Evaluation of Anti-Ulcer activity of Tephrosia purpurea Linn Pers Leaf Extract in Wistar Rats

India is known for its traditional medicinal system – Ayurveda, Siddha and Unani. There are several references in our ancient literature about the miraculous curing properties of the plant-based drugs. “Rig Veda and Atharva veda” seems to be the earliest record of use of plant in the medicine. A stomach ulcer involves an erosion in a person’s gastrointestinal tract. ‘Peptic’ is derived from Greek word “Peptikos” who’s meaning is related to digestion. Peptic ulcer occurs in the part of the gastrointestinal track which is exposed to gastric acid and pepsin (i.e) the stomach and duodenum. The extract of Tephrosia purpurea flowers against viruses and is very good antibacterial against Gram +ve and Gram -ve strain. The Plant extract was prepared and the phytochemical analysis was performed. The extract was administered with animals. The drug were administered orally once daily for 2 days and 45 min prior to pyloric ligation. The animals are sacrificed after four hours of pylorus ligation. The result indicates that, Flavonoids and Tannins have shown to be present in the TPAL treated groups. Since flavanoids antagonize aggressive factor which play a decisive role in the pathogenesis of gastric lesion and also enhance defence factor to protect the gastric mucosa from injury. Flavanoids diminish histamine secretion from mast cell by inhibition of histidine decarboxylase and stimulate PG biosynthesis. So the antiulcer activity of TPAL may be attributed to its flavonoid content. The study concluded that TPAL has an anti ulcer activity which may be due to protection and the strengthening of the mucosal defensive factor like mucus, bicarbonate, prostaglandin.

Nimesulide Mechanism of Action: Focus on Histamine

Objective of the Review: To analyse available information on the nimesulide mechanism of action, namely of recent studies of COXindependent effects of nimesulide, affecting primarily histamine-mediated reactions. Key Points. Fast and lasting anti-inflammatory and analgetic effects of nimesulide are a result of a number of actions not associated with cyclooxygenase 2 inhibition. Of utmost interest are effects associated with suppression of immune and non-immune histamine secretion. Conclusion. An interesting effect of nimesulide is an impact on histamine secretion; it explains more pronounced analgetic and anti-inflammatory effect of nimesulide and a low risk of respiratory and GIT side effects. Keywords: nonsteroidal anti-inflammatory drugs, cyclooxygenase, histamine, nimesulide.

Effects ofAngelica gigasNakai as an Anti-Inflammatory Agent inIn VitroandIn VivoAtopic Dermatitis Models

We investigated the cellular and molecular mechanisms mediating the effects ofAngelica gigasNakai extract (AGNE) through the mitogen-activated protein kinases (MAPKs)/NF-κB pathway usingin vitroandin vivoatopic dermatitis (AD) models. We examined the effects of AGNE on the expression of proinflammatory cytokines and chemokines in human mast cell line-1 (HMC-1) cells. Compound 48/80-induced pruritus and 2,4-dinitrochlorobenzene- (DNCB-) induced AD-like skin lesion mouse models were also used to investigate the antiallergic effects of AGNE. AGNE reduced histamine secretion, production of proinflammatory cytokines including interleukin- (IL-) 1β, IL-4, IL-6, IL-8, and IL-10, and expression of cyclooxygenase- (COX-) 2 in HMC-1 cells. Scratching behavior and DNCB-induced AD-like skin lesions were also attenuated by AGNE administration through the reduction of serum IgE, histamine, tumor necrosis factor-α(TNF-α), IL-6 levels, and COX-2 expression in skin tissue from mouse models. Furthermore, these inhibitory effects were mediated by the blockade of the MAPKs and NF-κB pathway. The findings of this study proved that AGNE improves the scratching behavior and atopy symptoms and reduces the activity of various atopy-related mediators in HMC-1 cells and mice model. These results suggest the AGNE has a therapeutic potential in anti-AD.

Knockout of histidine decarboxylase decreases bile duct ligation-induced biliary hyperplasia via downregulation of the histidine decarboxylase/VEGF axis through PKA-ERK1/2 signaling

Histidine is converted to histamine by histidine decarboxylase (HDC). We have shown that cholangiocytes 1) express HDC, 2) secrete histamine, and 3) proliferate after histamine treatment via ERK1/2 signaling. In bile duct-ligated (BDL) rodents, there is enhanced biliary hyperplasia, HDC expression, and histamine secretion. This studied aimed to demonstrate that knockdown of HDC inhibits biliary proliferation via downregulation of PKA/ERK1/2 signaling. HDC−/− mice and matching wild-type (WT) were subjected to sham or BDL. After 1 wk, serum, liver blocks, and cholangiocytes were collected. Immunohistochemistry was performed for 1) hematoxylin and eosin, 2) intrahepatic bile duct mass (IBDM) by cytokeratin-19, and 3) HDC biliary expression. We measured serum and cholangiocyte histamine levels by enzyme immunoassay. In total liver or cholangiocytes, we studied: 1) HDC and VEGF/HIF-1α expression and 2) PCNA and PKA/ERK1/2 protein expression. In vitro, cholangiocytes were stably transfected with shRNA-HDC plasmids (or control). After transfection we evaluated pPKA, pERK1/2, and cholangiocyte proliferation by immunoblots and MTT assay. In BDL HDC−/− mice, there was decreased IBDM, PCNA, VEGF, and HDC expression compared with BDL WT mice. Histamine levels were decreased in BDL HDC−/−. BDL HDC−/− livers were void of necrosis and inflammation compared with BDL WT. PKA/ERK1/2 protein expression (increased in WT BDL) was lower in BDL HDC−/− cholangiocytes. In vitro, knockdown of HDC decreased proliferation and protein expression of PKA/ERK1/2 compared with control. In conclusion, loss of HDC decreases BDL-induced biliary mass and VEGF/HIF-1α expression via PKA/ERK1/2 signaling. Our data suggest that HDC is a key regulator of biliary proliferation.

H. pyloriacutely inhibits gastric secretion by activating CGRP sensory neurons coupled to stimulation of somatostatin and inhibition of histamine secretion

Acute Helicobacter pylori infection produces hypochlorhydria. The decrease in acid facilitates survival of the bacterium and its colonization of the stomach. The present study was designed to identify the pathways in oxyntic mucosa by which acute H. pylori infection inhibits acid secretion. In rat fundic sheets in an Ussing chamber, perfusion of the luminal surface with H. pylori in spent broth (103–108cfu/ml) or spent broth alone (1:105to 1:100final dilution) caused a concentration-dependent increase in somatostatin (SST; maximal: 200 ± 20 and 194 ± 9% above basal; P < 0.001) and decrease in histamine secretion (maximal: 45 ± 5 and 48 ± 2% below basal; P < 0.001); the latter was abolished by SST antibody, implying that changes in histamine secretion reflected changes in SST secretion. Both responses were abolished by the axonal blocker tetrodotoxin (TTX), the sensory neurotoxin capsaicin, or the CGRP antagonist CGRP8-37, implying that the reciprocal changes in SST and histamine secretion were due to release of CGRP from sensory neurons. In isolated rabbit oxyntic glands, H. pylori inhibited basal and histamine-stimulated acid secretion in a concentration-dependent manner; the responses were not affected by TTX or SST antibody, implying that H. pylori can directly inhibit parietal cell function. In conclusion, acute administration of H. pylori is capable of inhibiting acid secretion directly as well as indirectly by activating intramural CGRP sensory neurons coupled to stimulation of SST and inhibition of histamine secretion. Activation of neural pathways provides one explanation as to how initial patchy colonization of the superficial gastric mucosa by H. pylori can acutely inhibit acid secretion.