Ginger facilitates cholinergic activity possibly due to blockade of muscarinic autoreceptors in rat stomach fundus

Ginger (Zingiber officinale) is a universally known food plant reputed for its medicinal use in gastrointestinal disorders as a prokinetic and laxative. We recently showed that 70% aqueous-methanolic extract of ginger (Zo.Cr) exhibits prokinetic activity in rats via activation of post-synaptic muscarinic M3 receptor in rat stomach fundus. In view of the physiological significance of pre-synaptic muscarinic M1 and M2 autoreceptors, this study was undertaken to further look into the possible mode of action of the prokinetic effect of ginger through inhibition of pre-synaptic muscarinic receptors. Isolated tissue bath experiments were performed with Sprague-Dawley rat stomach fundus strip preparations immersed in Kreb\u27s solution at 37 degrees C. Carbachol (CCh) maximum responses (1 microM) were obtained in rat stomach fundus. Zo.Cr, given in multiple increasing bolus concentrations (0.01-0.1 mg/ml) 10 min prior to administration of CCh, potentiated the CCh peak responses showing that it is possibly inhibiting the pre-synaptic muscarinic receptors. Like wise, increasing bolus concentrations of pirenzepine (0.03-0.3 microM) and himbacine (0.01-0.03 microM), standard muscarinic M1 and M2 antagonists respectively, also potentiated the CCh responses. These results show that ginger, in addition to having a direct cholinergic agonistic effect on the post-synaptic M3 receptors, also has a possible inhibitory effect on pre-synaptic muscarinic autoreceptors, similar to standard muscarinic antagonists, thus reiterating the gastric stimulant effect of this age-old plant

Providing a setup and opportunities for better training of postdoctoral research fellows in an academic environment

Thousands of young researchers come from different parts of the world every year to take up postdoctoral (postdoc) research fellowship positions in the developed countries. In the US alone, there were 48,601 postdocs in the year 2005 working in different labs in the fields of science, health and engineering. Many pursue this option for lack of other alternatives. Expectedly, these individuals face a lot of difficulties in making this transition from being a student to becoming an employee of an institution. Many institutions are prepared to make this transition and period of stay easy for their fellows while others are not equipped at all. The presence of a postdoc office (established by an institution) or an association (formed by the fellows) can be of immense help to postdocs. Additionally, the availability of institutional professional development and leadership programs can also help to nurture and polish postdoc fellows into future faculty members and valuable members of the community at large. To name a few, these professional development programs can focus on communication and presentation skills, medical education, teaching and learning, bioethics and mentorship. There is an urgent need to address some or all of these issues so that better training environment and opportunities are available to this group of postdoc fellows

Ginger attenuates acetylcholine-induced contraction and Ca2+ signaling in murine airway smooth muscle cells.

Asthma is a chronic disease characterized by inflammation and hypersensitivity of airway smooth muscle cells (ASMCs) to different spasmogens. The past decade has seen increased use of herbal treatments for many chronic illnesses. Ginger (Zingiber officinale) is a common food plant that has been used for centuries in treating respiratory illnesses. In this study, we report the effect of its 70% aqueous methanolic crude extract (Zo·Cr) on acetylcholine (ACh)-induced airway contraction and Ca2+ signalling in ASMCs using mouse lung slices. Airway contraction and Ca2+ signalling, recorded via confocal microscopy, were induced with ACh, either alone or after pretreatment of slices with Zo·Cr and (or) verapamil, a standard Ca2+ channel blocker. ACh (10 μmol/L) stimulated airway contraction, seen as decreased airway diameter, and also stimulated Ca2+ transients (sharp rise in [Ca2+]i) and oscillations in ASMCs, seen as increased fluo-4-induced fluorescence intensity. When Zo·Cr (0.3–1.0 mg/mL) was given 30 min before ACh administration, the ACh-induced airway contraction and Ca2+ signalling were significantly reduced. Similarly, verapamil (1 μmol/L) also inhibited agonist-induced airway contraction and Ca2+ signalling, indicating a similarity in the modes of action. When Zo·Cr (0.3 mg/mL) and verapamil (1 μmol/L) were given together before ACh, the degree of inhibition was the same as that observed when each of these blockers was given alone, indicating absence of any additional inhibitory mechanism in the extract. In Ca2+-free solution, both Zo·Cr and verapamil, when given separately, inhibited Ca2+ (10 mmol/L)-induced increase in fluorescence and airway contraction. This shows that ginger inhibits airway contraction and associated Ca2+ signalling, possibly via blockade of plasma membrane Ca2+ channels, thus reiterating the effectiveness of this age-old herb in treating respiratory illnesse

Studies on antihypertensive and antispasmodic activities of Andropogon muricatus Retz

The aqueous-methanolic crude extract of Andropogon muricatus (Am.Cr) was investigated pharmacologically to determine some of its medicinal uses in cardiovascular and gastrointestinal disorders. A series of in vivo and in vitro studies were conducted to evaluate dose-dependent effects of Am.Cr on mean arterial pressure (MAP), cardiac and vascular contractions, and to further investigate the potential mechanism of action. Intravenous administration of Am.Cr (10-50 mg/kg) caused a fall (18%-56%) in MAP in normotensive rats under anesthesia. When tested in isolated guinea pig atria, Am.Cr (0.03-5.0 mg/mL) exhibited a cardiodepressant effect on the rate and force of spontaneous contractions. In isolated rabbit aorta, Am.Cr caused inhibition of K+ (80 mmol/L)-induced contractions at a lower concentration than of phenylephrine. In isolated rabbit jejunum preparations, Am.Cr (0.01-0.10 mg/mL) caused relaxation of spontaneous and high K+ (80 mmol/L)-induced contractions, suggesting that the spasmolytic effect is mediated possibly through calcium channel blockade (CCB). The CCB activity was confirmed when pretreatment of the tissue with Am.Cr (0.03-0.1 mg/mL) shifted the Ca2+ dose-response curves to the right, similar to that caused by verapamil. These data indicate that the blood pressure-lowering and spasmolytic effects of Am.Cr are mediated possibly through a calcium channel blocking activity. Phytochemical screening of Am.Cr revealed the presence of phenols, saponins, tannins, and terpenes, which may be responsible for the observed vasodilator, cardiodepressant, and antispasmodic activities. This study shows potential with respect to its medicinal use in cardiovascular and gut disorders

Cardiovascular and airway relaxant activities of peony root extract

Paeonia emodi (peony) is a well known plant used medicinally to treat hypertension, palpitations, and asthma. Despite its popularity, there are few reports in the scientific literature examining its use in such conditions. We prepared a 70% ethanolic extract of peony root (Pe.Cr) and applied it to segments of guinea pig atria and trachea and rat aorta suspended separately in tissue baths. Activity against arachidonic acid (AA)-induced platelet aggregation was measured in human platelet-rich plasma. Airway relaxant effect was evaluated against acetylcholine (ACh)-induced airway contraction in mouse lung slices loaded with fluo-4. Pe.Cr (0.3–10 mg/mL) showed an atropine-resistant negative inotropic effect in atria. In rat aorta, an endothelium-independent vasodilatory effect (0.3–10 mg/mL) was seen in phenylephrine- and high-K+-induced contractions. Pe.Cr (0.01–1 mg/mL) also inhibited AA-induced platelet aggregation. In isolated trachea, Pe.Cr (0.3–10 mg/mL) relaxed carbachol- and histamine-induced contractions independently of β-adrenergic receptors. In mouse lung slices, Pe.Cr (0.3–1 mg/mL) inhibited ACh-induced airway narrowing and oscillations of intracellular Ca2+ in airway smooth muscle cells. The results showed cardiosuppressant, vasodilatory, antiplatelet, and tracheal and airway relaxant activities of peony, providing potential justification for its medicinal use in different hyperactive cardiovascular and respiratory disorders

Muscarinic, Ca(++) antagonist and specific butyrylcholinesterase inhibitory activity of dried ginger extract might explain its use in dementia

Ginger rhizome (Zingiber officinale) has been used for centuries to treat dementia in South Asia. This study was undertaken to possibly justify its use. A 70% aqueous/methanolic extract of dried ginger (Zo.Cr) was used. Zo.Cr tested positive for the presence of terpenoids, flavonoids, secondary amines, phenols, alkaloids and saponins. When tested on isolated rat stomach fundus, Zo.Cr showed a spasmogenic effect (0.03-5.00 mg mL(-1)), it relaxed the tissue at concentrations \u3e= 5 mg mL(-1). The stimulant effect was resistant to blockade by hexamethonium and methysergide, but sensitive to atropine, indicating activity via muscarinic receptors. In atropinized (0.1 mu M) preparations, Zo.Cr (0.3-3.0 mg mL(-1)) relaxed high K(+) (80 mM)-induced contractions, indicating Ca(++) antagonism in addition to the muscarinic effect. This possible Ca(++) antagonist activity was investigated in Ca(++)-free conditions, with the inhibitory effect of the extract tested against contractions induced by externally administered Ca(++). Zo.Cr (0.1-0.3 mg mL(-1)), similar to verapamil (0.03-0.10 mu M), shifted the contractions induced by externally administered Ca(++) to the right, thus suggesting an inhibitory interaction between Zo.Cr and voltage-operated Ca(++) channels. Zo.Cr (0.1-3.0 mu g mL(-1)) also potentiated acetylcholine peak responses in stomach fundus, similar to physostigmine, a cholinesterase inhibitor. Zo.Cr, in an in-vitro assay, showed specific inhibition of butyrylcholinesterase (BuChE) rather than acetylcholinesterase enzyme. Different pure compounds of ginger also showed spasmolytic activity in stomach fundus, with 6-gingerol being the most potent. 6-Gingerol also showed a specific anti-BuChE effect. This study shows a unique combination of muscarinic, possible Ca(++) antagonist and BuChE inhibitory activities of dried ginger, indicating its benefit in dementia, including Alzheimer\u27s disease