Inclusion criteria

Studies that satisfied the following requirements were included: peer-reviewed scholarly publications, published in English, concentrated on marine organisms, especially Scylla serrata, and chemical components, pharmacological actions, or reported ethnopharmacological applications.

Exclusion criteria

The following were not included: abstracts of conferences, duplicates, research that only uses animal testing, and articles that are irrelevant and unrelated to the review’s goals.

A total of 400 records were found. 380 studies were evaluated after duplicates were eliminated, and 150 of them were eliminated. After 230 articles’ full texts were evaluated, 153 were eliminated. The review ultimately comprised 77 studies (Figure 2). ToxRTool for in vitro studies and SYRCLE for animal studies were used to evaluate methodological quality and bias risk. Additionally, a simplified rubric was used to evaluate study design, data dependability, and reporting transparency.

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Figure 2. Study selections for review.

Antioxidant activity

Reactive oxygen species like superoxide anion (O₂^–), perhydroxy radical (HOO^•), hydrogen peroxide (H₂O₂), hydroxyl radical (^•OH), alkoxy radical (RO^•), and peroxy radicals (ROO^•) can cause oxidative stress in cells. All organisms have either enzymatic or non-enzymatic antioxidant defensive systems for protecting the cells from various injuries [39]. Compared to terrestrial organisms, marine organisms are very sensitive to oxidative stress due to climate change in the sea, and the stress could be heat or ultraviolet radiation and this stress leads to the production of metabolites for their defense mechanism [40].

The antioxidant potential of Scylla serrata by DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS [2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)] assay methods has been determined and was found as 35% and 41% for soluble chitosan, 19% and 33% for haemolymph, and 49% and 61% for muscle extract, respectively. The muscle extract exhibited the highest activity [41]. Using molecular modeling and docking techniques, a recent study revealed the molecular basis of the interactions between SOD (superoxide dismutase) inhibitors and extracellular-SOD in the Scylla serrata. According to the GOLD findings, Pro72, Asp102, and Thr103 are commonly the sites where SOD inhibitors and Ec-SOD of Scylla serrata interact [42]. In Scylla serrata, SOD is an important antioxidant enzyme that promotes innate immunity and guards against oxidative stress. The SOD gene’s crucial function in stress protection and evolutionary adaptation was established by its isolation and sequencing [43]. In a study, using Scylla serrata shell flour, the average output of astaxanthin produced with varying acetone concentrations was 3.29 g. The antioxidant activity at the optimal acetone concentration of 65% had the IC₅₀ value of 805.837 μg/mL [44]. Scylla serrata extract had an IC₅₀ value of 2.25 ppm, indicating very significant antioxidant activity. This finding suggests that 50% of DPPH radicals can be inhibited by a small amount of the extract [45]. A study revealed that soil and water characteristics like temperature, salinity, and mineral load had a significant impact on Scylla serrata’s oxidative stress and antioxidant enzyme activity. The highest antioxidant enzyme activity was found in the hepatopancreas, which rose in dry seasons and had a positive correlation with physicochemical stresses [46].

With an IC₅₀ of 65.25 ppm, Scylla serrata ethanol extracts demonstrated dose-dependent antioxidant activity in the DPPH experiment, suggesting high antioxidant potential [47]. Allantoin, CAT, and GR were important regulators of oxidative stress, and allantoin plays a part in Scylla serrata’s seasonal antioxidant homeostasis [48]. Crab-derived antioxidants have shown potential activity in various in vitro models. In the future, oxidative stress-related diseases like cardiovascular, neurodegenerative, and metabolic disorders may be treated with the isolated compounds from the crab.

Anticancer activity

Many bioactive compounds from different marine sources have been found to inhibit the proliferation of several cancer cells. The mud crab soup Scylla serrata has shown antiproliferative and anticancer properties on the Jurkat leukemic T-cell line by MTT colorimetric technique with an inhibitory concentration of 35% (v/v) in a dose and time-dependent manner compared to the standard drug cisplatin [49]. Strong antibacterial activity and the formation of homogeneous spherical chitosan/silver nanocomposites were demonstrated by the chitosan derived from Scylla serrata shells, which also demonstrated anticancer potential against the MCF-7 cell line [50]. High molecular weight (HMW) chitosan and low molecular weight (LMW) chitosan have been found effective against breast cancer (MCF-7), cervical cancer (HeLa), and osteosarcoma (Saos-2) cell lines at IC₅₀ values of 1.68, 1.0, 1.7 mg/mL for HMW and 1.76, 1.0, and 1.63 mg/mL for LMW chitosan, respectively [51]. Haemocyanin (HC) (95 kDa), a copper-containing respiratory protein, was isolated from the haemolymph of the mud crab Scylla serrata. The IC₅₀ of HC was found at 80 µg/mL against lung cancer (A549) cell lines [52].

Lectins are a group of glycoproteins of non-immune origin, specific to carbohydrates, and have at least two carbohydrate-binding sites. They are found in plants, animals, and microorganisms. Lectins’ precipitating and agglutinating properties are similar to antibodies, but like antibodies, they do not synthesize immunoglobulins. Due to their specificity to a certain type of carbohydrate, they can be used as a target in the drug delivery system and as a cancer biomarker for recognizing malignant tumor cells for the diagnosis and prognosis of cancer [53, 54]. Scylliin-2 (calcium-dependent monomeric lectin; 75 kDa) from the haemolymph of mud crabs had high sensitivity towards polyvalent Tn/T containing glycoproteins, a type of antigen present on the surface of the tumor cells. The mitogenic property of isolated Scylliin-2 was tested against BALB/c splenocytes, and 10 μg/mL of Scylliin-2 showed significant activity against BALB/c splenocytes. The IC₅₀ value of Scylliin-2 on HepG2 was 80 μg/mL [55]. Chitin was evaluated for cytotoxicity at doses of 1, 25, 50, 75, and 100 μg/mL. It has shown cytotoxicity with an IC₅₀ of 64.39 ± 1.315 μg/mL against HepG2 cells [56].

Antidyslipidemic agent

In comparison to pravastatin (IC₅₀ = 6.95 ± 0.189 μg/mL; 92.82% inhibition), chitin derived from mangrove crab shells demonstrated modest HMG CoA reductase inhibition (IC₅₀ = 36.65 ± 0.082 μg/mL; 68.73% inhibition at 100 μg/mL). Enzyme inhibition was indicated by the decrease in mevalonate synthesis. Strong binding affinities (−3.6 to −5.8 kcal/mol) to important targets of lipid metabolism were found by in silico research. The blood-brain barrier permeability and non-toxicity were verified by ADMET analysis. Stable binding to HMG CoA reductase was demonstrated using molecular dynamics simulations [56].

Anti-anaemic activity

In a three-week in vivo study, oral administration of Scylla serrata extract (7.0 mg protein/kg and 52 mg protein/kg) has shown an antianemic effect in Wistar rats through alleviation of RBC, Hb, haematocrit (HCT), and mean corpuscular haemoglobin (MCH) levels [57].

Antimicrobial activity

Crabs and other aquatic organisms have the property to release antimicrobial peptides, as part of their innate immune system, since they are exposed to various bacterial strains and live in numerous contaminated environments. These peptides are released not only from the crab haemolymph but also from the exoskeleton. Recently, many researchers have exclusively studied and reported the antibacterial properties of the mud crab Scylla serrata. Six crab species’ haemolymph extracts exhibited antibacterial efficacy against ten bacterial strains (n = 3). The most significant zone of inhibition (ZOI) was demonstrated by Scylla tranquebarica (10 mm, V. cholerae), Scylla serrata (6–6.5 mm, maximum against L. delbrueckii subsp. bulgaricus), and Macrophthalmus depressus (5 mm) [58]. An antibacterial protein, SSAP (Scylla serrata antimicrobial protein; 11 kDa), from granular hemocytes, was isolated, characterized, and evaluated against gram-negative and gram-positive bacterial strains. The inhibitory concentration (MIC) of SSAP was in the order P. aeruginosa (12.5–25 μg/mL), E. coli (25–50 μg/mL), S. pyogenes (25–50 μg/mL), and S. aureus (50–100 μg/mL) [59].

The natural polysaccharide chitin, which was extracted from the carapace, chelate legs, and walking legs of crabs, had antibacterial action against S. aureus (8.4–10.4 mm), S. epidermidis (7.9–9.7 mm), B. subtilis (7.5–9.1 mm), P. aeruginosa (5.6–7.2 mm), and P. mirabilis (5.3–6.8 mm). Disk diffusion was used to measure activity (4.5 mm discs, nutritional broth, 1 × 10⁸ CFU/mL, 37°C, 17 h, n = 3), with DMSO and penicillin serving as the negative and positive controls, respectively. Millimeters were used to measure the zones of inhibition [60]. After being extracted from Scylla serrata haemolymph (β-GBP: 100 kDa), β-GBP and HC were structurally confirmed using FTIR, XRD, CD, and HPLC. At 50–100 μg/mL, Scylla serrata beta-glucan binding protein (Ss-β-GBP) demonstrated dose-dependent antibiofilm effects and immunomodulatory action (yeast agglutination, phagocytosis, PO enhancement). When tested against both gram-positive (E. faecalis, S. aureus) and gram-negative (E. coli, P. aeruginosa) bacteria, its antibacterial activity revealed MICs < 60 μg/mL. At 100 μg/mL, HC also produced zones of inhibition against V. harveyi (17 mm), V. alginolyticus (16.5 mm), V. vulnificus (16 mm), and V. parahaemolyticus (14.5 mm), demonstrating bacteriostatic actions. Although in vivo and clinical validation are still needed, our results demonstrate the therapeutic potential of Scylla serrata haemolymph proteins [61].

Scygonadin (10.8 kDa) is an anionic antimicrobial peptide isolated and purified from the seminal plasma of Scylla serrata, which has shown potent activity against Micrococcus luteus at IC₉₀ of 0.125 mg/mL [62]. Two antimicrobial peptides, Sc-ALF (Scylla-anti-lipopolysaccharide) and Sc-crustin (Scylla crustin), from the haemocytes of the mud crab with molecular weights of 11.17 kDa and 10.24 kDa, respectively have been reported for the first time [63]. Haemolymph was extracted from the dactylus area of the walking legs of Scylla serrata, allowed to clot, centrifuged (450 g, 10 min, 4°C), and the serum that resulted was used right away. Under controlled conditions, the MTT colorimetric test was used to measure the antibacterial activity against crustacean pathogens (V. harveyi, V. vulnificus, V. alginolyticus, V. parahaemolyticus, and V. anguillarum) and bacteria obtained from crabs (Bacillus sp., B. flexus, E. coli, and P. aeruginosa). Crab serum (1.224 mg protein) has shown potent antibacterial properties against Bacillus sp. N1, B. flexus N3, E. coli, and some of the pathogenic strains of crabs like V. harveyi, V. alginolyticus, and V. vulnificus, and found that a 14 kDa protein in the serum was responsible for the activity [64].

Chitosan derived from the shell of Scylla serrata showed significant antibacterial action against both gram-positive and gram-negative bacteria, such as Bacillus, Pseudomonas, E. coli, and Staphylococcus. Along with advantageous structural and physicochemical traits, the isolated chitosan demonstrated robust antibacterial qualities, especially against E. coli, indicating its possible uses in microbiology and medicinal science [65]. Antibacterial haemocyanin (AB-Hcy) from the serum of the mud crab Scylla serrata was characterized, and AB-Hcy (15 μg/mL) has shown bacteriolytic properties against Bacillus sp. N1, B. flexus N3, E. coli, P. aeruginosa, V. harveyi, V. parahaemolyticus, and V. vulnificus. The highest activity has been shown against V. harveyi (0.248 units·min⁻¹·mg protein) and E. coli (0.202 units·min⁻¹·mg protein). The growth of crustacean pathogenic bacteria was also significantly inhibited by AB-Hcy [66]. Some of the reported antimicrobial compounds from mud crab Scylla serrata are tabulated (Table 3).

Although these compounds have shown antibacterial activity in vitro, indicating the possibility of further investigation as therapeutic agents, their safety and efficacy in vivo have not been investigated, and translational applications should be handled carefully with additional preclinical validation.

Neuroprotective activity of Scylla serrata edible crab Rasayana

Traditional medicine has long utilized Karkataka Taila (KT), a classic Ayurvedic Rasayana made from Scylla serrata for neurological health and regeneration. It has long been thought to promote nervous system function and increase vitality. According to current experimental research, KT may have neuroprotective and anti-Parkinson’s benefits. In vitro experiments with human neuroblastoma (SH-SY5Y) cells showed that KT decreased oxidative stress (ROS and SOD) and neuroinflammatory markers (IL-6, IL-1β, TNF-α, and nitrite) while raising dopamine levels. Studies conducted in vivo on male Wistar rats showed protective effects on behavioral performance as well as improvements in oxidative stress, neuroinflammation, and dopamine levels [69]. However, it is too early to determine whether these findings are relevant to humans. Dosimetry issues and the formulation’s standardization caused by variations in the marine and herbal components present major obstacles to clinical translation. For KT to be safe, effective, and reproducible in possible therapeutic applications, strict pharmacological validation and consistent preparation procedures are required. The key pharmacological activities of Scylla serrata based on published scientific evidence are illustrated in Figure 6.

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Figure 6. Mechanism map.