Gastrointestinal Issues in Depression, Anxiety, and Neurodegenerative Diseases: A Systematic Review on Pathways and Clinical Targets Implications.

INTRODUCTION: Multiple illnesses commonly involve both the Central Nervous System (CNS) and the Gastrointestinal Tract (GI) simultaneously. Consistent evidence suggests that neurological disorders impair GI tract function and worsen the symptomatology and pathophysiology of digestive disorders. On the other hand, it has been proposed that early functional changes in the GI tract contribute to the genesis of several CNS illnesses. Additionally, the role played by the gut in these diseases can be seen as a paradigm for how the gut and the brain interact. METHODS: We mentioned significant GI symptoms and discussed how the GI tract affects central nervous system illnesses, including depression, anxiety, Alzheimer's disease, and Parkinson's disease in this study. We also explored potential pathophysiological underpinnings and novel targets for the creation of future therapies targeted at gut-brain connections. RESULTS & DISCUSSION: In this situation, modulating the gut microbiota through the administration of fecal microbiota transplants or probiotics may represent a new therapeutic option for this population, not only to treat GI problems but also behavioral problems, given the role that dysbiosis and leaky gut play in many neurological disorders. CONCLUSION: Accurate diagnosis and treatment of co-existing illnesses also require coordination between psychiatrists, neurologists, gastroenterologists, and other specialties, as well as a thorough history and thorough physical examination.

Usnic acid enantiomers restore cognitive deficits and neurochemical alterations induced by Aß1-42 in mice.

Alzheimer's disease (AD) is the most prevalent form of dementia with a complex pathophysiology not fully elucidated but with limited pharmacological treatment. The Usnic acid (UA) is a lichen secondary metabolite found in two enantiomeric forms: (R)-(+)-UA or (S)-(-)-UA, with antioxidant and anti-inflammatory potential. Thus, given the role of neuroinflammation and oxidative injury in the AD, this study aimed to investigate experimentally the cognitive enhancing and anti-neuroinflammatory effects of UA enantiomers. First, the interactions of UA on acetylcholinesterase (AChE) was assessed by molecular docking and its inhibitory capability on AChE was assessed in vitro. In vivo trials investigated the effects of UA enantiomers in mice exposed to Aß1-42 peptide (400 pmol/mice) intracerebroventricularly (i.c.v.). For this, mice were treated orally during 24 days with (R)-(+)-UA or (S)-(-)-UA at 25, 50, or 100 mg/kg, vehicle, or donepezil (2 mg/kg). Animals were submitted to the novel object recognized, Morris water maze, and inhibitory-avoidance task to assess the cognitive deficits. Additionally, UA antioxidant capacity and neuroinflammatory biomarkers were measured at the cortex and hippocampus from mice. Our results indicated that UA enantiomers evoked complex-receptor interaction with AChE like galantamine in silico. Also, UA enantiomers improved the learning and memory of the animals and in parallel decreased the myeloperoxidase activity and the lipid hydroperoxides (LOOH) on the cortex and hippocampus and reduced the IL-1ß levels on the hippocampus. In summary, UA restored the cognitive deficits, as well as the signs of LOOH and neuroinflammation induced by Aß1-42 administration in mice.

Curcumin protects remote organs against injury that is caused by intestinal ischemia and reperfusion

In addition to several local pathophysiological consequences, intestinal injury that is caused by ischemia and reperfusion can result in the development of lesions in remote organs. Curcumin has therapeutic potential because of its antiinflammatory and antioxidant effects. The present study evaluated the effects of curcumin on oxidative and inflammatory parameters in the liver and kidneys in rats that were subjected to intestinal ischemia and reperfusion. The rats were subjected to 45 min. of ischemia followed by 7 days of reperfusion and treated daily with 60 mg kg-1 curcumin. The liver and kidneys were collected, weighed, and biochemically analyzed. Intestinal ischemia and reperfusion increased levels of lipid hydroperoxide (LOOH), decreased levels of reduced glutathione (GSH), and increased the enzymatic activity of superoxide dismutase (SOD), glutathione S-transferase (GST), and myeloperoxidase (MPO) in the liver. Intestinal ischemia and reperfusion decreased kidney weight and increased GST activity in the kidneys. Curcumin prevented these changes in the liver and kidneys. Intestinal ischemia and reperfusion mainly affected the liver, promoting inflammation and oxidative stress. The kidneys underwent repair much earlier than the liver, in which they did not present alterations of MPO or main parameters of oxidative stress after 7 days of reperfusion. Treatment with curcumin had beneficial effects, ameliorating or even preventing injury that was caused by intestinal ischemia and reperfusion in the liver and kidneys in rats

Prolonged diuretic and saluretic effect of nothofagin isolated from Leandra dasytricha (A. Gray) Cogn. leaves in normotensive and hypertensive rats: Role of antioxidant system and renal protection.

Although the acute diuretic effect of nothofagin has been recently demonstrated, its effects after dose-repeated treatment have not yet been explored. For that, male Wistar normotensive (NTR) and spontaneously hypertensive rats (SHR) were orally treated, once a day, with vehicle (VEH: distilled water; 1 ml/kg), hydrochlorothiazide (HCTZ; 10 mg/kg) or nothofagin (NOT; 1 mg/kg). The cumulative diuretic index and urinary electrolytes excretion were measured each 24 h. On the last day of the experiment (7th day), urine, blood and kidney samples were collected for biochemical and molecular analyzes. The urinary volume of both NTR and SHR were significantly increased with the treatment with NOT (from the second to the seventh day of treatment), with final values reaching an increase of 56% and 82%, respectively, when compared with VEH-treated group. This effect was associated with increased levels of urinary excretion of Na+ and Cl-, without any changes on K+ excretion. None of the treatments modified urinary pH or density values. Importantly, neither the NOT nor the HCTZ caused any change in body weight following the dose-repeated treatment, and also did not provoke an electrolytic disturbance. Regarding the renal analyzes, when compared with the vehicle-treated NTR group, the activity of superoxide dismutase (SOD) and the reduced glutathione (GSH) levels in kidney homogenates of the SHR group were decreased, while the generation of lipid hydroperoxides were significantly increased. The daily treatment with NOT was able to restore the GSH levels and SOD activity, as well as reduced the lipoperoxidation in the kidney homogenates obtained from SHR animals. Finally, NOT significantly augmented the levels of nitrite, a marker of nitric oxide production, in the plasma obtained from SHR group when compared with the vehicle-treated only NTR. This study revealed the prolonged diuretic and saluretic effect of nothofagin in normotensive and hypertensive rats. Our data also showed the renal protective effects of nothofagin by the improvement of antioxidative capacity, as well as by the augmented bioavailability of plasma nitric oxide in the hypertensive group.