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Natural products have been the main sources of new drugs. The different strategies have been developed to find the new drugs based on natural products. The traditional and ethic medicines have provided information on the therapeutic effects and resulted in some notable drug discovery of natural products. The special activities of the medicine plants such as the side effects have inspired scientists to develop the novel small molecular. The microorganisms and the endogenous active substances from human or animal also become the important approaches to the drug discovery. The tremendous progress in technology led to the new strategies in drug discovery from natural products. The bioinformation and artificial intelligence have facilitated the research and development of natural products. We will provide a scene of strategies and technologies for drug discovery from natural products in this review., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2020. Published by Elsevier Inc.)

Ethnopharmacological Relevance: The plant Anchusa italica Retz. (Anchusa azurea Mill.) has been traditionally used in Uygur medicine for the treatment of cardiovascular and cerebrovascular diseases in China. Our previous study showed that total flavonoids from Anchusa italica Retz. (TFAI) exhibited potent cardioprotection in acute ischemia/reperfusion injured rats., Aim of the Study: This study was undertaken to investigate the effects of TFAI on chronic myocardial infarction (MI) in mice and the underlying mechanism., Materials and Methods: Total flavonoids were extracted from the whole herb of Anchusa italica Retz. and were characterized using HPLC-MS analysis. The left anterior descending branch of the coronary artery was ligated to simulate MI injury in mice. After surgery, mice were orally fed with TFAI at the doses of 10, 30 and 50 mg/kg body weight/day for a total of four weeks. Cardiac function and infarct size were measured, and inflammatory mediators were detected. Hematoxylin and eosin (H&E) staining and Masson's trichrome staining were performed on heart sections. The apoptotic factors, such as Bax, Bcl-2 and cleaved caspase 3, as well as the key proteins in the PI3K/Akt/mTOR signaling pathway were examined by Western blot., Results: The content of total flavonoids in TFAI was 56.2%. Four weeks following the MI surgery, TFAI enhanced the survival rate in post-MI mice. TFAI treatment at the doses of 30 and 50 mg/kg remarkably reduced infarct size and improved cardiac function as indicated by elevated EF and FS. Assay of the inflammatory factors showed that sera levels of TNF-α, IL-1β and IL-6 were markedly decreased by TFAI treatment compared to the MI group. H&E staining and Masson's trichrome staining demonstrated that TFAI suppressed myocyte hypertrophy and cardiac fibrosis as indicated by the decreased cross-section area and collagen volume. Western blot analysis showed that cleaved caspase 3 and Bax/Bcl-2 were significantly downregulated following TFAI treatment. Furthermore, TFAI treatment significantly suppressed the activation of the PI3K/Akt/mTOR signaling pathway., Conclusions: Our data suggest that TFAI exerts a potent protective effect against chronic MI injury, and its beneficial effects on cardiac function and cardiac remodeling might be attributable, at least in part, to anti-inflammation and inhibition of the PI3K/Akt/mTOR signaling pathway., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This study aimed to investigate the total phenolic content (TPC), the identification of the common compounds by HPLC-ESI-MS and HPLC-ESI-MS-TOF and the inhibitory effects against class A-type β-lactamase (GES-22 variant, produced recombinantly) in methanolic extracts (MEs) of four Algerian seaweeds [Ulva intestinalis, Codium tomentosum, Dictyota dichotoma and Halopteris scoparia]. The TPC varied among the four species, ranging between 0.93 ± 0.65 and 2.66 ± 1.33 mg GAEs/g DW. C.tomentosum had higher total phenol content than other seaweeds while, all of them inhibited uncompetitively GES-22 activity in a dose-dependent manner. Nitrocefin was used as chromogenic substrate to evaluate the inhibitory effect on GES-22. The methanolic extract of D.dichotoma exhibited significant inhibitory effect on GES-22 (IC 50  = 13.01 ± 0.046 μg/mL) more than clavulanate, sulbactam and tazobactam (classical β-lactam inhibitors) (IC 50  = 68.38 ± 0.17 μg/mL, 52.68 ± 0.64 μg/mL, and 29.94 ± 0.01 μg/mL, respectively). IC 50 of the other ME of U.intestinalis, C.tomentosum, and H.scoparia were 16.87 ± 0.10 μg/mL, 16.54 ± 0.048 μg/mL, and 25.72 ± 0.15 μg/mL, respectively. Except H. scoparia, other three seaweed extracts showed almost two times or more inhibition on GES-22. Furthermore, four common compounds in these MEs were identified, α-linolenic acid (C18:3ω3), linoleic acid (C18:2ω6), oleic acid (C18:1ω9), the eicosanoid precursors ''arachidonic acid'' (C20:4ω6). Baicalein (C15H10O5) was identified in U.intestinalis and D.dichotoma seaweeds. The fact that all seaweed extracts inhibited the GES-22 better than commercial samples makes these seaweeds candidate for discovering new inhibitors against β-lactamases. Besides that, they contain important components with potential health benefits., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Abstract: Ethnopharmacological relevance: Salvianolic acid A (SAA) is one of the main water-soluble components isolated from Salvia miltiorrhiza Bunge. Pharmacological researches revealed that it had various curative activities after oral and intravenous administration, including beneficial effects on diabetes and its complications, cardioprotective effect, anti-platelet aggregation, and so on. However, there is no report regarding the pharmacokinetics of SAA in beagle dogs after oral administration up to now. Aim of the study: To study the pharmacokinetics of different doses of SAA in beagle dogs and figure out the absolute bioavailability and dose proportionality of SAA after oral administration. Materials and methods: Male and female beagle dogs were orally administered SAA 5, 10 and 20mg/kg randomly. The plasma drug concentration was detected by a rapid, sensitive and reproducible liquid chromatography–mass spectrometry (LC–MS) method. The pharmacokinetic parameters were calculated from plasma concentration–time data using the DAS pharmacokinetic software Data Analysis System Version 3.0 program. Results: After single-dose oral administration of SAA, the mean peak plasma concentration (C max) values for groups treated with 5, 10 and 20mg/kg doses ranged from 14.38 to 38.18µg/L, and the mean area under the concentration–time curve (AUC(0–t)) values ranged from 38.77 to 130.33 (µg/L⋅h). SAA showed lack of dose proportionality over the dose range 5–20mg/kg, based on the power model. However, the increase in systemic exposure with dose appeared linear. The absolute bioavailability was calculated to range from 1.47% to 1.84%. Conclusion: The pharmacokinetic properties of SAA in beagle dogs after oral administration were characterized as rapid oral absorption, quick clearance, and poor absolute bioavailability. Systemic exposure exhibited lack of dose proportionality over the dose range 5–20mg/kg. Furthermore, a readily preparative LC–MS method was demonstrated in this study for the research of traditional Chinese medicine. [Copyright &y& Elsevier]

Abstract: Baicalein, a flavonoid originally isolated from the root of Scutellaria baicalensis Georgi, has numerous pharmacological activities. Up to now, several studies regarding the pharmacokinetic profiles of baicalein have been described, while there is no such study reported in monkey, the species which is more similar to human. The purpose of this study was to investigate the pharmacokinetic profiles of baicalein after oral administration in monkeys. After orally administrating three doses of baicalein in monkeys, multi-peaks of the plasma concentration–time curves were observed and the non-linear pharmacokinetics for baicalein and its metabolite baicalin were found at doses of 50–500mg/kg. In order to calculate the absolute bioavailability, the intravenous pharmacokinetic study was also carried out after intravenous administration of 10mg/kg baicalein. The absolute bioavailability of baicalein in different doses was ranged from 13.1% to 23.0%. In this study, baicalein and baicalin were determined by LC–MS method. The chromatographic separation was performed on Agilent Poroshell 120 SB-C18 column (2.7μm, 2.1×50mm). Baicalein and baicalin were detected by single quadrupole mass spectrometer equipment with electrospray ionization interface with the selected ion monitoring mode. The assay was linear for both baicalein and baicalin with the correlation coefficients>0.99. The intra- and inter-day precisions for baicalein and baicalin were all less than 15% by relative standard deviation. The analytes were stable during samples storage and handling, and no matrix effects were observed. The method we developed in this study was sensitive, precise, stable and producible. [Copyright &y& Elsevier]

Ethnopharmacological relevance Methyl salicylate-2-O- β - d -lactoside (MSL) is one of the main active components isolated from Gaultheria yunnanensis , which is a traditional Chinese medicine used to treat arthritis and various aches and pains. Pharmacological researches showed that MSL had various effective activities in both in vivo and in vitro experiments. However, the pharmacokinetics features and oral bioavailability of MSL in primates were not studied up to now. Aim To study the pharmacokinetics of different doses of MSL in rhesus monkeys and investigate the absolute bioavailability of MSL after oral administration. Materials and methods Male and female rhesus monkeys were either orally administrated with MSL 200, 400 and 800 mg/kg or received an intravenous dose of 20 mg/kg randomly. The levels of MSL and salicylic acid (SA) in plasma were simultaneous measured by a simple, sensitive and reproducible high performance liquid chromatography method. Results Mean peak plasma concentration values for groups treated with 200, 400 and 800 mg/kg doses ranged from 48.79 to 171.83 μg/mL after single-dose oral administration of MSL, and mean area under the concentration–time curve values ranged from 195.16 to 1107.76 μg/mL h. Poor linearity of the kinetics of SA after oral administration of MSL was observed in the regression analysis of the C max -dose plot ( r 2 =0.812), CL-dose plot ( r 2 =0.225) and AUC (0− t ) -dose plot ( r 2 =0.938). Absolute bioavailability of MSL was assessed to be 118.89±57.50, 213.54±58.98 and 168.72±76.58%, respectively. Conclusions Bioavailability of MSL after oral administration in rhesus monkeys was measured for the first time. Pharmacokinetics parameters did not appear to be dose proportional among the three oral doses of treatments, and MSL showed an apparent absolute bioavailability in excess of 100% in rhesus monkeys based on the present study. In addition, a rapid, sensitive and reliable HPLC method was established and demonstrated for the research of traditional Chinese medicine in this study. [ABSTRACT FROM AUTHOR]