Cytotoxicity of Some Sri Lankan Seaweed Extracts

Algae are known to produce a large number of secondary metabolites with a variety of biological activities. Methanol extracts of 24 seaweeds collected around Sri Lanka were subjected to antibacterial, anti fungal and cytototoxicity studies. Although, none of them were active against the tested bacteria and fungi, some showed cytotoxic activity evidenced the brine shrimp lethality bio assay. Out of the 24 species, nine species (Halimeda discoidea, Sargassum spp., Dictyota spp.-l, Dictyota spp.-2, Amphiroa anceps, Amphiroa fragilissima, Cheilosporum acutilobum, Galaxaura lapidescens, and Tricleocarpa fragilis) showed LC50 value below 1000 gg/ml. Many red algae caused brine shrimp death compared to the brown and green algae tested. Of the eight brown seaweeds, 3 showed LC50 value below 1000 gg/ml, whereas only one of the six green seaweeds tested was effective. The highest activity was recorded in methanol extract of Halimeda discoidea (LC50 0.05 ug ml-I ) compared to the other seaweeds. Further, four species caused brine shrimp death below the level of positive control, 4-hydroxy-2methylquinoline (30.15 Pig ml-I). These preliminary results suggest that the seaweeds could be exploited for the isolation of anti tumor compound

New brominated sesquiterpenes from the red alga Laurencia hetroclada Harvey, and their immunosuppressive activity studies

Red algae of the genus Laurencia Harvey (Ceramiales, Rhodomelaceae) is a complex genus, encompassing a large variety of morphologicallycomplex algal species. In continuation of our work on chemistry and biological activity studies of some Sri Lankan seaweeds, we examined the chemistry of MeOH extract of Laurencia hetroclada collected from Tangalle coast. Above extract was subjected to column chromatography followed by PTLC gave a new brominated sesquiterpene 1 along with two known compounds, algoane 2, and caulerpin 3. The 13C NMR spectrum along with the DEPT experiments of 1 revealed only 15 carbon signals corresponding to four methyls, five methylene, one methine and five quaternary carbons. The 1H NMR (CD3OD, 500 MHz) spectrum of 1 showed signals due to three methyls, four methylenes, and two methine protons. The singlets resonated at 1.25 (3H, s), 1.27 (3H, s), and 1.85 (3H, s) were assigned to Me-8’, Me-6’, and Me-9’, respectively. The characteristic downfield proton at 4.83 (dd, J = 4.2,15 Hz) was assigned to H-4, geminal to the Br atom, whereas the proton that resonated at 3.96 (d, J = 1.7 Hz) was assigned to the oxymethine H- 1. Furthermore, the olefinic singlet resonated at 5.26 was assigned to Ha-7’ and Hb-7. The down field carbon atoms resonated at 110.2 and 165.2 were assigned to olefinic carbon atoms. The positive CI MS of 1 showed the molecular ion peak [M+H]+ at m/z 349 along with isotopic peak at m/z 351 (1:1), indicating the presence of a Br atom in the molecule. The above MS data were found to be consistent with the molecular formula C15H25O4Br with 3 degrees of unsaturation. A comparison of the NMR spectroscopic data of 1 with those of 2 suggested a similar skeleton with differences in substitution pattern and unsaturation sites. From the above spectral data, the structure of 1 was confirmed as a new natural product 4-bromo-5-methyl-2-(3’-hydroxy-1’,3’- dimethyl-2’ methylenecyclopentyl) cyclohexane-1,2,5- triol. Caulerpin (3) showed a significant dose suppressive effect with an IC50 5.8 ± 1.0 μg/mL on Tcell proliferation assay

Reduced growth rate of aged muscle stem cells is associated with impaired mechanosensitivity

Aging-associated muscle wasting and impaired regeneration are caused by deficiencies in muscle stem cell (MuSC) number and function. We postulated that aged MuSCs are intrinsically impaired in their responsiveness to omnipresent mechanical cues through alterations in MuSC morphology, mechanical properties, and number of integrins, culminating in impaired proliferative capacity. Here we show that aged MuSCs exhibited significantly lower growth rate and reduced integrin-a7 expression as well as lower number of phospho-paxillin clusters than young MuSCs. Moreover, aged MuSCs were less firmly attached to matrigel-coated glass substrates compared to young MuSCs, as 43% of the cells detached in response to pulsating fluid shear stress (1 Pa). YAP nuclear localization was 59% higher than in young MuSCs, yet YAP target genes Cyr61 and Ctgf were substantially downregulated. When subjected to pulsating fluid shear stress, aged MuSCs exhibited reduced upregulation of proliferation-related genes. Together these results indicate that aged MuSCs exhibit impaired mechanosensitivity and growth potential, accompanied by altered morphology and mechanical properties as well as reduced integrin-a7 expression. Aging-associated impaired muscle regenerative capacity and muscle wasting is likely due to aging-induced intrinsic MuSC alterations and dysfunctional mechanosensitivity