*4.2. Antimicrobial Activity*

Susceptibility testing of harmful microorganisms (e.g., bacteria and fungi) in the presence of possible compounds of interest is the focus of antimicrobial activity assays. Microbial infections can cause life-threatening illnesses, resulting in millions of deaths each year. Despite the fact that the discovery of penicillin pushed many aggressive pathogenic bacteria back, many strains evolved and developed remarkable resistance mechanisms to most antibiotics [238]. Variable solvents have different antibacterial action depending on their solubility and polarity. As a result, chemical compounds isolated from various seaweeds should be optimized for antibacterial activity by selecting the optimal solvent system [239]. Micro-algal cell-free extracts are already being studied as food and feed additives in an attempt to replace synthetic antibacterial chemicals currently in use. According to Tuney et al. [240], the antibacterial action of the extract is attributable to various chemical agents found in the extract, such as flavonoids, triterpenoids, and other phenolic compounds or free hydroxyl groups. Extraction procedures, solvents used, and the time window in which samples were collected all have the potential to alter antibacterial activity [241]. A variety of organic solvents had previously been recommended for screening algae for antibacterial activity.

Pérez et al. [242] demonstrated that seaweed extracts are effective at suppressing a variety of pathogens, including *E. coli* and *Salmonella*. The majority of the research looked at crude seaweed extracts of the chemicals in ethanol or methanol crude extract. It is unclear from these investigations whether the antibacterial activity is due to a single molecule or a combination of chemicals working together. Phytochemicals were shown in several investigations to produce significant bacterial cell-membrane damage by disrupting membrane integrity [243]. The active phytochemical substances can penetrate the bacterium after the membrane has been disrupted and interfere with DNA, RNA, protein, or polysaccharide formation, resulting in bacterial cell inactivation [244]. Two of the most common types of seaweeds, namely, the total phenolic, total flavonoid, and antibacterial properties of *Padina boryana* Thivy and *Enteromorpha* sp. marine algae were extensively examined, and the authors revealed that both seaweeds show antimicrobial activity against multiple pathogens [245].

## *4.3. Anticancer Activity*

Cancers are life-threatening diseases that are considered to be a major public health issue around the world [246,247]. Uncontrolled cell development spreads into the surrounding tissues, resulting in the formation of a tumor mass [248]. Much research has looked into the anticancer potential of natural compounds derived from seaweeds, as well as the signaling pathways involved in anticancer activity [249]. Because those secondary metabolites have no hazardous effects, they have seen a lot of progress in the treatment of numerous diseases, including cancer. Thymoquinone (TQ) is one of the most important bioactive elements of black seeds, and it has been found to have numerous health advantages, including cancer prevention and treatment. Following on this, Algotiml et al. [250] studied the effect of biosynthesized Red Sea marine algal silver nanoparticles AgNPs on anticancer and antibacterial properties and the authors stated that due to their relatively moderate side effects, marine resources are currently being increasingly examined for antibacterial and anticancer medication prospects.

According to Palanisamy et al. [251], Fucoidans derived from Sargassum polycystum show antiproliferative characteristics at 50 g/mL. Additionally, Usoltseva et al. [252] also showed that native and deacetylated fucoidans (at 200 g/mL) from the brown seaweeds *Sargassum duplicatum*, *Sargassum feldmannii*, impeded colony formation in human colon cancer cells (DLD-1, HCT-116 or HT-29). According to findings of previous study [253], fucoidan extracted from the Brown seaweed Sargassum cinereum displays potent anticancer or apoptotic effects via preventing metastasis. In B-16 (mouse melanoma), CT-26 (murine colon cancer), HL-60 (human promyelocytic leukemia), or U-937 (human leukemic monocyte lymphoma) cell lines, polysaccharides produced through Pheophyceae *Ecklonia cava* show putative antiproliferative properties [254].

In addition, kappa-carrageenan extracted from *Hypnea musciformis* (Hm-SP) decreased proliferation of MCF-7 or SH-SY5Y cancer cell lines [255]. Additionally, polysaccharides derived from *Sargassum fusiforme* (SFPS) reduced SPC-A-1 cell proliferation in vitro and tumor formation in vivo [256]. Additionally, Ji and Ji [257] found that commercial laminaran (400–1600 g/mL) inhibited the growth of human colon cancer LoVo cells through stimulating mitochondrial or DR pathways. Additionally, Fucoidans isolated from *Undaria pinnatifida* have anticancer potential comparable to commercial fucoidans in cell lines Hela (human cervical), PC-3 (human prostate), HepG2 (human hepatocellular liver carcinoma), or A549 (carcinomic human alveolar basal epithelial) [258]. Moreover, previous study reported that fucoidan isolated from *Sargassum hemiphyllum* may increase miR-29b expression in human hepatocellular carcinoma cells, which aids in the lowering of DNA methyltransferase 3B expression [259]. Moreover, Fucoidans from *Fucus vesiculosus* were revealed to have anticancer potential, inducing apoptosis in MC3 human mucoepidermoid carcinoma cells via caspase-dependent apoptosis signaling cascade [260] (Figure 9).

**Figure 9.** Demonstrate the ability of algal polysaccharide (SP)-based customized signals produced from sea algae to cause tumor cell death (apoptosis). Adapted from ref. [233] obtained from mdpi journals.

#### *4.4. Antidiabetics Activity*

As a result of an unhealthy lifestyle, obesity, and stress, diabetes is becoming a global illness. Additionally, obesity has been on the rise in Saudi Arabia as a result of changing lifestyles and socioeconomic status [260,261]. There is a close association between obesity and type 2 diabetes. Drugs that suppress the enzymes α-glucosidase and α-amylase, which break down starch into glucose before it is absorbed into the bloodstream, could be used to treat diabetes [262]. It is necessary to look for effective therapeutic natural medications with less side effects. Garcimartn et al. [263] showed that a α-glucosidase inhibitory effect on restructured pork treated with seaweeds such as *Undaria pinnatifida*, *Himanthalia elongata*, and *Porphyra umbilicalis* caused a reduction in the blood glucose absorption. *Padina tetrastromatica* phenolic extracts inhibited both α-glucosidase and α-amylase, with higher inhibition linked with a higher phenolic concentration in the extracts. The extracts inhibited α-glucosidase (IC50 value of 28.8 g mL−1) and -amylase (IC50 value of 47.2 g mL−1) by 38.9 and 26.8%, respectively [264]. Similarly, α-glucosidase inhibitory action was observed in methanol, ethanol, and acetone extracts of *Durvillea antarctica*, methanol extracts of *Ulva* sp., and acetone extracts of Lessonia spicata [265]. Methanol extracts of *Padina tenuis* (400 μg mL<sup>−</sup>1) and ethanol extract of *Eucheuma denticulatum* (10 mg mL−1) and *Sargassum polycystum* (10 mg mL<sup>−</sup>1) significantly inhibited α-amylase by 60%, 67%, and 46%, respectively [266]. Recently, the acetone extract (80%) of brown seaweed Turbinaria decurrens was studied for its antihyperglycemic effects in alloxan induced diabetic wistar male rats [267]. The results showed a significant reduction in postprandial blood glucose levels of seaweed extracts treated rats to 180.33 mg dL−<sup>1</sup> and 225.33 mg dL−<sup>1</sup> at the dose of 300 mg/kg body weight and 150 mg/kg body weight, respectively, compared to diabetic control (565.0 mg dL<sup>−</sup>1) and positive control (115.33 mg dL−1). The bioactive compounds derived from algae and their application is illustrated in Table 9.


**Table 9.** Bioactive compounds derived from algae and their applications.


**Table 9.** *Cont.*


#### **5. Seaweeds in Bio-Manufacturing Applications**

Modern consumers are well aware of the nutritional value of food and the negative impact that synthetic preservatives may have worse effect on their health, so it is unsurprising that they prefer fresh and lightly preserved foods that are free of chemical preservatives, but contain natural compounds that may benefit their health [306].
