Unveiling myricetin's pharmacological potency: A comprehensive exploration of the molecular pathways with special focus on PI3K/AKT and Nrf2 signaling.

Myricetin can be found in the traditional Chinese medicinal plant, Myrica rubra. Myricetin is a flavonoid that is present in many vegetables, fruits, and plants and is considered to have strong antioxidant properties as well as a wide range of therapeutic applications. Growing interest has been piqued by its classification as a polyphenolic molecule because of its potential therapeutic benefits in both the prevention and management of numerous medical conditions. To clarify myricetin's traditional medical uses, modern research has investigated various pharmacological effects such as antioxidant, anticancer, anti-inflammation, antiviral, antidiabetic, immunomodulation, and antineurodegenerative effects. Myricetin shows promise as a nutritional flavonol that could be beneficial in the prevention and mitigation of prevalent health conditions like diabetes, cognitive decline, and various types of cancer in humans. The findings included in this study indicate that myricetin has a great deal of promise for application in the formulation of medicinal products and nutritional supplements since it affects several enzyme activities and alters inflammatory markers. However, comprehensive preclinical studies and research studies are necessary to lay the groundwork for assessing myricetin's possible effectiveness in treating these long-term ailments. This review summarizes both in vivo and in vitro studies investigating myricetin's possible interactions through the nuclear factor-E2-related factor 2 (Nrf2) as well as PI3K (phosphatidylinositol 3-kinase)/AKT (protein kinase B) signaling pathways in an attempt to clarify the compound's possible clinical applicability across a range of disorders.

The impact of timing, type, and method of instillation of intraperitoneal local anaesthetic in laparoscopic abdominal surgery: a systematic review and network meta-analysis.

BACKGROUND: Pain is common after laparoscopic abdominal surgery. Intraperitoneal local anaesthetic (IPLA) is effective in reducing pain and opioid use after laparoscopic surgery, although the optimum type, timing, and method of administration remains uncertain. We aimed to determine the optimal approach for delivering IPLA which minimises opioid consumption and pain after laparoscopic abdominal surgery. METHODS: MEDLINE, Embase, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were systematically searched for randomised controlled trials comparing different combinations of the type (bupivacaine vs lidocaine vs levobupivacaine vs ropivacaine), timing (pre-vs post-pneumoperitoneum at the beginning or end of surgery), and method (aerosol vs liquid) of IPLA instillation in patients undergoing any laparoscopic abdominal surgery. A network meta-analysis was conducted to ascertain the optimum approach for delivering IPLA resulting in the least cumulative opioid consumption and pain (overall and localising to the shoulder) 24 h after surgery. Certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) assessments (PROSPERO ID: CRD42022307595). RESULTS: Twenty-five RCTs were included, among which 15 different combinations of delivering IPLA were analysed across 2401 participants. Aerosolised bupivacaine instilled at the end of surgery, before deflation of the pneumoperitoneum, was associated with significantly less postoperative opioid consumption compared with all other approaches for delivering IPLA (98.7% of comparisons; moderate certainty), aside from liquid levobupivacaine instilled before surgery and during or after creation of the pneumoperitoneum (mean difference -11.6, 95% credible interval: -26.1 to 2.5 i.v. morphine equivalent doses). There were no significant differences between different IPLA approaches regarding overall pain scores and incidence of shoulder pain up to 24 h after surgery. CONCLUSIONS: There are limited studies and low-quality evidence to conclude on the optimum method of delivering IPLA in laparoscopic abdominal surgery. While aerosolised bupivacaine instilled at the end of surgery but before deflation of the pneumoperitoneum minimises postoperative opioid consumption, pain scores up to 24 h did not differ between the different modalities of delivering IPLA. The generalisability of these results is limited by the lack of utilisation of non-opioid analgesics in most trials. SYSTEMATIC REVIEW PROTOCOL REGISTRATION: PROSPERO CRD42022307595.

An Insight into the Promising Therapeutic Potential of Chicoric Acid.

The pharmacological treatments that are now recommended for the therapy of chronic illnesses are examined in a great number of studies to determine whether or not they are both safe and effective. Therefore, it is important to investigate various alternative therapeutic assistance, such as natural remedies derived from medicinal plants. In this context, chicoric acid, classified as a hydroxycinnamic acid, has been documented to exhibit a range of health advantages. These include antiviral, antioxidant, anti-inflammatory, obesity-preventing, and neuroprotective effects. Due to its considerable pharmacological properties, chicoric acid has found extensive applications in food, pharmaceuticals, animal husbandry, and various other commercial sectors. This article provides a comprehensive overview of in vitro and in vivo investigations on chicoric acid, highlighting its beneficial effects and therapeutic activity when used as a preventative and management aid for public health conditions, including diabetes, cardiovascular disease, and hepatic illnesses like non-alcoholic steatohepatitis. Moreover, further investigation of this compound can lead to its development as a potential phytopharmaceutical candidate.

High Mobility Group Box 1 Protein: A Plausible Therapeutic Molecular Target in Parkinson's disease.

Parkinson's disease (PD) is a widespread neurodegenerative disorder that exerts a broad variety of detrimental effects on people's health. Accumulating evidence suggests that mitochondrial dysfunction, neuroinflammation, α-synuclein aggregation and autophagy dysfunction may all play a role in the development of PD. However, the molecular mechanisms behind these pathophysiological processes remain unknown. Currently, research in PD has focussed on high mobility group box 1 (HMGB1), and different laboratory approaches have shown promising outcomes to some level for blocking HMGB1. Given that HMGB1 regulates mitochondrial dysfunction, participates in neuroinflammation, and modulates autophagy and apoptosis, it is hypothesised that HMGB1 has significance in the onset of PD. In the current review, research targeting multiple roles of HMGB1 in PD pathology was integrated, and the issues that need future attention for targeted therapeutic approaches are mentioned.

Dietary, Herbal and Nutritional Interventions for Managing Rheumatoid Arthritis: A Review.

Rheumatoid arthritis (RA) is a systemic, inflammatory disease that affects joints and leads to progressive cartilage and bone deterioration. The susceptibility to RA is determined by genetic and environmental factors. Recently, many efforts have been undertaken to develop natural compounds capable of reducing the symptoms of RA to avoid the negative effects of the current anti-inflammatory drugs. Interestingly, substantial data has revealed that nutritional, and herbal supplements may be effective adjuvants in reducing the symptoms of RA by influencing the pathogenic inflammatory processes. In this context, various kinds of food, phenolic substances, spices like ginger, and turmeric, several vitamins, and probiotics are reported to control the activity of inflammatory molecules implicated in the pathophysiology of RA and therefore, have proved successful in slowing the course of this arthritic illness. Therefore, the goal of this review article is to compile various findings on RA that have revealed illuminating information about the antiinflammatory, antioxidant, analgesic, immunomodulatory, and bone erosion-preventing properties of nutritional, and herbal components. Conclusively, this review concentrates on natural ingredients that may enhance overall well-being, promote health, and lessen the risk of RA.

Erucic Acid: A Possible Therapeutic Agent for Neurodegenerative Diseases.

Neurodegenerative disorders are among the most common life-threatening disorders among the elderly worldwide and are marked by neuronal death in the brain and spinal cord. Several studies have demonstrated the beneficial role of dietary fatty acids in different brain disorders. This is due to their neurotrophic, antioxidant, and anti-inflammatory properties. Furthermore, extensive evidence shows that an unbalanced intake of certain dietary fatty acids increases the risk of neuropsychiatric diseases. Several research has been done on erucic acid, an ingestible omega-9 fatty acid that is found in Lorenzo's oil. Erucic acid was previously thought to be a natural toxin because of its negative effects on heart muscle function and hepatic steatosis, but it has been discovered that erucic acid is regularly consumed in Asian countries through the consumption of cruciferous vegetables like mustard and rapeseed oil with no evidence of cardiac harm. Erucic acid can also be transformed into nervonic acid, a crucial element of myelin. Therefore, erucic acid may have remyelinating effects, which may be crucial for treating different demyelinating conditions. Also, erucic acid exerts antioxidant and anti-inflammatory effects, suggesting its possible therapeutic role in different neurodegenerative disorders. Considering the fruitful effects of this compound, this article reviews the probable role of erucic acid as a pharmacological agent for treating and managing different neurodegenerative disorders.

Therapeutic implications of crocin in Parkinson's disease: A review of preclinical research.

Parkinson's disease is among the most common forms of neurodegenerative illness, with present treatment being primarily symptomatic and frequently coming with substantial adverse effects. Neuronal degeneration may arise due to a variety of pathological events, like inflammatory responses, neurotransmitter dysregulation, oxidative damage, mitochondrial malfunction, apoptosis, and genetic factors. The health issue and financial burden brought on by Parkinson's disease can worsen as the population ages. In the search for new and secure therapeutic agents for Parkinson's disease, several natural compounds have been shown to exert considerable neuroprotective benefits. Crocin, a naturally occurring carotenoid molecule, was found to have neuroprotective potential in the therapy of this disorder. Taking into account, the outcomes of various studies and the restorative actions of crocin, the present study emphasized the protective ability of crocin in this disease. Given the strong evidence supporting the neuroprotective ability of crocin, it is inferred that crocin inhibits inflammatory, apoptotic, and antioxidant processes through multiple mechanisms. Therefore, this compound is considered a safe and effective therapeutic choice for neurodegenerative illnesses like Parkinson's disease. However, more research on its efficacy as a treatment of Parkinson's disease is needed, specifically examining its mechanisms and the results obtained in clinical trials.

The PI3K-AKT pathway: A plausible therapeutic target in Parkinson's disease.

Parkinson's disease is a common progressive and multifactorial neurodegenerative disease, characterized by the loss of midbrain dopaminergic neurons. Numerous pathological processes including, inflammation, oxidative stress, mitochondrial dysfunction, neurotransmitter imbalance, and apoptosis as well as genetic factors may lead to neuronal degeneration. With the emergence of aging population, the health problem and economic burden caused by PD also increase. Phosphatidylinositol 3-kinases-protein kinase B (PI3K-AKT) signaling pathway regulates signal transduction and biological processes such as cell proliferation, apoptosis and metabolism. According to reports, it regulates neurotoxicity and mediates the survival of neurons. Accumulating evidences indicate that some natural products can play a neuroprotective role by activating PI3K-AKT pathway, providing an effective resource for the discovery of potential therapeutic drugs. The current review provides an overview of the PI3K-AKT signaling pathway and review the relationship between this signaling pathway and PD.

Efficacy and safety of laparoscopic Roux-en-Y gastric bypass in symptomatic patients following fundoplication failure: a meta-analysis.

Revisional surgery may be required in a subset of patients who remain symptomatic despite undergoing laparoscopic fundoplication (LF) for gastroesophageal reflux disease (GERD). While revisional LF (RLF) is feasible in these patients, laparoscopic Roux-en-Y gastric bypass (LRYGB) may serve as an alternative, although its efficacy and safety remains unknown. This study aimed to determine the outcomes of LRYGB in symptomatic patients following failed LF for GERD. MEDLINE, EMBASE, and PubMed databases were systematically searched for studies reporting LRYGB outcomes in symptomatic adults despite undergoing LF for GERD. Postoperative symptom resolution, recurrence of heartburn and dysphagia, proton pump inhibitor (PPI) use, and body mass index (BMI) reduction were assessed to determine LRYGB efficacy. Postoperative morbidity and mortality were used to evaluate LRYGB safety. Twenty-two studies with 1523 patients were included. Pooled rates of symptom resolution, recurrence of heartburn and dysphagia, PPI use, morbidity, and mortality were 71.6% (95% CI 59.4-86.4), 15.6% (8.9-27.3), 20.7% (12.5-34.3), 29.6% (18.8-46.5), 39.5% (29.9-52.3), and 2.2% (1.2-4.0), respectively, following LRYGB. Similar rates were observed after RLF. However, BMI reduction was significantly greater after LRYGB compared with RLF (mean difference 6.1 kg/m2, 4.8-7.4; p < 0.0001). LRYGB resulted in symptom relief in a majority of patients, and proved comparable to RLF regarding symptom recurrence and PPI use. Morbidity and mortality following LRYGB also did not differ from RLF. However, LRYGB was associated with considerably greater weight loss relative to RLF. Therefore, LRYGB is efficacious and an acceptable revisional procedure in symptomatic GERD patients who have previously undergone LF.

Naringenin: A prospective therapeutic agent for Alzheimer's and Parkinson's disease.

Neurodegenerative disorders (NDs) are a cluster of progressive, severe, and disabling disorders that affect millions of people worldwide and are on the surge. These disorders are characterized by the gradual loss of a selectively vulnerable group of neurons. Due to the complex pathophysiological mechanisms behind neurodegeneration and despite enormous efforts and understanding of the occurrence and progression of NDs, there is still a lack of an effective treatment for such diseases. Therefore, the development of a new therapeutic strategy for NDs is an unmet clinical need. Various natural compounds extracted from medicinal plants or fruits have shown promising activities in treating different types of NDs by targeting multiple signaling pathways. Among natural entities, flavonoids have incited a rise in public and scientific interest in recent years because of their purported health-promoting effects. Dietary supplementation of flavonoids has been shown to mitigate the severity of NDs such as Parkinson's disease (PD), Alzheimer's disease (AD), and dementia by their antioxidant effects. Naringenin is a citrus flavonoid that is known to possess numerous biological activities like antioxidant, anti-proliferative, and anti-inflammatory activities. Therefore, naringenin has emerged as a potential therapeutic agent that exerts preventive and curative effects on several neurological disorders. Increasing evidence has attained special attention on the variety of therapeutic targets along with complex signaling pathways of naringenin, which suggest its possible therapeutic applications in several NDs. Derived from the results of several pre-clinical research and considering the therapeutic effects of this compound, this review focuses on the potential role of naringenin as a pharmacological agent for the treatment and management of Alzheimer's and Parkinson's disease. The overall neuroprotective effects and different possible underlying mechanisms related to naringenin are discussed. In the light of substantial evidence for naringenin's neuroprotective efficacy in several experimental paradigms, this review suggests that this molecule should be investigated further as a viable candidate for the management of Alzheimer's and Parkinson's disease, with an emphasis on mechanistic and clinical trials to determine its efficacy. PRACTICAL APPLICATIONS: Naringenin is a flavanone, aglycone of Naringin, predominantly found in citrus fruits with a variety of pharmacological actions. Naringenin has been shown to exhibit remarkable therapeutic efficacy and has emerged as a potential therapeutic agent for the management of a variety of diseases such as various heart, liver, and metabolic disorders. Similarly, it has shown efficacy in neurodegenerative illnesses. Therefore, this review enables us to better understand the neuroprotective effects and different possible underlying mechanisms of naringenin. Also, this review provides a new indication to manage the symptoms of NDs like AD and PD. Furthermore, naringenin will be useful in the field of medicine as a new active ingredient for the treatment of neurodegenerative disorders like AD and PD.