Monoterpene-flavonoid conjugates from Sarcandra glabra and their autophagy modulating activities.

Fourteen new monoterpene-flavonoid conjugates including four monoterpene-conjugated chalcones (glabratins A-D, 1-4), seven monoterpene-conjugated dihydrochalcones (glabratins E-K, 5-11), and three monoterpene-conjugated flavanones (glabratins L-N, 12-14), together with four known analogues (15-18) were isolated from the aerial parts of Sarcandra glabra. The structures and the absolute configurations of these compounds were elucidated by the spectroscopic data, single-crystal X-ray diffraction, and electronic circular dichroism (ECD) calculations. Compounds 1, 4-6, 9-14, and 18 showed obvious cell autophagy-inducing activities at 25 µM in HEK293 cells. Furthermore, the bioassay results also showed that 18 induced cell autophagy in a dose dependent manner. Our findings revealed a rare class of monoterpene-flavonoid conjugates in nature and firstly reported their autophagy-inducing activities.

Integrating Network Pharmacology and Component Analysis Study on Anti-Atherosclerotic Mechanisms of Total Flavonoids of Engelhardia roxburghiana Leaves in Mice.

Engelhardia roxburghiana Wall. leaves are widely used to develop herbal teas in southeast of China due to medicinal use for diabetes mellitus and hyperlipidemia. Studies have demonstrated that the total flavonoids of E. roxburghiana leaves (TFER) exhibited regulatory effects on blood glucose and lipids. To clarify the active ingredients of TFER and their targets in treating atherosclerosis, the present study integrated chemical analysis, network pharmacology analysis and animal experimental studies. Firstly, high performance liquid chromatography-mass spectrometry/mass spectrometry (HPLC/MS/MS) was utilized to identify components of TFER. Then, active ingredients were screened by oral bioavailability (OB) and drug-likeness (DL) index. Thirdly, network was constructed to predict major targets of active ingredients against atherosclerosis. Finally, to verify parts of predicted signaling, Apoe-/- mice were used to develop atherosclerosis. Atherosclerotic plaques in aorta were evaluated by echocardiography. Then, serum lipids, target genes expressions in thoracic aorta were determined by qRT-PCR and ELISA methods. Chemical analysis revealed 10 components in TFER sample, 7 of which acted as active ingredients, including naringenin, kaempferol, quercetin, isoengeletin, engeletin, astilbin and quercitrin. KEGG pathway analysis highly enriched in some inflammatory signalings, including NF-κB signaling, Toll-like receptor signaling and TNF signaling. The animal studies indicated that TFER reduced atherosclerotic plaques size in aorta and significantly decreased the serum lipids, down-regulated NF-κB signaling by decreasing mRNA level of NF-κB p65 subunit, TNF-α and VCAM-1, as well as IL-1ß expressions in thoracic aorta, eventually alleviating atherosclerosis progression, which was in consistent with our prediction.

Active fraction of Polyrhachis vicina Rogers (AFPR) suppressed breast cancer growth and progression via regulating EGR1/lncRNA-NKILA/NF-κB axis.

Breast cancer (BC) is a major contributor of cancer-associated mortality in women. It is essential to find new therapeutic targets and drugs. Polyrhachis vicina Rogers is one of the Traditional Chinese Medicine (TCM). Our previous studies have shown an active fraction of Polyrhachis vicina Rogers (AFPR) has significant anti-inflammatory activity, suggesting its anti-cancer effect. Here, we aimed to explore the inhibitory effects of AFPR on BC and reveal its mechanism. The effects of AFPR on BC were examined by cell proliferation assay, wound healing assay, invasion assay and xenograft assay. Microarray sequencing, qRT-PCR, Western blot, chromatin immunoprecipitation assay and luciferase reporter assay were performed to investigate the regulation of AFPR on related genes and underlying mechanisms. As a result, AFPR suppressed BC cell growth, migration and invasion and inhibited tumor growth. LncRNA NKILA was most prominently upregulated in AFPR-treated MCF7 cells. AFPR inactivated NF-κB signaling pathway via regulating NKILA. Furthermore, AFPR regulated the expression of NKILA by inhibiting its transcript suppressor EGR1. This study firstly indicated that AFPR was a potential inhibitor of BC development via regulating EGR1/NKILA/NF-κB axis.

Hepatotoxicity and mechanism study of chrysophanol-8-O-glucoside in vitro.

To better understand the hepatotoxicity of anthraquinone glycosides, the hepatotoxicity of six anthraquinone glycosides was evaluated. The results show that chrysophanol-8-O-glucoside(C8G) has strong hepatotoxicity and can lead to increased LDH leakage and ROS, decreased GSH and MMP in L-02 hepatocytes. The results of C8G hepatotoxicity proteomics shows that, a total of 773 differentially expressed proteins were screened and analyzed using GO analysis and Pathway enrichment analysis. Our results show that C8G can lead to abnormal oxidative phosphorylation by inhibiting the function of mitochondrial complexes, resulting in decreased mitochondrial membrane potential (MMP), increased reactive oxygen species (ROS), and eventually resulting in mitochondrial damage and apoptosis. Western blot results verified the accuracy of quantitative proteomic results, and also evaluated the expression of Bax, caspase-3, -8, -9, Bcl-2, Cyt C in the mitochondria and cytosolic. The mitochondrial respiratory chain complexes activity assay result also confirmed that C8G could inhibit the activity of all mitochondrial complexes. The results of this study indicate that the hepatotoxicity mechanism of C8G is related to mitochondrial dysfunction, especially the mitochondrial complex function.

Gut microbiota: a new angle for traditional herbal medicine research.

Traditional Herbal Medicine (THM) has been used for thousands of years, and is popular worldwide due to its effectiveness in a variety of diseases. THM has also formed the basis of the discovery of modern drugs like artemisinin and paclitaxel. However, at present, studies that focus on development in the field of THM are stagnant because currently, the effective ingredients in the herbal formulations and the ambiguity of the underlying mechanisms of action are unknown. In this review, we have investigated the studies available that focused on the efficacy, active ingredients and bioavailability of THM, and the function of gut microbiota in THM-mediated treatment of disease. We hypothesized that most THMs treat diseases via three mechanisms: (1) metabolizing into active metabolites by the action of gut microbiota, (2) regulation of gut microbiota balance, and (3) regulating the fermentation products of the gut microbes. Therefore, focusing on these aspects can help elucidate the pharmacodynamic constituents of THM preparations, and their therapeutic mechanisms of action.

Glycyrrhetinic acid modified and pH-sensitive mixed micelles improve the anticancer effect of curcumin in hepatoma carcinoma cells.

Curcumin (CUR), a natural polyphenolic compound existing in plants, exhibits anticancer potential in inhibiting the growth of various types of human cancer. However, the poor aqueous solubility and low bioavailability limit its clinical applications. pH-sensitive macromolecule F68-acetal-PCL (FAP) and active targeting macromolecule F68-glycyrrhetinic acid (FGA) were designed to fabricate mixed micelles for efficient delivery of CUR. The thin film hydration method was used to prepare CUR loaded mixed (MIX/CUR) micelles. The drug loading rate (DL) of MIX/CUR micelles was 6.31 ± 0.92%, which remained stable for 15 days at 4 °C. The particle size and zeta potential of the MIX/CUR micelles were 91.06 ± 1.37 nm and -9.79 ± 0.47 mV, respectively. The MIX/CUR micelles exhibited pH sensitivity in a weak acid environment, and showed rapid particle size variation and drug release. In addition, in vitro tests demonstrated that MIX/CUR micelles induced higher cytotoxicity and apoptosis than free CUR, non-pH-sensitive F68-PCL (FBP)/CUR micelles and pH-sensitive FAP/CUR micelles in SMMC7721 and Hepa1-6 cells. Besides, mixed micelles were more effective than FBP and FAP micelles in a cell uptake experiment, which was medicated by a GA receptor. All in all, these results indicated that MIX/CUR micelles could be regarded as an ideal drug administration strategy against hepatoma carcinoma cells.

Phenolic Constituents Isolated from the Twigs of Cinnamomum cassia and Their Potential Neuroprotective Effects.

Seven new α,ß-diphenyl-γ-butyrolactones (1-7), three new lignans (8-10), five new neolignans (11-15), two new 1,3-biphenylpropanoids (16 and 17), and a new flavonol galactoside-lignan ester (18), together with 43 known compounds (19-61), were isolated from the twigs of Cinnamomum cassia. Their structures were elucidated by spectroscopic data analysis as well as chemical methods. The α,ß-diphenyl-γ-butyrolactones are a class of unique natural compounds that have only been isolated from C. cassia. Compounds 11 and 12 are rare examples of neolignans possessing a 1,2-dioxetane moiety. Compound 13 is a new oxyneolignan possessing a unique C-9-O-C-9' linkage between the benzopyran and cinnamyl alcohol moieties. Compound 15 is the first example of a natural neolignan possessing a 2-styryl-3-phenyltetrahydrofuran skeleton. The isolated compounds were evaluated for their neuroprotective activities against tunicamycin-induced cytotoxicity in SH-SY5Y cells. Compounds 3, 5, 10, 11, 12, 20, 36, and 56 showed statistically significant neuroprotective activity with EC50 values ranging between 21 and 75 µM.