[Prediction of quality markers and medicinal value of sea buckthorn leaves based on network pharmacology, content determination, and activity evaluation].

The leaves of sea buckthorn(Hippophae rhamnoides), considered as common food raw materials, have records of medicinal use and diverse pharmacological activities, showing a potential medicinal value. However, the active substances in the sea buckthorn leaves and their mechanisms of action remain unclear. In addition, due to the extensive source and large variety variations, the quality evaluation criteria of sea buckthorn leaves remain to be developed. To solve the problems, this study predicted the main active components, core targets, key pathways, and potential pharmacological effects of sea buckthorn leaves by network pharmacology and molecular docking. Furthermore, ultra-performance liquid chromatography with diode-array detection(UPLC-DAD) was employed to determine the content of active components and establish the chemical fingerprint, on the basis of which the quality markers of sea buckthorn leaves were predicted and then verified by the enzyme activity inhibition method. The results indicated that sea buckthorn leaves had potential therapeutic effects on a variety of digestive tract diseases, metabolic diseases, tumors, and autoimmune diseases, which were consistent with the ancient records and the results of modern pharmacological studies. The core targets of sea buckthorn leaves included PTPN11, AKT1, PIK3R1, ESR1, and SRC, which were mainly involved in the PI3K-AKT, MAPK, and HIF-1 signaling pathways. In conclusion, the active components of sea buckthorn leaves are associated with the rich flavonoids and tannins, among which quercitrin, narcissoside, and ellagic acid can be used as the quality markers of sea buckthorn leaves. The findings provide a reference for the quality control and further development and utilization of sea buckthorn leaves as medicinal materials.

Swertia cincta Burkill alleviates LPS/D-GalN-induced acute liver failure by modulating apoptosis and oxidative stress signaling pathways.

Swertia cincta Burkill is widely distributed along the southwestern region of China. It is known as "Dida" in Tibetan and "Qingyedan" in Chinese medicine. It was used in folk medicine to treat hepatitis and other liver diseases. To understand how Swertia cincta Burkill extract (ESC) protects against acute liver failure (ALF), firstly, the active ingredients of ESC were identified using liquid chromatography-mass spectrometry (LC-MS), and further screening. Next, network pharmacology analyses were performed to identify the core targets of ESC against ALF and further determine the potential mechanisms. Finally, in vivo experiments as well as in vitro experiments were conducted for further validation. The results revealed that 72 potential targets of ESC were identified using target prediction. The core targets were ALB, ERBB2, AKT1, MMP9, EGFR, PTPRC, MTOR, ESR1, VEGFA, and HIF1A. Next, KEGG pathway analysis showed that EGFR and PI3K-AKT signaling pathways could have been involved in ESC against ALF. ESC exhibits hepatic protective functions via anti-inflammatory, antioxidant, and anti-apoptotic effects. Therefore, the EGFR-ERK, PI3K-AKT, and NRF2/HO-1 signaling pathways could participate in the therapeutic effects of ESC on ALF.

Integration of network pharmacology, transcriptomics and molecular docking reveals two novel hypoglycemic components in snow chrysanthemum.

Our previous studies uncovered the glucose-lowering properties of snow chrysanthemum tea, however, the active ingredients and underlying mechanisms were yet to be uncovered. Flavonoids are the most active and abundant components in snow chrysanthemum tea. In this study, we treated leptin-deficient diabetic ob/ob or high-fat diet (HFD)-induced C57BL/6 J obese mice with or without total flavonoids of snow chrysanthemum (TFSC) for 14 weeks. Results indicated that TFSC ameliorated dyslipidemia and fatty liver, thereby reducing hyperlipidemia. Further mechanism experiments, including RNA-seq and experimental validation, revealed TFSC improved glycolipid metabolism primarily by activating the AMPK/Sirt1/PPARγ pathway. Additionally, by integrating UPLC, network pharmacology, transcriptomics, and experimental validation, we identified two novel hypoglycemic compounds, sulfuretin and leptosidin, in TFSC. Treatment with 12.5 µmol/L sulfuretin obviously stimulated cellular glucose consumption, and sulfuretin (3.125, 6.25 and 12.5 µmol/L) significantly mitigated glucose uptake damage and reliably facilitated glucose consumption in insulin-resistant HepG2 cells. Remarkably, sulfuretin interacted with the ligand-binding pocket of PPARγ via three hydrogen bond interactions with the residues LYS-367, GLN-286 and TYR-477. Furthermore, a concentration of 12.5 µmol/L sulfuretin effectively upregulated the expression of PPARγ, exhibiting a comparable potency to a renowned PPARγ agonist at 20 µmol/L. Taken together, our findings have identified two new hypoglycemic compounds and revealed their mechanisms, which significantly expands people's understanding of the active components in snow chrysanthemum that have hypoglycemic effects.

Investigating the chemical profile of Rheum lhasaense and its main ingredient of piceatannol-3'-O-ß-D-glucopyranoside on ameliorating cognitive impairment.

Rheum lhasaense A. J. Li et P. K. Hsiao, a stout herb plant from the Polygonaceae, is a typical Tibetan folk herb with heat-clearing and detoxifying effects, but does not have the typical laxative effect compared with other rhubarb plants. Nevertheless, its chemical composition and pharmacological activities still lack in-depth research. The present study endeavored to analyze the possible phytochemical constituents in R. lhasaense and explore the main compound piceatannol-3'-O-ß-D-glucopyranoside (PG) effect on cognitive impairment and its underlying mechanism. The chemical profile of R. lhasaense discovered 46 compounds, including 27 stilbenoids and 13 gallotannins using UPLC-Q-TOF-MS/MS. The UPLC determined the contents of 6 main stilbenoids, among which the content of PG was the highest, up to 61.06 mg/g. Moreover, behavioral tests showed that PG (40 mg/kg and 160 mg/kg) administration markedly ameliorated memory impairments of scopolamine-induced mice. Biochemical parameters showed that PG treatment alleviated the levels of Ach, AchE, and inflammatory factors while elevating the levels of antioxidants in mice. In addition, network pharmacology was performed to reveal PG exert an mild cognitive impairment effect by participating in neurodegenerative disease pathways, proliferation and apoptosis-, and inflammation-related pathways. Eventually, the results of molecular docking and the qRT-PCR revealed that PG down-regulated the mRNA expressions of MMP3, MMP9 and BACE1 in cognitive impairment mice brain tissue. In conclusion, our results demonstrated that PG mitigated scopolamine-induced cognitive dysfunction in mice by targeting the BACE1-MMP3/9 pathway, and PG might be a promising mild AD drug candidate.

Novel active compounds and the anti-diabetic mechanism of mulberry leaves.

Mulberry (Morus alba L.) leaves have long been considered beneficial in traditional Chinese medicine to treat infectious and internal diseases. Recently studies have discovered that the mulberry leaf's total flavonoids (MLF) display excellent hypoglycemia properties. However, the active ingredients and their molecular mechanisms are still uncharacterized. In this study, we explored the hypoglycemic effects of MLF and mulberry leaf polysaccharides (MLP) on ob/ob mice, an animal model of type 2 diabetes mellitus (T2DM), compared with Ramulus Mori (Sangzhi) alkaloid (RMA). Network pharmacology was employed to identify the potential available targets and active compounds of MLF and RMA against hyperglycemia. Molecular docking, an insulin-resistant cell model and qPCR were employed to verify the antidiabetic activity of the critical compounds and the gene expression profiles of the top molecular targets. Here, the results showed that MLF and MLP improved glucose uptake in insulin-resistant hepatocytes. MLF, MLP and RMA alleviated insulin resistance and glucose intolerance in ob/ob mice. Unlike MLF and MLP, RMA administration did not influence the accumulation of intrahepatic lipids. Network pharmacology analysis revealed that morusin, kuwanon C and morusyunnansin L are the main active compounds of MLF and that they amend insulin resistance and glycemia via the PI3K- Akt signaling pathway, lipid and atherosclerosis pathways, and the AGE-RAGE signaling pathway. Moreover, 1-deoxynojirimycin (DNJ), fagomine (FA), and N-methyl-1-deoxynojirimycin are the primary active ingredients of RMA and target carbohydrate metabolism and regulate alpha-glucosidase activity to produce a potent anti-diabetic effect. The molecular docking results indicated that morusin, kuwanon C and morusyunnansin L are the critical bioactive compounds of MLF. They had high affinities with the key targets adenosine A1 receptor (ADORA1), AKT serine/threonine kinase 1 (AKT1), peroxisome proliferator-activated receptor gamma (PPARγ), and glycogen synthase kinase 3 beta (GSK3ß), which play crucial roles in the MLF-mediated glucose-lowering effect. Additionally, morusin plays a role in amending insulin resistance of hepatocytes by repressing the expression of the ADORA1 and PPARG genes. Our results shed light on the mechanism behind the glucose-lowering effects of MLF, suggesting that morusin, kuwanon C, and morusyunnansin L might be promising drug leads for the management of T2DM.

Integrating network pharmacology analysis and pharmacodynamic evaluation for exploring the active components and molecular mechanism of moutan seed coat extract to improve cognitive impairment.

Paeonia suffruticosa (Moutan) is a traditional medicinal plant in China. Its seed coat is rich in resveratrol oligomer, especially suffruticosol B (SB). Previous studies had shown that the seed coat extracts of Paeonia suffruticosa (PSCE) had good cholinesterase inhibitory activity and neuroprotective effect, but the effective dose range was unknown, and the pharmacodynamic components and molecular mechanism of PSCE had not been discussed. The current study aimed to screen the pharmacodynamic components in PSCE and investigate the improvement effect of PSCE and the selected SB on scopolamine-induced cognitive dysfunction in mice and its mechanism. The results of high-throughput sequencing and bioinformatics analysis showed that suffruticosol B (SB) and trans-gnetin H (GH) might be the main active components of PSCE; PSCE might improve cognitive dysfunction through p53, HIF-1, MAPK, and PI3K-Akt signaling pathways, while SB and GH might improve cognitive dysfunction through HIF-1 signaling pathway. SB and GH had good molecular docking activity with the target of HIF-1 signaling pathway. The pharmacodynamic activities of PSCE and SB were further verified by behavioral experiments. PSCE and SB could improve the recognition ability of familiar and new objects and shorten the escape latency in the Morris Water Maze test (PSCE 120 mg∙kg-1, p < 0.05; SB 60 mg∙kg-1, p < 0.01); PSCE and SB could increase Ach and GSH levels, enhance the activities of ChAT, SOD and CAT, decrease the levels of IL-1ß, IL-6, and TNF-α, and decrease the activity of AChE. In conclusion, the results indicated that PSCE might exert pharmacodynamic activity through multiple components, targets, and pathways, and SB and GH might be the main active components of PSCE. PSCE and SB might improve cognitive dysfunction by regulating cholinergic, antioxidant, and anti-inflammatory effects. These results indicated that PSCE and SB might be potential anti-AD drug candidates, providing a scientific basis for the development and utilization of Moutan bark.

Grey Wolf Optimizer for Variable Selection in Quantification of Quaternary Edible Blend Oil by Ultraviolet-Visible Spectroscopy.

A novel swarm intelligence algorithm, discretized grey wolf optimizer (GWO), was introduced as a variable selection tool in edible blend oil analysis for the first time. In the approach, positions of wolves were updated and then discretized by logical function. The performance of a wolf pack, the iteration number and the number of wolves were investigated. The partial least squares (PLS) method was used to establish and predict single oil contents in samples. To validate the method, 102 edible blend oil samples containing soybean oil, sunflower oil, peanut oil and sesame oil were measured by an ultraviolet-visible (UV-Vis) spectrophotometer. The results demonstrated that GWO-PLS models can provide best prediction accuracy with least variables compared with full-spectrum PLS, Monte Carlo uninformative variable elimination-PLS (MCUVE-PLS) and randomization test-PLS (RT-PLS). The determination coefficients (R2) of GWO-PLS were all above 0.95. Therefore, the research indicates the feasibility of using discretized GWO for variable selection in rapid determination of quaternary edible blend oil.

A network pharmacology approach to identify the mechanisms and molecular targets of curcumin against Alzheimer disease.

BACKGROUND: Alzheimer disease (AD) is a degenerative brain disease, which may lead to severe memory loss and other cognitive disorders. However, few effective drugs are available in the clinic at present. Curcumin, a major ingredient of traditional Chinese medicine, Curcuma Longa, has various pharmacological activities. Therefore, exploring clinical drugs based on the inhibition of AD pathological features is imperative. METHODS: First, we utilized the HERB database and Swisstarget Prediction database to get the related targets of curcumin and intersected with the AD targets. The intersection targets were used to construct the protein-protein interaction network and performed gene ontology and kyoto encyclopedia of genes and genomes analyses. Further, we obtained targets of curcumin against AD-related tau and aß pathology via the AlzData database. These targets were applied to perform GEO and receiver operating characteristic analyses. Finally, the reliability of the core targets was evaluated using molecular docking technology. RESULTS: We identified 49 targets of curcumin against AD, and kyoto encyclopedia of genes and genomes pathway enrichment analysis demonstrated that the Alzheimer disease pathway (has05010) was significantly enriched. Even more, we obtained 16 targets of curcumin-related Aß and tau pathology. Among these targets, 8 targets involved the Alzheimer disease pathway and the biological process analyses showed that positive regulation of cytokine production (GO:0001819) was significantly enriched. Bioinformatic analyses indicated that HMOX1, CSF1R, NFKB1, GSK3B, BACE1, AR, or PTGS1 expression was significantly different compared to the control group in the AD patients. Finally, molecular docking studies suggested these genes have a good binding force with curcumin. CONCLUSIONS: In this study, we identified curcumin exerted the effect of treating AD by regulating multitargets and multichannels through the method of network pharmacology.

Weighted multiscale support vector regression for fast quantification of vegetable oils in edible blend oil by ultraviolet-visible spectroscopy.

Weighted multiscale support vector regression combined with ultraviolet-visible (UV-Vis) spectra for quantitative analysis of edible blend oil is proposed. In the approach, UV-Vis spectra of the training set are decomposed into a certain number of intrinsic mode functions (IMFs) and a residue by empirical mode decomposition (EMD) at first. Then support vector regression (SVR) sub-models are built on each IMF and residue. For prediction set, the spectra are decomposed as done on the training set and the final predictions are obtained by integrating SVR sub-model predictions by weighted average. The weight of the sub-model is the reciprocal of the fourth power of the root mean square error of cross-validation (RMSECV). For predicting peanut oil in binary blend oil and sesame oil in ternary blend oil, the proposed method has superiority in root mean square error of prediction (RMSEP) and correlation coefficient (R) compared with SVR and partial least squares (PLS).

Tibetan medicine Kuan-Jin-Teng exerts anti-arthritic effects on collagen-induced arthritis rats via inhibition the production of pro-inflammatory cytokines and down-regulation of MAPK signaling pathway.

BACKGROUND: The stems of Tinospora sinensis (Lour.) Merr commonly named "Kuan-Jin-Teng" in Chinese, have been used to treat rheumatoid arthritis as a Tibetan medicine. PURPOSE: The effects of the EtOAc fraction of ethanolic extract from the stems of T. sinensis (KJT) on the pro-inflammatory cytokines and MAPK pathway were studied in collagen-induced arthritis (CIA) model. STUDY DESIGN: Anti-arthritic activity of KJT was investigated in CIA model. METHODS: The chemical constituents of KJT were analyzed by LC-MS and HPLC. The CIA model was established with injecting the bovine CII emulsified in Freund's adjuvant in Wistar rats. Several doses of KJT (50.0, 100.0 and 200.0 mg/kg) were administrated via oral gavage to CIA rats daily for 4 weeks. The anti-arthritic activity of KJT was investigated by clinical arthritis scoring, paw swelling inspection and hyperalgesia measurement, as well as radiological and histological analysis in CIA rats. The impacts of KJT on the activation of MAPK pathway, production of pro-inflammatory cytokines (TNF-α, IL-1ß and IL-17) in ankle joints, serum, and spleen in CIA rats were examined by western blot, immunohistochemical staining, ELISA, and quantitative real-time PCR respectively. Lastly, the effects of KJT on production of the nitric oxide (NO) and pro-inflammatory cytokines as well as the regulation of the phosphorylation of p38 and Erk were detected in lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophage cells. RESULTS: KJT significantly alleviated the paw swelling, hyperalgesia and arthritic severity, and reduced the synovial tissue proliferation and inflammatory cell infiltration in the CIA rats. Moreover, KJT suppressed the production of TNF-α, IL-1ß, and IL-17 in ankle joints, serum, and spleen and reversed the up-regulation of the phosphorylation of p38 and Erk in CIA rats. KJT was also demonstrated to inhibit the production of NO and pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6), and phosphorylation of p38 and Erk in LPS-stimulated RAW264.7 cells. CONCLUSION: These results suggest the mechanisms of KJT performing its anti-arthritis effect may be attributed to inhibiting the production of pro-inflammatory cytokines and down-regulating the MAPK signaling pathway.

Enantioconvergent hydrolysis of styrene epoxides by newly discovered epoxide hydrolases in mung bean.

[reaction: see text] Two novel epoxide hydrolases were discovered in mung bean (Phaseolus radiatus L.) for the first time, either of which can catalyze enantioconvergent hydrolysis of styrene epoxides. Their regioselectivity coefficients are more than 90% for the p-nitrostyrene oxide. Furthermore, the crude mung bean powder was also shown to be a cheap and practical biocatalyst, allowing a one-step asymmetric synthesis of chiral (R)-diols from racemic epoxides, in up to >99% ee and 68.7% overall yield (after recrystallization).