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Undoable and Permanent [2+2] Cycloaddition Side effects associated with Heteroallenes to some Gallaphosphene.
DHA also altered the cellular composition in the spleen, which is the makeup of the T cells, dendritic cells (DCs), and macrophages. DHA recovered Th17-related profile with decreased frequency of IL-17+CD4+T cells from splenocyte of mice. Furthermore, DHA also inhibited the concentration of IL-17 from Th17 cells and the expression of Th17 cell-related transcription factors retinoid-related orphan receptor-gamma t (ROR-γt) in vitro. In addition, phosphorylation of signal transducer and activator of transcription-3 (STAT3) was significantly reduced in DHA treatment mice, suggesting that the IL-23/Th17 axis plays a pivotal role. Conclusion DHA inhibits the progression of psoriasis by regulating IL-23/Th17 axis and is expected to be an effective drug for the treatment of psoriasis.In the last decades, the search for natural products with biological applications as alternative treatments for several inflammatory diseases has increased. In this respect, terpenes are a family of organic compounds obtained mainly from plants and trees, such as tea, cannabis, thyme, and citrus fruits like lemon or mandarin. These molecules present attractive biological properties such as analgesic and anticonvulsant activities. Furthermore, several studies have demonstrated that certain terpenes could reduce inflammation symptoms by decreasing the release of pro-inflammatory cytokines for example, the nuclear transcription factor-kappa B, interleukin 1, and the tumor necrosis factor-alpha. Thus, due to various anti-inflammatory drugs provoking side effects, the search and analysis of novel therapeutics treatments are attractive. In this review, the analysis of terpenes' chemical structure and their mechanisms in anti-inflammatory functions are addressed. Additionally, we present a general analysis of recent investigations about their applications as an alternative treatment for inflammatory diseases. Furthermore, we focus on terpenes-based nanoformulations and employed dosages to offer a global perspective of the state-of-the-art.Metformin is the first-line anti-diabetic drug for type 2 diabetes. It has been found to significantly reduce liver aminotransferase in nonalcoholic fatty liver disease (NAFLD). However, whether metformin improves NAFLD progression remains controversial. Sirtuin 1 (SIRT1), an NAD+-dependent deacetylase, plays a vital role in hepatic steatosis and inflammation. Here, we investigated the effect of metformin on steatohepatitis and the role of SIRT1 in diet-induced obese (DIO) mice. The results showed that metformin significantly reduced body weight and fat mass of DIO mice. In addition, metformin also alleviated adiposity and hepatic steatosis, and greatly upregulated uncoupling protein 1 (UCP1) expression in adipose tissues of DIO mice. Unexpectedly, the effects of metformin on reducing body weight and alleviating hepatic steatosis were not impaired in Sirt1 heterozygous knockout (Sirt1 +/- ) mice. However, SIRT1-deficiency remarkably impaired the effects of metformin on lowering serum transaminases levels, downregulating the mRNA expression of proinflammatory factors, and increasing the protein level of hepatic Cholesterol 25-Hydroxylase (CH25H), a cholesterol hydroxylase in cholesterol catabolism. In summary, we demonstrated that metformin alleviates steatohepatitis in a SIRT1-dependent manner, and modulation of M1 polarization and cholesterol metabolism may be the underlying mechanism.Natural chemical compounds have been widely investigated for their programmed necrosis causing characteristics. One of the conventional methods for screening such compounds is the use of concentrated plant extracts without isolation of active moieties for understanding pharmacological activity. For the last two decades, modern medicine has relied mainly on the isolation and purification of one or two complicated active and isomeric compounds. The idea of multi-target drugs has advanced rapidly and impressively from an innovative model when first proposed in the early 2000s to one of the popular trends for drug development in 2021. Alternatively, fragment-based drug discovery is also explored in identifying target-based drug discovery for potent natural anticancer agents which is based on well-defined fragments opposite to use of naturally occurring mixtures. This review summarizes the current key advancements in natural anticancer compounds; computer-assisted/fragment-based structural elucidation and a multi-target approach for the exploration of natural compounds.In the past two decades, pandemics of several fatal coronaviruses have posed enormous challenges for public health, including SARS-CoV (2003), MERS-CoV (2012), and SARS-CoV-2 (2019). Among these, SARS-CoV-2 continues to ravage the world today and has lead to millions of deaths and incalculable economic damage. Till now, there is no clinically proven antiviral drug available for SARS-CoV-2. However, the bioactive molecules of natural origin, especially medicinal plants, have been proven to be potential resources in the treatment of SARS-CoV-2, acting at different stages of the viral life cycle and targeting different viral or host proteins, such as PLpro, 3CLpro, RdRp, helicase, spike, ACE2, and TMPRSS2. They provide a viable strategy to develop therapeutic agents. This review presents fundamental biological information on SARS-CoV-2, including the viral biological characteristics and invasion mechanisms. It also summarizes the reported natural bioactive molecules with anti-coronavirus properties, arranged by their different targets in the life cycle of viral infection of human cells, and discusses the prospects of these bioactive molecules for the treatment of COVID-19.Background The hypomethylating agents (HMAs) azacitidine (AZA) and decitabine (DAC) have been widely used in patients with acute myeloid leukemia (AML) and higher-risk myelodysplastic syndrome (HR-MDS). However, few direct clinical trials have been carried out to compare the efficacy and adverse events (AEs) between these two agents. The clinical choice between them is controversial. A systematic review and network meta-analysis (NMA) was performed to compare the efficacy, safety, and survival of DAC and AZA in AML and HR-MDS patients. Methods We systematically searched MEDLINE, Embase, Web of Science, and Cochrane Library through March 15, 2021. Randomized controlled trials (RCTs) on AML or HR-MDS patients comparing the efficacy and safety between DAC and AZA or comparing one of HMAs to conventional care regimens (CCR) were selected. Results Eight RCTs (n = 2,184) were identified in the NMA. Four trials compared AZA to CCR, and four compared DAC to CCR. Direct comparisons indicated that, compared to CCR, bot (low-certainty evidence), while AZA experienced lower frequent grade 3/4 cytopenia than patients receiving DAC treatment.Traditionally, plants of the genus Calotropis have been used to cure various common diseases. The present research work explores the chemical and biological characterization of one of the most common species of this genus, i.e., Calotropis gigantea (L.) Dryand (syn. Calotropis gigantea (L.) Dryand.), having multiple folklore applications. The ethanolic extract of leaves of Calotropis gigantea (L.) Dryand was analyzed for the phytochemical composition by determining the total bioactive (total phenolic and total flavonoid) contents and UHPLC-MS secondary metabolites analysis. For phytopharmacological evaluation, in vitro antioxidant (including DPPH, ABTS, FRAP, CUPRAC, phosphomolybdenum, and metal chelation antioxidant assays) activities, enzyme inhibition potential (against AChE, BChE, α-amylase, and tyrosinase enzymes), and in vivo wound healing potential were determined. The tested extract has been shown to contain considerable flavonoid (46.75 mg RE/g extract) and phenolic (33.71 mg GAE/g extract) contents. The plant extract presented considerable antioxidant potential, being the most active for CUPRAC assays. Secondary metabolite UHPLC-MS characterization, in both the positive and negative ionization modes, indicated the tentative presence of 17 different phytocompounds, mostly derivatives of sesquiterpene, alkaloids, and flavonoids. Similarly, the tested extract exhibited considerable inhibitory effects on tyrosinase (81.72 mg KAE/g extract), whereas it showed weak inhibition ability against other tested enzymes. Moreover, in the case of in vivo wound healing assays, significant improvement in wound healing was observed in both the tested models at the doses of 0.5 percent w/w (p less then 0.001) and 2.0 percent w/w (p less then 0.01) on the 16th day. The outcomes of the present research work suggested that C. gigantea (L.) Dryand plant extract could be appraised as a potential origin of bioactive molecules having multifunctional medicinal uses.Sonneratia apetala Buch-Ham., an exotic mangrove species with antidiabetic, antibacterial, and antioxidant capacities, mainly distributes in the southeast coastal areas in China. RRx-001 nmr The present work investigated the protective effects of Sonneratia apetala leaves and branches extraction (SAL) on hyperuricemia (HUA) in mice. Potassium oxonate (PO) and hypoxanthine (HX) were used to establish the HUA model by challenge for consecutive 7 days. Results revealed that SAL inhibited the increases in kidney weight and index compared to the vehicle group. Meanwhile, SAL significantly decreased the levels of uric acid (UA), creatinine (CRE), and blood urea nitrogen (BUN) in serum. Additionally, SAL inhibited the activity of xanthine oxidase (XOD) in the liver. SAL ameliorated PO- and HX-induced histopathological changes. Moreover, it regulated oxidative stress markers including malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD) activity, and glutathione (GSH) content. Also, SAL inhibited the increases in reents.Sepsis is a dysregulated systemic response to infection, and no effective treatment options are available. Acacetin is a natural flavonoid found in various plants, including Sparganii rhizoma, Sargentodoxa cuneata and Patrinia scabiosifolia. Studies have revealed that acacetin potentially exerts anti-inflammatory and antioxidative effects on sepsis. In this study, we investigated the potential protective effect of acacetin on sepsis and revealed the underlying mechanisms using a network pharmacology approach coupled with experimental validation and molecular docking. First, we found that acacetin significantly suppressed pathological damage and pro-inflammatory cytokine expression in mice with LPS-induced fulminant hepatic failure and acute lung injury, and in vitro experiments further confirmed that acacetin attenuated LPS-induced M1 polarization. Then, network pharmacology screening revealed EGFR, PTGS2, SRC and ESR1 as the top four overlapping targets in a PPI network, and GO and KEGG analyses revealed the top 20 enriched biological processes and signalling pathways associated with the therapeutic effects of acacetin on sepsis. Further network pharmacological analysis indicated that gap junctions may be highly involved in the protective effects of acacetin on sepsis. Finally, molecular docking verified that acacetin bound to the active sites of the four targets predicted by network pharmacology, and in vitro experiments further confirmed that acacetin significantly inhibited the upregulation of p-src induced by LPS and attenuated LPS-induced M1 polarization through gap junctions. Taken together, our results indicate that acacetin may protect against sepsis via a mechanism involving multiple targets and pathways and that gap junctions may be highly involved in this process.
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