Plant-Derived Fermented Products: An Interesting Concept for Human Health.

The health benefits of fermenting plant-derived products remain an underexplored domain. Plants and other natural products serve as medicinal agents when consumed as part of our diets, and the role of microorganisms in fermentation garners significant scientific interest. The present narrative review investigates the effects of fermentation of substances such as plants, algae, and fungi on their therapeutic and related purposes. Among the microorganisms used in fermentation, lactic acid bacteria are often linked to fermented products, particularly dairy and animal-based ones, and take center stage. These microorganisms are adept at synthesizing vitamins, active peptides, minerals, proteinases, and enzymes. Plant-derived fermented products are a significant source of active peptides, phytochemicals, flavonoids, and bioactive molecules with a profound impact on human health. They exhibit anti-inflammatory, anticarcinogenic, antiatherosclerotic, antidiabetic, antimicrobial, and antioxidant properties, the effects being substantiated by experimental studies. Clinical investigations underscore their effectiveness in managing diverse health conditions. Various studies highlight a synergy between microorganisms and plant-based materials, with fermentation as an innovative method for daily food preparation or a treatment option for specific ailments. These promising findings highlight the need for continued scientific inquiry into the impact of fermentation-derived products in clinical settings. Clinical observations to date have offered valuable insights into health improvement for various disorders. This current narrative review explores the impact of natural and plant-originated fermented products on health and well-being.

Empagliflozin protective effects against cisplatin-induced acute nephrotoxicity by interfering with oxidative stress and inflammation in Wistar rats.

Cisplatin (Cis) is a platinum-based antineoplastic drug used in various types of cancers. This drug can induce nephrotoxicity as a cause of acute kidney injury (AKI) by inducing oxidative stress and inflammation. Empagliflozin (Empa) is a newly developed inhibitor of sodium-glucose cotransporter-2 (SGLT2) approved as an antidiabetic medication for patients with type 2 diabetes mellitus. In addition to its blood glucose-lowering effect, Empa has been shown to exert anti-inflammatory and anti-oxidant properties. The current study aimed to investigate the protective effects of Empa on Cis-induced nephrotoxicity in rats. Male Wistar albino rats were divided into five groups, each of six rats: Sham group (received vehicle for 7 days), Control group (received vehicle for 7 days and Cis injection on day 2), Cis + Empa10 (received 10mg/kg Empa for 7 days and Cis injection on day 2), Cis + Empa30 (received 30mg/kg Empa for 7 days and Cis injection on day 2) and, Empa 30 (received 30mg/kg Empa for 7 days). One day after the last injection in each group, rats were weighed and then sacrificed to analyze the hematological, biochemical, and histological parameters. Cis markedly increased levels of inflammatory parameters such as renal tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, and myeloperoxidase (MPO) activity. Notably, malondialdehyde (MDA), blood urea nitrogen (BUN), and creatinine levels were enhanced after Cis administration. Also, the chemotherapeutic agent significantly reduced antioxidant indicators such as renal catalase (CAT), glutathione peroxidase (GpX), and superoxide dismutase (SOD). Furthermore, histopathological examinations also revealed severe renal damage following Cis treatment which was improved by Empa administration. Empa treatment at both doses (10 mg/kg and 30 mg/kg) reversed Cis-induced changes in all the above renal parameters. In conclusion, Empa has protective effects on Cis-induced nephrotoxicity by inhibition of oxidative stress and inflammation.

Protective Effects of Plant-Derived Compounds Against Traumatic Brain Injury.

Inflammation in the nervous system is one of the key features of many neurodegenerative diseases. It is increasingly being identified as a critical pathophysiological primitive mechanism associated with chronic neurodegenerative diseases following traumatic brain injury (TBI). Phytochemicals have a wide range of clinical properties due to their antioxidant and anti-inflammatory effects. Currently, there are few drugs available for the treatment of neurodegenerative diseases other than symptomatic relief. Numerous studies have shown that plant-derived compounds, in particular polyphenols, protect against various neurodegenerative diseases and are safe for consumption. Polyphenols exert protective effects on TBI via restoration of nuclear factor kappa B (NF-κB), toll-like receptor-4 (TLR4), and Nod-like receptor family proteins (NLRPs) pathways. In addition, these phytochemicals and their derivatives upregulate the phosphatidylinositol-3-Kinase/Protein Kinase B (PI3K/AKT) and nuclear factor erythroid 2-related factor 2 (Nrf2) pathways, which have critical functions in modulating TBI symptoms. There is supporting evidence that medicinal plants and phytochemicals are protective in different TBI models, though future clinical trials are needed to clarify the precise mechanisms and functions of different polyphenolic compounds in TBI.

Therapeutic effects of anti-diabetic drugs on traumatic brain injury.

AIMS: In this narrative review, we have analyzed and synthesized current studies relating to the effects of anti-diabetic drugs on traumatic brain injury (TBI) complications. METHODS: Eligible studies were collected from Scopus, Google Scholar, PubMed, and Cochrane Library for clinical, in-vivo, and in-vitro studies published on the impact of anti-diabetic drugs on TBI. RESULTS: Traumatic brain injury (TBI) is a serious brain disease that is caused by any type of trauma. The pathophysiology of TBI is not yet fully understood, though physical injury and inflammatory events have been implicated in TBI progression. Several signaling pathways are known to play pivotal roles in TBI injuries, including Nuclear factor erythroid 2-related factor 2 (Nrf2), High mobility group box 1 protein/Nuclear factor kappa B (HMGB1/NF-κB), Adiponectin, Mammalian Target of Rapamycin (mTOR), Toll-Like Receptor (TLR), Wnt/ß-catenin, Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT), Nod-like receptor protein3 (NLRP3) inflammasome, Phosphoglycerate kinase 1/Kelch-like ECH-associated protein 1 (PGK1/KEAP1)/Nrf2, and Mitogen-activated protein kinase (MAPK) . Recent studies suggest that oral anti-diabetic drugs such as biguanides, thiazolidinediones (TZDs), sulfonylureas (SUs), sodium-glucose cotransporter-2 inhibitors (SGLT2is), dipeptidyl peptidase-4 inhibitors (DPPIs), meglitinides, and alpha-glucosidase inhibitors (AGIs) could have beneficial effects in the management of TBI complications. These drugs may downregulate the inflammatory pathways and induce antioxidant signaling pathways, thus alleviating complications of TBI. CONCLUSION: Based on this comprehensive literature review, antidiabetic medications might be considered in the TBI treatment protocol. However, evidence from clinical trials in patients with TBI is still warranted.

Cinnamic Acid Ameliorates Acetic Acid-induced Inflammatory Response through Inhibition of TLR-4 in Colitis Rat Model.

BACKGROUND: Cinnamic acid, an active compound in cinnamon spp., has anti-inflammatory and antioxidant characteristics and is favorable in managing inflammatory bowel diseases. OBJECTIVES: Evaluate cinnamic acid's effects on colitis in rats. METHODS: To induce colitis in experimental rats, excluding the sham group, a 4% intrarectal solution of acetic acid was administered. The rats were then given oral doses of cinnamic acid at 30, 45, and 90 mg/kg for two days. The animals were assessed for macroscopic and microscopic changes, and the levels of inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and myeloperoxidase (MPO) were measured using Eliza kits. Additionally, real-time PCR was performed to examine the gene level of toll-like receptor 4 (TLR-4) in the colon. RESULTS: Effective reduction of inflammation in acetic acid-induced colitis was achieved through Cinnamic acid administration at doses of 45 and 90 mg/kg. The decrease was achieved by inhibiting the activities of TNF-α, IL-6, and MPO while downregulating the expression of TLR-4. It is important to note that macroscopic and microscopic evaluations were significant in determining the effectiveness of cinnamic acid in reducing inflammation. CONCLUSION: Downregulation of inflammatory cytokines and TLR-4 expression may contribute to cinnamic acid's anti-inflammatory effect.

Systematic Review on Herbal Preparations for Controlling Visceral Hypersensitivity in Functional Gastrointestinal Disorders.

BACKGROUND: Visceral hypersensitivity (VH) is an overreaction of the gastrointestinal (GI) tract to various stimuli and is characterized by hyperalgesia and/or allodynia. VH contributes to the etiology of many GI dysfunctions, particularly irritable bowel syndrome (IBS). Although the exact mechanisms underlying VH are yet to be found, inflammation and oxidative stress, psychosocial factors, and sensorimotor alterations may play significant roles in it. OBJECTIVE: In this review, we provide an overview of VH and its pathophysiological function in GI disorders. Adverse effects of synthetic drugs may make herbal agents a good candidate for pain management. Therefore, in this review, we will discuss the efficacy of herbal agents in the management of VH with a focus on their anti-inflammatory and antioxidant potentials. METHODS: Data were extracted from clinical and animal studies published in English between 2004 and June, 2020, which were collected from PubMed, Google Scholar, Scopus, and Cochrane Library. RESULTS: Overall, Radix, Melissia, Glycyrrhizae, Mentha, and Liquorice were the most efficient herbals for VH management in IBS and dyspepsia, predominantly through modulation of the mRNA expression of transient receptor potential vanilloid type-1 (TRPV1) and suppression of 5- hydroxytryptamine 3 (5-HT3) or the serotonin receptors. CONCLUSION: Considering the positive effects of herbal formulations in VH management, further research on novel herbal and/or herbal/chemical preparations is warranted.

LRRK2; Communicative Role in the Treatment of Parkinson's Disease and Ulcerative Colitis Overlapping.

BACKGROUND: Involvement of gastrointestinal inflammation in Parkinson's disease (PD) pathogenesis and movement have progressively emerged. Inflammation is involved in the etiology of both PD and inflammatory bowel disease (IBD). Transformations in leucine-rich recurrent kinase 2 (LRRK2) are among the best hereditary supporters of IBD and PD. Elevated levels of LRRK2 have been reported in stimulated colonic tissue from IBD patients and peripheral invulnerable cells from irregular PD patients; thus, it is thought that LRRK2 directs inflammatory cycles. OBJECTIVE: Since its revelation, LRRK2 has been seriously linked in neurons, albeit various lines of proof affirmed that LRRK2 is profoundly communicated in invulnerable cells. Subsequently, LRRK2 might sit at a junction by which stomach inflammation and higher LRRK2 levels in IBD might be a biomarker of expanded risk for inconsistent PD or potentially may address a manageable helpful objective in incendiary sicknesses that increment the risk of PD. Here, we discuss how PD and IBD share covering aggregates, especially regarding LRRK2 and present inhibitors, which could be a helpful objective in ongoing treatments. METHOD: English data were obtained from Google Scholar, PubMed, Scopus, and Cochrane library studies published between 1990-December 2022. RESULT: Inhibitors of the LRRK2 pathway can be considered as the novel treatment approaches for IBD and PD treatment. CONCLUSION: Common mediators and pathways are involved in the pathophysiology of IBD and PD, which are majorly correlated with inflammatory situations. Such diseases could be used for further clinical investigations.

Spinal Muscular Atrophy Treatment: The MTOR Regulatory Intervention.

Spinal muscular atrophy (SMA) is a hereditary disorder affecting neurons and muscles, resulting in muscle weakness and atrophy. Most SMA cases are diagnosed during infancy or early childhood, the most common inherited cause of infant mortality without treatment. Still, SMA might appear at older ages with milder symptoms. SMA patients demonstrate progressive muscle waste, movement problems, tremors, dysphagia, bone and joint deformations, and breathing difficulties. The mammalian target of rapamycin (mTOR), the mechanistic target of rapamycin, is a member of the phosphatidylinositol 3-kinase-related kinase family of protein kinases encoded by the mTOR gene in humans. The mTOR phosphorylation, deregulation, and autophagy have shown dissimilarity amongst SMA cell types. Therefore, exploring the underlying molecular process in SMA therapy could provide novel insights and pave the way for finding new treatment options. This paper provides new insight into the possible modulatory effect of mTOR/ autophagy in SMA management.

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.

Therapeutic approaches for cholestatic liver diseases: the role of nitric oxide pathway.

Cholestasis describes bile secretion or flow impairment, which is clinically manifested with fatigue, pruritus, and jaundice. Neutrophils play a crucial role in many diseases such as cholestasis liver diseases through mediating several oxidative and inflammatory pathways. Data have been collected from clinical, in vitro, and in vivo studies published between 2000 and December 2021 in English and obtained from the PubMed, Google Scholar, Scopus, and Cochrane libraries. Although nitric oxide plays an important role in the pathogenesis of cholestatic liver diseases, excessive levels of NO in serum and affected tissues, mainly synthesized by the inducible nitric oxide synthase (iNOS) enzyme, can exacerbate inflammation. NO induces the inflammatory and oxidative processes, which finally leads to cell damage. We found that natural products such as baicalin, curcumin, resveratrol, and lycopene, as well as chemical likes ursodeoxycholic acid, dexamethasone, rosuvastatin, melatonin, and sildenafil, are able to markedly attenuate the NO production and iNOS expression, mainly through inducing the nuclear factor κB (NF-κB), Janus kinase and signal transducer and activator of transcription (JAK/STAT), and toll like receptor-4 (TLR4) signaling pathways. This study summarizes the latest scientific data about the bile acid signaling pathway, the neutrophil chemotaxis recruitment process during cholestasis, and the role of NO in cholestasis liver diseases. Literature review directed us to propose that suppression of NO and its related pathways could be a therapeutic option for preventing or treating cholestatic liver diseases.

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.

Juglone Mediates Inflammatory Bowel Disease Through Inhibition of TLR-4/NF KappaB Pathway in Acetic Acid-induced Colitis in Rats.

BACKGROUND: Juglone is a phenolic bioactive compound with antimicrobial, antitumour, antioxidant, and anti-inflammatory characteristics. Given its anti-inflammatory and antioxidant effects, it was selected for evaluation in the inflammatory bowel diseases (IBD) model. OBJECTIVE: The current study was performed to evaluate the therapeutic impacts of the juglone in acetic acid-induced colitis in male Wistar rats. METHODS: Juglone was extracted from Pterocarya fraxinifolia via maceration method. Colitis was induced in 36 male Wistar rats (n = 6), except in the sham group, 1 ml of acetic acid 4% was administered intrarectally. Twenty-four hours after induction of colitis, in 3 groups, juglone was administered orally (gavage) at 3 doses of 50, 100, and 150 mg/kg for 2 successive days (once a day). Other groups included the control group (only treated with acetic acid), sham group (normal saline), and standard group (Dexamethasone). To evaluate the inflammation sites, macroscopic and microscopic markers were assessed. The mRNA expression of interleukin (IL)-1ß, and tumor necrosis factor-alpha (TNF)-α were assessed by real-time PCR, while myeloperoxidase (MPO) was measured spectrophotometrically. ELISA assay kits were used to determine the colonic levels of SOD, ROS, NF-κB, and TLR-4. RESULTS: Macroscopic and microscopic assessments revealed that juglone significantly decreased colonic tissue damage and inflammation at 150 mg/kg. Juglone at 100, 150 mg/kg significantly decreased the TNF-α, MPO, and TLR-4 levels, as well as the SOD activity. All juglone-treated groups reduced the NF-κB levels compared to the control group (p < 0.001). The compound decreased the IL-1ß, and ROS levels at the concentration of 150 mg/kg. Juglone attenuated colitis symptoms, reduced inflammation cytokines, declined neutrophil infiltration, and suppressed IL- 1ß and TNF-α expressions in acetic acid-induced colitis rats. It may be proposed that juglone improved colitis in animal model through suppression of inflammatory parameters and downregulation of the NF-κB-TLR-4 pathway. CONCLUSION: Juglone exhibited anti-inflammatory and antioxidant effects in the experimental colitis model and could be a therapeutic candidate for IBD. Juglone should be a subject for further animal and clinical trials in IBD models and for safety concerns.

An Overview of the Pharmacological Properties of Calebin-A.

The natural polyphenol, calebin-A, was recently discovered and identified as a novel phytopharmaceutical with anti-inflammatory, anti-tumor, and antiproliferative properties. Calebin-A occurs naturally in trace quantities in Curcuma longa/C cassia, commonly known as turmeric, from the Zingiberaceae family. Calebin-A is a curcumin analog or 'chemical cousin' of curcumin with a similar chemical structure. Although few research studies have been conducted on the pharmacological and therapeutic properties of calebin-A, it is a very promising molecule with a variety of pharmacological properties. Some studies have suggested that calebin-A is helpful in treating various cancers due to its inhibitory effect on cell growth and anti-inflammatory properties. Other studies have suggested that calebin-A may improve neurocognitive status associated with neurodegeneration caused by Alzheimer's disease (AD) by inhibiting the aggregation of ß-amyloid. Finally, several studies have proposed that calebin-A may potentially be therapeutically beneficial in treating patients with obesity. This novel compound downregulates nuclear factor (NF)-κB-mediated processes involved with cancer, such as tumor cell invasion, proliferation, metastasis, and, most profoundly, inflammation. Moreover, calebin-A influences the activities of mitogen-activated protein kinases (MAPKs) in cancer cells. The present review identifies and discusses the pharmacological and phytochemical properties of calebin-A, as well as its therapeutic benefits and limitations, for future scientists and clinicians interested in exploring calebin-A's medicinal qualities.

Sodium Glucose Transporter-2 Inhibitors (SGLT2Is)-TLRs Axis Modulates Diabetes.

Diabetes affects millions of people worldwide and is mainly associated with impaired insulin function. To date, various oral anti-diabetic drugs have been developed, of which, the sodium glucose transporter-2 inhibitors (SGLT2Is) are of the most recent classes that have been introduced. They differ from other classes in terms of their novel mechanism of actions and unique beneficial effects rather than just lowering glucose levels. SGLT2Is can protect body against cardiovascular events and kidney diseases even in non-diabetic individuals. SGLT2Is participate in immune cell activation, oxidative stress reduction, and inflammation mediation, thereby, moderating diabetic complications. In addition, toll like receptors (TLRs) are the intermediators of the immune system and inflammatory process, thus it's believed to play crucial roles in diabetic complications, particularly the ones that are related to inflammatory reactions. SGLT2Is are also effective against diabetic complications via their anti-inflammatory and oxidative properties. Given the anti-inflammatory properties of TLRs and SGLT2Is, this review investigates how SGLT2Is can affect the TLR pathway, and whether this could be favorable toward diabetes.

Pharmacological activities of turmerones.

Turmerones are major bioactive compounds of Curcuma species with several beneficial pharmacological activities. In addition, various in vivo and in vitro studies noted that turmerones could affect different cytokines, metabolic pathways, and targets. Turmerones will have the potential to be a candidate agent to lessen many pathological and immunological conditions as a result of these pharmacological activities. In this review, we provided information about the pharmacological actions of turmerones using search engines such as PubMed, Google Scholar, Scopus, and Web of Science.

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: 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.

Licofelone Attenuates Acetic Acid-Induced Colitis in Rats Through Suppression of the Inflammatory Mediators.

Licofelone is a dual Cyclooxygenase 1,2 (COX1,2)/5-lipoxygenase) 5-LOX (inhibitor with analgesic and anti-inflammatory effects with possible functions on inflammatory bowel disease (IBD), which is a chronic recurrent condition with no particular treatment. This study evaluated the anti-inflammatory effects of licofelone on acetic acid-induced colitis in rats. Ten groups of male Wistar rats (n = 6) were used. Sham, control group, licofelone at doses of 2.5, 5, and 10 mg/kg, L-NG-nitro arginine methyl ester (L-NAME) (10 mg/kg, i.p.), aminoguanidine (AG) (100 mg/kg, i.p.), 30 min before using licofelone (10 mg/kg). Also, three groups received L-NAME, aminoguanidine, or dexamethasone. Macroscopic, microscopic, and biochemical analysis of myeloperoxidase (MPO), and nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß), superoxide dismutase (SOD), reactive oxygen species (ROS), and Toll-like receptor 4 (TLR-4) were assessed in colon tissue. Licofelone at a dose of 10 mg/kg attenuated colitis, increased SOD activity, and significantly reduced colonic levels of the abovementioned inflammatory factors. In addition, licofelone improved macroscopic and microscopic symptoms in the acetic acid-induced colitis model. Moreover, the concurrent use of nitric oxide synthase (NOS) inhibitors with 10 mg/kg of licofelone reversed the observed positive effects, demonstrating the function of nitric oxide in IBD pathogenesis and the probable mechanism for licofelone in the healing process of induced colitis. A reduced level of inflammatory factors confirmed the anti-inflammatory activity of licofelone as a dual COX1,2/5-LOX inhibitor. Furthermore, outcomes revealed the protective role of licofelone in treating experimental colitis. The findings are suggestive of the potential use of licofelone in IBD.

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.

Management of Hemorrhagic Fever Viruses: Intervention of Natural and Synthetic Products.

BACKGROUND: Viral hemorrhagic fevers (VHFs) are a group of clinical syndromes caused by several different RNA virus families, including several members of the arenavirus, bunyavirus, filovirus, and flavivirus families. VHFs have high mortality rates, and they have been associated with vascular permeability, malaise, fever, variable degrees of hemorrhage, reduced plasma volume, and coagulation abnormalities. To treat such conditions, antigen-presenting cells target dysregulated immune reactions and productive infections. Monocytes and macrophages produce inflammatory cytokines that damage adaptive immunity, while infected dendritic cells fail to mature correctly, compromising adaptive immunity. Inflammation and uncontrolled virus replication are associated with vascular leakage and coagulopathy. OBJECTIVE: VHF infects both humans and animals and if not treated, causes hemorrhagic manifestations and lethal platelet dysfunction. Besides pharmacological and immunological solutions, the intervention of natural products for VHF management is of great interest. In this review, we gathered current data about the effectiveness of natural products for VHF management. METHODS: Data were extracted from Scopus, Google Scholar, PubMed, and Cochrane library in terms of clinical and animal studies published in English between 1981 to February 2022. RESULTS: Several plants from diverse families and species were identified with antiviral activity against VHF. The combination of botanical therapeutics and multitarget synergistic therapeutic effects is now the widely accepted explanation for the treatment of VHF. Most of these herbal therapeutics have shown promising immunomodulatory effects in vivo and in vitro VHF models. They can probably modulate the immune system in VHF-infected subjects mainly by interfering with certain inflammatory mediators involved in various infectious diseases. CONCLUSION: Natural, in particular, herbal sources can be valuable for the management of various VHFs and their related complications.