Anti-inflammatory Compounds Research Articles

Encapsulation of resveratrol in alginate microcapsules using internal gelation technique: Fabrication, characterization and release kinetics

Resveratrol (RES) is a proven anticancer, antioxidant, anti-inflammatory, and cardioprotective compound. However, low bioavailability, poor water solubility, and sensitivity to UV light and heat limit RES's use in food applications. In this study, we aim to protect RES by encapsulating it in sodium alginate (NaAlg) matrix using internal gelation, followed by drying the moist microencapsulates using spray and freeze-drying techniques. The spray-dried microencapsulates exhibited a smaller mean diameter (5.57 ± 2.40 μm), higher encapsulation efficiency (91.32 ± 1.98%), and higher ζ-potential (−61.9 ± 2.33 mV) compared to freeze-dried microencapsulates. SEM images revealed the smooth and spherical surface of the spray-dried microencapsulates, while the freeze-dried samples exhibited irregular shapes and porous textures. FTIR results showed polyelectrolyte interactions between NaAlg, RES, and CaCO3. XRD and DSC results confirmed the incorporation of RES in the NaAlg matrix. Spray-dried microencapsulates demonstrate the highest RES retention of 80.89 ± 0.70% and 78.59 ± 0.27% after 4 h of UV light and thermal treatments, respectively. In vitro release studies showed that spray-dried microencapsulates demonstrate a delayed gastric release compared to freeze-dried microencapsulates. The release mechanism of RES from the microencapsulates was effectively described by the Shalin-Peppas model.

T and Z, partial seed coat patterning genes in common bean, provide insight into the structure and protein interactions of a plant MBW complex.

Flavonoids are secondary metabolites associated with plant seed coat and flower color. These compounds provide health benefits to humans as anti-inflammatory and antioxidant compounds. The expression of the late biosynthetic genes in the flavonoid pathway is controlled by a ternary MBW protein complex consisting of interfacing MYB, beta-helix-loop-helix (bHLH), and WD40 Repeat (WDR) proteins. P, the master regulator gene of the flavonoid expression in common bean (Phaseolus vulgaris L.), was recently determined to encode a bHLH protein. The T and Z genes control the distribution of color in bean seeds and flowers and have historically been considered regulators of the flavonoid gene expression. T and Z candidates were identified using reverse genetics based on genetic mapping, phylogenetic analysis, and mutant analysis. Domain and AlphaFold2 structure analyses determined that T encodes a seven-bladed β-propeller WDR protein, while Z encodes a R2R3 MYB protein. Deletions and SNPs in T and Z mutants, respectively, altered the 3D structure of these proteins. Modeling of the Z MYB/P bHLH/T WDR MBW complex identified interfacing sequence domains and motifs in all three genes that are conserved in dicots. One Z MYB motif is a possible beta-molecular recognition feature (β-MoRF) that only appears in a structured state when Z MYB is modeled as a component of a MBW complex. Complexes containing mutant T and Z proteins changed the interaction of members of the complex in ways that would alter their role in regulating the expression of genes in the flavonoid pathway.

Medicinal Plants and Bioactive Compounds with Potential Anti-inflammatory and Antidiabetic Activities: A Review

Background: Inflammation is a complex process. Persistent and uncontrolled inflammation may act as an etiologic factor for many chronic disorders like diabetes. Objective: This review aims to classify the anti-inflammatory and antidiabetic medicinal plants, their traditional uses, and their active compounds that have been tested for their anti-inflammatory and antidiabetic effects. Methods: We checked scientific publications in various electronic databases from 1981 to 2021. All the molecular structures were provided in ADC/ChemSketch. Results: We reviewed 58 species, belonging to 39 families. These species have long been used in traditional medicine to cure a variety of ailments, including, dysentery, typhoid fever, anemia, digestive and cardiac disorders, as well as diabetes and inflammation. Asteraceae represents the dominant family. The most potent anti-inflammatory and antidiabetic active compounds were reviewed including myricetin, quercetin, hesperetin, rutin, luteolin, chlorogenic acid, vanillic acid, gallic acid, ferulic acid, benzoic acid, cinnamic acid, gentisic acid, camphor, 1,8-cineol, p-cymene, limonene, linalool, thymoquinone, carvacrol, aromadendrine, α-pinene, lycopene, phytol, imperatorin, chalepin, hexadecanoic acid, linoleic acid, tellimagrandin I, and trigalloyl glucose. Conclusion: This review indicates that medicinal plants have many therapeutic dynamics against inflammation and diabetes that could be exploited for the discovery of therapeutic preparation or agent for treating the two illnesses at the same time.

Protective effects of curcumin against spinal cord injury.

In parallel with population aging, the prevalence of neurological and neurodegenerative diseases has been dramatically increasing over the past few decades. Neurodegenerative diseases reduce the quality of life of patients and impose a high cost on the health system. These slowly progressive diseases can cause functional, perceptual, and behavioral deficits in patients. Therefore, neurodegenerative impairments have always been an interesting subject for scientists and clinicians. One of these diseases is spinal cord injury (SCI). SCI can lead to irreversible damage and is classified into two main subtypes: traumatic and non-traumatic, each with very different pathophysiological features. This review aims to gather relevant information about the beneficial effects of curcumin (Cur), with specific emphasis on its anti-inflammatory properties towards spinal cord injury (SCI) patients. The review collates data from extensive in-vitro, in-vivo, and clinical trials documenting the effects of CUR on SCI. It examines the modulation of pathophysiological pathways and regulation of the inflammatory cascades after CUR administration. Various pathophysiological processes involving the nuclear factor erythroid 2-related factor 2 (Nrf2), nuclear factor kappa B (NF-kB), and transforming growth factor beta (TGF-β) signaling pathways have been suggested to exacerbate damages resulting from SCI. CUR administration showed to modulate these signaling pathways which lead to attenuation of SCI complications. Anti-inflammatory compounds, particularly CUR, can modulate these pathophysiological pathways and regulate the inflammatory cascades. CUR, a well-known natural product with significant anti-inflammatory effects, has been extensively documented in experimental and clinical trials. Curcumin's potential to alter key steps in the Nrf2, NF-kB, and TGF-β signaling pathways suggests that it may play a role in attenuating SCI complications.

Optimization of bioactivities of solvent extracts of bark and heartwood of Pterocarpus marsupium and exploration of neuroprotective effect linking to the major Phytoconstituents

The study aims to evaluate the neuroprotective properties of Pterocarpus marsupium Roxb. The bioactive optimized hydroalcohol-extracted fractions of bark (PMBHA) and heartwood (PMHHA) at 300 and 400 mg/kg were examined in rats with scopolamine-induced neurotoxicity to study oxidative, neurochemical, and neuroinflammation biomarkers. Phenol and flavonoid-rich radical scavengers in contributing total antioxidant capacities of PMBHA and PMHHA quenched peroxyl radicals and protected the cellular membrane and lipoproteins from ROS in DPPH, ORAC, and CAP-e tests. In anticholinesterase activities, PMBHA inhibited AChE (IC50: 54.40 ± 0.98 µg/mL) and BChE (IC50: 50.95 ± 0.98 µg/mL) mixed-competitively, while PMHHA inhibited cholinesterase activities (AChE: 42.23 ± 0.54, and BChE: 47.19 ± 0.65 µg/mL) competitively. Dosage at 300 and 400 mg/kg of PMBHA and PMHHA improved serum and brain oxidative indicators (MDA, SOD, CAT, and GSH), and restored proinflammatory cytokines (TNF-α, and IL-6) leading to enhanced brain cholinesterase and β-secretase levels in neurotoxic rats. GC-MS reported antioxidant, anti-inflammatory, and neuroprotective compounds of PMBHA catechol, thiamet-G, d-Gala-l-ido-octonic amide, falcarinol, D-mannose, ribitol, 1,2,4-cyclopentanetrione, 3-(2-pentenyl)-, hexadecanoic acid methyl ester, n-hexadecanoic acid, oleic acid, and 3,5-Dimethoxybenzyl alcohol, α-epi-7-epi-5-Eudesmol, 1 R,4aR,7 R,8aR)-7-(2-Hydroxypropan-2-yl)-1,4a-dimethyldecahydro naphthalen-1-ol, arctiol, 1,1,4,7-tetramethyldecahydro-1 H-cyclopropa[e]azulene-4,7-diol, 2-Propen-1-ol, 3-(2,6,6-trimethyl-1-cyclohexen-1-yl), 4-t-Butyl-2-[4-nitrophenyl]phenol in PMHHA were responsible in neuroprotection in neurotoxic rats. However, heartwood demonstrated better neuroprotective activities than the bark of P. marsupium due to some of the key compounds (1 R,4aR,7 R,8aR)-7-(2-Hydroxypropan-2-yl)-1,4a-dimethyldecahydronaphthalen-1-ol, 2-Propen-1-ol, 3-(2,6,6-trimethyl-1-cyclohexen-1-yl)-, 4-t-Butyl-2-[4-nitrophenyl]phenol, 1,1,4,7-Tetramethyldecahydro-1 H-cyclopropa[e]azulene-4,7-diol.

Hypericum perforatum Alleviates Ovalbumin-Induced Asthma through Downregulating TH2 and Upregulating TH1 Related Parameters in BALB/C Mice

Background: Allergic asthma is a chronic and inflammatory disease of the respiratory tract, which is characterized by inflammation, airway obstruction and swelling. Anti-inflammatory compounds can be used to improve the disease severity. Hypericum perforatum (HP)/ St. John’s wort has been used in the treatment of many diseases due to its anti-inflammatory effects. Therefore, this study was performed to investigate the effects of HP on TH1 and TH2 parameters in an animal model of allergic asthma. Methods: Thirty BALB/c mice were sensitized with subcutaneous injection and inhalation of ovalbumin and then administered different doses of HP post-sensitization. Histological analysis of the lungs was performed. The effects of HP on mRNA expression of T-bet and GATA3 (TH1 and TH2 transcription factors, respectively), IFN-γ, IL-4 and IL-10 in the spleen were determined by real-time PCR. The protein levels of IFN-γ, IL-4 and IL-10 cytokines were also determined by ELISA technique in the serum of mice. Results: HP extract (HPE) reduced the clinical severity in asthma-induced mice, and a reduction in the inflammatory cell infiltration in the lung. Furthermore, treatment with HPE inhibited asthma-related mediators as well as increased the anti-inflammatory parameters compared to the control. The study also showed that treatment with HPE significantly increased IFN-γ, IL-10 and T-bet, while decreasing the level of IL-4 and GATA3 in mice treated with HPE. Conclusion: The data indicated that HPE can attenuate allergic asthma autoimmune responses by inhibiting infiltration of immune cell in the lung and TH2-related parameters. It is reasonable to assume that HPE has significant effects in the treatment of allergic asthma.

Soymilk yogurt fermented using Pediococcus pentosaceus TOKAI 759m improves mice gut microbiota and reduces pro-inflammatory cytokine production.

This study aimed to determine the anti-inflammatory activities and bioactive compounds of soymilk yogurt prepared using Lactiplantibacillus plantarum TOKAI 17 or Pediococcus pentosaceus TOKAI 759m. Mice were divided into five groups: normal diet (ND), soymilk, soymilk yogurt using L. plantarum TOKAI 17 (SY 17) or P. pentosaceus TOKAI 759m (SY 759m), and 0.5×109 cells of each starter strain (BC 17 or BC759m). In the SY 759m group, the serum pro-inflammatory cytokine levels and the cytotoxicity of natural killer cells were attenuated compared to the ND group. In the cecum microbiota, the abundances of butyrate-producing bacteria increased in the SY 759m and BC 17 groups. Furthermore, SY 759m metabolites contained high levels of aglycone isoflavone, adenine and showed a significant decrease in CCL-2 and interleukin-6 production in lipopolysaccharide-induced macrophage. In conclusion, soymilk yogurt produced using P. pentosaceus TOKAI 759m modulates the gut microbiota and can potentially prevent pro-inflammatory cytokine production.

Cyy-272, an indazole derivative, effectively mitigates obese cardiomyopathy as a JNK inhibitor

Obesity has shown a global epidemic trend. The high-lipid state caused by obesity can maintain the heart in a prolonged low-grade inflammatory state and cause ventricular remodeling, leading to a series of pathologies, such as hypertrophy, fibrosis, and apoptosis, which eventually develop into obese cardiomyopathy. Therefore, prolonged low-grade inflammation plays a crucial role in the progression of obese cardiomyopathy, making inflammation regulation an essential strategy for treating this disease. Cyy-272, an indazole derivative, is an anti-inflammatory compound independently synthesized by our laboratory. Our previous studies revealed that Cyy-272 can exert anti-inflammatory effects by inhibiting the phosphorylation and activation of C-Jun N-terminal kinase (JNK), thereby alleviating lipopolysaccharide (LPS)-induced acute lung injury (ALI). The current study aimed to evaluate the potential of Cyy-272 to mitigate the occurrence and progression of obese cardiomyopathy through the inhibition of the JNK signaling pathway. Our results indicate that the compound Cyy-272 has encouraging therapeutic effects on obesity-induced cardiac injury. It significantly inhibits inflammation in cardiomyocytes and heart tissues induced by high lipid concentrations, further alleviating the resulting hypertrophy, fibrosis, and apoptosis. Mechanistically, the protective effect of Cyy-272 on obese cardiomyopathy can be attributed to its direct inhibition of JNK protein phosphorylation. In conclusion, we identified a novel compound, Cyy-272, capable of alleviating obese cardiomyopathy and confirmed that its effect is achieved through direct inhibition of JNK.

Regulation of Intestinal Inflammation by Walnut-Derived Bioactive Compounds.

Walnuts (Juglans regia L.) have shown promising effects in terms of ameliorating inflammatory bowel disease (IBD), attributed to their abundant bioactive compounds. This review comprehensively illustrates the key mechanisms underlying the therapeutic potential of walnuts in IBD management, including the modulation of intestinal mucosa permeability, the regulation of inflammatory pathways (such as NF-kB, COX/COX2, MAPCK/MAPK, and iNOS/NOS), relieving oxidative stress, and the modulation of gut microbiota. Furthermore, we highlight walnut-derived anti-inflammatory compounds, such as polyunsaturated fatty acids (PUFA; e.g., ω-3 PUFA), tocopherols, phytosterols, sphingolipids, phospholipids, phenolic compounds, flavonoids, and tannins. We also discuss unique anti-inflammatory compounds such as peptides and polysaccharides, including their extraction and preparation methods. Our review provides a theoretical foundation for dietary walnut supplementation in IBD management and provides guidance for academia and industry. In future, research should focus on the targeted isolation and purification of walnut-derived anti-inflammatory compounds or optimizing extraction methods to enhance their yields, thereby helping the food industry to develop dietary supplements or walnut-derived functional foods tailored for IBD patients.

Anti-inflammatory Effect of Dictyopteis undulata in RAW 264.7 Cells

Purpose: This study aimed to analyze the anti-inflammatory effects of <i>Dictyopteris undulata</i> extract on skin using RAW 264.7 cells.Methods: Its anti-inflammatory effects on RAW 264.7 cells were evaluated by measuring the cell viability, gene expression levels (<i>IL-1α/IL-1β/IL-6</i> and <i>TNF-α</i>), and nitric oxide (NO)/prostaglandin E2 (PGE<sub>2</sub>) production.Results: Quantitative real-time polymerase chain reaction showed that the <i>D. undulata</i> extract decreased the mRNA levels of <i>IL-1α/IL-1β/IL-6</i> and <i>TNF-α</i>. Additionally, PGE<sub>2</sub>/NO detection revealed that <i>D. undulata</i> extract exhibited anti-inflammatory properties.Conclusion: <i>D. undulata</i> extract is a potential anti-inflammatory compound. Further study on the anti-inflammatory mechanisms of <i>D. undulata</i> extract would facilitate the development of cosmeceutics and pharmacological treatments.

Immunoexpression of aortic endothelial P-selectin and serum apolipoprotein A-1 levels after administration of arabica (Coffea arabica) and robusta (Coffea canephora) coffee bean extracts: In vivo study in atherosclerosis rat model.

Atherosclerosis is a leading cause of cardiovascular disease-related death worldwide. Some studies suggested that the natural ingredients in coffee may negatively affect cardiovascular diseases, while other studies indicated that coffee contains anti-inflammatory compounds that are beneficial for cardiovascular diseases. The aim of this study was to measure the expression of P-selectin in aortic endothelial cells and the level of serum apolipoprotein A-1 (ApoA-1) in an atherosclerosis rat model after the administration of arabica and robusta coffee bean extracts at mild-moderate and high doses. An experimental study was conducted with a complete randomized design using 36 adult male white rats (Rattus norvegicus) divided into six groups: negative control (NC), positive control (PC), arabica mild-moderate dose (A1), arabica high dose (A2), robusta mild-moderate dose (R1), and robusta high dose (R2). Animals were induced atherosclerosis with atherogenic feed and then were treated with arabica and robusta coffee bean extracts at two different doses for four weeks. The results showed that the expression of P-selectin in the group of rats treated with robusta coffee bean extract was lower than arabica coffee bean extract group. Rats with robusta coffee bean extract mild-moderate dose had the highest ApoA-1 levels compared to other groups significantly (p<0.05). The level of ApoA-1 was higher in both mild-moderate and high dose of robusta coffee groups compared to the negative control group (both with p<0.001). In conclusion, mild-moderate intake of robusta coffee bean extract could reduce aortic P-selectin immunoexpression and increase serum ApoA-1 levels in an atherosclerosis rat model.

AD16 attenuates neuroinflammation induced by cerebral ischemia through down-regulating astrocytes A1 polarization

A1 polarization of astrocytes mediated prolonged inflammation contributing to brain injury in ischemic stroke. We have previously shown that AD16 protects against neonatal hypoxic-ischemic brain damage in vivo and oxygen-glucose deprivation in vitro. More recently, AD16 has demonstrated safety, tolerability, and favorable pharmacokinetics in a randomized controlled phase I trial. In this study, we utilized a rat model of transient middle cerebral artery occlusion (tMCAO) to explore whether the anti-inflammatory compound AD16 protects against ischemic brain injury by regulating A1 polarization and its underlying mechanisms. Our results showed that AD16 treatment significantly reduced the brain infarcted volume and improved neurological function in tMCAO rats. GO analysis results show that differential genes among the Sham, tMCAO and AD16 treatment groups are involved in the regulation of cytokine and inflammatory response. KEGG enrichment pathways analysis mainly enriched in cytokine-cytokine receptor interaction, viral protein interaction with cytokine-cytokine receptor, TNF, chemokine, NF-κB and IL-17 signaling pathway. Furthermore, AD16 treatment decreased the permeability of the blood-brain barrier and suppressed neuroinflammation. AD16 treatment also significantly reduced the polarization of A1 and inhibited NF-κB and JAK2/STAT3 signaling pathways. This study demonstrates that AD16 protects against brain injury in ischemic stroke by reducing A1 polarization to suppress neuroinflammation through downregulating NF-κB and JAK2/STAT3 signaling. Our findings uncover a potential molecular mechanism for AD16 and suggest that AD16 holds promising therapeutic potential against cerebral ischemia.

Metabolomics-based profiling of anti-inflammatory compounds from Mentha spicata in shanghe, China

Mentha spicata is a popular herb used in foods, cosmetics, and medicines. In the present study, liquid chromatography-mass spectrometry-based metabolomics analysis and the zebrafish model were used to investigate the potential biomarkers of M. spicata growing in Shanghe County (Shandong Province, China) and their anti-inflammatory properties. Network pharmacology and molecular docking were performed to screen the main targets of the characteristic compounds to understand their mechanisms of action. Nine potential markers including sugars (1,2), polyphenolic acids (3–5), and flavonoids (6–9) were identified from the species. The inhibitory effects on leukocyte migration confirmed that compounds 1 and 3–9 played a positive role in the protective effect of Shanghe M. spicata (SM) extract against inflammation. Akt (protein kinase B), EGFR (epidermal growth factor receptor), and MMP9 (matrix metalloproteinase 9) were the core target proteins of the identified compounds in the anti-inflammatory process. The most significant Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment terms were response to abiotic stimulus (Biological Process), carbohydrate derivative binding (Molecular Function), and pathways in cancer. In docking simulations, 3-p-coumaroylquinic acid (3-PC, 4) and cirsimaritin (CN, 7) exhibited the highest potential affinity to the active sites of Akt and EGFR proteins, respectively; additionally, 5-demethylsinensetin (5-DS, 9) and luteolin (LN, 6) were considered the most suitable ligands for the MMP9 protein. The present study highlighted the use of SM resources as functional products with health benefits.

Fisetin is a selective adenosine triphosphate-competitive inhibitor for mitogen-activated protein kinase kinase 4 to inhibit lipopolysaccharide-stimulated inflammation.

The mitogen-activated protein kinase kinase 4 (MKK4), a member of the MAP kinase kinase family, directly phosphorylates and activates the c-Jun NH2-terminal kinases (JNK), in response to proinflammatory cytokines and cellular stresses. Regulation of the MKK4 activity is considered to be a novel approach for the prevention and treatment of inflammation. The aim of this study was to identify whether fisetin, a potential anti-inflammatory compound, targets MKK4-JNK cascade to inhibit lipopolysaccharide (LPS)-stimulated inflammatory response. RAW264 macrophage pretreated with fisetin following LPS stimulation was used as a cell model to investigate the transactivation and expression of related-inflammatory genes by transient transfection assay, electrophoretic mobility shift assay (EMSA), or enzyme-linked immunosorbent assay (ELISA), and cellular signaling as well as binding of related-signal proteins by Western blot, pull-down assay and kinase assay, and molecular modeling. The transactivation and expression of cyclooxygenase-2 (COX-2) gene as well as prostaglandin E2 (PGE2) secretion induced by LPS were inhibited by fisetin in a dose-dependent manner. Signaling transduction analysis demonstrated that fisetin selectively inhibited MKK4-JNK1/2 signaling to suppress the phosphorylation of transcription factor AP-1 without affecting the NF-κB and Jak2-Stat3 signaling as well as the phosphorylation of Src, Syk, and TAK1. Furthermore, in vitro and ex vivo pull-down assay using cell lysate or purified protein demonstrated that fisetin could bind directly to MKK4. Molecular modeling using the Molecular Operating Environment™ software indicated that fisetin docked into the ATP-binding pocket of MKK4 with a binding energy of -71.75 kcal/mol and formed a 1.70 Å hydrogen bound with Asp247 residue of MKK4. The IC50 of fisetin against MKK4 was estimated as 2.899 μM in the kinase assay, and the ATP-competitive effect was confirmed by ATP titration. Taken together, our data revealed that fisetin is a potent selective ATP-competitive MKK4 inhibitor to suppress MKK4-JNK1/2-AP-1 cascade for inhibiting LPS-induced inflammation.

Pain healing potential of famous traditional fermented Rhododendron (Lali-Guras) beverages from Indo-Nepal Himalaya: In vitro and in silic o evaluation

Abstract This in vitro and in silico study was designed to validate acclaimed anti-inflammatory or pain-relieving properties of fermented ethnic beverages prepared from Rhododendron or Guras flowers in the Singalila ridge- the famous Rhododendron growing region of the Himalayas. Traditional beverages Guras wine and its distilled version Guras Raksi were considered in this study which were collected from Gairibas, a village situated in Indo-Nepal Singalila Ridge of the Himalayas. In vitro protein (albumin) denaturation inhibition assay was conducted to evaluate anti-inflammatory activity of the samples and later GC-MS analysis was carried out to identify anti-inflammatory compounds present in those beverages. From GC-MS results, eleven major metabolites such as 5-hydroxymethylfurfural; quinic acid; clionasterol; l-(+)-ascorbic acid, 2,6-dihexadecanoate; d-sorbitol; cis-cinnamic acid; tyrosol; lupeol; methyl commate A; 2-hydroxy-gamma-butyrolactone; and 1,3-propanediol, 2-(hydroxymethyl)- 2-nitro- were chosen for molecular docking with human cyclooxygenase-1 (hCOX-1), an important targets in the drug-design for nonsteroidal anti-inflammatory drugs. Among all query compounds, phytosterol- clionasterol and triterpenoid- lupeol and methyl commate A exhibited considerably high binding energy scores (&lt;-8 kcal/mol) even compared to anti-inflammatory drugs- acetaminophen and ibuprofen. Outcome of this research affirmed the potential of Gurasbased traditional drinks in the healing of different forms of high-altitudinal stress induced pain.

Geraniin from the methanol extract of Pilea mongolica suppresses LPS-induced inflammatory responses by inhibiting IRAK4/MAPKs/NF-κB/AP-1 pathway in HaCaT cells

The skin acts as a vital barrier, shielding the body from external threats that can trigger dryness, itching, and inflammation. Pilea mongolica, a traditional Chinese medicinal herb, holds promise for various ailments, yet its anti-inflammatory properties remain understudied. This study aimed to explore the potential anti-inflammatory effects of the methanol extract of P. mongolica (MEPM) and its underlying molecular mechanisms and active compounds in LPS-stimulated human keratinocytes. MEPM treatment, at concentrations without cytotoxicity, significantly decreased NO productions and the iNOS, IL-6, IL-1β, and TNF-α levels in LPS-induced HaCaT cells. Moreover, MEPM suppressed IRAK4 expression and phosphorylation of JNK, ERK, p38, p65, and c-Jun, suggesting that the anti-inflammatory effects of MEPM result from the inhibition of IRAK4/MAPK/NF-κB/AP-1 signaling pathway. Through LC/MS/MS analysis, 30 compounds and 24 compounds were estimated in negative and positive modes, respectively, including various anti-inflammatory compounds, such as corilagin and geraniin. Through HPLC analysis, geraniin was found to be present in MEPM at a concentration of 18.87 mg/g. Similar to MEPM, geraniin reduced iNOS mRNA expression and inhibited NO synthesis. It also decreased mRNA and protein levels of inflammatory cytokines, including IL-6 and TNF-α, and inhibited IRAK4 expression and the phosphorylation of MAPKs, NF-κB, and AP-1 pathways. Therefore, it can be inferred that the anti-inflammatory effects of MEPM are attributable to geraniin. Thus, MEPM and its active compound geraniin are potential candidates for use in natural functional cosmetics.

Five anti-inflammatory compounds from the resins of Liquidambar orientalis

Five undescribed compounds, including a triterpenoid (1), three phenylpropanoids [(±)−2 and 4], and an aromatic compound (3), as well as six known analogues (5–10), were isolated from the resins of Liquidambar orientalis Mill. Their structures, including absolute configurations, were determined by using spectroscopic and computational methods, and the five new compounds displayed anti-inflammatory activities in LPS-induced RAW264.7 cells.

Taming the storm: potential anti-inflammatory compounds targeting SARS-CoV-2 MPro.

In severe COVID-19 cases, an exacerbated inflammatory response triggers a cytokine storm that can worsen the prognosis. Compounds with both antiviral and anti-inflammatory activities show promise as candidates for COVID-19 therapy, as they potentially act against the SARS-CoV-2 infection regardless of the disease stage. One of the most attractive drug targets among coronaviruses is the main protease (MPro). This enzyme is crucial for cleaving polyproteins into non-structural proteins required for viral replication. The aim of this review was to identify SARS-CoV-2 MPro inhibitors with both antiviral and anti-inflammatory properties. The interactions of the compounds within the SARS-CoV-2 MPro binding site were analyzed through molecular docking when data from crystallographic structures were unavailable. 18 compounds were selected and classified into five different superclasses. Five of them exhibit high potency against MPro: GC-376, baicalein, naringenin, heparin, and carmofur, with IC50 values below 0.2μM. The MPro inhibitors selected have the potential to alleviate lung edema and decrease cytokine release. These molecules mainly target three critical inflammatory pathways: NF-κB, JAK/STAT, and MAPK, all previously associated with COVID-19 pathogenesis. The structures of the compounds occupy the S1/S2 substrate binding subsite of the MPro. They interact with residues from the catalytic dyad (His41 and Cys145) and/or with the oxyanion hole (Gly143, Ser144, and Cys145), which are pivotal for substrate recognition. The MPro SARS-CoV-2 inhibitors with potential anti-inflammatory activities present here could be optimized for maximum efficacy and safety and be explored as potential treatment of both mild and severe COVID-19.

Inhibition of angiogenesis and metastasis in colorectal cancer cell lines through KRAS-associated signaling pathways by 2-methoxy-6-undecyl-1,4-benzoquinone

Colorectal cancer (CRC), the third most prevalent cancer globally, presents formidable hurdles in treatment owing to factors such as therapeutic resistance and genetic mutations affecting primary drug targets. 2-methoxy-6-undecyl-1,4-benzoquinone (BQ), derived from Ardisia crispa roots, has emerged as a potent anti-inflammatory and anti-angiogenic compound with substantial potential, as evidenced by previous studies. This study aimed to explore the potential of BQ in suppressing angiogenesis and metastasis in the human CRC cell lines LoVo and HCT116. Various in vitro and in silico studies have been conducted to elucidate the potential pathway(s) of BQ. BQ was highly cytotoxic, with an IC50 of 7.01 ± 0.6 μM in HCT116 and 9.58 ± 0.8 μM in LoVo cells. Moreover, BQ induced notable apoptotic activity and suppressed migration, invasion, and adhesion in both cell lines. The inhibition of MMP-2 suggests the potential of BQ to impede extracellular matrix degradation and CRC cell metastasis. BQ inhibits the expression of key proteins involved in angiogenesis and metastasis, including VEGF-A, VEGF-C, BRAF, ERK, KRAS, PI3K, and AKT. Molecular docking simulations illustrated the robust binding of BQ to CRC protein receptors. BQ holds promise in impeding CRC progression by targeting angiogenesis and metastasis, particularly through inhibition of the KRAS/BRAF/ERK and KRAS/PI3K/AKT signaling pathways.

Is oral nano-curcumin formulation a safe and effective measure for preventing cisplatin-induced nephrotoxicity in cancer patients?

Nephrotoxicity is one of the most important complications in cancer patients under treatment with cisplatin-containing regimens. Curcumin, as the most important active component of Curcuma longa, is an antioxidant and anti-inflammatory compound. In this clinical trial, we assessed the preventive effect of nano-curcumin oral formulation against cisplatin-induced nephrotoxicity in cancer patients. In this triple-blind clinical trial 30 cancer patients on cisplatin were randomly included in the treatment group, receiving nano-curcumin 40 mg capsules ( n = 15) or the placebo group ( n = 15) twice a day during four chemotherapy courses. Kidney function was measured at the beginning of the study and then at the end of each course of chemotherapy. There was no significant difference in acute kidney injury occurrence rate and creatinine and blood urine nitrogen serum levels between the treatment and placebo groups at the end of each chemotherapy course ( P value >0.05). Just at the end of the first course, the difference was close to significant ( P = 0.055). We also found no difference in mortality and recurrence rate in an average 30-month follow-up. Nano-curcumin in the prescribed dose and duration was not effective in preventing cisplatin-induced nephrotoxicity in cancer patients in comparison with the placebo. Further studies with larger sample size using different doses and duration of nano-curcumin are recommended.