The pathogenesis of inflammatory bowel disease (IBD) is related to genetic susceptibility, enteric dysbiosis, and uncontrolled, chronic inflammatory responses that lead to colonic tissue damage and impaired intestinal absorption. As a consequence, patients with IBD are prone to nutrition deficits after each episode of disease resurgence. Nutritional supplementation, especially for protein components, is often implemented during the remission phase of IBD. Notably, ingested nutrients could affect the progression of IBD and the prognostic outcome of patients; therefore, they should be cautiously evaluated prior to being used for IBD intervention. Arginine (Arg) is a semi-essential amino acid required for protein synthesis and intimately associated with gut pathophysiology. To help optimize arginine-based nutritional intervention strategies, the present work summarizes that during the process of IBD, patients manifest colonic Arg deficiency and the turbulence of Arg metabolic pathways. The roles of Arg–nitric oxide (catalyzed by inducible nitric oxide synthase) and Arg–urea (catalyzed by arginases) pathways in IBD are debatable; the Arg–polyamine and Arg–creatine pathways are mainly protective. Overall, supplementation with Arg is a promising therapeutic strategy for IBD; however, the dosage of Arg may need to be carefully tailored for different individuals at different disease stages. Additionally, the combination of Arg supplementation with inhibitors of Arg metabolic pathways as well as other treatment options is worthy of further exploration.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease caused by many factors including colonic inflammation and microbiota dysbiosis. Previous studies have indicated that celastrol (CSR) has strong anti-inflammatory and immune-inhibitory effects. Here, we investigated the effects of CSR on colonic inflammation and mucosal immunity in an experimental colitis model, and addressed the mechanism by which CSR exerts the protective effects. We characterized the therapeutic effects and the potential mechanism of CSR on treating UC using histological staining, intestinal permeability assay, cytokine assay, flow cytometry, fecal microbiota transplantation (FMT), 16S rRNA sequencing, untargeted metabolomics, and cell differentiation. CSR administration significantly ameliorated the dextran sodium sulfate (DSS)-induced colitis in mice, which was evidenced by the recovered body weight and colon length as well as the decreased disease activity index (DAI) score and intestinal permeability. Meanwhile, CSR down-regulated the production of pro-inflammatory cytokines and up-regulated the amount of anti-inflammatory mediators at both mRNA and protein levels, and improved the balances of Treg/Th1 and Treg/Th17 to maintain the colonic immune homeostasis. Notably, all the therapeutic effects were exerted in a gut microbiota-dependent manner. Furthermore, CSR treatment increased the gut microbiota diversity and changed the compositions of the gut microbiota and metabolites, which is probably associated with the gut microbiota-mediated protective effects. In conclusion, this study provides the strong evidence that CSR may be a promising therapeutic drug for UC.

Traumatic brain injury (TBI) is the leading cause of disability and death, and the social burden of mortality and morbidity caused by TBI is significant. Under the influence of comprehensive factors, such as social environment, lifestyle, and employment type, the incidence of TBI continues to increase annually. Current pharmacotherapy of TBI mainly focuses on symptomatic supportive treatment, aiming to reduce intracranial pressure, ease pain, alleviate irritability, and fight infection. In this study, we summarized numerous studies covering the use of neuroprotective agents in different animal models and clinical trials after TBI. However, we found that no drug has been approved as specifically effective for the treatment of TBI. Effective therapeutic strategies for TBI remain an urgent need, and attention is turning toward traditional Chinese medicine. We analyzed the reasons why existing high-profile drugs had failed to show clinical benefits and offered our views on the research of traditional herbal medicine for treating TBI.

Aims: Gastrointestinal (GI) dysfunction, as a common peripheral‐organ complication after traumatic brain injury (TBI), is primarily characterized by gut inflammation and damage to the intestinal mucosal barrier (IMB). Previous studies have confirmed that TongQiao HuoXue Decoction (TQHXD) has strong anti‐inflammatory properties and protects against gut injury. However, few have reported on the therapeutic effects of TQHXD in a TBI‐induced GI dysfunction model. We aimed to explore the effects of TQHXD on TBI‐induced GI dysfunction and the underlying mechanism thereof.Methods: We assessed the protective effects and possible mechanism of TQHXD in treating TBI‐induced GI dysfunction via gene engineering, histological staining, immunofluorescence (IF), 16S ribosomal ribonucleic acid (rRNA) sequencing, real‐time polymerase chain reaction (RT‐PCR), enzyme‐linked immunosorbent assay (ELISA), Western blot (WB), and flow cytometry (FCM).Results: TQHXD administration ameliorated TBI‐induced GI dysfunction by modulating the abundance and structure of bacteria; reconstructing the destroyed epithelial and chemical barriers of the IMB; and improving M1/M2 macrophage, T‐regulatory cell (Treg)/T helper 1 cell (Th₁), as well as Th₁₇/Treg ratios to preserve homeostasis of the intestinal immune barrier. Notably, Cluster of Differentiation 36 (CD36)/15‐lipoxygenase (15‐LO)/nuclear receptor subfamily 4 group A member 1 (NR4A1) signaling was markedly stimulated in colonic tissue of TQHXD‐treated mice. However, insufficiency of both CD36 and (C‐X3‐C motif) chemokine receptor 1 (CX3CR1) worsened GI dysfunction induced by TBI, which could not be rescued by TQHXD.Conclusion: TQHXD exerted therapeutic effects on TBI‐induced GI dysfunction by regulating the intestinal biological, chemical, epithelial, and immune barriers of the IMB, and this effect resulted from the stimulation of CD36/NR4A1/15‐LO signaling; however, it could not do so when CX3CR1 and CD36 were deficient. TQHXD might therefore be a potential drug candidate for treating TBI‐induced GI dysfunction.