Marine algae are an important source of bioactive metabolites in drug development and nutraceuticals. Diabetes mellitus is a metabolic disorder and the third leading cause of death worldwide due to lifestyle changes associated with rapid urbanization. Due to the adverse side effects of currently available antidiabetic drugs, search for an effective natural-based antidiabetic drug is important to combat diabetes and its complications. Therefore, in lieu with herbal drug development, it is important to find the potential benefits of seaweeds for the management of type 2 diabetes as they are underexplored yet in Sri Lanka. Among the marine seaweeds, natural bioactive compounds are abundant in brown algae with potentials in application as active ingredients in drug leads and nutraceuticals. Bioactive secondary metabolites are derived from numerous biosynthetic pathways of marine algae which contribute to various chemical and biological properties. Phlorotannins present in marine brown algae exhibited antidiabetic activities through different mechanisms such as the inhibitory effect of enzyme targets mainly by inhibiting the enzymes such as α-amylase, α-glucosidase, angiotensin-converting enzymes (ACE), aldose reductase, dipeptidyl peptidase-4, and protein tyrosine phosphatase 1B (PTP 1B) enzyme. In addition, phlorotannins derived from brown algae have the ability to reduce diabetic complications. Hence, the present review focuses on the different antidiabetic mechanisms of secondary bioactive compounds present in marine brown algae.

Obesity and diabetes are major metabolic disorders which are prevalent worldwide. Algae has played an important role in managing these disorders. In this study, Gracilaria edulis, a marine red algae, was investigated for antioxidant and hypoglycemic potential using in vitro models. De-polysaccharide methanol extract of G. edulis was sequentially partitioned with hexane, chloroform, ethyl acetate, and antioxidants, and hypoglycemic potentials were evaluated using multiple methods. High antioxidant potential was observed in the ethyl acetate fraction in terms of ferric reducing antioxidant power, iron chelating, and DPPH and ABTS radical scavenging activities, while the crude methanol extract exhibited potent oxygen radical-absorbance capacity. Potent α-amylase inhibitory activity was observed in the ethyl acetate fraction, while the ethyl acetate fraction was effective against α-glucosidase inhibition. Glucose diffusion was inhibited by the ethyl acetate fraction at 180 min, and the highest antiglycation activity was observed in both chloroform and ethyl acetate fractions. Additionally, gas chromatography-mass spectrometry analysis of the ethyl acetate fraction revealed the presence of several potent anti-diabetic compounds. In conclusion, G. edulis exhibited promising antidiabetic potential via multiple mechanisms. The ethyl acetate fraction exhibited the strongest hypoglycemic and antiglycation potential among the four fractions, and hence the isolation of active compounds is required to develop leads for new drugs to treat diabetes.

The current study determined the cytotoxic and apoptotic potential of the polyphenol-rich methanol extract of Chnoospora minima (C. minima) and its fractions against human breast adenocarcinoma (MCF-7) and rhabdomyosarcoma (RMS) cells. MTT and neutral red assays were used to determine cytotoxicity. The clonogenic assay evaluated the antineoplastic activity, while the apoptotic activity was determined by cellular morphological changes, caspase 3/7 activity, and DNA fragmentation. Morphological alterations in apoptosis were observed by an inverted phase-contrast microscope and Hoechst 33342 staining methods. The total phenolic, flavonoids, alkaloids, and antioxidant activity in the hexane and chloroform fractions were determined, based on their cytotoxic activity. The hexane fraction of C. minima effectively reduced the cell growth that is concentration-dependent in human RMS and MCF-7 cell lines. It also exhibited low cytotoxicity on Vero cells. The characteristic cellular and nuclear apoptotic morphological features were observed. A noticeable caspase 3/7 activation and the fragmented DNA were detected only in the hexane fraction treated RMS cells, whereas MCF-7 cells showed low caspase 3/7 activation due to a lack of caspase 3 and no evidence of having a typical ladder pattern of apoptosis. Further analysis revealed that the hexane fraction-treated RMS cells upregulated the p53 gene twofold (2.72) compared to the p21 (0.77) gene, whereas in the MCF-7 cells, a 2.21-fold upregulation of p53 was observed compared to the p21 (0.64) gene. The hexane fraction exhibited moderate total phenolics, flavonoids, alkaloids content, and antioxidant activity. According to the different antioxidant mechanisms, hexane and chloroform fractions showed the highest antioxidant activities by FRAP and ORAC assays, respectively. GC-MS analysis of hexane fraction revealed the presence of methyl tetradecanoate (38.314%) as the most abundant compound. The study’s findings highlighted that the non-polar compounds present in the hexane fraction of C. minima suppressed cell proliferation and induced apoptosis-mediated cell death in RMS and MCF-7 cells, mainly via the activation of the p53 gene. Hence, the isolation of compounds is warranted. However, more studies are required to understand the mechanistic insights of these observations.

Marine seaweeds are a promising source of bioactive secondary metabolites that can be utilized in drug development and nutraceuticals. Diabetes mellitus is a leading non-communicable disease, and it is the third leading cause of death worldwide. Among the types of diabetes, type 2 became the major health problem as it is associated with severe health complications. Since available oral hypoglycemic drugs cause several adverse effects, it is worth searching for a natural cure with fewer or no side effects that may benefit patients with type 2 diabetes. Among the marine seaweeds, brown and red seaweeds are extensively studied for the anti-diabetic activity compared to the green seaweeds. Bioactive compounds present in marine seaweeds possess anti-diabetic potential through diverse mechanisms, mainly by reducing postprandial hyperglycemia and associated complication. Most of the studies emphasized that the marine seaweeds control the hyperglycemic condition by inhibiting carbohydrate hydrolyzing α-amylase,α glucosidase enzymes, and the inhibitory effect of dipeptide peptidase-4 that are involved in the degradation of incretins. Similarly, bioactive compounds in marine seaweeds can reduce diabetes complications by inhibiting angiotensin-converting enzymes, aldose reductase, protein tyrosine phosphatase 1B enzyme. This chapter focuses on the anti-diabetic potential of marine brown, green, and red seaweeds through different mechanisms.

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