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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.

To understand the impacts of peanut worms Sipunculus nudus on the prokaryotic community composition in a tidal flat, an onsite investigation was conducted in Suixi in the Beibu Gulf (109.82E, 21.35N) in the burrow sediments, non‐burrow sediments and the sediments without peanut worm disturbance (control). The16S rRNA gene Illumina MiSeq sequencing was used to investigate the microbial communities and their response to bioturbation by S. nudus in a sandy tidal flat. A total of 18 bacteria phyla were detected, and Proteobacteria and Cyanobacteria constituted the majority of the prokaryotic community in the samples. The distribution of the relative abundances of genera showed that approximately 6.99%–17% of the reads in the samples were classified into 25 known genera. Sulfate‐reducing bacteria (Desulfococcus and Desulfosarcina) were the most abundant taxa, followed by Thermodesulfovibrionaceae LCP‐6, indicating that sulfate reduction is the main process in the sandy tidal flat. The abundances of Desulfococcus, LCP‐6 and Cyanobacterium in the non‐burrow sediment were greater than in the burrow sediment, suggesting that the anoxic condition is more suitable for Desulfococcus and LCP‐6 when the activity of S. nudus is absent. The biomass of Cyanobacterium was decreased by the feeding bioturbation of S. nudus. Meanwhile, the relative abundance of the Bacteroidetes Luteimonas in the burrow sediments was significantly greater than in the non‐burrow sediment, and there was a strong relationship between S. nudus bioturbation and increased in oxygen contents and oxidation‐reduction potentials in the burrow sediment. The abundances of Desulfococcus and LCP‐6 were greater in the middle layer (20–30 cm) than in the top layer in the non‐burrow sediment. However, the middle and bottom layers (20–30, 30–40 cm) had higher abundances of these genera than did the upper layers (0–10, 10–20 cm) in the burrow sediments. The abundances of the Fusobacteria Propionigenium and the Spirochaetes Spirochaeta were greater in the middle and bottom layers (20–30 cm, 30–40 cm) than in the top layers (0–10, 10–20 cm) in the burrow sediment, but this phenomenon was not found in the non‐burrow sediment. This study demonstrates that bioturbation by S. nudus plays an important role in reshaping the bacterial community composition in intertidal regions. In this study, the microbial community in the sandy tidal flat was different from the other mud tidal flat, while most of the abundant bacterial group were similar. Proteobacteria and Cyanobacteria constitute the majority of the microbial community in the samples, and sulfate reduction and nitrification were the main circulating processes in bottom layers. The microbial community can be affected by the physicochemical characteristics of sediments, which was susceptible to bioturbation of S. nudus.

This study investigated the radioprotective effect of Sipunculus nudus L. polysaccharide (SNP) in combination with WR-2721, rhIL-11 and rhG-CSF on irradiated mice. A total of 70 Imprinting Control Region (ICR) mice were divided into seven groups: the control group, the model group and five administration groups. All groups, except the control group, were exposed to a 5 Gy 60Co γ-ray beam. Blood parameters [including white blood cell (WBC), red blood cell (RBC) and platelet counts and hemoglobin level] were assessed three days before irradiation, and the on the 3rd, 7th and 14th days after irradiation. Spleen, thymus and testicular indices, DNA contents of bone marrow cells, bone marrow nucleated cells, sperm counts, superoxide dismutase (SOD), malondialdehyde (MDA), testosterone and estradiol levels in the serum were assessed on the 14th day after irradiation. The combined administration of SNP, WR-2721, rhIL-11 and rhG-CSF exerted synergistic recovery effects on peripheral blood WBC, RBC and platelet counts and hemoglobin levels in irradiated mice, and synergistic promotion effects on spleen, thymus, testicle, bone marrow nucleated cells and sperm counts in irradiated mice. The synergistic administration increased the serum SOD activities and serum testosterone content of irradiated mice, but synergy decreased the content of serum MDA and estradiol in irradiated mice. These results suggest that the combined administration of SNP, WR-2721, rhIL-11 and rhG-CSF should increase the efficacy of these drugs for acute radiation sickness, protect immunity, hematopoiesis and the reproductive organs of irradiated-damaged mice, and improve oxidation resistance in the body.

Marine organisms constitute unlimited resource of bioactive substances due to their high biodiversity and represent a valuable source of new compounds. This study optimized the alkali-extraction conditions and antioxidant activities of soluble polysaccharides from the body wall of Sipunculus nudus. The effects of solid-liquid ratio, extraction duration, extraction temperature, and alkali concentration on the yield of S. nudus polysaccharides (SNP) were examined, according to which the optimal combination of extraction parameters was obtained by an orthogonal test. The relative influencing importance of different extraction parameters on the yield of SNP followed the order as solid-liquid ratio > extraction temperature > alkali concentration > extraction duration. The highest extraction yield, 1.98%, was achieved under an optimal extraction condition: temperature 60℃, solid-liquid ratio 1:6 g mL?1, duration 5 h, and alkali (NaOH) mass fraction 6%. The in vitro antioxidant activities examination showed that extracted SNP under this optimized condition had strong power in reducing certain hydroxyl and superoxide radical scavenging abilities. The promising results showed that extracted SNP could be a potent natural antioxidant.

The optimal dietary protein to energy ( P / E ) ratio for juvenile peanut worm Sipunculus nudus Linnaeus (initial average weight 46.16 ± 0.07 mg) was determined using practical diets in a 3 × 3 factorial experiment. Three dietary protein levels (38, 43, and 48 %) and three lipid levels (6, 9, and 12 %) were tested, yielding P / E ratios of 19.5–26.4 mg protein kJ −1 . Each diet was fed to juveniles in three plastic tanks (65 × 55 × 45 cm) for 56 days. S. nudus juveniles fed a diet containing 43 % protein and 9 % lipid, yielding a P / E ratio of 23.1 mg protein kJ −1 , presented the highest specific growth rate among the treatments ( P  < 0.05). The highest protease and lipase activities were observed in S. nudus juveniles fed a diet with a P / E ratio of 23.1 mg protein kJ −1 . Carcass moisture and ash contents were not significantly affected by the dietary P / E ratio ( P  > 0.05). Carcass protein content improved as dietary protein increased at each lipid level, and carcass lipid content improved as dietary lipid increased at each protein level. The results indicate that feeding S. nudus a diet containing 43 % protein and 9 % lipid, with a P / E ratio of 23.1 mg protein kJ −1 , leads to optimal growth performance.

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.

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.

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.