5
  92. Wu, Z., Yang, L., Wang, R., Yang, J., Liang, P., Ren, W. and Yu, H. (2024) Exploring the mechanism of asiatic acid against atheroscle rosis based on molecular docking, molecular dynamics, and ex perimental verification. Pharmaceuticals (Basel) 17, 969. https://doi.org/10.3390/ph17070969
  93. Yang, G., Seok, J. K., Kang, H. C., Cho, Y. Y., Lee, H. S. and Lee, J. Y. (2020) Skin barrier abnormalities and immune dysfunction in atopic dermatitis. Int. J. Mol. Sci. 21, 2867.
  94. Yusuf, S. N. A. M., Mood, C. N. A. C., Ahmad, N., Sandai, D., Lee, C. K. and Lim, V. (2020) Optimization of biogenic synthesis of silver nanoparticles from flavonoid-rich Clinacanthus nutans leaf and stem aqueous extracts. R. Soc. Open Sci. 7, 200065.
  95. Zeldin, J., Chaudhary, P. P., Spathies, J., Yadav, M., D'Souza, B. N., Alishahedani, M. E., Gough, P., Matriz, J., Ghio, A. J., Li, Y., Sun, A. A., Eichenfield, L. F., Simpson, E. L. and Myles, I. A. (2023) Exposure to isocyanates predicts atopic dermatitis prevalence and disrupts therapeutic pathways in commensal bacteria. Sci. Adv. 9, eade8898. https://doi.org/10.1126/sciadv.ade8898
  96. Zulkipli, I. N., Rajabalaya, R., Idris, A., Sulaiman, N. A. and David, S. R. (2017) Clinacanthus nutans: a review on ethnomedicinal uses, chemical constituents and pharmacological properties. Pharm. Biol. 55, 1093-1113. https://doi.org/10.1080/13880209.2017.1288749