Ceratonia siliqua pods (Carob) methanol extract alleviates doxorubicin-induced nephrotoxicity via antioxidant, anti-inflammatory and anti-apoptotic pathways in rats.

Doxorubicin (DOX) is an anti-neoplastic therapy, but its use is limited by its deleterious toxic effects including nephrotoxicity and cardiotoxicity. This work aimed at assessing the potential protective effect of Ceratonia siliqua methanol extract (CME) on DOX-induced nephrotoxicity in 5 groups of Wistar rats. Nephrotoxicity was induced experimentally by intraperitoneal (IP) injection of DOX (15 mg/kg). DOX increased serum creatinine, urea, sodium, and potassium levels. It elevated MDA levels in the renal tissue but decreased the concentration of GSH and the activity of GST, CAT, and SOD. Meanwhile, it decreased the level of immunomodulatory anti-inflammatory mediators: IL-10 and TGF-ß, as well as the activity of MPO but increased the level of IL-6, TNF-α, and caspase-3 in the renal tissue. DOX has upregulated COX-2, caspase-9, and Bax gene expression and downregulated the Bcl-2 gene expression. Immunolabeling of renal tubular epithelium in DOX-intoxicated rats was moderate to strong against Bax, COX-2, and NF-kß and weak against Bcl-2. Treatment with CME significantly restored the levels of kidney function parameters and the levels of oxidative stress markers. It stimulated the production of IL-10 and TGF-ß and decreased the level of IL-6 and TNF-α. CME reverted the gene expression of COX-2, caspase-9, and Bax. Microscopically, CME alleviated the DOX-induced renal damage. Phytochemical analysis revealed the presence of 26 compounds in the CME. No signs of acute toxicity were recorded by CME up to 4000 mg/kg b. wt. orally into mice. Finally, CME could effectively alleviate the deleterious effects of DOX on the kidney. The safety of carob extract encourages its use in the preparation of valuable therapeutic agents.

Current perspective on veterinary drug and chemical residues in food of animal origin.

The marked increase in the demand for animal protein of high quality necessitates protecting animals from infectious diseases. This requires increasing the use of veterinary therapeutics. The overuse and misuse of veterinary products can cause a risk to human health either as short-term or long-term health problems. However, the biggest problem is the emergence of resistant strains of bacteria or parasites. This is in addition to economic losses due to the discarding of polluted milk or condemnation of affected carcasses. This paper discusses three key points: possible sources of drug and chemical residues, human health problems, and the possible method of control and prevention of veterinary drug residues in animal products.

Anti-inflammatory activity of Jasminum grandiflorum L. subsp. floribundum (Oleaceae) in inflammatory bowel disease and arthritis models.

Our study has renewed interest in the genus Jasmine for the treatment of chronic inflammatory conditions. Aerial parts of Jasminum grandiflorum L. subsp. floribundum total methanolic extract (JTME) were tested for its therapeutic potential as an anti-inflammatory agent using two experimental models in rats; acetic acid (AA) induced ulcerative colitis and adjuvant induced arthritis. The administration of JTME showed anti-inflammatory activity in a dose dependent manner. JTME, 400 mg/kg was like prednisolone, 2 mg/kg p.o. (the reference drug), since it improved the tissues of the colon clinically, macro and microscopically (ulcer index), and histopathological (scoring). It reduced the intestinal expression of pro-inflammatory cytokines in the colonic mucosa; IFNγ, TNFα, IL-6, IL-1, and MPO. It also preserved tight junctions in intestinal epithelial cells by counter-regulating claudin-5 and occludin levels additionally, it had a potent antioxidant activity. The expressions of NF-κB p65, TNF-α and caspase-3 in rats administered AA (2 mL of 4% solution, once, intrarectally) were significantly increased, where the lowest expression was scored in JTME, 400 mg/kg group. In the adjuvant induced model of rheumatoid arthritis, the TJME, 400 mg/kg reduced the levels of cathepsin D, iNOS, NO, RF, CRP, CPP and elevated the total antioxidant capacity of tissues. Additionally, it maintained bones without histopathological lesions, articular cartilage damage, and inflammation of the synovial membrane and periarticular tissues, in contrast to arthritic rats. Finally, we report a new detailed study to validate the medicinal importance of Jasminum for the chronic inflammatory disorders with immune dysfunction with anti-inflammatory and antioxidant effects.

Unravelling the anthelmintic bioactives from Jasminum grandiflorum L. subsp. Floribundum adopting in vitro biological assessment.

ETHNOPHARMACOLOGICAL RELEVANCE: Jasminum grandiflorum L. is a medicinal plant widely used in the traditional system of Medicine as an anthelmintic in ringworm infections, for treating ulcers, stomatitis, skin diseases, and wounds. AIM OF THE STUDY: The emergence of resistance by different parasites to currently used chemicals has been reported. There are increasing needs for more effective and safer parasiticides. Therefore, the current study was designed to investigate the methanolic extract of the aerial parts of J. grandiflorum subsp. Floribundum (JGTE) to confirm its traditional uses as anthelmintic through a bioassay-guided fractionation and isolation of the active components with anthelmintic activity. MATERIALS AND METHODS: The JGTE was partitioned into dichloromethane (DCM-F) and n-butanol (BuOH-F) fractions. The JGTE, fractions, and the isolated compounds were tested in vitro for their anthelmintic activity using two nematodes; one larval stage of cestode and one arthropod. Four major compounds were isolated from the most active fraction (BuOH-F) including two flavonoids and two secoirridoid glycosides, identified as kaempferol-3-O-neohesperoside (1), rutin (2), oleuropein (3), and ligstroside (4). RESULTS: Among the isolated compounds from most active fraction (BuOH-F), rutin (2) displayed the highest anthelmintic activity in a dose-dependent activity with IC50 of 41.04 µg/mL against H. muscae adult worm, followed by ligstroside (4) with IC50 of 50.56 µg/mL. CONCLUSIONS: These findings could advocate the traditional use of J. grandiflorum L. and provide further insight into the anthelmintic activity of flavonoids.

Characterization of Nuclear Progesterone Receptor Isoforms in the Term Equine Placenta.

In equine parturition, the role of progestins along with the nuclear progesterone receptor (nPR) signaling pathway in the placenta is not completely clarified. The progestins play an integral role in maintaining myometrial quiescence during the late stage of pregnancy via acting on nPR isoforms (PRA and PRB; PRB is more active than PRA). The current study aimed to determine the PRA and PRB expressions in the term equine placenta at the gene and protein levels. Six term equine placentas were used in this study. Reverse transcription polymerase chain reaction (RT-PCR) was used to quantify the mRNA expression for PRA and PRB. The protein expression was detected using the Western Blot technique. The results revealed that the mRNA and protein expressions for PRA were significantly higher (P < 0.0001) in the term equine placental tissue compared to the mRNA and protein expressions of PRB. These results demonstrated that nPRs are detectable in the term placenta of mares and PRA is the dominant isoform expressed. The present findings raised the possibility that the PRA plays an important role in the parturition process and expulsion of the placenta in mares.

Benzodioxole-Pyrazole Hybrids as Anti-Inflammatory and Analgesic Agents with COX-1,2/5-LOX Inhibition and Antioxidant Potential.

Two series of benzodioxole-pyrazole hybrids were synthesized and the IC50 values for in vitro inhibition of the enzymes cyclooxygenase 1/2 (COX-1, COX-2) and 5-lipoxygenase (5-LOX) were investigated. All compounds were tested for their in vivo anti-inflammatory and analgesic potentials using diclofenac sodium as a reference standard. Compounds 4, 11, 17, 20, 21, 26, and 27, which showed good analgesic and/or anti-inflammatory activities, were also evaluated for their ability to inhibit tumor necrosis factor (TNF)-α production, myeloperoxidase and proteinase, beside their antioxidant activity. Collectively, compounds 11, 17, and 26 displayed significant anti-inflammatory, analgesic, and antioxidant activities, beside dual COX-2 and 5-LOX inhibition. Among these, compound 26 showed high selectivity for in vitro COX-1/COX-2 inhibition, whereas the analogs 11 and 17 noticeably ameliorated the TNF-α level by 85.19 and 97.71%, respectively. A molecular docking study was performed to investigate the possible binding mode of compounds 11, 17, and 26 with the active sites of the COX-2 and 5-LOX enzymes, where they showed nearly the same binding pattern as that of celecoxib and meclofenamic acid, respectively.

Anti-inflammatory, antipyretic and antioxidant effect of some medicinal plant extracts.

The anti-inflammatory, antipyretic and antioxidant effect of the methanol extract of Alhgi maurorum, Conyza dioscoridis and Convolvulus fatmensis was investigated. The antiinflammatory effect was studied using carageenan-induced rat paw edema, while the antipyretic effect was estimated using Brewer's yeast-induced hyperpyrexia in rats. The antioxidant activity was evaluated using 2,2-diphenyl-1-picryhydrazyl (DPPH) free radical scavenging activity method of different concentrations of the plant extracts using ascorbic acid as a standard antioxidant. The results revealed that oral administration of Alhgi maurorum and Convolvulus fatmensis at 1 g/ kg exhibited anti-inflammatory effect comparable to the standard diclofenac sodium (0.03 g/kg). The anti-inflammatory effect of Conyza dioscoridis appeared at lower doses 0.5g/kg. In all cases the maximum effect was obtained 2h after administration. None of the tested plant extracts showed antipyretic effect. The tested plant extracts showed variable degrees of antioxidant activity. Conyza dioscoridis showed the highest antioxidant effect (91.14%) and Alhgi maurorum has the least (28.78%) compared to the standard ascorbic acid (87.8%).

Immunological studies on Amaranth, Sunset Yellow and Curcumin as food colouring agents in albino rats.

The use of food dyes is at least controversial because they are only of essential role. Moreover many of them have been related to health problems mainly in children that are considered a very vulnerable group. This study was carried out to investigate the effect of oral administration of Amaranth, Sunset Yellow and Curcumin for 4 weeks at doses of 47, 315 and 157.5 mg/kg b. wt. and after 2 weeks all animals were immunostimulated by intra peritoneal injection of sheep RBCs 10% (1 ml/rat). Body weight, relative body weight, total and differential leukocytes count, mononuclear cell count, delayed hypersensitivity, total protein and serum fractions were determined. Results revealed that oral administration of Amaranth, Sunset Yellow and Curcumin did not affect the body weight gain or the spleen weight. On the other hand Sunset Yellow and Curcumin significantly decreased the weight of thymus gland of the rats. Total leukocyte count were not affected while Amaranth and Curcumin-treated rats revealed a significant decrease in neutrophiles and monocytes and a compensatory increase in lymphocytes. Moreover, oral administration of Sunset Yellow revealed a significant decrease in monocyte percent. Amaranth, Sunset Yellow and Curcumin significantly decreased the delayed hyper sensitivity. Total serum protein, albumin, total globulin and albumin/globulin (A/G) ratio were not affected by administration of the colouring agents. Oral administration of Amaranth increases the density of albumin band. On the other hand oral administration of Curcumin decreases the density of the albumin band. Oral administration of any of the tested colouring agents did not change the density of globulin region as compared to control group. In conclusion we found that both synthetic (Amaranth and Sunset Yellow) and natural (Curcumin) colouring agents used at doses up to 10 times the acceptable daily intake exerted a depressing effect on the cellular but not humoral immune response.

Evaluation of some medicinal plant extracts for antidiarrhoeal activity.

The antidiarrhoeal effect of seven plant extracts namely: the aerial parts of Euphorbia paralias L. (EP), Bidens bipinnata L. (BB), Cynachum acutum L. (CyAc), Diplotaxis acris (Forssk.) Boiss (DA), Convolvulus fatmensis (CF) and Schouwia thebaica Webb (ST) and the leaves of Plantago major L. (PM), was evaluated on castor oil-induced diarrhoea, gastrointestinal movement in rats (charcoal meal) and on the motility of duodenum isolated from freshly slaughtered rabbits. A significant antidiarrhoeal effect of the tested plant extracts against castor oil-induced diarrhoea in rats was achieved by 200 and 400 mg/kg. The tested plant extracts decreased the gastrointestinal movement as indicated by the significantly (p<0.05 to 0.001) decreased distance travelled by the charcoal meal. The large dose of the tested plant extracts was slightly more effective than the small one. The antidiarrhoeal effect was confirmed by the reported dose dependent inhibition of the motility of duodenum isolated from freshly slaughtered rabbits. The EP and PM methanol extract produced a transient stimulation followed by inhibition in doses of less than 0.05 and 1.6 mg/kg, respectively. Higher concentrations caused rapid muscle relaxation. Tannins, flavonoids, unsaturated sterols/triterpenes, carbohydrates, lactones and proteins/amino acids were reported as major active constituents of the tested plants.

Antidiarrhoeal activity of some Egyptian medicinal plant extracts.

The antidiarrhoeal activity of six Egyptian medicinal plant extracts (200 and 400 mg kg(-1)) and their effect on motility of isolated rabbit's duodenum was investigated. Phytochemical screening of the plant extracts for their active constituents was also carried out by TLC. Oral administration of methanol extract from Conyza dioscoridis (CD) or Alhagi maurorum (AM) in a 200 mg kg(-1) dose exhibits a significant antidiarrhoeal effect against castor oil-induced diarrhoea, while Mentha microphylla (MM), Convolvulus arvensis (CA), Conyza linifolia (CL) produced no significant effect. In a dose of 400 mg kg(-1), Mentha microphylla, Conyza dioscoridis, Alhagi maurorum, Zygophyllum album (ZA), and Conyza linifolia produced a significant (P<0.01) effect, while Convolvulus arvensis produced no antidiarrhoeal effect in rats. Methanol extract of Mentha microphylla, Conyza dioscoridis, Zygophyllum album, and Convolvulus arvensis induced a dose-dependent (0.4-2.8 mg ml(-1)) relaxation of rabbit's duodenal smooth muscle. Alhagi maurorum and Conyza linifolia increased the contractile force in concentrations between 0.4 and 1.6 mg ml(-1). Higher concentrations (>3.2 mg ml(-1)) caused a rapid depressant effect. The depressant effect induced by Alhagi maurorum (in a higher dose) and Zygophyllum album appeared to be due to calcium channel blocking effect, since CaCl(2) could not restore the contractile response of the tissue impregnated in calcium free-medium. However, a ganglionic blocking effect appeared to be a possible mechanism of action of Mentha microphylla and Conyza dioscoridis since a stimulant dose of nicotine could not restore the contractile response of the tissue. The effect of Convolvulus arvensis and Conyza linifolia was not through any of the common mediators. Phytochemical screening revealed the presence of tannins, flavonoids, unsaturated sterols/triterpenes, carbohydrates, lactones and proteins/amino acids as major constituents.