The anti-TH17 polarization effect of Indigo naturalis and tryptanthrin by differentially inhibiting cytokine expression

Cheng, Hao; Kuo, Yi Zih; Chang, Che Ying; Chang, Chun‐Han; Fang, Wei; Chang, Chen Ni; Pan, Shiyan; Lin, Jin Yuarn; Wu, Li-Wha

doi:10.1016/j.jep.2020.112760

Cited by 21 publications

(17 citation statements)

References 39 publications

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“…Among the different T cell subsets, a population of IL17-producing T helper cells (TH17) has been shown to be involved in model systems of autoimmunity (Weaver et al, 2007). Recently Cheng et al (Cheng et al, 2020) reported that TRYP exhibits anti-TH17 activity through its ability to repress the expression of several cytokines required for TH17 polarization.…”

Section: Discussionmentioning

confidence: 99%

“…However, we found here that both TRYP and TRYP-Ox have relatively low anti-AChE effects, suggesting that AChE is probably not a therapeutic target for these compounds in CIA or CAIA. Note that TRYP has been reported to act on multiple signaling cascades associated with inflammation, including TNF/NF-κB and IL-6/STAT3 ( Wang et al., 2018 ), leukotriene secretion ( Pergola et al., 2012 ), and several cytokines required for TH17 polarization ( Cheng et al., 2020 ). TRYP has also been reported to inhibit macrophage nitric oxide and prostaglandin E production upon exposure to oxidative stress ( Ishihara et al., 2000 ), as well as inhibit cyclooxygenase-2 and indoleamine 2,3-dioxygenase activities ( Danz et al., 2001 ; Pergola et al., 2012 ; Yang et al., 2013 ).…”

Section: Discussionmentioning

confidence: 99%

“…Recently Cheng et al. ( Cheng et al., 2020 ) reported that TRYP exhibits anti-TH17 activity through its ability to repress the expression of several cytokines required for TH17 polarization.…”

Section: Discussionmentioning

confidence: 99%

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Therapeutic Effects of Tryptanthrin and Tryptanthrin-6-Oxime in Models of Rheumatoid Arthritis

et al. 2020

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Rheumatoid arthritis (RA) is a chronic autoimmune disease involving joint and bone damage that is mediated in part by proteases and cytokines produced by synovial macrophages and fibroblast-like synoviocytes (FLS). Although current biological therapeutic strategies for RA have been effective in many cases, new classes of therapeutics are needed. We investigated anti-inflammatory properties of the natural alkaloid tryptanthrin (TRYP) and its synthetic derivative tryptanthrin-6-oxime (TRYP-Ox). Both TRYP and TRYP-Ox inhibited matrix metalloproteinase (MMP)-3 gene expression in interleukin (IL)-1b-stimulated primary human FLS, as well as IL-1b-induced secretion of MMP-1/3 by FLS and synovial SW982 cells and IL-6 by FLS, SW982 cells, human umbilical vein endothelial cells (HUVECs), and monocytic THP-1 cells, although TRYP-Ox was generally more effective and had no cytotoxicity in vitro. Evaluation of the therapeutic potential of TRYP and TRYP-Ox in vivo in murine arthritis models showed that both compounds significantly attenuated the development of collagen-induced arthritis (CIA) and collagen-antibody-induced arthritis (CAIA), with comparable efficacy. Collagen II (CII)specific antibody levels were similarly reduced in TRYP-and TRYP-Ox-treated CIA mice. TRYP and TRYP-Ox also suppressed proinflammatory cytokine production by lymph node cells from CIA mice, with TRYP-Ox being more effective in inhibiting IL-17A, granulocyte-macrophage colony-stimulating factor (GM-CSF), and receptor activator of nuclear factor-kB ligand (RANKL). Thus, even though TRYP-Ox generally had a better in vitro profile, possibly due to its ability to inhibit c-Jun N-terminal kinase (JNK), both TRYP and TRYP-Ox were equally effective in inhibiting the clinical symptoms and damage associated with RA. Overall, TRYP and/or TRYP-Ox may represent potential new directions for the pursuit of novel treatments for RA.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Therapeutic Effects of Tryptanthrin and Tryptanthrin-6-Oxime in Models of Rheumatoid Arthritis

et al. 2020

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“…Indirubin in indigo naturalis can inhibit wnt/β-Catenin signal transduction by restoring the expression of wif-1, inhibit the expression of TGase1 and down-regulate CDK1 to inhibit the proliferation of keratinocytes [ 62 – 64 ]. Tryptophan, another active component of indigo naturalis, has been proved to have the ability to inhibit keratinocytes, which is stronger than indigo and indirubin [ 65 , 66 ]. Tryptophan can also inhibit the activity of apelin promoter, and inhibit the proliferation and migration of vascular endothelial cells by causing G 2 /M phase arrest, inhibiting Akt and FAK pathway, thus achieving anti angiogenesis effect [ 67 ].…”

Section: Pharmacology and Mechanismsmentioning

confidence: 99%

“…The clinical observation of indigo naturalis in treating psoriasis has been reported in the 1980 s, and the overall cure rate is 69.6% [ 80 ]. According to the modern research results, indigo naturalis mainly treats psoriasis by inhibiting the excessive proliferation of keratinocytes, regulating the body immunity, reducing inflammation and anti angiogenes [ 62 – 65 , 67 ]. At present, indigo naturalis is mostly used as external preparation in treating psoriasis vulgaris and nail psoriasis (Table 1 ).…”

Section: Clinical Applicationsmentioning

confidence: 99%

From natural dye to herbal medicine: a systematic review of chemical constituents, pharmacological effects and clinical applications of indigo naturalis

Yang

Zhang

et al. 2020

Chin Med

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Background Indigo naturalis is a blue dye in ancient, as well as an extensive used traditional Chinese medicine. It has a wide spectrum of pharmacological properties and can be used to treat numerous ailments such as leukemia, psoriasis, and ulcerative colitis. This article aims to expand our understanding of indigo naturalis in terms of its chemical constituents, pharmacological action and clinical applications. Methods We searched PubMed, web of science, CNKI, Google academic, Elsevier and other databases with the key words of “Indigo naturalis”, and reviewed and sorted out the modern research of indigo naturalis based on our research results. Results We outlined the traditional manufacturing process, chemical composition and quality control of indigo naturalis, systematically reviewed traditional applictions, pharmacological activities and mechanism of indigo naturalis, and summarized its clinical trials about treatment of psoriasis, leukemia and ulcerative colitis. Conclusions Indigo naturalis has a variety of pharmacological activities, such as anti-inflammatory, antioxidant, antibacterial, antiviral, immunomodulatory and so on. It has very good clinical effect on psoriasis, leukemia and ulcerative colitis. However, it should be noted that long-term use of indigo naturalis may produce some reversible adverse reactions. In summarize, indigo naturalis is an extremely important drug with great value and potential.

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Natural alternatives targeting psoriasis pathology and key signaling pathways: a focus on phytochemicals

et al. 2023

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The anti-TH17 polarization effect of Indigo naturalis and tryptanthrin by differentially inhibiting cytokine expression

Cited by 21 publications

References 39 publications

Therapeutic Effects of Tryptanthrin and Tryptanthrin-6-Oxime in Models of Rheumatoid Arthritis

Therapeutic Effects of Tryptanthrin and Tryptanthrin-6-Oxime in Models of Rheumatoid Arthritis

From natural dye to herbal medicine: a systematic review of chemical constituents, pharmacological effects and clinical applications of indigo naturalis

Natural alternatives targeting psoriasis pathology and key signaling pathways: a focus on phytochemicals

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