ABSTRACT
Anxiety and depression disorders are highly prevalent neurological disorders (NDs) that impact up to one in three individuals during their lifetime. Addressing these disorders requires reducing their frequency and impact, understanding molecular causes, implementing prevention strategies, and improving treatments. Cyclic nucleotide monophosphates (cNMPs) like cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), cyclic uridine monophosphate (cUMP), and cyclic cytidine monophosphate (cCMP) regulate the transcription of genes involved in neurotransmitters and neurological functions. Evidence suggests that cNMP pathways, including cAMP/cGMP, cAMP response element binding protein (CREB), and Protein kinase A (PKA), play a role in the physiopathology of anxiety and depression disorders. Plant and mushroom-based compounds have been used in traditional and modern medicine due to their beneficial properties. Bioactive compound metabolism can activate key pathways and yield pharmacological outcomes. This review focuses on the molecular mechanisms of bioactive compounds from plants and mushrooms in modulating cNMP pathways. Understanding these processes will support current treatments and aid in the development of novel approaches to reduce the prevalence of anxiety and depression disorders, contributing to improved outcomes and the prevention of associated complications.
Subject(s)
Depression , Nucleotides, Cyclic , Humans , Nucleotides, Cyclic/metabolism , Nucleotides, Cyclic/pharmacology , Depression/drug therapy , Cyclic GMP/metabolism , Cyclic AMP/metabolism , Plants/metabolism , Anxiety/drug therapyABSTRACT
The co-administration of 3α-hydroxymasticadienoic acid (3α-OH MDA) and diligustilide (DLG) generates a synergist gastroprotective effect on indomethacin-induced gastric damage. However, the related protective activities of the compounds alone (or in combination) remain unclear. In the present study, we evaluated the anti-inflammatory and antioxidative activities, as well as the potential modulation of important gasotransmitters of each compound individually and in combination using the indomethacin-induced gastric damage model. Male Wistar rats were treated orally with the 3α-OH MDA, DLG, or their combination (at a fixed ratio of 1:1, 1:3, and 3:1) 30 min before the generation of gastric mucosal lesions with indomethacin (30 mg/kg, p.o.). Three hours later, the gastric injury (mm2) was determined. Results from these experiments indicate, in addition to maintaining basal levels of PGE2, the gastroprotective effect of the pre-treatment with 3α-OH MDA (70%), DLG (81%), and their combination (72%) which was accompanied by significant decreases in leukocyte recruitment, as well as decreases in TNF-α and LTB4 gastric levels (p < 0.05). We also found that the pre-treatment maintains the basal antioxidant enzyme activities (SOD) and gastric NO and H2S production even in the presence of indomethacin (p < 0.05). In conclusion, when 3α-OH MDA-DLG is given at a 1:1 combination ratio, the gastroprotective effect and the inflammatory, antioxidant, and gaso-modulation properties are not different from those of treatments using the maximum doses of each compound, revealing that this combination produces promising results for the treatment of gastric ulcers.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Anti-Ulcer Agents/pharmacology , Antioxidants/pharmacology , Gastric Mucosa/drug effects , Stomach Ulcer/prevention & control , Triterpenes/pharmacology , Animals , Dinoprostone/metabolism , Disease Models, Animal , Drug Therapy, Combination , Gastric Mucosa/metabolism , Gastric Mucosa/pathology , Hydrogen Sulfide/metabolism , Indomethacin , Leukotriene B4/metabolism , Male , Nitric Oxide/metabolism , Rats, Wistar , Stomach Ulcer/metabolism , Stomach Ulcer/pathology , Superoxide Dismutase/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
(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 Na2S and sodium nitroprusside to elucidate participation in the action of DLG. We also evaluated the production of H2S 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 H2S 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 H2S formation.
