Calcined lotus leaf-derived carbon dots: enhanced hemostasis, anti-inflammatory, immunomodulatory properties for...

Ulcerative Colitis (UC) is a chronic condition characterized by damage to the intestinal mucosal barrier, resulting in bleeding, increased oxidative stress, persistent inflammation, and immune dysregulation. Lotus Leaf (LL), recognized for its dual role as both food and medicine, has demonstrated significant antioxidant and anti-inflammatory properties. Furthermore, its calcined derivative, Lotus Leaf Charcoal (LLC), enhances its astringent, hemostatic, and antidiarrheal effects, positioning it as a promising candidate for the management of UC in both dietary and medicinal contexts. This study aims to explore the potential of LLC in the treatment of UC and its material basis. LLC was prepared by simulating traditional calcination processes through high-temperature pyrolysis at 450 °C, and it was found to contain a large number of spherical nanoparticles uniformly distributed in the range of 0.5-3 nm, exhibiting good dispersibility and stability. In vitro and in vivo experiments demonstrate that LLC exhibits a dose-dependent hemostatic effect which significantly increases platelet (PLT) count, elevates fibrinogen (FIB) concentration, and shortens activated partial thromboplastin time (APTT) and thrombin time (TT). Additionally, LLC shows excellent free radical scavenging abilities against DPPH•, ABTS+•, •OH, and O2-• radicals. Furthermore, LLC exhibits remarkable gastrointestinal stability and long-term retention. In the dextran sulfate sodium (DSS)-induced mouse model of UC, LLC significantly alleviates weight loss, reduces the disease activity index (DAI) and colonic mucosal injury index (CMDI), improves colonic shortening and tissue pathological damage. It downregulates the levels of pro-inflammatory factors such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), decreases indicators of oxidative stress like reactive oxygen species (ROS) and malondialdehyde (MDA), and may inhibit pyroptosis of colonic epithelial cells by suppressing the excessive activation of the NLRP3/Caspase-1/GSDMD signaling pathway. Additionally, it modulates the ratio of CD4+/CD8+ T cells and the Th17/Treg balance in the spleen, thereby restoring immune homeostasis. Additionally, LLC upregulates the expression of tight junction proteins Claudin-1 and Occludin, promoting intestinal barrier repair, and increases the abundance of beneficial bacteria while inhibiting the proliferation of harmful bacteria, ultimately reshaping the intestinal microbiota structure. In summary, LLC contains a substantial amount of carbon nanodots, which improve UC through multiple mechanisms, including mucosal repair, hemostasis, antioxidant effects, anti-inflammatory actions, pyroptosis inhibition, immune modulation, and microbiota regulation. These findings provide a preclinical foundation for developing carbon-based therapeutics for UC.