Abstract
Researches on spicatoside A (SpiA)-containing natural products suggest the possibility of SpiA as a potential laxative to alleviate chronic constipation. However, no studies have been conducted with single compound administration of SpiA. To verify the laxative effects and mechanism of action of SpiA on chronic constipation, we investigated alterations in the excretion parameters, histological structure, and cholinergic regulation of the enteric nerve in the colons of Institute of Cancer Research (ICR) mice with loperamide (Lop)-induced constipation after exposure to 20 mg/kg of SpiA. Decrease in the number, weight and water contents of stools in the Lop+Vehicle treated group significantly recovered after SpiA treatment, and alterations in the histological structure and transmission electron microscopy (TEM) images were improved in the Lop+SpiA treated group. Similar recovery effects were observed in the ability for mucin secretion and expression of the membrane water channel gene (aquaporin 8, AQP8). Furthermore, significant improvements were observed in the acetylcholinesterase (AChE) activity and acetylcholine receptors’ (AChRs) downstream signaling pathway after treatment of SpiA. The levels of gastrointestinal (GI) hormones including cholecystokinin (CCK) and gastrin were also remarkably enhanced in the Lop+SpiA treated group as compared to the Lop+Vehicle treated group. The expression of receptor tyrosine kinase (C-kit) and protein gene product 9.5 (PGP9.5) in Cajal and neural cells, as well as the phosphorylation of myosin light chain (MLC) in smooth muscle cells, were recovered after SpiA exposure. Taken together, the results of the present study provide the first strong evidence that SpiA improves chronic constipation through muscarinic cholinergic regulation of the enteric nerve in a Lop-induced constipation ICR mice model.
Highlights
Spicatoside A (SpiA) belongs to the class of steroidal saponins, which are known complex mixtures having highly branched oligosaccharide moieties and are found to be distributed in various plants [1,2].They are known to exert a wide range of pharmacological effects including anti-inflammatory, anti-asthma, anti-osteoclastogenesis, neurite outgrowth, memory consolidation and anti-cancer [3].The anti-inflammatory, anti-asthma and neurite outgrowth activities of SpiA have received great attention since these properties are correlated with chronic human diseases [4,5,6]
The decrease in stool excretion parameters were remarkably recovered in the Lop + SpiA treated group when compared to the Lop + Vehicle treated group (Figure 1B and Table 1)
The urine volume in the Lop + SpiA treated group showed a reversal in the pattern from the stool excretion parameters, while no significant differences in body weight and food intake were observed (Table 1)
Summary
Spicatoside A (SpiA) belongs to the class of steroidal saponins, which are known complex mixtures having highly branched oligosaccharide moieties and are found to be distributed in various plants [1,2].They are known to exert a wide range of pharmacological effects including anti-inflammatory, anti-asthma, anti-osteoclastogenesis, neurite outgrowth, memory consolidation and anti-cancer [3].The anti-inflammatory, anti-asthma and neurite outgrowth activities of SpiA have received great attention since these properties are correlated with chronic human diseases [4,5,6]. Spicatoside A (SpiA) belongs to the class of steroidal saponins, which are known complex mixtures having highly branched oligosaccharide moieties and are found to be distributed in various plants [1,2]. They are known to exert a wide range of pharmacological effects including anti-inflammatory, anti-asthma, anti-osteoclastogenesis, neurite outgrowth, memory consolidation and anti-cancer [3]. The anti-inflammatory, anti-asthma and neurite outgrowth activities of SpiA have received great attention since these properties are correlated with chronic human diseases [4,5,6]. The above studies provide some information regarding the possible correlation between improvement of intestinal bowel diseases and steroidal saponin, no studies have directly investigated the laxative effects of SpiA in the constipated animal model
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