This study indicates that R. rosea inhibits the metabolic capacity of CYP2C9 in humans. Although the effect is modest, it might be clinically relevant during treatment with CYP2C9 substrates with a narrow therapeutic index, such as phenytoin and warfarin.

Sleeve gastrectomy induces hypergastrinemia, lowers HbA1c, and improves glycemic control in Goto-Kakizaki rats. Sleeve gastrectomy is superior to duodenojejunostomy as treatment of type 2 diabetes mellitus in this animal model.

Context: Rhodiola rosea L. (Crassulaceae) products are popular natural remedies with a worldwide distribution. Recent studies have revealed potent CYP inhibition by R. rosea extracts both in vitro and in vivo, but information on in vitro CYP inhibition by commercial products are lacking. Variations in commercial R. rosea product quality have also been published. Objective: This study evaluates the variation of in vitro CYP inhibition potential and product quality of six commercially available R. rosea products. Materials and methods: Human CYPs isolated from baculovirus-infected cell system were incubated with testosterone (CYP3A4), dextromethorphan (CYP2D6) or phenacetin (CYP1A2). Positive CYP inhibitors ketoconazole (CYP3A4), quinidine (CYP2D6) and b-naphtoflavone (CYP1A2) were used as controls. Quantification of rosavin, rosarin, rosin, tyrosol and salidroside were used to evaluate R. rosea content. Results: IC 50 values ranged from 7.2-106.6 lg/mL for CYP3A4, 13.0-186.1 lg/mL for 2D6 and 10.7-116.0 lg/mL for 1A2. The tincture formulation of R. rosea was the strongest inhibitor giving the lowest IC 50 values of 7.2 ± 0.7, 13 ± 1.7 and 10.7 ± 5.6 lg/mL, respectively. CYP3A4 was significantly more inhibited by the different products than CYP1A2 (p < .05). One of the six products did not contain any rosavin, rosarin or rosin and is not a R. rosea product. Constituent concentrations were not linked to enzyme inhibition. Discussion and conclusion: The present results show a large variation in inhibitory potential between the products. Several of the products demonstrate similar inhibition levels as the product Arctic Root already proven to inhibit CYP enzyme activity in man.ARTICLE HISTORY

A commercial Rhodiola rosea (R. rosea) product has previously demonstrated CYP2C9 inhibition in humans. The purpose of this study was to provide in vitro inhibitory data for this particular interaction and to classify the mechanism of the interaction. Another aim was to examine the in vitro influence of ethanol on the CYP2C9 activity. Human CYP2C9 (wild type) isolated from a baculovirus‐infected cell system was incubated with 0.8 μmol/L losartan for 20 min. Sulfaphenazole was used as a positive control. The commercial R. rosea product “Arctic Root” was used as test inhibitor. Formation of the CYP2C9‐produced losartan metabolite EXP‐3174 was determined by validated LC‐MS/MS methodology. Possible mechanism‐based (irreversible) inhibition was evaluated using time‐ and NADPH‐dependent inhibition assays. Kinetic constants (K m, V max, and K i) were calculated from a Lineweaver‐Burk plot. Mode of inhibition was determined. CYP2C9 was inhibited by “Arctic Root” with an IC 50 (extract concentration yielding 50% reduction in enzyme activity) of 19.2 ± 2.7 μg/mL. Inhibitor concentrations of 20 μg/mL and 40 μg/mL yielded Ki values of 16.37 μg/mL and 5.59 μg/mL, respectively. The Lineweaver‐Burk plot showed noncompetitive inhibition mode. No time‐ or NADPH‐dependent inhibition was observed. The presence of ethanol inhibited CYP2C9 activity in a concentration‐dependent manner. In conclusion, the commercial R. rosea product “Arctic Root” demonstrated noncompetitive inhibition of CYP2C9 in vitro. Further work identifying the constituents responsible for this inhibition is needed.

Background Respiratory rate (RR) is arguably the most important vital sign to detect clinical deterioration. Change in RR can also, for example, be associated with the onset of different diseases, opioid overdoses, intense workouts, or mood. However, unlike for most other vital parameters, an easy and accurate measuring method is lacking. Objective This study aims to validate the radar-based sleep monitor, Somnofy, for measuring RRs and investigate whether events affecting RR can be detected from personalized baselines calculated from nightly averages. Methods First, RRs from Somnofy for 37 healthy adults during full nights of sleep were extensively validated against respiratory inductance plethysmography. Then, the night-to-night consistency of a proposed filtered average RR was analyzed for 6 healthy participants in a pilot study in which they used Somnofy at home for 3 months. Results Somnofy measured RR 84% of the time, with mean absolute error of 0.18 (SD 0.05) respirations per minute, and Bland-Altman 95% limits of agreement adjusted for repeated measurements ranged from –0.99 to 0.85. The accuracy and coverage were substantially higher in deep and light sleep than in rapid eye movement sleep and wake. The results were independent of age, sex, and BMI, but dependent on supine sleeping position for some radar orientations. For nightly filtered averages, the 95% limits of agreement ranged from −0.07 to −0.04 respirations per minute. In the longitudinal part of the study, the nightly average was consistent from night to night, and all substantial deviations coincided with self-reported illnesses. Conclusions RRs from Somnofy were more accurate than those from any other alternative method suitable for longitudinal measurements. Moreover, the nightly averages were consistent from night to night. Thus, several factors affecting RR should be detectable as anomalies from personalized baselines, enabling a range of applications. More studies are necessary to investigate its potential in children and older adults or in a clinical setting.