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 asα-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.

Marine algae are found to be excellent in their nutritional and potential therapeutic properties. This study explores the antidiabetic and anticancer potential of fractionated polyphenolic extract of Caulerpa racemosa, green macroalgae. Crude polyphenolic extract (CPE) of C. racemosa and its fractions (n-hexane, ethyl acetate, chloroform, and distilled water) were tested for its total phenol and flavonoid contents and antioxidant potential. The ethyl acetate fraction was subjected to gas chromatography/mass spectrometry (GC/MS). The in vitro antidiabetic activity was assessed by alpha-amylase, glucosidase inhibition and anti-glycation assays. Also, in-silico studies were conducted to test the binding affinities between caulerpin with alpha-glucosidase enzyme and estrogen receptor (ER) active sites. Each fraction was tested for its in vitroin vitroanticancer activity by CellTiter-Glo and MTT cell proliferation assays. The total phenolic and flavonoid contents and the antioxidant potential of the crude extract were observed to be dose dependent. The GC/MS analysis of the ethyl acetate fraction yielded 47 peaks, whereas n-hexadecanoic acid and hexadecanoic acid methyl ester showed the highest compatibility percentages of 99% and 96%, respectively. The CPE exhibited a higher potential in both alpha-amylase inhibitory and anti-glycation activities. The ethyl acetate fraction was more effective against alpha-glucosidase inhibition. Molecular docking revealed a high binding affinity between the alpha-glucosidase enzyme and caulerpin and showed high binding affinity toward caulerpin, with H-bond interactions. The in vitro anticancer analyses revealed that chloroform fraction and CPE exhibited moderate activity on the KAIMRC1 cell line. Also, the CPE exhibited high specificity compared to the standard drug in anticancer studies. Our findings evidence the pharmacological potential of the CPE of C. racemosa, and bioactive compounds of the species may be utilized as lead molecules to develop anti-diabetic and anti-cancer drugs.

Leaves of Passiflora suberosa L. (Family: Passifloraceae; common name: wild passion fruit, devil’s pumpkin) are used in Sri Lankan traditional medicine for treating diabetes. The present study investigated the in vivo ability of P. suberosa leaves to manage blood sugar status and associated cholesterol levels. Mechanisms of action and toxicity were also determined. Phytochemical screening of aqueous extracts of P. suberosa leaves and carbohydrate content of the leaves were determined according to previously published methods. In two group of male mice (n = 9), effects on fasting and random blood glucose levels (BGLs) of different acute doses (0, 25, 50, 100 and 200 mg/kg) of the aqueous leaf extract (ALE) were evaluated at 1, 3, and 5 h post-treatment. In another set of mice, the fasting BGL was evaluated following treatment of 0 or 50 mg/kg ALE (dose prescribed in traditional medicine) for 30 consecutive days. The lipid profile, some mechanism of ALE action (diaphragm glucose uptake, glycogen content in the liver and skeletal muscles) and its toxicity (behavioural observation, food and water intake, hepatoxicity) were also assessed following 30-day treatment. However, sucrose and glucose tolerance tests and intestinal glucose uptake were conducted to determine portion of mechanisms of action following single dose of 50 mg/kg ALE. Phytochemical screening revealed the presence of alkaloids, unsaturated sterols, triterpenes, saponins, flavonoids, tannins and proanthocyanidins. Carbohydrate content of the leaves was 12.97%. The maximum hypoglycemic effect was observed after 4 h of 50 and 100 mg/kg ALE administration. The extract decreased fasting BGL (18%) following an oral sucrose challenge and inhibited (79%) glucose absorption from the intestine. Correspondingly, the levels of glycogen in the liver (61%) and in the skeletal muscles (57%) were found be higher than that of the control group. The levels of total cholesterol (17%) and tri-glyceraldehyde levels (12%) found to be reduced in treated groups. Furthermore, no significant toxic effects were observed in treated groups. The present results suggest that the leaves of P. suberosa can be used to manage blood glucose and cholesterol levels. Isolation of active compounds are recommended for further analysis.

Although the antidiabetic efficacy of Nyctanthes arbor-tristis flowers has been reported, antiproliferative and anti-obesity activities are yet to be explored. We examined the anti-obesity and antiproliferative potentials of different fractions (hexane, chloroform, ethyl acetate, methanol) of N. abor-tristis flower extract for the first time using 3T3-L1 cells, primary peripheral blood mononuclear cells (PBMC) isolated from healthy and adult acute myeloid (AML) and chronic lymphocytic leukemia (CLL) patients, recombinant Jurkat T cells, and MCF7 cell lines. The in vitro hypoglycemic activity was evaluated using the inhibition of α-amylase enzyme and glucose uptake by yeast cells. The percentage glucose uptake and α-amylase inhibitory activity increased in a dose-dependent manner in the crude and the tested fractions (hexane and ethyl acetate). Inhibition of the 3T3-L1 cells’ differentiation was observed in the ethyl acetate and chloroform fractions, followed by the hexane fraction. Antiproliferative analyses revealed that Nyctanthes exerted a high specific activity against anti-AML and anti-CLL PBMC cells, especially by the hexane and ethyl acetate fractions. The gas chromatography/mass spectrometry analysis indicated the presence of 1-heptacosanol (hexane fraction), 1-octadecene (hexane and chloroform fractions), and other organic compounds. Molecular docking demonstrated that phenol,2,5-bis(1,1-dimethylethyl) and 4-hydroxypyridine 1-oxide compounds showed specificity toward survivin protein, indicating the feasibility of N. abor-tristis in developing new drug leads against leukemia.