Arbutus unedo L., (Ericaceae) inhibits intestinal glucose absorption and improves glucose tolerance in rodents.

ETHNOPHARMACOLOGICAL RELEVANCE: Arbutus unedo L., (Ericaceae) is one of the most traditional plants commonly used to treat diabetes in people living in Eastern Morocco region particularly in Taza and Beni Mellal. AIM OF THE STUDY: The aim of the study was to find if there is a scientific support to the ethnopharmacological relevance use of Arbutus unedo L., roots bark (AU) to treat diabetes. MATERIALS AND METHODS: We studied the effects of crude aqueous extract of AU on intestinal glucose absorption using short-circuit current technique in vitro and oral glucose tolerance test in vivo. RESULTS: The aqueous extract of AU (10 µg/mL to 1 mg/mL) induced concentration-dependent inhibition of sodium-dependent glucose transport across isolated mouse jejunum. The maximal inhibition was obtained with 1 mg/mL, which exhibited more than 80% of the Phloridzin inhibition with an IC50 close to 216 µg/mL. A 6-week AU ingestion (2 g/(kg day)), improved oral glucose tolerance as efficiently as metformin (300 mg/(kg day)). Arbutus unedo L. and metformin also reduced body weight. CONCLUSIONS: Arbutus unedo L. roots bark aqueous extract directly inhibited the electrogenic intestinal absorption of glucose in vitro. In addition it improved oral glucose tolerance and lowered body weight in rats after chronic oral administration in vivo. These results add a scientific support to the ethnopharmacological relevance use of Arbutus unedo L. roots bark to treat diabetes.

Hibiscus sabdariffa increases hydroxocobalamin oral bioavailability and clinical efficacy in vitamin B12 deficiency with neurological symptoms.

The aim of the study was to evaluate the bioavailability and clinical benefits of oral new formulation (HB12 ) of hydroxocobalamin (Hdrx) with Hibiscus sabdariffa (HS). First, in an observational study, a cohort of 30 vitamin B12 -deficient patients (vit B12 < 200 pg/mL) with neurological symptoms received oral fixed dose of Hdrx containing 15 mg Hdrx daily for 10 days followed by 15 mg monthly. Clinical benefits were evaluated on haematological and biochemical parameters, and neurological improvement at days 10 and 90 compared to day 0. To understand the mechanism, intestinal mucosa from mice were mounted in vitro in Ussing chambers to measure Hdrx Fluxes. In the clinical study, serum vitamin B12 level increased from 55.1 ± 36.9 to 1330 ± 335.5 pg/mL at day 10 and 431.0 ± 24.27 pg/mL at day 90, without overt adverse effects. In mice ileum, (i) intestinal bioavailability of Hdrx increased in dose-dependent manner with HB12 . The apparent permeability of Hdrx was Papp = 34.9 ± 4.6 × 10-6 cm/s in the presence of 3 mg/mL (HB12 B) compared to the control Papp = 6.2 ± 0.7 × 10-6 cm/s. (ii) Total transepithelial electrical conductance (Gt ) increased in dose-dependent manner with HB12 , Gt = 161.5 ± 10.8 mS/cm² with HB12 B (Hdrx 1 mg + HS 3 mg) compared to the control Hdrx, Gt = 28.7 ± 4.0 mS/cm². In conclusion, the clinical study suggests that injections are not required when Hdrx is given orally. Intestinal bioavailability of Hdrx increased in vitro when it was used concomitantly with HS.

Metronidazole or Cotrimoxazole therapy is associated with a decrease in intestinal bioavailability of common antiretroviral drugs.

Metronidazole (MTZ) and Cotrimoxazole (CTX) are used in HIV/AIDS patients eligible for antiretroviral treatment. The objective of this animal study was to determine whether pre-treatment with antibiotics affects the intestinal bioavailability of Atazanavir (ATV) and Ritonavir (RTV). After oral administration of 1 mg MTZ and CTX for 7 days, the rat colonic mucosa were analyzed for mucus thickness or placed in Ussing chambers to measure ATV and RTV net transepithelial fluxes (Jnet). 1. In control rats, the mucus thickness was 43.3±7.6 µm and 40.7±6.9 µm, in proximal and distal colon, respectively. In proximal colon, the thickness was 57.2±8.8 and 58.2±6.9 µm after MTZ and CTX, respectively whereas in distal colon, the thickness was 121.1±38.4 and 170.5±35.0 µm (P<0.05) respectively. 2. Transepithelial conductance was reduced after MTZ or CTX in the proximal and distal colon. 3. In control, net ATV secretion was observed both in proximal (-0.36±0.02 µg.hr(-1) cm(-2)) and distal colon (-0.30±0.08 µg.hr(-1) cm(-2)). After MTZ and CTX, it was increased in the proximal colon by two 2 fold and 4 fold, respectively and in the distal colon by 3 fold and 5 fold, respectively. 4. In control, there was no net active RTV transport either in proximal (+0.01±0.01 µg.hr(-1) cm(-2)) or distal colon (+0.04±0.01 µg.hr(-1) cm(-2)). After MTZ and CTX, secretion was increased 5 fold and 10 fold, respectively, in the proximal colon and two fold and 5 fold, respectively in the distal colon (p<0.001). In conclusion, after MTZ and CTX therapy, the mucus layer was enlarged, passive permeability was decreased and ATV and RTV were actively secreted by the colonic epithelium suggesting that, in rat, the intestinal bioavailability of ATV and RTV is impaired after antibiotic therapy.

Antisecretory effect of prescribed appetite stimulator drug cyproheptadine in rat intestine.

Cyproheptadine (Cph) is an antiserotoninergic and antihistaminergic agent with alpha-blocking activity and central sedative effect. Cph has been found to be effective in stimulating appetite, but to our knowledge, its direct effects on the intestine have not been documented. We aimed to assess the antisecretory effects of Cph in rat proximal colon using Ussing chambers' technique. In basal and serotonin (5-HT)-stimulated conditions, Cph induced a dose-dependent reduction in short-circuit current (Isc). This effect was different in fed vs. fasted rats (EC50 = 1.9 × 10(-5 ) m and 4.9 × 10(-5 ) m, respectively). As expected, Cph induced a marked dose-dependent rightward shift of the concentration-response curve to 5-HT (pA2 = 5.4). The effect of Cph was found to be close to that of antisecretory agents in the following sequence: peptide YY > somatostatin > clonidine > Cph > C7-sorbin. To our knowledge, this is the first demonstration that Cph has a direct effect on the inhibition of electrogenic ionic secretion in intestinal epithelium in vitro. Our results indicate that Cph can modulate the intestinal transport of electrolytes and provide a new insight into the peripheral effects of this drug, which is frequently prescribed as appetite stimulator in developing countries.