Strong Anti-inflammatory Activity Research Articles

Penifuranone A: A Novel Alkaloid from the Mangrove Endophytic Fungus Penicillium crustosum SCNU-F0006.

One previously undescribed alkaloid, named penifuranone A (1), and three known compounds (2-4) were isolated from the mangrove endophytic fungus Penicillium crustosum SCNU-F0006. The structure of the new alkaloid (1) was elucidated based on extensive spectroscopic data analysis and single-crystal X-ray diffraction analysis. Four natural isolates and one new synthetic derivative of penifuranone A, compound 1a, were screened for their antimicrobial, antioxidant, and anti-inflammatory activities. Bioassays revealed that penifuranone A (1) exhibited strong anti-inflammatory activity in vitro by inhibiting nitric oxide (NO) production in lipopolysaccharide-activated RAW264.7 cells with an IC50 value of 42.2 μM. The docking study revealed that compound 1 exhibited an ideal fit within the active site of the murine inducible nitric oxide synthase (iNOS), establishing characteristic hydrogen bonds.

Evaluation of In vitro anti-inflammatory activity and In-silico pharmacokinetics and molecular docking study of Horsfieldia iryaghedhi

Background: Phytochemicals are still a valuable source to develop clinically important drugs in treating chronic and acute diseases. Inflammation is a response to an injurious stimulus of the body and novel therapeutic agents are needed to alleviate the condition with minimum side effects. Aims and Objectives: To investigate in vitro anti-inflammatory activity of methanol and aqueous leaf, bark, and combination extracts of plant Horsfieldia iryaghedhi by heat-induced egg albumin denaturation method and to analyze the phytochemicals of Horsfieldia iryaghedhi for their anti-inflammatory potential against cyclooxygenase- 2 (COX-2) using molecular docking. Methodology: Matured and fully expanded fresh leaves and barks of H. iryaghedhi were collected, and the extractions were obtained cold maceration using 99.9% methanol and distilled water as solvents. A concentration series was then developed, and the anti-inflammatory activity was evaluated against Diclofenac sodium as the positive control, using the heat-induced egg albumin denaturation method. Further, selected phytochemicals were tested against COX-2 enzyme (PDB ID: 5IKR) using site-specific molecular docking with autodock vina and the binding energies and pharmacokinetic and toxicity parameters were evaluated. Results: The methanol and aqueous extracts have shown a moderate to strong concentration-dependent anti-inflammatory activity with reference to standard Diclofenac sodium (IC50 116.4 μg/ml) and Methanol bark extract exhibited potent anti-inflammatory activity compared to other extracts (IC50 293 μg/ml). Further, Methanol and aqueous extracts showed a statistically significant correlation between concentration and percentage inhibition (p<0.05, R2 ≈1). The molecular docking results suggest that the phytochemicals available on the plant have possible COX-2 inhibitory activity and the compounds selected (Methyl 2,4-dihydroxy-6-methylbenzoate and N, N-Dimethyl-5-methoxy tryptamine) even got favourable toxicity and pharmacokinetic parameters confirming their drugability. Conclusion: Methanol bark extract of Horsfieldia iryaghedhi have marked in vitro anti-inflammatory activity. The results indicate a solid possibility of lead discovery of anti- inflammatory agents from the bark and leaves of Horsfieldia iryaghedhi. However, further molecular dynamics studies and in vivo tests may be required to confirm the findings.

In-silico design and synthesis of curcumin derivatives with enhanced antibacterial and anti-inflammatory activities

Since curcumin and curcuminoids include potential functional groups (such as α, β-unsaturated β-diketone, α, β-unsaturated ketone, and β 0-hydroxy-α, β-unsaturated ketone linked with aromatic rings on both sides), they have been the subject of much discussion. These groups have anti-inflammatory, anti-cancer, and antioxidant qualities, among other bioactivities. Using spectroscopic techniques, novel compounds of curcumin were created and described. This study assessed the antibacterial and anti-inflammatory properties of PDB ID:1IU 4 and PDB ID: 4LHF molecular docking, utilizing in silico models. In terms of binding affinity, compounds C-04 and C-05 they had a greater affinity for the 1IU4 and 4LHF, respectively. Using the Agar disc diffusion plate method (500μg/mL), the derivatized compounds were evaluated for their in-vitro antibacterial properties against two strains: S. Aureus and E. coli. When compared to conventional ciprofloxacin, compound C-04 demonstrated good to exceptional antibacterial efficacy against two distinct strains. they were further tested utilizing the carrageenan-induced paw edema method for anti-inflammatory efficacy. By using the HRBC membrane stabilizing test method, Compound C-05 showed strong anti-inflammatory action, while Compounds C-05 &and C-06 demonstrated noteworthy anti-inflammatory activity.

The Long-Acting Serine Protease Inhibitor mPEG-SPA-MDSPI16 Alleviates LPS-Induced Acute Lung Injury.

Anti-inflammatory drugs have become the second-largest class of common drugs after anti-infective drugs in animal clinical care worldwide and are often combined with other drugs to treat fever and viral diseases caused by various factors. In our previous study, a novel serine protease inhibitor-encoding gene (MDSPI16) with improved anti-inflammatory activity was selected from a constructed suppressive subducted hybridization library of housefly larvae. This protein could easily induce an immune response in animals and had a short half-life, which limited its wide application in the clinic. Thus, in this study, mPEG-succinimidyl propionate (mPEG-SPA, Mw = 5 kDa) was used to molecularly modify the MDSPI16 protein, and the modified product mPEG-SPA-MDSPI16, which strongly inhibited elastase production, was purified. It had good stability and safety, low immunogenicity, and a long half-life, and the IC50 for elastase was 86 nM. mPEG-SPA-MDSPI16 effectively inhibited the expression of neutrophil elastase and decreased ROS levels. Moreover, mPEG-SPA-MDSPI16 exerted anti-inflammatory effects by inhibiting activation of the NF-κB signaling pathway and the MAPK signaling pathway in neutrophils. It also exerted therapeutic effects on a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. In summary, mPEG-SPA-MDSPI16 is a novel anti-inflammatory protein modified with PEG that has the advantages of safety, nontoxicity, improved stability, and strong anti-inflammatory activity in vivo and in vitro and is expected to become an effective anti-inflammatory drug.

The relationship between aflatoxin B1 with the induction of extrinsic/intrinsic pathways of apoptosis and the protective role of taraxasterol in TM3 leydig cell line

Aflatoxins B1 (AFB1) a dangerous type of aflatoxin, poses a serious threat to human health. Meanwhile, Taraxasterol, a bioactive compound in dandelion, exhibits strong anti-inflammatory and antioxidant activity. Therefore, the aim of this study was to investigate the impact of AFB1 on the intrinsic and extrinsic pathways of apoptosis, as well as evaluate the protective role of taraxasterol in the TM3 Leydig cell line. Cell viability was evaluated using an MTT assay, measuring the effects of 3.6 µM AFB1 and varying concentrations of taraxasterol. Expression levels of Caspase 3,8, and 9 were analyzed with RT-qPCR, and flow cytometry was used to assess cell cycle progression and apoptotic alterations. The findings of this study demonstrated that exposure to 3.6 µM of AFB1 resulted in an upregulation of Caspase 3 and Caspase 9 expression, indicating an activation of apoptotic pathways in TM3 cells. Additionally, the analysis of apoptosis revealed a significant increase in cellular apoptosis at this AFB1 concentration. However, when TM3 cells were exposed to 5 µM of taraxasterol, a downregulation of Caspase 3 and Caspase 9 expression was observed, suggesting a protective effect against apoptosis. Moreover, the apoptotic rate in TM3 cells was reduced in the presence of 5 µM of taraxasterol. Consequently, this study highlights the potential of taraxasterol as a protective agent against AFB1-induced apoptosis and suggest its potential application in regulating cell survival and apoptosis-related processes. Further investigations are necessary to elucidate the underlying mechanisms and evaluate the clinical implications of taraxasterol in the context of fertility disorders and other conditions associated with AFB1 exposure.

The Valorization of Wastes and Byproducts from Cruciferous Vegetables: A Review on the Potential Utilization of Cabbage, Cauliflower, and Broccoli Byproducts.

The management of vegetable waste and byproducts is a global challenge in the agricultural industry. As a commonly consumed vegetable crop, cruciferous vegetables marked higher amounts of wastage during their supply chain processes, with a significant contribution from cabbage, cauliflower, and broccoli. Therefore, the sustainable and resource-efficient utilization of discarded materials is crucial. This review explores potential applications of cruciferous vegetable waste and byproducts, spotlighting cabbage, cauliflower, and broccoli in food, medicinal, and other industries. Their significance of being utilized in value-added applications is addressed, emphasizing important biomolecules, technologies involved in the valorization process, and future aspects of practical applications. Cabbage, cauliflower, and broccoli generate waste and low-processing byproducts, including leaves, stems, stalks, and rot. Most of them contain high-value biomolecules, including bioactive proteins and phytochemicals, glucosinolates, flavonoids, anthocyanins, carotenoids, and tocopherols. Interestingly, isothiocyanates, derived from glucosinolates, exhibit strong anti-inflammatory and anticancer activity through various interactions with cellular molecules and the modulation of key signaling pathways in cells. Therefore, these cruciferous-based residues can be valorized efficiently through various innovative extraction and biotransformation techniques, as well as employing different biorefinery approaches. This not only minimizes environmental impact but also contributes to the development of high-value-added products for food, medicinal, and other related industries.

Studies on the Effects of Fermentation on the Phenolic Profile and Biological Activity of Three Cultivars of Kale.

Fermentation is used not only to preserve food but also to enhance its beneficial effects on human health and achieve functional foods. This study aimed to investigate how different treatments (spontaneous fermentation or fermentation with the use of starter culture) affect phenolic content, antioxidant potential, and cholinesterase inhibitory activity in different kale cultivars: 'Halbhoner Grüner Krauser', 'Scarlet', and 'Nero di Toscana'. Chosen samples were further tested for their protective potential against the Caco-2 cell line. HPLC-MS analysis revealed that the fermentation affected the composition of polyphenolic compounds, leading to an increase in the content of rutin, kaempferol, sinapinic, and protocatechuic acids. In general, kale cultivars demonstrated various antioxidant activities, and fermentation led to an increase in total phenolic content and antioxidant activity. Fermentation boosted anti-cholinesterase activity most profoundly in 'Nero di Toscana'. Extracts of spontaneously fermented 'Scarlet' (SS) and 'Nero di Toscana' (NTS) showed cytoprotective properties, as revealed by the malondialdehyde (MDA), lactate dehydrogenase (LDH), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) assays. Additionally, strong anti-inflammatory activity of NTS was shown by decreased release of cytokines IL-1β and TNF-α. Collectively, the conducted studies suggest fermented kale cultivars as a potential source for functional foods.

Anticolorectal Cancer Activity of Bilobalide in Patient-Derived Colorectal Cancer Organoids and AOM/DSS Mouse Model

Bilobalide has shown strong anti-inflammatory activity. Colorectal cancer (CRC) is closely associated with inflammation. However, no studies have reported on the use of bilobalide for treating CRC. This study aims to evaluate the effect of bilobalide on CRC prevention. Enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (RT-qPCR), Western blotting, and immunofluorescence showed that bilobalide significantly inhibits the M2 polarization of macrophages dependent on phorbol 12-myristate 13-acetate (PMA) and interleukin-4 (IL-4). Analysis of signaling pathways showed that the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and signal transducer and activator of transcription 3 (STAT3) was regulated. In particular, human CRC organoids were established. Western blotting, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL), and analysis of cell viability and morphology further supported the hypothesis that the anti-CRC effects of bilobalide could be explained by its ability to suppress M2 macrophage polarization and promote M1 transformation. C57BL/6 mice treated with azoxymethane (AOM)/dextran sodium sulfate (DSS) were divided into three groups, i.e., control, AOM/DSS, low (2.5 mg/kg), and high (5 mg/kg). High-dose bilobalide markedly inhibited the progression of CRC, as evidenced by the increased body weight, decrease in disease activity index (DAI) death rate, and alleviation of colon length reduction and tumorigenesis. According to the in vivo results, reduced levels of inflammatory cytokines in the serum included tumor necrosis factor (TNF-α), IL-6, IL-1β, and IL-10. Bilobalide reduced oxidative stress indices, lipid peroxide (LPO), and malondialdehyde (MDA) and increased reduced glutathione (GSH). In addition, the expression of proliferating cell nuclear antigen (PCNA), Ki67, cellular Myc (c-Myc), and CD206 was downregulated in the drug-treated groups, as confirmed by the immunohistochemical staining. Collectively, these results indicated that bilobalide administration improve experimental CRC by inhibiting M2 macrophage polarization and oxidative stress. Thus, bilobalide may prevent CRC and serve as a potential therapeutic target for CRC.

Ameliorative effect of an acidic polysaccharide from Phellinus linteus on ulcerative colitis in a DSS-induced mouse model

Phellinus linteus, a rare medicinal fungus, displays strong antitumor and anti-inflammatory activities because of its active metabolites, particularly polysaccharides. We investigated effects of P. linteus acidic polysaccharide (PLAP) on amelioration of dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) in a mouse model, and associated mechanisms. PLAP treatment alleviated major UC symptoms (weight loss, reduced food intake, increased disease activity index), and ameliorated histopathological colon tissue damage, reduced levels of pro-inflammatory factors (TNF-α, IL-6, IL-1β), enhanced anti-inflammatory factor IL-10 level, reduced levels of oxidative stress-related enzymes iNOS and MPO, and enhanced expression of tight junction proteins (ZO-1, occludin, claudin-1). qPCR analysis revealed that PLAP downregulated phosphorylation levels of p65 and p38 and transcriptional level of TLR-4. High-throughput sequencing showed that PLAP restored gut microbiota diversity and species abundances in the UC model, and gas chromatographic analysis showed that it increased levels of beneficial short-chain fatty acids. Our findings indicate that PLAP has strong potential for development as an anti-UC agent based on its reduction of inflammation and oxidative stress levels, modulation of gut microbiota composition, and promotion of normal intestinal barrier function.

GCMS and HPLC profiling, antioxidant and anti-inflammatory activities of Crotalaria medicaginea Lamk

Inflammation is the underlying process to many degenerative diseases such as emphysema, cancer, Alzheimer's, arthritis, diabetes, and more recently COVID-19. The overproduction of free radicals in the cells is the major factor that leads to inflammation due to oxidative stress. These free radicals damage macromolecules in cells, including nucleic acids, proteins, lipids, and polyunsaturated fatty acids, through oxidation, thus affecting cell metabolism. Antioxidants can delay the oxidation of these molecules through inhibition of oxidizing chain reactions and can be helpful in treating inflammatory diseases. Crotalaria medicaginea Lamk (Fabaceae) is an important medicinal plant that is not extensively explored for its biological and pharmacological potential on scientific grounds. In this study, in vitro antioxidant and anti-inflammatory activities of the crude methanolic extract and different solvent fractions of the plant were determined. Phenolics, flavonoids, tannins, and saponins were quantified in each plant sample. The crude extract was characterized for its phytochemical constituents through GC–MS and HPLC analysis. Strong antioxidant and anti-inflammatory activities of plant extracts were recorded which can be attributed to the presence of phenolics, flavonoids, saponins, terpenes, and tannins in these extracts. GC–MS analysis confirmed the presence of Hexadecanoic acid, methyl ester, 9,12-Octadecadienoic acid (Z,Z)-, methyl ester, and 9-Octadecenoic acid, methyl ester, (E)- as major compounds while HPLC analysis confirmed the presence of gallic acid, taxifolin, quercetin and kaempferol in the plant.

Highly polar chemical constituents from whole herb of Scindapsus officinalis

Macroporous resin column chromatography, MCI medium pressure column chromatography, and semi-preparative high performance liquid chromatography were employed to isolate the chemical components from the aqueous extract of the whole herb of Scindapsus officinalis. The structures of the compounds were identified based on the physical and chemical properties and the spectroscopic data. Ten compounds were isolated from the aqueous extract and identified as 3,4-dihydroxyphenylethyl-8-O-[β-D-apiofuranosyl-(1→4)]-β-D-glucopyranoside(1), alternamide B(2), 3,4-dihydroxyphenylethyl-O-β-D-glucopyranoside(3), 1-(4-hydroxy)-phenylethyl-β-D-galactopyranoside(4), 3,4-dihydroxyphenylethyl-8-O-[β-D-apiofuranosyl-(1→2)]-β-D-glucopyranoside(5), hydroxytyrosol-4-O-β-D-glucopyranoside(6), 3,5-dihydroxyphenylethyl-3-O-β-D-glucopyranoside(7), salidroside(8), dihydroisoquinolone(9), and 4-methoxybenzenepropanol-3-O-β-D-glucopyranoside(10). Among them, compound 1 was a new one, and compounds 2-10 were obtained from S. officinalis for the first time. The RAW264.7 cells were exposed to lipopolysaccharide for the mode-ling of inflammation, and the cells were then used to examine anti-inflammatory activities of the compounds. The results showed that compounds 6 and 7 had strong anti-inflammatory activities, while compounds 1, 2, and 5 had moderate anti-inflammatory activities.

Withaperuvin O, a new withanolide from Physalis peruviana L

Physalis peruviana L. (Solanaceae) has been used in tropical and subtropical countries of the world as medicinal and fruit trees. In this study, a new withanolide named withaperuvin O (1) and seven known ones, including physalolactone B-3-O-β-D-glucopyranoside (2), withanolide J (3), physapruin A (4), physaperuvin G (5), withaperuvin (6), withaperuvin C (7) and 28-hydroxywithaperuvin C (8), were isolated from the whole plants of P. peruviana. Their structures were elucidated based on extensive spectroscopic analyses including NMR and HR-ESI-MS. The bioactivities of these compounds against lipopolysaccharide (LPS)-induced NO production in RAW264.7 cells and cytotoxicity against HepG2 were tested. Compound 3 showed strong anti-inflammatory activities with IC50 3.55 ± 0.12 µM (compared to positive control L-NMMA 7.72 ± 0.46 µM). Compounds 3 and 4 inhibited HepG2 cell line with the IC50 values of 2.01 ± 0.12 µM, 0.96 ± 0.05 µM, respectively (Ellipticine, 0.32 ± 0.02 µM). Our study indicated that compounds 3 and 4 could be new potential natural products for the development of anti-inflammatory and anti-cancer agents.

Ultrasound assisted biogenic synthesis of Palladium nanoparticles using Cocculus hirsutus leaf extract: Antimicrobial, anti-inflammatory and catalytic activities

We have synthesized palladium nanoparticles (PdNPs) from aqueous leaf extract of Cocculus hirsutus (CH) by ultra-sonication in an easy, non-toxic, and eco-friendly manner. PdNPs synthesized were analyzed using UV–vis, FT-IR, powder XRD, TEM, and DLS instruments. From UV–vis spectra, the Surface Plasmon Resonance (SPR) signal indicated that the formation of PdNPs. The synthesized PdNPs shows spherical shape, crystalline and polydispersibility nature with a mean particle size of 10±3 nm was observed from XRD and TEM. FTIR analysis reveals the active role of phenolic constituents from CH leaf extract in reduction and surface functionalization of nanoparticles. The stability of the PdNPs was assessed by devious the Zeta potential analysis. The as-prepared PdNPs showed antibacterial efficacy (maximum zone of inhibition is 11.20 mm for S. typhimurium) and antifungal efficacy (maximum zone of inhibition is 32.80 mm for C. albicans) against disease causing human pathogens, strong anti-inflammatory activity for BSA denaturation and blistering catalytic activity against 4-NP reduction up to 5 cycles (6 min; 100 % reduction, rate constant is 0.532 min−1). The potency of the anti-inflammatory activity was found to be 90 % using PdNPs against the standard drug Diclofenac sodium (90 %) for 500 µg/mL. The above mentioned activities were used to evaluate the effectiveness of the PdNPs in treating bacterial, inflammation related conditions and also as an effective catalyst in wastewater treatment.

Potent bioactive metabolites from Olea ferruginea

Seven known (1-7) and one new compound (8) were isolated and identified from the stem of Olea ferruginea. The species has been recognised as a new source for six of the known metabolites (1, 3, 4, 5, 6, and 7). Based on detailed spectroscopic analyses, these compounds were identified as scopoletin (1), 8-ketosetosterol (2), (+)-cycloolivil (3), (+)-africanal (4), isovanilic acid (5), hydroxytyrosol acetate (6), vanillic acid (7), and cycloolivil A (8). The crude extracts and purified compounds were analysed for their Leishmanicidal, anti-glycation, anti-cancer, and anti-inflammatory activities. n-Hexane fraction was found to be the most active (among all the fractions), against Leishmania parasites, exhibiting 97.85% inhibition at 15 μg/mL. However, none of the extracts showed any significant anti-glycation or anti-cancer potential, all the fractions, except the aqueous layer, displayed moderate to low anti-inflammatory activity. Compound 1 was found to have strong anti-inflammatory activity, exhibiting 96.7% stimulation at 25 μg/mL.

NYCTANTHES ARBORTRITIS LINN: AN ETHNOPHARMACOLOGICAL MIRACULOUS NATURAL RESOURCE

Nyctanthes arbortritis (Parijat tree) is a medicinal plant that has long been utilized in a variety of Ayurvedic formulations to treat a range of ailments. Many medicinal qualities like analgesic, antipyretic, antifungal, antibacterial, and anti-cancer properties, have been identified through comprehensive research on the pharmacological screening of Nyctanthes arbortritis. It has been demonstrated that the plant both inhibits the growth of certain cancer cells and has cytotoxic effects on them. As a promising therapy option for a range of inflammatory and pain related disorders, the extracts of its different plant parts have also been discovered to possess strong anti-inflammatory and analgesic activity. The plant extracts also have strong antifungal and antibacterial properties, which makes them a possible medicinal source for the creation of novel antibiotics. In this article, we have represented the collective scientific information about the various phytoconstituents and pharmacological activities of the Nyctanthes arbortritis.

Isoliquiritin Ameliorates Ulcerative Colitis in Rats through Caspase 3/HMGB1/TLR4 Dependent Signaling Pathway.

Isoliquiritin belongs to flavanol glycosides and has a strong antiinflammatory activity. This study sought to investigate the anti-inflammatory effect of isoliquiritin and its underlying mechanism. The inflammatory (trinitro-benzene-sulfonic acid-TNBS-induced ulcerative colitis (UC)) model was established to ascertain the effect of isoliquiritin on the caspase-3/HMGB1/TLR4 pathway in rats. We also explored its protective effect on intestinal inflammation and its underlying mechanism using the LPS-induced inflammation model of Caco-2 cells. Besides, Deseq2 was used to analyze UCassociated protein levels. Isoliquiritin treatment significantly attenuated shortened colon length (induced by TNBS), disease activity index (DAI) score, and body weight loss in rats. A decrease in the levels of inflammatory mediators (IL-1β, I IL-4, L-6, IL-10, PGE2, and TNF-α), coupled with malondialdehyde (MDA) and superoxide dismutase (SOD), was observed in colon tissue and serum of rats after they have received isoliquiritin. Results of techniques (like western blotting, real-time PCR, immunohistochemistry, and immunofluorescence-IF) demonstrated the potential of isoliquiritin to decrease expressions of key genes in the TLR4 downstream pathways, viz., MyD88, IRAK1, TRAF6, NF-κB, p38, and JNK at mRNA and protein levels as well as inhibit HMGB1 expression, which is the upstream ligand of TLR4. Bioinformational analysis showed enteritis to be associated with a high expression of HMGB1, TLR4, and caspase-3. Isoliquiritin could reduce intestinal inflammation and mucosal damage of TNBS-induced colitis in rats with a certain anti-UC effect. Meanwhile, isoliquiritin treatment also inhibited the expression of HMGB1, TLR4, and MyD88 in LPS-induced Caco-2 cells. These results indicated that isoliquiritin could ameliorate UC through the caspase-3/HMGB1/TLR4-dependent signaling pathway.

A Biomimetic Multifunctional Nanoframework for Symptom Relief and Restorative Treatment of Acute Liver Failure.

Acute liver failure (ALF) is a rare and serious condition characterized by major hepatocyte death and liver dysfunction. Owing to the limited therapeutic options, this disease generally has a poor prognosis and a high mortality rate. When ALF cannot be reversed by medications, liver transplantation is often needed. However, transplant rejection and the shortage of donor organs still remain major challenges. Most recently, stem cell therapy has emerged as a promising alternative for the treatment of liver diseases. However, the limited cell delivery routes and poor stability of live cell products have greatly hindered the feasibility and therapeutic efficacy of stem cell therapy. Inspired by the functions of mesenchymal stem cells (MSCs) primarily through the secretion of several factors, we developed an MSC-inspired biomimetic multifunctional nanoframework (MBN) that encapsulates the growth-promoting factors secreted by MSCs via combination with hydrophilic or hydrophobic drugs. The red blood cell (RBC) membrane was coated with the MBN to enhance its immunological tolerance and prolong its circulation time in blood. Importantly, the MBN can respond to the oxidative microenvironment, where it accumulates and degrades to release the payload. In this work, two biomimetic nanoparticles, namely, rhein-encapsulated MBN (RMBN) and N-acetylcysteine (NAC)-encapsulated MBN (NMBN), were designed and synthesized. In lipopolysaccharide (LPS)/d-galactosamine (D-GalN)-induced and acetaminophen (APAP)-induced ALF mouse models, RMBN and NMBN could effectively target liver lesions, relieve the acute symptoms of ALF, and promote liver cell regeneration by virtue of their strong antioxidative, anti-inflammatory, and regenerative activities. This study demonstrated the feasibility of the use of an MSC-inspired biomimetic nanoframework for treating ALF.

Ocrelizumab reduces cortical and deep grey matter loss compared to the S1P-receptor modulator in multiple sclerosis.

Ocrelizumab (OCR) and Fingolimod (FGL) are two high-efficacy treatments in multiple sclerosis which, besides their strong anti-inflammatory activity, may limit neurodegeneration. To compare the effect of OCR and FGL on clinical and MRI endpoints. 95 relapsing-remitting patients (57 OCR, 38 FGL) clinically followed for 36months underwent a 3-Tesla MRI at baseline and after 24months. The annualized relapse rate, EDSS, new cortical/white matter lesions and regional cortical and deep grey matter volume loss were evaluated. OCR reduced the relapse rate from 0.48 to 0.04, FGL from 0.32 to 0.05 (both p < 0.001). Compared to FGL, OCR-group experienced fewer new white matter lesions (12% vs 32%, p = 0.005), no differences in new cortical lesions, lower deep grey matter volume loss (- 0.12% vs - 0.66%; p = 0.002, Cohen's d = 0.54), lower global cortical thickness change (- 0.45% vs - 0.70%; p = 0.036; d = 0.42) and reduced cortical thinning/volume loss in several regions of interests, including those of parietal gyrus (d-range = 0.65-0.71), frontal gyrus (d-range = 0.47-0.60), cingulate (d-range = 0.41-0.72), insula (d = 0.36), cerebellum (cortex d = 0.72, white matter d = 0.44), putamen (d = 0.35) and thalamus (d = 0.31). The effect on some regional thickness changes was confirmed in patients without focal lesions. When compared with FGL, patients receiving OCR showed greater suppression of focal MRI lesions accumulation and lower cortical and deep grey matter volume loss.

Pterostilbene attenuates heart failure by inhibiting myocardial ferroptosis through SIRT1/GSK-3β/GPX4 signaling pathway

Sustained myocardial injury due to hypertension and diabetes mellitus leads to production of endogenous reactive oxygen species (ROS) and insufficient myocardial antioxidant capacity, increasing the risk of cardiomyocyte ferroptosis. Ferroptosis is a nonapoptotic form of cell death driven by unrestricted lipid peroxidation. Dysfunction of the glutathione peroxidase 4 (GPX4) antioxidant system also plays an important role in ferroptosis. Cardiomyocyte ferroptosis ultimately leads to myocardial deterioration, such as inflammation, fibrosis, and cardiac remodeling, resulting in structural and functional changes. Pterostilbene (PTS), a demethylated derivative of resveratrol, exhibits strong anti-inflammatory and antioxidative activities. In this study, we used in vitro experiments to explore ferroptosis induced by angiotensin II (Ang II) of primary cardiac myocytes (CMs) and in vivo experiments to prepare a transverse aortic constriction (TAC)-induced cardiac dysfunction mouse model. PTS can significantly ameliorate Ang II-induced cardiomyocyte ferroptosis in vitro and reduce cardiac remodeling, while improving cardiac function in mice after TAC in vivo. Further mechanistic investigations revealed that PTS exerts its protective effect through the SIRT1/GSK-3β/GPX4 pathway. After siRNA-mediated knockdown of SIRT1 or GPX4 in CMs, the protective effects of PTS on cardiomyocytes were abolished. This study provides important theoretical support for the potential of PTS to attenuate pathological cardiac remodeling and heart failure and provides a preliminary exploration of the molecular pathways involved in its protective mechanism.

Natural Polysaccharides Derived from Fruits and Mushrooms with Antiinflammatory and Antioxidant Effects

Abstract: A large class of substances known as polysaccharides have a wide range of advantageous therapeutic and nutritional properties. Polysaccharides found in plants and plant components are extracted for the use in treating a number of diseases. Since ancient times, these polysaccharides have been utilized for human wellness. With no or minimal adverse effects, the polysaccharides that were extracted and refined from the fruits exhibit strong antioxidant, antiinflammatory, immunoregulatory, and hepatoprotective action. These fruit polysaccharides are isolated and purified using numerous chromatographic methods. In this review, the polysaccharide obtained from sources such as Rubus chingii, Mulberry, Glycyrrhiza glabra, Lilium davidii, Flammulina velutipes, Angelica sinesis, and Diospyros kaki have been discussed along with their biological activities including DPPH radical scavenging activity, ABTS free radical scavenging assay, Hydroxyl radical scavenging activity and assay for oxygen free radical absorption capacity (ORAC) listed in various studies.