Popov AM et al. (2023), Carotenoids from Starfish Patiria pectinifera: ...

ECB-ART-52518

Mar Drugs 2023 Aug 27;219:. doi: 10.3390/md21090470.

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Carotenoids from Starfish Patiria pectinifera: Therapeutic Activity in Models of Inflammatory Diseases.

Popov AM , Kozlovskaya EP , Klimovich AA , Rutckova TA , Vakhrushev AI , Hushpulian DM , Gazaryan IG , Makhankov VV , Son OM , Tekutyeva LA .

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The carotenoids mixture (MC) isolated from the starfish Patiria. pectinifera contains more than 50% astaxanthin, 4-6% each zeaxanthine and lutein, and less pharmacologically active components such as free fatty acids and their glycerides. Astaxanthin, the major component of MC, belongs to the xanthophyll class of carotenoids, and is well known for its antioxidant properties. In this work, in vitro and in vivo studies on the biological activity of MC were carried out. The complex was shown to exhibit anti-inflammatory, anti-allergic and cancer-preventive activity, without any toxicity at a dose of 500 mg/kg. MC effectively improves the clinical picture of the disease progressing, as well as normalizing the cytokine profile and the antioxidant defense system in the in vivo animal models of inflammatory diseases, namely: skin carcinogenesis, allergic contact dermatitis (ACD) and systemic inflammation (SI). In the skin carcinogenesis induced by 7,12-dimethylbenzanthracene, the incidence of papillomas was decreased 1.5 times; 1% MC ointment form in allergic contact dermatitis showed an 80% reduced severity of pathomorphological skin manifestations. Obtained results show that MC from starfish P. pectinifera is an effective remedy for the treatment and prevention of inflammatory processes.

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	Figure 1. The high-performance liquid chromatography (HPLC) chromatogram of carotenoids mixture of starfish P. pectinifera (a) and sample of astaxanthin (90%, Sigma-Aldrich, St. Louis, MO, USA) (b). Chromatographic conditions: HPLC was carried out on a chromatograph LaChrom 2000 (Hitachi/Merck, Darmstadt, Germany) equipped with UV detector L-7400, pump L-7100, thermostat L-7300, integrator D-7500; column, Agilent Technologies Zorbax Eclipse XDB-C18, 3.5 µm (75 mm × 4.6 mm) with guard column Hypersil ODS, 5 µm (4.0 mm × 4.0 mm); detection, UV 475 nm; solvent, acetonitrile/water (85/15, v/v) with 1% glacial acetic acid; flow rate, 0.2 mL/min; thermostated at 30 °C. Abbreviations: MC—carotenoid mixture of starfish P. pectinifera.
	Figure 2. Dynamics of skin cancer incidence (a) and changes in the size of papillomas (b) (y-axis) in the experimental groups of animals. The data are presented from the moment the first changes appeared on the DMBA-treated animal skin areas (5 weeks after the start of the experiment). The results are presented as m ± SD (standard deviation) (n = 10), * p ≤ 0.05, ** p ≤ 0.01, compared with C(−) group. Abbreviations: C(−)—negative control; RA—rosmarinic acid (positive control); MC—carotenoids mixture of starfish P. pectinifera.
	Figure 3. The profile of cytokines (y-axis, pg/mL) in blood serum (a) and skin homogenate (b), the level of malonic dialdehyde (MDA) (c) and total bilirubin (d) in the blood serum of animals (y-axis, µmol/L) at experimental modeling of skin carcinogenesis. The results are presented as m ± SD (standard deviation) (n = 10), * p ≤ 0.05, p ≤ 0.01, * p ≤ 0.01, compared with the C(−) group; ## p ≤ 0.01, ### p ≤ 0.01, C(−) group compared to C(i) group. Abbreviations: C(−)—negative control; C(i)–intact control; RA—rosmarinic acid (positive control); MC—carotenoids mixture of starfish P. pectinifera; IL-1,4,10,17—interleukins-1,4,10,17; IFN-γ—interferon-gamma; TNF-α—tumor necrosis factor; GM-CSF—granulocyte–macrophage colony-stimulating factor.
	Figure 4. Indicators of the level of erythema (y-axis) caused by DNFB in different groups of animals after each day of treatment (x-axis). The results are presented as m ± SD (standard deviation) (n = 8), * p ≤ 0.05, *** p ≤ 0.01 (paired Student’s t-test). Abbreviations: DNFB—2,4-dinitrofluorobenzene; C(−)—negative control; C(+)—positive control ointment “Fucidin”; Mco—ointment, containing 1% carotenoids mixture of starfish P. pectinifera.
	Figure 5. The level of cytokines in the blood serum (y-axis, optical density at λ 450 nm) in the experimental model of allergic contact dermatitis (ACD) induced by DNFB. Blood samples were obtained 24 h after the last application of the ointments. The results are presented as m ± SD (standard deviation) (n = 8), * p ≤ 0.05, p ≤ 0.01, * p ≤ 0.01, compared with the C(−) group; # p ≤ 0.05, ## p ≤ 0.01, C(−) group versus C(i) group. Abbreviations: DNFB—2,4-dinitrofluorobenzene; C(−)—negative control; C(i)–intact control; C(+)—positive control ointment “Fucidin”; Mco—ointment containing 1% carotenoids mixture of starfish P. pectinifera; IL-2,4,6,10—interleukins–2,4,6,10; IFN-γ—interferon-gamma; TNF-α—tumor necrosis factor; GM-CSF—granulocyte–macrophage colony-stimulating factor.
	Figure 6. The content of cytokines (a) (y-axis, pg/mL), malonic dialdehyde (MDA) (b) and total bilirubin (c) (y-axis, in µmol/L) in the blood serum. The results are presented as m ± SD (standard deviation) (n = 6), * p ≤ 0.05, p ≤ 0.01, * p ≤ 0.01, compared with the C(−) group; # p ≤ 0.05, ## p ≤ 0.01, ### p ≤ 0.01, C(−) group versus C(i) group. Abbreviations: C(−)—negative control, C(i) —intact control; Dex-1, Dex-10—“Dexamethasone” in doses of 1 and 10 mg/kg, respectively; MC-1, MC-10—oxygenated carotenoid complex of starfish P. pectinifera at doses of 1 and 10 mg/kg, respectively; MDA—malonic dialdehyde; IL-2,4,6,10—interleukins–2,4,6,10; IFN-γ—interferon-gamma; TNF-α—tumor necrosis factor.

References [+] :

Arunkumar, The macular carotenoids: A biochemical overview. 2020, Pubmed