Medicinal Plant Research 2025, Vol.15, No.6, 254-263 http://hortherbpublisher.com/index.php/mpr 260 7.3 Evidence and limitations of existing human clinical trials Several RCTs and meta-analyses support the effectiveness and safety of curcumin and extracts from Curcuma longa for indications such as osteoarthritis, arthritis, and some autoimmune diseases, with efficacy comparable to NSAIDs but fewer adverse events. However, most are small, of short duration, and have variable formulations; as a result, results cannot be generalized, and optimal dosing cannot be established (Fuloria et al., 2022; Panknin et al., 2023). More high-quality clinical trials with larger samples are needed. 7.4 Regulation and application of functional foods and supplements Curcumin is generally considered by regulatory agencies, such as the US FDA and EFSA, as a food additive and supplement, allowing an acceptable daily intake of 0-3 mg/kg body weight (Turck et al., 2021). It is now being widely used in functional foods, nutraceuticals, and supplements; however, challenges still exist concerning product quality and standardization. Curcumin's poor bioavailability, rapid metabolism, and instability impede the pharmaceutical development of curcumin, despite promising preclinical and clinical data (Hassanzadeh et al., 2020; Jacob et al., 2024). Nanotechnology and various new formulations have been under study, but only a few are approved for use by regulatory agencies, and long-term safety of new delivery systems needs further investigation (Jacob et al., 2024). 8 Concluding Remarks During the last several decades, research into Curcuma longa and its principal curcuminoid, curcumin, has identified multifaceted biological activities relevant to inflammation and immune regulation. There is accumulating evidence from cell-based studies, animal models, and early-phase clinical investigations that curcumin has anti-inflammatory actions through modulating key molecular targets, including the NF-κB, MAPKs, JAK/STAT, and PI3K/Akt/mTOR pathways. In parallel, curcumin was shown to regulate innate and adaptive immune responses through modulation of macrophage polarization, T-cell differentiation, cytokine secretion, and inflammasome activation. Such cumulative data point to a comprehensive, mechanistically linked network whereby curcumin dampens inflammatory processes and restores immune homeostasis. With a broad mechanistic profile combined with an increasing volume of preclinical and clinical data, curcumin is a promising natural candidate for therapeutic use in the treatment of chronic inflammatory and immune-related diseases. The benefits accruing in models of metabolic syndrome, arthritis, neuroinflammation, cardiovascular disorders, and certain types of cancers have emphasized the wide therapeutic scope of this agent. Though challenges persist regarding poor bioavailability, novel delivery systems, including nanoparticles, liposomes, phospholipid complexes, and structural analogs, have greatly improved its pharmacokinetic profile. This development further reinforces translational prospects for curcumin, strengthening the scientific rationale underlying its development as an adjunctive or stand-alone therapeutic agent. Despite these promising findings, many knowledge gaps still persist that need to be filled before curcumin could be integrated into evidence-based clinical practice. Mechanistic investigations will be required to define further target specificity, dose-response relationships, and interactions in complex inflammatory and immune networks. Larger-scale, well-controlled clinical trials are needed for the transparent validation of efficacy, safety, and long-term disease outcomes. Concepts on bioavailability enhancement strategies, metabolic diversification, and gut microbiota interactions will also continue to improve our understanding of the physiological behavior and further the therapeutic potential of curcumin. Ongoing interdisciplinary investigation will strengthen not only the scientific underpinnings of curcumin-based therapeutics but also the rational development of more effective, natural-product-driven interventions for chronic inflammatory disease. Acknowledgments The authors are deeply grateful to the research team for their patient assistance and strong support during the progress of the study and the compilation of relevant materials. The authors also sincerely thank the two anonymous reviewers for their valuable comments and constructive suggestions during the review process, which provided important assistance in the improvement and refinement of the manuscript.
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