Physiology and Pharmacology

en Anti-inflammatory and immunomodulatory effects of β-D-mannuronic acid (M2000): From autoimmune diseases to inflammatory-related disorders Clinical Physiology/Pharmacology Clinical Physiology/Pharmacology Review Review Background: Autoimmune disorders (ADs) are characterised by pathological activation of the immune system that results in chronic inflammation and tissue damage. β-D-mannuronic acid (M2000), a seaweed-derived monomeric NSAID, shows immunomodulatory properties. The review explores the therapeutic potential across autoimmune, neurodegenerative, metabolic, and infectious conditions based on the literature. Methods: A literature search was conducted using a narrative approach in PubMed, Scopus, Google Scholar, and ClinicalTrials.gov databases in order to find original studies published up to 2026. Experimental data, preclinical and clinical, were gathered and summarized in terms of its biochemical properties, immunomodulatory mechanisms, inflammatory signaling pathways, and therapeutic potential. Results: M2000 is known to inhibit pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-17, IL-21, IL-22, IL-23, IFN-γ) and to normalize immune homeostasis by regulating the Th1/Th17, Tregs, and APCs. Mechanistically, it inhibits TLR2/4–IRAK1–TRAF6 and PI3K/Akt, MAPK/ERK, and JAK/STAT pathways, and hence the activation of NF-κB. It also acts as a regulator of immune-related miRNAs (miR-155, miR-126, miR-125a-5p; miR-146a regulation is context-dependent), decreases ROS, and increases the antioxidant defenses. The evidence indicates cytokine storm suppression and hematologic recovery. Conclusion: M2000 is a multi-target immunomodulator that targets inflammatory signaling, immune cell activity, oxidative stress, and epigenetic regulation. However, current clinical evidence is geographically concentrated in specific research centers, limiting immediate external validity. Furthermore, shared inflammatory pathways (such as NF-κB or IL-6) across diseases do not imply transferable therapeutic efficacy. International multi-center randomized controlled trials are needed to clarify its mechanism of action and therapeutic potential in modern clinical practice. Autoimmune Diseases,Inflammation,Mannuronic acid,Non-Autoimmune Disorders 0 0 http://ppj.phypha.ir/browse.php?a_code=A-10-2589-2&slc_lang=en&sid=1 Azade Yazdi 62a.yazdi@gmail.com No Department of Medicine, Na.C., Islamic Azad University, Najafabad, IranClinical Research Development Center, Na.C., Islamic Azad University, Najafabad, Iran Mobina Imaniyan Mobinaimaniyan81@gmail.com No Department of Midwifery, Nursing and Midwifery Sciences Development Research Center, Na.C., Islamic Azad University, Najafabad, Iran Majid Ghajari ghajarimajid2013@gmail.com No 1. Department of Medicine, Na.C., Islamic Azad University, Najafabad, Iran2. Clinical Research Development Center, Na.C., Islamic Azad University, Najafabad, Iran Maral Arbabzadeh maralarbabzadeh1380@gmail.com No 1. Department of Medicine, Na.C., Islamic Azad University, Najafabad, Iran2. Clinical Research Development Center, Na.C., Islamic Azad University, Najafabad, Iran Nasrin Zare zarenasrin@gmail.com 0000000238255039 Yes Department of Medicine, Na.C., Islamic Azad University, Najafabad, Iran