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Journal of Pharmaceutical Analysis Dec 2023This review aims to identify in vivo studies investigating the potential of plant substances and their natural molecules in managing inflammatory bowel disease (IBD).... (Review)
Review
This review aims to identify in vivo studies investigating the potential of plant substances and their natural molecules in managing inflammatory bowel disease (IBD). Specifically, the objective is to examine the impact of these substances on interleukins and other key inflammatory signaling markers. Relevant articles published up to December 2022 were identified through a search of the PubMed, Scopus, Web of Science, and Embase databases. The search used keywords including "inflammatory bowel disease", "medicinal plants", "natural molecules", "anti-inflammatory", and "ulcerative colitis", and identified 1,878 potentially relevant articles, of which 89 were included in this review after completion of the selection process. This study provides preclinical data on natural products (NPs) that can potentially treat IBD, including ulcerative colitis. The main actions of these NPs relate to their effects on nuclear factor kappa B (NF-κB), the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway, the regulation of T helper 17/regulatory T cells balance, and oxidative stress. The ability of these NPs to inhibit intestinal inflammation appears to be dependent on lowering levels of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and IL-17, via the Jun N-terminal kinase (JNK)1, NF-κβ-p65, and STAT3 pathways. In addition, NPs were shown to reduce oxidative stress and the severity of ulcerative colitis, as well as increase the activity of antioxidant enzymes. These actions suggest that NPs represent a promising treatment for IBD, and potentially have greater efficacy and safety than current treatments.
PubMed: 38223446
DOI: 10.1016/j.jpha.2023.09.012 -
Journal of Pharmaceutical Analysis Dec 2023Excessive -acetyl--benzoquinone imine (NAPQI) formation is a starting event that triggers oxidative stress and subsequent hepatocyte necrosis in acetaminophen (APAP)...
Excessive -acetyl--benzoquinone imine (NAPQI) formation is a starting event that triggers oxidative stress and subsequent hepatocyte necrosis in acetaminophen (APAP) overdose caused acute liver failure (ALF). glutathionylation is a reversible redox post-translational modification and a prospective mechanism of APAP hepatotoxicity. Glutaredoxin-1 (Glrx1), a glutathione-specific thioltransferase, is a primary enzyme to catalyze deglutathionylation. The objective of this study was to explored whether and how Glrx1 is associated with the development of ALF induced by APAP. The knockout mice () and liver-specific overexpression of () mice were produced and underwent APAP-induced ALF. Pirfenidone (PFD), a potential inducer of Glrx1, was administrated preceding APAP to assess its protective effects. Our results revealed that the hepatic total protein glutathionylation (PSSG) increased and the Glrx1 level reduced in mice after APAP toxicity. mice were more sensitive to APAP overdose, with higher oxidative stress and more toxic metabolites of APAP. This was attributed to Glrx1 deficiency increasing the total hepatic PSSG and the glutathionylation of cytochrome p450 3a11 (Cyp3a11), which likely increased the activity of Cyp3a11. Conversely, mice were defended against liver damage caused by APAP overdose by inhibiting the glutathionylation and activity of Cyp3a11, which reduced the toxic metabolites of APAP and oxidative stress. PFD precede administration upregulated Glrx1 expression and alleviated APAP-induced ALF by decreasing oxidative stress. We have identified the function of Glrx1 mediated PSSG in liver injury caused by APAP overdose. Increasing Glrx1 expression may be investigated for the medical treatment of APAP-caused hepatic injury.
PubMed: 38223455
DOI: 10.1016/j.jpha.2023.08.004 -
PloS One 2024The pathogenesis of anal sacculitis has not been extensively investigated, although atopic dogs seem to be predisposed to the disease. The aim of this study was... (Comparative Study)
Comparative Study
The pathogenesis of anal sacculitis has not been extensively investigated, although atopic dogs seem to be predisposed to the disease. The aim of this study was therefore to characterize and compare the bacterial microbiota and pro-inflammatory cytokines in the anal sacs of dogs from three groups (healthy dogs, untreated atopic dogs and atopic dogs receiving antipruritic treatment or allergen-specific immunotherapy) in order to determine whether changes could be at the origin of anal sacculitis in atopic dogs. Bacterial populations of anal sac secretions from fifteen healthy dogs, fourteen untreated and six treated atopic dogs were characterized by sequencing the V4 region of the 16S rRNA gene using Illumina technology. Proinflammatory cytokines were analyzed with the Luminex multiplex test. Community membership and structure were significantly different between the anal sacs of healthy and untreated atopic dogs (P = 0.002 and P = 0.003, respectively) and between those of untreated and treated atopic dogs (P = 0.012 and P = 0.017, respectively). However, the community structure was similar in healthy and treated atopic dogs (P = 0.332). Among the proinflammatory cytokines assessed, there was no significant difference between groups, except for interleukin 8 which was higher in the anal sacs of untreated atopic dogs compared to treated atopic dogs (P = 0.02), and tumor necrosis factor-alpha which was lower in the anal sacs of healthy dogs compared to treated atopic dogs (P = 0.04). These results reveal a dysbiosis in the anal sacs of atopic dogs, which may partially explain the predisposition of atopic dogs to develop bacterial anal sacculitis. Treatments received by atopic dogs (oclacitinib, desloratadine and allergen-specific immunotherapy) shift the microbiota of the anal sacs towards that of healthy dogs. Further studies are required to identify significant cytokines contributing to anal sacculitis in atopic dogs.
Topics: Animals; Dogs; Cytokines; Dog Diseases; Anal Sacs; Male; Microbiota; Female; RNA, Ribosomal, 16S; Dermatitis, Atopic; Case-Control Studies; Bacteria
PubMed: 38814946
DOI: 10.1371/journal.pone.0298361 -
Analytical Cellular Pathology... 2023Early reperfusion into the myocardium after ischemia causes myocardial ischemia-reperfusion (I/R) injury and ferroptosis was involved. Ischemia activates the expression...
Early reperfusion into the myocardium after ischemia causes myocardial ischemia-reperfusion (I/R) injury and ferroptosis was involved. Ischemia activates the expression of a series of oxidative stress genes and their downstream regulatory genes, including ferroptosis-related genes such as nuclear factor E2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4), and SLC7A11. This study adopted primary cardiomyocytes and I/R in rats to evaluate the ferroptosis and changing of Nrf2-SLC7A11/heme oxygenase-1 (HO-1) and . Online analysis tools were used to predict the possible target Kelch-like ECH-associated protein 1 (Keap1) of miR-432-5p. The mimic of miR-432-5p plasmid was constructed to verify the effect of miR-432-5p on ferroptosis. We found that hypoxia/reoxygenation (H/R) in cardiomyocytes and I/R in rats induced lipid peroxidation and ferroptosis in cardiomyocytes. The activation of the Nrf2-SLC7A11/HO-1 pathway protects cardiomyocytes from ferroptosis. Downregulation of miR-432-5p has been confirmed in H/R cardiomyocytes () and cardiomyocytes in myocardial infarction rats (). Upregulation of miR-432-5p inhibited ferroptosis of cardiomyocytes induced by RAS-selective lethal 3 (RSL3), an inhibitor of GPX4 and ferroptosis inducer through decreasing the binding protein of Nrf2, Keap1, which was confirmed by bioinformatics and mutation assay. Knockdown Nrf2 attenuates the protection effect of miR-432-5p on H/R cardiomyocytes. Intravenous delivery of liposome carriers of miR-432-5p remarkably ameliorated cardiomyocyte impairment in the I/R animal model. In conclusion, miR-432-5p inhibits the ferroptosis in cardiomyocytes induced by H/R by activating Nrf2/SLC7A11 axis by degrading Keap1 and is a potential drug target for clinical myocardial infarction treatment.
Topics: Animals; Rats; Ferroptosis; Hypoxia; Ischemia; Kelch-Like ECH-Associated Protein 1; MicroRNAs; Myocardial Infarction; Myocardial Reperfusion Injury; Myocytes, Cardiac; NF-E2-Related Factor 2
PubMed: 37822721
DOI: 10.1155/2023/1293200 -
Bilateral Transposition Flap for Postoperative Anal Stenosis after Reconstruction for Paget Disease.Plastic and Reconstructive Surgery.... Aug 2023One of the complications of anal surgery or disease is anal stenosis. To release the tension of the anus, a tension-releasing incision in the perianal skin and various...
One of the complications of anal surgery or disease is anal stenosis. To release the tension of the anus, a tension-releasing incision in the perianal skin and various anoplasty procedures are usually considered. The aim of this article is to describe a straightforward technique with local flaps for severe anal stenosis after anal reconstruction. A 57-year-old man presented to the clinic with diverticulitis secondary to severe anal stenosis, and reported difficulty with defecation after perianal skin resection around the anus and surgery to create a V-Y advancement flap for perianal primary Paget disease 9 months previously. After improvement of the diverticulitis using antibiotics, bilateral transposition flaps were transferred to release the anal stenosis. The surgical treatment for severe anal stenosis has been known to entail several complications, including infection, incontinence, anal mucosal ectropion, pruritus, wound dehiscence, and restenosis. In this severe case, because the scars were situated at the 6 o'clock and 12 o'clock positions on the anus due to the previous V-Y advancement flap, bilateral rotation flaps were transferred from the 3 o'clock and 9 o'clock positions of the anus to prevent wound dehiscence and partial flap necrosis. Three months later, the size of the anus was unchanged, but additional surgery was performed at the patient's request. A bilateral transposition flap procedure was used, with flaps designed and elevated from the 6 o'clock and 12 o'clock positions. The postoperative course was uneventful, and the anal stenosis was improved.
PubMed: 37547347
DOI: 10.1097/GOX.0000000000005142 -
Journal of Pharmaceutical and... Sep 2023Non-alcoholic fatty liver disease (NAFLD) is a clinical syndrome characterized by hepatocyte steatosis and adipose accumulation with the main lesion in the hepatic...
Non-alcoholic fatty liver disease (NAFLD) is a clinical syndrome characterized by hepatocyte steatosis and adipose accumulation with the main lesion in the hepatic lobule, but without a history of excessive alcohol consumption. NAFLD ranges from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), and may further accumulate fibrosis leading to cirrhosis. Many studies have found that ginseng can treat NAFLD. (20 R)-Panaxadiol (PD) is a panax ginseng diol type compound, has been proved that can treat the obesity. This study wants to investigate the effect of PD on non-alcoholic liver disease. We used 20 ob/ob mice and 10 C57BL/6 J mice. C57BL/6 J mice as CONTROL group, ob/ob mice were divided into model group and PD group. In PD group, ob/ob mice were treated with PD for eight weeks(10 mg/kg, the CON and OB group was given the same amount of sodium carboxymethyl cellulose), detected the weight, food intake and serum index, observed the HE staining of liver and intestine, performed the 16 S rRNA and untargeted metabolomics analysis used mice feces, and verify the results by detect the expression of TNF-α, MDA and SOD. In vivo results, PD can improve abnormal glucose and lipid metabolism and liver function. In 16 S rRNA result, we found beneficial bacteria Muribaculaceae and Lactobacillus increased; in untargeted metabolomics analysis, inflammatory metabolites prostaglandin (PG) and lipopolysaccharide (LPS) decreased, antioxidant metabolites FAD and lipoic acid increased. Then, we proceeded the association analysis of gut microbiota and metabolites, the result showed gut microbiota have strongly associated with anti-inflammatory and antioxidant metabolites. In addition, PD improves intestinal wall integrity. Meanwhile, the expression of TNF-α、MDA and SOD were detected, it was verified that PD has the effect of antioxidant and anti-inflammation. Our study showed that PD, as an active ingredient of ginseng, can play an anti-inflammatory and antioxidant role by improving intestinal metabolites, thereby preventing and treating non-alcoholic fatty liver disease to a certain extent.
Topics: Mice; Animals; Non-alcoholic Fatty Liver Disease; Antioxidants; Tumor Necrosis Factor-alpha; Mice, Inbred C57BL; Liver; Obesity; Superoxide Dismutase; Metabolomics; Feces
PubMed: 37473506
DOI: 10.1016/j.jpba.2023.115555 -
Frontiers in Pharmacology 2024Epilepsy is a prevalent neurological disease where neuroinflammation plays a significant role in epileptogenesis. Recent studies have suggested that (APS) have...
Epilepsy is a prevalent neurological disease where neuroinflammation plays a significant role in epileptogenesis. Recent studies have suggested that (APS) have anti-inflammatory properties, which make them a potential candidate for neuroprotection against central nervous system disease. Nevertheless, the extent of their effectiveness in treating epilepsy remains enigmatic. Therefore, our study aims to investigate the potential of APS to mitigate epileptogenesis and its comorbidities by exploring its underlying mechanism. Initially, we employed pentylenetetrazol-induced seizure mice to validate APS' effectiveness. Subsequently, we employed network pharmacology analysis to probe the possible targets and signaling pathways of APS in treating epilepsy. Ultimately, we verified the key targets and signaling pathways experimentally, predicting their mechanisms of action. APS have been observed to disturb the acquisition process of kindling, leading to reduced seizure scores and a lower incidence of complete kindling. Moreover, APS has been found to improve cognitive impairments and prevent hippocampal neuronal damage during the pentylenetetrazole (PTZ)-kindling process. Subsequent network pharmacology analysis revealed that APS potentially exerted their anti-epileptic effects by targeting cytokine and toll-like receptor 4/nuclear factor kappa B (TLR4/NF-κB) signaling pathways. Finally, experimental findings showed that APS efficiently inhibited the activation of astrocytes and reduced the release of pro-inflammatory mediators, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). In addition, APS impeded the activation of the TLR4/NF-κB signaling cascade in a PTZ-induced kindling mouse model. The outcomes of our study suggest that APS exerts an impact on epileptogenesis and mitigates cognitive impairment by impeding neuroinflammatory processes. The mechanism underlying these observations may be attributed to the modulation of the TLR4/NF-κB signaling pathway, resulting in a reduction of the release of inflammatory mediators. These findings partially agree with the predictions derived from network pharmacology analyses. As such, APS represents a potentially innovative and encouraging adjunct therapeutic option for epileptogenesis and cognitive deficit.
PubMed: 38405667
DOI: 10.3389/fphar.2024.1336122 -
JGH Open : An Open Access Journal of... Dec 2023Pouchitis is a common complication after restorative ileal pouch-anal anastomosis following proctocolectomy for ulcerative colitis. Antibiotic-dependent or...
BACKGROUND AND AIM
Pouchitis is a common complication after restorative ileal pouch-anal anastomosis following proctocolectomy for ulcerative colitis. Antibiotic-dependent or antibiotic-refractory chronic pouchitis (CP), which is a common cause of pouch failure affecting 15-20% of patients, is challenging to treat. The efficacy of second-line immunomodulator and biologic therapy remains poorly defined. We present a pooled analysis of real-world efficacy data from peer-reviewed full-text manuscripts, focusing on immunomodulator and biologic therapies in CP.
METHODS
Embase and PubMed databases were searched for full-text articles describing the treatment of CP. We performed a systematic review and pooled analysis of published studies to assess the efficacy of immunomodulators, including thiopurines and methotrexate, and biologics including antitumor necrosis factor, anti-integrin, and interleukin-12/23 antagonists. Clinical and endoscopic response and remission rates were combined for pooled analyses. Rates of treatment discontinuation and safety were also assessed.
RESULTS
Pooled analysis comprised 20 full-text articles (485 patients). Overall clinical response rate was 46% (95% CI: 35-59%) and clinical remission rate was 35% (95% CI: 21-52%). Overall endoscopic response and remission rates were 41% (95% CI: 18-68%) and 15% (95% CI: 5-39%), respectively. Individual agents' safety profile was reassuring, with vedolizumab being the most favorable.
CONCLUSION
The real-world efficacy data of immunomodulators in the treatment of CP is insufficient. Vedolizumab and ustekinumab appeared effective and safe for CP, whereas anti-TNFs showed higher rates of adverse events. The high heterogeneity within the studies is attributed to the real-world study design, obfuscating drug efficacy comparisons across the studies. Further studies are required to define the comparative effectiveness of available treatments of CP.
PubMed: 38162843
DOI: 10.1002/jgh3.13000 -
World Journal of Gastroenterology Oct 2023Treatment of infantile-onset inflammatory bowel disease (IO-IBD) is often challenging due to its aggressive disease course and failure of standard therapies with a need...
BACKGROUND
Treatment of infantile-onset inflammatory bowel disease (IO-IBD) is often challenging due to its aggressive disease course and failure of standard therapies with a need for biologics. Secondary loss of response is frequently caused by the production of anti-drug antibodies, a well-known problem in IBD patients on biologic treatment. We present a case of IO-IBD treated with therapeutic drug monitoring (TDM)-guided high-dose anti-tumor necrosis factor therapy, in which dose escalation monitoring was used as a strategy to overcome anti-drug antibodies.
CASE SUMMARY
A 5-mo-old boy presented with a history of persistent hematochezia from the 10 d of life, as well as relapsing perianal abscess and growth failure. Hypoalbuminemia, anemia, and elevated inflammatory markers were also present. Endoscopic assessment revealed skip lesions with deep colic ulcerations, inflammatory anal sub-stenosis, and deep fissures with persistent abscess. A diagnosis of IO-IBD Crohn-like was made. The patient was initially treated with oral steroids and fistulotomy. After the perianal abscess healed, adalimumab (ADA) was administered with concomitant gradual tapering of steroids. Clinical and biochemical steroid-free remission was achieved with good trough levels. After 3 mo, antibodies to ADA (ATA) were found with undetectable trough levels; therefore, we optimized the therapy schedule, first administering 10 mg weekly and subsequently up to 20 mg weekly (2.8 mg/kg/dose). After 2 mo of high-dose treatment, ATA disappeared, with concomitant high trough levels and stable clinical and biochemical remission of the disease.
CONCLUSION
TDM-guided high-dose ADA treatment as a monotherapy overcame ATA production. This strategy could be a good alternative to combination therapy, especially in very young patients.
Topics: Male; Humans; Adalimumab; Abscess; Neoplasm Recurrence, Local; Inflammatory Bowel Diseases; Antibodies; Steroids; Infliximab
PubMed: 37900586
DOI: 10.3748/wjg.v29.i38.5428