The current study was performed to assess the effects of carob pod aqueous extracts (CPAE, pulp, seeds or mixture) on gastrointestinal transit (GIT) and intestinal epithelium permeability. In this aspect, male rats fasted for 16 hours were used and given by oral administration NaCl (0.9%, control group) or various doses of CPAE (50, 100 and 200 mg kg⁻¹, b.w.). Two other groups of rats (batch tests) received clonidine (an alpha-2 adrenergic agonist, 1 mg kg⁻¹) or yohimbine (an alpha-2 adrenergic antagonist, 2 mg kg⁻¹). Two hours later, all animals were given a test meal containing charcoal and gum arabic in water. 30 minutes later, rats were anesthetized, a laparotomy was performed and the distance traveled by the meal compared to the total length of the small intestine was measured. Regarding the effect of CPAE on diarrhoea, the extract was administered orally to three groups of rats (ten in each group). Two other groups received normal saline (10 mL kg⁻¹) and loperamide (10 mg kg⁻¹) as a negative and standard group. Compared with the control group, the animals treated with the CPAE of pulp, seeds or a mixture (50% pulp and 50% seeds) of mature carob, showed a significant increase (3–25%) of GIT in a dose-dependent manner. By contrast, the CPAE of immature carob pods significantly and dose dependently decreased (3–19%) the GIT and diarrhoea (66–87%). However, clonidine and yohimbine respectively decreased (58%) and increased (30%) the GIT. More importantly, using the Ussing chamber system, we found that aqueous extracts of mature and immature carob pods significantly and dose-dependently increased or decreased intestinal epithelium permeability. The results indicate that carob possesses significant laxative and anti-diarrheal activities due to its opposite effects both on gastrointestinal propulsion and permeability. These findings confirm that the degree of maturity of carob characterized by a different phytochemical composition may be responsible for these actions.

Zizyphus lotus L. (Desf.) (Z. lotus) is a medicinal plant largely distributed all over the Mediterranean basin and is traditionally used by Moroccan people to treat many illnesses, including kidney failure. The nephrotoxicity of gentamicin (GM) has been well documented in humans and animals, although the preventive strategies against it remain to be studied. In this investigation, we explore whether the extract of Zizyphus lotus L. (Desf.) Fruit (ZLF) exhibits a protective effect against renal damage produced by GM. Indeed, twenty-four Wistar rats were separated into four equal groups of six each (♂/♀ = 1). The control group was treated orally with distilled water (10 mL/kg); the GM treated group received distilled water (10 mL/kg) and an intraperitoneal injection of GM (80 mg/kg) 3 h after; and the treated groups received ZLF extract orally at the doses 200 or 400 mg/kg and injected intraperitoneally with the GM. All treatments were given daily for 14 days. At the end of the experiment, the biochemical parameters and the histological observation related the kidney function was explored. ZLF treatment has significantly attenuated the nephrotoxicity induced by the GM. This effect was indicated by its capacity to decrease significantly the serum creatinine, uric acid, urea, alkaline phosphatase, gamma-glutamyl-transpeptidase, albumin, calcium, sodium amounts, water intake, urinary volume, and relative kidney weight. In addition, this effect was also shown by the increase in the creatinine clearance, urinary creatinine, uric acid, and urea levels, weight gain, compared to the rats treated only with the GM. The hemostasis of oxidants/antioxidants has been significantly improved with the treatment of ZLF extract, which was shown by a significant reduction in malondialdehydes levels. Histopathological analysis of renal tissue was correlated with biochemical observation. Chemical analysis by HPLC-DAD showed that the aqueous extract of ZLF is rich in phenolic compounds such as 3-hydroxycinnamic acid, catechin, ferulic acid, gallic acid, hydroxytyrosol, naringenin, p- coumaric Acid, quercetin, rutin, and vanillic acid. In conclusion, ZLF extract improved the nephrotoxicity induced by GM, through the improvement of the biochemical and histological parameters and thus validates its ethnomedicinal use.