Hepatoprotective and Antihyperglycemic Effects of Sea Grapes (Caulerpa spp.) as a Potential Therapeutic Approach for NAFLD and NASH

Abstract

Non-alcoholic fatty liver disease (NAFLD) and its advanced form, non-alcoholic steatohepatitis (NASH), are increasingly prevalent metabolic liver disorders characterized by hepatic lipid accumulation, oxidative stress, inflammation, and insulin resistance. Despite their global burden, effective pharmacological treatments remain limited, which highlights the need for safe and multi-targeted natural alternatives. This literature review summarizes current evidence from in vitro, in vivo, and early clinical studies investigating the hepatoprotective and antihyperglycemic properties of Caulerpa spp., including C. lentillifera, C. racemosa, C. taxifolia, and C. prolifera. The review focuses on research published between 2015 and 2025 related to Caulerpa bioactivity, liver protection, glucose regulation, oxidative stress, lipid metabolism, and gut microbiota modulation. Across the reviewed studies, Caulerpa-derived bioactive compounds such as polysaccharides, carotenoids, peptides, and polyphenols consistently demonstrated hepatoprotective and metabolic benefits. Supplementation improved antioxidant enzyme activities, including superoxide dismutase, catalase, and glutathione, while reducing malondialdehyde levels, thereby protecting hepatocytes from oxidative damage that contributes to NAFLD progression. Several studies also reported downregulation of lipogenic genes such as SREBF1, FAS, and ACC, together with activation of SIRT1 and AMPK signalling pathways, which reduced hepatic triglyceride accumulation. Extracts from C. taxifolia and C. prolifera exhibited strong alpha-amylase and alpha-glucosidase inhibition, improving glucose regulation. In addition, Caulerpa supplementation was shown to restore intestinal barrier integrity and modify gut microbiota composition, leading to lower endotoxin levels and reduced hepatic inflammation. The only available human clinical trial demonstrated a significant reduction in fasting glucose following C. racemosa supplementation, supporting its potential for clinical application. Overall, the evidence indicates that Caulerpa species exert multi-pathway hepatoprotective and antihyperglycemic effects. However, further studies are required to standardize extract preparation, determine optimal dosage, and assess long-term safety. Caulerpa spp. demonstrates promising preclinical potential. However, further translational research and rigorous clinical trials are warranted to validate these findings and determine its feasibility as a nutraceutical for NAFLD, NASH, and metabolic syndrome.