Genotoxicity and osteogenic potential of sulfated polysaccharides from Caulerpa prolifera seaweed

Abstract

Marine algae are sources of novel bioactive molecules and present a great potential for biotechnological and biomedical applications. Although green algae are the least studied type of seaweed, several of their biological activities have already been described. Here, we investigated the osteogenic potential of Sulfated Polysaccharide (SP)-enriched samples extracted from the green seaweed Caulerpa prolifera on human mesenchymal stem cells isolated from Wharton jelly (hMSC-WJ). In addition, the potential genotoxicity of these SPs was determined by cytokinesis-block micronucleus (CBMN) assay. SP-enriched samples did not show significant cytotoxicity towards hMSCs-WJ at a concentration of up to 10μg/mL, and after 72h of exposure. SP enrichment also significantly increased alkaline phosphatase (ALP) activity, promoting calcium accumulation in the extracellular matrix. Among the SP-enriched samples, the CP0.5 subfraction (at 5μg/mL) presented the most promising results. In this sample, ALP activity was increased approximately by 60%, and calcium accumulation was approximately 6-fold above the negative control, indicating high osteogenic potential. This subfraction also proved to be non-genotoxic, according to the CBMN assay, as it did not induce micronuclei. The results of this study highlight, for the first time, the potential of these SPs for the development of new therapies for bone regeneration.

Antioxidant Fucoidans Obtained from Tropical Seaweed Protect Pre-Osteoblastic Cells from Hydrogen Peroxide-Induced Damage

“…The antioxidant activity of fucans and fucoidans was first well described by Athukorala et al [31]. Subsequently, many other papers have shown antioxidant activity of fucans, fucoidans, extracts and fractions rich in these molecules, as can be seen in excellent reviews recently published [32,33,34]. In general, the data have shown that these compounds are good electron donors and metal chelators; however, their ability to scavenging reactive species, such as superoxide and hydroxyl ions, is lower than other antioxidant agents [12,32,33,34].…”

“…Subsequently, many other papers have shown antioxidant activity of fucans, fucoidans, extracts and fractions rich in these molecules, as can be seen in excellent reviews recently published [32,33,34]. In general, the data have shown that these compounds are good electron donors and metal chelators; however, their ability to scavenging reactive species, such as superoxide and hydroxyl ions, is lower than other antioxidant agents [12,32,33,34]. This fact was also observed with fucoidans-rich extracts obtained from different seaweeds of the class Dictyotales [22,35], as was observed with FRFs of D. mertensii (Figure 2).…”

Bioinformatic Characterization of Sulfotransferase Provides New Insights for the Exploitation of Sulfated Polysaccharides in Caulerpa

“…The administration of extracts from this Caulerpa species to mice with gastric damage induced normalized levels of glutathione and thiobarbituric acid together with an increased involvement of prostaglandins [36]. Furthermore, a collection of SPs was purified from Brazilian Caulerpa prolifera, showing a sulfate/total sugar ratio from 0.03 to 0.44 [37]. Among these, CP0.5 showed the major amount of sulfate and osteogenic induction potential on human mesenchymal stem cells, increasing alkaline phosphatase activity and calcium accumulation [37].…”

“…Furthermore, a collection of SPs was purified from Brazilian Caulerpa prolifera, showing a sulfate/total sugar ratio from 0.03 to 0.44 [37]. Among these, CP0.5 showed the major amount of sulfate and osteogenic induction potential on human mesenchymal stem cells, increasing alkaline phosphatase activity and calcium accumulation [37]. Caulerpa mexicana Gastroprotective effects (reduction of ethanol damage) Sulfated polysaccharides [36] Caulerpa okamurae Anti-inflammatory; increases of insulin sensitivity in adipocytes and macrophages Not specified [26] Caulerpa prolifera Osteogenic potential Sulfated polysaccharides [37] Caulerpa racemosa Antinociceptive and anti-inflammatory effects Sulfated polysaccharides [30] Caulerpa scalpelliformis Non-specific immunity and disease resistance in fish (Nile tilapia) Not specified [44] Caulerpa sertularioides Antibacteric activity vs. V. parahaemolyticus and V. alginolyticus Not specified [45] Caulerpa Sp Antiaeging and UV protection action on mice Not specified [28] Hence, despite there being a plethora of studies on potential pharmaceutical properties of members of Caulerpa, to our knowledge, no bioinformatic, biochemical or phylogenetic comprehensive studies have been performed so far on key enzymes of the pathways of this secondary metabolism of Caulerpa.…”

“…Furthermore, a collection of SPs was purified from Brazilian Caulerpa prolifera , showing a sulfate/total sugar ratio from 0.03 to 0.44 [ 37 ]. Among these, CP0.5 showed the major amount of sulfate and osteogenic induction potential on human mesenchymal stem cells, increasing alkaline phosphatase activity and calcium accumulation [ 37 ].…”