Diligustilide releases H2S and stabilizes S-nitrosothiols in ethanol-induced lesions on rat gastric mucosa

Abstract

(Z,Z')-Diligustilide (DLG) or levistolide A is a dimeric phthalide isolated from Ligusticum porteri (Osha), the roots of which are used in the traditional treatment of many diseases including gastric aches. However, its action has not been completely elucidated. We analyzed the contributions of hydrogen sulfide and S-nitrosothiols to the action of DLG. Animals were pretreated with freshly formed in vitro nitrosothiol using NaS and sodium nitroprusside to elucidate participation in the action of DLG. We also evaluated the production of HS in vivo and in real time on the stomach via a specific electrode introduced into the stomachs of anaesthetized animals pretreated with DLG. Treatment with 10 mg/kg DLG increases gastric HS production in vivo from 7.8 ± 0.81 ppm to 13.1 ± 3.01 ppm and prevents the decrease in gastric injury caused by absolute ethanol. In addition, it maintains endogenous concentrations of GSH and NO. Exogenous S-nitrosothiols protect the gastric mucosa from damage, suggesting that the action of DLG might be associated with S-nitrosothiol and HS formation.

Gastroprotective Properties of Nanoemulsion of Ligusticum porteri Volatile Oil in Rats

“…Our findings showed that there was no significant decrease in NO levels in any of the treatment groups; only a slight tendency to decline in the indomethacin-treated (damage) group. In this sense, considering that the previous studies by Velázquez-Moyado et al (2018) report that DLG prevents the depletion of NO level in the ethanol gastric damage model, and more important that DLG was not found in our GC-MS analysis of the volatile oil of L. porteri, we propose that the volatile oil of L. porteri does not participate in the modulation of NO, although there is another mechanism involved in NSAID-related gastropathy, such as the inflammatory pathway (Wallace and Granger 1996;Wallace and Ma 2001), oxidative stress (Wallace 2008;Bindu et al 2013), or a decrease in the mucosal blood flow (Asako et al 1992). In these mechanisms, the expression of cytokines involved such as LTB 4 and TNF-α (Bindu et al 2013;Wallace et al 2011) and transcription factors (e.g., NFκβ or Nrf2) (Bindu et al 2013;Pineda-Peña et al 2018) might be modulated by (Z)-3butylidenephthalide, the major monomeric phthalides found in this volatile oil.…”

“…H 2 S has been shown to be cytoprotective for the GI tract in animal studies (Wallace 2010). Velázquez-Moyado et al (2018) reported that Z,Z´diligustilide (DLG), the major compound in the hexane extract of L. porteri, might be responsible for the regulation of H 2 S liberation as a possible mechanism in the gastroprotective action in an ethanol-induced gastric damage model. Interestingly in our study, the GC-MS analysis reported that the volatile oil does not contain DLG.…”

“…It is known that prostaglandins coordinate the protection of the gastric mucosa against harmful agents, and their actions include the regulation of mucosal blood flow, enhancing mucus and bicarbonate production (or secretion), inhibition of gastric acid secretion, and downregulation of the inflammatory responses (Wallace 2008;Lanas 2009). Furthermore, it has also been reported that gasotransmitters, such as nitric oxide (NO) and hydrogen sulfide (H 2 S), play a critical role in the mucosal protection, acting as endogenous mediators that can modulate the integrity of the tissues and exhibit gastroprotective properties against different types of aggressive agents (Martin et al 2001;Gemici et al 2015;Velázquez-Moyado et al 2018). The common drugs used for the treatment of NSAID-induced damage in the upper GI tract include the administration of proton pump inhibitors (PPI) and histamine H2-receptor antagonists (H2RA), which are inhibitors of gastric acid secretion (Wallace 2016).…”

H2S Donors Reverse Age-Related Gastric Malfunction Impaired Due to Fructose-Induced Injury via CBS, CSE, and TST Expression

“…Several animal and human studies suggest that postprandial hyperglycemia related to excessive fructose consumption causes cellular and subcellular oxidative damage, and accelerates the age-related decline in cytoprotection by developing oxidative damage related to a modification in H 2 S-NO cross-talk and redox homeostasis (Guan et al, 2012;Cao and Bian, 2018). The process of age-associated increased susceptibility to gastric cytotoxic factors involves several vascular associated molecular signaling pathways, which has a bi-directional detrimental role on the gastric mucosal defense (Yonezawa et al, 2007;Velaźquez-Moyado et al, 2018). It has been shown that the key role in gastroprotection at the advanced age belongs to the endothelial dysfunction, reduced mucosal defense, amplified susceptibility to injury by a variety of injurious agents and its dramatic consequences on older patients with hyperglycemia could be expected.…”

Mexican Plants and Derivates Compounds as Alternative for Inflammatory and Neuropathic Pain Treatment—A Review

“…The tea from L. porteri roots also produce analgesia [ 72 ]. Furthermore, the pharmacological effects of this herb have been demonstrated in the treatment of gastric ulcers [ 73 , 74 , 75 ]. Other pharmacological properties of L. porter , such as sedation, anti-spasmolytic [ 76 ], anti-inflammatory [ 77 ] and antinociceptive properties [ 78 , 79 ], have been observed in preclinical assays.…”