Under the invasion of foreign pathogens and harmful stimuli, the inflammatory response is activated as the first line of defense which helps the body repair damaged tissues and remove irritants and damaged cells. When the inflammatory response is overheated, it will cause pathological changes and lead to serious diseases such as allergies, rheumatoid arthritis, and cancer. Macrophages are natural immune cells that activate the cascades of pro-inflammatory factors and play an important role in stimulating the immune system and triggering an inflammatory response. In addition, anti-inflammatory cytokines play an essential role in inflammation regulation. Many studies have elucidated the underlying molecular mechanism of various inflammatory pathological processes caused by stimuli. Among different pathways, there are several classical inflammatory pathways: NF-κB, MAPKs, and JAK/STAT signal pathways. Recently, the non-classical Hippo pathway has been highlighted in inflammatory responses of macrophage. However, the molecular mechanism of autoimmune modulation or anti-inflammatory potential remains unknown. Therefore, the exploration of the molecular mechanisms of autoimmune modulation or anti-inflammatory response, and the discovery of novel therapeutic options have become research hotspots.

COX-1 and -2 inhibitors are the mainstays to treat inflammatory symptoms. However, there is an increasing risk of gastrointestinal side effects with COX non-selective nonsteroidal anti-inflammatory drugs (NSAIDs). To cope with the limitations of NSAIDs, COX-2 selective inhibitors were developed to eliminate gastrointestinal toxicity and achieve the anti-inflammatory benefit. However, COX-2 inhibitors were taken off the pharmaceutical market due to multiple kinds of severe side effects, including cardiovascular diseases, ulcers, and bleeding within the gastrointestinal tract. Moreover, the overall outcome is very limited in terms of new clinical medicines/interventions (including prevention). Historically, medicinal plants and natural products have been the mainstay of healthcare systems. During the last three decades, more than 50% of the clinically approved pharmaceutical drugs have developed either directly or indirectly from natural products, mostly plant-derived secondary metabolites. Therefore, the research community is seeking effective anti-inflammatory inhibitors from medicinal plants.

Meanwhile, certain natural products from medicinal plants, like glycyrrhizic acid, andrographolide, and resveratrol have already demonstrated notable anti-inflammatory activity, individually or as adjuvants of clinical drugs. However, lots of plant species with putative autoimmune modulation or anti-inflammatory potential remains untapped. It is high time to make these natural products to undertake a systematic investigation of drug discovery with modern tools. For example, the prediction of mechanisms of Traditional Chinese Medicine prescriptions for autoimmune and anti-inflammatory modulation was analyzed in KEGG pathways and GO terms associated with biological processes, molecular functions, and cellular components. High-throughput screening and high-content screening were used to discover novel autoimmune-modulating or anti-inflammatory plant products. Natural products’ molecular target screening using CRISPR/Cas9-sgRNA libraries or fishing-rod strategy can be also used to analyze the contribution of each molecular target to natural products’ effects. Cutting edge technologies such as RNA-sequence were combined to clarify the multi-target and synergistic mechanism of natural products’ effects.

In this Research Topic, we welcome pharmacology-focused Original Research, Reviews, Mini-reviews, Methods, and Opinion articles that relate to, but are not limited to, the following subtopics:
• The molecular mechanisms of autoimmune diseases, or inflammatory diseases occurrence.
• Medicinal plants as a repository of prospective autoimmune modulation, or anti-inflammatory phytochemicals with broad-spectrum autoimmune modulating or anti-inflammatory activity.
• Methodology of screening strategy for the discovery of novel autoimmune-modulating or anti-inflammatory plant products.
• Traditional/local medicinal formulations based on crude plant parts/extracts showing the prospective autoimmune-modulating or anti-inflammatory properties.
• Synthetic analogs of phytochemicals with potential autoimmune modulating or anti-inflammatory/synergistic properties.
• Plant products as adjuvants, in combination with standard autoimmune-modulating or anti-inflammatory therapeutics.
• Clinical application of plant products in the management of autoimmune diseases, or inflammatory diseases.
• Future directions for research on the potential of the autoimmune and inflammatory diseases of medicinal plants.
• The molecular mechanisms of natural products’ autoimmune-modulating or anti-inflammatory effects.
• The natural products’ molecular targets, the multi-target and synergistic mechanism of natural products’ autoimmune-modulating or anti-inflammatory effects.

Note to authors:
Only medicinal plant products with well-defined composition and plant extracts with standardized chemical constituents will be considered in this project.

All the manuscripts submitted will be peer-reviewed and need to fully comply with the Four Pillars of Best Practice in Ethnopharmacology (you can freely download the full version here).

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