Effectiveness of natural biomaterials in the protection and healing of experimentally induced gastric mucosa Ulcer in rats.

BACKGROUND: A gastric ulcer is a painful lesion of the gastric mucosa that can be debilitating or even fatal. The effectiveness of several plant extracts in the therapy of this illness has been demonstrated in traditional pharmacopoeias. AIM: this study was aimed to see if propolis, ginseng in normal or nano form, and amygdalin might help in preventing the ulcerative effects of absolute ethanol. METHODS: Gastroprotective properties of pretreatments before ethanol gavage in rats were compared to omeprazole. The ulcer and stomach parameters (ulcerated regions) were measured (mm2), ulcer inhibition percentage, the stomachs were assessed macroscopically with gastric biopsy histological examinations. RESULTS: Amygdalin, normal and nano ginseng, nano propolis followed by propolis all showed great efficacy in protecting the cyto-architecture and function of the gastric mucosa. The number of ulcerated sites was greatly reduced, and the percentage of stomach protection was increased. Histopathological examination had confirmed great protective effects of the nanoformulations followed by amygdalin. The protection and healing rate was completed to about 100% in all tested materials while ulcer areas were still partially unhealed in normal propolis and omeprazole. Quantitative assay of the m-RNA levels Enothelin 1(ET-1), leukotriene4 (LT-4), and caspase 3(Cas-3) genes and Histamine were done and revealed significant up-regulations in ethanol group and the maximum protective effect was reported with ginseng nano, moreover the histamine content was significantly decreased with nano- formulated extracts. CONCLUSION: Amygdalin and the nanoformulated ginseng and propolis had exhibited a marked protective effect against the ulcerative toxic effects of ethanol.

Natural Anti-inflammatory and Anti-allergy Agents: Herbs and Botanical Ingredients.

Allergies have been known to be an abnormally vigorous immune response in which the immune system fights off an allergen or antigen, initiating mast cells to release histamine into the blood. Substances that prevent mast cells from releasing histamine are considered antiallergic agents. The drugs utilized to treat allergy are mast cell stabilizers, steroids, anti-histamine, leukotriene receptor antagonists, and decongestants. Anti-histamine drugs have side effects such as drowsiness, confusion, constipation, difficulty urinating, blurred vision, etc. The use of medicinal plants for the effective and safe management of diseases has recently received much attention. Various herbs are utilized for their antiallergic and anti-histaminic properties. Some of the herbs useful in the management of allergic diseases of the respiratory tract, like Piper longum, Ocimum tenuiflorum, Solanum xanthocarpum have been discussed. Ample scientific evidence is available for the anti-histaminic and antiallergic activity of Azadirachta indica, Aloe vera, Tinospora cordifolia, and many other such herbs are safer to use as antiallergic agents have been reported. The review summarizes a wide variety of herbs and botanical ingredients with their common scientific names and distribution for easy identification and usage as safe antiallergic agents and discusses their molecular mechanisms involved in combating allergic reactions.

Patho-Pharmacological Research of Anti-allergic Natural Products Targeting Antihistamine-Sensitive and -Insensitive Allergic Mechanisms.

Histamine H1 receptor (H1R) has a special up-regulation mechanism by the stimulation of H1R, mediated by protein kinase C-delta (PKCδ) signaling and H1R gene expression, resulting increase in H1R signaling. Increase in H1R mRNA in nasal mucosa was induced after the provocation of nasal hypersensitivity model rats and suppressed by the pre-treatment of antihistamines. Improvement of nasal symptoms and suppression of H1R mRNA expression in nasal mucosa were also observed by the pre-treatment of antihistamines in pollinosis patients. Elucidation of a correlation between symptoms and H1R mRNA level suggests that H1R gene is an allergic disease (AD)-susceptibility gene, targeted by antihistamines. Similar to antihistamines, pre-treatment of Kujin extract, an anti-allergic Kampo medicine improved nasal symptoms and suppressed H1R mRNA expression in nasal hypersensitivity model rats. (-)-Maackiain targeting heat shock protein 90 (Hsp90) was isolated as an inhibitor of PKCδ signaling-mediated H1R gene expression from Kujin extract. In addition to H1R-mediated activation of H1R gene expression as the first mechanism, nuclear factor of activated T-cells (NFAT)-mediated IL-9 gene expression is suggested to participate to allergic symptoms as the second mechanism insensitive to antihistamines. Pyrogallol and proanthocyanidin suppressing IL-9 gene expression were discovered from Awa-tea and lotus root knots, respectively. Combination therapy using medicines suppressing both H1R gene expression and IL-9 gene expression is promising for outstanding alleviation of AD. Multifactorial diseases involving H1R gene expression may be treated by the combination therapy with antihistamine and complementary drugs, and diseases involving PKCδ signaling may be treated by drugs targeting Hsp90.

Gastroprotective and ulcer healing effects of hydroethanolic extract of leaves of Caryocar coriaceum: Mechanisms involved in the gastroprotective activity.

This work aimed to determine the chemical fingerprint of hydroethanolic extract of leaves of Caryocar coriaceum (HELCC) and the gastroprotective activity. The chemical fingerprint of HELCC was analyzed by HPLC-DAD, to quantify total phenols and flavonoids were carried out by Folin-Ciocalteu reagent and aluminum chloride assay, while in vitro antioxidant activity was evaluated by the DPPH method. The methods used to determine pharmacological activity were: gastroprotective screening test in classical models of induced acute and chronic gastric lesions and physical barrier test. Further assays were performed to demonstrate the involvement of NO, prostaglandins, ATP-dependent potassium channels, TRPV, noradrenergic α2 receptors, histamines, and opioids. The DPPH method demonstrated the antioxidant activity of the extract, in vitro, explained by the presence of polyphenols and flavonoids. Oral administration of the extract, previously dissolved in deionized water, at a dose of 100 mg/kg decreased the lesions induced by indomethacin, acidified ethanol, ethanol and acetic acid by 75.0, 72.8, 69.4 and 86.2% respectively. It was demonstrated that opioid receptors, α2-adrenergic receptors and primary afferent neurons sensitive to capsaicin were involved in the mechanism of gastric protection, in addition to the contribution of NO and prostaglandins. The results show that extract is a promising candidate for the treatment of gastric ulcers.

Survey of immuno-allergological ultra high dilution research.

BACKGROUND: Experiments about basic research in Immuno-allergology reported by M. Bastide and B. Poitevin in Ultra High Dilution (1994) have been appraised from a 20 year perspective. The numerous experiments published mainly focus on immunological regulation, inflammatory process and basophil activation. They are analyzed according to one essential criterion: repeatability. METHODS: The commentary reflects the research details made available in a recently published literature review, also published in French. RESULTS: The regulatory effect of high dilution of bursin on immune response has been observed in multiple experiments but not reproduced by independent teams. The immunomodulating effect of Thymulin has been confirmed in mice. Rhus toxicodendron has an anti-inflammatory activity on different models, from mother tincture (TM) to very high dilutions. The homeopathic complex Canova activates macrophages in vitro and in vivo, induces lymphocyte proliferation, and reduces the size of tumors and mortality of sarcoma-bearing mice. Some homeopathic medicines used in clinical inflammation modulate in vitro the neutrophil activation, with variability in the protocols used and in the medicines tested. In allergology, high dilution histamine has an inhibitory effect on basophil activation in multicenter trials and with independent teams, either with methods implying a change in basophil staining or with flow cytometry. However, high dilution histamine had no effect in some well-conducted experiments. The inhibitory effect of Apis mellifica has not been studied with the flow cytometry method, as well as the activation of basophil by anti-IgE high dilution, published in Nature. CONCLUSIONS: Despite considerable research activity in immuno-allergology and a great increase in the number of publications, there is still not in this domain a "gold standard" trial in basic research in homeopathy. The most studied system, the inhibitory effect of histamine high dilutions on basophil activation, requires clarifications of various factors, including individual sensitivity. For scientific and epistemological reasons, the same work should be carried out for independent reproduction of the experiments conducted with anti-IgE and Apis mel high dilution, in complement of the new axes of research in immunoallergology developed since 20 years.

TPI 1020, a novel anti-inflammatory, nitric oxide donating compound, potentiates the bronchodilator effects of salbutamol in conscious guinea-pigs.

Inhaled corticosteroids are regularly co-administered with beta(2)-adrenoceptor agonists. This study evaluates in conscious guinea-pigs the bronchodilator effect, alone or combined with salbutamol, of TPI 1020, a novel anti-inflammatory corticosteroid and nitric oxide (NO) donor derived from budesonide. Guinea-pigs received inhaled histamine (3 mM) and specific airway conductance (sG(aw)) measured. Responses to histamine were measured before and on the next day 15 min after a 15 min inhalation of vehicle, salbutamol, TPI 1020, budesonide, the NO-donor, S-nitroso-N-acetylpenicillamine (SNAP), or combinations of these drugs. Salbutamol and TPI 1020 caused concentration-dependent bronchodilatation measured as inhibition of histamine-induced bronchoconstriction. TPI 1020-induced bronchodilatation was blocked by the guanylyl cyclise inhibitor, ODQ, indicating cGMP-dependence through released NO. While salbutamol at 80 microM did not exert significant bronchodilatation, significant inhibitions were observed when co-administered with TPI 1020, 0.11 and 0.33 mM. The combined effects of TPI 1020 and salbutamol lasted significantly longer than either drug alone. Inhaled budesonide was a weak bronchodilator and when co-administered with salbutamol there was enhanced bronchodilatation. Addition of the NO-donor, SNAP (0.1 mM), to the budesonide/salbutamol combination, also improved the inhibition of histamine-induced bronchoconstriction. This study has shown that TPI 1020 potentiates the bronchodilator activity of salbutamol, and their combination lasted longer than either drug administered individually. Both the corticosteroid and NO-releasing activities of TPI 1020 appear to be required for the potentiation of salbutamol. Combination of TPI 1020 with a beta(2)-adrenoceptor agonist may therefore be useful against acute bronchoconstriction episodes in asthma, and may offer an opportunity for reducing doses of inhaled beta(2)-adrenoceptor agonists.

Estudo da participação dos receptores histaminérgicos centrais dos tipos H1 e H2 no controle da ingestão de água / Study of participation of central histaminergic types H1 and H2 in the control of water intake

Diferentes grupos de pesquisa têm se dedicado à investigação dos mecanismos cerebrais de controle da sede. O avanço neste campo da Neurociência tem trazido importantes contribuições para a compreensão da regulação da homeostasia hidrossalina, o que pode levar a futuras aplicações clínicas. Desde a década de 1950 tem sido sugerido que a histamina pode atuar como neuromodulador/neurotransmissor no sistema nervoso central, entretanto sua função ainda não é clara, especialmente no que concerne ao controle da homeostasia hidrossalina. Assim o objetivo do presente trabalho foi investigar o papel das vias histaminérgicas centrais no controle da ingestão hídrica e ingestão de água pós-prandial. Foram utilizados quatro modelos de estudo: ingestão hídrica em animais normoidratados, em animais desidratados por privação hídrica e por sobrecarga de sódio e pós-prandial. No primeiro grupo ratos normoidratados receberam microinjeções bilaterais no núcleo ventromedial hipotalâmico (VMH), de HTMT, agonista específico para os receptores histaminérgicos do tipo H1, nas doses de 100 e 200 nmol e dimaprite agonista para os receptores H2 na dose de 100 nmol. No segundo grupo, animais em privação hídrica por 14 horas "overnight" foram injetados no VMH com mepiramine, antagonista dos receptores histaminérgicos H1, e cimetidine, antagonista específico para os receptores H2 nas doses de 100 e 200 nmol. No terceiro grupo foi realizado em animais sob desidratação osmótica induzida por sobrecarga da salina hipertônica (solução salina 9% num volume de 10% do peso corporal). Nesses três grupos o volume ingerido pelos animais foi monitorado a cada 15 minutos durante 2 horas. No quarto grupo as 18:00 horas foram aplicadas microinjeçóes de mepiramine e cimetidine na dose de 200 nmol para a investigação da ingestão hídrica pós-prandial. A ingestão alimentar e o volume hídrico ingeridos deste grupo foram monitorados a cada 30 minutos durante as primeiras 4 horas do período noturno e ao fim deste período (6:00 h)...

Effects of Azadirachta indica extract on gastric ulceration and acid secretion in rats.

The effect of Azadirachta indica extract on gastric ulceration was studied in albino rats. Azadirachta indica extract (100-800 mg/kg p.o., 100-25 mg/kg i.p.) significantly inhibited gastric ulceration induced by indomethacin (40 mg/kg). Administration of 800 mg/kg p.o. and 250 mg/kg i.p. caused 100% cytoprotection against indomethacin (40mg/kg, i.p.)-induced gastric ulceration. This action was accompanied by a dose-dependent decrease in total gastric acidity. In order to investigate the probable mechanism of Azadirachta indica antiulcer activity, the effect of the extract alone and in combination with histamine (1mg/kg) and cimetidine (0.12 mg/kg) on gastric acid secretion in situ was studied. Azadirachta indica (250 mg/kg) significantly inhibited the basal and histamine-induced gastric acid secretion. Cimetidine seemed to augment Azadirachta indica inhibition of gastric acid secretion. The results suggest that the stem bark extract of Azadirachta indica possesses antiulcer agents, which probably act via histamine H(2) receptor.

Induction of prolonged tenderness in patients with tension-type headache by means of a new experimental model of myofascial pain.

Tenderness is the most prominent abnormal finding in patients with tension-type headache (TTH). Recently we developed a model of myofascial tenderness using intramuscular infusion of a combination of bradykinin, serotonin, histamine and prostaglandin E2. We aimed to examine tenderness after this combination in patients with episodic TTH (ETTH). Fifteen patients and 15 healthy controls completed the study. Participants received the combination into the non-dominant trapezius muscle in a randomized, double-blinded and placebo-controlled design. Local tenderness and stimulus-response functions, mechanical pain thresholds (PPDT) in the temporal region and on the finger, and total tenderness score (TTS) were recorded. A local, prolonged, and mild to moderate tenderness was reported both in patients (P = 0.001) and in controls (P = 0.001) after the combination compared with the placebo. The response to the combination tended to be increased in patients. The stimulus-response function was leftward shifted after the combination, compared with baseline in both groups. No changes in PPDT or TTS were found after the infusions, whereas baseline PPDTs were decreased in ETTH compared with controls (PPDTfinger: P = 0.033; PPDTtemporal: P = 0.015). Intramuscular infusion of a combination of endogenous substances induced prolonged tenderness in both patients with episodic TTH and healthy subjects. The present results suggest an increased excitability of peripheral muscle afferents in TTH.

[Hepatoprotective effects of gamma-L-glutamylhistamine]. / Gepatoprotektornaia aktivnost' gamma-L-glutamilgistamina.

The influence of gamma-GluHA and glutarylhistamine on the lipid peroxidation, cholesterol, phospholipid and liver aminotransferase activity was investigated using carbon tetrachloride-induced model of subacute liver damage. Pretreatment of rats with gamma-GluHA and glutarylhistamine prevented liver necrosis and normalized activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in blood plasma, lipid peroxidation in the liver and plasma, lipid profiles and cholesterol content in the liver and plasma.

Systemic administration of histamine reduces reovirus type 2-induced insulitis in suckling DBA/1 mice.

Previously we suggested that reovirus type 2 (Reo-2) infection induced autoimmune insulitis, resulting in mild diabetes in suckling mice. The effect of histamine (a lymphocyte function suppressor) on Reo-2-induced insulitis was examined. Systemic histamine administration reduced the development of insulitis and blood glucose elevation. Endogenous interleukin-2 (IL-2) activity by splenic cells and the production of antibodies to pancreatic islet cells were reduced by histamine treatment. In addition, histamine treatment increased cyclic adenosine monophosphate (cAMP) concentrations in the plasma. These results further suggest that the insulitis seen in Reo-2 infection in suckling mice is induced by an immune reaction.

Transdermal histamine in multiple sclerosis: part one -- clinical experience.

Histamine has a long history of therapeutic use in many diseases, including multiple sclerosis (MS). Recently, transdermal histamine has been successfully employed for the amelioration of symptoms of both relapsing-remitting and progressive multiple sclerosis. This paper summarizes preliminary experiences with transdermal histamine for MS at the Tahoma Clinic: 67 percent of 55 patients using histamine transdermal cream had improvements in one or more areas, including extremity strength, balance, bladder control, fatigue, activities of daily living, and cognitive functioning, sustained for periods of up to three months. One-third of patients had improvements in three or more areas of functioning. Five possible mechanisms of action are postulated: augmentation of subnormal cerebral tissue levels of histamine; improved electrical function of demyelinated fibers; increased cerebral blood flow; suppression of autoimmune responses; and stimulation of remyelination. These will be discussed in detail in Part 2 of this article.

A randomized equivalence trial comparing the efficacy and safety of Luffa comp.-Heel nasal spray with cromolyn sodium spray in the treatment of seasonal allergic rhinitis.

BACKGROUND: The objective of the clinical study was to investigate the efficacy and tolerance of a homeopathic nasal spray in cases of hay fever (seasonal allergic rhinitis) in comparison with the conventional intranasal cromolyn sodium therapy. PATIENTS AND METHODS: In total, 146 outpatients with symptoms of hay fever were enrolled into the clinical study (randomized, double-blind, equivalence trial) (time of treatment: 42 days). The homeopathic remedy (Luffa comp.-Heel trade mark Nasal Spray, dosage: 0.14 ml per application, 4 times per a day / naris) consisted of a fixed combination made up of Luffa operculata, Galphimia glauca, histamine, and sulfur. The main outcome measure of the efficacy was the quality of life as measured by means of the Rhinoconjunctivitis Quality of Life-Questionnaire (RQLQ). The tolerance of the trial medication was registered by means of global assessment, rhinoscopy, recording of adverse events and with the aid of vital and laboratory parameters. RESULTS: The results of the study demonstrate a quick and lasting effect of the treatment. This effect was independent from the medication applied and produced a nearly complete remission of the hay fever symptoms. The RQLQ global score changed significantly in the course of the treatment, indicating therapeutic equivalence between the two forms of treatment. Adverse systemic effects did not occur. Local adverse events appeared in 3 patients. CONCLUSIONS: The study proved that, for the treatment of hay fever, the homeopathic nasal spray is as efficient and well tolerable as the conventional therapy with cromolyn sodium.