Ocean & seas: Huge biomedical resources for anti-infection
As biomedical scientists, we know that marine products are beneficial to human health. The scientists are developing chemicals and novel therapeutic drugs from marine natural products (MNPs) with anti-tuberculosis activity and H. pylori infection [6, 7], and defensive effects against viral infection, including the SARS-CoV-2 and HIV-1 [8, 9]. We expect that these compounds could be employed to treat and prevent infectious diseases, including COVID-19 and AIDS, if truly having significant antiviral activities. However, there are still huge challenges in the discovery and development of marine drugs.
The crude extracts from marine organisms contain compounds capable of inhibiting inflammation and potential bioactive molecules [10]. Echinochrome pigment extracted from sea urchin has an insightful antiulcer healing effect [11]. Bis (3-bromo-4,5-dihydroxybenzyl) ether (BBDE, C14H12Br2O5), a novel bromophenol isolated from the red alga Polysiphonia morrowii [12], is useful for treating inflammatory diseases due to the inhibition of LPS-induced inflammation in macrophage cells by inhibiting the ROS-mediated ERK signaling pathway and reducing inflammatory mediators.
As we known, MNPs are important biomedical resources for anti-infection. There are more than 1600 new steroidal structures isolated from marine organisms. Some steroids can regulate the farnesoid X receptor (FXR) and the pregnane X receptor (PXR). Novel FXR and PXR agonists and antagonists can target human diseases, e.g., intestinal inflammation [13]. Marine invertebrate glycans (ascidians and sea cucumbers) could be used as starting material for new therapeutics due to anticoagulant activity and anti-inflammation [14].
Sea cucumbers are widely consumed in traditional medicine and food. Holothuria grisea agglutinin (HGA) has demonstrated the ability to modulate the inflammatory response in models of inflammation in vivo. Moreover, it is the first marine invertebrate lectin that showed an anti-inflammatory effect [15]. Fucosylated chondroitin sulfate (fCS) extracted from the sea cucumber Holothuria forskali, as an inhibitor of selectin interactions, plays vital roles in inflammation and metastasis progression [16]. Sea cucumbers-derived sterol sulfate effectively attenuated inflammation by increasing serum adiponectin and reducing pro-inflammatory cytokine release [17].
A novel cathelicidin (Hc-CATH) from the sea snake Hydrophis cyanocinctus, has potent both antimicrobial and anti-inflammatory activity by inhibiting the LPS-induced production of nitric oxide (NO) and pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6, is a potent candidate for the development of peptide antibiotics [18]. A small-molecule compound isolated from marine-derived fungus, bis-N-norgliovictin, significantly inhibits lipopolysaccharide (LPS, ligand of TLR4)-induced tumor necrosis factor-α (TNF-α) production, and exhibits potent anti-inflammatory effect both in vitro and in vivo [19]. Hence, it can be a useful therapeutic candidate for the treatment of sepsis and other inflammatory diseases.
As a novel marine metabolite isolated from the sponge Fasciospongia cavernosa, Cacospongionolide B showed topical anti-inflammatory activity and reduced the inflammatory response of adjuvant arthritis [20], could be used as new anti-inflammatory agents. Four drug candidates from novel bioactive sponge [21]: IPL576,092, HTI-286 (Taltobulin), EPI-506 (Ralaniten acetate), and AQX-1125, can be used for treatment of not only inflammation but also cancer.
As bioactive molecules with the anti-inflammatory activity, microalgae-derived Oxylipins (OXLs) have the therapeutic potential in inflammatory diseases [22], could act as agonist of PPAR-γ and consequently inhibit NFκB signaling pathway activation, thus lowering the production of inflammatory markers. Avarol is a marine sesquiterpenoid hydroquinone with anti-inflammatory and antipsoriatic properties [23], it inhibits several key biomarkers up-regulated in the inflammatory response of psoriatic skin. The marine compound didemnin B decreases the activity of the cell types implicated in liver inflammation and fibrosis in vitro [24].