Wenshenyang recipe treats infertility through hormonal regulation and inflammatory responses revealed by transcriptome analysis and network pharmacology.

The Wenshenyang recipe (WSYR) has the effect of treating infertility, but the mechanisms underlying this activity have not been fully elucidated. In this study, network pharmacology and RNA sequencing were combined, with database-based "dry" experiments and transcriptome analysis-based "wet" experiments used conjointly to analyse the mechanism of WSYR in the treatment of infertility. In the dry analysis, 43 active compounds in WSYR and 44 therapeutic targets were obtained through a database search, 15 infertility pathways were significantly enriched, and key targets, such as ESR1, TP53, AKT1, IL-6, and IL-10 were identified. Then the wet experiments were performed to detect the expression changes of the 412 genes from 15 infertility pathways identified by dry analysis. HK-2 cells were treated with the three herbs of WSYR and subjected to targeted RNA sequencing. Based on the results, 92 of the 412 genes in 15 infertility pathways were identified as DEGs. Additionally, key targets, such as ESR2, STAT1, STAT3, and IL6, were also identified in the wet experiments. RT-qPCR experiments further verified that WSYR played an anti-inflammatory role by upregulating IL-4 and IL-10 and Epimedium brevicornu Maxim (Yinyanghuo) showed broader effect than Drynaria fortunei (Kunze) J. Sm (Gusuibu) and Cistanche deserticola Y.C.Ma (Roucongrong). By screening compounds of WSYR using molecular docking models of ESR1 and ESR2, it was further found that xanthogalenol in Gusuibu, arachidonate in Roucongrong, and anhydroicaritin in Yinyanghuo had good affinity for estrogen receptors. These findings provide evidence for an estrogen-regulating role of the three herbs in WSYR.

Dendrocalamus latiflorus and its component rutin exhibit glucose-lowering activities by inhibiting hepatic glucose production via AKT activation.

The potential medicinal value of Ma bamboo (Dendrocalamus latiflorus), one of the most popular and economically important bamboo species in China, has been underestimated. In the present study, we found that D. latiflorus leaf extract (DLE) reduced fasting blood glucose levels, body weight, and low-density lipoprotein cholesterol with low liver toxicity in db/db mice. In addition, gene expression profiling was performed and pathway enrichment analysis showed that DLE affected metabolic pathways. Importantly, DLE activated the AKT signaling pathway and reduced glucose production by downregulating glucose-6-phosphatase (G6PC) and phosphoenolpyruvate carboxykinase 1 (PCK1) expression. Moreover, network pharmacology analysis identified rutin as an active component in DLE through targeting insulin growth factor 1 receptor (IGF1R), an upstream signaling transducer of AKT. Due to its hypoglycemic effects and low toxicity, DLE may be considered an adjuvant treatment option for type 2 diabetes patients.

Biological Response Profiling Reveals the Functional Differences of Main Alkaloids in Rhizoma Coptidis.

Rhizoma Coptidis (RC) is a widely used traditional Chinese medicine. Although modern research has found that some alkaloids from RC are the pharmacologically active constituents, the differences in their biological effects are not completely clear. This study analyzed the differences in the typical alkaloids in RC at a systematic level and provided comprehensive information on the pharmaceutical mechanisms of the different alkaloids. The ethanol RC extract (RCE) was characterized using HPLC assay. HepG2, 3T3-L1, and RAW264.7 cells were used to detect the cytotoxicity of alkaloids. Transcriptome analyses were performed to elucidate the cellular pathways affected by RCE and alkaloids. HPLC analysis revealed that the typical alkaloids of RCE were berberine, coptisine, and palmatine. Coptisine and berberine displayed a stronger inhibitory effect on cell proliferation than palmatine. The overlapping ratios of differentially expressed genes between RCE and berberine, coptisine, and palmatine were 70.8%, 52.6%, and 42.1%, respectively. Pathway clustering analysis indicated that berberine and coptisine possessed a certain similarity to RCE, and both compounds affected the cell cycle pathway; moreover, some pathways were uniquely enriched by berberine or coptisine. Berberine and coptisine had different regulatory effects on genes involved in lipid metabolism. These results provide comprehensive information on the pharmaceutical mechanisms of the different RC alkaloids and insights into their better combinatory use for the treatment of diseases.

White tea and its active polyphenols lower cholesterol through reduction of very-low-density lipoprotein production and induction of LDLR expression.

Emerging in vivo and vitro data suggest that white tea extract (WTE) is capable of favourably modulating metabolic syndrome, especially by ameliorating abnormal lipid metabolism. Microarray-based gene expression profiling was performed in HepG2 cells to analyze the effects of WTE from a systematic perspective. Gene Ontology and pathway analysis revealed that WTE significantly affected pathways related to lipid metabolism. WTE significantly downregulated apolipoprotein B (APOB) and microsomal triglyceride transfer protein (MTTP) expression and thereby reduced the production of very-low-density lipoprotein. In the meanwhile, WTE stimulated low-density lipoprotein-cholesterol (LDL-c) uptake through targeting low-density lipoprotein receptor (LDLR), as a consequence of the activation of sterol regulatory element-binding protein 2 (SREBP2) and peroxisome proliferator-activated receptor δ (PPARδ). Furthermore, WTE significantly downregulated triglycerides synthetic genes and reduced intracellular triglycerides accumulation. Besides, we demonstrated that the tea catechins epigallocatechin-3-gallate (EGCG) and epicatechin-3-gallate (ECG) are abundant in WTE and contribute to the regulation of cholesterol metabolism related genes, including LDLR, MTTP and APOB. Our findings suggest white tea plays important roles in ameliorating abnormal lipid metabolism in vitro.

Identification of Carpesium cernuum extract as a tumor migration inhibitor based on its biological response profiling in breast cancer cells.

BACKGROUND: Breast cancer is one of the most lethal cancers in women when it reaches the metastatic stage. The plant Carpesium cernuum has been used as an anti-inflammatory, analgesic, and detoxifying agent in Chinese folk medicine. However, the inhibitory activity and molecular mechanisms of Carpesium cernuum in breast cancer cells have not been investigated. METHODS: RNA sequencing experiments were performed to elucidate the cellular pathways affected by Carpesium cernuum extract (CCE). Cell viability and EdU incorporation assays were conducted to determine the effect of CCE on cell proliferation. The inhibitory effects of CCE on the expression levels of target genes were confirmed by qRT-PCR and Western blot. Cell migration and invasion were analysed with transwell chamber assays. RESULTS: Proliferation assays indicated that CCE inhibited cell proliferation in multiple cancer cell lines and the IC50 value of CCE was the smallest in MDA-MB-231 cells. Transcriptome analysis showed that CCE significantly affected the cell adhesion pathway. Further experiments revealed that CCE suppressed cell migration and invasion. The inhibitory effect on migration was likely mediated by targeting TIMP1, MMP9, CD44 and COL4A2. The main active components of CCE were isolated, and CCE-derived sesquiterpene lactone substances could reproduce the inhibitory effect of CCE on cell migration and invasion. CONCLUSIONS: Overall, both molecular and phenotypic assays showed that CCE has potential in the treatment of breast cancer, especially for the treatment of breast cancer metastasis. CCE-derived sesquiterpene lactone substances are the foundation for the tumor inhibitory effect of CCE.

Caffeine-free hawk tea lowers cholesterol by reducing free cholesterol uptake and the production of very-low-density lipoprotein.

Medicinal plants show important therapeutic value in chronic disease treatment. However, due to their diverse ingredients and complex biological effects, the molecular mechanisms of medicinal plants are yet to be explored. By means of several high-throughput platforms, here we show hawk tea extract (HTE) inhibits Niemann-Pick C1-like 1 (NPC1L1)-mediated free cholesterol uptake, thereby inducing the transcription of low-density lipoprotein receptor (LDLR) downstream of the sterol response element binding protein 2 (SREBP2) pathway. Meanwhile, HTE suppresses hepatocyte nuclear factor 4α (HNF4α)-mediated transcription of microsomal triglyceride transfer protein (MTP) and apolipoprotein B (APOB), thereby decreasing the production of very-low-density lipoprotein. The catechin EGCG ((-)-epigallocatechin gallate) and the flavonoids kaempferol and quercetin are identified as the bioactive components responsible for the effects on the NPC1L1-SREBP2-LDLR axis and HNF4α-MTP/APOB axis, respectively. Overall, hawk tea works as a previously unrecognized cholesterol-lowering agent in a multi-target and multi-component manner.