With the development of chemistry, active ingredients of TCMs and herbs have been further identified by chemists. Despite the wide variety of ingredients in TCM and their complex interactions with the human body, it is still quite difficult to disclose the molecular mechanisms, which severely hampers TCM modernization and internationalization. Therefore, herbs and herb formulas are perspectives for promoting human health against diseases. Recently, TCM presented a remarkable effectiveness of high epidemic COVID-19 treatment through various approaches ( Li et al., 2021a). In the concepts of traditional Chinese medicine (TCM) theory, herbs and herb formulas have been extensively used for treating multiple diseases for thousands of years. Additionally, drugs targeting JAK/STAT signaling may effectively assist in the treatment of COVID-19 by restricting cytokine storm syndrome ( Luo et al., 2020 Solimani et al., 2021), and three severe COVID-19 cases are reported to be observed to have sustained improvements in outcome with ruxolitinib, which targets the JAK/STAT pathway ( Rojas and Sarmiento, 2021).Ĭhinese herbs, which have widespread distribution throughout China, are the gold resources in China. Interestingly, even if tofacitinib is the only FDA-approved drug indirectly related to the STAT3 target, it is still more effective than most of these first-line drugs for RA patients, especially in patients with methotrexate-resistant active RA. Evidence demonstrates that tofacitinib, a pan-Janus kinase (JAK) inhibitor, is the only FDA-approved drug for RA treatment that downregulated STAT3 signaling mainly by inhibiting JAK expression ( Miklossy et al., 2013). JAK/STAT signaling regulates many cellular processes essential to maintaining cell homeostasis, whose dysregulation contributes to cancer progressions and inflammatory and autoimmune disorders and COVID-19 emergencies ( Chen et al., 2021a Solimani et al., 2021).Īctivation of the JAK/STAT signaling pathway and involved diseases.Ī wide spectrum of diseases has been alleviated by treating with JAK inhibitors. More specifically, its clinical applications have become increasingly important with the discovery of novel clinical syndromes caused by mutations in JAK and STAT genes ( Luo et al., 2021a). JAK/STAT is now recognized as one of the central mediators of widespread and varied human physiological processes. An overview of the JAK/STAT signaling pathway is presented in Figure 1. Subsequently, phospho-JAKs result in docking with different STATs, which causes dimerization of STATs, translocation into the nucleus, and initiate the transcription process ( Stark et al., 2018). In response to cytokines binding to specific JAKs, JAKs located in the cytoplasm undergo conformational changes, causing autophosphorylation or transphosphorylation. Moreover, intracellular tyrosine kinases are activated by the abundance of membrane receptors binding to corresponding cytokines. STAT activation is triggered by Janus kinases (JAKs), which are intracellular tyrosine kinases. Signal transducer and activator of transcriptions (STATs) family members play distinct roles in cell differentiation, tissue repair, and anti-tumor immunity. Our study will provide support for revealing TCM, their active compounds that treat diseases, and the underlying mechanism, further improving the rapid spread of TCM to the world. In this review, we summarized various herbs, herb formulas, natural compounds, and phytochemicals isolated from herbs that have the potential for regulating multiple biological processes via modulation of the JAK/STAT signaling pathway based on the published work. With the development of chemistry and pharmacology, active ingredients of TCM and herbs and underlying mechanisms have been further identified and confirmed by pharmacists and chemists, which improved, to some extent, awkward limitations, approval, and applications regarding TCM and herbs. However, Chinese herbs and herb formulas are characterized by complicated components, resulting in various targets and pathways in treating diseases, which limits their approval and applications. Chinese herbs in traditional Chinese medicine (TCM), which are widespread throughout China, are the gold resources of China and have been extensively used for treating multiple diseases for thousands of years. Therefore, influences on the STAT signaling pathway have potential and perspective approaches for diverse diseases. Moreover, tofacitinib and baricitinib as the JAK/STAT inhibitors have been recently approved by the FDA for rheumatology disease treatment. Abnormal activation of the STAT pathway can contribute to disease progressions under various conditions. JAK/STAT signaling pathways are closely associated with multiple biological processes involved in cell proliferation, apoptosis, inflammation, differentiation, immune response, and epigenetics.
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