Eye Diseases: When the Solution Comes from Plant Alkaloids.

Plants are an incredible source of metabolites showing a wide range of biological activities. Among these, there are the alkaloids, which have been exploited for medical purposes since ancient times. Nowadays, many plant-derived alkaloids are the main components of drugs used as therapy for different human diseases. This review deals with providing an overview of the alkaloids used to treat eye diseases, describing the historical outline, the plants from which they are extracted, and the clinical and molecular data supporting their therapeutic activity. Among the different alkaloids that have found application in medicine so far, atropine and pilocarpine are the most characterized ones. Conversely, caffeine and berberine have been proposed for the treatment of different eye disorders, but further studies are still necessary to fully understand their clinical value. Lastly, the alkaloid used for managing hypertension, reserpine, has been recently identified as a potential drug for ameliorating retinal disorders. Other important aspects discussed in this review are different solutions for alkaloid production. Given that the industrial production of many of the plant-derived alkaloids still relies on extraction from plants, and the chemical synthesis can be highly expensive and poorly efficient, alternative methods need to be found. Biotechnologies offer a multitude of possibilities to overcome these issues, spanning from genetic engineering to synthetic biology for microorganisms and bioreactors for plant cell cultures. However, further efforts are needed to completely satisfy the pharmaceutical demand.

Evaluation and estimation of diuretic activity of the linalyl acetate in the rats.

This study aimed to explore the diuretic activity of linalyl acetate (LA). LA is an essential oil, it is an integral phyto-constituent of various plants. In this study, acute and chronic diuretic activities were explored by measuring the levels of different electrolytes and pH in the urine of experimental rats. Rats were divided into five groups. The control group was given 10 mg/kg normal saline, the treated group was given 10 mg/kg furosemide, and the remaining 3 groups received different doses of LA including 25, 50, and 75 mg/kg through intraperitoneal route, to determine its diuretic potential. Urine volume for acute diuretic activity was measured for 6 hours however for chronic diuretic activity was measured for 6 days. For a comparative study of LA with a control group and treated group with reference drug, diuretic index was used. Moreover, the underlying mechanism of the diuretic activity was also explored by comparing atropine, L-NAME, and indomethacin. The results of each group with 6 rats in each group were obtained by ± standard error of the mean of every group. Analysis of Variance (ANOVA) was used for statistical analysis. Results revealed that the LA 75 mg/kg dose showed comparable results as of furosemide. Moreover, this study revealed the involvement of muscarinic receptors to produce diuresis in comparison with atropine with very little involvement of prostanoids and no effect on NO pathway induced by indomethacin and L-NAME respectively. It is concluded that LA possess anti-diuretic potential. Muscarinic receptors might be involved in producing diuretic effects.

Supplemental treatment to atropine improves the efficacy to reverse nerve agent induced bronchoconstriction.

Exposure to highly toxic organophosphorus compounds causes inhibition of the enzyme acetylcholinesterase resulting in a cholinergic toxidrome and innervation of receptors in the neuromuscular junction may cause life-threatening respiratory effects. The involvement of several receptor systems was therefore examined for their impact on bronchoconstriction using an ex vivo rat precision-cut lung slice (PCLS) model. The ability to recover airways with therapeutics following nerve agent exposure was determined by quantitative analyses of muscle contraction. PCLS exposed to nicotine resulted in a dose-dependent bronchoconstriction. The neuromuscular nicotinic antagonist tubocurarine counteracted the nicotine-induced bronchoconstriction but not the ganglion blocker mecamylamine or the common muscarinic antagonist atropine. Correspondingly, atropine demonstrated a significant airway relaxation following ACh-exposure while tubocurarine did not. Atropine, the M3 muscarinic receptor antagonist 4-DAMP, tubocurarine, the ß2-adrenergic receptor agonist formoterol, the Na+-channel blocker tetrodotoxin and the K+ATP-channel opener cromakalim all significantly decreased airway contractions induced by electric field stimulation. Following VX-exposure, treatment with atropine and the Ca2+-channel blocker magnesium sulfate resulted in significant airway relaxation. Formoterol, cromakalim and magnesium sulfate administered in combinations with atropine demonstrated an additive effect. In conclusion, the present study demonstrated improved airway function following nerve agent exposure by adjunct treatment to the standard therapy of atropine.

Evaluation of phytochemical, anti-oxidant and cardiac depressant effect of Rumex dentatus by using Langendorff's isolated heart apparatus.

Rumex dentatus has been used traditionally for ailment of cardiovascular diseases. The aim of the present study was to assess cardiovascular effects in isolated perfused rabbit heart. Aqueous and n-butanolic fractions were assessed for their effect on perfusion pressure (PP), force of contraction (FC) and heart rate (HR) of rabbit heart using Langendorff's method. The possible mechanisms of action of extracts/fraction were assessed with and without application of different agonist/antagonist. Phytochemical, toxicity and anti-oxidant activities were also determined. Both extracts at 1mg/mL dose produced a highly significant decrease in FC and HR but PP remained unchanged. Moreover, aqueous fraction of Rumex dentatus at 0.001mg/mL dose produced a highly significant decrease in FC and HR but no significant change in PP was observed. Atropine 10-5 M did not inhibit the cardiac depressant response of both fractions. Furthermore, both fractions blocked the positive ionotropic and chronotropic effects of adrenaline and calcium chloride. Phytochemical studies have shown the presence of some phytochemicals. Acute and sub-chronic toxicity studies demonstrated that test extracts are safe and produced no significant changes in haematological and biochemical parameters. Crude extract showed significant antioxidant activity like ascorbic acid. This study revealed that this plant have good cardiac depressant effect.

Ketamine and xylazine effects in murine model of acute pancreatitis.

Ketamine and xylazine (Ket/Xyl) are anesthetic agents that target neural pathways and are commonly used in combination in mouse studies. Since neural pathways can modulate acute pancreatitis severity, we asked if Ket/Xyl affect disease severity. C57BL/6 mice were treated with six hourly injections of cerulein to induce mild acute pancreatitis. Mice were also treated with and without ketamine, xylazine, and Ket/Xyl before pancreatitis induction in vivo and in vitro. Ket/Xyl pretreatment in vivo increased selected parameters of pancreatitis severity such as trypsin activity and edema; these effects were predominantly mediated by xylazine. Ket/Xyl also changed markers of autophagy. These in vivo effects of Ket/Xyl were not attenuated by atropine. The drugs had no little to no effect on pancreatitis responses in isolated pancreatic cells or lobules. These findings suggest that Ket/Xyl administration can have substantial effect on acute pancreatitis outcomes through nonmuscarinic neural pathways. Given widespread use of this anesthetic combination in experimental animal models, future studies of inflammation and injury using Ket/Xyl should be interpreted with caution.NEW & NOTEWORTHY Ketamine and xylazine anesthetic agent administration before acute pancreatitis induction in mice lead to changes in pancreatitis responses independent of acute pancreatitis induction. Future studies should consider the potential effects of anesthesia administration when studying disease processes associated with inflammation and injury.

Efficacy of atropine and scopolamine on airway contractions following exposure to the nerve agent VX.

Nerve agents are highly toxic organophosphorus compounds that inhibit acetylcholinesterase resulting in rapid accumulation of the neurotransmitter acetylcholine (ACh) causing a cholinergic syndrome including respiratory failure. In the present study, respiratory responses and antimuscarinic treatment efficacy was evaluated ex vivo using rat precision-cut lung slices (PCLS) exposed to the nerve agent VX. The respiratory effects were evaluated either by adding exogenous ACh directly to the culture medium or by applying electric-field stimulation (EFS) to the PCLS to achieve a release of endogenous ACh from neurons in the lung tissue. The airway contraction induced by both methods was enhanced by VX and resulted in lingering airway recovery, in particular when airways were exposed to a high VX-dose. Both contractions induced by EFS and exogenously added ACh were significantly reduced by administration of the antimuscarinic drugs atropine or scopolamine. Two additions of atropine or scopolamine after maximal ACh-induced airway response was demonstrated effective to reverse the contraction. By adding consecutive doubled doses of antimuscarinics, high efficiency to reduce the cholinergic airway response was observed. However, the airways were not completely recovered by atropine or scopolamine, indicating that non-muscarinic mechanisms were involved in the smooth muscle contractions. In conclusion, it was demonstrated that antimuscarinic treatment reversed airway contraction induced by VX but supplemental pharmacological interventions are needed to fully recover the airways. Further studies should therefore clarify the mechanisms of physiological responses in lung tissue following nerve agent exposures to improve the medical management of poisoned individuals.

Anti-Nociceptive and Anti-Inflammatory Effects of Stem Bark Extract of Ficus Capensis Thunb (Moraceae) by Bioactivity Fractionation.

OBJECTIVE: This study investigated the antinociceptive and anti-inflammatory activities of the aqueous extract of Ficus capensis (AEFC) by bio-guided fractionation. METHODS: The anti-nociceptive and anti-inflammatory effects of AEFC (250, 500, 1000 mg/kg, i.p) were assessed using acetic acid-induced writhing, hot plate, tail-flick, formalin tests, and carrageenan- induced paw edema, respectively. The AEFC was fractionated base on polarity difference into butanol, ethyl acetate, and n-hexane fractions. The fractions (500 mg/kg) obtained were subjected to the same experimental procedures mentioned above. The EAF, which exerted the most productive activities, was further subjected to fractionation procedures that yielded six fractions (labeled CF1-CF6). These fractions (200 mg/kg) were tested for potential antinociceptive and anti-inflammatory activities. Notable antagonists (Naloxone and atropine) of the nociceptive pathway were used to evaluate the mechanism of the antinociceptive action of F. capensis. RESULTS AND DISCUSSION: The AEFC, BF, EAF, and CF4 caused a significant (p<0.05) reduction in the number of abdominal writhes, an increase in reaction time against the hot plate, tail-flick tests, and a significant (p<0.05) inhibition in both phases of formalin test. The AEFC, BF, EAF, CF4, and CF6 caused a significant (p<0.05) inhibition of paw edema development due to carrageenan. Atropine significantly reversed the antinociceptive effect of CF4 in both phases of the formalin test. The results obtained revealed that CF4 produced central and peripheral antinociceptive effects, while CF6 is peripherally mediated. CONCLUSION: The results support the traditional uses of F. capensis in the treatment of various diseases associated with pain and inflammation. The column fraction CF4 exhibited muscarinic receptor- mediated antinociceptive activity.

Acetylcholine acts on songbird premotor circuitry to invigorate vocal output.

Acetylcholine is well-understood to enhance cortical sensory responses and perceptual sensitivity in aroused or attentive states. Yet little is known about cholinergic influences on motor cortical regions. Here we use the quantifiable nature of birdsong to investigate how acetylcholine modulates the cortical (pallial) premotor nucleus HVC and shapes vocal output. We found that dialyzing the cholinergic agonist carbachol into HVC increased the pitch, amplitude, tempo and stereotypy of song, similar to the natural invigoration of song that occurs when males direct their songs to females. These carbachol-induced effects were associated with increased neural activity in HVC and occurred independently of basal ganglia circuitry. Moreover, we discovered that the normal invigoration of female-directed song was also accompanied by increased HVC activity and was attenuated by blocking muscarinic acetylcholine receptors. These results indicate that, analogous to its influence on sensory systems, acetylcholine can act directly on cortical premotor circuitry to adaptively shape behavior.

Phytochemical analysis and reappraisal of diuretic activity of Delphinium brunonianum Royle and its mode of action in experimental rats.

The aim of this study was the evaluation of diuretic potential of Delphinium brunonianum. Acute diuretic effect in rats was evaluated 8 h after administration of various doses of crude extract, fractions and hydrochlorthiazide. While, prolonged effect of butanolic fraction was assessed after 7days of oral administration in rats. Thereafter, involvement of different pathways in diuretic activity was also appraised. Furthermore, polyphenolic contents in butanolic fraction were assessed using HPLC/UV-VIS technique. All doses of extract and fractions induced a prominent increase in urine and Na+ excretion with no effect on excretion of K+. Prior administration of indomethacin and atropine considerably avoided the diuretic effect of butanolic fraction. Regarding the quantitative chemical analysis the polyphenolic contents were recorded as 28.78 µg/mg. Thus results of present investigation suggested that Delphinium brunonianum possess remarkable diuretic potential.

Elucidation of the possible mechanism of analgesic action of methanol stem bark extract of Uapaca togoensis pax in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Uapaca togoensis is a medicinal plant used traditionally in Africa for the treatment of rheumatism, epilepsy, cough, pneumonia, vomitting and fever. Previously, the analgesic activity of its methanol stem bark extract has been scientifically demonstrated. However, the mechanism responsible for this activity remains to be investigated. AIM OF THE STUDY: To elucidate the possible mechanism(s) through which the methanol stem bark extract of Uapaca togoensis (MEUT) exhibits analgesic activity in mice. MATERIALS AND METHODS: Analgesic activity of MEUT was evaluated using acetic acid-induced abdominal writhing test in mice at doses of 250, 500 and 1000 mg/kg orally. For the mechanistic studies, mice were pre-treated with Naloxone (2 mg/kg), Atropine (1 mg/kg), Yohimbine (1 mg/kg), Glibenclamide (10 mg/kg), Prazosin (1 mg/kg) and Yohimbine (1 mg/kg) 15 min prior to MEUT (1000 mg/kg) administration, then assessed using AAWT 1 h later. Data was analysed using One way Anova followed by Bonferroni post hoc test. RESULTS: The extract (at the doses of 250, 500 and 1000 mg/kg) and morphine (10 mg/kg) significantly (p < 0.05) decreased the number of abdominal writhes. Naloxone (opioid receptor antagonist), Atropine (muscarinic receptor antagonist) and Glibenclamide (ATP-sensitive K+ channel blocker) significantly (p < 0.05) reversed the analgesic effect of MEUT. On the other hand, Prazosin and Yohimbine (α1 and α2 receptor antagonists respectively) had no effect on the analgesic action of MEUT. CONCLUSION: The results obtained from this study suggests the possible involvement of opioidergic, cholinergic and sensitive potassium ATP channel pathways in the analgesic activity of the methanol stem bark extract of Uapaca togoensis.

Ex-vivo abortifacient activity of Androsace foliosa n-hexane leaves extract on isolated rabbit uterus.

Androsace foliosa is a medicinal herb utilized in different areas of Pakistan for abortifacient, diabetic and liver complications. In the current research, the possible action of the n-hexane leaves extract of the Androsace foliosa on isolated rabbit uterus was examined. Abortifacient activity was examined in the existence of standard antagonist e.g. atropine and salbutamol and a uterine tonic like oxytocin. The isolated rabbit uterus is initially treated with 1mg/kg stilboesterol for 1 complete day. The consequence of oxytocin as uterine contraction agonist was observed. Additionally, antagonists e.g. salbutamol (2µg) and atropine (1-2mg) on the uterine contractile action of the extract were also examined. The A. foliosa n-hexane leaves extract fashion dose correlated amplification in the force of uterine contraction comparable to oxytocin. The drug oxytocin was pragmatic to amplify the uterine contractile action of the extract. Meanwhile pre-treating the tissue with either atropine or salbutamol earlier than administrating the extract indicates the inhibitory action of the drugs on the action of the extract.

Effect of Atropine on Adrenergic Responsiveness of Erythrocyte and Heart Rhythm Variability in Outbred Rats with Stimulation of the Central Neurotransmitter Systems.

Single injection of muscarinic cholinoceptor blocker atropine (1 mg/kg) to outbred male rats reduced ß-adrenergic responsiveness of erythrocytes (by 2.2 times) and the content of epinephrine granules on erythrocytes (by 1.5 times), significantly increased HR and rigidity of the heart rhythm, and manifold decreased the power of all spectral components of heart rhythm variability. Stimulation of the central neurotransmitter systems increased ß-adrenergic responsiveness of erythrocytes (by 15-26%), decreased the number of epinephrine granules on erythrocytes (by 25-40%), and increased HR and cardiac rhythm intensity. These changes were most pronounced after stimulation of the serotoninergic system. Administration of atropine against the background of activation of central neurotransmitter systems did not decrease ß-adrenergic responsiveness of erythrocytes (this parameter remained at a stably high level and even increased during stimulation of the dopaminergic system), but decreased the number of epinephrine granules on erythrocytes, increased HR, and dramatically decreased the power of all components of heart rhythm variability spectrum. The response to atropine was maximum against the background of noradrenergic system activation and less pronounced during stimulation of the serotoninergic system. Thus, substances that are complementary to cholinergic receptors modulated adrenergic effect on the properties of red blood cells, which, in turn, can modulate the adrenergic influences on the heart rhythm via the humoral channel of regulation. Stimulation of central neurotransmitter systems that potentiates the growth of visceral adrenergic responsiveness weakens the cholinergic modulation of the adrenergic influences, especially with respect to erythrocyte responsiveness. Hence, changes in the neurotransmitter metabolism in the body can lead to coupled modulation of reception and reactivity to adrenergic- and choline-like regulatory factors at the level of erythrocyte membranes, which can be important for regulation of heart rhythm.

Preclinical evaluation of the diuretic and saluretic effects of (-)-epicatechin and the result of its combination with standard diuretics.

Several studies have suggested that (-)-epicatechin-containing foods and plant extracts benefit conditions that affect the cardiovascular system, such as hypertension and endothelial dysfunction. However, no study was conducted so far to evaluate the potential of this flavonoid on diuretic activity assay. For that, female Wistar normotensive (NTR) and spontaneously hypertensive rats (SHR) received a single oral treatment with (-)-epicatechin (EPI), hydrochlorothiazide (HCTZ) or just vehicle (VEH). The effects of EPI in combination with diuretics for clinical use, as well as with L-NAME, atropine and indomethacin were also explored. Cumulative urine volume, plasma and urinary parameters were evaluated at the end of 8 h experiment. When given to NTR and SHR, at doses of 0.3, 1 and 3 mg/kg, EPI was able to stimulate both diuresis and saluresis (Na+, K+ and Cl-), without interfering with plasma electrolyte content or urinary pH and uric acid values, when compared with VEH-treated only rats. The combination with HCTZ, but not with furosemide or amiloride, successfully strengthened EPI-induced diuresis. This effect was not accompanied by a potentiation of the saluretic effects. On the other hand, when given EPI in combination with amiloride, a significant increase in Cl- excretion and maintenance of the potassium-sparing effects characteristic of this class of diuretics were detected. In addition, the diuretic effect of EPI was enhanced after pretreatment with L-NAME and its action was significantly precluded in the presence of indomethacin, a cyclooxygenase inhibitor. In conclusion, this study shows the diuretic and saluretic properties of EPI in rats, adding another biological activity whose effect may contribute to the different positive actions already described.

GLP-1 receptor agonist liraglutide exerts central action to induce ß-cell proliferation through medulla to vagal pathway in mice.

Endogenous GLP-1 and GLP-1 receptor agonists (GLP-1RAs) regulate glucose metabolism via common and distinct mechanisms. Postprandial release of GLP-1 is modest and it is degraded by DPP-4 within 2 min, and hence it cannot enter the brain in substantial amount. In contrast, DPP-4-resistant GLP-1RAs are administered at 10 times higher concentration than endogenous GLP-1 level, which enables them to reach several brain regions including ARC and AP, the areas implicated in glucose metabolism. Hence, some of the effects of GLP-1RAs observed clinically and experimentally, including pancreatic ß-cell proliferation, are thought to involve the brain. However, the effects of centrally acting GLP-1/GLP-1RAs on glucose metabolism and underlying neural mechanism are unclear. This study aimed to establish the link of central GLP-1/GLP-1RA action to pancreatic ß-cell proliferation. Both subcutaneous (SC) and intracerebroventricular (ICV) injections of liraglutide increased the number of pancreatic ß-cells expressing Ki67 and PCNA, proliferation markers, in C57BL/6J mice. This effect was induced by single ICV administration of liraglutide at relatively low dose that was incapable of suppressing food intake. These SC and ICV liraglutide-induced effects were inhibited by 50% and 70%, respectively, by pretreatment with atropine, a muscarinic receptor blocker. ICV liraglutide induced c-Fos expression in the area postrema (AP), nucleus tractus solitaries (NTS), and dorsal motor nucleus of the vagus (DMX) of the brain stem. These results demonstrate that central action of liraglutide induces pancreatic ß-cell proliferation via the pathway involving the brain stem AP/NTS/DMX area and vagus nerve. This route is highly sensitive to GLP-1/GLP-1RA. Hence, this brain-pancreatic ß-cell pathway may operate in type 2 diabetic patients treated with GLP-RAs and serve to counteract the reduction of ß-cell mass.

In vivo nonspecific immunomodulatory and antispasmodic effects of common purslane (Portulaca oleracea Linn.) leaf extracts in ICR mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Portulaca oleracea (common purslane) is used in traditional medicine to cure various illnesses. However, its immune-protective properties and antispasmodic effects still need more pharmacological data if the plant will be utilized in herbal and drug formulations. Therefore, the present study determined the capacity of this plant species to modulate nonspecific immune responses and to confirm its antispasmodic activity in vivo in ICR mice. MATERIALS AND METHODS: Phagocytic activity of peritoneal macrophage, splenic lymphocyte proliferation and plasma lysozyme levels were measured in mice that were immunosuppressed using cyclophosphamide and treated with the ethyl acetate extract of Portulaca oleracea. In addition, the charcoal meal transit test was used to measure intestinal motility using ethanolic (EtOH), hexane (HEX), and ethyl acetate (EA) solvent extracts. Phytochemical analysis was undertaken and DPPH scavenging properties of the three solvent extracts were also determined. RESULTS: The EA extract of P. oleracea exhibited immunoactivity through significant increase in phagocytosis and higher proliferative response in splenic lymphocytes. Plasma lysozyme level was also higher in EA-treated mice at high dose but this was not statistically significant. Decreased intestinal motility was also exhibited in mice treated with the three leaf solvent extracts compared to the negative control and the acetylcholine-treated group. The antispasmodic activity of the solvent extracts was comparable to that of the atropine-treated group. Phytochemical analysis showed the presence of tannins in EA extract in addition to alkaloids and steroids. The EtOH and HEX extracts contain alkaloids, steroids and terpenoids. DPPH scavenging activity was highest in the EA extract. CONCLUSIONS: The present study showed that the EA extract of P. oleracea leaves ameliorated the immunosuppressive action of cyclophosphamide in mice. The results also indicated that the three solvent extracts of the plant decreased smooth muscle spasms in mice ileum. However, further experiments are warranted to further isolate the plant's immunoactive component. Also, the mechanisms involved in the immunoactivity and antispasmodic properties of P. oleracea deserve full elucidation.

Evaluation of the Influence of Three Newly Developed Bispyridinium Anti-nicotinic Compounds (MB408, MB442, MB444) on the Efficacy of Antidotal Treatment of Nerve Agent Poisoning in Mice.

The influence of three newly developed bispyridinium antinicotinic compounds (the non-oximes MB408, MB442 and MB444) on the therapeutic efficacy of a standard antidotal treatment (atropine in combination with an oxime) of acute poisoning by the organophosphorus nerve agents tabun and soman was studied in mice. The therapeutic efficacy of atropine in combination with an oxime with or without one of the bispyridinium non-oximes was evaluated by determination of the LD50 values of the nerve agents and measurement of the survival time after supralethal poisoning. Addition of all the tested non-oximes increased significantly the therapeutic efficacy of atropine in combination with an oxime against tabun poisoning. They also positively influenced the number of surviving mice 6 hr after supralethal poisoning with tabun. However, they were only slightly effective for the treatment of soman poisoning. The benefit of the tested bispyridinium non-oximes was dose-dependent. To conclude, the addition of bispyridinium non-oximes to the standard antidotal treatment of acute poisoning with tabun was beneficial regardless of the chosen non-oxime, but only slightly beneficial in the case of soman poisoning.

The Screening of Anticholinergic Accumulation by Traditional Chinese Medicine.

Many Western drugs can give rise to serious side effects due to their ability to bind to acetylcholine receptors in the brain. This aggravates when they are combined, which is known as anticholinergic accumulation (AA). Some bioactives in Traditional Chinese Medicine (TCM) are known to block acetylcholine receptors and thus potentially cause AA. The AA of TCM was screened by quantifying the displacement of [³H] pirenzepine on acetylcholine receptors in a rat brain homogenate. We used a new unit to express AA, namely the Total Atropine Equivalents (TOAT). The TOAT of various herbs used in TCM was very diverse and even negative for some herbs. This is indicative for the broadness of the pallet of ingredients used in TCM. Three TCM formulas were screened for AA: Ma Huang Decotion (MHD), Antiasthma Simplified Herbal Medicine intervention (ASHMI), and Yu Ping Feng San (YPFS). The TOAT of ASHMI was indicative for an additive effect of herbs used in it. Nevertheless, it can be calculated that one dose of ASHMI is probably too low to cause AA. The TOAT of YPFS was practically zero. This points to a protective interaction of AA. Remarkably, MHD gave a negative TOAT, indicating that the binding to the acetylcholine receptors was increased, which also circumvents AA. In conclusion, our results indicate that TCM is not prone to give AA and support that there is an intricate interaction between the various bioactives in TCM to cure diseases with minimal side effects.

Chemical composition and diuretic, natriuretic and kaliuretic effects of extracts of Mimosa bimucronata (DC.) Kuntze leaves and its majority constituent methyl gallate in rats.

OBJECTIVES: Some species of the genus Mimosa showed promising results in previous investigations, which include diuretic effect; however, no chemical analyses or animal model has been conducted so far to evaluate the biological properties of M. bimucronata. METHODS: Male Wistar rats received the oral treatment with vehicle; hydrochlorothiazide; methanolic extract from M. bimucronata (MEMB), dichloromethane (DCM) and ethyl acetate (EA) fractions or methyl gallate (MG). The cumulative urine volume, electrolytes excretion, pH and osmolality were determined at the end of the experiment. KEY FINDINGS: The chemical studies demonstrated that the phenolic compounds are the majorities in the plant, with the MG being the main substance identified. We showed that MEMB and EA fraction, but not DCM, exhibited diuretic and saluretic effects. Similarly, the MG also revealed diuretic, natriuretic and kaliuretic properties to both normotensive and spontaneously hypertensive rats. Atropine, a muscarinic receptor antagonist, fully prevented MG-induced diuresis and saluresis. In addition, MG did not alter the viability of A7r5 and L929 cell lines and neither stimulated nitric oxide generation. CONCLUSIONS: These findings suggest that M. bimucronata extracts and its majority compound MG present diuretic, natriuretic and kaliuretic properties, which was dependent on the activation of muscarinic acetylcholine receptor.

Central command increases muscular oxygenation of the non-exercising arm at the early period of voluntary one-armed cranking.

This study aimed to examine whether central command increases oxygenation in non-contracting arm muscles during contralateral one-armed cranking and whether the oxygenation response caused by central command differs among skeletal muscles of the non-exercising upper limb. In 13 male subjects, the relative changes in oxygenated-hemoglobin concentration (Oxy-Hb) of the non-contracting arm muscles [the anterior deltoid, triceps brachii, biceps brachii, and extensor carpi radialis (ECR)] were measured during voluntary one-armed cranking (intensity, 35-40% of maximal voluntary effort) and mental imagery of the one-armed exercise for 1 min. Voluntary one-armed cranking increased (P < 0.05) the Oxy-Hb of the triceps, biceps, and ECR muscles to the same extent (15 ± 4% of the baseline level, 17 ± 5%, and 16 ± 4%, respectively). The greatest increase in the Oxy-Hb was observed in the deltoid muscle. Intravenous injection of atropine (10-15 µg/kg) and/or propranolol (0.1 mg/kg) revealed that the increased Oxy-Hb of the arm muscles consisted of the rapid atropine-sensitive and delayed propranolol-sensitive components. Mental imagery of the exercise increased the Oxy-Hb of the arm muscles. Motor-driven passive one-armed cranking had little influence on the Oxy-Hb of the arm muscles. It is likely that central command plays a role in the initial increase in oxygenation in the non-contracting arm muscles via sympathetic cholinergic vasodilatation at the early period of one-armed cranking. The centrally induced increase in oxygenation may not be different among the distal arm muscles but may augment in the deltoid muscle.

Electroacupuncture treatment partly promotes the recovery time of postoperative ileus by activating the vagus nerve but not regulating local inflammation.

Postoperative ileus (POI) after abdominal surgery significantly lowers the life quality of patients and increase hospital costs. However, few treatment strategies have successfully shortened the duration of POI. Electroacupuncture (EA) is a modern way of administering acupuncture and widely used in various gastrointestinal (GI) diseases in the world. Here, we studied the effect of EA on POI and its underlying mechanisms. Intestinal manipulation resulted in significant delays of GI transit, colonic transit and gastric emptying. Surgery also up-regulated c-fos in nucleus of the solitary tract (NTS) and induced inflammation response in the small intestine. Further, operation and inhale anesthesia inhibited NTS neuron excitation duration for the whole observation time. EA administered at ST36 indeed shortened the recovery time of GI and colonic transit, and significantly increased the gastric emptying. EA also significantly activated the NTS neurons after operation. However, there was no anti-inflammation effect of EA during the whole experiment. Finally, atropine blocked the regulatory effect of EA on GI function, when it was injected after surgery, but not before surgery. Thus, the regulatory effect of EA on POI was mainly mediated by exciting NTS neurons to improve the GI tract transit function but not by activating cholinergic anti-inflammatory pathway.