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Medically reviewed by Dr. Samuel Sarmiento, M.D., MPH on August 3, 2023

Shikonin, the primary active component of the traditional Chinese medicinal herb “ZiCao,” has exhibited a broad range of pharmacological effects, including anti-inflammatory, anti-tumor, and antioxidant activity. Recent research demonstrates its potential for treating immune-related inflammatory diseases like multiple sclerosis, asthma, lupus nephritis, and inflammatory bowel disease by modulating cytokine expression and targeting critical signaling pathways.

Shikonin is the main active compound in the traditional Chinese medicinal herb “ZiCao.” Shikonin exhibits a wide range of pharmacological actions, such as anti-inflammatory, anti-tumor, and antioxidant effects. A study in the journal Biomedicine & Pharmacotherapy has reviewed the recent advances in the use of shikonin for treating immune-related inflammatory diseases and the underlying mechanisms.

Shikonin’s Anti-Inflammatory and Potential Neuroprotective Effects on Multiple Sclerosis

In a mouse model of multiple sclerosis, the use of shikonin led to significant reductions in TNF-α and IFN-γ expression, as well as increases in TGF-β and glutathione peroxidase-1 activity. This suggests anti-inflammatory activity and potential neuroprotective effects in multiple sclerosis.

Shikonin’s Impact on Glucose Metabolism and Diabetes

Shikonin promotes glucose uptake by adipocytes and skeletal muscles, improving glucose tolerance and reducing blood glucose levels. It can also inhibit adipocyte differentiation and prevent obesity. These findings are promising for the management of diabetes.

Shikonin’s Potential Therapeutic Role in Asthma

Research findings that indicate the possible therapeutic role of shikonin in asthma include inhibition of eosinophil expression and cytokine production and modulation of the extracellular signal-regulated kinase (ERK)/nuclear factor-kappa B (NF-κB) signal pathway.

Therapeutic Potential of Shikonin in Lupus Nephritis and Inflammatory Bowel Disease

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In a mouse model of lupus nephritis, shikonin showed significant inhibition of the anti-dsDNA antibody and down-regulation of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression. In an inflammatory bowel disease mouse model, shikonin displayed reduced inflammation, inhibition of COX-2 and peroxidase in the affected tissue, down-regulation of cytokine expression, and inhibition of NF-κB and STAT3 pathways.

Shikonin’s Immunomodulatory Effects on T-Cells and B-Cells

Shikonin exerts an immunosuppressive effect by inhibiting T-cell proliferation and pro-inflammatory cytokine expression. Shikonin inhibits T-cell differentiation into Th17, thereby reducing Th17-mediated inflammation. It may also increase iTreg cell secretion and promote CD4 +Foxp3 +Treg differentiation. Furthermore, shikonin can inhibit M2 pyruvate kinase activity, B-cell proliferation, and immunoglobulin production. More research is needed to fully understand its effects on B-cell activation and antibody production.   

Shikonin’s Therapeutic Potential in Autoimmune Diseases

Shikonin may exert a therapeutic role in autoimmune diseases by inhibiting pro-inflammatory cytokines such as TNF- α, IL-6, and IL-lβ, while increasing the anti-inflammatory cytokines IL-10, TGF- β, and IFN- β. These cytokines are crucial in the pathogenesis of numerous autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, psoriasis, atherosclerosis, chronic hepatitis, pulmonary fibrosis, and inflammatory bowel disease. 

Shikonin’s Impact on Autoimmune Disease Signaling Pathways

Shikonin also targets key signaling pathways involved in the pathogenesis of autoimmune diseases. It inhibits NF-κB, which mediates inflammation and cytokine expression. It also suppresses the expression of IL-17 and inhibits the JAK/STAT3 signal pathway. Additionally, shikonin inhibits the mitogen-activated protein kinase pathway, known for its role in cell proliferation and apoptosis.

As these findings are from animal models, further research is needed to verify clinical efficacy and safety for human application.

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Guo, Y., Zhou, M., Mu, Z., Guo, J., Hou, Y., Xu, Y., & Geng, L. (2023). Recent advances in shikonin for the treatment of immune-related diseases: Anti-inflammatory and immunomodulatory mechanisms. Biomedicine & Pharmacotherapy, 165, 115138. https://doi.org/10.1016/j.biopha.2023.115138