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Diclofenac is an extensively used nonsteroidal anti-inflammatory drug, but gastrointestinal liabilities and cardiovascular complications take the shine away from such a widely prescribed drug. On the other hand, rutin, a dietary bioflavonoid, has quite a few pharmacological attributes to improve the efficacy and reduce the dose-related toxicities of diclofenac through the intended food-drug/herb-drug interaction. The aim of the present research work was to investigate the role of rutin on pharmacokinetic modulation and the consequent efficacy of diclofenac. At first, pharmacodynamics and pharmacokinetics of diclofenac as alone and in the presence of rutin were investigated orally in a rat model. Then, mechanistic studies were performed to explain the effect of rutin on improvement in oral exposure as well as the efficacy of diclofenac using a battery of in-vitro / in-situ / in-vivo studies. Results displayed that rutin enhanced efficacy as well as oral bioavailability of diclofenac in rats. A marked increase in permeability of diclofenac by rutin was displayed that is linked to inhibition of Breast Cancer Resistance Protein (BCRP) transporters. There was no significant effect of rutin on the modulation of intestinal transit, CYP2C9 inhibition in human liver microsomes, and CYP2C9/CYP2C11 expression in rat liver tissues to boost the oral exposure of diclofenac. Rutin is found to be an inhibitor for BCRP transporters and can act as an oral bioavailability enhancer for a drug like diclofenac.

Clinical significance of Rutin (RUT) is limited by poor dissolution rate and low oral bioavailability. The study was designed to improve the physicochemical and therapeutic potential of the drug by formulating nanosuspension (NS) for osteoporosis. Rutin nanosuspension (RUT-NS) was prepared after screening a range of stabilizers and their combinations at a different concentration by antisolvent precipitation technique. Effect of precipitation on crystallinity (differential scanning calorimetry DSC, X-ray diffraction studies XRD), morphology (scanning electron microscopy, SEM) and chemical interaction (attenuated total reflectance fourier-transform infrared spectroscopy ATR-FTIR) were studied through biophysical techniques. An optimized nanosuspension exhibited a minimum particle size of 122.85 ± 5.02 nm with higher dissolution of RUT-NS (87. 63 ± 2.29%) as compared to pure drug (39.77 ± 2.8 6%). The enhanced intestine absorption and apparent permeability were achieved due to the improved particle size, surface area and dissolution. RUT-NS displayed greater (3 folds) AUC 0-24 h than pure drug. In vitro assays with RUT-NS depicted an increased cell proliferation, antioxidant (ROS) activity and osteocalcin production in MG-63 osteoblast cells. The augmented biochemical in vivo biomarkers and bone quality proved the protective effect of RUT-NS. The results supported RUT-NS as a potential therapy for maintaining bone health.

Buckwheat is a crop that has gained considerable interest worldwide due to its nutritional, economical, and pharmaceutical values. To ensure food and nutritional security in a scenario of global climate change, this pseudocereal is a competent alternative to staple crops. With rising knowledge regarding the nutraceutical potential, the popularity of this species is expected to increase further in coming years. The main bioactive component of this species is rutin that has been proven to have a wide range of health-promoting benefits. Due to breeding constraints, asynchronous maturity, seed shattering, and restricted distribution, this species holds the status of an underutilized or neglected crop in many parts of the world. In the North-western Himalayan zone, it is an integral part of local dietary intake and is grown as a second crop after harvesting barley and peas. Fagopyrum esculentum and F. tataricum are the species of buckwheat cultivated in the North-western Himalayas. However, more studies in the direction of conservation, utilization, and genetic amelioration of plant genetic resources are needed to sustain food security in Southeast Asia. The present review paper accentuates the multicore potential of buckwheat besides highlighting the commercial and pharmaceutical perspective. This article also focuses on the conservation and sustainable utilization of Himalayan gene pools, desirable agronomic traits, and genetic diversity besides focusing on the biochemical and molecular response of Fagopyrum to biotic and abiotic stress including modulation of the rutin content. The role of biotechnological interventions and future prospects are also summarized.

Rutinose and five R-beta-rutinosides were obtained by means of rutin-degrading reaction in water or aqueous alcohol (ROH, R = methyl, ethyl, propyl, isopropyl, and benzyl) with rutin-degrading enzyme as catalyst and rutin as starting material in 84-94% yields, of which methyl-beta-rutinoside, propyl-beta-rutinoside, isopropyl-beta-rutinoside, and benzyl-beta-rutinoside are firstly reported in this paper. Based on spectral analysis, the structures of all products were elucidated.

Tomato juice containing rutin (quercetin-3-rutinoside) was ingested by healthy volunteers and ileostomists. Blood and urine collected over 24 h were analysed by HPLC with photodiode array (PDA) and tandem mass spectrometric detection. Low concentrations of isorhamnetin-3-glucuronide (Cmax = 4.3 +/- 1.5 nmoles/l) and quercetin-3-glucuronide (Cmax = 12 +/- 2 nmoles/l) were detected in plasma of healthy subjects. Metabolites appeared in blood after 4 h indicating absorption from the large intestine. Nine metabolites of rutin were detected in urine but with considerable variation in total amount (40 +/- 1-4981 +/- 115 nmoles over 24 h). No metabolites were detected in plasma or urine of ileostomists and 86 +/- 3% of the ingested rutin was recovered in ileal fluid. In subjects with an intact large intestine, but not ileostomists, rutin was catabolised with the appearance of 3,4-dihydroxyphenylacetic acid, 3-methoxy-4-hydroxyphenylacetic acid and 3-hydroxyphenylacetic acid in urine accounting for 22% of rutin intake.

A highly soluble quercetin glycoside, alphaG-rutin, is a glucose adduct of insoluble rutin, and intestinal absorption and metabolism of alphaG-rutin has not been known. We investigated the intestinal absorption and metabolism of alphaG-rutin by using portal and duodenal cannulated rats and the isolated rat intestinal mucosa. After a duodenal instillation of alphaG-rutin (150 mumol), intact alphaG-rutin, rutin and quercetin were appeared in the portal blood and these concentrations were similarly increased at 15 min. Portal quercetin reached a peak value at 60 min, and the value was higher than those of alphaG-rutin and rutin at that time. Quercetin-conjugates were also increased 30 min after the instillation. The remaining of alphaG-rutin metabolites, mainly rutin, in the intestine were 58% of instilled alphaG-rutin after 150 min. In the experiment by using the isolated mucosa of the jejunum, ileum and cecum, alphaG-rutin and rutin, but not quercetin, appeared in the serosal sides of all segments, and they were increased linearly from 10 to 100 mmol/l of mucosal alphaG-rutin. We also showed portal injected alphaG-rutin was very rapidly cleared from the blood, and appeared a large amount of conjugates. In conclusion, a soluble flavonoid-glycoside, alphaG-rutin, was absorbed as glycosides into the portal blood. A part of alphaG-rutin was hydrolyzed to rutin, but not to aglycone, through the intestine.

Antioxidant status was assayed in leaves of two local lesion hosts of tobacco mosaic virus (TMV), namely in wild-type Xanthi-nc tobacco and in NahG transgenic tobacco, the latter of which is not able to accumulate salicylic acid (SA) and therefore is unable to develop systemic acquired resistance (SAR). Activities of several enzymes related to antioxidative defense, and the levels of glutathione, chlorogenic acid and rutin were studied. The majority of antioxidant enzymes were less active in uninfected NahG tobacco than in Xanthi-nc. Furthermore, important enzymatic and non-enzymatic antioxidants were down-regulated in TMV-infected NahG plants, as compared to Xanthi-nc. Correspondingly, SA pretreatment primed the leaves for stronger induction of antioxidants in infected Xanthi-nc, but not in NahG tobaccos. The antioxidant status of NahG tobacco even decreased after an attempted induction of SAR, while the antioxidative level increased in Xanthi-nc leaves in which the SAR was successfully induced. After infection, a greater accumulation of superoxide and H2O2, and a more intensive necrotization was positively correlated with the reduced capability of NahG leaf tissue to detoxify reactive oxygen species.

The kinetics of several processes involving the potential antioxidant role of urate in physiological systems have been investigated by pulse radiolysis. While the monoanionic urate radical, .UH-, can be produced directly by oxidation with .Br2- or .OH, it can also be generated by oxidation with the neutral tryptophan radical, .Trp, with a rate constant of 2 x 10(7) M-1s-1. This radical, .UH-, reacts with .O2- with a rate constant of 8 x 10(8) M-1s-1. Also, .UH- is reduced by flavonoids, quercetin and rutin in CTAB micelles at rate constants of 6 x 10(6) M-1s-1 and 1 x 10(6) M-1s-1, respectively. These results can be of value by providing reference data useful in further investigation of the antioxidant character of urate in more complex biological systems.

The effect of the nature of the sugar moiety on quercetin absorption has been investigated in rats. Four groups of rats received an experimental meal containing 20 mg of quercetin equivalents, supplied as quercetin, quercetin 3-O-beta-glucoside, quercetin 3-O-beta-rhamnoside or rutin. Four hours after the meal, the metabolites identified in hydrolysed plasma were identical in all groups (3'- and 4'-methylquercetin). However, the total concentration of metabolites was markedly different: 11.2+/-1.8, 2.5+/-2.0 and 33.2+/-3.5 microM for the quercetin, rutin, and quercetin 3-glucoside meals respectively. After quercetin 3-rhamnoside consumption, we failed to detect any metabolites in the plasma. These data suggest that the 3-O-glucosylation improves the absorption of quercetin in the small intestine, whereas the binding of a rhamnose to the aglycone markedly depresses it. Additional experiments have shown that the higher plasma levels measured after quercetin 3-glucoside meal compared to the quercetin meal were maintained throughout the 24-hour period following the meal. Using a multi-electrode coulometric detection, together with suitable chromatographic conditions, we were able to distinguish between the conjugated and the glycosylated forms. Thus, we clearly showed the absence of quercetin 3-O-beta-glucoside in the plasma from rats fed a diet containing this glucoside. This result suggests that quercetin 3-O-beta-glucoside is hydrolysed before or during its intestinal absorption.