The ocean, occupying over 70% of the Earth’s surface, harbors complex ecosystems and rich biodiversity, thereby serving as a critical reservoir of biologically active compounds with pharmaceutical potential (Rigogliuso et al., 2023). Marine natural products, including proteins, peptides, and polysaccharides, have demonstrated significant utility in promoting cutaneous wound healing, bone/cartilage tissue regeneration, and the development of advanced biomaterials for healthcare applications (Lim et al., 2019; Salvatore et al., 2020; Tajbakhsh et al., 2021; Elkhenany et al., 2025).

Recent scientific attention has increasingly focused on cephalopod-derived compounds, particularly from members of the order Octopoda known for their exceptional bioactive properties. Octopus is the taxonomic term for marine mollusks within the class Cephalopoda and family Octopusidae. Modern phylogenetic research has classified these organisms into five distinct subfamilies based on morphological and genetic evidence: Octopodinae, Eledoninae, Graneledoninae, Megaleledoninae and Bathypolypodinae. Biochemical analyses have identified amino acids, fatty acids, proteins, and peptides as the primary bioactive constituents in octopus, with glycosaminoglycans and specific peptide fractions demonstrating multifunctional therapeutic effects including immunomodulatory responses, lactogenic support, broad-spectrum antibacterial activity, and potent free radical scavenging capacity ( Figure 1 ) (Lei et al., 2007; Oliveira et al., 2019; Cai et al., 2020). Octopus-derived peptides have garnered significant attention in recent years due to their potential for anti-microbial, anti-oxidant, anti-hypertensive and anti-tumoral properties (Ben Slama-Ben Salem et al., 2017; Sudhakar and Nazeer, 2017; Imran et al., 2023a). The suckers structure on the octopus arm provides ideas for the design of microneedles and robotic arms (Xie et al., 2023; Chen et al., 2024). The regenerative ability of octopuses may have potential for development in tissue repair and nerve regeneration (Imperadore and Fiorito, 2018).

This review systematically summarized octopus resource distribution, global trade volume, processing methods, nutrients, bioactive compounds and biomedical applications, and discussed the shortcomings of octopus peptides in quality control. While substantial advancements have been achieved in understanding octopus regeneration mechanisms, comprehensive investigations are essential to assess their translational potential in clinical contexts, particularly within regenerative medicine and wound healing applications.

At present, 136 species of octopus have been discovered worldwide, with a wide distribution across tropical and temperate waters, particularly along the Mediterranean, Pacific, and Atlantic coasts (Octopus Cuvier, 1798, n.d). In China, Octopus ocellatus, Octopus variabilis and Octopus vulgaris are recorded as marine traditional Chinese medicine, possessing properties that nourish blood and replenish qi, dredge collaterals to promote lactation, and detoxify and promote granulation. Beyond their medicinal value, the diversity of octopus species in Chinese waters has garnered significant attention. An analysis of octopus species diversity in the Bohai Sea, Yellow Sea, East China Sea, and South China Sea reveals that 37 species of octopus, classified into 10 genera within the Octopodidae family, are present in these waters, representing approximately 27% of the globally identified species ( Figure 2 ) (Zheng et al., 2023).

This biodiversity, along with the species’ nutritional attributes, forms the basis of their commercial viability in food and pharmaceutical industries. Octopus is widely demanded in world import and export trade due to its high protein content and essential micronutrients composition. Since 2000, China has been a major exporter of octopus. In 2023, China, Spain, Vietnam and Morocco emerged as the dominant exporters of octopus (live, fresh, chilled and processed) globally, while South Korea, Japan, Italy and the United States were the main importers of octopus ( Figure 3 ) (Ospina-Alvarez et al., 2022). Over the past two decades, the trade landscape has not evolved significantly. By 2023, the catch of octopus in China was 112100 tons, an increase of 1.96% compared to 2022 (Ministry Agriculture and Rural Affairs of the People‘s Republic of China et al., 2024). These sustained production capacities and trade volumes support the functional food development of octopus.

To optimize the recovery of these bioactive constituents, contemporary extraction methodologies have been systematically developed, primarily encompassing aqueous solvent extraction, ethanolic fractionation, enzymatic hydrolysis, and their combinatorial applications (Hernández-Zazueta et al., 2021). Different extraction portions of octopus demonstrated specific bioactivities. The bioactive compounds of octopus extracts are presented in Figure 4 .

Enzymatic hydrolysis, leveraging protease cocktails, is a well- established method for isolating bioactive peptides from octopus, ensuring efficient cleavage of protein matrices under controlled conditions. Commonly selected enzymes include neutral protease, alcalase, trypsin, papain and pepsin ( Table 1 ). Cai et al. utilized neutrase for the production of octopus peptides. After homogenizing octopus, the sample was mixed with twice its volume of distilled water. The process was initiated by incubating the mixture with 3000 U/g neutrase at pH 6.5 and 50°C for 5 hours. Then, heat inactivation was carried out at 100°C for 10 minutes. After that, the mixture was centrifuged to remove insoluble particles before filtration. Finally, it was further filtered using Vivaflow 10000 and 5000 molecular weight cutoff PES ultrafiltration membranes to obtain three fractions with molecular weights of >10 kDa, 5–10 kDa and <5 kDa for subsequent studies (Cai et al., 2020).

Fu et al. used neutral protease, alkaline protease, flavor protease, trypsin, and composite protease to extract fish oil from octopus’ viscera and optimized the sample processing. The optimized sample preparation conditions were determined as follows: application of neutral protease, enzymolysis at 50°C, a solid-to-liquid ratio of 1:0.5, an enzyme dosage of 3500 U/g, and a reaction duration of 4 hours. Under these optimized parameters, the oil extraction rate was determined to be 74.81%, demonstrating the efficiency of the established protocol (Fu et al., 2020).

Wen et al. used distilled water and enzymolysis with combination of papain and trypsin digestion to extract polysaccharides from the mantle and wrist of Octopus ocellatus (O. ocellatus) and found that the average molecular weights of these polysaccharides extracted from O. ocellatus ranged from 127.9 to 266.4 kDa. In terms of monosaccharide composition, the major component of the polysaccharides extracted from the mantle of O. ocellatus was glucose, along with traces of mannose, N-acetylglucosamine and glucuronic acid. In contrast, the monosaccharide compositions of the polysaccharides extracted from the wrist included mannose, N-acetylglucosamine, glucuronic acid and glucosamine, with small amounts of galactose, fucose and fructose (Wen et al., 2010).

In addition, after ultrasonic treatment of the edible portion of Amphioctopus marginatus with n-hexane for 3–4 h, the residue was extracted with ethyl acetate-methanol 1:1 v/v, 6 × 500 mL) for 6 h, and the supernatant was separated and purified to obtain Δ⁵ steroid analogues (Paulose and Chakraborty, 2022).

Octopus generates a large amount of waste during the sample preparation process, causing problems such as resource waste and environmental pollution. These wastes possess significant nutritional value; proper handling can improve the utilization rate of octopus wastes. The proportion of content of polyunsaturated fatty acids in total oil extracted from octopus viscera is 50.51%; with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content reaching 37.30% (Fu et al., 2020). Zheng established the optimal conditions for extracting fish oil from the byproduct of O. ocellatus, the results showed that the extraction rate was 53.50% ± 1.04% under the conditions of alkaline protease, hydrolysis time 3 h and temperature 50 °C (Zheng, 2018). (Huang et al., 2016). investigated the effects of four common proteolytic enzymes—alkaline protease, neutral protease, papain, and animal protease A5—on octopus processing by-products, evaluating the amino acid composition and antioxidant properties of the resulting hydrolysates. Among the tested enzymes, animal protease A5 produced the highest mass fraction of complex amino acids (57.12%). This indicates that animal proteases may better hydrolyze most of the protein in octopus’ leftovers into amino acids. Additionally, compared with other enzymes, the papain-generated hydrolysate exhibited better hydroxyl radical (·OH) scavenging activity (IC₅₀ value of 0.56 mg/mL), and the alkaline protease hydrolysate demonstrated superior Fe²⁺ chelating ability (IC₅₀ of 0.46 mg/mL). Food-derived metal-chelating peptides (MCPs) may prevent metal deficiency by inhibiting metal precipitation induced by gastrointestinal conditions and exogenous compounds (Yu et al., 2024). Complementing these findings, Wu et al. developed a novel octopus processing by-products protein hydrolysate (OSPH) and identified that the amides and carboxylates in OSPH may be binding sites for chelation. OSPH Ca chelates exhibit good stability and high calcium absorption efficiency in simulated human gastrointestinal environments and improved the utilization rate of octopus by-products, which may help promote economic circulation and reduce environmental pollution (Wu et al., 2019). Yu et al. treated octopus by-products with Arazyme enzyme. They compared the enzyme dosage, enzymatic hydrolysis time and solid-liquid ratio through orthogonal experiments. The results showed that the optimal conditions were water-to-materials ratio as 1:15 (w/v), an enzyme dosage of 300 U/g and an enzymatic hydrolysis time of 3 hours, the content of peptides in this condition was 5.08 mg/mL (Yu et al., 2011). These findings establish theoretical frameworks for octopus byproduct utilization, offering both functional food development guidelines and resource optimization strategies.

Taurine (a sulfur-containing amino sulfonic acid) has multiple activities such as anti-inflammatory, anti-oxidant, maintaining homeostasis, inhibiting organ fibrosis and promoting brain tissue and intellectual development that provide developmental benefits for infants and young children (Demarçay, 1838; Qaradakhi et al., 2020; Beggan et al., 2023; Hu et al., 2024; Ju et al., 2024). Due to its significant biological activity, there is increasing interest in efficiently extracting taurine from natural sources. Jia and Chen determined the optimal process parameters for taurine extraction from octopus by-products through orthogonal experiments, which included: extraction temperature of 80 °C, ethanol concentration of 80%, solid-liquid ratio of 1:12, extraction time of 2 h, and extraction times of 3. Under these optimized conditions, the taurine extraction rate reached 0.93%, demonstrating the effectiveness of the established protocol (Jia and Chen, 2012).

The variations in extraction techniques mentioned above influence the yield of bioactive components and further highlight the potential divergence in biological activities among different constituents. Building on this, further exploration of the pharmacological mechanisms of key nutrients in octopus extracts has become a pivotal step in advancing their translation from laboratory research to clinical applications. Modern studies have revealed that Octopus has various biological activities. Octopuses are a nutrient-rich food containing essential proteins and minerals and also acting as functional foods due to their bioactive components with health benefits (Li et al., 2023). The nutrients of octopus include moisture, protein, fat, ash, and carbohydrates ( Table 2 ). Octopus is abundant in amino acids, fatty acids and mineral elements. Peptides, proteins, polysaccharides and bioactive biogenic amines were isolated from octopus through different methods ( Supplementary Table S1 ). As illustrated, the biological activities of octopus were summarized in Figure 5 . At present, extensive pharmacological studies have been carried out on the bioactive components of octopuses. However, quantitative analysis of these bioactive components remains scarce. In future research, advanced techniques such as metabolomics and pharmacokinetics should be employed to fill the existing knowledge gaps (Yu et al., 2022; Cheng et al., 2024).

The octopus, with its highly sophisticated and adaptable biology, is an ideal model for biomedical application research. Octopus arms are distributed with suckers and the special structure and micro-serrations of these suckers give octopuses great potential in biomaterial applications, its regenerative capabilities are particularly relevant to the field of regenerative medicine ( Figure 8 ) (Baik et al., 2017; Hwang et al., 2022; Lee et al., 2024b).

A novel biomimetic material, developed using microstructural features inspired by octopus tentacles and suckers, has been designed as a controlled-release nitric oxide (NO) carrier for biomedical applications. This carrier significantly reduces inflammation in diabetic skin injuries in type I diabetic rats, promote the production of vascular endothelial growth factor, thereby stimulating blood vessel regeneration (Chen et al., 2024). In addition to structural applications, the biomimetic properties of octopuses have inspired the development of novel drug delivery systems. Luo et al. designed two types of suction patches based on the structure of octopus suction cups, a simple suction cup (SC) and the other is a suction cup orifice design (SCOD). Pharmacokinetic experiments in beagle dogs showed that the SCOD patch significantly improved the bioavailability of desmopressin compared with SC. In addition, participants in human studies demonstrated high patient compliance (Luo et al., 2023). Wu et al. designed an adhesive patch with excellent mechanical properties, adhesion and biocompatibility based on octopus suction cups. In the adhesion to the liver surface in laboratory rabbits for 24 h, histological analysis revealed no apparent tissue damage, lesions, inflammation, or noticeable abnormality observed in the major organs of all the laboratory rabbits, and may be developed as a new apparatus for liver traction in laparoscopic surgery (Wu et al., 2024). Zhu et al. engineered a bioinspired patch that emulates the tentacle adhesion and venom-delivery mechanisms of the blue-ring octopus. This innovative device enables precisely controlled, on-demand drug release and demonstrates robust adhesion to tissue surfaces. Experiments have shown that the patch significantly accelerates ulcer healing, inhibits tumor growth, and has good biocompatibility and potential for smart wearables (Zhu et al., 2023b). An octopus-inspired flexible multivalent penetrating system was designed as a non-viral vector. In human corneal epithelial cells and human conjunctival epithelial cells have observed high fluorescence intensity and low toxicity. In a retinoblastoma-bearing mice model, local infusion can effectively inhibit the expression of intraocular tumor proteins. This study provides a new method for gene therapy (Jiang et al., 2019). Another type of transdermal delivery patch features a double-layer suction cup cluster inspired by octopus tentacles. The upper layer mimics the central protrusion of octopus suckers to enhance negative pressure adsorption, while the lower layer incorporates a flexible cup-shaped structure that conforms to skin texture, expands the contact area, and generates negative pressure via finger pressing to enable non-invasive transdermal drug delivery. In an atopic dermatitis model, this design demonstrated a 44% reduction in serum IgE, a 56% decrease in IL-4, and a 45% reduction in epidermal thickness, alongside high biocompatibility and low irritation, providing an efficient and safe new strategy for transdermal drug delivery (Lee et al., 2024a).

The arm regeneration process in octopuses follows a well-defined sequence: the protrusion of the central nervous axis and contraction of the wound’s edge, the appearance of a bud-shaped hemisphere, the development of the regenerating tissue into a conical shape, the appearance of rough suckers, the appearance of chromatophores and regenerated arm functional reconstruction (Imperadore and Fiorito, 2018). This morphological progression correlates with specific cellular events observed in recent studies. Molecular analyses reveal blood cells and connective tissue cells may play a major role in the neural regeneration ability of O. vulgaris. After 30–45 days of nerve resection, axons passed through the injury gap into the stellate ganglion and formed a network. By 5 months post-injury, angiogenesis occurs alongside nerve fibers regeneration to re-establish the functional connection between the brain and the periphery (Imperadore et al., 2017, 2019). Histological evidence demonstrates O. vulgaris may rapidly repair wounds within 24 hours after the arm is amputated through various mechanisms such as tissue contraction, epithelial cell migration and the coalescing of cells at the site of injury (Shaw et al., 2016). Imperadore et al. used label free multiphoton microscopy to study the regeneration process of O. vulgaris and found that dermal contraction and blood cell debris clearance were involved in wound healing. After healing, new tissues, cells and nerve fibers were generated with proliferative characteristics (Imperadore et al., 2022). Translating this biological phenomenon to human medicine could transform treatments for traumatic injuries, neurodegenerative diseases, and organ loss. Neuron regeneration and synaptic regeneration provide ideas for the treatment of AD and PD. The neural regeneration ability of octopus may not only inform stem cell therapies but also establish novel targets for neurodegenerative disease research (Qian et al., 2020; Qu et al., 2021).

This review presents a summary of the distribution, nutrients, bioactive compounds properties, regenerative ability and processing methods of marine octopus. Octopuses are mainly distributed in tropical and temperate waters. They have abundant resources and are widely distributed around the world, demonstrating significant research value. China, Spain, Vietnam and Morocco are among the main export countries of octopuses, while South Korea, Japan, Italy and the United States are the primary import countries.

The main nutrients in octopuses include small molecular components such as amino acids, fatty acids and trace elements, as well as both small and large molecular components like proteins, peptides, biogenic amines and polysaccharides. Octopus-derived peptides exhibit diverse biological activities. These include promoting lactation in SD rats, reducing urine output in diabetic rats, enhancing urinary osmolality, and decreasing mortality in Candida albicans-infected zebrafish, among others. Octopus peptide-based products exhibit significant commercialization potential. If further researched and developed, these bioactive components could demonstrate enormous potential in functional foods, nutritional supplements, clinical translation, and other domains. However, the current quality evaluation system for these peptides still requires substantial improvement. During octopus processing, substantial by-products is generated. Proper extraction of these can obtain valuable ingredients such as taurine, fish oil, and octopamine. These methods not only enhance the utilization efficiency of octopus resources but also effectively mitigate resource waste and environmental pollution.

Moreover, the unique structural characteristics and self-repair capabilities of octopuses suggest their potential positive applications in tissue engineering, nerve repair, and the treatment of neurodegenerative diseases. The advancement of microneedle technology serves as a promising demonstration, while micro-serrated structures have been mimicked, manufacturing these textures at a clinical grade—with consistent adhesion strength and sterility—remains continuous validation. Regulatory approval for such novel devices would require rigorous testing on parameters like biocompatibility and shelf life. In addition, the application of octopus neuron regeneration and wound healing faces significant challenges. Simulating the dynamic regulatory mechanisms of octopus stem cells also presents a significant challenge. Octopus neural regeneration highly relies on the rapid activation and differentiation of local stem cell niches. In contrast, the nervous systems of mammals (including humans) lack comparable stem cell reserves or exhibit lower activation efficiency. Additionally, OA levels in mammals are extremely low. A key challenge in clinical translation is how to mimic octopamine’s neuroprotective effects through pharmacological interventions or gene editing while avoiding interference with existing metabolic network diseases. In the future, interdisciplinary collaboration may emerge as a critical breakthrough. Developing mammalian-specific regeneration signaling pathway activators for precise intervention in nerve injury sites appears feasible. For instance, constructing vascularized organoids and AI-driven dynamic pathological models could overcome the limitations of existing animal models and in vitro systems, authentically replicating the multicellular interaction mechanisms within the human neural regeneration microenvironment. Additionally, the advancement of ethical frameworks must be prioritized, particularly in establishing long-term risk monitoring systems for stem cell activation and chimeric brain technology applications. Future research should further dissect molecular details such as lactate metabolism reprogramming and epigenetic regulation in octopus’ regeneration and uncover their conserved associations with the human nervous system through multi-omics techniques, thereby accelerating the transition from basic mechanism analysis to clinical therapy development and ultimately achieving revolutionary breakthroughs.