Effects of Total Saponins from Dioscorea Nipponica Makino on Monosodium Urate-Induced M1-Polarized Macrophages through Arachidonic Acid Signaling Pathway: An in vitro Study / 中国结合医学杂志

OBJECTIVE@#To investigate and reveal the underlying mechanism of the effect of total saponins from Dioscoreae nipponica Makino (TSDN) on the arachidonic acid pathway in monosodium urate (MSU) crystal-induced M1-polarized macrophages.@*METHODS@#M1 polarization of RAW264.7 cells were induced by 1 µ g/mL lipopolysaccharide (LPS). The methylthiazolyldiphenyl-tetrazolium bromide method was then used to screen the concentration of TSDN. MSU (500 µ g/mL) was used to induce the gouty arthritis model. Afterwards, 10 µ g/L TSDN and 8 µ mol/L celecoxib, which was used as a positive control, were added to the above LPS and MSU-induced cells for 24 h. The mRNA and protein expressions of cyclooxygenase (COX) 2, 5-lipoxygenase (5-LOX), microsomal prostaglandin E synthase derived eicosanoids (mPGES)-1, leukotriene B (LTB)4, cytochrome P450 (CYP) 4A, and prostaglandin E2 (PGE2) were tested by real-time polymerase chain reaction and Western blotting, respectively. The enzyme-linked immunosorbent assay was used to test the contents of M1 markers, including inducible nitric oxid synthase (NOS) 2, CD80, and CD86.@*RESULTS@#TSDN inhibited the proliferation of M1 macrophages and decreased both the mRNA and protein expressions of COX2, 5-LOX, CYP4A, LTB4, and PGE2 (P<0.01) while increased the mRNA and protein expression of mPGES-1 (P<0.05 or P<0.01). TSDN could also significantly decrease the contents of NOS2, CD80, and CD86 (P<0.01).@*CONCLUSION@#TSDN has an anti-inflammation effect on gouty arthritis in an in vitro model by regulating arachidonic acid signaling pathway.

Mechanism of Action of Traditional Chinese Medicine Against Prostatic Carcinoma： A Review / 中国实验方剂学杂志

Prostatic carcinoma （PCa） is one of the most common male malignancies， accounting for 10% of all male cancers， and has become a global health problem. At present， it is mainly tackled with radical prostatectomy and endocrine therapy. However， most patients will develop drug resistance， allowing the progression of PCa into castration-resistant prostate cancer （CRPC）. Guided by the principles of holism and treatment based on syndrome differentiation， traditional Chinese medicine （TCM） alleviates cancer pain， regulates immune balance， and improves the quality of life of patients via multiple targets， multiple pathways， and multiple mechanisms without inducing obvious side effects， thus better exerting the preventive and therapeutic effects against PCa. This paper retrieved relevant articles concerning PCa intervention with TCM published in recent five years from PubMed and China National Knowledge Infrastructure （CNKI）， and summarized the molecular mechanism of PCa， its etiology and pathogenesis in TCM， and TCM interventions. The findings showed that the active ingredients of Chinese medicinals， single Chinese medicinals and Chinese medicinal compounds inhibited PCa by interfering with not only the classical pathways of PCa such as androgen receptor（AR）， Wnt/β-catenin， PI3K/Akt/mTOR， and NF-κB but also other pathways like ERS/UPR， RIPK， CIP2A/PP2A/ERK， EGFR， etc. The intervention of active ingredients from Chinese medicinals in PCa has been explored extensively， but there are fewer studies on single Chinese medicinals and Chinese medicinal compounds that can better reflect the unique advantages of TCM. Further research is needed to provide an important theoretical and experimental basis for the development of novel anti-PCa Chinese medicinal products and their clinical application.

Mechanism of Total Saponins from Dioscoreae Nipponicae Rhizoma to Treat Gouty Arthritis by Regulating M1/M2 Polarization of Macrophages / 中国实验方剂学杂志

Objective:To illustrate the effect of M1/M2 polarization of macrophages on gouty arthritis models induced with monosodium urate and reveal the molecular mechanism of total saponins from Dioscoreae Nipponicae Rhizoma to treat gouty arthritis. Method:A total of 72 male SD rats were randomly divided into four groups： normal group， model group， total saponin group （160 mg·kg^-1）， celecoxib group （43.3 mg·kg^-1）， with 18 rats in each group. Gouty arthritis models were induced by injecting monosodium urate into ankle joints bilaterally. Histopathology changes of ankle joints were observed by hematoxylin-eosin（HE） staining. Immunohistochemistry method was used to detect the protein expression change of CD68， interleukin-4（IL-4）， inducible nitric oxide synthase （iNOS） and transforming growth factor-<italic>β</italic>₁（TGF-<italic>β</italic>₁）. Result:HE staining results showed that the inflammation of the model group was most obvious on the third day after modeling， and the disease was in the acute stage. On day 5， the inflammation was alleviated， and on day 8， the inflammation was still present but close to normal. The total saponin group and celecoxib group could improve the pathological changes of synovial tissue， and the effect of total saponin group was more obvious. Immunohistochemical results were as follows. Compared with the normal group. The expression of CD68 and iNOS in the model group increased on the 3rd，5th and 8th day of administration （<italic>P</italic><0.01）. Compared with the model group， the total saponins group could reduce the expression of CD68 and iNOS （<italic>P</italic><0.05，<italic>P</italic><0.01）on the 3rd day of administration， and significantly reduced them expression on the 5th and 8th days （<italic>P</italic><0.01）. Compared with the normal group， IL-4 and TGF-<italic>β</italic>₁ expression were increased in the model group when the drug was given for three days（<italic>P</italic><0.01）. Total saponin group could enhance IL-4 expression（<italic>P</italic><0.05）and decreased the TGF-<italic>β</italic>₁ expression（<italic>P</italic><0.01）. Compared with normal group， the expression of IL-4 in the model group decreased on the 5th and 8th day of administration （<italic>P</italic><0.01）， and the expression of TGF-<italic>β</italic>₁ in the model group decreased on the 5th day of administration（<italic>P</italic><0.01）. Compared with the model group， the total saponins group could increase the expression of IL-4 and TGF-<italic>β</italic>₁ at 5 d and 8 d after administration （<italic>P</italic><0.01）. Conclusion:Total saponins from Dioscoreae Nipponicae Rhizoma has the potential effect to treat gouty arthritis by regulating M1/M2 polarization.

Formation of neutrophil extracellular traps and their effects on autoimmune diseases / 中国中药杂志

Neutrophil extracellular traps(NETs) are networks of extracellular fibers primarily composed of DNA, histones, granular proteins, and cytoplasmic proteins and released to the outside of cells by neutrophils under the stimulation of bacteria, fungi, viruses, parasites, etc. NETs are generated in two forms, suicidal NETs and vital NETs, according to different stimuli. NETs have both anti-inflammatory and pro-inflammatory effects. On the one hand, they can play the anti-microbial role to resist inflammation by capturing, fixing, and killing invading pathogens, which is a special way for neutrophils to exert host defenses. On the other hand, in case of excessive formation or insufficient elimination, they can cause tissue damage directly, and also promote the release of inflammatory factors by recruiting other pro-inflammatory cells or proteins to further expand the inflammatory response, which is related to the pathologies of many diseases. In autoimmune diseases, NETs as important sources of autoantigens, can act as danger-associated molecular patterns( DAMPs) and activate the nucleotide-binding oligomerization domain leucine-rich repeats containing pyrin domain 3(NLRP3) inflammasome and complement system, thereby breaking self-tolerance and accelerating autoimmune inflammation. In addition, NETs can also activate other immune cells(such as B cells, antigen-presenting cells, and T cells) and regulate the acquired immune response. The present study reviewed the correlation of NETs with diseases such as systemic lupus erythematosus(SLE), rheumatoid arthritis(RA), and gouty arthritis(GA) to reveal the effect of dynamic balance between formation and clearance of NETs in autoimmune diseases and provide a theoretical basis for the investigation of underlying mechanisms and targeted therapies of traditional Chinese medicine.

Effect of Autophagy in Treatment of Tumors with Traditional Chinese Medicine / 中国实验方剂学杂志

The cure of tumors is a difficulty in the world, and both the quality of life and the survival rate of patients remain low. Therefore, it is very meaningful to find a drug target to inhibit the occurrence and development of tumors. In recent years, autophagy or self-phagocytosis has become a hotspot of medical research. It can remove damaged or excess organelles from cells, be survived from external environmental pressures, and affect the survival, metabolism, differentiation, aging and death of tumor cells. The biological behavioral process plays important roles in remodeling and maintaining the dynamic balance of cell survival, especially in close relations to tumor development. Autophagy is also a double-edged sword in effect on a single tumor cell and the entire tumor. When the autophagy of the tumor cells is abnormal, or the cells are unable to remove the damaged substances in time under the conditions of hypoxia and nutrient deficiency, autophagy is beneficial to the proliferation and survival of the tumor cells. Contrarily, moderate autophagy acts as an inhibitor of tumors and has an anti-tumor effect. Traditional Chinese medicine (TCM) has a long history of controlling tumors, with the advantages of low toxicity and multiple targets. Through overall and local therapies, it has a comprehensive therapeutic effect in cancer. With the deepening of tumor autophagy research, in addition to western medicine researches on tumor autophagy, there are also domestic and foreign researches on the autophagy in single herb and TCM compounds. The latest insights into the molecular mechanism of autophagy have led to the discovery of potential drug targets. At the same time, TCM researches have made some progress in tumor autophagy. The authors review the research progress of autophagy in TCM and the research progress of effect of TCM in regulating tumor autophagy, in the hopes to provide useful reference for effect of TCM in the treatment of autophagy.

Biopharmaceutics classification system of Chinese materia medica of berberine in Gegen Qinlian decoction / 中国中药杂志

One of the top-level researches of biopharmaceutics classification system of Chinese materia medica (CMMBCS) is the study on single component in compound Chinese medicine. The medicines shall be classified according to its solubility and intestinal permeability, as well as the ascending degree in multicomponent environment. Based on above, we chose berberine as the main object to explore the change rules of its solubility and intestinal permeability in Gegen Qinlian decoction. Shaking flask-HPLC was used to detect the solubility changes of berberine in compounds. The qualitative investigation of berberine in intestinal absorption was measured by everted gut sac, and the quantitative research of berberine in intestinal absorption was measured by single-pass intestinal perfusion experiment, while the qualitative and quantitative research of berberine absorption into blood was measured by in intestinal perfusion with venous sampling experiment.

Overall intestinal permeability of multiple components in lotus leaves / 中国中药杂志

In the study of biopharmaceutics classification system of Chinese materia medica (CMMBCS), the interactions of multiple components in the absorption should be taken into consideration in simultaneous multi-component determination. To investigate the absorption of multiple components, the in vitro everted gut sac model was used in this study, wtih lotus leaves as the research object. Aquantitative analysis was also carried out for the known components in this study. Totally 19 components in lotus extracts were absorbed by the intestinal tract, the Papp levels of the known components were nuciferine (1×10⁻⁵-1×10⁻⁶ cm•s⁻¹), rutin (1×10⁻⁶-1×10⁻⁷ cm•s⁻¹), hyperoside (1×10⁻⁶ cm•s⁻¹), isoquercitrin (1×10⁻⁶-1×10⁻⁷ cm•s⁻¹) and astragalin (1×10⁻⁶-1×10⁻⁷ cm•s⁻¹), respectively. These components showed a low permeability under a multi-component environment. This study was carried out to lay a foundation for further relevant target studies for different categories of components.