Subsequently, over forty compounds, comprising luteolin, darutoside, and kaempferol, corresponding to distinct peaks, were tentatively ascertained through the alignment of their empirical molecular formulas and mass fragmentations.
Our investigation revealed that SO and its active compound, luteolin, displayed anti-RA activity, significantly inhibiting TLR4 signaling, both within laboratory settings and in living subjects. These findings affirm the significance of network pharmacology in the identification of herbal-based therapeutics for diseases, and they also suggest the development potential of SO and its associated active compounds as anti-rheumatic drugs.
Our investigations revealed that SO and its active compound, luteolin, demonstrate anti-rheumatic activity, powerfully suppressing TLR4 signaling pathways in both laboratory and animal models. These findings not only showcase network pharmacology's effectiveness in discovering herb-based therapies for illnesses but also point towards the potential of SO and its active compounds as novel anti-rheumatic drug options.
Traditional Chinese Medicine frequently utilizes Sargentodoxa cuneata and Patrinia villosa (S&P) as natural herbal treatments for inflammatory disorders; however, the underlying modes of action necessitate further research and investigation.
The purpose of this study was to investigate the anti-inflammatory activities and decipher the implicated mechanism of S&P extract.
Through the application of liquid chromatography-tandem mass spectrometry (LC-MS/MS), the presence of S&P extract components was first confirmed. CCK8, LDH, adhesion, and transwell assays were used to detect the effects of S&P extract on the viability and migratory ability of macrophages. Cytokine release and the transition in macrophage phenotypes were determined using cytometric bead arrays and flow cytometry. RNA sequencing and LC-MS/MS-based metabolic analysis, used in an integrative approach, uncovered the potential mechanism. The expression of related proteins was subsequently confirmed by means of western blotting.
Macrophage proliferation, migration, and morphology were impacted by S&P treatment following LPS stimulation, along with a suppression of nitric oxide production and iNOS expression. Additionally, the extract suppressed the creation of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and decreased the expression of M1 markers CD11c and CD16/32. It concurrently encouraged the production of interleukin-10 (IL-10) and stimulated the expression of M2 markers CD206 and arginase 1 (Arg1). Analysis of RNA sequencing data showed that S&P extract treatment increased the expression of genes crucial for M2 macrophage function, such as Il10, Ccl17, Ccl22, and Cd68. The S&P extract demonstrably mitigated the metabolic disruptions induced by lipopolysaccharide (LPS), as evidenced by metabolomics results focusing on M1 macrophages and glycolysis-related genes, including Stat1, Il18, Cd80, Cd86, Nos2, Il6, Pik3ap1, Raf1, Pdhb, and others. KEGG analysis revealed that the majority of these metabolites were engaged in glucose metabolism, a process central to tumor necrosis factor (TNF), phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), glycolysis, and mitogen-activated protein kinase (MAPK) pathways. In vitro experiments corroborated the extract's substantial inhibition of focal adhesion kinase (FAK), phosphatidylinositol 3-kinase (PI3K), and protein kinase B (Akt) phosphorylation, and the expression of glucose metabolic proteins. Defactinib, a FAK inhibitor, caused a further reduction in the expression of M1/M2 phenotypic markers and the phosphorylation of FAK, PI3K, and Akt.
In LPS-induced inflammation, S&P extract orchestrates the transition of macrophages from M1 to M2 polarization, improving tissue repair by influencing the glucose metabolism and FAK/PI3K/Akt pathway.
In LPS-induced inflammation, S&P extract treatment can induce a shift in macrophage polarization, moving them from the M1 to the M2 phenotype, through modulation of glucose metabolism and the FAK/PI3K/Akt pathway.
Approximately 175 species of the Scorzonera L. genus are primarily located in temperate and arid zones of Central Europe, Central Asia, and Africa. The review explores the traditional uses of twenty-nine Scorzonera species in treating colds, fevers, lung ailments, asthma, indigestion, malignant stomach tumors, liver diseases, jaundice, kidney problems, mastitis, female genital tract infections, herpes zoster, venomous skin ulcers, rheumatic pain, diabetes, atherosclerosis, headaches, hypertension, dysentery, morning sickness, snakebites, and various other conditions.
This review draws upon a substantial collection of published scientific research, sourced from databases like Elsevier, Web of Science, PubMed, Springer, Wiley, Taylor & Francis, Google Scholar, CNKI, Baidu Scholar, ResearchGate and other relevant publications, including the 1997 Flora of China, Chinese herbal literature, and Chinese PhD and Masters dissertations.
Research on the 81 Scorzonera genus encompasses traditional applications, phytochemical aspects, and pharmacological analyses. The 54 Scorzonera species examined have proven to contain 421 distinct chemical constituents, encompassing sesquiterpenoids, monoterpenes, diterpenes, triterpenoids, steroids, quinic acid derivatives, flavonoids, cumarinoids, lignanoids, phenylpropanoids, stilbene derivatives, benzylphthalides, kava lactones, phenolics, aliphatic acids, phthalic acids, alkanes, vitamins, sugars, alkaloids, and other substances. Supplementary to the already mentioned substances, volatile oils, polysaccharides, tannins, amino acids, enzymes, and inorganic elements are additionally present. 55 Scorzonera species' extracts and compounds demonstrate extensive pharmacological activity including, but not limited to, anti-inflammatory, antinociceptive, wound healing, anti-cancer, hepatoprotective, anti-microbial, anti-ulcerogenic, antidiarrheal, antidiabetic, hypolipidemic, antioxidant, cerebral ischemia repair, antidepressant, immunomodulatory, and enzyme inhibitory effects. The study of certain species encompasses pharmacokinetic and histological distribution, toxicity, product extraction procedures, quick-freezing processing technology, as well as synthesized metabolite investigation. A chemotaxonomic perspective is also presented concerning Scorzonera.
From traditional practices to future prospects, this review details the usage, phytochemistry, pharmacology, toxicology, chemotaxonomy, diverse applications, and future trends of the Scorzonera genus. Nevertheless, just one-third of the Scorzonera species have been examined up to this point. Future endeavors, including biological and chemical investigations, and the pursuit of further applications, may be informed by this review.
A review of the Scorzonera genus includes traditional uses, phytochemical properties, pharmacological studies, toxicity data, chemotaxonomic analyses, various applications, and future research potential. In contrast, the research efforts on Scorzonera species have only reached approximately one-third of their total variety. This review can serve as a blueprint for future endeavors, including further research into biological and chemical processes, and the exploration of new applications.
During the Qing dynasty, Wang Ang, a renowned physician, recorded the standardized herbal prescription Longdan Xiegan decoction (LXD) in the Medical Formula Collection. This treatment has seen extensive use in cases of vulvovaginal candidiasis (VVC). Despite its proven effectiveness, the exact manner in which it exerts its influence is yet to be fully elucidated.
LXD's effect on alleviating VVC is dependent on the Toll-like receptor/MyD88 pathway and the subsequent activation of the NLRP3 inflammasome, a process requiring further elucidation.
Ninety-six female Kunming mice were randomly partitioned into six distinct groups: control, a VVC model group, and three LXD treatment groups (10, 20, and 40 mL/kg), as well as a positive control group administered fluconazole. Mice were treated vaginally with the Candida albicans (C.) strain. To produce a 1:10 Candida albicans solution, 20 liters were used.
After a five-minute suspension, colony-forming units per milliliter were monitored daily for changes in their state. Fungal biomass Continuous dilution methods were used to quantify the number of colony-forming units. Employing Gram, periodic acid-Schiff, Papanicolaou, and hematoxylin and eosin staining procedures, the researchers determined the extent of the infection. The enzyme-linked immunosorbent assay (ELISA) technique was utilized to measure the levels of the proinflammatory cytokines, interleukin-1 (IL-1) and interleukin-18 (IL-18). BIO2007817 The protein expression of TLR2, TLR4, MyD88, NF-κB, NLRP3, ASC, and caspase-1 was quantified via western blotting analysis.
C. albicans infection caused significant damage to the vaginal mucosa, characterized by a proliferation of fungal organisms, an increase in neutrophil infiltration, and the subsequent stimulation of proinflammatory cytokine release into the vaginal cavity. C. albicans activity resulted in elevated levels of TLR2, TLR4, MyD88, NF-κB, NLRP3, ASC, and caspase-1 expression in vaginal tissue. Next Generation Sequencing The 20 and 40 mL/kg LXD groups demonstrated a decrease in the amount of fungus, the formation of hyphae, and the adhesion of C. albicans. The Hematoxylin and eosin staining procedure indicated a diminished inflammatory response and a recovery of the stratum corneum in the 20 mL/kg LXD and 40 mL/kg LXD treatment groups. Vaginal lavage samples treated with LXD (20 and 40 mL/kg) exhibited a substantial decrease in IL-1, IL-18 levels, and neutrophil abundance, accompanied by a concomitant reduction in the expression of TLR2, TLR4, MyD88, NF-κB, NLRP3, ASC, and caspase-1.
A systematic investigation of LXD's therapeutic impact on protein expression and pathological conditions was meticulously conducted in VVC mice. LXD's effects on mice included eliminating vaginal hyphae invasion, diminishing neutrophil recruitment, and reducing TLR/MyD88 pathway protein and NLRP3 inflammasome expression. The above results definitively point to LXD's significant regulatory influence on the NLRP3 inflammasome, potentially via the TLR/MyD88 signaling pathway, and its possible therapeutic utility in VVC.