Open Access 12-04-2025 | Obesity | Special Feature: Review

Potential of siphonaxanthin, a green algal carotenoid, to prevent obesity and related diseases

Authors: Yuki Manabe, Tatsuya Sugawara

Published in: Journal of Natural Medicines

Abstract

The increasing prevalence of obesity and its related diseases, including diabetes mellitus and metabolic dysfunction-associated fatty liver disease, has become a significant social problem. These diseases are believed to be preventable through healthy diet and exercise habits, and the investigation of food ingredients that are useful for prevention of these diseases is actively ongoing. Carotenoids are the major lipophilic pigments responsible for yellow-to-red colors in our diet, and the ingestion of certain carotenoids has been reported to prevent obesity. For example, β-carotene suppresses adipogenic differentiation of mouse preadipocyte line 3T3-L1 through its provitamin A activity. Fucoxanthin, a carotenoid found in brown algae, also has the similar effect via a different mechanism and is used as an active ingredient in foods with functional claims in Japan. In contrast, siphonaxanthin, a carotenoid found in some green algae such as Caulerpa lentillifera (commonly known as sea grape), exhibited stronger biological activities than other carotenoids in cell-based studies; it significantly suppressed adipogenic differentiation of 3T3-L1 cells even at low concentrations where β-carotene and fucoxanthin did not show inhibitory effects. However, its practical applications have not yet been realized. This review summarizes the studies on the anti-obesity effects of carotenoids and discusses the potential of siphonaxanthin as a novel functional food ingredient.

Graphical Abstract

Takaichi S (2020) Carotenoids in phototrophic microalgae: Distributions and biosynthesis. In: Jacob-Lopes E, Queiroz MI, Zepka LQ (eds) Pigments from microalgae handbook. Springer, New York

Hayashi S, Kawagoshi M, Hayashi Y, Manabe Y, Sugawara T (2018) Survey of carotenoids content in green algae. Trac Nutr Res 35:47–51

Maoka T, Fujiwara Y, Hashimoto K, Akimoto N (2005) Carotenoids in three species of corbicula clams, Corbicula japonica, Corbicula sandai, and Corbicula sp. (Chinese Freshwater Corbicula Clam). J Agric Food Chem 53:8357–8364. https://doi.org/10.1021/jf058088tCrossRefPubMed

Sugawara T, Ganesan P, Li Z, Manabe Y, Hirata T (2014) Siphonaxanthin, a green algal carotenoid, as a novel functional compound. Mar Drugs 12:3660–3668. https://doi.org/10.3390/md12063660CrossRefPubMedPubMedCentral

Ganesan P, Noda K, Manabe Y, Ohkubo T, Tanaka Y, Maoka T, Sugawara T, Hirata T (2011) Siphonaxanthin, a marine carotenoid from green algae, effectively induces apoptosis in human leukemia (HL-60) cells. BBA Gen Subjects 1810:497–503. https://doi.org/10.1016/j.bbagen.2011.02.008CrossRef

Manabe Y, Takii Y, Sugawara T (2020) Siphonaxanthin, a carotenoid from green algae, suppresses advanced glycation end product-induced inflammatory responses. J Nat Med 74:127–134. https://doi.org/10.1007/s11418-019-01354-zCrossRefPubMed

Matsumoto M, Hosokawa M, Matsukawa N, Hagio M, Shinoki A, Nishimukai M, Miyashita K, Yajima T, Hara H (2010) Suppressive effects of the marine carotenoids, fucoxanthin and fucoxanthinol on triglyceride absorption in lymph duct-cannulated rats. Eur J Nutr 49:243–249. https://doi.org/10.1007/s00394-009-0078-yCrossRefPubMed

Du X, Bai M, Huang Y, Jiang Z, Chen F, Ni H, Li Q (2018) Inhibitory effect of astaxanthin on pancreatic lipase with inhibition kinetics integrating molecular docking simulation. J Funct Foods 48:551–557. https://doi.org/10.1016/j.jff.2018.07.045CrossRef

Shamarao N, Chethankumar M (2022) Antiobesity drug-likeness properties and pancreatic lipase inhibition of a novel low molecular weight lutein oxidized product, LOP6. Food Funct 13:6036–6055. https://doi.org/10.1039/D1FO04064BCrossRefPubMed

10.

Sheng L, Qian Z, Zheng S, Xi L (2006) Mechanism of hypolipidemic effect of crocin in rats: crocin inhibits pancreatic lipase. Eur J Pharmacol 543:116–122. https://doi.org/10.1016/j.ejphar.2006.05.038CrossRefPubMed

11.

Kawada T, Aoki N, Kamei Y, Maeshige K, Nishiu S, Sugimoto E (1990) Comparative investigation of vitamins and their analogues on terminal differentiation, from preadipocytes to adipocytes, of 3T3-L1 cells. Comp Biochem Physiol A Physiol 96:323–326. https://doi.org/10.1016/0300-9629(90)90699-SCrossRef

12.

Kawada T, Kamei Y, Fujita A, Hida Y, Takahashi N, Sugimoto E, Fushiki T (2000) Carotenoids and retinoids as suppressors on adipocyte differentiation via nuclear receptors. BioFactors 13:103–109. https://doi.org/10.1002/biof.5520130117CrossRefPubMed

13.

Hessel S, Eichinger A, Isken A, Amengual J, Hunzelmann S, Hoeller U, Elste V, Hunziker W, Goralczyk R, Oberhauser V, von Lintig J, Wyss A (2007) CMO1 deficiency abolishes vitamin A production from β-carotene and alters lipid metabolism in mice. J Biol Chem 282:33553–33561. https://doi.org/10.1074/jbc.M706763200CrossRefPubMed

14.

Lobo GP, Amengual J, Li HNM, Golczak M, Bonet ML, Palczewski K, von Lintig J (2010) β, β-Carotene decreases peroxisome proliferator receptor γ activity and reduces lipid storage capacity of adipocytes in a β, β-carotene oxygenase 1-dependent manner. J Biol Chem 285:27891–27899. https://doi.org/10.1074/jbc.M110.132571CrossRefPubMedPubMedCentral

15.

delaSeña C, Narayanasamy S, Riedl KM, Curley RW Jr, Schwartz SJ, Harrison EH (2013) Substrate specificity of purified recombinant human β-carotene 15,15′-oxygenase (BCO1). J Biol Chem 288:37094–37103. https://doi.org/10.1074/jbc.M113.507160CrossRef

16.

Shirakura Y, Takayanagi K, Mukai K, Tanabe H, Inoue M (2011) β-Cryptoxanthin suppresses the adipogenesis of 3T3-L1 cells via RAR activation. J Nutr Sci Vitaminol 57:426–431. https://doi.org/10.3177/jnsv.57.426CrossRefPubMed

17.

Matsumoto A, Mizukami H, Mizuno S, Umegaki K, Nishikawa J, Shudo K, Kagechika H, Inoue M (2007) β-Cryptoxanthin, a novel natural RAR ligand, induces ATP-binding cassette transporters in macrophages. Biochem Pharmacol 74:256–264. https://doi.org/10.1016/j.bcp.2007.04.014CrossRefPubMed

18.

Hara H, Takahashi H, Mohri S, Murakami H, Kawarasaki S, Iwase M, Takahashi N, Sugiura M, Goto T, Kawada T (2019) β-Cryptoxanthin induces UCP-1 expression via a RAR pathway in adipose tissue. J Agric Food Chem 67:10595–10603. https://doi.org/10.1021/acs.jafc.9b01930CrossRefPubMed

19.

Ziouzenkova O, Orasanu G, Sukhova G, Lau E, Berger JP, Tang G, Krinsky NI, Dolnikowski GG, Plutzky J (2007) Asymmetric cleavage of β-carotene yields a transcriptional repressor of retinoid X receptor and peroxisome proliferator-activated receptor responses. Mol Endocrinol 21:77–88. https://doi.org/10.1210/me.2006-0225CrossRefPubMed

20.

Inoue M, Tanabe H, Matsumoto A, Takagi M, Umegaki K, Amagaya S, Takahashi J (2012) Astaxanthin functions differently as a selective peroxisome proliferator-activated receptor γ modulator in adipocytes and macrophages. Biochem Pharmacol 84:692–700. https://doi.org/10.1016/j.bcp.2012.05.021CrossRefPubMed

21.

Takahashi N, Goto T, Taimatsu A, Egawa K, Katoh S, Kusudo T, Sakamoto T, Ohyane C, Lee JY, Kim Y, Uemura T, Hirai S, Kawada T (2009) Bixin regulates mRNA expression involved in adipogenesis and enhances insulin sensitivity in 3T3-L1 adipocytes through PPARγ activation. Biochem Biophys Res Commun 390:1372–1376. https://doi.org/10.1016/j.bbrc.2009.10.162CrossRefPubMed

22.

Takahashi S, Waki N, Mohri S, Takahashi H, Ara T, Aizawa K, Suganuma H, Kawada T, Goto T (2018) Apo-12′-lycopenal, a lycopene metabolite, promotes adipocyte differentiation via peroxisome proliferator-activated receptor γ activation. J Agric Food Chem 66:13152–13161. https://doi.org/10.1021/acs.jafc.8b04736CrossRefPubMed

23.

Bajaj M, Suraamornkul S, Pratipanawatr T, Hardies LJ, Pratipanawatr W, Glass L, Cersosimo E, Miyazaki Y, DeFronzo RA (2003) Pioglitazone reduces hepatic fat content and augments splanchnic glucose uptake in patients with type 2 diabetes. Diabetes 52:1364–1370. https://doi.org/10.2337/diabetes.52.6.1364CrossRefPubMed

24.

Maeda H, Hosokawa M, Sashima T, Takahashi N, Kawada T, Miyashita K (2006) Fucoxanthin and its metabolite, fucoxanthinol, suppress adipocyte differentiation in 3T3-L1 cells. Int J Mol Med 18:147–152. https://doi.org/10.3892/ijmm.18.1.147CrossRefPubMed

25.

Okada T, Nakai M, Maeda H, Hosokawa M, Sashima T, Miyashita K (2008) Suppressive effect of neoxanthin on the differentiation of 3T3-L1 adipose cells. J Oleo Sci 57:345–351. https://doi.org/10.5650/jos.57.345CrossRefPubMed

26.

Li ZS, Noda K, Fujita E, Manabe Y, Hirata T, Sugawara T (2015) The green algal carotenoid siphonaxanthin inhibits adipogenesis in 3T3-L1 preadipocytes and the accumulation of lipids in white adipose tissue of KK-Ay mice. J Nutr 145:490–498. https://doi.org/10.3945/jn.114.200931CrossRefPubMed

27.

Gopal SS, Eligar SM, Vallikannan B, Ponesakki G (2021) Inhibitory efficacy of lutein on adipogenesis is associated with blockage of early phase regulators of adipocyte differentiation. BBA Mol Cell Biol Lipids 1866:158812. https://doi.org/10.1016/j.bbalip.2020.158812CrossRef

28.

Yim MJ, Hosokawa M, Mizushina Y, Yoshida H, Saito Y, Miyashita K (2011) Suppressive effects of amarouciaxanthin A on 3T3-L1 adipocyte differentiation through down-regulation of PPARγ and C/EBPα mRNA expression. J Agric Food Chem 59:1646–1652. https://doi.org/10.1021/jf103290fCrossRefPubMed

29.

Kotake-Nara E, Hase M, Kobayashi M, Nagao A (2016) 3′-Hydroxy-ε, ε-caroten-3-one inhibits the differentiation of 3T3-L1 cells to adipocytes. Biosci Biotechnol Biochem 80:518–523. https://doi.org/10.1080/09168451.2015.1095066CrossRefPubMed

30.

Li Z, Zheng J, Luo X, Manabe Y, Hirata T, Sugawara T (2020) Absorption and tissue distribution of siphonaxanthin from green algae. Mar Drugs 18:291. https://doi.org/10.3390/md18060291CrossRefPubMedPubMedCentral

31.

Manabe Y, Nitta T, Ichihara M, Maoka T, Sugawara T (2025) Dehydrometabolites of siphonaxanthin, a carotenoid from green algae, suppress TLR1/2-induced inflammatory response more strongly than siphonaxanthin. J Biol Chem. https://doi.org/10.1016/j.jbc.2025.108246CrossRefPubMedPubMedCentral

32.

Nagao A, Maoka T, Ono H, Kotake-Nara E, Kobayashi M, Tomita M (2015) A 3-hydroxy β-end group in xanthophylls is preferentially oxidized to a 3-oxo ε-end group in mammals. J Lipid Res 56:449–462. https://doi.org/10.1194/jlr.P055459CrossRefPubMedPubMedCentral

33.

Serra F, Bonet ML, Puigserver P, Oliver J, Palou A (1999) Stimulation of uncoupling protein 1 expression in brown adipocytes by naturally occurring carotenoids. Int J Obes 23:650–655. https://doi.org/10.1038/sj.ijo.0800897CrossRef

34.

Sidossis L, Kajimura S (2015) Brown and beige fat in humans: thermogenic adipocytes that control energy and glucose homeostasis. J Clin Invest 125:478–486. https://doi.org/10.1172/JCI78362CrossRefPubMedPubMedCentral

35.

Maeda H, Hosokawa M, Sashima T, Funayama K, Miyashita K (2005) Fucoxanthin from edible seaweed, Undaria pinnatifida, shows antiobesity effect through UCP1 expression in white adipose tissues. Biochem Biophys Res Commun 332:392–397. https://doi.org/10.1016/j.bbrc.2005.05.002CrossRefPubMed

36.

Sharma PP, Godhwani T, Baskaran V (2022) Anti-lipogenic and thermogenic potency of Padina tetrastromatica bioactives in hypertrophied 3T3-L1 cells and their efficacy based thermogenic food supplement to mitigate obesity. Algal Res 65:102695. https://doi.org/10.1016/j.algal.2022.102695CrossRef

37.

Zhu R, Wei J, Liu H, Liu C, Wang L, Chen B, Li L, Jia Q, Tian Y, Li R, Zhao D, Mo F, Li Y, Gao S, Wang X-D, Zhang D (2020) Lycopene attenuates body weight gain through induction of browning via regulation of peroxisome proliferator-activated receptor γ in high-fat diet-induced obese mice. J Nutr Biochem 78:108335. https://doi.org/10.1016/j.jnutbio.2019.108335CrossRefPubMed

38.

Liu M, Zheng M, Cai D, Xie J, Jin Z, Liu H, Liu J (2019) Zeaxanthin promotes mitochondrial biogenesis and adipocyte browning via AMPKα1 activation. Food Funct 10:2221–2233. https://doi.org/10.1039/C8FO02527DCrossRefPubMed

39.

Choi M, Yun JW (2023) β-Carotene induces UCP1-independent thermogenesis via ATP-consuming futile cycles in 3T3-L1 white adipocytes. Arch Biochem Biophys 739:109581. https://doi.org/10.1016/j.abb.2023.109581CrossRefPubMed

40.

Zheng J, Manabe Y, Sugawara T (2020) Siphonaxanthin, a carotenoid from green algae Codium cylindricum, protects Ob/Ob mice fed on a high-fat diet against lipotoxicity by ameliorating somatic stresses and restoring anti-oxidative capacity. Nutr Res 77:29–42. https://doi.org/10.1016/j.nutres.2020.02.001CrossRefPubMed

41.

Bauzá-Thorbrügge M, Peris E, Zamani S, Micallef P, Paul A, Bartesaghi S, Benrick A, Wernstedt Asterholm I (2023) NRF2 is essential for adaptative browning of white adipocytes. Redox Biol 68:102951. https://doi.org/10.1016/j.redox.2023.102951CrossRefPubMedPubMedCentral

42.

Maeda H, Hosokawa M, Sashima T, Miyashita K (2007) Dietary combination of fucoxanthin and fish oil attenuates the weight gain of white adipose tissue and decreases blood glucose in obese/diabetic KK-Ay mice. J Agric Food Chem 55:7701–7706. https://doi.org/10.1021/jf071569nCrossRefPubMed

43.

Tsukui T, Konno K, Hosokawa M, Maeda H, Sashima T, Miyashita K (2007) Fucoxanthin and fucoxanthinol enhance the amount of docosahexaenoic acid in the liver of KKAy obese/diabetic mice. J Agric Food Chem 55:5025–5029. https://doi.org/10.1021/jf070110qCrossRefPubMed

44.

Maeda H, Hosokawa M, Sashima T, Funayama K, Miyashita K (2007) Effect of medium-chain triacylglycerols on anti-obesity effect of fucoxanthin. J Oleo Sci 56:615–621. https://doi.org/10.5650/jos.56.615CrossRefPubMed

45.

Hosokawa M, Miyashita T, Nishikawa S, Emi S, Tsukui T, Beppu F, Okada T, Miyashita K (2010) Fucoxanthin regulates adipocytokine mRNA expression in white adipose tissue of diabetic/obese KK-Ay mice. Arch Biochem Biophys 504:17–25. https://doi.org/10.1016/j.abb.2010.05.031CrossRefPubMed

46.

Beppu F, Hosokawa M, Niwano Y, Miyashita K (2012) Effects of dietary fucoxanthin on cholesterol metabolism in diabetic/obese KK-Ay mice. Lipids Health Dis 11:112. https://doi.org/10.1186/1476-511X-11-112CrossRefPubMedPubMedCentral

47.

Iwasaki S, Widjaja-Adhi MAK, Koide A, Kaga T, Nakano S-i, Beppu F, Hosokawa M, Miyashita K (2012) In vivo antioxidant activity of fucoxanthin on obese/diabetes KK-Ay mice. Food Nutr Sci 3:1491–1499. https://doi.org/10.4236/fns.2012.311194CrossRef

48.

Nishikawa S, Hosokawa M, Miyashita K (2012) Fucoxanthin promotes translocation and induction of glucose transporter 4 in skeletal muscles of diabetic/obese KK-Ay mice. Phytomedicine 19:389–394. https://doi.org/10.1016/j.phymed.2011.11.001CrossRefPubMed

49.

Beppu F, Hosokawa M, Yim M-J, Shinoda T, Miyashita K (2013) Down-regulation of hepatic stearoyl-CoA desaturase-1 expression by fucoxanthin via leptin signaling in diabetic/obese KK-A mice. Lipids 48:449–455. https://doi.org/10.1007/s11745-013-3784-4CrossRefPubMed

50.

Hao Z (2020) Astaxanthin improves serum cytokine expression and semen quality of diabetes mellitus KKAy mice. Chem-Biol Interact 332:109303. https://doi.org/10.1016/j.cbi.2020.109303CrossRefPubMed

51.

Goto T, Takahashi N, Kato S, Kim Y-I, Kusudo T, Taimatsu A, Egawa K, Kang M-S, Hiramatsu T, Sakamoto T, Uemura T, Hirai S, Kobayashi M, Horio F, Kawada T (2012) Bixin activates PPARα and improves obesity-induced abnormalities of carbohydrate and lipid metabolism in mice. J Agric Food Chem 60:11952–11958. https://doi.org/10.1021/jf303639fCrossRefPubMed

52.

Hu KQ, Liu C, Ernst H, Krinsky NI, Russell RM, Wang X-D (2006) The biochemical characterization of ferret carotene-9′,10′-monooxygenase catalyzing cleavage of carotenoids in Vitro and in Vivo. J Biol Chem 281:19327–19338. https://doi.org/10.1074/jbc.M512095200CrossRefPubMed

53.

Chung J, Koo K, Lian F, Hu KQ, Ernst H, Wang X-D (2012) Apo-10′-lycopenoic acid, a lycopene metabolite, increases sirtuin 1 mRNA and protein levels and decreases hepatic fat accumulation in ob/ob mice. J Nutr 142:405–410. https://doi.org/10.3945/jn.111.150052CrossRefPubMedPubMedCentral

54.

Ni Y, Nagashimada M, Zhuge F, Zhan L, Nagata N, Tsutsui A, Nakanuma Y, Kaneko S, Ota T (2015) Astaxanthin prevents and reverses diet-induced insulin resistance and steatohepatitis in mice: a comparison with vitamin E. Sci Rep 5:17192. https://doi.org/10.1038/srep17192CrossRefPubMedPubMedCentral

55.

Yang S, Li J, Yan L, Wu Y, Zhang L, Li B, Tong H, Lin X (2024) Molecular mechanisms of fucoxanthin in alleviating lipid deposition in metabolic associated fatty liver disease. J Agric Food Chem 72:10391–10405. https://doi.org/10.1021/acs.jafc.4c00590CrossRefPubMed

56.

Wu C, Zhang C, Li F, Yan Y, Wu Y, Li B, Tong H, Lang J (2024) Fucoxanthin mitigates high-fat-induced lipid deposition and insulin resistance in skeletal muscle through inhibiting PKM1 activity. J Agric Food Chem 72:18013–18026. https://doi.org/10.1021/acs.jafc.4c03677CrossRefPubMed

57.

Zheng J, Li Z, Manabe Y, Kim M, Goto T, Kawada T, Sugawara T (2018) Siphonaxanthin, a carotenoid from green algae, inhibits lipogenesis in hepatocytes via the suppression of liver X receptor α activity. Lipids 53:41–52. https://doi.org/10.1002/lipd.12002CrossRefPubMed

58.

Manabe Y, Hirata T, Sugawara T (2019) Inhibitory effect of carotenoids on ligand-induced lipid raft translocation of immunoreceptors. J Oleo Sci 68:149–158. https://doi.org/10.5650/jos.ess18204CrossRefPubMed

59.

Manabe Y, Tomonaga N, Maoka T, Sugawara T (2021) Multivariate analysis reveals that unsubstituted β-ring and C8-keto structures are important factors for anti-inflammatory activity of carotenoids. Nutrients 13:3699. https://doi.org/10.3390/nu13113699CrossRefPubMedPubMedCentral

Title: Potential of siphonaxanthin, a green algal carotenoid, to prevent obesity and related diseases
Authors: Yuki Manabe
Tatsuya Sugawara
Publication date: 12-04-2025
Publisher: Springer Nature Singapore
Keywords: Obesity
Obesity
Steatotic Liver Disease
Published in: Journal of Natural Medicines
Print ISSN: 1340-3443
Electronic ISSN: 1861-0293
DOI: https://doi.org/10.1007/s11418-025-01897-4

Navigating neuroimaging in Alzheimer disease care

Springer Medicine

Potential of siphonaxanthin, a green algal carotenoid, to prevent obesity and related diseases

Abstract

Graphical Abstract

Navigating neuroimaging in Alzheimer disease care

Springer Medicine

Abstract

Graphical Abstract

Please log in to get access to this content