A traditional Chinese remedy points to a natural skin habitat: indirubin (indigo naturalis) for psoriasis and the <i>Malassezia</i>
 metabolome

Gaitanis, Georgios; Magiatis, Prokopios; Velegraki, Aristea; Bassukas, Ioannis D.

doi:10.1111/bjd.16807

Cited by 15 publications

(8 citation statements)

References 5 publications

(14 reference statements)

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“…Ambient environmental conditions and host factors (hygiene, genetic predisposition, age and immune status) can cause shifts in skin microbial communities and induce Malassezia ‐associated diseases . Malassezia , apart from Malassezia folliculitis, causes seborrhoeic dermatitis (SD), pityriasis versicolor (PV), aggravates the head and neck variant of atopic dermatitis and is recently suggested to participate in psoriasis through mechanisms that include aryl hydrocarbon receptor downstream pathways . Malassezia yeasts have been also associated with catheter‐related fungemia, sepsis and invasive infections in immunocompromised patients on parenteral nutrition …”

Section: Resultsmentioning

confidence: 99%

Critical synthesis of available data in Malassezia folliculitis and a systematic review of treatments

Vlachos

Henning

Gaitanis

et al. 2020

Acad Dermatol Venereol

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Folliculitis is an inflammatory process involving the hair follicle, frequently attributed to infectious causes. Malassezia, an established symbiotic yeast that can evolve to a skin pathogen with opportunistic attributes, is a common source of folliculitis, especially when intrinsic (e.g. immunosuppression) or extrinsic (high ambient temperature and humidity, clothing) impact on the hair follicle and the overlying skin microenvironment. Our aim was to critically review the pathophysiology and clinical characteristics of Malassezia folliculitis, to describe laboratory methods that facilitate diagnosis and to systematically review treatment options. Malassezia folliculitis manifests as a pruritic, follicular papulopustular eruption distributed on the upper trunk. It commonly affects young to middle-aged adults and immunosuppressed individuals. Inclusion into the differential diagnosis of folliculitis is regularly oversighted, and the prerequisite-targeted diagnostic procedures are not always performed. Sampling by tape stripping or comedo extractor and microscopic examination of the sample usually identifies the monopolar budding yeast cells of Malassezia without the presence of hyphae. However, confirmation of the diagnosis with anatomical association with the hair follicle is performed by biopsy. For systematic review of therapies, PubMed was searched using the search string "(malassezia" [MeSH Terms] OR "malassezia" [All Fields] OR pityrosporum [All Fields]) AND "folliculitis" [MeSH Terms] and EMBASE was searched using the search string: 'malassezia folliculitis.mp OR pityrosporum folliculitis.mp'. In total, 28 full-length studies were assessed for eligibility and 21 were selected for inclusion in therapy evaluation. Conclusively Malassezia folliculitis should be considered in the assessment of truncal, follicular skin lesions. Patient's history, comorbidities and clinical presentation are usually indicative, but microscopically and histological examination is needed to confirm the diagnosis. Adequate samples obtained with comedo extractor and serial sections in the histological material are critical for proper diagnosis. Therapy should include systemic or topical measures for the control of the inflammation, as well as the prevention of recurrences.

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Section: Resultsmentioning

confidence: 99%

Critical synthesis of available data in Malassezia folliculitis and a systematic review of treatments

Vlachos

Henning

Gaitanis

et al. 2020

Acad Dermatol Venereol

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“…In the skin, indirubin was shown to attenuate psoriasis-like skin lesions in imiquimod-induced and Stat3-transgenic mouse models 6,7 . Topical application of indirubin also improved human psoriasis in a clinical trial without causing serious adverse events 8,9 . Indirubin is known to exert its biological function via xenobiotic aryl hydrocarbon receptor (AHR) 10 .…”

Section: Introductionmentioning

confidence: 92%

Indirubin-pregnane X receptor-JNK axis accelerates skin wound healing

Tanaka

Uchi

Ito

et al. 2019

Sci Rep

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Indirubin is a potent anti-inflammatory phytochemical derived from indigo naturalis. It is also endogenously produced in the intestine and detected in the circulation in mammals. Indirubin exerts its biological functions via two xenobiotic receptor systems: aryl hydrocarbon receptor (AHR) and pregnane X receptor (PXR); however, its effects on wound healing remain elusive. To investigate whether indirubin promotes wound healing, we utilized an in vitro scratch injury assay and in vivo full-thickness mouse skin ulcer model and assessed wound closure. Indirubin significantly accelerated wound closure in both the scratch assay and the skin ulcer model. Using inhibitors of cell proliferation or migration, indirubin was found to upregulate the migratory but not the proliferative capacity of keratinocytes. Activation of AHR/PXR by indirubin was confirmed by their nuclear translocation and subsequent upregulation of CYP1A1 (AHR), or UGT1A1 mRNA (PXR) and also by luciferase reporter assay (PXR). Although both AHR and PXR were activated by indirubin, its pro-migratory capacity was canceled by PXR inhibition but not by AHR inhibition and was dependent on the JNK pathway. Moreover, activated PXR was detected in the nuclei of re-epithelialized keratinocytes in human skin ulcers. In conclusion, this study shows that the indirubin-PXR-JNK pathway promotes skin wound healing.

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“…With the advantage of being generally safe and having few side effects, great attention has been paid to natural products in the past few decades [ 8 , 9 ]. Indirubin (IR), isolated from indigo naturalis, has been shown to improve psoriasis without causing any serious adverse events [ 10 , 11 ]. Previous studies have shown that IR could alleviate psoriasis via regulation of keratinocyte proliferation and reduces inflammatory processes [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Transdermal Delivery of Indirubin-Loaded Microemulsion Gel: Preparation, Characterization and Anti-Psoriatic Activity

et al. 2022

IJMS

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Psoriasis is an immune disease caused by rapid and incomplete differentiation of skin basal cells. Natural products such as indirubin have historically served as excellent sources for the treatments of psoriasis. However, the poor solubility and bioavailability due to its plane and rigid crystal structure, which limits its efficacy. Herein, to improve the efficacy of indirubin, a hydrogel-based microemulsion drug delivery system was developed for transdermal delivery. The mean droplet size of the optimized microemulsion was 84.37 nm, with a polydispersity index (PDI) less than 0.2 and zeta potential value of 0~−20 mV. The transdermal flux and skin retention of indirubin at 24 h were 47.34 ± 3.59 μg/cm2 and 8.77 ± 1.26 μg/cm2, respectively. The optimized microemulsion was dispersed in carbomer 934 hydrogel to increase the consistency. The indirubin-loaded microemulsion gel was tested on an imiquimod-induced psoriasis mouse model. Results showed that this preparation can improve psoriasis symptoms by down-regulating the expression of IL-17A, Ki67, and CD4+T. This experiment provides great scalability for researchers to treat psoriasis, avoid first-pass effects, and increase the concentration of targeted drugs.

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A traditional Chinese remedy points to a natural skin habitat: indirubin (indigo naturalis) for psoriasis and the Malassezia metabolome

Abstract: Linked Article: Lin et al. Br J Dermatol 2018; 178:124–31.

Cited by 15 publications

References 5 publications

Critical synthesis of available data in Malassezia folliculitis and a systematic review of treatments

Critical synthesis of available data in Malassezia folliculitis and a systematic review of treatments

Indirubin-pregnane X receptor-JNK axis accelerates skin wound healing

Transdermal Delivery of Indirubin-Loaded Microemulsion Gel: Preparation, Characterization and Anti-Psoriatic Activity

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