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.

Modern Approaches to the Elimination of Visceral Pain

In modern medicine, one of the most common situations requiring emergency care is biliary or renal colic as a manifestation of abdominal pain syndrome. In both cases, smooth muscle spasm plays an important role in the pathogenesis of visceral pain syndrome. Taking into account the fact that, regardless of the chosen treatment tactics, at the first stage it is necessary to stop pain, the question arises about the choice of a drug strategy for the relief of these conditions. It used to be thought that the more intense the pain, the more indications for the prescription of narcotic drugs, which were considered reference analgesics. In recent years, the world has become embroiled in an «opioid crisis». This prompted clinicians to consider the use of drugs from other groups, namely, non-steroidal anti-inflammatory drugs and antispasmodics alone or in combination, which turned out to be no less effective and, often, safer in comparison with narcotic analgesics. New opportunities for effective treatment of visceral pain are opened by the drug Neospastil® (PJSC «Pharmaceutical Company «Darnitsa»), which combines the benefits of nonsteroidal anti-inflammatory drugs (ketorolac tromethamine) with antispasmodic effect of cholinolytics, ganglioblockers and phenytoin phenytoin. The drug increases the effectiveness of analgesia, as well as the control of muscle spasm.

Study of Antispasmodic and Antidiarrheal Activities of Tagetes lucida (Mexican Tarragon) in Experimental Models and Its Mechanism of Action

Tagetes lucida has been used in traditional medicine as a remedy to alleviate several gastrointestinal disorders that provoke stomachaches, abdominal cramps, and diarrhea. However, there is not enough scientific evidence that supports these effects. Therefore, the purpose of this study was to evaluate antispasmodic and antidiarrheal activities of aqueous extract of T. lucida (AqExt-TL) as well as its mechanism of action in experimental models. Antispasmodic activity and the mechanism of action of AqExt-TL were assessed on segments of the guinea pig ileum precontracted with KCl, acetylcholine (ACh), or electrical field stimulation (EFS). Furthermore, the antispasmodic effect of two coumarins (umbelliferone and herniarin) previously identified in this species was evaluated. Antidiarrheal activity of AqExt-TL was determined using the charcoal meal test in mice. AqExt-TL showed antispasmodic activity in segments of the guinea pig ileum precontracted with KCl (83.7 ± 1.9%) and ACh (77.2 ± 5.3%) at the maximal concentration; however, practically, it did not alter the contractions induced by EFS (10.1 ± 2.2%). Antispasmodic activity of AqExt-TL was not significantly altered by hexamethonium (a ganglionic blocker) or L-NAME (an inhibitor of nitric oxide synthase). However, this extract decreased the maximal contractile response to calcium (82.7 ± 8.5%), serotonin (68.1 ± 8.5%), and histamine (63.9 ± 5.9%) in their concentration-response curves. Umbelliferone and herniarin also induced an antispasmodic effect on tissues precontracted with KCl. In addition, low doses of AqExt-TL reduced to 50% the distance traveled by charcoal meal in the gastrointestinal transit model in mice as loperamide, an antidiarrheal agent, did. These results provided evidence of the antispasmodic and antidiarrheal activity of T. lucida, which supports its use in the folk medicine in relieving symptoms in some gastrointestinal disorders. In the antispasmodic effect, the blockade of histaminergic and serotoninergic pathway as well as the calcium channels seems to be involved. Finally, umbelliferone and herniarin could be partially responsible for the antispasmodic activity induced by T. lucida.

Clinical and laboratory efficacy of hypoosmolar solution for oral rehydration in children with intestinal infections

There is a high incidence of acute intestinal infections in the Russian Federation. Children rapidly develop clinical manifestations of acute intestinal infections. The severity and outcome of the disease are largely determined by the dehydration syndrome. The article presents the results of the effectiveness of oral rehydration in 2 groups of children with acute intestinal infection from 3 months to 7 years old, treated with hypoosmolar glucose-saline solution “Gastrolit with chamomile extract” (n=215) or “Rehydron” (n=188) in the complex treatment of intestinal infections with the dehydration syndrome of I or II degree. The groups were comparable by sex, age, clinical manifestations of the disease. It was found that “Gastrolit with chamomile extract” eliminates water-electrolyte disorders, relieves metabolic acidosis and has anti-inflammatory, antiseptic and antispasmodic effect on the intestine and relieves symptoms of dehydration faster than “Rehydron” in children with acute intestinal infection.

Antispasmodic Effect of Essential Oils and Their Constituents: A Review

The antispasmodic effect of drugs is used for the symptomatic treatment of cramping and discomfort affecting smooth muscles from the gastrointestinal, billiary or genitourinary tract in a variety of clinical situations.The existing synthetic antispasmodic drugs may cause a series of unpleasant side effects, and therefore the discovery of new molecules of natural origin is an important goal for the pharmaceutical industry. This review describes a series of recent studies investigating the antispasmodic effect of essential oils from 39 plant species belonging to 12 families. The pharmacological models used in the studies together with the mechanistic discussions and the chemical composition of the essential oils are also detailed. The data clearly demonstrate the antispasmodic effect of the essential oils from the aromatic plant species studied. Further research is needed in order to ascertain the therapeutic importance of these findings.