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Adenosine, a nucleoside, regulates various systems, such as the cardiovascular, immune, and nervous systems, by binding to Adenosine receptors. To elucidate the role of Adenosine in Osteoporosis, this study employed an experimental approach involving the stimulation of bone formation in osteoporotic zebrafish and the reduction of reactive oxygen levels in a glucocorticoid-induced zebrafish model of Osteoporosis with oxidative stress. Adenosine significantly promoted the proliferation of MC3T3-E1 cells and increased the activity of alkaline phosphatase (ALP). It also elevated nitric oxide, glutathione, and superoxide dismutase levels while decreasing malondialdehyde. The target of Adenosine’s impact on Osteoporosis with oxidative stress was elucidated through network pharmacology, revealing the PI3K/Akt pathway, a finding corroborated through RT-qPCR analysis. Hence, we present the mechanism through which Adenosine can be utilized to prevent and manage Osteoporosis accompanied by oxidative stress, distinct from the previously identified mode of action of Adenosine in osteoporosis treatment.

Background: Obesity is gradually becoming a widespread health problem, and treatment using natural compounds has seen an increasing trend. As a by-product of hazelnut, hazel leaf is usually disposed of as waste, but it is widely used in traditional and folk medicines around the world. Aim of this study: Based on previous studies, the effects of the regulation of lipid metabolism and the mechanism of hazel leaf polyphenol extraction obesity were investigated. Methods: In this study, a high-fat diet-fed mouse model of obesity and 3T3-L1 preadipocytes were established. The ameliorative effects of the hazel leaf polyphenol extract on obesity and the regulating lipid metabolisms were explored based on network pharmacology, gut microbiota, and molecular docking. Results: Network pharmacology showed that hazel leaf polyphenols may play a role by targeting key targets, including PPARγ, and regulating the PPAR signaling pathway. They significantly improved body weight gain, the liver index, and adiposity and lipid levels; regulated the gut microbiota and short-chain fatty acid contents; down-regulated the expression of lipid synthesis proteins SREBP1c, PPARγ, and C/EBP-α; and up-regulated the expression of p-AMPK in obese mice. They inhibited the differentiation of 3T3-L1 cells, and the expression of related proteins is consistent with the results in vivo. The molecular docking results indicated that gallic acid, quercetin-3-O-beta-D-glucopyranoside, quercetin, myricetin, and luteolin-7-O-glucoside in the hazel leaf polyphenol extract had strong binding activities with PPARγ, C/EBP-α, and AMPK. Conclusions: The results demonstrate that the hazel leaf polyphenol extract can improve obesity by regulating lipid metabolism, which provides a valuable basis for developing health products made from hazel leaf polyphenols in the future.

Tenghuang Jiangu Wan (THJGW) is a commonly utilized treatment for osteoarthritis (OA), yet its pharmacodynamic material basis and molecular mechanism remain inadequately understood. This study systematically characterized the in vitro and in vivo chemical components of THJGW using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The pharmacodynamic material basis of THJGW in the treatment of OA was explored through a target network pharmacology approach and molecular docking technology. Cellular experiments were subsequently employed to validate the molecular mechanisms. Consequently, a total of 134 components from THJGW were identified in vitro, comprising 45 flavonoids, 10 iridoid glycosides, 39 phenylethanoid glycosides, 9 phenylpropanoids, 11 organic acids, 4 phenolics, and 16 other compounds. Additionally, 38 prototype absorbed components in serum were characterized for the purpose of network construction. 11 key components and 10 core targets (VEGFA, STAT3, RELA/NF-κB p65, PIK3R1, PIK3CA, MMP9, MMP1, IL-6, HDAC1, and FGF2) were determined by the target network pharmacology. Through Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, it was found that these intersection targets are associated with various signaling pathways such as pathways in cancer, lipid and atherosclerosis, and prostate cancer. Notably, the lipid and atherosclerosis pathway was closely linked to OA. The molecular docking results demonstrated strong binding affinities of the three core targets: IL-6, STAT3, and RELA/NF-κB p65. These results suggest that these targets may play a significant role for THJGW in treating OA. In vitro experiments showed that THJGW had notable protective effects on LPS-induced RAW264.7 macrophages by reducing levels of TNF-α and IL-6, and inhibiting phosphorylation expression of STAT3 and NF-κB p65 proteins related to the lipid and atherosclerosis pathway. This study provides insight into the pharmacodynamic material basis and mechanism of action for THJGW in the treatment of OA, which provide scientific evidence for the scientific application and improvement of quality standards for THJGW.

Derived from hazelnuts, hazel leaf has been utilized in traditional folk medicine for centuries in countries such as Portugal, Sweden, and Iran. In our previous investigations, we conducted a preliminary assessment of the hazel leaf polyphenol extract (referred to as ZP) and identified nine compounds, such as kaempferol and chlorogenic acid, in its composition. ZP has shown promising properties as an antioxidant and anti-inflammatory agent. Our research has revealed that ZP has protective effects against cisplatin-induced acute kidney injury (AKI). We conducted a comprehensive examination of both the pathological and ultrastructural aspects and found that ZP effectively ameliorated renal tissue lesions and mitigated mitochondrial damage. Moreover, ZP significantly suppressed malondialdehyde levels while increasing glutathione and catalase concentrations in the kidneys of AKI-induced mice. ZP decreased the number of apoptotic cells and decreased pro-apoptotic protein expression in the kidneys of mice and human renal tubular epithelial cells (HK-2). Furthermore, treatment with ZP increased the levels of proteins marking anti-ferroptosis, such as GPX4, FTH1, and FSP1, in experiments both in vivo and in vitro. We elucidated the underlying mechanisms of ZP’s actions, revealing its inhibitory effect on Yap phosphorylation and its regulation of Lats expression, which exert a protective influence on the kidneys. Furthermore, we found that inhibiting the Hippo pathway compromised ZP’s nephroprotective effects in both in vitro and in vivo studies. In summary, this research shows that ZP exhibits renoprotective properties, effectively reducing oxidative damage, apoptosis, and ferroptosis in the kidneys by targeting the Hippo pathway.

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.

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-1β, 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.

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.

Abstract Background Non-alcoholic fatty liver is one of the most common comorbidities of diabetes. It can cause disturbance of glucose and lipid metabolism in the body, gradually develop into liver fibrosis, and even cause liver cirrhosis. Mangiferin has a variety of pharmacological activities, especially for the improvement of glycolipid metabolism and liver injury. However, its poor oral absorption and low bioavailability limit its further clinical development and application. The modification of mangiferin derivatives is the current research hotspot to solve this problem. Methods The plasma pharmacokinetic of mangiferin calcium salt (MCS) and mangiferin were monitored by HPLC. The urine metabolomics of MCS were conducted by UPLC-Q-TOF-MS. Results The pharmacokinetic parameters of MCS have been varied, and the oral absorption effect of MCS was better than mangiferin. Also MCS had a good therapeutic effect on type 2 diabetes and NAFLD rats by regulating glucose and lipid metabolism. Sixteen potential biomarkers had been identified based on metabolomics which were related to the corresponding pathways including Pantothenate and CoA biosynthesis, fatty acid biosynthesis, citric acid cycle, arginine biosynthesis, tryptophan metabolism, etc. Conclusions The present study validated the favorable pharmacokinetic profiles of MCS and the biochemical mechanisms of MCS in treating type 2 diabetes and NAFLD.

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-β1 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-β/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.

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.

The aim of this study was to explore the antipyretic role and mechanism of Saposhnikoviae Radix (SR). To achieve the objectives TCM-ingredient-target network and PPI network were constructed by TCMSP, TTD, DisGenet, OMIM databases and Cytoscape 3.7.2 software, and topology analysis was performed on the PPI network. KEGG signaling pathways were analyzed using DAVID database, and molecular docking verification was performed on the core targets after topology analysis. Subsequently, 24 rats were randomly divided into control group, model group, wild high-dose group and wild low-dose group, 6 rats in each group. Results of in vivo experiments showed that high-dose group (P<0.01) and low-dose group (P<0.01) significantly decreased body temperature in rats; high-dose group significantly decreased TNF-α, IL-1β and IL-6 levels (P<0.01), and low-dose group significantly decreased TNF-α and IL-6 levels (P<0.01); high-dose group significantly decreased BAX, caspase3, COX2 and TNF-α protein expression levels in hypothalamus (P<0.01 or P<0.05), and low-dose group significantly increased BCL2 protein expression levels (P<0.01). It was found that SR can significantly inhibit lipopolysaccharide-induced fever in rats with elevated body temperature, reduce serum TNF-α, IL-1β and IL-6 levels, reduce the hypothalamus COX2, caspase3 and Bax protein expression levels and improve BCL2 protein expression levels, play an antipyretic effect. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) is widely used clinically for the treatment of various malignant tumors, but it is accompanied by severe body toxic reactions, especially cardiac toxicity. This article explores the effects of pilose antler peptide (PAP) on DOX-induced myocardial injury and related mechanisms through in vitro experiments. Different concentrations of DOX were used to treat H9c2 cells for 6, 12, 24, and 48 h, respectively, to determine the IC50. Different concentrations of PAP were treated to H9c2 cells for 24, 48, and 72 h to determine the effect of PAP on H9c2 cells. The experiment was divided into control group, DOX group, PAP group and DOX+PAP group. Lactate dehydrogenase (LDH) leakage and creatine kinase MB (CK-MB) level were used to detect cell viability, flow cytometry was used to detect cell cycle and apoptosis, and immunofluorescence was used to detect Bax and Bcl-2 expression. The protein levels of TGF-β / Smad / ERK signaling pathway were detected by Western blot. We found that PAP significantly increased cell viability after DOX-induced injury, reduced LDH, CK-MB levels, up-regulated Bcl-2 expression and down-regulated Bax expression levels. In addition, PAP can delay cell G2/M phase arrest, reduce apoptosis, significantly reduce TGF-β1 protein levels and Smad2, Smad3, ERK phosphorylation levels. These results suggest that PAP can protect DOX-induced H9c2 damage by inhibiting the TGF-β / Smad / ERK signaling pathway. [ABSTRACT FROM AUTHOR]

[Objective] To research the protective effects of antiradiation gel of RADIX SCUTELLARIAE and RADIX ET RHIZOMA GINSENG (ShenQin Antiradiation Gel) on skin and immune system injury induced by UVB irradiation. [Methods] After ShenQin Antiradiation Gel administration and UVB irradiation, changes of visceral index, skin histomorphology, and lymphocyte and blood plalelel count were observed, transformation rate of splenic lymphocyte was detected by MIT method; and SOD activity in skin tissue homogenate was detected by enzymes and biochemical method. [Results] ShenQin Antiradiation Gel could enhance the thymus index and lymphocyte count, increase the transformation rale of splenic lymphocyte and the SOD activity in skin tissue of mice. [Conclusions] ShenQin Antiradiation Gel could resist UVB irradiation, and significantly protected the iuunune system and skin tissue of mice. [ABSTRACT FROM AUTHOR]