High dilutions of homeopathic remedies induce relaxation of rat aorta precontracted with Noradrenalin

BACKGROUND Homeopathic potencies have been reported to produce alteration of contraction in isolated rat ileum in an organ bath. Potentized homeopathic drugs like Lycopus V and Aurum met are used for the treatment of hypertension. AIM The purpose of this study is to see whether Lycopus V 30 CH and Aurum met 30 CH could produce relaxation of isolated rat aorta in the organ bath. METHODS The aorta of rats were dissected out, placed in Krebs-Henseleit solution, cleared of connective tissue and endothelium and cut into 2-2.5 mm long rings. The rings were fixed in organ baths with the upper end connected by a string to an isometric transducer which was finally attached through a data acquisitation equipment to a computer. Aurum met 30 CH Lycopus V 30 CH, and their medium 90% ethanol were added separately to the bathing fluid containing the aorta rings which were precontracted with noradrenalin (NA). RESULTS Both the drugs produced significant relaxation of the aorta (p

Antispasmodic Effect of Asperidine B, a Pyrrolidine Derivative, through Inhibition of L-Type Ca2+ Channel in Rat Ileal Smooth Muscle

Antispasmodic agents are used for modulating gastrointestinal motility. Several compounds isolated from terrestrial plants have antispasmodic properties. This study aimed to explore the inhibitory effect of the pyrrolidine derivative, asperidine B, isolated from the soil-derived fungus Aspergillus sclerotiorum PSU-RSPG178, on spasmodic activity. Isolated rat ileum was set up in an organ bath. The contractile responses of asperidine B (0.3 to 30 µM) on potassium chloride and acetylcholine-induced contractions were recorded. To investigate its antispasmodic mechanism, CaCl2, acetylcholine, Nω-nitro-l-arginine methyl ester (l-NAME), nifedipine, methylene blue and tetraethylammonium chloride (TEA) were tested in the absence or in the presence of asperidine B. Cumulative concentrations of asperidine B reduced the ileal contraction by ~37%. The calcium chloride and acetylcholine-induced ileal contraction was suppressed by asperidine B. The effects of asperidine B combined with nifedipine, atropine or TEA were similar to those treated with nifedipine, atropine or TEA, respectively. In contrast, in the presence of l-NAME and methylene blue, the antispasmodic effect of asperidine B was unaltered. These results suggest that the antispasmodic property of asperidine B is probably due to the blockage of the L-type Ca2+ channel and is associated with K+ channels and muscarinic receptor, possibly by affecting non-selective cation channels and/or releasing intracellular calcium.

Effects of Steganotaenia Araliacae Root Extract on Contractile Function of Isolated Rat Ileum

Background: Various parts of a small tree, Steganotaenia araliacaeare used as medicine in local traditional settings in Zambia to initiate and augment parturition although very little is documented about its physiological and pharmacological effects. Steganotaenia araliacaecold extract has been observed to cause contractions of uterus in rats but its effect on non-uterine muscle is unclear. The aim of this study was to establish the contractile effect of Steganotaenia araliacaecold extract on isolated rat ileum smooth muscle.Method: Animals were sacrificed by cervical dislocation. Abdominal incisions were made to expose and dissect three ileum segments from each rat. The ileum segments were immediately transferred and mounted in the organ bath containing Tyrode solution. The contractile effects of acetylcholine (a reference agonist) and Steganotaenia araliacaecold extract on ileum segments were investigated starting with the least effective doses, thereafter doubling the doses until maximal tissue response was observed. Antagonists that include atropine, indomethacin, mepyramine, ondansetron and nifedipine in the presence and absence of Steganotaenia araliacaecold extract were also investigated to establish the mechanism of actionResults: Steganotaenia araliacaecold extract increased the contractile force of isolated rat ileum in a dose-response manner but had no significant effects on the frequency of the spontaneous contractions. Pre-treating the tissue with atropine, indomethacin, mepyramine or ondansetron did not inhibit the contractile force of Steganotaenia araliacaecold extract, while pre-treating the tissue with nifedipine inhibited its contractile force by 100% (p<0.05)Conclusion: The cold root extract of Steganotaenia araliacae induced contractions on isolated rat ileum smooth muscle in a dose response manner by probable activation of calcium channels. It is possible that SAEᶜif used in high doses may cause severe abdominal cramps an effect that needs to be noted as it is being used in parturition.

Comparative spasmolytic effect between Cinnamomum tamala and Cinnamomum verum leaf essential oils and eugenol through in vitro and in silico approaches

Cinnamomum tamala and Cinnamomum verum are known for their folk medicinal usage in treating gastrointestinal ailments. The spasmolytic activity of essential oils was studied using isolated rat ileum. The results indicate that C. tamala, despite having a lower content of eugenol (60%), shows a spasmolytic potential of 68.01 ± 2.63% (EC50 = 110.12 ± 13.58 μg/mL) while C. verum with rich eugenol (80%) shows lesser spasmolytic potential (38.96 ± 0.63%) and fails to attain an EC50 value. Upon comparison with standard eugenol’s percentage of spasmolytic (35.68 ± 2.57%), it is evident that the action of these essential oils does not solely rely on the major component but the synergistic role in association with other components of the mixture influences the pharmacological action of the essential oils. In silico docking of phytochemicals of leaf essential oils with M2 (M2AChR) and M3 muscarinic (M3AChR) and nicotinic acetylcholine receptor (nAChR) was carried out to determine the type of receptors through which the essential oils had spasmolytic potential. The binding affinity for eugenol with nAChR shows a better docking score than M2AChR and M3AChR.

Dragon’s Blood Regulates Rac1-WAVE2-Arp2/3 Signaling Pathway to Protect Rat Intestinal Epithelial Barrier Dysfunction Induced by Simulated Microgravity

Dragon’s Blood is a red resin from Dracaena cochinchinensis (Lour.) S.C. Chen (Yunnan, China). As a traditional Chinese medicinal herb, it has shown protective effects on intestinal disorders. Microgravity could alter intestinal homeostasis. However, the potential herbal drugs for preventing intestine epithelial barrier (IEB) dysfunction under microgravity are not available. This study aimed to investigate the effects of Dragon’s Blood (DB) on microgravity-induced IEB injury and explore its underlying mechanism. A rat tail-suspension model was used to simulate microgravity (SMG). Histomorphology, ultrastructure, permeability, and expression of junction proteins in jejunum, ileum, and colon of SMG rats were determined. Proteomic analysis was used to identify differentially expressed proteins (DEPs) in rat ileum mucosa altered by DB. The potential mechanism of DB to protect IEB dysfunction was validated by western blotting. The effects of several components in DB were evaluated in SMG-treated Caco-2 cells. DB protected against IEB disruption by repairing microvilli and crypts, inhibiting inflammatory factors, lowering the permeability and upregulating the expression of tight and adherens junction proteins in the ileum of SMG rats. Proteomic analysis showed that DB regulated 1080 DEPs in rat ileum mucosa. DEPs were significantly annotated in cell–cell adhesion, focal adhesion, and cytoskeleton regulation. DB increased the expression of Rac1-WAVE2-Arp2/3 pathway proteins and F-actin to G-actin ratio, which promoted the formation of focal adhesions. Loureirin C in DB showed a protective effect on epithelial barrier injury in SMG-treated Caco-2 cells. DB could protect against IEB dysfunction induced by SMG, and its mechanism is associated with the formation of focal adhesions mediated by the Rac1-WAVE2-Arp2/3 pathway, which benefits intestinal epithelial cell migration and barrier repair.

Effects of Funchicórea®, a Traditional Brazilian Herbal Complex, on Intestinal Motility in Healthy and Constipated Rodents

Ethnopharmacological Relevance: The traditional herbal medicinal product Funchicórea® has been widely used in clinical practice for the treatment of intestinal colic and constipation in newborns. However, no scientific data on the herbal product to prove its efficacy is available. Aim of the Study: This study aimed to evaluate the laxative and spasmolytic actions of Funchicórea®. Materials and Methods: Wistar rats (Rattus norvegicus) and Swiss mice (Mus musculus) of both sex, were used. In vivo pharmacological assays were performed to evaluate the stimulating effect on the gastrointestinal tract, and in vitro studies to verify its spasmodic activity. Results: Funchicórea® increased the motility of the small intestine in male mice at doses of 100 mg/kg (161.66±14.86 %, n=6) and 200 mg/kg (151.04±17.17 %, n=6) compared to control (100.00±10.49 %, n=6). However, this drug did not induce any change in intestinal transit in female mice. The intestinal transit of male mice treated with loperamide (3 mg/kg/day, during three days) was reduced 66.25±7.49 % (n=8) compared to the control group (100.00±5.16%, n=8) and we observed the normalization of the intestinal transit in constipated animals treated with Funchicórea® 100 mg/Kg (98.42±6.33 %, and 200 mg/kg (99.32±8.47%, n=7). Similar results were observed in the quantification for 24 hours of male and female rats faeces constipated by loperamide (3 mg/kg/day three days), however, in both animals groups treated with Funchicórea® 100 mg/kg (1.24±2.90 g, male; 3.60±0.80 g, female, n=6) and 200 mg/Kg (8.70±2.01 g, male, 10.03±1.30 g, female, n=6) the levels of faeces returned to basal values compared to constipated group (4.01±1.43 g, male; 1.70±0.10 g, female, n=6). In addition, Funchicórea® (0.01-1000 μg/mL) elicited relaxation in rat ileum pre-contracted by KCl 40 mM (Emax=97.5±7.0 %, n=7) and carbachol (1 μM, Emax=100.0±7.0 %, n=7). Conclusion: The results obtained demonstrated that the herbal medicine Funchicórea® acts by stimulating the intestine of rats and mice and has spasmolytic activity in isolated rat ileum.

Restoration of intestinal mucosal in Euphorbia kansui-treated severe acute pancreatitis rats is based on HMGB1/MFG-E8 expression

Background: The pathogenesis of severe acute pancreatitis (SAP) is mediated substantially by dysfunctions in the intestinal barrier. Euphorbia kansui (EK) is a medicinal plant used widely in traditional Chinese medicine to treat inflammation; however, its efficacy and mechanism of action in SAP treatment is not yet well understood. Objective: To investigate the role of EK in intestinal barrier tissue repair and in the pathogenesis and development of SAP. Methods: The rat SAP model was established by a retrograde injection of sodium taurocholate into the pancreatic bile duct. The SAP model group and the SAP + EK treatment groups were divided into 6 subgroups according to timing: 2, 6, 12, 24, 48, or 72 h after inducing SAP. The progression of the SAP rats and of the rats receiving the EK treatment was evaluated using the ascites volume, serum amylase and plasma endotoxin levels, and histological grading of intestinal mucosal damage. In addition, serum inflammatory factor contents were measured using enzyme-linked immunosorbent assay (ELISA) tests and apoptotic cells in damaged ileum tissue were detected using TUNEL staining. Apoptosis markers and other signaling proteins in intestinal mucosal cells were detected by immunohistochemical assays and then validated by combining these data with quantitative polymerase chain reactions and western blotting. Results: Compared with the results of the SAP model rats, the results of the rats that received EK treatment demonstrated that EK could effectively reduce the ascites volume and serum amylase and plasma endotoxin levels. EK treatment also greatly reduced the abnormal intestinal morphological alterations in the rat SAP model and significantly downregulated the serum contents of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. EK treatment inhibited the elevation of capapse-3, inhibited the decrease of the Bcl-2 protein, and decreased the number of apoptotic cells in rat ileum tissue. Finally, EK treatment abrogated the increase of HMGB1 and the suppression of MFG-E8 protein expression in the SAP + EK rat ileum tissue. Conclusion: EK suppresses SAP pathogenesis by restoring intestinal barrier function and modulating the HMGB1/MFG-E8 signaling axis.

Glabridin alleviates ischemia/reperfusion-induced functional failure of smooth muscle of rat ileum by upregulating the cAMP

Despite the development of modern medicine, alternative medicine, which has not lost its timeliness, remains attractive for the treatment of various diseases. Glabridin, a major flavonoid of Glycyrrhiza glabra, is known for its antioxidant and anti-inflammatory activity. The aim of this study was: 1) to determine the possible protective role of glabridin against ischemia/reperfusion (I/R) injury of the intestine; 2) to evaluate the in vitro contractile responses of ileum smooth muscles to acetylcholine after an intestinal I/R; and 3) to explain the underlying molecular mechanism of its effect. Rats were assigned to groups of six rats each; 1) I/R, 2) gla10, 3) gla20, 4) gla40, 5) N5-[imino(nitroamino)methyl]-L-ornithine, methyl ester monohydrochloride (L-NAME)+gla40, and 6) Sham group. The healing effect of glabridin was abolished by L-NAME. Glabridin did not cause contractility of the smooth muscles to acetylcholine-induced contractile responses in intestinal I/R. Yet, it increased to spontaneous basal activity.