Quercetin, naringenin, ?-sitosterol, luteolin, and stigmasterol, key bioactive elements in Lianhu Qingwen, were observed to influence host cytokines and adjust the immune response to COVID-19. Against COVID-19, Lianhua Qingwen Capsule's pharmacological activity was found significantly linked to genes including androgen receptor (AR), myeloperoxidase (MPO), epidermal growth factor receptor (EGFR), insulin (INS), and aryl hydrocarbon receptor (AHR). The treatment of COVID-19 saw synergistic activity exhibited by four botanical drug pairs contained in Lianhua Qingwen Capsule. Evaluations of clinical studies confirmed the medicinal potential of administering Lianhua Qingwen Capsule along with established medical treatments in the context of COVID-19. The four primary pharmacological mechanisms of Lianhua Qingwen Capsule in the treatment of COVID-19 are, in conclusion, identified. The therapeutic effects of Lianhua Qingwen Capsule on COVID-19 have been observed.
Through investigation, this study explored the impact and mechanisms of Ephedra Herb (EH) extract on adriamycin-induced nephrotic syndrome (NS), offering a foundation for potential experimental NS interventions. The renal function-altering effects of EH extract were studied using hematoxylin and eosin staining, creatinine measurements, urea nitrogen measurements, and kidn injury molecule-1 quantification. Inflammatory factors and oxidative stress levels were quantitatively assessed using kits. Flow cytometry was employed to quantify reactive oxygen species, immune cells, and apoptosis levels. Employing a network pharmacological strategy, potential targets and mechanisms of action of EH extract in treating NS were predicted. Protein expression levels of apoptosis-related proteins, CAMKK2, p-CAMKK2, AMPK, p-AMPK, mTOR, and p-mTOR in kidney tissue were detected by employing Western blot analysis. The EH extract's effective material basis was scrutinized using the MTT assay. Compound C (CC), an inhibitor of the AMPK pathway, was introduced to analyze its influence on adriamycin-induced cellular harm. Rats administered EH extract showed significant improvements in kidney health, characterized by reduced inflammation, oxidative stress, and apoptotic cell death. AMP-mediated protein kinase The CAMKK2/AMPK/mTOR signaling pathway is implicated in the effect of EH extract on NS, as observed through network pharmacology and Western blot validation. The effect of methylephedrine was to substantially improve the condition of NRK-52e cells, which were previously injured by adriamycin. Methylephedrine's positive impact on AMPK and mTOR phosphorylation was definitively diminished by the presence of CC. EH extract, in the aggregate, may improve renal health by influencing the CAMKK2/AMPK/mTOR signaling pathway. Moreover, methylephedrine is likely to be among the foundational materials that comprise the EH extract.
Renal interstitial fibrosis is the defining pathway within chronic kidney disease, ultimately resulting in end-stage renal failure. Although, the core function of Shen Qi Wan (SQW) regarding Resting Illness Fatigue (RIF) is not completely understood. Utilizing current research methodologies, we investigated Aquaporin 1 (AQP1)'s contribution to SQW-induced tubular epithelial-to-mesenchymal transition (EMT). For an in-depth investigation into SQW's protective effect against EMT, both in vivo and in vitro studies were carried out, employing a RIF mouse model induced by adenine and a TGF-1-stimulated HK-2 cell model, with a focus on the involvement of AQP 1. Subsequently, the molecular process responsible for the impact of SQW on EMT was investigated using HK-2 cells in which AQP1 was knocked down. Kidney injury and renal collagen buildup in adenine-treated mice were ameliorated by SQW, which augmented E-cadherin and aquaporin-1 protein expression and reduced vimentin and smooth muscle alpha-actin expression. Similarly, the administration of SQW-enriched serum significantly brought a halt to the EMT process in TGF-1-induced HK-2 cells. A notable enhancement in the expression of both snail and slug was observed in HK-2 cells consequent to the AQP1 knockdown. A decrease in AQP1 expression resulted in a rise in the mRNA levels of vimentin and smooth muscle actin, and a corresponding decrease in E-cadherin. A decrease in the expression of E-cadherin and CK-18 was observed in HK-2 cells after AQP1 knockdown, contrasting with a rise in vimentin expression. These experimental outcomes displayed a promotion of EMT following AQP1 knockdown. Moreover, silencing AQP1 eliminated the protective impact of serum containing SQW on epithelial-mesenchymal transition in HK-2 cells. In brief, SQW impacts the EMT process within RIF by promoting the expression of AQP1.
Platycodon grandiflorum (Jacq.) A. DC., a renowned medicinal plant, is frequently employed in traditional East Asian medicine. Triterpene saponins, isolated from the source *P. grandiflorum*, represent the key biologically active compounds, polygalacin D (PGD) among them being recognized for its anti-tumor activity. Nonetheless, the way it targets and eradicates hepatocellular carcinoma cells is not known. This research aimed to examine the inhibitory effects of PGD on hepatocellular carcinoma cells and to understand the underlying mechanisms. PGD's inhibitory effect on hepatocellular carcinoma cells was substantial, involving apoptosis and autophagy. Apoptosis-related and autophagy-related protein expression analysis implicated mitochondrial apoptosis and mitophagy pathways in this phenomenon. PFTα p53 inhibitor Subsequently, upon using particular inhibitors, we found that apoptosis and autophagy displayed a reciprocal, reinforcing action. Another investigation into autophagy showed that the application of PGD fostered mitophagy by increasing the levels of BCL2 interacting protein 3-like (BNIP3L). Through our research, we determined that PGD's primary effect on hepatocellular carcinoma cells involved the triggering of mitochondrial apoptosis and mitophagy. As a result, preimplantation genetic diagnosis (PGD) can function as a trigger for apoptosis and autophagy in the development of novel antitumor agents.
Anti-tumor responses triggered by anti-PD-1 antibodies are heavily contingent upon the intricate immune microenvironment within the tumor. This study was designed to determine if there was a mechanistic relationship between Chang Wei Qing (CWQ) Decoction and the enhancement of anti-tumor activity in patients receiving PD-1 inhibitor therapy. Next Generation Sequencing A significant anti-tumor effect was observed in patients with mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC) treated with PD-1 inhibitors, demonstrating a marked difference from the results in patients with mismatch repair-proficient/microsatellite stable (pMMR/MSS) CRC. Employing immunofluorescence double-label staining, the differential time course of dMMR/MSI-H and pMMR/MSS CRC patients was determined. Murine tumor tissue's T-lymphocyte populations were characterized by flow cytometry. Using Western blotting, the expression of PD-L1 protein was assessed in mouse tumor tissue. To examine the intestinal mucosal barrier in mice, hematoxylin-eosin staining and immunohistochemistry methods were utilized. Furthermore, the structure of the gut microbiota in these mice was determined using 16S rRNA-gene sequencing. The subsequent analysis involved Spearman's correlation to determine the correlation between the gut microbiota and tumor-infiltrating T-lymphocytes. The results from the study on dMMR/MSI-H CRC patients showed more CD8+T cells and a greater expression level of PD-1 and PD-L1 proteins. Within living organisms, CWQ augmented the anti-tumor efficacy of the anti-PD-1 antibody, concomitantly boosting the infiltration of CD8+ and PD-1+CD8+ T lymphocytes within the tumor microenvironment. Moreover, the concurrent application of CWQ and anti-PD-1 antibody resulted in a lower level of intestinal mucosal inflammation than the inflammation observed with anti-PD-1 antibody alone. Combined CWQ and anti-PD-1 antibody treatment resulted in elevated PD-L1 protein, reduced Bacteroides gut bacteria, and increased abundances of Akkermansia, Firmicutes, and Actinobacteria. The number of Akkermansia was found to be positively associated with the proportion of infiltrated CD8+PD-1+, CD8+, and CD3+ T cells. Likewise, CWQ might potentially alter the TIME by changing the gut microbial balance and thus boost the anti-cancer response to PD-1 inhibitor treatment.
The material basis of pharmacodynamics and the effective mechanisms are central to comprehending the action of Traditional Chinese Medicines (TCMs) in the treatment of diseases. TCMs' effectiveness in complex diseases is evidenced by their multi-component, multi-target, and multi-pathway approaches, resulting in satisfactory clinical outcomes. Explaining the complex relationships between TCM practices and illnesses demands a pressing need for fresh perspectives and innovative methodologies. A novel paradigm, network pharmacology (NP), is presented for the purpose of discovering and visualizing the intricate interaction networks of Traditional Chinese Medicine (TCM) therapies in combating complex diseases. The development and implementation of NP methods have significantly advanced studies on TCM safety, efficacy, and mechanisms, which has subsequently contributed to its heightened credibility and widespread appeal. The dominant emphasis on individual organs in medical practice, and the inflexible 'one disease-one target-one drug' principle, obstructs the understanding of intricate diseases and the development of efficient drug solutions. Hence, a shift in emphasis is necessary, moving from outward expressions and symptoms to the fundamental mechanisms and root causes in comprehending and revising existing medical conditions. Over the last two decades, the emergence of sophisticated, intelligent technologies, including metabolomics, proteomics, transcriptomics, single-cell omics, and artificial intelligence, has significantly enhanced and profoundly integrated NP, showcasing its substantial value and potential as a revolutionary drug discovery approach.