**7. Conclusions and Research Prospects**

Chronic inflammation plays a crucial role in the development of various diseases, such as inflammatory bowel disease, rheumatoid arthritis, and asthma. Controlling the progression of inflammation is a critical step in the management of these diseases. The available steroidal and nonsteroidal anti-inflammatory drugs significantly reduce chronic inflammation, but many of them can have adverse effects, such as gastrointestinal distress and liver, heart, kidney, and endocrine dysfunction, when taken long-term. In this review, the PubMed, Scopus, Web of Science, ACS, ScienceDirect, SpringerLink, and MDPI databases were searched using various combinations of keywords for publications pertaining to the anti-inflammatory potential of compounds originating from the three echinoderms: sea cucumbers, sea urchins, and starfish. Due to the immense richness and diversity of marine organisms and their natural products, it is extremely difficult to cover all of the pertinent literature, even though a broad coverage was anticipated. The major bioactive compounds isolated from sea cucumbers are fucoidan, fucosylated chondroitin sulfate, triterpenoid glycosides, small peptides, lipids, and fatty acids such as the EPA derivatives (EPA-PC and EPA-PE) sphingolipids and frondanol. Similarly, sea urchins are well-documented to produce bioactive compounds such as EchA, spine and shell pigments, polysaccharides, stomopnolides, and small peptides. Starfish also produce a diverse range of bioactive compounds, including pentaregulosides, protolinckiosides, plancipyrroside, astebatherioside, and oxygenated steroid and fatty acids. These bioactive compounds from echinoderms suppress the expression and activation of major proinflammatory cytokines such as IL-6, TNFα, IL1β, IL-10, MIP-1, etc. by the inhibition of the NF-kB and MAPK signaling pathways. Moreover, the classical COX and LOX inflammation pathway inhibitions by these compounds are also documented in this review. In addition, compounds isolated from these echinoderms also inhibit ROS generation, as well as NO production.

Research into marine-derived anti-inflammatory lead compounds has received little consideration compared to anticancer leads; however, this is evolving very rapidly. In this review article, we presented anti-inflammatory compounds isolated from various species of sea cucumbers, sea urchins, and starfish, including their chemical structures. Many compounds, such as fucoidan, fucosylated chondroitin sulfate, eicosapentaenoic acid derivatives, and echinochrome A, have been investigated in detail for their antiinflammatory activity and molecular mechanisms. Moreover, some novel compounds, such as glycosides from starfish, have been studied well in terms of their chemical structure and SAR with a target but only screened for preliminary anti-inflammatory activity (such as COX and 5-LOX inhibitory activity). These need further investigation to establish their molecular mechanisms. Marine pharmacology research faces many obstacles. For example, the isolation of bioactive compounds from marine organisms is extremely difficult, as they live in a complex and biodiverse environment, and it is difficult to mimic such an environment in the laboratory for their cultivation to obtain a large quantity of active substances. The future prospects in marine pharmacology should focus on following: (1) the reproduction of compounds by the chemical synthesis of established marine-derived anti-inflammatory leads to increase their production and overcome cultivation obstacles, (2) the chemical modification of existing marine-derived anti-inflammatory leads (analogs) to enhance their potency and efficacy, (3) develop lead compound libraries for large and rapid random high-throughput screening methods, (4) industry collaboration to translate preclinical leads into the clinical pipeline, and (5) establish comprehensive and efficient separation and purification techniques. The planet is gifted with vast and diverse coastlines by nature that are a treasure of bioactive compounds that have not been exploited. The scientific community should consider taking up further research to find other, potentially valuable marine drugs.

In conclusion, this review can serve as a well-documented reference for research progress on the development of potential drugs from marine sources against various chronic inflammatory conditions.

**Author Contributions:** H.G.: Conceptualization, Literature collection, Methodology, Investigation, and Writing—Original Draft. M.K.: Methodology, Investigation, and Writing—Original Draft. T.E.A.: Conceptualization, Resources, Methodology, Writing—Review and Editing, and Supervision. R.K.J.: Conceptualization, Resources, Methodology, Writing—Review and Editing, and Supervision. All authors have read and agreed to the published version of the manuscript.

**Funding:** This manuscript received publication fee support from Mohammed Bin Rashid University of Medicine and Health Sciences.

**Acknowledgments:** This work was supported in part by Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU) and the Al Jalila Foundation for Post-Doctoral Research Fellowship awards to H.G. and M.K.

**Conflicts of Interest:** The authors declare no conflict of interest.

## **References**

