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Strongylocentrotus nudus egg polysaccharide (SEP) extracted from sea urchins has potential anticancer activity. However, little is known about its pharmacokinetic properties. To investigate the pharmacokinetics of SEP, it was radiolabeled with tritium. Furthermore, a sensitive, selective, and rapid liquid scintillation counter (LSC) method for quantifying 3 H-SEP in biological matrix was validated. The lower quantification limit of the method was 4 Bq. The relative standard deviations (RSDs) of the intra- and inter-day precision were <3.0% and <3.9%, respectively. 3 H-SEP was successfully applied to investigate the pharmacokinetics of SEP after intravenous administration of 20, 40, and 80 mg/kg (40 μCi/kg) in rats and 5, 10, and 20 mg/kg (6 μCi/kg) in beagles. The AUC (0-t) of SEP at three different doses was 487.81 ± 39.99 mg/L*h, 1,003.10 ± 95.94 mg/L*h, and 2,188.84 ± 137.73 mg/L*h in rats and 144.12 ± 3.78 mg/L*h, 322.62 ± 28.03 mg/L*h, and 754.17 ± 37.79 mg/L*h in beagles. The terminal elimination half-life (t 1/2 ) of SEP was longer in beagles (204.29 ± 139.34 h) than in rats (35.48 ± 6.04 h). The concentration of SEP in plasma declined rapidly in both rats and beagles. All the study results provide detailed pharmacokinetic profiles of SEP in two kinds of animals, which will be helpful for further development.

Marine collagen peptides have high potential in promoting skin wound healing. This study aimed to investigate wound healing activity of collagen peptides derived from Sipunculus nudus (SNCP). The effects of SNCP on promoting healing were studied through a whole cortex wound model in mice. Results showed that SNCP consisted of peptides with a molecular weight less than 5 kDa accounted for 81.95%, rich in Gly and Arg. SNCP possessed outstanding capacity to induce human umbilical vein endothelial cells (HUVEC), human immortalized keratinocytes (HaCaT) and human skin fibroblasts (HSF) cells proliferation and migration in vitro. In vivo, SNCP could markedly improve the healing rate and shorten the scab removal time, possessing a scar-free healing effect. Compared with the negative control group, the expression level of tumor necrosis factor-α, interleukin-1β and transforming growth factor-β1 (TGF-β1) in the SNCP group was significantly down-regulated at 7 days post-wounding (p < 0.01). Moreover, the mRNA level of mothers against decapentaplegic homolog 7 (Smad7) in SNCP group was up-regulated (p < 0.01); in contrast, type II TGF-β receptors, collagen I and α-smooth muscle actin were significantly down-regulated at 28 days (p < 0.01). These results indicate that SNCP possessed excellent activity of accelerating wound healing and inhibiting scar formation, and its mechanism was closely related to reducing inflammation, improving collagen deposition and recombination and blockade of the TGF-β/Smads signal pathway. Therefore, SNCP may have promising clinical applications in skin wound repair and scar inhibition.

The pathogenesis of hypertension is related to many factors including active angiotensin-I-converting enzyme (ACE) and excess reactive oxygen species (ROS), the combination of ACE inhibition and antioxidant activity in one compound might be useful for the treatment of hypertension. Sipunculus nudus L contain high protein content, which can be used as a valuable raw material to prepare bio-active peptides. In this study, two novel tripeptides, LPK and PRP, with dual bioactivity of ACE inhibition and antioxidant were purified and identified from the worm. The antioxidant activities of LPK and PRP are dose-dependent, including 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide anion and hydroxyl radical scavenging activities. Moreover, the antioxidant activity of PRP was stronger than that of LPK. In addition, LPK and PRP also show higher ACE inhibitory activity, with IC50 of 6.54 and 0.42 mM, respectively. Molecular docking simulation showed that both the peptides could interact with the active ACE sites via hydrogen bonds, which can reduce the production of Ang II, thereby; LPK and PRP treatment could decrease Ang II-triggered superoxide production, and meanwhile, the peptides treatment could directly remove excess reactive oxygen species. The above-mentioned advantageous effects appeared to involve the stress of the RAS and scavenging ROS, both were benefit to treat hypertension. This research showed that LPK and PRP had potential to be developed as antihypertension agents, which might be a new strategy for high value utilization of Sipunculus nudus L as functional food material.

In this study, the sea food Sipunculus nudus L. was hydrolyzed by trypsin, and peptides were isolated and purified from the hydrolysates. As a result, two novel nonapeptides were identified by LC–MS–MS with amino sequences of GFAGDDAPR and GLGGLSPEK. The ACEI activity were determined and the IC50 values of the peptides for ACE inhibition activity were 0.76 mmol/L and 0.91 mmol/L, respectively. The results showed that both peptides had ACE inhibitory activity. Analysis of the Lineweaver–Burk plot demonstrated that these peptides served as non-competitive ACE inhibitors. Molecular docking study showed that these peptides could interact with the active site of ACE mainly through hydrogen bonding and electrostatic force. The amino acid residue that plays a key role in ACE inhibitory activity was its C-terminal Arg. It is therefore suggested that S. nudus may be a useful raw material for the production of antihypertensive peptides which can offer therapeutic and commercial benefits as an ingredient in functional foods.

This study aimed to purify and characterize immunoregulatory peptides from Sipunculus nudus L. and to explore the underlying mechanisms. Ultrafiltration, gel filtration chromatography, and reverse phase high‐performance liquid chromatography (RP‐HPLC) were used to purify the peptide following enzymatic hydrolysis. Rates of lymphocyte proliferation and phagocytosis as well as nitric oxide (NO) production levels were used as indicators of immunoregulatory activity to screen the fractions. The amino acid sequence of the peptide, designated as SNLP, was identified as Arg–Val–Lys–Gly–Lys–Ile–Leu–Ala–Lys–Arg–Leu–Asn (RVKGKILAKRLN) by liquid chromatography–tandem mass spectrometry (LC–MS/MS). Treatment with the synthetic SNLP increased the proliferation and phagocytosis of RAW 264.7 macrophages and promoted the secretion of tumor necrosis factor‐ɑ (TNF‐α), interleukin‐6 (IL‐6), interleukin‐1β (IL‐1β), and NO levels. The mRNA levels of these cytokines and iNOS were also increased by SNLP. Our results provide preliminary evidence suggesting that SNLP acts as a dual immunomodulatory peptide with immunostimulatory and anti‐inflammatory activities. In summary, SNLP derived from Sipunculus nudus L. is a potent immunoregulatory peptide and represents a potential functional food or immunoregulatory drug. A novel natural potent immunoregulatory peptide: SNLP was identified from Sipunculus nudus L. Synthesized SNLP increased the proliferation and phagocytosis of RAW 264.7 macrophages, and promoted the secretion of TNF‐ɑ, IL‐6, IL‐1β, and NO. Our results provided preliminary evidence that SNLP is the two‐way immunomodulatory peptides with immunostimulatory and anti‐inflammatory activities. In summary, SNLP derived from Sipunculus nudus L. is a potent immunoregulatory peptide and it has great potentials as functional food or immunoregulatory drug.

Current thrombolytic therapies primarily function by converting plasminogen into plasmin, a process dependent on the fibrin–activator complex. This dependence, coupled with the substantial molecular size of plasmin, constrains its effectiveness in degrading D-dimer and restricts its diffusion within thrombi. Here, we introduce a small facultative plasminogen-independent thrombolytic enzyme, snFPITE, isolated from Sipunculus nudus . Compared to traditional thrombolytic agents, snFPITE does not require plasminogen for thrombolysis, although its presence enhances lytic activity. This enzyme fully degrades cross-linked fibrin without leaving residual nondegradable D-dimer and generates a smaller fibrinolytic-active agent from plasminogen. A series of male rats and mice models further confirm that snFPITE is a safety injectable thrombolytic agent. Mechanistically, snFPITE activates plasminogen and degrades fibrin(ogen) in a multisite cleavage manner. snFPITE is inhibited by plasminogen activator inhibitor 1 and α2-antiplasmin via a competitive inhibition. We further identify 28 snFPITE candidate sequences, of which 10 are confirmed as functional genes. Many thrombolytic agents depend on plasminogen, leading to D-dimer accumulation. Here, Tang et al. report a plasminogen-independent thrombolytic enzyme that degrades blood clots and D-dimer without plasminogen.

Accumulation of yolk precursor protein in the oviparous egg is essential for embryo growth. Transferrin-like protein, also known as major yolk protein, is a major precursor protein in sea urchins and sea cucumbers. In sea urchins, a new yolk protein was recently detected in Strongylocentrotus intermedius and Mesocentrotus nudus eggs. This protein, tentatively named yolk-related protein (YRP), was thought to have important physiological functions for sea urchin gonadal growth and gametogenesis. To understand the relationship between YRP and vitellogenesis, we investigated the molecular structure of sea urchin YRP, quantified the transcript levels during oogenesis, and identified the presence of YRP in coelomic fluid. Using molecular cloning, we characterized one cDNA that encoded YRP (mn-yrp). Structural analysis revealed that mn-YRP is an apolipoprotein B (ApoB)-like protein that belongs to the large lipid transfer protein superfamily. Quantification of mn-yrp (mn-apob) transcripts showed that mn-apob is mainly expressed in the stomach during gonadal growth. Immunobiochemical methods using antiserum revealed that mn-ApoB was present in the coelomic fluid. These results indicate that ApoB has a role in the transport of nutrients, such as sugar, lipids, and carotenoids, from the digestive tract to eggs via coelomic fluid in sea urchin.

The present study investigated the protective effects and possible mechanisms of an ultrafiltration fraction of Sipunculus nudus hydrolysate (UFSH) on cisplatin-induced kidney damage in a mouse model. The results showed that UFSH significantly attenuated cisplatin-induced nephrotoxicity by inhibiting increases in blood urea nitrogen (BUN) and serum creatinine (SCr). Additionally, UFSH treatment significantly alleviated cisplatin-induced renal histopathological changes, such as significant dilation of renal tubules, cast formation, and tubular cell necrosis, as well as tubulointerstitial fibrosis. Moreover, UFSH decreased cisplatin-induced oxidative stress by increasing the activities of antioxidant enzymes SOD and GSH-Px, while reducing the malondialdehyde (MDA) level in the kidney. Furthermore, UFSH significantly inhibited cisplatin-induced increases in inflammatory cytokines, including Interleukin 1-beta (IL-1β), Interleukin-6 (IL-6), and Tumor necrosis factor-alpha (TNF-α). Western blotting revealed that UFSH inhibited the phosphorylation of the inflammation-associated MAPK/NF-κB signaling pathway, lowered the expression of the apoptosis-related protein Bax, and reversed the reduction in the anti-apoptotic Bcl-2 protein. This investigation demonstrated that UFSH can ameliorate cisplatin-induced nephrotoxicity by mitigating oxidative stress, inflammation, and apoptosis.

Mesocentrotus nudus is an important aquaculture species in East Asia, valued for its gonads as the only edible part. However, the molecular basis of gonadal differentiation in this species remains poorly understood. In this study, we determined that morphological gonadal differentiation occurs when individuals reach a test diameter of approximately 40 mm. Amino acid profiling revealed sex-specific differences between ovaries and testes, with higher levels of lysine, proline, alanine, and glutamic acid in testes, suggesting sexual dimorphism in metabolic demand. To investigate the regulatory mechanisms involved, we conducted integrated transcriptomic and metabolomic analyses between differentiated and undifferentiated gonads. Differentially expressed genes (DEGs) and differentially expressed metabolites (DEMs) including retinoic acid, linoleic acid, and arachidonic acid, were significantly enriched in retinol metabolism, steroid biosynthesis, and amino acid metabolic pathways. Several key genes, such as GATA4 , CYP17A1 , and HSD17B , were identified as potential markers for gonadal differentiation. Furthermore, components of the TGF-β signaling pathway ( Smads , Rbx1 , SKP ) and retinol metabolism genes ( CYP26 , CYP1A , CYP3A ) exhibited sex-biased expression patterns. This study provides novel insights into the molecular mechanisms underlying sex differentiation in sea urchins and lays a molecular foundation for the development of sex-control breeding strategies.

Sea urchin gonads are a delicious seafood item of high commercial value. Our past studies have revealed that the gonads of the sea urchin Mesocentrotus nudus fed the basal frond portion of fresh Saccharina kelp (BS) or the sporophylls of fresh Undaria (SU) during May–July are of high-quality. The present study investigated the flavor and taste of BS and SU gonads in comparison with those from non-fed M. nudus (NF) using gas chromatography–mass spectrometry (GC–MS) and gas chromatography (GC)-sniffing techniques, and a taste-sensing system. Data of the estimated intensity of taste (EIT) were compared with assessment of gonads from M. nudus collected from an Eisenia bed (fishing ground) and a barren in July. Gonads from both BS and SU released pleasant green, sour, and fruity aromas characteristic of butyl acetate, which are here recognized essential flavor components of high-quality gonads. The gonads of BS and SU had a strong umami taste compared to those of NF, and the Eisenia bed and the barren. The most marketable M. nudus gonads were assessed to be those with green and fruity aromas from butyl acetate, sweet aroma from benzaldehyde, umami EIT > 13.8, bitterness EIT < 3.1, and without any unpleasant sulfurous odor from sulfur-containing compounds.