Rutin

Occurrence, isolation and characteristic features
(Chemical nature, uses in pharmacy, medicinal and health benefits) of Rutin

1. Rutin Kaustav Dey M. Pharm Pharmacognosy 1 st Sem University Institute of Pharmaceutical Sciences Panjab University

2. Contents Introduction Occurrence Extraction & Isolation Chemistry Properties Development of Rutin as Phytopharmaceuticals Functional properties & Mechanism of Action Medicinal and Health Benefits

3. Introduction Discovered in 1842 and it has been used in medicine to treat vascular disorder s related to capillary permeability and fragility. The concentrations of rutin reported in grapes and buckwheat are the highest among the other plant species. Among the flavonoids, rutin belongs to the flavonols and it is the glycoside form of quercetin. Rutin has significant antioxidant, chelating, and antimicrobial properties , and therefore many beneficial health effects.

4. Introduction Therefore, can be incorporated into functional foods or used in nutraceuticals and medicinal products . Antioxidant and anti-inflammatory effects of rutin have been extensively studied in neurodegenerative disorders and brain pathologies in which rutin has demonstrated a potential neuroprotective role.

5. Introduction Rutin is also called vitamin P, which originally described the group of  flavonoids . P stands for “permeability” (penetrability), because flavonoids are able to contribute to reducing the permeability of blood vessels. There is not enough scientific data to provide a recommended dose of rutin . The appropriate dose for you may depend on factors including age, gender, and medical history.  The usual recommendation is 250 mg two times a day . Adults using rutin to treat osteoarthritis may be advised to take 250 mg three times per day, or every 12 hours.

6. Occurrence It was first reported in Ruta graveolens L . (Common Rue) (Family - Rutaceae ) which gave its name to this compound. Rutin has been found in the extracts obtained from the skin of different grape (Vitis vinifera L.) (Family - Vitaceae) varieties . Buckwheat (Fagopyrum esculentum) (Family - Polygonaceae ) is one of the most important commercial sources of rutin . However, rutin is not found in cereals and pseudocereals . Vitis vinifera L. (common grape vine) Buckwheat

7. Occurrence It is present in parts of capers, onions, green asparagus, and sea buckthorn, among others. The content in leaves of St. John’s wort and capers is high and ranges from 2.4 mg/100 g to 2.7 mg/100g, respectively. Some environmental factors such as ultraviolet (UV) radiation may have also an impact on rutin content

8. Extraction & Isolation There are different extraction methods for plant-based rutin , using different techniques such as ultrasound, microwave, mechanochemical, infrared, and pressure-assisted methods . There is also a high variability in the efficiency of rutin extraction due to different factors such as the raw material, extraction temperature, process duration, and solvent-to-sample ratio . Phytochemical studies revealed the presence of flavonoidal structure, by using chromatographic and spectroscopic techniques, 2-(3,4-dihydroxyphenyl)- 5,7-dihydroxy-3- [ α- L- rhamnopyranosyl -(1-6)- β- D- glucopyranosyloxy ]-4H-chromen-4-one i.e., rutin is identified.

9. Identification Phytochemical studies can reveal the presence of flavonoidal structure, by using chromatographic and spectroscopic techniques , 2-(3,4-dihydroxyphenyl)- 5,7-dihydroxy-3- [ α- L- rhamnopyranosyl -(1-6)- β- D- glucopyranosyloxy ]-4H-chromen-4-one i.e., rutin is identified.

10. Chemistry IUPAC Name - 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-oxo-4H-chromen-3-yl 6-O-( 6-deoxy- α- L- mannopyranosyl )- β- D-glucopyranoside Molecular Formula- C 27 H 30 O 16 Molecular Weight- 610.5 D altons

11. Chemistry Chemical name - quercetin-3-O-rutinoside It is a flavonol glycoside that is also known as vitamin P. The phenolic part of the molecule is linked to sugar (this is the hydrophilic part of the molecule), increasing the solubility of the molecule in water.

12. Chemistry This characteristic is associated with the presence in their structures of hydroxyl groups bound to aromatic rings. Rutin also exhibits metal chelating properties, inhibiting metal-ion-induced peroxidations . Quantitative analysis of rutin can be made by chromatographic methods, mainly high-performance, thin-layer chromatography and high-performance liquid chromatography.

13. Physical & Chemical Properties Morphology - yellow crystalline powder. Melting Point- 125 °C Solubility - 0.125 mg/mL in pyridine Soluble in alkali but only slightly soluble in water . Rutin is Dextrorotatory in neutral and acidic solvent and levorotatory in alkaline solvents . Rutin on hydrolysis yields quercetin, rhamnose and glucose.

14. Development of Rutin as Phytopharmaceuticals The low water solubility of rutin (0.125 g/L) represents a limitation to its incorporation into food supplements or phytopharmaceuticals. The stability of rutin to processing conditions, and its possible interactions with other food components, is also important. Rutin has in vitro antioxidant properties. Rutin to the development of phytopharmaceuticals has a disadvantage associated with its low solubility in water , affecting its bioavailability and absorption.

15. Development of Rutin as Phytopharmaceuticals Therefore, nowadays, different techniques have been investigated that allow the development of phytopharmaceuticals with rutin and at the same time improve their delivery in the intestinal tract and therapeutic efficacy, such as the encapsulation of rutin by nanostructured lipid carriers designed with phosphatidylcholine to form phytosomes that overcome the low water solubility of rutin .

16. Functional Properties & Mechanism of Action Health benefits of rutin can be influenced by its quantity and its bioavailability for absorption Normally, the daily intake of rutin varies between 1.5 and 70 mg/kg depending on the nutritional habit of an individual Rutin is hardly absorbed by intestinal membranes Rutin is extensively metabolized at the large intestine where it delivers quercetin, suggesting that quercetin or rutin metabolites in the colon are the responsible for quercetin-mediated pharmacological effects.

17. Benefits & Uses Rutin is a dietary flavonoid which has many therapeutic properties, mainly attributed to its potent antioxidant and anti-inflammatory activities Prevent neurodegenerative disorders, cardiovascular diseases, and skin cancer

18. Benefits & Uses

19. Neuroprotective Effect of Rutin Neuroprotective effect of this flavonoid is one of the most studied because of the increasing prevalence of neurological disorders and brain pathologies in the world’s population. The brain is very susceptible to oxidative damage and its low levels of antioxidant protection convert flavonoids, such as rutin , into potential pharmacological agents due to their antioxidant properties. Moreover, inflammation and glial cell activation have been related with the onset of several neurodegenerative disorders and rutin has also important anti-inflammatory effects.

20. Neuroprotective Effect of Rutin The neuroprotective potential of rutin in terms of its previously mentioned properties has been evaluated using different animal models and cell types. In several Alzheimer’s disease models, it has been demonstrated that rutin can prevent cognitive impairment by reducing neuroinflammation and also inhibiting β-amyloid and cytotoxicity by attenuation of oxidative stress reduction of TNF-α and IL-1β production in microglia, and by inhibition of β-secretase enzyme activity.

21. Role of Rutin Mechanism of action Main findings in studies Antimicrobial effects Inhibits DNA gyrase Prevents cytoplasmic membrane function Inhibits energy metabolism In combination of rutin with morin, quercetin, kaempherol , myricetin and fisetin against S. enteritidis, the antibacterial action gets enhance, significantly Anti-arthritic activity Inhibits nitric oxide production from macrophages and T-cells proliferation The dual effects of rutin (e.g., anti-arthritic and anti- candidal ) is useful as an all-in-one treatment for septic arthritis.

22. Role of Rutin Mechanism of Action Main findings in studies Antioxidant activity Neutralizes free radicals Chelates transition metals The antioxidant capacity of rutin is depended on its concentration. The inhibitory effect of rutin on the lipid peroxidation increases with an increase in its concentration. Anticancer activity Inhibits cell proliferation Removes reactive oxygen species The tumor size and number of papillomas significantly decreases by rutin treatment. Level of lipid peroxidase reduces significantly by rutin treatment

23. Role of Rutin Mechanism of action Main findings in studies Anti-inflammatory activity Inhibits eicosanoid biosynthesis, COX, lipoxygenase and PLA2 activities The significant dose dependent inhibitory effect of rutin is there Anti-diabetic activity Enhances the release of insulin from islets of langerhans , decreases in the expression of resistin , increases in the expression of PPAR gene Decrease in the fasting plasma glucose, as well as increase in insulin levels in diabetic group after a period of 45 days' oral administration of rutin is there

24. Role of Rutin Mechanism of action Main findings in studies Anti-allergic activity Inhibits mast cell activation through the inhibition of Ca2+ influx, histamine, leukotrienes and prostaglandins release By rutin treatment, a significant increase in mast cells occurs. The reduction of ROS levels in antigen ± IgE activated mast cells occurs. Histamine released from mast cells is also inhibited by rutin

25. References Alam , F., Badruddeen , Kharya , A. K., Juber , A., & Khan, M. I. (2020). Naringin: Sources, Chemistry, Toxicity, Pharmacokinetics, Pharmacological Evidences, Molecular Docking and Cell line Study . Research Journal of Pharmacy and Technology , 13 (5). https://doi.org/10.5958/0974-360X.2020.00447.3 David, A. V. A., Arulmoli , R., & Parasuraman, S. (2016). Overviews of Biological Importance of Quercetin: A Bioactive Flavonoid . Pharmacognosy Reviews , 10 (20), 84. https://doi.org/10.4103/0973-7847.194044 Frutos , M. J., Rincón-Frutos , L., & Valero-Cases, E. (2019). Rutin. Nonvitamin and Nonmineral Nutritional Supplements , 111–117. https://doi.org/10.1016/B978-0-12-812491-8.00015-1 Garg, A., Garg, S., Zaneveld , L. J. D., & Singla, A. K. (2001). Chemistry and pharmacology of the citrus bioflavonoid hesperidin . Phytotherapy Research , 15 (8). https://doi.org/10.1002/ptr.1074 Panche , A. N., Diwan, A. D., & Chandra, S. R. (2016). Flavonoids: An overview . In Journal of Nutritional Science (Vol. 5). Cambridge University Press. https://doi.org/10.1017/jns.2016.41

26. Thank You