Anti-proliferative and anti-migratory effects of hyperforin in 2D and 3D artificial constructs of human dermal fibroblasts – A new option for hypertrophic scar treatment?

Füller, Jendrik; Müller‐Goymann, Christel C.

doi:10.1016/j.ejpb.2017.03.003

Cited by 18 publications

(19 citation statements)

References 27 publications

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“…Therefore, these authors claimed that HP could be a therapeutic material for the topical treatment of inflammatory skin disorders. Beside, Fuller and Muller-Goymann [25] determined reduced proliferation, migration activity and contraction ability of fibroblast, and advised to use hyperforin for treatment of hypertrophic scars rather than promoting wound healing. In this study, a secondary healing model in the palatal keratinized mucosa has been utilized to mimic the healing of gingivectomy operation.…”

Section: Discussionmentioning

confidence: 99%

Palatal Mukozal Hasar Oluşturulan Tavşanlarda Profilaktik Hypericum Perforatum Yağ Uygulamasının Antioksidan Özellikleri

Günpınar

Kiliç²,

Tosun³

et al. 2020

Celal Bayar Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi

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Bu çalışma, tavşanlarda tedavi öncesi (t) topikal Hypericum perforatum (HP) yağı uygulamasının antioksidan ve yumuşak doku yara iyileştirici özelliklerini belirlemek amacıyla yapıldı. Gereç ve Yöntem: Otuz altı Yeni Zelanda albino tavşanı, rastgele olarak t-HP yağı (test, n = 18) ve t-zeytin yağı (kontrol, n = 18) gruplarına ayrıldı. Test ve kontrol gruplarındaki tavşanların her biri cerrahi öncesi topikal olarak HP veya zeytinyağı ile ön işleme tabi tutuldu. Alınan dişeti biyopsileri, re-epitelizasyon (RE) ve granülasyon dokusu olgunlaşması (GTM) açısından analiz edildi. Genel yara görünümü, eritem ve epitelyal birleşme skorlaması yapılarak klinik görünüm değerlendirildi. VEGF ve FGF-2 düzeyleri immünohistokimyasal olarak analiz edildi. Doku katalaz (CAT) ve malondialdehid (MDA) seviyeleri ELISA yöntemi ile belirlendi. Tüm değerlendirmeler cerrahi sonrası 3., 7. ve 14. günlerde gerçekleştirildi. Bulgular: t-HP yağı uygulaması yapılan grupta, t-zeytinyağı uygulaması yapılan gruba göre daha yüksek epitelyal birleşme (7. günde) ve genel yara görünüm skorları (7. ve 14. günlerde) tespit edildi (p <0.05). Diğer taraftan, RE skorları gruplar arasında farklı değildi (p>0.05). Pozitif olarak boyanmış FGF-2 hücrelerinin sayısı, test grubunda kontrol grubundan daha yüksekti (p <0.05), ancak gruplar arasında pozitif boyanmış VEGF damar sayısı açısından anlamlı bir fark yoktu (p>0.05). t-HP yağı uygulaması, t-zeytinyağı uygulamasına göre doku CAT seviyelerini arttırırken, doku MDA seviyelerini düşürdü (p <0.05). Sonuç: Bu çalışmadan elde edilen sonuçlar, topikal HP yağının tedavi öncesi uygulanmasının antioksidan etkilere sahip olduğunu, taşıyıcısı olan zeytinyağı ile karşılaştırıldığında sekonder yara iyileşmesini hızlandırmak amacıyla kullanılabileceğini göstermiştir.

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Section: Discussionmentioning

confidence: 99%

Palatal Mukozal Hasar Oluşturulan Tavşanlarda Profilaktik Hypericum Perforatum Yağ Uygulamasının Antioksidan Özellikleri

Günpınar

Kiliç²,

Tosun³

et al. 2020

Celal Bayar Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi

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“…When the wound heals, fibroblasts exhibit apoptotic phenotypes . In proliferative hypertrophic scars, the fibroblasts remained active and showed reduced apoptosis .…”

Section: Discussionmentioning

confidence: 99%

“…When the wound heals, fibroblasts exhibit apoptotic phenotypes. 21 In proliferative hypertrophic scars, the fibroblasts remained active and showed reduced apoptosis. 22 Here, WG449E promoted HSF apoptosis by inducing the expression of cleaved caspase-3, suggesting that the compound reduces the population of hypertrophic scar fibroblasts not only by inhibiting cell proliferation but also by inducing cell apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Research on function and mechanisms of a novel small molecule WG449E for hypertrophic scar

Shao

Tang

et al. 2019

Acad Dermatol Venereol

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Background Hypertrophic scars are complications of severe wound healing characterized by excessive fibrosis associated with aberrant function of fibroblasts. However, no available drugs can be utilized to effectively treat these scars. The transforming growth factor β (TGFβ) signalling pathway regulates collagen synthesis and plays an important role in scar formation. Objectives To evaluate the anti‐scar effects of TGFβ inhibitors in vitro and in vivo. Methods Col1α2‐luciferase reporter assay was used to screen the compounds suppress type I collagen gene transcription. Sulforhodamine B colorimetric assay and colony formation assay were used to test the compound's effect on cell proliferation. Wound healing and transwell assay were performed to test the cell migration and invasion. Western blotting, immunofluorescence, immunohistochemistry and Q‐PCR assay were used to determine the protein and mRNA levels. 3D cell contraction assay was used to examine the cell contraction. Flow cytometry was performed to analyse cell apoptosis. Masson stain, H&E stain and immunochemistry were used to analyse the scar formation in vivo. Results WG449E, as one of the most potent inhibitors, was identified to significantly downregulate the mRNA and protein levels of collagen in hypertrophic scar‐derived fibroblasts through inhibiting Smad2/3 phosphorylation. WG449E inhibited the proliferation, migration and contraction of fibroblasts in vitro and in vivo. In addition, WG449E induced cell apoptosis through the activation of cleaved‐caspase3. Moreover, WG449E significantly attenuated hypertrophic scar formation and collagen deposition in a mechanical load‐induced mouse model. Conclusions WG449E is a potential candidate for the treatment of hypertrophic scars.WG449E downregulates the mRNA and protein levels of collagen in hypertrophic scar‐derived fibroblasts through inhibiting Smad2/3 phosphorylation and nucleic localization. WG449E blocks HSF migration and invasion by regulating F‐actin assignment. In addition, WG449E induces HSF apoptosis through the activation of cleaved‐caspase3.

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“…The bulk of the SJW phyto‐complex is encompassed by a broad spectrum of secondary metabolites, mainly naphthodianthrones (hypericins) and polyprenylated polycyclic acylphloroglucinols (hyperforins; Figure D). However, its antidepressant and skin healing properties are mainly due to its hyperforin content . Translucent oil glands are the storage organelle for hyperforin but hypericin is housed in dark nodules distributed in leaves and flowers (Figure C, D).…”

Section: Introductionmentioning

confidence: 99%

“…First, because they are devoid of hypericin, which diminishes the need of costly CO 2 ‐based supercritical extraction; second, they are free from chlorophyll, whose presence is known to interfere with the downstream processing . Recently, pure hyperforin has been proven to have anti‐proliferative and anti‐migratory effects in 2D and 3D artificial skin constructs of human dermal fibroblasts . In this context, the downstream processing of the hyperforin‐rich petroleum ether extract and its use as a potential anti‐proliferative agent using human keratinocytes, fibroblasts as well artificial skin constructs were investigated in detail .…”

Section: Introductionmentioning

confidence: 99%

Toward enhanced hyperforin production in St. John's wort root cultures

Gaid

Grosch

Möller

et al. 2019

Engineering in Life Sciences

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During the past decades, several trials targeted a stable, sustainable and economic production of St. John's wort (Hypericum perforatum) extract. The value of this extract stems from its use to treat depression and skin irritation due to its hyperforin content. Previously, hyperforin‐forming in vitro root cultures were established. Here, detailed growth and production kinetics have been analyzed over 40 days of cultivation. In the first 10 days, sucrose was completely hydrolyzed to glucose and fructose. The ammonium consumption supported the increase in the biomass and hyperforin production. When sucrose was replaced with glucose/fructose, the linear growth phase started 6 days earlier and resulted in a higher space‐time‐yield. The maximum hyperforin production was 0.82 mg L−1 day−1, which was 67 % higher than in the sucrose‐supplemented standard cultivation. Buffering the sucrose‐supplemented medium with phosphate caused a 2.7‐fold increase in the product to biomass yield coefficient. However, the combination of monosaccharides and buffering conditions did not cause an appreciable improvements in the production performance of the shake flask approaches. A potential scalability from flask to lab‐scale stirred bioreactors has been demonstrated. The results obtained offer a basis for a scalable production of hyperforin and a sustainable source for a tissue culture‐based phytomedicine.

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Anti-proliferative and anti-migratory effects of hyperforin in 2D and 3D artificial constructs of human dermal fibroblasts – A new option for hypertrophic scar treatment?

Cited by 18 publications

References 27 publications

Palatal Mukozal Hasar Oluşturulan Tavşanlarda Profilaktik Hypericum Perforatum Yağ Uygulamasının Antioksidan Özellikleri

Palatal Mukozal Hasar Oluşturulan Tavşanlarda Profilaktik Hypericum Perforatum Yağ Uygulamasının Antioksidan Özellikleri

Research on function and mechanisms of a novel small molecule WG449E for hypertrophic scar

Toward enhanced hyperforin production in St. John's wort root cultures

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