Phenylethanoid glycosides extract from Cistanche deserticola ameliorates atherosclerosis in apolipoprotein E-deficient mice and regulates intestinal PPARγ-LXRα-ABCA1 pathway.

OBJECTIVES: This study was aimed to evaluate the protective effects of phenylethanoid glycosides extract from Cistanche deserticola against atherosclerosis and its molecular mechanism. METHODS: Total phenylethanoid glycosides were extracted and purified from C. deserticola, and the C. deserticola extract (CDE) was used to treat a mice model of atherosclerosis. KEY FINDINGS: CDE containing 81.00% total phenylethanoid glycosides, with the contents of echinacoside and acteoside being 31.36% and 7.23%, respectively. A 13-week of CDE supplementation (1000 mg/kg body weight/day) significantly reduced atherosclerotic lesions in the aortic sinus and entire aorta in ApoE-/- mice fed with a high-fat diet. In addition, varying doses of CDE (250, 500 and 1000 mg/kg body weight/day) lowered plasma total cholesterol, triglyceride and non-high-density lipoprotein cholesterol levels. Transcriptomic analysis of the small intestine revealed the changes enriched in cholesterol metabolic pathway and the activation of Abca1 gene. Further validation using real-time quantitative PCR and western blot confirmed that CDE significantly increased the mRNA levels and protein expressions of ABCA1, LXRα and PPARγ. CONCLUSIONS: Our results demonstrate the beneficial effects of C. deserticola on atherosclerotic plaques and lipid homeostasis, and it is, at least partially, by activating PPARγ-LXRα-ABCA1 pathway in small intestine.

Application of highly efficient and lowly toxic bufadienolides screened from toad skin in lymphatic chemotherapy for colorectal cancer through a lymphatic metastatic model.

BACKGROUND: Lymph node metastasis (LNM) remains a major obstacle to treat colorectal cancer (CRC). Increasing evidences have suggested that bufadienolides contain several fractions displaying antitumor activity and may be applied in lymphatic chemotherapy. However, effects of the highly efficient and lowly toxic (HELT) bufadienolides on CRC in lymphatic chemotherapy have not been reported. METHODS: Adenosine triphosphate tumor chemosensitivity assays (ATP-TCA) was performed to detect the inhibition rate (IR) of fractions of bufadienolides to cytokine-induced killer (CIK) cells and tumor cells. HELT fraction-loaded emulsions of different concentrations were prepared. Nude mouse bearing HCT116 tumors in footpad received high-dose emulsion (HD-E), middle-dose emulsion (MD-E), low-dose emulsion (LD-E), control emulsion (CE), Cinobufacini Injection (CI), or normal saline (NS), respectively. Hematoxylin and eosin (H&E) staining, Flow Cytometry (FCM), enzyme-linked immune sorbent assay (ELISA) and hematological examination were applied to evaluate therapeutic effects and potential toxicity. RESULTS: F18 and F19 were screened out as HELT fractions in vivo and F18-loaded emulsions of different concentrations for lymphatic administration were prepared. We confirmed that HD-E and MD-E produced obvious antitumor activities in footpad tumors and LNM compared with other groups in vitro. We also verified the effects of F18-loaded emulsions on activating hematopoietic function, stimulating proliferation of the spleen and natural killer (NK) cells, and promoting the secretion of IFN-γ and IgG1, although HD-E performed mild toxicity on liver. CONCLUSION: The present study demonstrated that lymphatic chemotherapy with HELT fraction of bufadienolides could be an effective approach to the treatment of CRC patients with LNM.

AO-BBO: A Novel Optimization Algorithm and Its Application in Plant Drug Extraction.

INTRODUCTION: It is well-known that the biogeography-based optimization (BBO) algorithm lacks searching power in some circumstances. MATERIAL & METHODS: In order to address this issue, an adaptive opposition-based biogeography-based optimization algorithm (AO-BBO) is proposed. Based on the BBO algorithm and opposite learning strategy, this algorithm chooses different opposite learning probabilities for each individual according to the habitat suitability index (HSI), so as to avoid elite individuals from returning to local optimal solution. Meanwhile, the proposed method is tested in 9 benchmark functions respectively. RESULT: The results show that the improved AO-BBO algorithm can improve the population diversity better and enhance the search ability of the global optimal solution. The global exploration capability, convergence rate and convergence accuracy have been significantly improved. Eventually, the algorithm is applied to the parameter optimization of soft-sensing model in plant medicine extraction rate. CONCLUSION: The simulation results show that the model obtained by this method has higher prediction accuracy and generalization ability.

Postharvest Ultrasound-Assisted Freeze-Thaw Pretreatment Improves the Drying Efficiency, Physicochemical Properties, and Macamide Biosynthesis of Maca (Lepidium meyenii).

A novel technique of ultrasound-assisted freeze-thaw pretreatment (UFP) was developed to improve the drying efficiency of maca and bioactive amide synthesis in maca. The optimal UFP conditions are ultrasonic processing 90 min at 30 °C with 6 freeze-thaw cycles. Samples with freeze-thaw pretreatment (FP), ultrasound pretreatment (UP), and UFP were prepared for further comparative study. A no pretreatment (NP) sample was included as a control. The results showed that UFP improved the drying efficiency of maca slices, showing the highest effective moisture diffusivity (1.75 × 10-9 m2 /s). This result was further supported by low-field nuclear magnetic resonance (LF-NMR) analysis and scanning electron microscopy (SEM). The rehydration capacity and protein content of maca slices were improved by UFP. More importantly, contents of bioactive macamides and their biosynthetic precursors were increased in 2.5- and 10-fold, respectively. In conclusion, UFP is an efficient technique to improve drying efficiency, physicochemical properties, and bioactive macamides of maca, which can be applied in the industrial manufacture of maca products.

Hepatotoxicity of Eupatorium adenophorum extracts and the identification of major hepatotoxic components.

Eupatorium adenophorum can induce liver toxicity in animals. For the safe utilisation of the weed, the hepatotoxic components need to be discovered. In this study, in vitro hepatotoxicity of different extracts from E. adenophorum were determined on human hepatocyte cell line L02 and hepatocellular carcinoma cell line HepG2. The results showed that water extracts of E. adenophorum exhibited no hepatotoxicity in vitro while high concentrations of the organic solvent extracts had obvious hepatotoxicity. Sesquiterpenes may contribute to the toxicity based on the comparison of composition analysis. Three cadinene sesquiterpenes were purified and identified as 9-oxo-10,11-dehydroageraphorone, 10Hα-9-oxo-ageraphorone and 10Hß-9-oxo-ageraphorone. In vitro hepatotoxic effects of these components were investigated, the IC50 of the three compounds were 122.53, 87.52, and 108.80 µM in L02 cells and 151.92, 104.48, and 138.08 µM in HepG2 cells by Cell Counting Kit-8 (CCK-8) assay. The three components were confirmed to be, at least partial, hepatotoxic components.

Danshen (Salvia miltiorrhiza) Compounds Improve the Biochemical Indices of the Patients with Coronary Heart Disease.

Danshen was able to reduce the risk of the patients with coronary heart disease (CHD), but the mechanism is still widely unknown. Biochemical indices (lipid profile, markers of renal and liver function, and homocysteine (Hcy)) are closely associated with CHD risk. We aimed to investigate whether the medicine reduces CHD risk by improving these biochemical indices. The patients received 10 Danshen pills (27 mg/pill) in Dashen group, while the control patients received placebo pills, three times daily. The duration of follow-up was three months. The serum biochemical indices were measured, including lipid profiles (LDL cholesterol (LDL-C), HDL-C, total cholesterol (TC), triglycerides (TG), apolipoprotein (Apo) A, ApoB, ApoE, and lipoprotein (a) (Lp(a))); markers of liver function (gamma-glutamyl transpeptidase (GGT), total bilirubin (TBil), indirect bilirubin (IBil), and direct bilirubin (DBil)); marker of renal function (uric acid (UA)) and Hcy. After three-month follow-up, Danshen treatment reduced the levels of TG, TC, LDL-C, Lp(a), GGT, DBil, UA, and Hcy (P < 0.05). In contrast, the treatment increased the levels of HDL-C, ApoA, ApoB, ApoE, TBil, and IBil (P < 0.05). Conclusion. Danshen can reduce the CHD risk by improving the biochemical indices of CHD patients.

Preparation, Phytochemical Investigation, and Safety Evaluation of Chlorogenic Acid Products from Eupatorium adenophorum.

Eupatorium adenophorum is widely distributed throughout the world's tropical and temperate regions. It has become a harmful weed of crops and natural environments. Its leaves contain bioactive compounds such as chlorogenic acid and may be used as feed additives. In this study, chlorogenic acid was extracted and separated from leaves of E. adenophorum. Three chlorogenic acid products were prepared with different purities of 6.11%, 22.17%, and 96.03%. Phytochemical analysis demonstrated that the main toxins of sesquiterpenes were almost completely removed in sample preparation procedure. The three products were evaluated for safety via in vitro and in vivo toxicological studies. All the products exhibited no cytotoxic effects at a dose of 400 µg/mL in an in vitro cell viability assay. When administered in vivo at a single dose up to 1.5 g/kg bw, all three products caused no signs or symptoms of toxicity in mice. These results encourage further exploration of extracts from E. adenophorum in feed additive application.

Enrichment and separation of chlorogenic acid from the extract of Eupatorium adenophorum Spreng by macroporous resin.

A simple and efficient chromatographic method for separation of chlorogenic acid from Eupatorium adenophorum Spreng extract was developed. The adsorption properties of nine macroporous resins were evaluated. NKA-II resin showed much better adsorption/desorption properties. The adsorption of chlorogenic acid on NKA-II resin at 25°C was well fitted to Langmuir isotherm model and pseudo-second-order kinetic model. The dynamic adsorption and desorption experiments were carried out on columns packed with NKA-II resin to optimize the separation process. The content of chlorogenic acid in the product increased to 22.17%, with a recovery yield of 82.41%.

Ultrasound-assisted aqueous two-phase extraction of phenylethanoid glycosides from Cistanche deserticola Y. C. Ma stems.

An efficient ultrasound-assisted aqueous two-phase extraction and enrichment process for phenylethanoid glycosides from Cistanche deserticola Y. C. Ma stems was developed in this work. An ethanol/ammonium sulfate system was chosen for the aqueous two-phase system due to its fine partitioning and recycling behaviors. Single-factor experiments and response surface methodology were used to optimize the process parameters of the ultrasound-assisted aqueous two-phase extraction. The optimal conditions were as follows: a salt concentration of 23.5%, an ethanol concentration of 20%, an extraction time of 37 min, an extraction temperature of 30°C, a liquid/solid ratio of 30:1 w/w, and an ultrasound power of 300 W. Under the above conditions, the extraction yields of echinacoside and acteoside (the main components of phenylethanoid glycosides) reached 5.35 and 6.22 mg/g dry material weight, respectively. The contents of echinacoside and acteoside in the extracts reached 27.56 and 30.23 mg/g, respectively, which were 2.46- and 2.58-fold higher than the amounts obtained in ultrasound-assisted extraction. In conclusion, ultrasound-assisted aqueous two-phase extraction was an efficient, ecofriendly, and economical method, and it may be a promising technique for extracting and enriching bioactive components from plants.

Adsorption properties and preparative separation of phenylethanoid glycosides from Cistanche deserticola by use of macroporous resins.

A simple and efficient chromatographic method for large-scale preparative separation of phenylethanoid glycosides (mainly contain echinacoside and acteoside) from Cistanche deserticola was developed. The adsorption properties of eight macroporous resins were evaluated. Three selected resins were further screened depending on the adsorption kinetics curves, in which HPD300 resin showed the best separation efficiency. The adsorption isotherm data on HPD300 resin were fitted to the Freundlich equation in certain concentration range. The dynamic adsorption and desorption experiments were carried out on columns packed with HPD300 resin to optimize the separation process. The breakthrough curves showed that acteoside had a higher affinity to the resin than echinacoside. The contents of echinacoside and acteoside in the product increased from 1.79% and 1.43% in the crude extracts to 16.66% and 15.17%, with recovery yields of 80.41% and 90.17%, respectively. The purity of total phenylethanoid glycosides in the product was 76.58%.