Echinochrome A (Ech A) is a naphthoquinoid pigment from sea urchins that possesses antioxidant, antimicrobial, anti-inflammatory and chelating abilities. Although Ech A is the active substance in the ophthalmic and cardiac drug Histochrome®, its underlying cardioprotective mechanisms are not well understood. In this study, we investigated the protective role of Ech A against toxic agents that induce death of rat cardiac myoblast H9c2 cells and isolated rat cardiomyocytes. We found that the cardiotoxic agents tert-Butyl hydroperoxide (tBHP, organic reactive oxygen species (ROS) inducer), sodium nitroprusside (SNP; anti-hypertension drug), and doxorubicin (anti-cancer drug) caused mitochondrial dysfunction such as increased ROS level and decreased mitochondrial membrane potential. Co-treatment with Ech A, however, prevented this decrease in membrane potential and increase in ROS level. Co-treatment of Ech A also reduced the effects of these cardiotoxic agents on mitochondrial oxidative phosphorylation and adenosine triphosphate level. These findings indicate the therapeutic potential of Ech A for reducing cardiotoxic agent-induced damage.

The aim of this study was to examine the in vitro antioxidant and antiviral activities of echinochrome A and echinochrome-based antioxidant composition against tick-borne encephalitis virus (TBEV) and herpes simplex virus type 1 (HSV-1). The antioxidant composition, which is a mixture of echinochrome A, ascorbic acid, and α-tocopherol (5:5:1), showed higher antioxidant and antiviral effects than echinochrome A. We suppose that echinochrome A and its composition can both directly affect virus particles and indirectly enhance antioxidant defense mechanisms in the hosting cell. The obtained results allow considering the echinochrome A and the composition of antioxidants on its basis as the promising agents with the both antioxidant and antiviral activities.

Echinochrome A (Ech A) is a natural pigment from sea urchins that has been reported to have antioxidant properties and a cardio protective effect against ischemia reperfusion injury. In this study, we ascertained whether Ech A enhances the mitochondrial biogenesis and oxidative phosphorylation in rat cardio myoblast H9c2 cells. To study the effects of Ech A on mitochondrial biogenesis, we measured mitochondrial mass, level of oxidative phosphorylation, and mitochondrial biogenesis regulatory gene expression. Ech A treatment did not induce cytotoxicity. However, Ech A treatment enhanced oxygen consumption rate and mitochondrial ATP level. Likewise, Ech A treatment increased mitochondrial contents in H9c2 cells. Furthermore, Ech A treatment up-regulated biogenesis of regulatory transcription genes, including proliferator-activated receptor gamma co-activator (PGC)-1α, estrogen-related receptor (ERR)-α, peroxisome proliferator-activator receptor (PPAR)-γ, and nuclear respiratory factor (NRF)-1 and such mitochondrial transcription regulatory genes as mitochondrial transcriptional factor A (TFAM), mitochondrial transcription factor B2 (TFB2M), mitochondrial DNA direct polymerase (POLMRT), single strand binding protein (SSBP) and Tu translation elongation factor (TUFM). In conclusion, these data suggest that Ech A is a potentiated marine drug which enhances mitochondrial biogenesis.

Quinones are widespread in nature and have been found in plants, fungi and bacteria, as well as in members of the animal kingdom. More than forty closely related naphthoquinones have been found in echinoderms, mainly in sea urchins but occasionally in brittle stars, sea stars and starfish. This review aims to examine controversial issues on the chemistry, biosynthesis, functions, stability and application aspects of the spinochrome class, a prominent group of secondary metabolites found in sea urchins. The emphasis of this review is on the isolation and structure of these compounds, together with evaluation of their relevant biological activities, source organisms, the location of origin and methods used for isolation and identification. In addition, the studies of their biosynthesis and ecological function, stability and chemical synthesis have been highlighted. This review aims to establish a focus for future spinochrome research and its potential for benefiting human health and well-being. Scheme 2 Synthesis of spinochrome E (6) as described by Borisova and Anufriev. 94 Reagents and conditions: (i) (EtO) 3 CH, reflux; (ii) NaNO 2 , EtOH, H 2 O, heating; (iii) Na 2 S 2 O 4 , H 2 O; (iv) AlCl 3 , PhNO 2 , heating, then 5% HCl, heating. Scheme 1 Synthesis of spinochromes as described by Singh et al. 90 Reagents and conditions: (i) AlCl 3 -NaCl, 195 C; (ii) MeONa, MeOH, reflux; (iii) conc. HBr, reflux.This journal is

Using high-performance liquid chromatography with diode-array detection and mass spectrometry (HPLC-DAD/MS) we investigated the composition of polyhydroxynaphthoquinone (PHNQ) pigments from sea urchins Strongylocentrotus pallidus, St. polyacanthus, St. droebachiensis, Brisaster latifrons and Echinarachnius parma, collected in the Sea of Okhotsk and the Bering Sea. Identification of PHNQ pigments from sea urchins St. polyacanthus, B. latifrons, and E. parma was performed for the first time. Among the usual PHNQ pigments, mono- and dimethoxy derivatives of spinochrome E, not previously found in other sea urchins, were discovered in St. polyacanthus and St. droebachiensis. In St. droebachiensis, two monomethoxy derivatives of echinochrome A were detected, isolated previously from only tropical sea urchins. It was found that the composition and total content of pigments of St. droebachiensis depends on the collection area of the sea urchins and its depth and varies from 88 to 331 μg/g of dry shells. Sea urchins St. pallidus, B. latifrons and E. parma had average values for PHNQ pigment content, approximately 30 μg/g, and St. polyacanthus had a low PHNQ content, 13 μg/g.

Echinochrome A (Echi A) improves mitochondrial function in the heart; however, its effects on skeletal muscle are still unclear. We hypothesized that Echi A administration during short-term exercise may improve exercise capacity. Twenty-four male Sprague-Dawley rats were randomly divided into the following groups: control group (CG), Echi A-treated group (EG), aerobic exercise group (AG), and aerobic exercise treated with Echi A group (AEG) (n = 6 per group). Echi A was administered intra-peritoneally (0.1 mg/kg of Echi A in 300 µL phosphate-buffered saline) daily 30 min before each exercise training. The AG and AEG groups performed treadmill running (20 m/min, 60 min/day) five days/week for two weeks. The exercise capacity was significantly higher in the AG and AEG groups compared to other groups. Interestingly, the exercise capacity increased more effectively in the AEG group. The body weight in the EG tended to be slightly lower than that in the other groups. There were no significant changes in the plasma lipids among the groups. However, the gastrocnemius muscle mitochondria content was greater in the EG and AEG groups. These findings show that Echi A administration after short-term endurance training enhances exercise capacity, which was associated with an increase in skeletal muscle mitochondrial content.

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The aminonaphthoquinone, spinamine E (5), was isolated for the first time from the sea urchins Strongylocentrotus pallidus (Sars G.O., 1872) and Mesocentrotus nudus (A. Agassiz, 1864). The structure of 5 was elucidated as 2-amino-3,5,6,7,8-pentahydroxy-1,4-naphthoquinone using 1D 1 H-, 13 C-and 2D NMR procedures, and HR-ESI mass-spectrometric data of 5 and its trimethyl ether. Spinamine E, as well as two other aminonaphthoquinones of sea urchins, echinamines A (2) and B (3), along with their hydroxylated analogues, spinochrome E (4) and echinochrome A (1), were tested for their ability to scavenge the stable DPPH radical and to inhibit lipid peroxidation. All investigated naphthoquinones obtained from the sea urchins showed a high antiradical activity, which was up to 1.5 times higher than that of α-tocopherol. Echinamine B showed the highest scavenging effect (EC 50 = 6.5•10-6 M); this effect decreases in the series 35124α-tocopherol. In a lipid peroxidation inhibition testing model, echinamine B and spinamine E showed the highest inhibitory effect. The stability of compounds 1-5 in weakly alkaline solutions was evaluated.