Lung protective effect of Punicalagin on LPS-induced acute lung injury in mice

Background: Punicalagin (Pun) is one of the main bioactive compounds in pomegranate peel, it possesses many properties, including antioxidant, anti-inflammation, and immunosuppressive activities. The study was aimed to investigate the protective effect and mechanisms of Pun on lipopolysaccharide (LPS) induced acute lung injury (ALI) in mice. Methods and Results: Forty-eight BALB/c male mice were used to establish ALI by intratracheal-instilled 2.4 mg/kg LPS, the mice were randomly divided into model and Pun (10, 20, 40 mg/kg) groups. The other twelve mice were intratracheal-instilled same volume of water as control. After 2 h of receiving LPS, mice were administrated drug through intraperitoneal injection. Lung index, histopathological changes, white blood cells and biomarkers in bronchoalveolar lavage fluid (BALF) were analyzed. The protein expression of total and phosphor p65, IκBα, ERK1/2, JNK and p38 in lung tissue was detected. The result showed that Pun could reduce the lung index and wet/dry weight ratio, improve lung histopathological injury. In addition, Pun decreased the inflammation cells and regulated the biomarkers in BALF. Furthermore, Pun dose-dependently reduced the phosphor protein levels of p65, IκBα, ERK1/2, JNK and p38 in lung tissue, which exhibited that the effect of Pun related to MAPKs pathway. More importantly, there is no toxicity was observed in the acute toxicity study of Pun. Conclusion: Pun improves LPS-induced ALI mainly through its anti-inflammatory properties, which is associated with NF-κB and MAPKs signaling pathways. The study implied that Pun maybe a potent agent against ALI in future clinic.

The potency of blumeatin and luteolin as caspase-1 inhibitor by molecular docking

COVID-19 infection induces inflammation by increasing cytokines such as IL-1b, IL-6, IL-18, IFN-γ, and TNF-α. IL-1b is generated by the involvement of caspase-1. Therefore, caspase-1 inhibitor can be potential for inflammation therapy caused by COVID-19 infection. This study aims to determine the potential of blumeatin and luteolin as anti-inflammatory agents by inhibiting caspase-1 using a molecular docking approach. This study was carried out by caspase-1 (PDB ID: 1RWK) preparation, blumeatin and luteolin structure optimization, docking protocol validation, and docking of blumeatin and luteolin on caspase-1. Bluematin and luteolin had a binding affinity of -5,63 kcal/mol and -5,93 kcal/mol, lower than Q158 native ligand (-3.92 kcal/mol). Similar amino acid residues in hydrogen bonds interaction were observed between Q158 native ligand, blumeatin, and luteolin with caspase-1 (GLN 283 and ARG 179). Blumeatin and luteolin are potentially anti-inflammation agents through the inhibition of the caspase-1 in silico.

CTRP3 as a novel biomarker in the plasma of Saudi children with autism

Background C1q/tumor necrosis factor-related protein-3 (CTRP3) has diverse functions: anti-inflammation, metabolic regulation, and protection against endothelial dysfunction. Methods The plasma level of CTRP3 in autistic patients (n = 32) was compared to that in controls (n = 37) using ELISA. Results CTRP3 was higher (24.7% with P < 0.05) in autistic patients than in controls. No association was observed between CTRP3 and the severity of the disorder using the Childhood Autism Rating Scale (CARS). A positive correlation between CARs and the age of patients was reported. Receiver operating characteristic (ROC) analysis demonstrated a low area under the curve (AUC) for all patients (0.636). Low AUCs were also found in the case of severe patients (0.659) compared to controls, but both values were statistically significant (P ≤ 0.05). Despite the small sample size, we are the first to find an association between CTRP3 and autism spectrum disorder (ASD).

Genetic Blockade of NAAA Cell-specifically Regulates Fatty Acid Ethanolamides (FAEs) Metabolism and Inflammatory Responses

N-Acylethanolamine acid amidase (NAAA) is a lysosomal enzyme responsible for the hydrolysis of fatty acid ethanolamides (FAEs). However, the role of NAAA in FAEs metabolism and regulation of pain and inflammation remains mostly unknown. Here, we generated NAAA-deficient (NAAA-/-) mice using CRISPR-Cas9 technique, and found that deletion of NAAA increased PEA and AEA levels in bone marrow (BM) and macrophages, and elevated AEA levels in lungs. Unexpectedly, genetic blockade of NAAA caused moderately effective anti-inflammatory effects in lipopolysaccharides (LPS)-induced acute lung injury (ALI), and poor analgesic effects in carrageenan-induced hyperalgesia and sciatic nerve injury (SNI)-induced mechanical allodynia. These data contrasted with acute (single dose) or chronic NAAA inhibition by F96, which produced marked anti-inflammation and analgesia in these models. BM chimera experiments indicated that these phenotypes were associated with the absence of NAAA in non-BM cells, whereas deletion of NAAA in BM or BM-derived cells in rodent models resulted in potent analgesic and anti-inflammatory phenotypes. When combined, current study suggested that genetic blockade of NAAA regulated FAEs metabolism and inflammatory responses in a cell-specifical manner.

Triamcinolone Acetonide-Loaded Nanoparticles Encapsulated By CD90+ MCSs-Derived Microvesicles Drive Anti-Inflammatory Properties and Promote Cartilage Regeneration After Osteoarthritis

Background: Osteoarthritis (OA) is a highly prevalent human degenerative joint disorder that has long plagued patients. Glucocorticoid injection into the intra-articular (IA) cavity provides potential short-term analgesia and anti-inflammation, but long-term IA causes loss of cartilage content. Synovial mesenchymal stem cells (MSCs) reportedly promote cartilage proliferation and increase cartilage content. Methods: The CD90+ MCSs-derived micro-vesicle (CD90@MV)-coated nanoparticle (CD90@NP) was developed. CD90+ MCSs were extracted from human synovial tissue. Cytochalasin B (CB) relaxed the interaction between the cytoskeleton and the cell membranes of CD90+ MCSs, stimulating CD90@MV secretion. The poly (lactic-co-glycolic acid) (PLGA) nanoparticle was coated with CD90@MV, and a model glucocorticoid, triamcinolone acetonide (TA), was encapsulated in CD90@NP (T-CD90@NP). Results: CD90@MV membrane proteins were similar to CD90+ MCSs, indicating that the CD90@MV bio-activity is similar to the cartilage proliferation-inducing CD90+ MCSs. The CD90@NP binding to injury cartilage primary cells was significantly stronger than the erythrocyte membrane-coated nanoparticles (RNP). In the rabbit OA model, long-term IA of T-CD90@NP showed significantly enhanced repair of damaged cartilage than TA and CD90+ MCSs treatments. In the rat OA model, short-term IA of T-CD90@NP showed effective anti-inflammatory ability similar to TA treatment. Moreover, long-term IA of T-CD90@NP induced cartilage to restart the cell cycle and reduced cartilage apoptosis. T-CD90@NP promotes regeneration of chondrocytes, reduces apoptosis via the FOXO pathway, and influences type 2 macrophage polarization to regulate inflammation through IL-10. Conclusion: This study confirms that T-CD90@NP promotes chondrocyte proliferation and anti-inflammation, improving the clinical glucocorticoid treatment plan.

Sesamol Attenuates Neuroinflammation by Regulating the AMPK/SIRT1/NF-κB Signaling Pathway after Spinal Cord Injury in Mice

Inflammation is one of the crucial mechanisms mediating spinal cord injury (SCI) progress. Sesamol, a component of sesame oil, has anti-inflammatory activity, but its mechanism in SCI remains unclear. We investigated if the AMPK/SIRT1/NF-κB pathway participated in anti-inflammation of sesamol in SCI. Sesamol could inhibit neuronal apoptosis, reduce neuroinflammation, enhance M2 phenotype microglial polarization, and improved motor function recovery in mice after SCI. Furthermore, sesamol increased SIRT1 protein expression and p-AMPK/AMPK ratio, while it downregulated the p-p65/p65 ratio, indicating that sesamol treatment upregulated the AMPK/SIRT1 pathway and inhibited NF-κB activation. However, these effects were blocked by compound C which is a specific AMPK inhibitor. Together, the study suggests that sesamol is a potential drug for antineuroinflammation and improving locomotor functional recovery through regulation of the AMPK/SIRT1/NF-κB pathway in SCI.

A Review of Pharmacology, Toxicity and Pharmacokinetics of 2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-Glucoside

Polygonum multiflorum Thunb. (He-shou-wu in Chinese), a Chinese botanical drug with a long history, is widely used to treat a variety of chronic diseases in clinic, and has been given the reputation of “rejuvenating and prolonging life” in many places. 2,3,4′,5-tetrahydroxystilbene-2-O-β-D-glucoside (TSG, C20H22O9) is the main and unique active ingredient isolated from Polygonum multiflorum Thunb., which has extensive pharmacological activities. Modern pharmacological studies have confirmed that TSG exhibits significant activities in treating various diseases, including inflammatory diseases, neurodegenerative diseases, cardiovascular diseases, hepatic steatosis, osteoporosis, depression and diabetic nephropathy. Therefore, this review comprehensively summarizes the pharmacological and pharmacokinetic properties of TSG up to 2021 by searching the databases of Web of Science, PubMed, ScienceDirect and CNKI. According to the data, TSG shows remarkable anti-inflammation, antioxidation, neuroprotection, cardiovascular protection, hepatoprotection, anti-osteoporosis, enhancement of memory and anti-aging activities through regulating multiple molecular mechanisms, such as NF-κB, AMPK, PI3K-AKT, JNK, ROS-NO, Bcl-2/Bax/Caspase-3, ERK1/2, TGF-β/Smad, Nrf2, eNOS/NO and SIRT1. In addition, the toxicity and pharmacokinetics of TSG are also discussed in this review, which provided direction and basis for the further development and clinical application of TSG.

Nrf2-Related Therapeutic Effects of Curcumin in Different Disorders

Curcumin is a natural polyphenol with antioxidant, antibacterial, anti-cancer, and anti-inflammation effects. This substance has been shown to affect the activity of Nrf2 signaling, a pathway that is activated in response to stress and decreases levels of reactive oxygen species and electrophilic substances. Nrf2-related effects of curcumin have been investigated in different contexts, including gastrointestinal disorders, ischemia-reperfusion injury, diabetes mellitus, nervous system diseases, renal diseases, pulmonary diseases, cardiovascular diseases as well as cancers. In the current review, we discuss the Nrf2-mediated therapeutic effects of curcumin in these conditions. The data reviewed in the current manuscript indicates curcumin as a potential activator of Nrf2 and a therapeutic substance for the protection of cells in several pathological conditions.

Role of Vitamin K in Intestinal Health

Intestinal diseases, such as inflammatory bowel diseases (IBDs) and colorectal cancer (CRC) generally characterized by clinical symptoms, including malabsorption, intestinal dysfunction, injury, and microbiome imbalance, as well as certain secondary intestinal disease complications, continue to be serious public health problems worldwide. The role of vitamin K (VK) on intestinal health has drawn growing interest in recent years. In addition to its role in blood coagulation and bone health, several investigations continue to explore the role of VK as an emerging novel biological compound with the potential function of improving intestinal health. This study aims to present a thorough review on the bacterial sources, intestinal absorption, uptake of VK, and VK deficiency in patients with intestinal diseases, with emphasis on the effect of VK supplementation on immunity, anti-inflammation, intestinal microbes and its metabolites, antioxidation, and coagulation, and promoting epithelial development. Besides, VK-dependent proteins (VKDPs) are another crucial mechanism for VK to exert a gastroprotection role for their functions of anti-inflammation, immunomodulation, and anti-tumorigenesis. In summary, published studies preliminarily show that VK presents a beneficial effect on intestinal health and may be used as a therapeutic drug to prevent/treat intestinal diseases, but the specific mechanism of VK in intestinal health has yet to be elucidated.