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.

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.

Ginger and its constituents: Role in treatment of inflammatory bowel disease.

Inflammatory bowel diseases (IBD), with obscure etiology, are rising and are of worldwide concern. Of the various components of IBD pathogenesis and progression, irritation appears to play a major part. Investigations on the molecular and cellular pathways that activate the IBD provide the focus for the development of useful therapies. Ginger (the rhizome of Zingiber officinale) has a broad spectrum of clinical applications due to its anti-inflammatory and anti-oxidative functions. Inflammation and oxidative stress are the key pathogenic factors in many diseases, including IBD. The most established components of ginger are phenolic compounds called gingerols. A wide range of pharmacological activities of the potential therapeutic benefit of Z. officinale have been detailed. In this regard, the anti-inflammatory activity of ginger has been documented by many researchers. It was shown that ginger is a potent inhibitor of the nuclear factor kappa B (NF-κB), signal transducer of activators of transcription (STATs), Nod-like receptor family proteins (NLRPs), toll-like receptors (TLRs), mitogen-activated protein kinase (MAPKs), and mTOR (mTOR) pathways, as well as inhibiting various pro-inflammatory cytokines. In the present report, the potential application of ginger in the management of IBD is reviewed in detail, with an emphasis on the relevant properties of ginger and its bioactive components. The significance of the functions, side effects, and delivery of ginger to the digestive system for particular application in IBD are also considered.

Prospects of Saffron and its Derivatives in Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia in the old age population, making it a worldwide concern. Unfortunately, few drugs have been presented for treatment of mild and moderate AD. To meet this need, more effective anti-AD agents are emerging. Accumulating evidence supports the beneficial roles of natural-based products in brain function, neurotransmission, neurogenesis, synaptogenesis, and the prevention of amyloid fibrillation and neuronal injury. Several in vitro, preclinical, and clinical studies suggest that saffron (its bioactive compounds) is a potential nutraceutical with antioxidant, radical scavenging, anti-inflammatory, hypolipidemic, hypotensive, neuroendocrine, and neuroprotective effects. It has also been proposed that saffron may delay the onset of AD, prevent its progression or help to attenuate the symptoms of the disease. Therefore, we performed a comprehensive search on this plant and its derivatives for AD treatment. Saffron and its active constituents interfere with AD by improving learning behavior, spatial memory, and cognitive function; protecting against neuronal loss; inhibiting beta-amyloid aggregation and neurotoxicity; preventing senile plaques and neurofibrillary tangle (NFT) formation; suppressing the acetylcholinesterase (AChE) activity; and reducing neuroinflammation. Given conclusive scientific findings, saffron and its derivatives might counter neurodegenerative diseases through multiple pathways. Further clinical trials are expected to confirm the neuroprotective properties of this herb and also to translate such findings to improve patients' outcomes.

Antibiotics with therapeutic effects on spinal cord injury: a review.

Accumulating evidence indicates that a considerable number of antibiotics exert anti-inflammatory and neuroprotective effects in different central and peripheral nervous system diseases including spinal cord injury (SCI). Both clinical and preclinical studies on SCI have found therapeutic effects of antibiotics from different families on SCI. These include macrolides, minocycline, ß-lactams, and dapsone, all of which have been found to improve SCI sequels and complications. These antibiotics may target similar signaling pathways such as reducing inflammatory microglial activity, promoting autophagy, inhibiting neuronal apoptosis, and modulating the SCI-related mitochondrial dysfunction. In this review paper, we will discuss the mechanisms underlying therapeutic effects of these antibiotics on SCI, which not only could supply vital information for investigators but also guide clinicians to consider administering these antibiotics as part of a multimodal therapeutic approach for management of SCI and its complications.

Transmembrane serine protease 2 and angiotensin-converting enzyme 2 anti-inflammatory receptors for COVID-19/inflammatory bowel diseases treatment.

Inflammatory bowel diseases (IBD) refer to a subgroup of chronic, progressive, long-term, and relapsing inflammatory disorders. IBD may spontaneously grow in the colon, and in severe cases may result in tumor lesions such as invasive carcinoma in inflamed regions of the intestine. Recent epidemiological reports indicate that old age and underlying diseases such as IBD contribute to severity and mortality in patients with coronavirus disease 2019 (COVID-19). Currently, the ongoing COVID-19 pandemic caused serious morbidity and mortality worldwide. It has also been shown that the transmembrane serine protease 2 is an essential factor for viral activation and viral engulfment. Generally, viral entry causes a 'cytokine storm' that induces excessive generation of proinflammatory cytokines/chemokines including interleukin (IL)-6, IL-2, IL-7, tumor necrosis factor-α, and interferon-γ. Future research could concentrate on developing inflammatory immunological responses that are efficient to encounter COVID-19. Current analysis elucidates the role of inflammation and immune responses during IBD infection with COVID-19 and provides a list of possible targets for IBD-regulated therapies in particular. Data from clinical, in vitro, and in vivo studies were collected in English from PubMed, Google Scholar, Scopus, and the Cochrane library until May 2021.

Interventions of natural and synthetic agents in inflammatory bowel disease, modulation of nitric oxide pathways.

Inflammatory bowel disease (IBD) refers to a group of disorders characterized by chronic inflammation of the gastrointestinal (GI) tract. The elevated levels of nitric oxide (NO) in serum and affected tissues; mainly synthesized by the inducible nitric oxide synthase (iNOS) enzyme; can exacerbate GI inflammation and is one of the major biomarkers of GI inflammation. Various natural and synthetic agents are able to ameliorate GI inflammation and decrease iNOS expression to the extent comparable with some IBD drugs. Thereby, the purpose of this study was to gather a list of natural or synthetic mediators capable of modulating IBD through the NO pathway. Electronic databases including Google Scholar and PubMed were searched from 1980 to May 2018. We found that polyphenols and particularly flavonoids are able to markedly attenuate NO production and iNOS expression through the nuclear factor κB (NF-κB) and JAK/STAT signaling pathways. Prebiotics and probiotics can also alter the GI microbiota and reduce NO expression in IBD models through a broad array of mechanisms. A number of synthetic molecules have been found to suppress NO expression either dependent on the NF-κB signaling pathway (i.e., dexamethasone, pioglitazone, tropisetron) or independent from this pathway (i.e., nicotine, prednisolone, celecoxib, ß-adrenoceptor antagonists). Co-administration of natural and synthetic agents can affect the tissue level of NO and may improve IBD symptoms mainly by modulating the Toll like receptor-4 and NF-κB signaling pathways.