[Research progress on Piperis Longi Fructus and predictive analysis of its quality markers].

Piperis Longi Fructus, made from the mature and immature fruit spikes of Piper longum, is a commonly used Mongolian medicine. In recent years, researchers have gradually deepened the research on ethnic medicines and found that Piperis Longi Fructus has significant effects in adjusting blood lipids and anti-cancer. Its new chemical components and pharmacological activities are also constantly updated. Subsequently, the development and application of Piperis Longi Fructus have attracted extensive attention. Thus, it is quite urgent to establish and improve a quality evaluation system for the medicine. On the basis of summarizing the chemical components and pharmacological effects of Piperis Longi Fructus and understanding the new concept of quality marker(Q-marker), the components which can be used as its Q-markers were analyzed from the aspects of the genetic relationship, traditional medicinal effects and properties, rules of compounding and compatibility, absorbed components and testability. The research can provide reference for the establishment of a quality evaluation system for Piperis Longi Fructus.

Wuwei Qingzhuo San Ameliorates Hyperlipidemia in Mice Fed With HFD by Regulating Metabolomics and Intestinal Flora Composition.

Hyperlipidemia is one of the most common metabolic disorders that threaten people's health. Wuwei Qingzhuo San (WQS) is a traditional Mongolian medicine prescription, which is widely used in Mongolia for the treatment of hyperlipidemia. Our previous studies found that it has hypolipidemic and hepatoprotective effects on hyperlipidemic hamsters. However, the underlying lipid-lowering mechanisms of WQS and its relationship with intestinal flora are not yet clear. In this study, 16 S rRNA gene sequencing and metabolomics were performed to investigate the action mechanism of WQS on hyperlipidemic mice induced by a high-fat diet (HFD). As a result, metabolic pathway enrichment analysis revealed that the intervention of WQS had obviously modulated the metabolism of α-linolenic acid and linoleic acid and the biosynthesis of bile acids. 16 S rRNA sequencing showed that WQS had altered the composition of the intestinal microbiota in hyperlipidemic mice fed with HFD and, especially, adjusted the relative abundance ratio of Firmicutes/Bacteroides. These findings provide new evidence that WQS can improve HFD-induced hyperlipidemia by regulating metabolic disorders and intestinal flora imbalance.

A unique understanding of traditional medicine of pomegranate, Punica granatum L. and its current research status.

ETHNOPHARMACOLOGICAL RELEVANCE: Pomegranate, Punica granatum L., has been used in traditional medicine in China and several regions of the world including Ayurveda, Islamic, and Persian for the treatment of atherosclerosis, diabetes, hypertension, hyperlipidemia, and several types of cancer, as well as for peptic ulcer and oral diseases for hundreds of years. Presently, pomegranate is treated as both a "medicine food homology" herbal medicine and a healthy food supplemental product. AIM OF THE STUDY: The aim of this work is to develop an overview of pomegranate in the context of the status of its traditional medicine theories, the spread along the Silk Road, ethnopharmacological uses, chemical compositions, pharmacological activities, toxicology, and the involved pathways. MATERIALS AND METHODS: Information on P. granatum L. was acquired from published materials, including monographs on medicinal plants, ancient and modern recorded classical texts; and pharmacopoeias and electronic databases (PubMed, Science Direct, Web of Science, Google Scholar, CNKI, and Wanfang Data). RESULTS: Pomegranate has been used in many traditional medical systems throughout history. It is widely cultivated in Central Asia and spread throughout China along the Silk Road. Many phytochemicals, such as tannins, organic acids, flavonoids, alkaloids, and volatile oils have been identified from different parts of pomegranate, these compounds have a wide range of activities, including antioxidant, antimicrobial, and anti-oncogenic properties, as well as conferring resistance to cerebrovascular disease. Furthermore, A summary of the four promising pharmacological pathways is provided. CONCLUSIONS: The traditional uses, chemical compositions, pharmacological activities, and signaling pathways of pomegranate are summarized comprehensively in the review. It can be treated as a guidance for the future clinical and basic research. The information provided in this review will be very useful for further studies to develop novel therapeutic directions for application of pomegranate.

Research progress on effective components of Chinese materia medica in regulating autophagy / 中国中药杂志

Autophagy is a highly conservative and multi-component activated energy metabolism and self-renewal mechanism, which plays a crucial regulatory role in maintaining the normal physiological state of cells and is involved in various pathological processes. In recent years, the mechanism study has made great progress in regulating autophagy with effective components of Chinese materia medica(CMM),which are reported to prevent and treat cancers, neurodegenerative diseases, cardiovascular diseases and metabolic and immune-related diseases. This review outlines the molecular regulation mechanisms of cell autophagy with CMM components in controlling the above-mentioned diseases. There are many relevant reports on the regulatory mechanisms of autophagy in tumor and cardiovascular cells with CMM monomers. The main chemical structural types are alkaloids, saponins, polyphenols, flavonoids and terpenes. And m-TOR pathway is the main mechanism relating to the regulatory mechanisms of autophagy with CMM. Therefore, the regulatory mec-hanisms of cell autophagy become a new research targeting strategy of therapies with CMM. This review provides evidences for the effectiveness and scientificity of CMM in regulating autophagy, in the expectation of providing references for the in-depth studies of CMM in the field of autophagy and the development of natural autophagy regulators.

Saikosaponin A Inhibits Breast Cancer by Regulating Th1/Th2 Balance.

Saikosaponin A (SSa) is isolated from the dried root of Radix Bupleuri, an herb widely used in traditional Chinese medicine, exerting antitumor activities. The T helper cell type 1(Th1)/Th2 balance is associated with antitumor immunity in breast cancer. The present study aimed to investigate the effects of SSa on Th1/Th2 balance in breast cancer and to explore the underlying mechanisms. Breast cancer in rats was induced by intragastrical administration of 7,12-dimethyl-benz[a] anthracene once (100 mg/kg). At d91, the rats suffering from tumors were randomly divided into three groups and treated with vehicle solution (control group), tamoxifen (TAM group), and SSa (SSa group) daily for 56 days, respectively. The tumor volume reduction ratio and tumor cell proliferation were detected to assess the antitumor effect of SSa. The positive staining numbers of CD8+ and CD4+ T cells infiltrated in breast tumors were measured by immunohistochemistry to evaluate the antitumor immunity of SSa. Cytokine levels in serum secreted by Th1 cells [interferon gamma (IFN-γ), interleukin (IL)-12] and Th2 cells (IL-4, IL-10) were detected to evaluate Th1/Th2 balance. The related molecules of IL-12/signal transducers and activators of transcription 4 (STAT4) pathway were detected by immunohistochemistry staining, RT-PCR, and Western blot to explore the mechanisms of SSa. The results showed that, compared with the control group, SSa significantly inhibited tumor growth and tumor cell proliferation. SSa enhanced antitumor immunity, which was demonstrated as increased CD8+ T cells and CD4+ T cells infiltrated in tumors. SSa shifted Th1/Th2 balance toward Th1, which was confirmed as increased serum IFN-γ and IL-12 levels, while decreased serum IL-4 and IL-10 levels. SSa increased IL-12, IL-12 receptor, and phosphorylated STAT4 expressions to promote Th1 differentiation. In conclusion, the present work suggested that SSa could inhibit breast cancer growth by shifting Th1/Th2 balance toward Th1. The underlying mechanism may involve activation of the IL-12/STAT4 pathway that induced Th1 differentiation.

Ling-Yang-Gou-Teng-decoction prevents vascular dementia through inhibiting oxidative stress induced neurovascular coupling dysfunction.

ETHNOPHARMACOLOGICAL RELEVANCE: Vascular dementia (VaD) is the common cognitive disorder derived mainly from lacunar stroke (LS). The oxidative stress induced neurovascular coupling (NVC) dysfunction involves in the pathogenesis of VaD. Currently, there is no specific drug for VaD. Ling-Yang-Gou-Teng -Decoction (LG), a well-known traditional Chinese formula, has been used for preventing VaD in clinic. AIM OF THE STUDY: In this study, we aimed to investigate the underlying mechanism of LG on VaD in rats. MATERIALS AND METHOD: VaD was replicated with autologous micro-thrombi against the background of hypercholesterolemia induced with high fatty diet. PTX (68.90 mg/kg/day), LG with three dosages (2.58, 8.14, 25.80 g/kg/day) was orally administrated to VaD rats, respectively. The NVC sensitivity was defined as the ratio of the microcirculative cerebral blood velocity (CBV) to the electroencephalograph (EEG) before and after penicillin stimulation. Behavioral performance, pathological changes of brain and oxidation related molecules were detected to assess the effects of LG on VaD. RESULTS: LG exhibited beneficial effects on the VaD, which was demonstrated as improved exploratory, learning and memory abilities, relieved vascular or neural pathological changes in cerebral cortex or hippocampus. LG maintained NVC sensitivity, which was confirmed as significantly increased ΔCBV and the elevated ratio of ΔCBV/ΔqEEG. The underlying mechanisms of LG was associated with antioxidant effects, which was confirmed as significantly decreased nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) expression, and increased superoxide dismutase 3 (SOD3) expression. LG also reduced iNOS, increased nNOS and eNOS expression to restore NO bioavailability. CONCLUSIONS: The results suggested that LG prevented VaD may associate with inhibiting oxidative stress, protecting NO bioavailability, and then maintaining NVC sensitivity.

Anti-angiogenic effects of Qingdu granule on breast cancer through inhibiting NFAT signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Qingdu granule (QDG), a traditional Chinese herbal prescription, had anti-tumor effect on breast cancer. However the underlying mechanism of QDG was unclear. THE AIM OF THIS STUDY: The present study aimed to investigate whether QDG could inhibit angiogenesis of breast cancer via acting on nuclear factor of activated T-cells (NFAT) signaling pathway. This was implicated in human umbilical vein endothelial cells (HUVECs) in vitro and breast cancer xenograft model in vivo. MATERIALS AND METHODS: The VEGF165 (15.58 ng/mL) induced human umbilical vein endothelial cells (HUVECs) were treated with serum samples containing tamoxifen (TAM), tacrolimus (FK506), or QDG with three dosages. The migration and canalization capacities of HUVECs were evaluated by transwell migration and tube formation assay. In 72 h-cultured HUVECs, The gene expression, protein amount, and nuclear translocation of NFATc3 were measured. The anti-tumor and anti-angiogenic effects of QDG in vivo were investigated in breast cancer xenograft model. The serum VEGF levels, microvessel density, and protein expressions (immunohistochemistry and western blot) of VEGF, VEGFR2 and NFATc3 were detected. RESULTS: The results showed that, QDG significantly inhibited HUVEC migration and tube formation. It downregulated NFATc3 gene expression, decreased NFATc3 protein amount, and reduced the ratio of NFATc3 nuclear translocation in HUVECs. In breast cancer xenograft model, QDG treatment significantly suppressed tumor growth, inhibited VEGF release, and decreased microvessel density. QDG reduced protein expressions of VEGF, VEGFR2 and NFATc3. CONCLUSION: The results suggested that QDG showed anti-angiogenic effects of breast cancer both in vitro and in vivo. The mechanism might be partially associated with inhibiting NFAT signaling pathway.

A model for anticancer surveillance was pharmacologically developed to evaluate vitality principle in breast cancer rats.

OBJECTIVE: To evaluate vitality principle in breast cancer rats by pharmacologically developing a model for anticancer surveillance. METHODS: The breast cancer in rats was replicated with 7,12-Dimethylbenz[a]anthracene (DMBA, i.g., 100 mg/kg) at d001. The anticancer surveillance was defined as the intervals between the primary sensitization and the first challenge stirred with complete Freund's adjuvant (CFA), the various intervals (k = 0.80) were dominated from d025 (600.00 h) to d095 (2288.82 h). The optimal surveillant status was confirmed with the median effective interval (EI50) from tumor volume regressive curve, for developing the pharmacodynamic model. The tumor and tumor infiltrating lymphocyte histopathology was used to confirm the immune surveillance being affected with CFA in breast cancer tumorigenesis. The availability of this model was confirmed with Shugan Liangxue prescription (SLP), from the vitality principle, and assured further from interleukin-12 levels. RESULTS: The regressive curve was set up between the intervals and tumor volumes, the EI50 in SLP-treated rats (1475.00 h, YSLP = 0.1026 + 0.8780/[1 + 10(27.1425-8.565x)]) was postponed, which was 1.87 multiple of the EI50 in CFA rats (791.40 h, y = -0.0525 + 0.9452/[1 + 10(30.4870-10.52x)], so did prepone the curve between the intervals and the immunological biomarker, serum interleukin-12 levels, the EI50 in SLP-treated rats (744.90 h, YSLP = -0.0145 + 0.7455/[1 + 10(52.09636-18.13x)]) be 0.78 multiple of the EI50 in CFA rats (960.10 h, YCFA = 0.2460 + 0.7270/[1 + 10 (-67.1546 + 22.52x)]), this immunological action being mediated the anticancer prognosis. Tumor histology was confirmed the more tumor infiltrating lymphocytes activated in SLP rats with CFA stirred immunity than rats only received CFA. CONCLUSION: The model for anticancer surveillance was pharmacologically established as the optimal interval (791.40 h) between the primary sensitization and the first challenge stirred with complete Freund's adjuvant. This available model was confirmed with SLP, from the vitality principle, for evaluating immunological effects against breast cancer.