Skip to main content

Advertisement

Log in

Daturataturin A Ameliorates Psoriasis by Regulating PPAR Pathway

  • Original Article
  • Published:
Biochemical Genetics Aims and scope Submit manuscript

Abstract

Psoriasis is a kind of severe immune-mediated systemic skin disorder, becoming a worldwide public health concern. Daturataturin A (DTA), a withanolide compound, exerts excellent anti-inflammatory and anti-proliferative properties. The objective of this study is to elucidate the effect of DTA on psoriasis and its potential mechanism. We established psoriasis-like keratinocytes model by stimulating HaCaT cells with M5 cocktail cytokines including Interleukin (IL)-17A, IL-22, oncostatin M, IL-1α, and tumor necrosis factor-α (TNF-α), followed by intervention with DTA. The potential effects and mechanisms of DTA on psoriasis were evaluated in vitro. DTA was found to be able to inhibit hyperproliferation, promote apoptosis, decrease the release of pro-inflammatory cytokines, downregulate keratin expression, and improve lipid metabolism via regulating the peroxisome proliferator-activated receptor (PPAR) signaling pathway by M5 cocktail cytokines stimulation in HaCaT cells. DTA ameliorated lipid metabolism of psoriasis and exerted the potential anti-psoriasis effects by regulating PPAR pathway in vitro, suggesting that DTA may act as a new therapeutic agent for psoriasis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Data availability

The datasets GSE14258 and GSE30999 used during the current study are available from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/).

References

  • Albanesi C, Madonna S, Gisondi P, Girolomoni G (2018) The interplay between keratinocytes and immune cells in the pathogenesis of psoriasis. Front Immunol 9:1549

    Article  PubMed  PubMed Central  Google Scholar 

  • Armstrong AW, Read C (2020) Pathophysiology, clinical presentation, and treatment of psoriasis: a review. JAMA 323(19):1945–1960

    Article  CAS  PubMed  Google Scholar 

  • Chen H, Tan H, Wan J, Zeng Y, Wang J, Wang H, Lu X (2023) PPAR-gamma signaling in nonalcoholic fatty liver disease: Pathogenesis and therapeutic targets. Pharmacol Ther 245:108391

    Article  CAS  PubMed  Google Scholar 

  • Cheng Y, Liu Y, Tan J, Sun Y, Guan W, Jiang P, Yang B, Kuang H (2020) Integrated serum metabolomics and network pharmacology approach to reveal the potential mechanisms of withanolides from the leaves of Datura metel L. on psoriasis. J Pharm Biomed Anal 186:113277

    Article  CAS  PubMed  Google Scholar 

  • Constantin C, Surcel M, Munteanu A, Neagu M (2023) Insights into nutritional strategies in psoriasis. Nutrients 15(16):3528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Deng Y, Chang C, Lu Q (2016) The inflammatory response in psoriasis: a comprehensive review. Clin Rev Allergy Immunol 50(3):377–389

    Article  CAS  PubMed  Google Scholar 

  • Di T, Zhai C, Zhao J, Wang Y, Chen Z, Li P (2021) Taxifolin inhibits keratinocyte proliferation and ameliorates imiquimod- induced psoriasis-like mouse model via regulating cytoplasmic phospholipase A2 and PPAR-gamma pathway. Int Immunopharmacol 99:107900

    Article  CAS  PubMed  Google Scholar 

  • Furue M, Furue K, Tsuji G, Nakahara T (2020) Interleukin-17A and keratinocytes in psoriasis. Int J Mol Sci 21(4):1275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gegotek A, Domingues P, Wronski A, Wojcik P, Skrzydlewska E (2018) Proteomic plasma profile of psoriatic patients. J Pharm Biomed Anal 155:185–193

    Article  CAS  PubMed  Google Scholar 

  • Greb JE, Goldminz AM, Elder JT, Lebwohl MG, Gladman DD, Wu JJ, Mehta NN, Finlay AY, Gottlieb AB (2016) Psoriasis. Nat Rev Dis Primers 2:16082

    Article  PubMed  Google Scholar 

  • Gu H, An HJ, Gwon MG, Bae S, Zouboulis CC, Park KK (2022) The effects of synthetic SREBP-1 and PPAR-gamma decoy oligodeoxynucleotide on acne-like disease in vivo and in vitro via lipogenic regulation. Biomolecules 12(12):1858

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Han X, Gross RW (2022) The foundations and development of lipidomics. J Lipid Res 63(2):100164

    Article  CAS  PubMed  Google Scholar 

  • Hjuler KF, Gormsen LC, Vendelbo MH, Egeberg A, Nielsen J, Iversen L (2017) Increased global arterial and subcutaneous adipose tissue inflammation in patients with moderate-to-severe psoriasis. Br J Dermatol 176(3):732–740

    Article  CAS  PubMed  Google Scholar 

  • Jeon YG, Kim YY, Lee G, Kim JB (2023) Physiological and pathological roles of lipogenesis. Nat Metab 5(5):735–759

    Article  CAS  PubMed  Google Scholar 

  • Joshi C, Chaudhari A, Joshi C, Joshi M, Bagatharia S (2022) Repurposing of the herbal formulations: molecular docking and molecular dynamics simulation studies to validate the efficacy of phytocompounds against SARS-CoV-2 proteins. J Biomol Struct Dyn 40(18):8405–8419

    Article  CAS  PubMed  Google Scholar 

  • Lee HJ, Kim M (2023) Challenges and future trends in the treatment of psoriasis. Int J Mol Sci 24(17):13313

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li T, Wei Z, Kuang H (2021) UPLC-orbitrap-MS-based metabolic profiling of HaCaT cells exposed to withanolides extracted from Datura metel L: insights from an untargeted metabolomics. J Pharm Biomed Anal 199:113979

    Article  CAS  PubMed  Google Scholar 

  • Li XF, Yin SQ, Li H, Yang YL, Chen X, Song B, Wu S, Wu YY, Wang H, Li J (2023) PPAR-gamma alleviates the inflammatory response in TNF-alpha-induced fibroblast-like synoviocytes by binding to p53 in rheumatoid arthritis. Acta Pharmacol Sin 44(2):454–464

    Article  CAS  PubMed  Google Scholar 

  • Liang H, Li J, Zhang K (2023) Pathogenic role of S100 proteins in psoriasis. Front Immunol 14:1191645

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin X, Meng X, Song Z, Lin J (2022) Peroxisome proliferator-activator receptor gamma and psoriasis, molecular and cellular biochemistry. Mol Cell Biochem 477(7):1905–1920

    Article  CAS  PubMed  Google Scholar 

  • Liu C, Chen H, Liu Y, Huang H, Yu W, Du T, Long X, Chen X, Chen Z, Guo S et al (2022a) Immunity: psoriasis comorbid with atherosclerosis. Front Immunol 13:1070750

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu X, Hu M, Ye C, Liao L, Ding C, Sun L, Liang J, Chen Y (2022b) Isosilybin regulates lipogenesis and fatty acid oxidation via the AMPK/SREBP-1c/PPARalpha pathway. Chem Biol Interact 368:110250

    Article  CAS  PubMed  Google Scholar 

  • Nowowiejska J, Baran A, Flisiak I (2023) Lipid alterations and metabolism disturbances in selected inflammatory skin diseases. Int J Mol Sci 24(8):7053

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qiu YY, Zhang J, Zeng FY, Zhu YZ (2023) Roles of the peroxisome proliferator-activated receptors (PPARs) in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Pharmacol Res 192:106786

    Article  CAS  PubMed  Google Scholar 

  • Raj D, Brash DE, Grossman D (2006) Keratinocyte apoptosis in epidermal development and disease. J Invest Dermatol 126(2):243–257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roy T, Banang-Mbeumi S, Boateng ST, Ruiz EM, Chamcheu RN, Kang L, King JA, Walker AL, Nagalo BM, Kousoulas KG et al (2022) Dual targeting of mTOR/IL-17A and autophagy by fisetin alleviates psoriasis-like skin inflammation. Front Immunol 13:1075804

    Article  CAS  PubMed  Google Scholar 

  • Schuler R, Brand A, Klebow S, Wild J, Veras FP, Ullmann E, Roohani S, Kolbinger F, Kossmann S, Wohn C et al (2019) Antagonization of IL-17A attenuates skin inflammation and vascular dysfunction in mouse models of psoriasis. J Invest Dermatol 139(3):638–647

    Article  PubMed  Google Scholar 

  • Seminotti B, Grings M, Glanzel NM, Vockley J, Leipnitz G (2023) Peroxisome proliferator-activated receptor (PPAR) agonists as a potential therapy for inherited metabolic disorders. Biochem Pharmacol 209:115433

    Article  CAS  PubMed  Google Scholar 

  • Sobolev V, Nesterova A, Soboleva A, Mezentsev A, Dvoriankova E, Piruzyan A, Denisova E, Melnichenko O, Korsunskaya I (2021) Analysis of PPARgamma signaling activity in psoriasis. Int J Mol Sci 22(16):8603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Su Y, Zhang F, Wu L, Kuang H, Wang Q, Cheng G (2022) Total withanolides ameliorates imiquimod-induced psoriasis-like skin inflammation. J Ethnopharmacol 285:114895

    Article  CAS  PubMed  Google Scholar 

  • Trovato E, Rubegni P, Prignano F (2022) Place in therapy of anti-IL-17 and 23 in psoriasis according to the severity of comorbidities: a focus on cardiovascular disease and metabolic syndrome. Expert Opin Biol Ther 22(12):1443–1448

    Article  CAS  PubMed  Google Scholar 

  • Wagner N, Wagner KD (2023) Pharmacological utility of PPAR modulation for angiogenesis in cardiovascular disease. Int J Mol Sci 24(3):2345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wei Z, Li T, Sun Y, Su H, Zeng Y, Wang Q, Kuang H (2021) Daturataturin A, a withanolide in Datura metel L., induces HaCaT autophagy through the PI3K-Akt-mTOR signaling pathway. Phytother Res: PTR 35(3):1546–1558

    Article  CAS  PubMed  Google Scholar 

  • Wu JJ, Kavanaugh A, Lebwohl MG, Gniadecki R, Merola JF (2022) Psoriasis and metabolic syndrome: implications for the management and treatment of psoriasis. J Eur Acad Dermatol Venereol 36(6):797–806

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu X, Ma Y, Wang L, Qin X (2023) A route for investigating psoriasis: from the perspective of the pathological mechanisms and therapeutic strategies of cancer. Int J Mol Sci 24(18):14390

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu S, Liu Y, Xiang L, Zhou F, Li H, Su Y, Xu X, Wang Q (2018) Metabolites Identification of bioactive compounds daturataturin A, daturametelin I, N-trans-feruloyltyramine, and cannabisin F from the seeds of Datura metel in rats. Front Pharmacol 9:731

    Article  PubMed  PubMed Central  Google Scholar 

  • Yang BY, Guo R, Li T, Wu JJ, Zhang J, Liu Y, Wang QH, Kuang HX (2014) New anti-inflammatory withanolides from the leaves of Datura metel L. Steroids 87:26–34

    Article  CAS  PubMed  Google Scholar 

  • Yu J, Zhao Q, Wang X, Zhou H, Hu J, Gu L, Hu Y, Zeng F, Zhao F, Yue C et al (2022) Pathogenesis, multi-omics research, and clinical treatment of psoriasis. J Autoimmun 133:102916

    Article  CAS  PubMed  Google Scholar 

  • Yuan LL, Cao CY (2023) Rehmannioside A inhibits TRAF6/MAPK pathway and improves psoriasis by interfering with the interaction of HaCaT cells with IL-17A. Clin Cosmet Investig Dermatol 16:2585–2596

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Q, Xie J, Li G, Wang F, Lin J, Yang M, Du A, Zhang D, Han L (2022) Psoriasis treatment using Indigo Naturalis: progress and strategy. J Ethnopharmacol 297:115522

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

Not applicable.

Author information

Authors and Affiliations

Authors

Contributions

Conceptualization, Methodology and Writing—Original Draft: ZW. Investigation and Formal Analysis: HZ and SY. Resources: CC. Writing—Review and Editing: HZ, SY, and CC. All authors had full access to the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Corresponding author

Correspondence to Cong Chen.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interests.

Ethical Approval

Not applicable.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 372 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wei, Z., Zhong, H., Yuan, S. et al. Daturataturin A Ameliorates Psoriasis by Regulating PPAR Pathway. Biochem Genet (2024). https://doi.org/10.1007/s10528-024-10680-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10528-024-10680-1

Keywords

Navigation