Skip to main content

Advertisement

Log in

Capsanthin, a Plant-Derived Xanthophyll: a Review of Pharmacology and Delivery Strategies

  • Review Article
  • Theme: Formulation and Delivery of Natural Products
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

Capsanthin, a brightly orange-red–coloured pigment responsible for the peculiar red colour of paprika fruits (Capsicum annuum), belongs to xanthophylls, a class of oxygen-containing carotenoids. The characteristic chemical structure of capsanthin containing a keto group in conjunction with a long chain of 11 conjugated dienes is responsible for its strong radical scavenging and singlet oxygen quenching ability. Chemopreventive, antitumour, skin photo-protective, anti-inflammatory, and antidiabetic activities demonstrated by capsanthin are a consequence of its potent antioxidant action. Anti-obesity, anti-adipogenic, and antihyperlipidaemic activities are some of the more important features of capsanthin. With natural origin, bright red colour, and array of health benefits, capsanthin has a potential to be translated into a commercial cosmeceutical, nutraceutical, and/or pharmaceutical. However, the very low aqueous solubility of capsanthin is responsible for its highly variable and poor oral bioavailability. Moreover, its susceptibility to degradation due to heat, light, oxygen, and moisture poses challenges in the development of stable formulations for this otherwise meritorious compound. The current review presents various pharmacological activities of capsanthin and their underlying mechanisms. The review further discusses hitherto explored formulation strategies to improve solubility and stability of capsanthin.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Xavier AAO, Pérez-Gálvez A. Carotenoids as a source of antioxidants in the diet. In: Stange C, editor. Carotenoids in nature. Springer: International Publishing; 2016. p. 359–75.

  2. Johnson EJ. The role of carotenoids in human health. Nutr Clin Care Off Publ Tufts Univ. 2002;5:56–65.

    Article  Google Scholar 

  3. Meléndez-Martínez AJ, Stinco CM, Mapelli-Brahm P. Skin carotenoids in public health and nutricosmetics: the emerging roles and applications of the UV radiation-absorbing colourless carotenoids phytoene and phytofluene. Nutrients. 2019;11.

  4. Cooperstone JL, Schwartz SJ. 20 - Recent insights into health benefits of carotenoids. In: Carle R, Schweiggert RM, editors. Handbook of natural pigments in food and beverages. Woodhead: Publishing; 2016. p. 473–97.

  5. Mohd Hassan N, Yusof NA, Yahaya AF, Mohd Rozali NN, Othman R. Carotenoids of Capsicum fruits: pigment profile and health-promoting functional attributes. Antioxidants. Multidisciplinary Digital Publishing Institute. 2019;8:469.

    Google Scholar 

  6. Arimboor R, Natarajan RB, Menon KR, Chandrasekhar LP, Moorkoth V. Red pepper (Capsicum annuum) carotenoids as a source of natural food colors: analysis and stability—a review. J Food Sci Technol. 2015;52:1258–71.

    Article  CAS  Google Scholar 

  7. Giuffrida D, Dugo P, Torre G, Bignardi C, Cavazza A, Corradini C, et al. Characterization of 12 Capsicum varieties by evaluation of their carotenoid profile and pungency determination. Food Chem. 2013;140:794–802.

  8. Shah SNM. Studies on metabolism of capsanthin and its regulation under different conditions in pepper fruits (Capsicum spp.). Annu Res Rev Biol. 2014;4:1106–20.

    Article  Google Scholar 

  9. Bikadi Z, Zsila F, Deli J, Mády G, Simonyi M. The supramolecular structure of self-assembly formed by capsanthin derivatives. Enantiomer J Stereochem. 2002;7:67–76.

    Article  CAS  Google Scholar 

  10. Minguez-Mosquera MI, Jaren-Galan M, Garrido-Fernandez J. Influence of the industrial drying processes of pepper fruits(Capsicum annuum Cv. Bola) for paprika on the carotenoid content. J Agric Food Chem American Chemical Society. 1994;42:1190–3.

    Article  CAS  Google Scholar 

  11. Molnár H, Kónya É, Zalán Z, Bata-Vidács I, Tömösközi-Farkas R, Szekacs A, et al. Chemical characteristics of spice paprika of different origins. Food Control. 2017;83.

  12. Zhao N, Wang Y-H, Ma R-Y. Extraction of capsanthin from hot red peppers. 2004;31.

  13. Dang Y-Y, Zhang H, Xiu Z-L. Three-liquid-phase extraction and separation of capsanthin and capsaicin from Capsicum annum L. Czech J Food Sci. 2014;32:109–14.

  14. Melgar-Lalanne G, Hernández-Álvarez AJ, Jiménez-Fernández M, Azuara E. Oleoresins from Capsicum spp.: extraction methods and bioactivity. Food Bioprocess Technol. 2017;10:51–76.

    Article  CAS  Google Scholar 

  15. Fernández-Bedmar Z, Alonso-Moraga A. In vivo and in vitro evaluation for nutraceutical purposes of capsaicin, capsanthin, lutein and four pepper varieties. Food Chem Toxicol. 2016;98:89–99.

    Article  Google Scholar 

  16. Jo SJ, Kim JW, Choi HO, Kim JH, Kim HJ, Woo SH, et al. Capsanthin inhibits both adipogenesis in 3T3-L1 preadipocytes and weight gain in high-fat diet-induced obese mice. Biomol Ther. 2017;25:329–36.

  17. Lee P, Yacyshyn BR, Yacyshyn MB. Gut microbiota and obesity: an opportunity to alter obesity through faecal microbiota transplant (FMT). Diabetes Obes Metab. 2019;21:479–90.

    Article  Google Scholar 

  18. An Y, Yan X, Li B, Li Y. Microencapsulation of capsanthin by self-emulsifying nanoemulsions and stability evaluation. Eur Food Res Technol. 2014;239:1077–85.

    Article  CAS  Google Scholar 

  19. Showing compound capsanthin (FDB015502) - FooDB [Internet]. 2021. Available from: https://foodb.ca/compounds/FDB015502

  20. PubChem. Capsanthin [Internet]. 2021 [cited Jan 26]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/5281228

  21. Kulkarni M, Goge N, Date A. Development of nanoemulsion preconcentrate of capsanthin with improved chemical stability. ASSAY Drug Dev Technol. 2019;18.

  22. Obesity and overweight [Internet]. [cited 2021 Jan 26]. Available from: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight

  23. Gopal SS, Maradgi T, Ponesakki G. Antiobese properties of carotenoids: an overview of underlying molecular mechanisms. In: Galanakis CM, editor. Carotenoids: properties, processing and applications. Academic: Press; 2020. p. 75-105.

  24. Dhiman S, Kumar V, Mehta CM, Gat Y, Kaur S. Bioactive compounds, health benefits and utilisation of Morus spp.– a comprehensive review. J Hortic Sci Biotechnol Taylor & Francis. 2020;95:8–18.

    Article  CAS  Google Scholar 

  25. Luisa Bonet M, Canas JA, Ribot J, Palou A. Carotenoids and their conversion products in the control of adipocyte function, adiposity and obesity. Arch Biochem Biophys. 2015;572:112–25.

    Article  CAS  Google Scholar 

  26. Kim S, Ha TY, Hwang I. Analysis, bioavailability, and potential healthy effects of capsanthin, natural red pigment from Capsicum spp. Food Rev Int - FOOD REV INT. 2009;25:198–213.

    Article  CAS  Google Scholar 

  27. Cuevas-Sierra A, Ramos López OO, Riezu-Boj J, Milagro F, Alfredo M. Diet, Gut microbiota, and obesity: links with host genetics and epigenetics and potential applications. Adv Nutr Bethesda Md. 2019;10:S17–30.

    Article  Google Scholar 

  28. Wu T, Gao Y, Hao J, Geng J, Zhang J, Yin J, et al. Capsanthin extract prevents obesity, reduces serum TMAO levels and modulates the gut microbiota composition in high-fat-diet induced obese C57BL/6J mice. Food Res Int. 2020;128:108774.

  29. Korb DR, Grenon SM, Willis TR, Gravely BT. System for outer eyelid heat and pressure treatment for treating meibomian gland dysfunction [Internet]. 2012 [cited 2021 Jan 26]. Available from: https://patents.google.com/patent/US20120136285A1/en?oq=Byung-hoon+%2cHan+Kim%2c+Jeong-won%2c+Seong-jun%2c+Cho+Hye-ok%2c+Choi+Kim%2c+Jeong-hwan%2c+Kim+Moo+Kang+Park+Il-kwon%2c+Lee+Seung-hwan%2c+inventor;+S+Biotech+Inc.%2cassignee.+Functional+food+and+pharmaceutical+compositions+for+anti-obesity+comprising+free+and+fatty+acyl-ester+type+forms+of+capsanthins+having+anti-adipogenic+activity.KR20120136285A.2012+

  30. KR101625927B1 - Functional food including capsanthin having enhanced capacities of spontaneous locomotor activity and anti-fatigue activity - Google Patents [Internet]. [cited 2021 Jan 26]. Available from: https://patents.google.com/patent/KR101625927B1/en?oq=Han+Byung-hoon%E2%80%8E%2c%E2%80%8EKim+Jung-won%E2%80%8E%2c%E2%80%8EChoo-joon%E2%80%8E%2c%E2%80%8EChoi+Hye-ok%E2%80%8E%2c%E2%80%8EKim+Jung-hwan%E2%80%8E%2c+Lee%E2%80%8E%2c%E2%80%8EHyo-sung%E2%80%8E%E2%80%8E+%E2%80%8E+inventor;+S+Biotech+Co.%2c+Ltd.%2c+assignee.+Functional+Food+including+capsanthin+having+enhanced+capacities+of+spontaneous+locomotor+activity+and+anti-fatigue+activity.+KR101625927B1.2016+

  31. Maeda H, Saito S, Nakamura N, Maoka T. Paprika pigments attenuate obesity-induced inflammation in 3T3-L1 adipocytes [Internet]. ISRN Inflamm. Hindawi; 2013 [cited 2021 Jan 26]. p. e763758. Available from: https://www.hindawi.com/journals/isrn/2013/763758/

  32. Dandona P, Aljada A, Bandyopadhyay A. Inflammation: the link between insulin resistance, obesity and diabetes. Trends Immunol. 2004;25:4–7.

    Article  CAS  Google Scholar 

  33. Aizawa K, Inakuma T. Dietary capsanthin, the main carotenoid in paprika (Capsicum annuum), alters plasma high-density lipoprotein-cholesterol levels and hepatic gene expression in rats. Br J Nutr. 2009;102:1760–6.

    Article  CAS  Google Scholar 

  34. Velasquez MT, Ramezani A, Manal A, Raj DS. Trimethylamine N-oxide: the good, the bad and the unknown. Toxins. 2016;8.

  35. Pérez-Gálvez A, Mínguez-Mosquera MI. Structure−reactivity relationship in the oxidation of carotenoid pigments of the pepper (Capsicum annuum L.). J Agric Food Chem. Am Chem Soc. 2001;49:4864–9.

    Google Scholar 

  36. Maoka T, Goto Y, Isobe K, Fujiwara Y, Hashimoto K, Mochida K. Antioxidative activity of capsorubin and related compounds from paprika (Capsicum annuum). J Oleo Sci. 2001;50:663–5.

    Article  CAS  Google Scholar 

  37. Kim J-S, Lee W-M, Rhee HC, Kim S. Red paprika (Capsicum annuum L.) and its main carotenoids, capsanthin and β-carotene, prevent hydrogen peroxide-induced inhibition of gap-junction intercellular communication. Chem Biol Interact. 2016;254:146–55.

    Article  CAS  Google Scholar 

  38. Nishino A, Yasui H, Maoka T. Reaction and scavenging mechanism of β-carotene and zeaxanthin with reactive oxygen species. J Oleo Sci. 2016;66.

  39. Murakami A, Nakashima M, Koshiba T, Maoka T, Nishino H, Yano M, et al. Modifying effects of carotenoids on superoxide and nitric oxide generation from stimulated leukocytes. Cancer Lett. 2000;149:115–23.

  40. Fernández-García E. Skin protection against UV light by dietary antioxidants. Food Funct The Royal Society of Chemistry. 2014;5:1994–2003.

    Article  Google Scholar 

  41. Fernández-García E, Carvajal-Lérida I, Pérez-Gálvez A. Carotenoids exclusively synthesized in red pepper (capsanthin and capsorubin) protect human dermal fibroblasts against UVB induced DNA damage. Photochem Photobiol Sci Off J Eur Photochem Assoc Eur Soc Photobiol. 2016;15:1204–11.

    Google Scholar 

  42. Nishino A, Sugimoto K, Sambe H, Ichihara T, Takaha T, Kuriki T. Effects of dietary paprika xanthophylls on ultraviolet light-induced skin damage: a double-blind placebo-controlled study. J Oleo Sci. 2018;67:863–9.

    Article  Google Scholar 

  43. Nishino H, Murakoshi M, Ii T, Takemura M, Kuchide M, Kanazawa M, et al. Carotenoids in cancer chemoprevention. Cancer Metastasis Rev. 2002;21:257–64.

  44. Housman G, Byler S, Heerboth S, Lapinska K, Longacre M, Snyder N, et al. Drug resistance in cancer: an overview. Cancers. 2014;6:1769–92.

  45. Narisawa T, Fukaura Y, Hasebe M, Nomura S, Oshima S, Inakuma T. Prevention of N-methylnitrosourea-induced colon carcinogenesis in rats by oxygenated carotenoid capsanthin and capsanthin-rich paprika juice. Proc Soc Exp Biol Med Soc Exp Biol Med N Y N. 2000;224:116–22.

    Article  CAS  Google Scholar 

  46. Kurkov SV, Loftsson T. Cyclodextrins. Int J Pharm. 2013;453:167–80.

    Article  CAS  Google Scholar 

  47. de Lima PN, da Silva DD, Costa VG, Falcão DQ, de Lima Araujo KG. Increasing solubility of red bell pepper carotenoids by complexation with 2-hydroxypropyl-β-cyclodextrin. Food Chem. 2016;208:124–31.

    Article  Google Scholar 

  48. Gomes LMM, Petito N, Costa VG, Falcão DQ, de Lima Araújo KG. Inclusion complexes of red bell pepper pigments with β-cyclodextrin: preparation, characterisation and application as natural colorant in yogurt. Food Chem. 2014;148:428–36.

    Article  CAS  Google Scholar 

  49. Chow PY, Gue SZ, Leow SK, Goh LB. Solid self-microemulsifying system (S-SMECS) for enhanced bioavailability and pigmentation of highly lipophilic bioactive carotenoid. Powder Technol. 2015;274:199–204.

    Article  CAS  Google Scholar 

  50. Qiu J, Zheng Q, Fang L, Wang Y, Min M, Shen C, et al. Preparation and characterization of casein-carrageenan conjugates and self-assembled microcapsules for encapsulation of red pigment from paprika. Carbohydr Polym. 2018;196:322–31.

  51. OSUNA-GARCIA JA, WALL MM, WADDELL CA. Natural antioxidants for preventing color loss in stored paprika. J Food Sci Wiley Online Library. 1997;62:1017–21.

    CAS  Google Scholar 

  52. Rodriguez P, Morais H, Mota T, Olivera S,  Forgács E, Cserhati T. Effect of storage conditions on the stability of pigments of paprika (Capsicum annuum) studied by HPLC and multivariate methods.  Acta Aliment. 1999;28:29–38.

  53. Morais H, Rodrigues P, Ramos C, Forgács E, Cserháti T, Oliveira J. Effect of ascorbic acid on the stability of beta-carotene and capsanthin in paprika (Capsicum annuum) powder. Nahr. 2002;46:118–33.

    Article  Google Scholar 

  54. Hamilton PB, Tirado FJ, Garcia-hernandez F. Deposition in egg yolks of the carotenoids from saponified and unsaponified oleoresin of red pepper (Capsicum annuum) fed to laying hens1,2. Poult Sci. 1990;69:462–70.

    Article  CAS  Google Scholar 

  55. Bruschi ML. Strategies to modify the drug release from pharmaceutical systems. 1st ed. Woodhead: Publishing; 2015.

  56. Xiao J, Huang G-Q, Wang S, Sun Y. Microencapsulation of capsanthin by soybean protein isolate-chitosan coacervation and microcapsule stability evaluation. J Appl Polym Sci. 2014;131.

  57. Huang G-Q, Xiao J, Qiu H, Yang J. Cross-linking of soybean protein isolate–chitosan coacervate with transglutaminase utilizing capsanthin as the model core. J Microencapsul. 2014;31:1–8.

    Article  Google Scholar 

  58. Chow PY, Gue SZ, Leow SK, Goh LB. The bioefficacy of microemulsified natural pigments in egg yolk pigmentation. Br Poult Sci. 2014;55:398–402.

    Article  CAS  Google Scholar 

  59. Gharsallaoui A, Roudaut G, Chambin O, Voilley A, Saurel R. Applications of spray-drying in microencapsulation of food ingredients: an overview. Food Res Int. 2007;40:1107–21.

    Article  CAS  Google Scholar 

  60. Rascón MP, Beristain CI, García HS, Salgado MA. Carotenoid retention and storage stability of spray-dried encapsulated paprika oleoresin using gum arabic and soy protein isolate as wall materials. LWT Food Sci Technol. 2011;44:549–57.

    Article  Google Scholar 

  61. Guadarrama-Lezama AY, Dorantes-Alvarez L, Jaramillo-Flores ME, Pérez-Alonso C, Niranjan K, Gutiérrez-López GF, et al. Preparation and characterization of non-aqueous extracts from chilli (Capsicum annuum L.) and their microencapsulates obtained by spray-drying. J Food Eng. 2012;112:29–37.

    Article  CAS  Google Scholar 

  62. No J, Shin M. Preparation and characteristics of octenyl succinic anhydride-modified partial waxy rice starches and encapsulated paprika pigment powder. Food Chem. 2019;295:466–74.

    Article  CAS  Google Scholar 

  63. CN109158061A - A kind of capsanthin microcapsule and the preparation method and application thereof - Google Patents [Internet]. [cited 2021 Jan 26]. Available from: https://patents.google.com/patent/CN109158061A/en?oq=+%E2%80%8ELi+Honglong%E2%80%8E%2c%E2%80%8E%E2%80%8E+%E2%80%8EXia+Huiting%E2%80%8E%E2%80%8E%2c+%E2%80%8EJinzi+Heng%E2%80%8E%E2%80%8E%2c%E2%80%8E%E2%80%8E+Wenjun+Li%E2%80%8E%E2%80%8E%2c+%E2%80%8E%E2%80%8EZheng%E2%80%8E%E2%80%8E%2c+%E2%80%8E%E2%80%8EXue%E2%80%8E%E2%80%8E%2c%E2%80%8E%E2%80%8E+%E2%80%8EChunfeng%E2%80%8E+inventor;+Henan+Zhongda+Hengyuan+Biotech+Co.%2c+Ltd.%2c+assignee.+A+kind+of+capsanthin+microcapsule+and+the+preparation+method+and+application+thereof.+CN109158061A.+2019+Jan+8.

  64. 卢庆国, 连运河, 田洪, 姚宝书. 水溶性辣椒红色素的制造方法 [Internet]. 2008 [cited 2021 Jan 26]. Available from: https://patents.google.com/patent/CN100402609C/en?oq=2.Lu+Qingguo%E2%80%8E%E2%80%8E%2c+%E2%80%8E%E2%80%8ELian+Canal%E2%80%8E%E2%80%8E%2c+Tianhong%E2%80%8E%E2%80%8E%2c++%E2%80%8E%E2%80%8EBaoshu%E2%80%8E%E2%80%8E+inventor;+Tianjin+Chenguang+Natural+Pigment+Co.%2c+Ltd.%2c+assignee.+Process+for+producing+water+soluble+capsanthin+pigment.+CN100402609C.2008+jul+16.

  65. 李勇, 刘温来, 王晓燕, 杨国强, 李田田. 食品级水分散辣椒红粉末的制作方法 [Internet]. 2017 [cited 2021 Jan 26]. Available from: https://patents.google.com/patent/CN106883640A/en?oq=3.+Li+Yong%E2%80%8E%E2%80%8E%2c++%E2%80%8E%E2%80%8E+%E2%80%8E%E2%80%8ELiu+Wen+to%E2%80%8E%E2%80%8E%2c+%E2%80%8E%E2%80%8E+%E2%80%8E%E2%80%8EXiaoyan%E2%80%8E%E2%80%8E%2c+%E2%80%8E%E2%80%8EGuoqiang%E2%80%8E%E2%80%8E%2c+%E2%80%8E%E2%80%8ETiantian%E2%80%8E%E2%80%8E%2c+inventor;+Shandong+Tianyin+Biological+Technology+Co.%2c+Ltd.%2c+assignee.+The+preparation+method+of+the+water-dispersion+capsicum+red+powder+of+food-grade.+CN106883640A.2017+jun+23.

  66. 王超, 王杉, 郑晗, 王东. 一种水溶辣椒红的制备方法 [Internet]. 2016 [cited 2021 Jan 26]. Available from: https://patents.google.com/patent/CN105295430A/en?oq=4.Wang+Chao%E2%80%8E%E2%80%8E%2c%E2%80%8EWangShu%E2%80%8E%E2%80%8E%2c%E2%80%8EZheng+Wei%E2%80%8E%E2%80%8E%2c%E2%80%8E%E2%80%8E+%E2%80%8E%E2%80%8EDong%E2%80%8E%E2%80%8E%2c+inventor;+Qingdao+Saite+Spice+Co.%2c+Ltd.%2cassignee.+A+kind+of+preparation+method+of+water-soluble+capsanthin.+CN105295430B.2017+jun+16

  67. 王超, 郑晗, 王东, 刘中华. 一种提高辣椒红稳定性的方法 [Internet]. 2017 [cited 2021 Jan 26]. Available from: https://patents.google.com/patent/CN106752069A/en?oq=5.Wang+Chao%2c+%E2%80%8EZheng+Wei%E2%80%8E%E2%80%8E%2c%E2%80%8E%E2%80%8E+%E2%80%8E%E2%80%8EDong%E2%80%8E%E2%80%8E%2c+inventor;+Qingdao+Saite+Spice+Co.%2c+Ltd.%E2%80%8E+.%2cassignee.+A+method+of+improving+capsanthin+stability.+CN106752069B.2018

  68. 안지윤, 하태열, 김지선. 적색 파프리카 추출물 또는 캡산틴을 유효성분으로 포함하는 근육 질환 예방, 개선 또는 치료용 조성물 [Internet]. 2019 [cited 2021 Jan 26]. Available from: https://patents.google.com/patent/KR102034314B1/en?oq=6.Aan+Ji-yoon%E2%80%8E%E2%80%8E%2cHa+Tae-yul+%2cKim%E2%80%8E%E2%80%8EJi-sun%E2%80%8E%E2%80%8E%2c+inventor;+Korea+Food+Research+Institute.%2c+assignee.+Composition+for+preventing%2c+improving+or+treating+muscular+disease+comprising+Red+Paprika+extract+or+capsanthin.KR102034314B1.2019

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Madhur Kulkarni.

Additional information

Guest Editors: Harsh Chauhan, Abhijit Date and Sonali Dhindwal

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kennedy, L.E., Abraham, A., Kulkarni, G. et al. Capsanthin, a Plant-Derived Xanthophyll: a Review of Pharmacology and Delivery Strategies. AAPS PharmSciTech 22, 203 (2021). https://doi.org/10.1208/s12249-021-02065-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1208/s12249-021-02065-z

KEY WORDS

Navigation