Indonesian Ciplukan Extract Inhibited TGF-β1/NF-κB Pathway in Experimental Psoriasis Mouse Models


  • Thianti Sylviningrum Doctorate Programme of Medical Science, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia
  • Brian Wasita Department of Anatomical Pathology, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia
  • Bambang Purwanto Department of Internal Medicine, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia
  • Harijono Kariosentono Department of Dermatology and Venereology, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia
  • Soetrisno Soetrisno Doctorate Programme of Medical Science, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia



Ciplukan extract, Physalis angulata L., TGF-β1/NF-κB pathway, Psoriasis


Background:The global prevalence of psoriasis, a chronic inflammatory skin disease, has substantially increased in the last decade. The increase activity of Transforming Growth Factor ß1 (TGFß1)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway which cause inflammation, is the major pathological mechanism in psoriasis. Current psoriasis treatment using chemical agents is hampered by the side-effects when used long-term, which underlines the need for alternative, low side-effect anti-psoriatic agents. The extract of Physalis angulata L., also known as Ciplukan in Indonesia, contains Physalins, compounds known for their anti-inflammatory effects, but whose effect on psoriasis has not been studied.

Objective:  This study aimed to investigate the effect of Ciplukan extract (CE) to TGFß1/NF-κB pathway in psoriasis mouse models.

Methods: This was experimental study with posttest-only control group design. The CE active ingredients were identified using Liquid chromatography-tandem mass spectrometry (LC-MS/MS). Twenty-five female imiquimod (IMQ) induced psoriasis-like dermatitis mice were allocated into five groups, with three groups receiving 7 days of 400, 800, and 1200 mg/kg bodyweight doses of CE, respectively, and two groups serving as control and IMQ groups. The NF-κB and TGFß1 expressions were evaluated using Allred score based on immunohistochemistry (IHC) staining. Histopathology and clinical psoriasis manifestations were assessed using Baker’s from Hematoxylin Eosin (HE) staining and Psoriasis Area Severity Index (PASI) scores. The Kruskal-Wallis followed by Mann Whitney tests were conducted for data analysis. The p-value < 0.05 was considered to be statistically different.  

Results: Based on LC-MS/MS test, Physalin B, D, and F were active ingredients from CE in ethyl acetate solution. An improvement in psoriasis inflammation was observed in 400 and 800 mg/kg bodyweight doses of CE, but only the dosage of 800 mg/kg BW significantly decreased of Allred scores from NF-κB and TGFß1 expressions; Baker’s and PASI scores compared to IMQ group (p<0.05). The 1200 mg/kg bodyweight doses of CE associated with acute toxicity signs and mortality, meanwhile dosage of 800 mg/kg BW showed the highest efficacy with lowest toxicity effect.

Conclusions: Ciplukan extract improved psoriasis manifestations via inhibition effect to TGFß1/NF-κB pathway and the extract might be developed as an alternative anti-psoriasis agent


Download data is not yet available.


Metrics Loading ...

Plum Analytics Artifact Widget Block


Parisi R, Symmons DP, Griffiths CE, Ashcroft DM. Global epidemiology of psoriasis: A systematic review of incidence and prevalence. J Invest Dermatol. 2013;133(2):377-85. PMid:23014338 DOI:

Mahil SK, Capon F, Barker JN. Update on psoriasis immunopathogenesis and targeted immunotherapy. Semin Immunopathol. 2016;38(1):11-27. PMid:26573299 DOI:

World Health Organization. Global Report on Psoriasis. Vol. 978. 1st ed. Switzerland: World Health Organization; 2016.

Thomsen SF, Skov L, Dodge R, Hedegaard MS, Kjellberg J. Socioeconomic costs and health inequalities from psoriasis: A cohort study. Dermatology. 2019;235(5):372-9. PMid:31238322 DOI:

Belinchón I, Rivera R, Blanch C, Comellas M, Lizán L. Adherence, satisfaction and preferences for treatment in patients with psoriasis in the European union: A systematic review of the literature. Patient Prefer Adherence. 2016;10:2357-67. PMid:27895471 DOI:

Hogan KA, Ravindran A, Podolsky MA, Glick AB. The TGF-β1 pathway is required for NFκB dependent gene expression in mouse keratinocytes. Cytokine. 2013;64:652-9. PMid:24075100 DOI:

El-Hadidi HH, Hassan AS, El-Hanafy G, Amr KS, Abdelmesih SF, Abdelhamid MF. Transforming growth factor-β1 gene polymorphism in psoriasis vulgaris. Clin Cosmet Investig Dermatol. 2018;11:415-9. PMid:30174452 DOI:

Mohammed J, Gunderson AJ, Khong HH, Koubek RD, Udey MC, Glick AB. TGF-β1 overexpression by keratinocytes alters skin dendritic cell homeostasis and enhances contact hypersensitivity. J Invest Dermatol. 2013;133(1):135-43. PMid:22832490 DOI:

Zhang Y, Meng XM, Huang XR, Wang XJ, Yang L, Lan HY. Transforming growth factor-β1 mediates psoriasis-like lesions via a Smad3-dependent mechanism in mice. Clin Exp Pharmacol Physiol. 2014;41(11):921-32. PMid:25132073 DOI:

Freudlsperger C, Bian Y, Contag Wise S, Burnett J, Coupar J, Yang X, et al. TGF-β and NF-κB signal pathway cross-talk is mediated through TAK1 and SMAD7 in a subset of head and neck cancers. Oncogene 2013;32:1549-59. DOI:

Benfield CT, Mansur DS, McCoy LE, Ferguson BJ, Bahar MW, Oldring AP, et al. Mapping the IκB kinase β (IKKβ)-binding interface of the B14 protein, a vaccinia virus inhibitor of IKKβ-mediated activation of nuclear factor κB. J Biol Chem. 2011;286(23):20727-35. PMid:21474453 DOI:

Ogawa E, Sato Y, Minagawa A, Okuyama R. Pathogenesis of psoriasis and development of treatment. J Dermatol. 2018;45(3):264-72. PMid:29226422 DOI:

Girolomoni G, Strohal R, Puig L, Bachelez H, Barker J, Boehncke WH, et al. The role of IL-23 and the IL-23/TH17 immune axis in the pathogenesis and treatment of psoriasis. J Eur Acad Dermatol Venereol. 2017;31(10):1616-26. PMid:28653490 DOI:

Katayama H. Development of psoriasis by continuous neutrophil infiltration into the epidermis. Exp Dermatol. 2018;27(10):1084-91. PMid:30019426 DOI:

Wang B, Han D, Li F, Hou W, Wang L, Meng L, et al. Elevated IL-22 in psoriasis plays an anti-apoptotic role in keratinocytes through mediating Bcl-xL/Bax. Apoptosis. 2020;25(9):663. PMid:32632545 DOI:

Yélamos O, Puig L. Systemic methotrexate for the treatment of psoriasis. Expert Rev Clin Immunol. 2015;11(5):553-63. PMid:25779551 DOI:

Fernández-Guarino M, Aboín-González S, Velázquez D, Barchino L, Cano N, Lázaro P. Phototherapy with narrow-band UVB in adult guttate psoriasis: Results and patient assessment. Dermatology. 2017;232(5):626-32. PMid:27883996 DOI:

Boehncke WH, Schön MP. Psoriasis. Lancet. 2015;386(9997):983-94. PMid:26025581 DOI:

Fan JJ, Liu X, Zheng XL, Zhao HY, Xia H, Sun Y. A novel cytotoxic physalin from physalis angulata. Nat Prod Commun. 2017;12:1589-91. DOI:

Ozawa M, Morita M, Hirai G, Tamura S, Kawai M, Tsuchiya A, et al. Contribution of cage-shaped structure of physalins to their mode of action in inhibition of NF-κB activation. ACS Med Chem Lett. 2013;4(8):730-5. PMid:24900739 DOI:

Yang Y, Yi L, Wang Q, Xie B, Sha C, Dong Y. Physalin B suppresses inflammatory response to lipopolysaccharide in RAW264.7 cells by inhibiting NF-κB signaling. J Chem. 2018;2018:7943140. DOI:

Ding N, Lu Y, Cui H, Ma Q, Qiu D, Wei X, et al. Physalin D inhibits RANKL-induced osteoclastogenesis and bone loss via regulating calcium signaling. BMB Rep. 2020;53(3):154-9. PMid:31964464 DOI:

Wu SY, Leu YL, Chang YL, Wu TS, Kuo PC, Liao YR, et al. Physalin F induces cell apoptosis in human renal carcinoma cells by targeting NF-kappaB and generating reactive oxygen species. PLoS One. 2012;7(7):40727. PMid:22815798 DOI:

Xiang D, Zou J, Zhu X, Chen X, Luo J, Kong L, et al. Physalin D attenuates hepatic stellate cell activation and liver fibrosis by blocking TGF-β/Smad and YAP signaling. Phytomedicine. 2020;78:153294. PMid:32771890 DOI:

World Health Organization. Research Guidelines for Evaluating the Safety and Efficacy of Herbal Medicines. 1st ed. Manila: World Health Organization; 1993.

Luo DQ, Wu HH, Zhao YK, Liu JH, Wang F. Original research: Different imiquimod creams resulting in differential effects for imiquimod-induced psoriatic mouse models. Exp Biol Med (Maywood). 2016;241(16):1733-8. PMid:27190266 DOI:

Van der Fits L, Mourits S, Voerman JS, Kant M, Boon L, Laman JD, et al. Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis. J Immunol. 2009;182(9):5836-45. PMid:19380832 DOI:

Pratiwi L, Fudholi A, Martien R, Pramono S. Ethanol extract, ethyl acetate extract, ethyl acetate fraction, and n-heksan fraction mangosteen peels (Garcinia mangostana L.) as source of bioactive substance free-radical scavengers. JPSCR J Pharm Sci Clin Res. 2016;1:71. DOI:

Zhang QW, Lin LG, Ye WC. Techniques for extraction and isolation of natural products: A comprehensive review. Chinese Med. 2018;13:20. PMid:29692864 DOI:

Chand P, Garg A, Singla V, Rani N. Evaluation of immunohistochemical profile of breast cancer for prognostics and therapeutic use. Niger J Surg. 2018;24(2):100-6. PMid:30283220 DOI:

Baker BS, Brent L, Valdimarsson H, Powles AV, Al-Imara L, Walker M, et al. Is epidermal cell proliferation in psoriatic skin grafts on nude mice driven by T-cell derived cytokines? Br J Dermatol. 1992;126(2):105-10. PMid:1536776 DOI:

Carceller E, Ballegeer M, Deckers J, Riccardi C, Bruscoli S, Hochepied T, et al. Overexpression of glucocorticoid-induced leucine zipper (GILZ) increases susceptibility to imiquimod-induced psoriasis and involves cutaneous activation of TGF-β1. Sci Rep. 2016;6:38825. PMid:27934944 DOI:

Li ZJ, Sohn KC, Choi DK, Shi G, Hong D, Lee HE, et al. Roles of TLR7 in activation of NF-κB signaling of keratinocytes by imiquimod. PLoS One. 2013;8(10):77159. PMid:24146965 DOI:

Adbullah TH, Latif II, Ibrahim KH. Role of tumor necrosis factor alpha and transforming growth factor beta as predictive marker for psoriasis patients. Diyala J Med. 2020;19:1-7. DOI:

Kasali FM, Kadima JN, Mpiana PT, Ngbolua KN, Tshibangu DST. Assessment of antidiabetic activity and acute toxicity of leaf extracts from Physalis peruviana L. in Guinea-pig. Asian Pac J Trop Biomed. 2013;3(11):841-6. DOI:

Yang Y, Jiang G, Zhang P, Fan J. Programmed cell death and its role in inflammation. Mil Med Res. 2015;2:1-12. PMid:26045969 DOI:




How to Cite

Sylviningrum T, Wasita B, Purwanto B, Kariosentono H, Soetrisno S. Indonesian Ciplukan Extract Inhibited TGF-β1/NF-κB Pathway in Experimental Psoriasis Mouse Models. Open Access Maced J Med Sci [Internet]. 2022 Mar. 21 [cited 2023 Mar. 22];10(A):938-46. Available from:

Most read articles by the same author(s)

1 2 > >>