Ramnosio: struttura chimica, funzioni biologiche, fonti naturali, applicazioni e sicurezza

Definizione
Il ramnosio è un monosaccaride deossi-esoso appartenente alla classe degli aldosi, con formula molecolare C₆H₁₂O₅. A differenza della maggior parte degli zuccheri naturali, si presenta prevalentemente nella forma L (L-ramnosio), una caratteristica relativamente rara. È uno dei pochi zuccheri metilati naturalmente presenti nei vegetali e nelle glicoproteine batteriche.

Ramnosio è un composto chimico organico, un monosaccaride, deossy-zucchero naturale. In natura si presenta nella forma L- e si ottiene con procedimento chimico dall'olivello spinoso e dalle alghe che appartengono alla famiglia delle Bacillariophyceae.

Il ramnosio è comunemente trovato come unità strutturale di glicani, glicosidi flavonoidi e polisaccaridi vegetali.

1. Proprietà chimiche

• Formula molecolare: C₆H₁₂O₅

• Peso molecolare: 164,16 g/mol

• Struttura:

  • zucchero a 6 atomi di carbonio

  • possiede un gruppo aldeidico in posizione 1

  • è un 6-deossi-L-mannosio, ovvero privo di un gruppo -OH in C6

  • può esistere in forma lineare o ciclica (piranosica o furanosica)

• Solubilità: altamente solubile in acqua

• Stato fisico: solido cristallino bianco, leggermente dolce

2. Fonti naturali

• Ampiamente distribuito in piante superiori, in particolare come:

  • parte dei glicosidi flavonoidi (es. rutinoside, naringina, quercitrina)

  • presente nella gomma arabica e in altri polisaccaridi vegetali

• Costituente di:

  • pareti cellulari batteriche (Gram-negativi)

  • lipopolisaccaridi (LPS)

  • glicolipidi e glicoproteine microbiche

3. Funzioni biologiche

• Nelle piante:

  • parte integrante dei metaboliti secondari, come flavonoidi glicosilati

  • coinvolto nella solubilità e stabilità dei composti fenolici

• Nei batteri:

  • importante nel riconoscimento cellulare e come antigene (LPS)

  • componente strutturale nelle superfici batteriche e biofilm

• Negli esseri umani:

  • non metabolizzato efficientemente, viene in parte escreto con le urine

  • non influisce significativamente sulla glicemia

4. Applicazioni

Cosmetica

• Utilizzato in prodotti anti-età per la sua capacità di:

  • ridurre la reattività cutanea

  • migliorare la barriera cutanea

  • stimolare la rigenerazione epidermica

• Presente in sieri e creme per pelli sensibili e mature

Agente aromatizzante. Lo scopo di questo ingrediente è modificare la soluzione per aggiungere sapore. Gli estratti di aromi naturali hanno un costo piuttosto elevato quindi le industrie cosmetiche e farmaceutiche ricorrono a sostanze sintetizzate che abbiano caratteristiche sensoriali per lo più simili agli aromi naturali o naturalmente equivalenti. Questo ingrediente è isolato attraverso processi chimici o è sintetizzato da sostanze chimiche.

CAS: 10030-85-0, 3615-41-6

Nutraceutica e alimentare

• Come parte di estratti vegetali (es. agrumi, tè verde, foglie di ulivo)

• In studi clinici per attività antinfiammatoria e antiossidante indiretta, attraverso i flavonoidi glicosilati

• Utilizzato in prodotti a base di fibre solubili e polifenoli

Farmaceutica e microbiologia

• Impiegato come substrato o marcatore nella caratterizzazione batterica

• Utilizzato come componente di vaccini sperimentali (es. legato a antigeni batterici)

• Impiegato in analisi strutturale di glicani complessi

5. Sicurezza e tollerabilità

• Generalmente riconosciuto come sicuro (GRAS)

• Nessuna tossicità acuta o cronica documentata a dosi alimentari

• Non è allergenico

• L’assorbimento intestinale è parziale → buona tollerabilità

• A dosi molto elevate può avere effetto osmotico blando (gas, feci molli)

6. Conclusione

Il ramnosio è un zucchero naturale e biologicamente attivo, importante nella struttura dei glicosidi vegetali e nelle interazioni microbiologiche. In campo cosmetico è apprezzato per i suoi effetti calmanti e rigeneranti sulla pelle, mentre in ambito nutraceutico si associa ai benefici dei flavonoidi.

Grazie alla sua origine vegetale, alla buona tollerabilità e alle proprietà funzionali, il ramnosio è un ingrediente sempre più presente in prodotti innovativi e ad alto valore aggiunto.

Sinonimi: 

L(+)-Rhamnose Monohydrate, l-(+)-Rhamnose monohydrate, (2R,3R,4S,5S)-2,3,4,5-Tetrahydroxyhexanal hydrate, rhamnose monohydrate, Rhamnose

Bibliografia__________________________________________________________________________

Novotná R, Škařupová D, Hanyk J, Ulrichová J, Křen V, Bojarová P, Brodsky K, Vostálová J, Franková J. Hesperidin, Hesperetin, Rutinose, and Rhamnose Act as Skin Anti-Aging Agents. Molecules. 2023 Feb 11;28(4):1728. doi: 10.3390/molecules28041728. 

Abstract. Aging is a complex physiological process that can be accelerated by chemical (high blood glucose levels) or physical (solar exposure) factors. It is accompanied by the accumulation of altered molecules in the human body. The accumulation of oxidatively modified and glycated proteins is associated with inflammation and the progression of chronic diseases (aging). The use of antiglycating agents is one of the recent approaches in the preventive strategy of aging and natural compounds seem to be promising candidates. Our study focused on the anti-aging effect of the flavonoid hesperetin, its glycoside hesperidin and its carbohydrate moieties rutinose and rhamnose on young and physiologically aged normal human dermal fibroblasts (NHDFs). The anti-aging activity of the test compounds was evaluated by measuring matrix metalloproteinases (MMPs) and inflammatory interleukins by ELISA. The modulation of elastase, hyaluronidase, and collagenase activity by the tested substances was evaluated spectrophotometrically by tube tests. Rutinose and rhamnose inhibited the activity of pure elastase, hyaluronidase, and collagenase. Hesperidin and hesperetin inhibited elastase and hyaluronidase activity. In skin aging models, MMP-1 and MMP-2 levels were reduced after application of all tested substances. Collagen I production was increased after the application of rhamnose and rutinose.

Chen W, Gu L, Zhang W, Motari E, Cai L, Styslinger TJ, Wang PG. L-rhamnose antigen: a promising alternative to α-gal for cancer immunotherapies. ACS Chem Biol. 2011 Feb 18;6(2):185-91. doi: 10.1021/cb100318z.

Abstract. The targeting of autologous vaccines toward antigen presenting cells (APCs) via the in vivo complexation between anti α-Gal (anti-Gal) antibodies and α-Gal antigens presents a promising cancer immunotherapy with enhanced immunogenicity. This strategy takes advantage of the ubiquitous anti-Gal antibody in human serum. In contrast to the α-Gal epitope, the recent identification of high titers of anti-l-rhamnose (anti-Rha) antibodies in humans reveals a new approach toward immunotherapy employing l-rhamnose (Rha) monosaccharides. In order to evaluate this simple antigen in preclinical applications, we have synthesized Rha-conjugated immunogens and successfully induced high titers of anti-Rha antibodies in wildtype mice. Moreover, our studies demonstrate for the first time that wildtype mice could replace α1,3galactosyltransferase knockout (α1,3GT KO) mice in such antigen/antibody-mediated vaccine design when developing cancer immunotherapies.

Lang S, Wullbrandt D. Rhamnose lipids--biosynthesis, microbial production and application potential. Appl Microbiol Biotechnol. 1999 Jan;51(1):22-32. doi: 10.1007/s002530051358. 

Abstract. Biosurfactants containing rhamnose and beta-hydroxydecanoic acid and called rhamnolipids are reviewed with respect to microbial producers, their physiological role, biosynthesis and genetics, and especially their microbial overproduction, physicochemical properties and potential applications. With Pseudomonas species, more than 100 g l-1 rhamnolipids were produced from 160 g l-1 soybean oil at a volumetric productivity of 0.4 g l-1 h-1. The individual rhamnolipids are able to lower the surface tension of water from 72 mN m-1 to 25-30 mN m-1 at concentrations of 10-200 mg l-1. After initial testing, rhamnolipids seem to have potential applications in combating marine oil pollution, removing oil from sand and in combating zoosporic phytopathogens. Rhamnolipids are also a source of L-rhamnose, which is already used for the industrial production of high-quality flavor components.

Giraud MF, Naismith JH. The rhamnose pathway. Curr Opin Struct Biol. 2000 Dec;10(6):687-96. doi: 10.1016/s0959-440x(00)00145-7. 

Abstract. L-Rhamnose is a deoxy sugar found widely in bacteria and plants. Evidence continues to emerge about its essential role in many pathogenic bacteria. The crystal structures of two of the four enzymes involved in its biosynthetic pathway have been reported and the other two have been submitted for publication. This pathway does not exist in humans, making enzymes of this pathway very attractive targets for therapeutic intervention.

Smith TN, Oppenheimer SB. Involvement of L(-)-rhamnose in sea urchin gastrulation: a live embryo assay. Zygote. 2015 Apr;23(2):222-8. doi: 10.1017/S0967199413000452.

Abstract. The sea urchin embryo is a National Institutes of Health model system that has provided major developments, and is important in human health and disease. To obtain initial insights to identify glycans that mediate cellular interactions, Lytechinus pictus sea urchin embryos were incubated at 24 or 30 h post-fertilization with 0.0009-0.03 M alpha-cyclodextrin, melibiose, L(-)-rhamnose, trehalose, D(+)-xylose or L(-)-xylose in lower-calcium artificial sea water (pH 8.0, 15°C), which speeds the entry of molecules into the interior of the embryos. While α-cyclodextrin killed the embryos, and L(-)-xylose had small effects at one concentration tested, L(-)-rhamnose caused substantially increased numbers of unattached archenterons and exogastrulated embryos at low glycan concentrations after 18-24 h incubation with the sugar. The results were statistically significant compared with the control embryos in the absence of sugar (P < 0.05). The other sugars (melibiose, trehalose, D(+)-xylose) had no statistically significant effects whatsoever at any of the concentrations tested. In total, in the current study, 39,369 embryos were examined. This study is the first demonstration that uses a live embryo assay for a likely role for L(-)-rhamnose in sea urchin gastrula cellular interactions, which have interested investigators for over a century.

Malagon I, Onkenhout W, Klok M, van der Poel PF, Bovill JG, Hazekamp MG. Rhamnose and rhamnitol in dual sugar permeability tests. J Pediatr Gastroenterol Nutr. 2006 Aug;43(2):265-6. doi: 10.1097/01.mpg.0000226379.41365.62. 

Abstract. Rhamnose is one of the sugars regularly used to conduct the dual sugar permeability test. For more than 30 years, it has been assumed that rhamnose is an inert sugar not metabolized by the human body and only fermented by some colonic bacteria into rhamnulose. While conducting an investigation on gut permeability in children undergoing cardiac surgery, increased concentrations of rhamnitol were found in the urine samples. The present report suggests that rhamnose is not an inert sugar and it is partially metabolized into rhamnitol by the human body.

Gasparini F, Franchi N, Spolaore B, Ballarin L. Novel rhamnose-binding lectins from the colonial ascidian Botryllus schlosseri. Dev Comp Immunol. 2008;32(10):1177-91. doi: 10.1016/j.dci.2008.03.006.

Abstract. In a full-length cDNA library from the compound ascidian Botryllus schlosseri, we identified, by BLAST search against UniProt database, five transcripts, each with complete coding sequence, homologous to known rhamnose-binding lectins (RBLs). Comparisons of the predicted amino acid sequences suggest that they represent different isoforms of a novel RBL, called BsRBL-1-5. Four of these isolectins were found in Botryllus homogenate after purification by affinity chromatography on acid-treated Sepharose, analysis by reverse-phase HPLC and mass spectrometry. Analysis of both molecular masses and tryptic digests of BsRBLs indicated that the N-terminal sequence of the purified proteins starts from residue 22 of the putative amino acid sequence, and residues 1-21 represent a signal peptide. Analysis by mass spectrometry of V8-protease digests confirmed the presence and alignments of the eight cysteines involved in the disulphide bridges that characterise RBLs. Functional studies proved the enhancing effect on phagocytosis of the affinity-purified material. Results are discussed in terms of phylogenetic relationships of BsRBLs with orthologous molecules from protostomes and deuterostomes.