Superoxide dismutase: a key target for the neuroprotective effects of curcumin.

Over the past few years, the prevalence of neurodegenerative diseases (NDD) has increased dramatically. The community health system is burdened by the high healthcare costs associated with NDD. Superoxide dismutase (SOD) is a type of metalloenzyme that possesses a distinct characteristic of protecting the body from oxidative stress through antioxidants. In this way, SOD supplementation may activate the endogenous antioxidant mechanism in various pathological conditions and could be used to neutralize free radical excess. Several factors are responsible for damaging DNA and RNA in the body, including the overproduction of reactive species, particularly reactive oxygen species (ROS) and reactive nitrogen species (RNS). Excessive ROS/RNS have deleterious effects on mitochondria and their metabolic processes, mainly through increased mitochondrial proteins, lipids and DNA oxidation. Studies have shown that oxidative stress is implicated in the etiology of many diseases, including NDD. It is thought that anti-inflammatory compounds, particularly phytochemicals, can interfere with these pathways and regulate inflammation. Extensive experimental and clinical research has proven that curcumin (Cur) has anti-inflammatory and anti-neurologic properties. In this review, we have compiled the available data on Cur's anti-inflammatory properties, paying special attention to its therapeutic impact on NDD through SOD.

TLR/mTOR inflammatory signaling pathway: novel insight for the treatment of schizophrenia.

The Toll-like receptor (TLR)/mammalian target of rapamycin (mTOR) signaling pathway is involved in the intracellular regulation of protein synthesis, specifically the ones that mediate neuronal morphology and facilitate synaptic plasticity. The activity of TLR/mTOR signaling has been disrupted, leading to neurodevelopment and deficient synaptic plasticity, which are the main symptoms of schizophrenia. The TLR receptor activates the mTOR signaling pathway and increases the elevation of inflammatory cytokines. Interleukin (IL)-6 is the most commonly altered cytokine, while IL-1, tumor necrosis factor, and interferon (IFN) also lead to SCZ. Anti-inflammatory and anti-oxidative agents such as celecoxib, aspirin, minocycline, and omega-3 fatty acids have shown efficiency against SCZ. As a result, inhibition of the inflammatory process could be suggested for the treatment of SCZ. So mTOR/TLR blockers represent the treatment of SCZ due to their inflammatory consequences. The objective of the present work was to find a novel anti-inflammatory agent that may block the mTOR/TLR inflammatory signaling pathways and might pave the way for the treatment of neuroinflammatory SCZ. Data were collected from experimental and clinical studies published in English between 1998 and October 2022 from Google Scholar, PubMed, Scopus, and the Cochrane library.

The role of natural products as PCSK9 modulators: A review.

A variety of mechanisms and drugs have been shown to attenuate cardiovascular disease (CVD) onset and/or progression. Recent researchers have identified a potential role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in modulating lipid metabolism and reducing plasma low density lipoprotein (LDL) levels. PCSK9 is the central protein in the metabolism of LDL cholesterol (LDL-C) owing to its major function in LDL receptor (LDLR) degradation. Due to the close correlation of cardiovascular disease with lipid levels, many in vivo and in vitro investigations are currently underway studying the physiological role of PCSK9. Furthermore, many studies are actively investigating the mechanisms of various compounds that influence lipid associated-disorders and their associated cardiovascular diseases. PCSK9 inhibitors have been shown to have significant impact in the prevention of emerging cardiovascular diseases. Natural products can effectively be used as PCSK9 inhibitors to control lipid levels through various mechanisms. In this review, we evaluate the role of phytochemicals and natural products in the regulation of PCSK9, and their ability to prevent cardiovascular diseases. Moreover, we describe their mechanisms of action, which have not to date been delineated.

The regulating effect of curcumin on NF-κB pathway in neurodegenerative diseases: a review of the underlying mechanisms.

Neurodegenerative diseases are part of the central nervous system (CNS) disorders that indicate their presence with neuronal loss, neuroinflammation, and increased oxidative stress. Several pathophysiological factors and biomarkers are involved in this inflammatory process causing these neurological disorders. The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is an inflammation element, which induced transcription and appears to be one of the important players in physiological procedures, especially nervous disorders. NF-κB can impact upon series of intracellular actions and induce or inhibit many inflammation-related pathways. Multiple reports have focused on the modification of NF-κB activity, controlling its expression, translocation, and signaling pathway in neurodegenerative disorders and injuries like Alzheimer's disease (AD), spinal cord injuries (SCI), and Parkinson's disease (PD). Curcumin has been noted to be a popular anti-oxidant and anti-inflammatory substance and is the foremost natural compound produced by turmeric. According to various studies, when playing an anti-inflammatory role, it interacts with several modulating proteins of long-standing disease signaling pathways and has an unprovocative consequence on pro-inflammatory cytokines. This review article determined to figure out curcumin's role in limiting the promotion of neurodegenerative disease via influencing the NF-κB signaling route. Preclinical studies were gathered from plenty of scientific platforms including PubMed, Scopus, Cochrane, and Google Scholar to evaluate this hypothesis. Extracted findings from the literature review explained the repressing impact of Curcumin on the NF-κB signaling pathway and, occasionally down-regulating the cytokine expression. Yet, there is an essential need for further analysis and specific clinical experiments to fully understand this subject.

The time interval between injection of nicotine and tremor initiation: a new index for evaluating nicotine efficacy in rodents.

Tremor is one of the effects of nicotine as a toxic substance, especially in animal models. The intensity and duration of tremors were used to evaluate the effect of nicotine on locomotor activity in laboratory animals. In our observations, the time interval between nicotine injection and the onset of tremor changed depending on the dose. Therefore, by increasing the dose of nicotine in rats, the time interval of tremor onset was also shortened. These results suggest that the time interval between nicotine injection and the onset of tremors can be used as a complementary index for better evaluation of nicotine-derived motor disturbances.

IDO/Kynurenine; novel insight for treatment of inflammatory diseases.

Inflammation and oxidative stress play pivotal roles in pathogenesis of many diseases including cancer, type 2 diabetes, cardiovascular disease, atherosclerosis, neurological diseases, and inflammatory diseases such as inflammatory bowel disease (IBD). Inflammatory mediators such as interleukins (ILs), interferons (INF-s), and tumor necrosis factor (TNF)-α are related to an extended chance of inflammatory diseases initiation or progression due to the over expression of the nuclear factor Kappa B (NF-κB), signal transducer of activators of transcription (STAT), nod-like receptor family protein 3 (NLRP), toll-like receptors (TLR), mitogen-activated protein kinase (MAPK), and mammalian target of rapamycin (mTOR) pathways. These pathways are completely interconnected. Theindoleamine 2,3 dioxygenase (IDO) subset of the kynurenine (KYN) (IDO/KYN), is a metabolic inflammatory pathway involved in production of nicotinamide adenine dinucleotide (NAD + ). It has been shown that IDO/KYN actively participates in inflammatory processes and can increase the secretion of cytokines that provoke inflammatory diseases. Data were extracted from clinical and animal studies published in English between 1990-April 2022, which were collected from PubMed, Google Scholar, Scopus, and Cochrane library. IDO/KYN is completely associated with inflammatory-related pathways, thus leading to the production of cytokines such as TNF-α, IL-1ß, and IL-6, and ultimately development and progression of various inflammatory disorders. Inhibition of the IDO/KYN pathway might be a novel therapeutic option for inflammatory diseases. Herein, we gathered data on probable interactions of the IDO/KYN pathway with induction of some inflammatory diseases.

The Relationship Between Psoriasis, COVID-19 Infection and Vaccination During Treatment of Patients.

Since the outbreak of the COVID-19 pandemic in December 2019, scientists worldwide have been looking for a way to control this global threat. One of the most successful and practical solutions has been the development and worldwide distribution of the COVID-19 vaccines. However, in a small percentage of cases, vaccination can lead to de novo development or exacerbation of immune or inflammatory conditions such as psoriasis. Due to the immunomodulatory nature of this disease, people affected by psoriasis and other related skin conditions have been encouraged to receive COVID-19 vaccines, which are immunomodulatory by nature. As such, dermatological reactions are possible in these patients, and cases of onset, exacerbation or change in the type of psoriasis have been observed in patients administered with COVID-19 vaccines. Considering the rarity and minor nature of some of these cutaneous reactions to COVID-19 vaccination, there is a general consensus that the benefits of vaccination outweigh the potential risks of experiencing such side effects. Nevertheless, healthcare workers who administer vaccines should be made aware of the potential risks and advise recipients accordingly. Furthermore, we suggest careful monitoring for potentially deleterious autoimmune and hyperinflammatory responses using point-of-care biomarker monitoring.

Statins: Beneficial Effects in Treatment of COVID-19.

The recent viral disease COVID-19 has attracted much attention. The disease is caused by SARS-CoV-19 virus which has different variants and mutations. The mortality rate of SARS-CoV-19 is high and efforts to establish proper therapeutic solutions are still ongoing. Inflammation plays a substantial part in the pathogenesis of this disease causing mainly lung tissue destruction and eventually death. Therefore, anti-inflammatory drugs or treatments that can inhibit inflammation are important options. Various inflammatory pathways such as nuclear factor Kappa B (NF-κB), signal transducer of activators of transcription (STAT), nod-like receptor family protein 3 (NLRP), toll-like receptors (TLRs), mitogen-activated protein kinase (MAPK), and mammalian target of rapamycin (mTOR) pathways and mediators, such as interleukin (IL)-6, IL-1ß, tumor necrosis factor-α (TNF-α), and interferon-γ (INF-γ), cause cell apoptosis, reduce respiratory capacity and oxygen supply, eventually inducing respiratory system failure and death. Statins are well known for controlling hypercholesterolemia and may serve to treat COVID-19 due to their pleiotropic effects among which are anti-inflammatory in nature. In this chapter, the anti-inflammatory effects of statins and their possible beneficial effects in COVID-19 treatment are discussed. Data were collected from experimental and clinical studies in English (1998-October 2022) from Google Scholar, PubMed, Scopus, and the Cochrane Library.

Impact of curcumin on p38 MAPK: therapeutic implications.

Curcumin (diferuloylmethane) is a herbal remedy which possesses numerous biological attributes including anti-inflammatory, anti-oxidant and anti-cancer properties. Curcumin has been shown to impact a number of signaling pathways including nuclear factor kappa B (NF-KB), reactive oxygen species (ROS), Wingless/Integrated (Wnt), Janus kinase-signal transducer and activator of mitogen-activated protein kinase (MAPK) and transcription (JAK/STAT). P38 belongs to the MAPKs, is known as a stress-activated MAPK and is involved in diverse biological responses. P38 is activated in various signaling cascades. P38 plays a role in inflammation, cell differentiation, proliferation, motility and survival. This cascade can serve as a therapeutic target in many disorders. Extensive evidence confirms that curcumin impacts the P38 MAPK signaling pathway, through which it exerts anti-inflammatory, neuroprotective, and apoptotic effects. Hence, curcumin can positively affect inflammatory disorders and cancers, as well as to increase glucose uptake in cells. This review discusses the pharmacological and therapeutic effects of curcumin as effected through p38 MAPK.

Statins block mammalian target of rapamycin pathway: a possible novel therapeutic strategy for inflammatory, malignant and neurodegenerative diseases.

Inflammation plays a critical role in several diseases such as cancer, gastric, heart and nervous system diseases. Data suggest that the activation of mammalian target of rapamycin (mTOR) pathway in epithelial cells leads to inflammation. Statins, the inhibitors of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA), seem to be able to inhibit the mTOR. Statins are considered to have favorable effects on inflammatory diseases by reducing the complications caused by inflammation and by regulating the inflammatory process and cytokines secretion. This critical review collected data on this topic from clinical, in vivo and in vitro studies published between 1998 and June 2022 in English from databases including PubMed, Google Scholar, Scopus, and Cochrane libraries.

Licofelone, a potent COX/5-LOX inhibitor and a novel option for treatment of neurological disorders.

Neurological disorders result in disability and morbidity. Neuroinflammation is a key factor involved in progression or resolution of a series of neurological disorders like Huntington disease (HD), Parkinson's disease (PD), Alzheimer's disease (AD), Spinal Cord Injury (SCI), and Seizure. Thereby, anti-inflammatory drugs have been developed to improve the neurodegenerative impairments. Licofelone is an approved osteoarthritis drug that inhibits both the COX (cyclooxygenase) and 5-LOX (lipoxygenase) pathways. Licofelone has pain-relieving and anti-inflammatory effects and it was shown to have neuroprotective properties in the central nervous system, which is implicated in its regulatory effect on the COX/5-LOX pathway, inflammatory cytokines, and immune responses. In this study, we briefly review the various features of neurological disorders and the function of COX/LOX in their flare up and current pharmacological products for their management. Moreover, this review attempts to summarize potential therapeutics that target the immune responses within the central nervous system. A better understanding of the interactions between Licofelone and the nervous systems will be crucial to demonstrate the possible efficacy of Licofelone in neurological disorders.

Current overview of opioids in progression of inflammatory bowel disease; pharmacological and clinical considerations.

Inflammatory bowel diseases (IBD) belong to a subgroup of persistent, long-term, progressive, and relapsing inflammatory conditions. IBD may spontaneously develop in the colon, resulting in tumor lesions in inflamed regions of the intestine, such as invasive carcinoma. The benefit of opioids for IBD treatment is still questionable, thereby we investigated databases to provide an overview in this context. This review demonstrates the controversial role of opioids in IBD therapy, their physiological and pharmacological functions in attenuating the IBD symptoms, and in improving inflammatory, oxidative stress, and the quality of life factors in IBD subjects. Data were extracted from clinical, in vitro, and in vivo studies in English, between 1995 and 2019, from PubMed, Google Scholar, Scopus, and Cochrane library. Based on recent reports, there are promising opportunities to target the opioid system and control the IBD symptoms. This study suggests a novel approach for future treatment of functional and inflammatory disorders such as IBD.

Curcumin as a therapeutic candidate for multiple sclerosis: Molecular mechanisms and targets.

Multiple sclerosis (MS) is a disease that has shown a considerable increase in prevalence in recent centuries. Current knowledge about its etiology is incomplete, and therefore it cannot be managed optimally utilizing targeted therapeutic regimens at each stage of the disease. MS progresses in different stages, beginning with a cascade of inflammation. The pivotal spark to initiate this cascade seems to be the migration of Th17 into the central nervous system across the blood-brain barrier (BBB) through the disrupted tight junctions. Coupling of interleukin (IL)-17 and IL-22 to their receptors in the BBB layer facilitates this migration. Subsequently, axon degeneration and the various manifestations of nerve-muscle disorders appear. Curcumin, a major component of turmeric, is derived from Curcuma longa, which belongs to the Zingiberaceae family. Numerous properties of curcumin have been identified recently, some of which can be effective in the treatment of MS, particularly the anti-inflammatory properties via inhibition of secretion of proinflammatory cytokines. In this paper, we will review the various properties and key effects of curcumin for the treatment of MS.

Natural flavonoids for the prevention of colon cancer: A comprehensive review of preclinical and clinical studies.

Flavonoids comprise a group of natural polyphenols consisting of more than 5,000 subtypes mostly existing in fruits and vegetables. Flavonoids consumption could potentially attenuate the incidence and recurrence risk of colorectal cancers through their antiperoxidative, antioxidant, and anti-inflammatory effects. In addition, these compounds regulate the mitochondrial function, balance the bacterial flora and promote the apoptosis process in cancerous cells. However, some previous data failed to show the effectiveness of flavonoids in reducing the risk of colorectal cancer. In this study, we have reviewed the efficacy of different flavonoids subtypes on the risk of colon cancer and molecular mechanisms involved in this process in both clinical and animal studies. In addition, we tried to elucidate the potential synergy between these compounds and current colorectal cancer treatments.

Polyphenols targeting diabetes via the AMP-activated protein kinase pathway; future approach to drug discovery.

Regarding the widespread progression of diabetes, its related complications and detrimental effects on human health, investigations on this subject seems compulsory. AMP-activated protein kinase (AMPK) is a serine/threonine kinase and a key player in energy metabolism regulation. AMPK is also considered as a prime target for pharmaceutical and therapeutic studies on disorders such as diabetes, metabolic syndrome and obesity, where the body energy homeostasis is imbalanced. Following the activation of AMPK (physiological or pharmacological), a cascade of metabolic events that improve metabolic health is triggered. While there are several publications on this subject, this is the first report that has focused solely on polyphenols targeting diabetes via AMPK pathway. The multiple characteristics of polyphenolic compounds and their favorable influence on diabetes pathogenesis, as well as their intersections with the AMPK signaling pathway, indicate that these compounds have a beneficial effect on the regulation of glucose homeostasis. PPs could potentially occupy a significant position in the future anti-diabetic drug market.

Effects of alpha lipoic acid and its derivative "andrographolid-lipoic acid-1" on ulcerative colitis: A systematic review with meta-analysis of animal studies.

We aimed to review and meta-analyze the inflammatory and oxidative factors following alpha lipoic acid (ALA) and its derivative "andrographolid-lipoic acid-1" (AL-1) in ulcerative colitis (UC). ALA plays an important role in scavenging intracellular radicals and inflammatory elements. AL-1 is found in herbal medicines with potent anti-inflammatory properties. Data were collected from the Google Scholar, PubMed, Scopus, Evidence-based medicine/clinical trials, and Cochrane library database until 2017, which finally resulted in 22 animal studies (70 rats and 162 mice). The beneficial effects of ALA or AL-1 on the most important parameters of UC were reviewed; also, studies were considered separately in mice and rats. Administration of ALA and AL-1 significantly reduced the tumor necrosis factor-α level compared with the controls, while data were not noteworthy in the meta-analysis (mean differences = -18.57 [95% CI = -42.65 to 5.51], P = 0.13). In spite of insignificant decrease in meta-analysis outcomes (differences = 6.92 [95% CI = -39.33 to 53.16], P = 0.77), a significant reduction in myeloperoxidase activity was shown following ALA or AL-1 treatment compared with the controls. Despite significant differences in each study, we had to exclude some studies to homogenize data for meta-analyzing as they showed insignificant results. Interleukin 6, cyclooxygenase-2, glutathione, malondialdehyde, superoxide dismutase, histopathological score, macroscopic and microscopic scores, disease activity index, body weight change, and colon length were also reviewed. Most studies have emphasized on significant positive effects of ALA and AL-1. Comprehensive clinical trials are obligatory to determine the precious position of ALA or AL-1 in the management of UC.

Role of toll-like receptors in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is the chronic inflammation of the gastrointestinal tract. Recently, studies of the interplay between the adaptive and innate immune responses have provided a better understanding of the immunopathogenesis of inflammatory disorders such as IBD, as well as identification of novel targets for more potent interventions. Toll-like receptors (TLRs) are a class of proteins that play a significant role in the innate immune system and are involved in inflammatory processes. Activation of TLR signal transduction pathways lead to the induction of numerous genes that function in host defense, including those for inflammatory cytokines, chemokines, and antigen presenting molecules. It was proposed that TLR mutations and dysregulation are major contributing factors to the predisposition and susceptibility to IBD. Thus, modulating TLRs represent an innovative immunotherapeutic approach in IBD therapy. This article outlines the role of TLRs in IBD, focusing on both animal and human studies; the role of TLR-targeted agonists or antagonists as potential therapeutic agents in the different stages of the disease is discussed.

Potentially effective natural drugs in treatment for the most common rheumatic disorder: osteoarthritis.

Osteoarthritis (OA) is a chronic condition in which imbalance between anabolic and catabolic mediators occurs leading to the destruction of homeostasis of articular cartilage. The current drugs in the management of OA can just alleviate symptoms. Hence, the research tendency toward exploration of novel sources has been grown up in order to achieve safe and efficacious drugs. Meanwhile, various components exist as novel natural drugs that may possess favorable properties for the management of OA. This review focuses on the most efficacious medicinal plants and their phytochemical agents, which have been consumed for the management of OA. Moreover, evaluation of their efficacy and molecular mechanisms of action are discussed based on numerous modern experimental investigations. More research is needed to develop therapeutic agents with disease-modifying properties to treat OA.

The role of Toll-like receptors in multiple sclerosis and possible targeting for therapeutic purposes.

The interaction between the immune and nervous systems suggests invaluable mechanisms for several pathological conditions, especially neurodegenerative disorders. Multiple sclerosis (MS) is a potentially disabling chronic autoimmune disease, characterized by chronic inflammation and neurodegenerative pathology of the central nervous system. Toll-like receptors (TLRs) are an important family of receptors involved in host defense and in recognition of invading pathogens. The role of TLRs in the pathogenesis of autoimmune disorders such as MS is only starting to be uncovered. Recent studies suggest an ameliorative role of TLR3 and a detrimental role of other TLRs in the onset and progression of MS and experimental autoimmune encephalomyelitis, a murine model of MS. Thus, modulating TLRs can represent an innovative immunotherapeutic approach in MS therapy. This article outlines the role of these TLRs in MS, also discussing TLR-targeted agonist or antagonists that could be used in the different stages of the disease.

Protective effect of hydroalcoholic olive leaf extract on experimental model of colitis in rat: involvement of nitrergic and opioidergic systems.

The aim of the present study is to investigate the possible protective effect of dry olive leaf extract (OLE) against acetic acid-induced ulcerative colitis in rats, as well as the probable modulatory effect of nitrergic and opioidergic systems on this protective impact. Olive leaf extract was administered (250, 500 and 750 mg/kg) orally for two successive days, starting from the colitis induction. To assess the involvement of nitrergic and opioidergic systems in the possible protective effect of OLE, L-NG-Nitroarginine Methyl Ester (10 mg/kg) and naltrexone (5 mg/kg) intraperitoneal (i.p.) were applied 30 min before administration of the extract for two successive days, respectively. Colonic status was investigated 48 h following induction through macroscopic, histological and biochemical analyses. Olive leaf extract dose-dependently attenuated acetic acid-provoked chronic intestinal inflammation. The extract significantly reduces the severity of the ulcerative lesions and ameliorated macroscopic and microscopic scores. These observations were accompanied by a significant reduction in the elevated amounts of TNF-α and interlukin-2 markers. Moreover, both systems blockage reversed protective effects of OLE in the rat inflammatory bowel disease model. These finding demonstrated, for the first time, a possible role for nitrergic and opioidergic systems in the aforementioned protective effect, and the extract probably exerted its impact increasing nitric oxide and opioid tones.