Indirubin: a novel topical agent in the treatment of psoriasis

Sekhon, Sahil; Koo, John

doi:10.1111/bjd.16074

Cited by 10 publications

(7 citation statements)

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“…Indigo Naturalis mainly contains indigo, indirubin, tryptanthrin and other alkaloids, as well as indigo ketone, terpenoids, sitosterol and amino acids [78,79]. Indigo and indirubin are the main components of Indigo Naturalis and are the two important indicators for the quality of Indigo Naturalis in the Chinese Pharmacopoeia [17], and indirubin is generally taken as the major effective constituents of Indigo Naturalis for the treatment of acute promyelocytic leukemia and inflammation and autoimmune diseases such as colitis and psoriasis [21,80,81]. However, we found that neither indigo nor indirubin could alleviate IAV-induced ALI by oral administration (data were shown in Additional file 1: Fig.…”

Section: Discussionmentioning

confidence: 99%

Beneficial effect of Indigo Naturalis on acute lung injury induced by influenza A virus

Tian

et al. 2020

Chin Med

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Background Infections induced by influenza viruses, as well as coronavirus disease 19 (COVID-19) pandemic induced by severe acute respiratory coronavirus 2 (SARS-CoV-2) led to acute lung injury (ALI) and multi organ failure, during which traditional Chinese medicine (TCM) played an important role in treatment of the pandemic. The study aimed to investigate the effect of Indigo Naturalis on ALI induced by influenza A virus (IAV) in mice. Method The anti-influenza and anti-inflammatory properties of aqueous extract of Indigo Naturalis (INAE) were evaluated in vitro. BALB/c mice inoculated intranasally with IAV (H1N1) were treated intragastrically with INAE (40, 80 and 160 mg/kg/day) 2 h later for 4 or 7 days. Animal lifespan and mortality were recorded. Expression of high mobility group box-1 protein (HMGB-1) and toll-like receptor 4 (TLR4) were evaluated through immunohistological staining. Inflammatory cytokines were also monitored by ELISA. Result INAE inhibited virus replication on Madin-Darby canine kidney (MDCK) cells and decreased nitric oxide (NO) production from lipopolysaccharide (LPS)-stimulated peritoneal macrophages in vitro. The results showed that oral administration of 160 mg/kg of INAE significantly improved the lifespan (P < 0.01) and survival rate of IAV infected mice, improved lung injury and lowered viral replication in lung tissue (P < 0.01). Treatment with INAE (40, 80 and 160 mg/kg) significantly increased liver weight and liver index (P < 0.05), as well as weight and organ index of thymus and spleen at 160 mg/kg (P < 0.05). Serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels were reduced by INAE administration (P < 0.05). The expression of HMGB-1 and TLR4 in lung tissue were also suppressed. The increased production of myeloperoxidase (MPO) and methylene dioxyamphetamine (MDA) in lung tissue were inhibited by INAE treatment (P < 0.05). Treatment with INAE reduced the high levels of interferon α (IFN-α), interferon β (IFN-β), monocyte chemoattractant protein-1 (MCP-1), regulated upon activation normal T cell expressed and secreted factor (RANTES), interferon induced protein-10 (IP-10), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) (P < 0.05), with increased production of interferon γ (IFN-γ) and interleukin-10 (IL-10) (P < 0.05). Conclusion The results showed that INAE alleviated IAV induced ALI in mice. The mechanisms of INAE were associated with its anti-influenza, anti-inflammatory and anti-oxidation properties. Indigo Naturalis might have clinical potential to treat ALI induced by IAV.

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Section: Discussionmentioning

confidence: 99%

Beneficial effect of Indigo Naturalis on acute lung injury induced by influenza A virus

Tian

et al. 2020

Chin Med

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“…Using a refined formulation (Lindioil), a recent report indicated that Lindioil ointment is more effective than vehicle for the treatment of nail psoriasis [10]. Because indirubin, the active component of indigo naturalis, is an effective component of IN, it may be a safe alternative for topical treatment of psoriasis, which is quite different from topical corticosteroids [41]. A double-blind, dosage-controlled trial of indirubin in IN reported that Lindioil ointment with 200 lg/g of indirubin is most effective [42].…”

Section: The Effectiveness Of Indigo Naturalis For Psoriasismentioning

confidence: 99%

“…A double-blind, dosage-controlled trial of indirubin in IN reported that Lindioil ointment with 200 lg/g of indirubin is most effective [42]. Because, according to an RCT, the therapeutic effects of topical treatment vary for psoriatic plaques, topical IN may be an alternative treatment for refractory psoriasis, which functions through a different mechanism of action [41]. Most studies have been performed by Li et al; a multicenter RCT is needed in the near future.…”

Section: The Effectiveness Of Indigo Naturalis For Psoriasismentioning

confidence: 99%

Treatment with indigo naturalis for inflammatory bowel disease and other immune diseases

Naganuma

2019

Immunological Medicine

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Indigo naturalis (IN) is a herbal medicine extracted from leaves and stems of plants and is a component of crude drugs used in China. Recently, IN was reported to be effective for treating (UC) and psoriasis. The mechanisms of IN for UC is not clear, but aryl hydrocarbon receptor ligand, the active components of IN, can promote mucosal healing by inducing the production of interleukin-22 from type-3 innate lymphocytes cells. Although IN is effective even for refractory cases, critical adverse effects including IN-induced colitis and pulmonary arterial hypertension should be concerned. Due to adverse effects of IN, topical treatment of IN is useful for distal UC as well as psoriasis to secure patients' safeties. Many refractory patients may be helped by IN if it becomes available in appropriate forms for clinical practice. In the near future, the mechanism that underlies the adverse effects of IN needs to be determined, and extraction of active ingredients with fewer side effects, investigated.

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“…Indirubin (IDRB) is a bisindole compound, which is the main active ingredient of Indigo naturalis (Sekhon & Koo, 2018). Traditionally, I. naturalis is a component widely used in traditional Chinese medicine (TCM), for example, Xilei‐san (Tao et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Indirubin regulates T cell differentiation by promoting αVβ8 expression in bone marrow‐derived dendritic cells to alleviate inflammatory bowel disease

Tao

Peng

et al. 2022

Phytotherapy Research

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Inflammatory bowel disease is a disease that can invade the whole digestive tract and is accompanied by immune abnormalities. Immune dysfunction involving dendritic cells (DCs) and T cells is recognized as a key factor in diseases. Indirubin (IDRB) exerts antiinflammatory effects and can help in treating immune diseases. This study aimed to isolate bone marrow‐derived dendritic cells (BMDCs) using lipopolysaccharide (LPS) to obtain mature DCs (mDCs). The expression of CD80, CD86, CD40, and MHC‐II was detected using flow cytometry after treatment with IDRB. αVβ8 siRNA was used to knock down αVβ8 in mDCs, and the expression of CD80, CD86, CD40, and MHC‐II was detected. Meanwhile, DCs were co‐cultured with T cells. Then, T cell differentiation was detected using flow cytometry, and the cytokine levels were detected using enzyme‐linked immunosorbent assay. The animal model of dextran sulfate sodium (DSS)‐induced inflammatory bowel disease was established in mice. After intervention with IDRB and αVβ8 shRNA, the intestinal tissues were evaluated using H&E staining, disease activity index (DAI) score, and histological damage index, and the corresponding factors and cytokines to regulatory T cells (Treg) and Th17 were measured. The results showed that αVβ8 was expressed in immature DCs and mDCs. CD80, CD86, CD40, and MHC‐II expression decreased after IDRB treatment in mDCs. Meanwhile, the expression of TNF‐α and TGF‐β also decreased after IDRB treatment. The effect of IDRB on the expression of CD80, CD86, CD40, MHC‐II, TNF‐α, and TGF‐β in mDCs was reversed by αVβ8 siRNA. The Treg differentiation increased after IDRB treatment, while the differentiation of Th17 cells was inhibited. This effect of IDRB was reversed by mDCs after treatment with αVβ8 siRNA. In vivo experiments showed that IDRB alleviated the symptoms of inflammatory bowel disease in animals. Enteritis significantly reduced, and the effect of IDRB was reversed by αVβ8 shRNA. The results suggested that IDRB regulated the differentiation of T cells by mediating the maturation of BMDCs through αVβ8. This study confirmed the therapeutic effect of IDRB in inflammatory bowel disease and suggested that IDRB might serve as a potential drug.

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Indirubin: a novel topical agent in the treatment of psoriasis

Abstract: Linked Article: Lin et al. Br J Dermatol 2018; 178:124–131.

Cited by 10 publications

References 10 publications

Beneficial effect of Indigo Naturalis on acute lung injury induced by influenza A virus

Beneficial effect of Indigo Naturalis on acute lung injury induced by influenza A virus

Treatment with indigo naturalis for inflammatory bowel disease and other immune diseases

Indirubin regulates T cell differentiation by promoting αVβ8 expression in bone marrow‐derived dendritic cells to alleviate inflammatory bowel disease

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