Ulcerative colitis is a condition of chronic inflammation affecting the large intestine. The disease is typically characterized by periods of active inflammation alternating with periods of remission. For patients with moderate to severe ulcerative colitis, the first line for induction therapy options includes biologic agents (with or without an immunomodulator) or glucocorticoids. This case highlights the first successful case of ulcerative colitis treated with adalimumab with mesalamine and azathioprine. The patient was initially treated with mesalamine and azathioprine which did not result in significant clinical improvement but the addition of subcutaneous adalimumab showed a remarkable response with drastic improvement in just one year of treatment. Hence, adalimumab could be considered as an option in the management of severe cases in Nepal.

Developing a next-generation oral drug delivery system with enhanced efficacy and limited side effects is highly desired for refractory diseases treatment such as colitis. The bioinspired assembly of drugs within food-grade plants highlights its potential value of this unique hybrid material. Herein, we report the preparation of drug-encapsulated vegetable nanobiohybrid superassembled frameworks as an oral food-grade drug delivery system (SAF-FGDD). The in situ superassembly of SAF-FGDD driven by natural transpiration from living plants is carried out through a sustainable and low-carbon manner, allowing for the assembly of distinct precursors inside edible living plants. As an example, mesalazine, an anti-inflammatory drug, is encapsulated in the frameworks for colitis treatment. The cell activity and feeding experiments of zebrafish and mice demonstrate the excellent efficacy of this SAF-FGDD. Compared with those of the control groups, the disease activity index scores and histological scores of the SAF-FGDD group were significantly decreased by 80% and 98%, respectively. The improved performance is attributed to the biocompatibility and protective effect of SAF-FGDD, allowing for abundant mesalazine to be released and act at the site of the intestine during the process of food digestion. In combination with mature soilless cultivation technology, plant-based organisms with natural structure-forming abilities possess broad commercial prospects in large-scale production of various food-grade functional materials.

A young adult man presented to an outlying emergency department with a sore throat, fever and chills. Upon failure of symptomatic management and a course of amoxicillin, he developed rectal pain and loose stools. Despite outpatient doxycycline treatment for presumed chlamydial proctitis, he developed worsening rectal pain and bloody stools. Results on abdominal and pelvic CT were consistent with proctitis. His symptoms worsened despite added metronidazole for bacterial proctitis. Workup revealed an elevated erythrocyte sedimentation rate, C reactive protein and calprotectin, suggestive of a diagnosis of inflammatory bowel disease (IBD). A colonoscopy revealed proximal tightness of the rectum, and pathology reported features suggestive of IBD. He was treated with prednisone and mesalamine. However, immunostaining positive for cytomegalovirus (CMV) confirmed a diagnosis of tissue-invasive CMV proctitis. This was further supported by serological testing for CMV consistent with a diagnosis of CMV proctitis preceded by a primary CMV infection of the pharynx.

Drug targeting is necessary to deliver drugs to a specific site of action at a rate dictated by therapeutic requirements. The pharmacological action of a drug can thereby be optimised while minimising adverse effects. Numerous colonic drug delivery systems have been developed to avoid such undesirable side effects; however, these systems lack site specificity, leaving room for further improvement. The objective of the present study was to explore the potential of amino-alkoxycarbonyloxymethyl (amino-AOCOM) ether prodrugs as a general approach for future colonic delivery. To circumvent inter- and intra-subject variabilities in enzyme activities, these prodrugs do not rely on enzymes but rather are activated via a pH-triggered intramolecular cyclisation-elimination reaction. As proof of concept, model compounds were synthesised and evaluated under various pH conditions, simulating various regions of the gastrointestinal tract (GIT). Probe 15 demonstrated excellent stability under simulated stomach- and duodenum-like conditions and protected 60% of the payload in a small intestine-like environment. Moreover, 15 displayed sustained release at colonic pH, delivering >90% of the payload over 38 h. Mesalamine (Msl) prodrugs 21 and 22 were also synthesised and showed better stability than probe 15 in the simulated upper GIT but relatively slower release at colonic pH (61-68% of Msl over 48 h). For both prodrugs, the extent of release was comparable to that of the commercial product Asacol. This study provides initial proof of concept regarding the use of a cyclisation-activated prodrug for colon delivery and suggests that release characteristics still vary on a case-by-case basis.

Acute interstitial nephritis (AIN) corresponds to a decline in kidney function due to an injury induced by drugs (in the majority of cases), infections, and autoimmune disorders. It is characterized by the presence of an interstitial inflammatory infiltrate in the kidney. Here, we describe a case of a man with a previous medical history relevant to ulcerative colitis (UC) who was admitted due to acute kidney injury (AKI) in the setting of AIN secondary to mesalazine.

Amyloid formation due to protein aggregation is associated with several amyloid diseases (amyloidosis). The use of small organic ligands as inhibitors of protein aggregation is an attractive strategy for the treatment of these diseases. In the present study, we evaluated the in vitro inhibitory and destabilizing effects of Mesalazine on human insulin fibrillation. To induce fibrillation, human insulin was incubated in 50 mM glycine buffer (pH 2.0) at 50 °C. The effect of Mesalazine on insulin amyloid aggregation was studied using spectroscopic, imaging, and computational approaches. Based on the results, the Mesalazine in a concentration-dependent manner (different ratios (1:0.1, 1:0.5, 1:1, and 1:5) of the insulin to Mesalazine) prevented the formation of amyloid fibrils and destabilized pre-formed fibrils. In addition, our molecular docking study confirmed the binding of Mesalazine to insulin through hydrogen bonds and hydrophobic interactions. Our findings suggest that Mesalazine may have therapeutic potential in the prevention of insulin amyloidosis and localized amyloidosis.

The coronavirus disease (COVID-19) pandemic represents a global health challenge, particularly considering concomitant diseases. Patients with inflammatory bowel diseases (IBD) can be considered a population at risk. On the other hand, the risk of developing IBD and COVID-19 have both been described as modulated by vitamin D (VD) levels. In this work, a cohort of 106 adult patients affected by IBD was prospectively enrolled, during the second wave of the pandemic in Italy. In these patients, VD plasma levels, demographic, and clinical characteristics were tested for a correlation/an association with the risk of infection with SARS-CoV-2 in the study period (anti-spike IgG positivity) and the severity of COVID-19 symptoms. By multivariate logistic regression analysis, VD supplementation (Odds Ratio; OR 0.116, p = 0.002), therapy with monoclonal antibodies (OR 0.227, p = 0.007), and the use of mesalazine (OR 2.968, p = 0.046) were found to be independent predictors of SARS-CoV-2 positivity. Moreover, hypertension was associated with severe disease (p = 0.019), while a VD level higher than 30 ng/mL (p = 0.031, OR 0.078) was associated with asymptomatic infection. No interplay between IBD activity and COVID-19 risk of infection or symptoms was observed. These results confirm the importance of VD levels in defining the risk of COVID-19 and give encouraging data about the safety of maintaining immunomodulatory treatments for IBD during the COVID-19 pandemic.

Ulcerative colitis (UC) is a global inflammatory bowel disease. This study aimed to assess the effects of icosapent ethyl on acetic acid-induced colitis in rats as well as the underlying mechanisms involved. 36 male Wister rats were equally divided into six groups: control, UC, mesalamine 100 mg/kg, icosapent 150mg/kg, icosapent 300 mg/kg, and EX527-icosapent 300 mg/kg groups. Except for control group, UC was induced by acetic acid instillation into colon. Drugs were administered once daily for one week then under thiopental anaesthesia, colons were excised. Colitis macroscopic and microscopic scores were assessed. A part of colon was homogenized for detection of malondialdehyde (MDA), inerleukin1 (IL-1β), tumor necrosis factor (TNF-α), superoxide dismutase (SOD), phosphorylated Akt (pAkt) and caspase 3 levels. Silent information regulator 1 (SIRT1), heme oxygenase 1 (HO-1), and nuclear factor erythroid 2 (Nrf2) mRNA expressions were detected. Mallory-stained colonic sections were examined for collagen fibres detection. Immunohistochemistry of NF-κB and p53 expressionsin colonic sections were assessed. Acetic acid induced colitis with increments in MDA, IL-1β, TNF-α, and caspase 3 levels while decreased SOD, pAkt, SIRT1, HO-1, and Nrf2 with increased collagen fibres as well as NF-κB and p53. Icosapent decreased macro& microscopic colitis scores, MDA, IL-1β, TNF-α, and caspase 3 levels while increased SOD, pAkt, SIRT1, HO-1, and Nrf2 with decreased collagen fibres as well as NF-κB and p53. The effects of icosapent 300 mg/kg were similar to mesalamine. Icosapent effects were antagonized by EX527. Icosapent alleviated acetic acid-induced colitis via its anti-inflammatory, antioxidant, and anti-apoptotic effects mediated in part by SIRT1 pathway activation.

We encapsulated MSZ in zein nanoparticles (NP-ZN) using a desolvation method followed by drying in a mini spray dryer. These nanoparticles exhibited a size of 266.6 ± 52 nm, IPD of 0.14 ± 1.1 and zeta potential of -36.4 ± 1.5 mV, suggesting colloidal stability. Quantification using HPLC showed a drug-loaded of 43.8 µg/mg. SEM demonstrated a spherical morphology with a size variation from 220 to 400 nm. A FTIR analysis did not show drug spectra in the NPs in relation to the physical mixture, which suggests drug encapsulation without changing its chemical structure. A TGA analysis showed thermal stability up to 300 °C. In vitro release studies demonstrated gastroresistance and a sustained drug release at pH 7.4 (97.67 ± 0.32%) in 120 h. The kinetic model used for the release of MSZ from the NP-ZN in a pH 1.2 medium was the Fickian diffusion, in a pH 6.8 medium it was the Peppas-Sahlin model with the polymeric relaxation mechanism and in a pH 7.4 medium it was the Korsmeyer-Peppas model with the Fickian release mechanism, or "Case I". An in vitro cytotoxicity study in the CT26.WT cell line showed no basal cytotoxicity up to 500 μg/mL. The NP-ZN showed to be a promising vector for the sustained release of MSZ in the colon by oral route.

Ulcerative colitis (UC) is one of the inflammatory bowel diseases (IBD). It is a chronic autoimmune inflammation of unclear etiology affecting the colon and rectum, characterized by unpredictable exacerbation and remission phases. Conventional treatment options for UC include mesalamine, glucocorticoids, immunosuppressants, and biologics. The management of UC is challenging, and other therapeutic options are constantly being sought. In recent years more attention is being paid to curcumin, a main active polyphenol found in the turmeric root, which has numerous beneficial effects in the human body, including anti-inflammatory, anticarcinogenic, and antioxidative properties targeting several cellular pathways and making an impact on intestinal microbiota. This review will summarize the current knowledge on the role of curcumin in the UC therapy.

Ulcerative colitis (UC), a pathological condition of inflammatory bowel disease, is a chronic inflammatory disorder that involves an abnormal immune response and epithelial barrier dysfunction. Although we have previously reported the anti-inflammatory effects of 7-hydroxyl-1-methylindole-3-acetonitrile (7-HMIA), a synthesized analog of arvelexin on macrophages and paw edema, its anti-colitis effect and its mechanism are not known. In this study, colitis was induced in mice model by 4% (w/v) dextran sodium sulfate (DSS) solution in drinking water for 9 days. At the same time, from the first day of administering drinking water containing DSS, the animals were treated with 5-aminosalicylic acid (5-ASA), 75 mg/kg/day, orally) or 7-HMIA (10 or 20 mg/kg/day, intraperitoneally), depending on the experimental group, respectively. The studies were terminated on the tenth day of the experiment. Our data showed that 7-HMIA reduced the disease activity index and spleen/body weight (S/B) ratio, and improved the shortened colon length comparable to the effects of 5-ASA observed in the DSS-exposed mice. 7-HMIA, like 5-ASA, inhibited the histological damage, such as a thickened colonic muscle layer and shortened crypt length in the colon of the mice with DSS-induced colitis. 7-HMIA restored the tight junction-related proteins (occludin, claudin-1, and claudin-2) and epithelial-mesenchymal transition-mediated proteins (E-cadherin, N-cadherin, and vimentin) in the colon tissue of mice with DSS-induced colitis. Additionally, 7-HMIA (20 mg/kg/day) showed the inhibitory effects similar to that of 5-ASA on the myeloperoxidase activity, interleukin (IL)-6 production, and expression levels of inducible nitric oxide synthase (iNOS), and even showed greater inhibition of IL-1β production in the DSS-induced mice. Furthermore, the DSS-induced activation of nuclear factor-kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) were effectively suppressed by 7-HMIA treatment like the effects of 5-ASA. Overall, our findings revealed that 7-HMIA decreased the severity of colitis by protecting the inflamed mucosal barrier by interfering with NF-κB and STAT3 activation.

Background The gut and gut microbiota, which were previously neglected in blood pressure regulation, are becoming increasingly recognized as factors contributing to hypertension. Diseases affecting the gut such as inflammatory bowel disease (IBD) present with aberrant energy metabolism of colonic epithelium and gut dysbiosis, both of which are also mechanisms contributing to hypertension. We reasoned that current measures to remedy deficits in colonic energy metabolism and dysbiosis in IBD could also ameliorate hypertension. Among them, 5-aminosalicylic acid (5-ASA; mesalamine) is a PPARγ (peroxisome proliferator-activated receptor gamma) agonist. It attenuates IBD by a dual mechanism of selectively enhancing colonic epithelial cell energy metabolism and ameliorating gut dysbiosis. Methods and Results A total of 2 groups of 11- to 12-week-old male, hypertensive, Dahl salt-sensitive (S) rats were gavaged with (n=10) or without (n=10) 5-aminosalicylic acid (150 mg/kg) for 4 weeks. Rats receiving 5-aminosalicylic acid treatment had a lower mean blood pressure than controls (145±3 mm Hg versus 153±4 mm Hg; P<0.0001). This reduction in blood pressure was accompanied by increased activity of PPARγ, increased expression of energy metabolism-related genes, and lowering of the Firmicutes/Bacteroidetes ratio in the colon, the reduction of which is a marker for the correction of gut dysbiosis. Furthermore, these data were consistent with the American Gut Project wherein the Firmicutes/Bacteroidetes ratio of non-IBD (n=611) patients was significantly lower than patients with IBD (n=631). Conclusions 5-Aminosalicylic acid could be repurposed for hypertension by specifically enhancing the gut energy metabolism and correction of microbiota dysbiosis.

Tuina can effectively alleviate ulcerative colitis-related symptoms, but the mechanism of action is unknown. The purpose of this research is to explore potential pathways for the treatment of tuina through gut microbiota and proteomics techniques. Thirty-two male BALB/c mice were divided into four groups, the control, model, mesalazine, and tuina groups. The ulcerative colitis model was established by freely drinking a 3% dextran sulphate sodium solution for 7 days. The mesalazine group and the tuina group, respectively, received 7 days of mesalazine and tuina treatment. Subsequently, their body weights, feces properties, colon length, histomorphological changes, gut microbiota, and colon proteomics were determined. Body weights, disease activity index score, colon histological scores, and microbiota diversity were restored in the tuina group. At the phylum level, Firmicutes was increased and Bacteroidota decreased. At the family level, Lachnospiraceae increased and Prevotellaceae decreased. At the genus level, the Lachnospiraceae_NK4A136_group was increased. Proteomics detected 370 differentially expressed proteins regulated by tuina, enriched to a total of 304 pathways, including biotin metabolism, Notch signaling pathway, linoleic acid metabolism, and autophagy. Tuina can effectively improve the symptoms of weight loss, fecal properties, and colon inflammation in ulcerative colitis mice and restore the gut microbiota diversity, adjusting the relative abundance of microbiota. The therapeutic effects of tuina may be achieved by modulating the signaling pathways of biotin metabolism, Notch signaling pathway, linoleic acid metabolism, and autophagy.

A woman in her 40s was referred for acute and chronic postprandial abdominal cramps on a background of relapsing remitting multiple sclerosis on ocrelizumab therapy as well as coeliac disease on a gluten-free diet, with a family history of ulcerative colitis. Initial colonoscopy demonstrated mild patchy colitis. The patient was trialled on mesalazine, which was ceased due to intolerance. Subsequently, she continued on mercaptopurine monotherapy for management of mild symptoms. Despite this, her symptoms rapidly progressed, with endoscopic and histological evidence of severe rectal-sparing pancolonic inflammation, consistent with severe ocrelizumab-induced colitis. This was refractory to intravenous methylprednisolone and intravenous cyclosporine rescue therapy, requiring surgical management with a subtotal colectomy and subsequent ileorectal anastomosis, after which she remained in clinical, endoscopic and histological remission.

5-Aminosalicylic acid (5-ASA) is a first-line defense drug used to treat mild cases of inflammatory bowel disease. When administered orally, the active pharmaceutical ingredient is released throughout the gastrointestinal tract relieving chronic inflammation. However, delayed and targeted released systems for 5-ASA to achieve optimal dose volumes in acidic environments remain a challenge. Here, we demonstrate the application of atomic layer deposition (ALD) as a technique to synthesize nanoscale coatings on 5-ASA to control its release in acidic media. ALD Al2O3 (38.0 nm) and ZnO (24.7 nm) films were deposited on 1 g batch powders of 5-ASA in a rotatory thermal ALD system. Fourier transform infrared spectroscopy, scanning electron microscopy, and scanning/transmission electron microscopy establish the interfacial chemistry and conformal nature of ALD coating over the 5-ASA particles. While Al2O3 forms a sharp interface with 5-ASA, ZnO appears to diffuse inside 5-ASA. The release of 5-ASA is studied in a pH 4 solution via UV-vis spectroscopy. Dynamic stirring, mimicking gut peristalsis, causes mechanical attrition of the Al2O3-coated particles, thereby releasing 5-ASA. However, under static conditions lasting 5000 s, the Al2O3-coated particles release only 17.5% 5-ASA compared to 100% release with the ZnO coating. Quartz crystal microbalance-based etch studies confirm the stability of Al2O3 in pH 4 media, where the ZnO films etch 41× faster than Al2O3. Such results are significant in achieving a nanoscale coating-based drug delivery system for 5-ASA with controlled release in acidic environments.

A 50-year-old man with a 20-year history of left-sided ulcerative colitis (UC) presented to our hospital with sudden onset of watery diarrhea. To this point, he had been treated with mesalazine 2.0 g/day for UC and had maintained remission. We considered that the UC had worsened. We immediately performed surveillance colonoscopy, which revealed a normal mucous membrane. The results of blood laboratory examinations were normal. Histopathology of colonic biopsies revealed new-onset collagenous colitis (CC), with a thickened subepithelial collagen band (SECB) and inactive UC. We herein report the importance of random colonic biopsies to diagnose CC even when the endoscopic appearance of the colon is normal in patients with inflammatory bowel disease with worsened diarrhea.

This study deciphered the mechanism of Shenling Baizhu Powder in treatment of mouse model of ulcerative colitis(UC) via NOD-like receptor thermoprotein domain 3(NLRP3) signaling pathway. After three days of adaptive feeding, 70 SPF-grade BALB/c mice were randomized into 7 groups: normal group, model group(dextran sodium sulfate, DSS), mesalazine group(DSS + 5-aminosalicylic acid, 5-ASA), NLRP3 inhibitor group(DSS + MCC950), and high-, medium-, and low-dose Shenling Baizhu Powder groups(DSS + high-, medium-, and low-dose Shenling Baizhu Powder), with 10 mice per group. The normal group had free access to double distilled water, and the remaining groups had free access to DSS-containing water to establish the acute UC model. Intragastric administration was started at the same time as modeling for one week. During the experiment, the general mental state and disease activity of each group of mice were recorded and scored. After the experiment, colon and serum samples were collected. The pathological changes in colon tissue were observed through hematoxylin-eosin(HE) staining. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the levels of interleukin-18(IL-18) and myeloperoxidase(MPO) in colon tissue and interleukin-1β(IL-1β) in serum. Immunofluorescence(IF) and immunohistochemistry(IHC) methods were employed to examine the expression of NLRP3 and IL-18 in colon tissue. Western blot was employed to measure the protein levels of NLRP3, apoptosis-associated speck-like protein(ASC), cystein-aspartate protease 1(caspase-1), and downstream inflammatory cytokines in colon tissue. Compared with the normal group, the modeling of UC increased the disease activity index(DAI), colon pathological injury score, IL-1β level in serum, and IL-18 and MPO levels in colon tissue(P<0.05, P<0.01). Furthermore, the modeling caused obvious pathological changes and up-regulated the expression of NLRP3, caspase-1, ASC, pro-IL-1β, cleaved-IL-1β, pro-IL-18, and cleaved-IL-18 in the colon(P<0.01). Compared with the model group, the administration of corresponding drugs decreased the DAI, pathological injury score, IL-1β level in serum, and IL-18 and MPO levels in colon tissue, and down-regulated the protein levels of NLRP3, caspase-1, ASC, pro-IL-1β, cleaved-IL-1β, pro-IL-18, and cleaved-IL-18 in the colon(P<0.05, P<0.01). According to the results of previous study and this study, we concluded that Shenling Baizhu Powder can alleviate the inflammatory response and intestinal damage of DSS-induced UC by regulating the expression of the proteins and inflammatory cytokines associated with NLRP3 signaling pathway.

To compare the effects of aminosalicylic acid, glucocorticoids and immunosuppressants on the expression levels of multidrug resistance genes in patients with ulcerative colitis (UC), with the aim of providing a theoretical and therapeutic basis for the diagnosis, treatment, and prevention of UC. Fresh colonic mucosal tissues or postoperative pathological biopsies from 148 UC patients were collected, and the distribution sites and morphology of P-glycoprotein (P-gp) were detected using immunohistochemical staining. RT-PCR was used to quantify the expression levels of multidrug resistance gene (MDR1) mRNA before and after the corresponding treatment, and the effects of aminosalicylic acid, glucocorticoids and immunosuppressive drugs on P-gp were compared. In addition, the effects of the three drugs on MDR1 mRNA were analyzed. Administration of 5-aminosalicylic acid (5-ASA) drugs did not correlate with MDR1 expression in UC, whereas administration of glucocorticoids and immunosuppressive drugs was positively correlated with MDR1 expression profile. The expression levels of MDR1 mRNA and its product P-gp were significantly upregulated in patients who did not respond to glucocorticoids and immunosuppressive drugs. 5-ASA had no effect on the expression levels of MDR1 and its product P-gp in patients with a confirmed diagnosis of UC. However, the use of glucocorticoids and immunosuppressants can increase the expression level of MDR1.

Mesalamine is a key drug in the treatment of ulcerative colitis (UC) for both induction and maintenance therapy. On the other hand, it is known that there are some cases of mesalamine intolerance that are difficult to distinguish from symptoms due to aggravation of UC. The aim of this study is to investigate the clinical characteristic of mesalamine intolerance in UC. A retrospective, observational study was conducted. We enrolled 31 patients who were diagnosed as mesalamine intolerance between April 2015 to March 2020. We examined clinical features, time to onset, drug types of mesalamine, DLST positive rate, colonoscopy findings, disease activity, and clinical course after diagnosis. The average dose of mesalamine was 3.69 g and DLST-positive was 57.1%. Within the first 2 weeks from the start of mesalamine, 51.6% showed symptoms of intolerance. The serum CRP level was relatively high at ≥10.0 mg/dl in 53.6% of the cases. There was no difference in clinical background, symptoms, or laboratory findings between patients with DLST-positive and negative. In this study, we clarified the clinical characteristics of mesalamine intolerant patients, and found no difference in the clinical background or success rate of desensitization therapy between positive and negative DLST cases.

Sulfasalazine and its active metabolite mesalamine are poorly excreted into breastmilk. However, rather high levels of the mesalamine metabolite N-acetyl-5-ASA appear in breastmilk and its effects on breastfed infants are unknown. Another sulfasalazine metabolite, sulfapyridine, also appears in milk and infant serum and might cause hemolysis, especially in newborn infants and in those with glucose-6-phosphate dehydrogenase (G6PD) deficiency. The time of greatest risk for hemolysis in fullterm newborns without G6PD deficiency might be as short as 8 days after birth.[1] Bloody diarrhea has occurred in an infant whose mother was taking sulfasalazine and a few cases of diarrhea have been reported in infants exposed to mesalamine in breastmilk, although the rate is not high. Most experts consider mesalamine derivatives to be safe during breastfeeding.[2-7] If sulfasalazine is required by the mother, it is not a reason to discontinue breastfeeding, but carefully observe breastfed infants for diarrhea. Other mesalamine derivatives that do not contain a sulfonamide are preferred.

(1) Background: Nuclear factor κB (NF-κB) is an important transcriptional regulator that regulates the inflammatory pathway and plays a key role in cellular inflammatory and immune responses. The presence of a high concentration of NF-κB is positively correlated with the severity of inflammation. Therefore, the inhibition of this pathway is an important therapeutic target for the treatment of various types of inflammation; (2) Methods: we designed and synthesized 23 mollugin derivatives and evaluated their inhibitory activity against NF-κB transcription; (3) Results: Compound 6d exhibited the most promising inhibitory activity (IC50 = 3.81 µM) and did not show any significant cytotoxicity against the tested cell lines. Investigation of the mechanism of action indicated that 6d down-regulated NF-κB expression, possibly by suppressing TNF-α-induced expression of the p65 protein. Most of the compounds exhibited potent anti-inflammatory activity. Compound 4f was the most potent compound with 83.08% inhibition of inflammation after intraperitoneal administration, which was more potent than mollugin and the reference drugs (ibuprofen and mesalazine). ADMET prediction analysis indicated that compounds 6d and 4f had good pharmacokinetics and drug-like behavior; (4) Conclusions: Several series of mollugin derivatives were designed, synthesized, and evaluated for NF-κB inhibitory activity and toxicity. These results provide an initial basis for the development of 4f and 6d as potential anti-inflammatory agents.

Controlled release is often preferred for orally administrated bioactive compounds and drugs. In this study, a nanocellulose (NC) incorporated oleogel encapsulation system was developed for controlled release of active agents. 5-Aminosalicylic acid (5-ASA), an anti-inflammatory drug to treat inflammatory bowel diseases, was used as an example core ingredient for demonstrating the efficacy of the system. Oleogels with/without NC incorporation encapsulating 5-ASA were prepared and tested by in vitro digestion study, and 5-ASA released from the matrix was quantified by a novel UV-Vis spectrometric method developed in this study. The oleogel encapsulation system was characterized by assessing the encapsulation efficiency, oxidative stability, gel hardness, microstructure, and thermal stability. Results showed that sorbitan tristearate-induced oleogel system successfully protected 5-ASA during GI digestion. The incorporation of NC solutions with different NC types, concentrations and volumes further modified the release rate. Specifically, the release of 5-ASA in NC incorporated matrix was <6 % in the gastric phase, and ranged between 17.42 % - 38.28 % in the small intestine depending on the added NC type and concentration. Additionally, the incorporation of NC improved physicochemical stability of the gel matrix. The new 5-ASA quantification method developed in this study is simpler and faster compared with currently available methods.