Analysis of Polyphenol Extract from Hazel Leaf and Ameliorative Efficacy and Mechanism against Hyperuricemia Zebrafish Model via Network Pharmacology and Molecular Docking.

Hazel leaf, a by-product of hazelnuts, is commonly used in traditional folk medicine in Portugal, Sweden, Iran and other regions for properties such as vascular protection, anti-bleeding, anti-edema, anti-infection, and pain relief. Based on our previous studies, the polyphenol extract from hazel leaf was identified and quantified via HPLC fingerprint. The contents of nine compounds including kaempferol, chlorogenic acid, myricetin, caffeic acid, p-coumaric acid, resveratrol, luteolin, gallic acid and ellagic acid in hazel leaf polyphenol extract (ZP) were preliminary calculated, among which kaempferol was the highest with 221.99 mg/g, followed by chlorogenic acid with 8.23 mg/g. The inhibition of ZP on α-glucosidase and xanthine oxidase activities was determined via the chemical method, and the inhibition on xanthine oxidase was better. Then, the effect of ZP on hyperuricemia zebrafish was investigated. It was found that ZP obviously reduced the levels of uric acid, xanthine oxidase, urea nitrogen and creatinine, and up-regulated the expression ofOAT1 and HPRT genes in hyperuricemia zebrafish. Finally, the targeted network pharmacological analysis and molecular docking of nine polyphenol compounds were performed to search for relevant mechanisms for alleviating hyperuricemia. These results will provide a valuable basis for the development and application of hazel leaf polyphenols as functional ingredients.

Integrated cell metabolomics and network pharmacology approach deciphers the anti-testosterone deficiency mechanisms of Bushen Zhuanggu Tang.

Testicular dysfunction is distinguished by a deficiency in testosterone levels, which can be attributed to the occurrence of oxidative stress injury in Leydig cells. The empirical prescription known as Bushen Zhuanggu Tang, developed by a highly experienced traditional Chinese medicine practitioner with six decades of clinical expertize, aligns with the traditional Chinese medicine principle of "kidney governing bone". Researchers have demonstrated that the administration of BSZGT can effectively enhance testosterone production. The objective of this study is to investigate the potential anti-testicular dysfunction effects of BSZGT and elucidate its underlying mechanism in an in vitro setting. Specifically, the impact of oxidative stress induced by H2O2 on the activity and testosterone levels of Leydig cells (TM3) was examined. Furthermore, the utilization of UPLC-QE-Qrbitrap-MS enabled the identification of the involvement of BSZGT in various metabolic pathways, including arginine biosynthesis, amino acyl-tRNA biosynthesis, Alanine, aspartate and glutamine metabolism, and Citrate Cycle, through the modulation of 25 distinct metabolites. Additionally, a network pharmacological analysis was conducted to investigate the pivotal protein targets associated with the therapeutic effects of BSZGT. The findings demonstrate the identification of six key proteins (CYP19A1, CYP1B1, ALOX5, ARG1, XDH, and MPO) that play a significant role in augmenting testicular function through their involvement in the ovarian steroid production pathway. In summary, our study presents a comprehensive research methodology that combines cell metabonomics and network pharmacology to enhance the discovery of new therapeutic agents for TD.

UPLC-MS/MS profiling, antioxidant and anti-inflammatory activities, and potential health benefits prediction of phenolic compounds in hazel leaf.

Hazel leaf, one of the by-products of hazelnut, which is widely used in traditional folk medicine around the world. In the present study, the profile of free, conjugated, and bound phenolic compounds from hazel leaf was detected and their antioxidant and anti-inflammatory activities were investigated. The potential health benefits of different phenolic compounds were also predicted. The results showed that the 35 phenolic substances of free, conjugated and bound forms were identified including phenolic acids, flavonoids and catechins. Most of the hazel leaf phenolics were presented in free form, followed by conjugated and bound form. All the fractions effectively inhibited the production of reactive oxygen species and malondialdehyde in TBHP-stimulated human umbilical vein endothelial cells by enhancing endogenous superoxide dismutase, and accordingly alleviated inflammatory cytokines (NO, IL-1ß, TNF-α, and IL-6) in LPS-stimulated RAW264.7 cells, showing obvious antioxidant and anti-inflammatory capacity. Moreover, combined with network pharmacology, the potential therapeutic effects and functional pathways of hazel leaf phenolics were predicted, which provided value basis for exploring their treatment on diseases and developing health products in the future.

Functional Mechanism of Ginsenoside Compound K on Tumor Growth and Metastasis.

Ginsenosides, as the most important constituents of ginseng, have been extensively investigated in cancer chemoprevention and therapeutics. Among the ginsenosides, Compound K (CK), a rare protopanaxadiol type of ginsenoside, has been most broadly used for cancer treatment due to its high anticancer bioactivity. However, the functional mechanism of CK in cancer is not well known. This review describes the structure, transformation and pharmacological activity of CK and discusses the functional mechanisms of CK and its metabolites, which regulate signaling pathways related to tumor growth and metastasis. CK inhibits tumor growth by inducing tumor apoptosis and tumor cell differentiation, regulates the tumor microenvironment by suppressing tumor angiogenesis-related proteins, and downregulates the roles of immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs). There is currently much research on the potential development of CK as a new strategy when administered alone or in combination with other compounds.

Pilose Antler Peptide-3.2KD Ameliorates Adriamycin-Induced Myocardial Injury Through TGF-ß/SMAD Signaling Pathway.

Adriamycin (ADR)-based combination chemotherapy is the standard treatment for some patients with tumors in clinical, however, long-term application can cause dose-dependent cardiotoxicity. Pilose Antler, as a traditional Chinese medicine, first appeared in the Han Dynasty and has been used to treat heart disease for nearly a thousand years. Previous data revealed pilose antler polypeptide (PAP, 3.2KD) was one of its main active components with multiple biological activities for cardiomyopathy. PAP-3.2KD exerts protective effects againt myocardial fibrosis. The present study demonstrated the protective mechanism of PAP-3.2KD against Adriamycin (ADR)-induced myocardial injury through using animal model with ADR-induced myocardial injury. PAP-3.2KD markedly improved the weight increase and decreased the HW/BW index, heart rate, and ST height in ADR-induced groups. Additionally, PAP-3.2KD reversed histopathological changes (such as disordered muscle bundles, myocardial fibrosis and diffuse myocardial cellular edema) and scores of the heart tissue, ameliorated the myocardial fibrosis and collagen volume fraction through pathological examination, significantly increased the protein level of Bcl-2, and decreased the expression levels of Bax and caspase-3 in myocardial tissue by ELISA, compared to those in ADR-induced group. Furthermore, ADR stimulation induced the increased protein levels of TGF-ß1 and SMAD2/3/4, the increased phosphorylation levels of SMAD2/3 and the reduced protein levels of SMAD7. The expression levels of protein above in ADR-induced group were remarkably reversed in PAP-3.2KD-treated groups. PAP-3.2KD ameliorated ADR-induced myocardial injury by regulating the TGF-ß/SMAD signaling pathway. Thus, these results provide a strong rationale for the protective effects of PAP against ADR-induced myocardial injury, when ADR is used to treat cancer.

Impact of TCM on Tumor-Infiltrating Myeloid Precursors in the Tumor Microenvironment.

The tumor microenvironment (TME) is composed of tumor cells, blood/lymphatic vessels, the tumor stroma, and tumor-infiltrating myeloid precursors (TIMPs) as a sophisticated pathological system to provide the survival environment for tumor cells and facilitate tumor metastasis. In TME, TIMPs, mainly including tumor-associated macrophage (TAM), tumor-associated dendritic cells (DCs), and myeloid-derived suppressor cells (MDSCs), play important roles in repressing the antitumor activity of T cell or other immune cells. Therefore, targeting those cells would be one novel efficient method to retard cancer progression. Numerous studies have shown that traditional Chinese medicine (TCM) has made extensive research in tumor immunotherapy. In the review, we demonstrate that Chinese herbal medicine (CHM) and its components induce tumor cell apoptosis, directly inhibiting tumor growth and invasion. Further, we discuss that TCM regulates TME to promote effective antitumor immune response, downregulates the numbers and function of TAMs/MDSCs, and enhances the antigen presentation ability of mature DCs. We also review the therapeutic effects of TCM herbs and their ingredients on TIMPs in TME and systemically analyze the regulatory mechanisms of TCM on those cells to have a deeper understanding of TCM in tumor immunotherapy. Those investigations on TCM may provide novel ideas for cancer treatment.

Scutellarein suppresses Aß-induced memory impairment via inhibition of the NF-κB pathway in vivo and in vitro.

The flavonoid compound scutellarin (Scu) is a traditional Chinese medicine used to treat a variety of diseases; however, the use of scutellarein (Scue), the hydrolysate of Scu, and its mechanisms of action in Alzheimer's disease (AD) have not been fully elucidated. In the present study, the effects of Scue on amyloid ß (Aß)-induced AD-like pathology were investigated. An in vitro model of inflammation and an aged rat model were used to confirm the effects of Scue. In vitro MTT assays and flow cytometry were used to assess the effects of Scue on cell viability and apoptosis, respectively. A Morris water maze was used to evaluate spatial learning and memory, and the levels of Aß deposition, superoxide dismutase, malondialdehyde, apoptosis, neuro-inflammatory factors and nuclear factor-κB (NF-κB) activation in hippocampal tissues in vivo were measured to determine the effect of Scue in AD. Scue may be protective, as it decreased the apoptosis of hippocampal cells in vitro, inhibited Aß-induced cognitive impairment, suppressed hippocampal neuro-inflammation and suppressed activation of NF-κB in vivo. Therefore, Scue may be a useful agent for the treatment of Aß-associated pathology in the central nervous system through inhibition of the protein kinase B/NF-κB signaling pathway and thus, future studies are required to investigate the efficacy of Scue in patients with AD.