Hyperhomocysteinemia decreases intestinal motility leading to constipation.

Elevated levels of plasma homocysteine (Hcy) called hyperhomocysteinemia (HHcy) have been implicated in inflammation and remodeling in intestinal vasculature, and HHcy is also known to aggravate the pathogenesis of inflammatory bowel disease (IBD). Interestingly, colon is the pivotal site that regulates Hcy levels in the plasma. We hypothesize that HHcy decreases intestinal motility through matrix metalloproteinase-9 (MMP-9)-induced intestinal remodeling leading to constipation. To verify this hypothesis, we used C57BL/6J or wild-type (WT), cystathionine ß-synthase (CBS(+/-)), MMP-9(-/-), and MMP-9(-/-) + Hcy mice. Intestinal motility was assessed by barium meal studies and daily feces output. Plasma Hcy levels were measured by HPLC. Expression of ICAM-1, inducible nitric oxide synthase, MMP-9, and tissue inhibitors of MMPs was studied by Western blot and immunohistochemistry. Reactive oxygen species (ROS) including super oxide were measured by the Invitrogen molecular probe method. Tissue nitric oxide levels were assessed by a commercially available kit. Plasma Hcy levels in the treated MMP-9 group mice were comparable to CBS(+/-) mice. Barium meal studies suggest that intestinal motility is significantly decreased in CBS(+/-) mice compared with other groups. Fecal output-to-body weight ratio was significantly reduced in CBS(+/-) mice compared with other groups. There was significant upregulation of MMP-9, iNOS, and ICAM-1 expression in the colon from CBS(+/-) mice compared with WT mice. Levels of ROS, superoxide, and inducible nitric oxide were elevated in the CBS(+/-) mice compared with other groups. Results suggest that HHcy decreases intestinal motility due to MMP-9-induced intestinal remodeling leading to constipation.

Antibacterial properties of traditionally used Indian medicinal plants.

In search of broad-spectrum antibacterial activity from traditionally used Indian medicinal plants, 66 ethanolic plant extracts were screened against nine different bacteria. Of these, 39 extracts demonstrated activity against six or more test bacteria. Twelve extracts showing broad-spectrum activity were tested against specific multidrug-resistant (MDR) bacteria, methicillin-resistant Staphylococcus aureus (MRSA) and extended spectrum beta-lactamases (ESbetaL)-producing enteric bacteria. In vitro efficacy was expressed in terms of minimum inhibitory concentration (MIC) values of plant extracts. MIC values ranged from 0.32-7.5 mg/ml against MRSA and 0.31-6.25 mg/ml against ESbetaL-producing enteric bacteria. The overall activity against all groups of bacteria was found in order of Plumbago zeylanica > Hemidesmus indicus > Acorus calamus > Camellia sinensis > Terminalia chebula > Terminalia bellerica > Holarrhena antidysenterica > Lawsonia inermis > Mangifera indica > Punica granatum > Cichorium intybus and Delonix regia. In addition, these extracts showed synergistic interaction with tetracycline, chloramphenicol and ciprofloxacin against S. aureus and/or Escherichia coli. The ethanolic extracts of more than 12 plants were found nontoxic to sheep erythrocytes and nonmutagenic, determined by Ames test using Salmonella typhimurium test strains (TA 97a, TA 100, TA 102 and TA 104). Based on above properties, six plants-Plumbago zeylanica, Hemidesmus indicus, Acorus calamus, Punica granatum, Holarrhena antidysenterica and Delonix regia-were further subjected to fractionation-based study. Ethyl acetate, acetone and methanol fractions of more than six plants indicated that the active phytocompounds were distributed mainly into acetone and ethyl acetate fractions, whereas they were least prevalent in methanol fractions as evident from their antibacterial activity against MDR bacteria. Gram-positive and Gram-negative MDR bacteria are almost equally sensitive to these extracts/fractions, indicating their broad-spectrum nature. However, strain- and plant extract-dependent variations in the antibacterial activity were also evident. Time-kill assay with the most promising plant fraction Plumbago zeylanica (ethyl acetate fraction) demonstrated killing of test bacteria at the level lower than its MIC. Further, identification of active constituents in each fraction and their additive and synergistic interactions are needed to exploit them in evaluating efficacy and safety in vivo against MDR bacteria.