Anti-Obesity Activities of the Compounds from Perilla frutescens var. acuta and Chemical Profiling of the Extract.

Perilla frutescens var. acuta (Lamiaceae) is widely used not only as an oil or a spice, but also as a traditional medicine to treat colds, coughs, fever, and indigestion. As an ongoing effort, luteolin-7-O-diglucuronide (1), apigenin-7-O-diglucuronide (2), and rosmarinic acid (3) isolated from P. frutescens var. acuta were investigated for their anti-adipogenic and thermogenic activities in 3T3-L1 cells. Compound 1 exhibited a strong inhibition against adipocyte differentiation by suppressing the expression of Pparg and Cebpa over 52.0% and 45.0%, respectively. Moreover, 2 inhibited the expression of those genes in a dose-dependent manner [Pparg: 41.7% (5 µM), 62.0% (10 µM), and 81.6% (50 µM); Cebpa: 13.8% (5 µM), 18.4% (10 µM), and 37.2% (50 µM)]. On the other hand, the P. frutescens var. acuta water extract showed moderate thermogenic activities. Compounds 1 and 3 also induced thermogenesis in a dose-dependent manner by stimulating the mRNA expressions of Ucp1, Pgc1a, and Prdm16. Moreover, an LC-MS/MS chromatogram of the extract was acquired using UHPLC-MS2 and it was analyzed by feature-based molecular networking (FBMN) and the Progenesis QI software (version 3.0). The chemical profiling of the extract demonstrated that flavonoids and their glycoside derivatives, including those isolated earlier as well as rosmarinic acid, are present in P. frutescens var. acuta.

2,3-Dimethoxycinnamic Acid from a Marine Actinomycete, a Promising Quorum Sensing Inhibitor in Chromobacterium violaceum.

An ethyl acetate extract of a marine actinomycete strain, Nocardiopsis mentallicus SCSIO 53858, isolated from a deep-sea sediment sample in the South China Sea, exhibited anti-quorum-sensing (QS) activity against Chromobacterium violaceum CV026. Guided by the anti-QS activity, a novel active compound was isolated and purified from the extract and was identified as 2,3-dimethoxycinnamic acid (2,3-DCA) through spectral data analysis. At a concentration of 150 µg/mL, 2,3-DCA exhibited robust inhibitory effects on three QS-regulated traits of C. violaceum CV026: violacein production, swarming motility, and biofilm formation, with inhibition rates of 73.9%, 65.9%, and 37.8%, respectively. The quantitative reverse transcription polymerase chain reaction results indicated that 2,3-DCA can disrupt the QS system in C. violaceum CV026 by effectively suppressing the expression of QS-related genes, including cviR, vioA, vioB, and vioE. Molecular docking analysis revealed that 2,3-DCA hinders the QS system by competitively binding to the same binding pocket on the CviR receptor as the natural signal molecule N-hexanoyl-L-homoserine lactone. Collectively, these findings suggest that 2,3-DCA exhibits promising potential as an inhibitor of QS systems, providing a potential solution to the emerging problem of bacterial resistance.

Anti-tyrosinase and antimelanogenic effect of cinnamic acid derivatives from Prunus mahaleb L.: Phenolic composition, isolation, identification and inhibitory activity.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional use of Prunus species against skin diseases and especially for skin lightning cosmeceutical purposes is widespread in many cultures. Prunus mahaleb L. is a well known food plant and used in the baking industry for flavoring. The fruit kernels (endocarp) are used in India for hyperpigmentation. AIM OF THE STUDY: To investigate the chemical composition with the antimelanogenesis effect of P. mahaleb seed and kernel extracts and isolated compounds. MATERIALS AND METHODS: Isolation studies performed from the methanol extracts obtained from kernels and structures were determined using NMR and MS analysis. Antimelanogenesis effect was determined by mushroom tyrosinase assay, cellular tyrosinase assay and melanin content assay using B16F10 murine melanoma cells. RESULTS: Five cinnamic acid derivatives were isolated and their structures (2-O-ß-glucopyranosyloxy-4-methoxy-hydrocinnamic acid (1), cis-melilotoside (2), dihydromelilotoside (3), trans-melilotoside (4), 2-O-ß-glucosyloxy-4-methoxy trans-cinnamic acid (5)) were elucidated using advanced spectroscopic methods. Mushroom tyrosinase enzyme inhibition of extracts, fractions and pure compounds obtained from P. mahaleb kernels were investigated and structure-activity relationship revealed. According to a detailed, comprehensive and validated LC-MS/MS technique analysis, vanilic acid (41.407 mg/g), protocatechuic acid (8.992 mg/g) and ferulic acid (4.962 mg/g) in the kernel ethylacetate fraction; quinic acid (14.183 mg/g), fumaric acid (8.349 mg/g) and aconitic acid (5.574 mg/g) were found as major phenolic compounds in the water fraction. The correlation of trace element copper content in extracts and fractions with mushroom enzyme activity was determined. By examining the enzyme kinetics of the compounds with effective cinnamic acid derivatives, inhibition types and enzyme binding constants Ki were calculated. Compounds 1,3 and 5 exhibited high noncompetitive tyrosinase inhibitory activity against L-tyrosine substrates, with IC50 values of 0.22, 0.31 and 0.37 mM respectively. In addition compounds 1, 3 and 5 showed dose-dependent inhibitory effects on intracellular tyrosinase and melanin levels in α-melanocyte-stimulating hormone (α-MSH)-induced B16F10 melanoma cells. CONCLUSIONS: Potent tyrosinase inhibitory compounds and extracts of P. mahaleb kernels suggest that it could be a new, non-toxic and inexpensive resource for the cosmeceutical industry and in skin diseases associated with hyperpigmentation.

Hygromycin A derivatives isolated from Streptomyces sp. PC-22 in the rhizosphere soil of Pulsatilla chinensis.

On the basis of the one strain-many compounds (OSMAC) strategy, two new hygromycin A derivatives (3, 4), together with six known compounds were isolated from a medicinal plant inter rhizospheric Streptomyces in Pulsatilla chinensis. The structures of 3 and 4 were elucidated using NMR and HRESIMS analyses. A plausible biosynthetic pathway for these compounds was discussed. All the compounds were evaluated for their antimicrobial and cytotoxic activities. Compound 5 exhibited potent inhibitory activity against S. aureus and B. subtilis with the MICs of 16 and 8 µg ml-1, while 4 showed weak inhibitory activity against S. aureus.

Determination of Phenolic Compounds in Various Propolis Samples Collected from an African and an Asian Region and Their Impact on Antioxidant and Antibacterial Activities.

The biological activities of propolis samples are the result of many bioactive compounds present in the propolis. The aim of the present study was to determine the various chemical compounds of some selected propolis samples collected from Palestine and Morocco by the High-Performance Liquid Chromatography-Photodiode Array Detection (HPLC-PDA) method, as well as the antioxidant and antibacterial activities of this bee product. The chemical analysis of propolis samples by HPLC-PDA shows the cinnamic acid content in the Palestinian sample is higher compared to that in Moroccan propolis. The results of antioxidant activity demonstrated an important free radical scavenging activity (2,2-Diphenyl-1-picrylhydrazyl (DPPH); 2,2'-azino-bis 3-ethylbenzothiazoline-6-sulphonic acid (ABTS) and reducing power assays) with EC50 values ranging between 0.02 ± 0.001 and 0.14 ± 0.01 mg/mL. Additionally, all tested propolis samples possessed a moderate antibacterial activity against bacterial strains. Notably, Minimum Inhibitory Concentrations (MICs) values ranged from 0.31 to 2.50 mg/mL for Gram-negative bacterial strains and from 0.09 to 0.125 mg/mL for Gram-positive bacterial strains. The S2 sample from Morocco and the S4 sample from Palestine had the highest content of polyphenol level. Thus, the strong antioxidant and antibacterial properties were apparently due to the high total phenolic and flavone/flavonol contents in the samples. As a conclusion, the activities of propolis samples collected from both countries are similar, while the cinnamic acid in the Palestinian samples was more than that of the Moroccan samples.

Honey Phenolic Compound Profiling and Authenticity Assessment Using HRMS Targeted and Untargeted Metabolomics.

Honey consumption is attributed to potentially advantageous effects on human health due to its antioxidant capacity as well as anti-inflammatory and antimicrobial activity, which are mainly related to phenolic compound content. Phenolic compounds are secondary metabolites of plants, and their content in honey is primarily affected by the botanical and geographical origin. In this study, a high-resolution mass spectrometry (HRMS) method was applied to determine the phenolic profile of various honey matrices and investigate authenticity markers. A fruitful sample set was collected, including honey from 10 different botanical sources (n = 51) originating from Greece and Poland. Generic liquid-liquid extraction using ethyl acetate as the extractant was used to apply targeted and non-targeted workflows simultaneously. The method was fully validated according to the Eurachem guidelines, and it demonstrated high accuracy, precision, and sensitivity resulting in the detection of 11 target analytes in the samples. Suspect screening identified 16 bioactive compounds in at least one sample, with abscisic acid isomers being the most abundant in arbutus honey. Importantly, 10 markers related to honey geographical origin were revealed through non-targeted screening and the application of advanced chemometric tools. In conclusion, authenticity markers and discrimination patterns were emerged using targeted and non-targeted workflows, indicating the impact of this study on food authenticity and metabolomic fields.

Screening out the anti-insomnia components from Prunella vulgaris L. based on plasma pharmacochemistry combined with pharmacodynamic experiments and UPLC-MS/MS analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Prunella vulgaris L. (P. vulgaris) is a medicinal plant belonging to the Labiatae family, and its dried spikes is called as Xiakucao in China, which is a common traditional Chinese medicine with the activities of clearing the liver and expelling fire, improving eyesight, dispersing nodules and detumescence. Modern pharmacological studies have proved that P. vulgaris has various pharmacological activities such as immunomodulatory, antiviral, antibacterial and anti-insomnia activities. AIMS OF THIS REVIEW: P. vulgaris have been reported to have anti-insomnia effects. Nevertheless, the pharmacodynamic substance basis of this anti-insomnia effect is still unclear. The aim of this study was to identify the active components responsible for evoking the anti-insomnia effect of P. vulgaris and to evaluate its anti-insomnia effect. MATERIALS AND METHODS: In this study, we proposed a method combined with pharmacodynamic experiments, extraction and enrichment of chemical components, and the plasma pharmacochemistry to screen out the anti-insomnia components of P. vulgaris. Firstly, the active eluted fraction of the ethanol extract was screened out based on pharmacodynamic tracing method, and then the chemical composition was analyzed systematically by UPLC-MS/MS. Thirdly, pharmacodynamic tracing method and silica gel column chromatography were employed to screen out the active fraction of 70% ethanol eluted fraction, and its bioactive components in vitro and in vivo were identified by UPLC-MS/MS. Finally, screening out the anti-insomnia components of P. vulgaris by comparing the difference between in vivo and in vitro components, and three potentially bioactive ingredients were validated experimentally. RESULTS: It was confirmed that the fraction eluted with 70% ethanol from macroporous adsorption resin column was responsible for the anti-insomnia efficacy, and 55 compounds were identified or preliminarily identified. Then totally 9 compounds in vitro and 12 compounds in vivo from the active fraction of 70% ethanol eluted fraction were tentatively identified. Among them, mangiferin, rosmarinic acid and salviaflaside were the prototype components of P. vulgaris, which indicated that the three compounds might play the key role in the anti-insomnia activities. In vivo, compared to blank control group, the three compounds significantly shortened the sleeping latency and prolonged the sleeping time produced by pentobarbital sodium. CONCLUSIONS: This study clarified that mangiferin, rosmarinic acid and salviaflaside were considered as the anti-insomnia components of P. vulgaris. This is the first study on screening out the active ingredients responsible for evoking the anti-insomnia effect of P. vulgaris. The three compounds of P. vulgaris may help develop one or more drugs to prevent or treat insomnia. Further investigations are recommended to define the mechanism of the anti-insomnia activity of P. vulgaris.

Preparative separation of six compounds from Salvia yunnanensis Radix using pH-zone-refining counter-current chromatography.

Phenolic acids are the main active components in Salvia yunnanensis Radix, which have significant effects such as cardiovascular protection, anti-thrombosis, anti-oxidant, and anti-inflammation. In this study, pH-zone-refining counter-current chromatography (pH-ZRCCC) was successfully applied to the preparative separation of phenolic acids from S. yunnanensis Radix. First, a two-phase solvent system composed of Pet-EtOAc-ACN-H2 O (1.5:2.5:1:5, v/v) [TFA (10 mM) was added in the upper phase and NH3 ·H2 O (30 mM) was added in the lower phase] was used for the separation of 4.0 g of the crude sample to obtain 55.6 mg of rosmarinic acid (1), 69.0 mg of caffeic acid (2), 18.9 mg of protocatechualdehyde (3), 14.6 mg of 8-epiblechnic acid 9-methyl ester (4), and a mixture containing two compounds. After the recovery, 1.3 g of the mixture was obtained and separated using the MtBE-H2 O (1:1, v/v) solvent system containing TFA (5 mM) and NH3 ·H2 O (60 mM) to obtain 259.9 mg of salvianolic acid B (5) and 28.75 mg of lithospermic acid (6). Moreover, a systematic separation pattern for separating the relatively low-polarity phenolic acids from natural products by pH-ZRCCC was summarized for the first time. This study provided technical support for the pharmacological activity and quality control research of S. yunnanensis Radix.

The Contents of Polyphenols in Perilla frutescens (L.) Britton var. frutescens (Egoma) Leaves are Determined by Vegetative Stage, Spatial Leaf Position, and Timing of Harvesting during the Day.

The leaf of Perilla frutescens (L.) Britton var. frutescens (egoma) is a rich source of polyphenolic compounds, including rosmarinic acid. However, there is still a lack of detailed information concerning the content of phenolic compounds in these leaves. Since some flavonoids were found as a conjugated form, leaves were used untreated or hydrolyzed using ß-glucuronidase for analysis. Enzymatic hydrolysis method successfully identified some polyphenols, which have not been reported before. Scutellarin, a flavone glucuronide with a molecular mass similar to that of luteolin 7-O-glucuronide, was present in egoma leaves. Scutellarin was the second most abundant polyphenolic compound, after rosmarinic acid. Egoma leaves at the top of the plant contained a higher amount of rosmarinic acid and scutellarin compared to that in the leaves below. The difference in plant growth stage also influenced the rosmarinic acid and scutellarin contents, while the time of harvesting during the day did rosmarinic acid contents only. This is the first time that scutellarin, a traditional Chinese medicine, widely used for the treatment of cerebrovascular disease, was quantitatively determined in egoma leaves. The present study may help adding value to egoma leaves, developing dietary supplements, functional foods, and cosmetics.

Inhibition of MMP2-PEX by a novel ester of dihydroxy cinnamic and linoleic acid from the seagrass Cymodocea serrulata.

Matrix metalloproteinases (MMPs) are pivotal for cancer cell migration and metastasis which are generally over-expressed in such cell types. Many drugs targeting MMPs do so by binding to the conserved catalytic domains and thus exhibit poor selectivity due to domain-similarities with other proteases. We report herein the binding of a novel compound [3-(E-3,4-dihydroxycinnamaoyloxyl)-2-hydroxypropyl 9Z, 12Z-octadeca-9, 12-dienoate; Mol. wt: 516.67 Da], (C1), isolated from a seagrass, Cymodocea serrulata to the unconserved hemopexin-like (PEX) domain of MMP2 (- 9.258 kcal/mol). MD simulations for 25 ns, suggest stable ligand-target binding. In addition, C1 killed an ovarian cancer cell line, PA1 at IC50: 5.8 µM (lesser than Doxorubicin: 8.6 µM) and formed micronuclei, apoptotic bodies and nucleoplasmic bridges whilst causing DNA laddering, S and G2/M phase dual arrests and MMP disturbance, suggesting intrinsic apoptosis. The molecule increased mRNA transcripts of BAX and BAD and down-regulated cell survival genes, Bcl-xL, Bcl-2, MMP2 and MMP9. The chemical and structural details of C1 were deduced through FT-IR, GC-MS, ESI-MS, 1H and 13C NMR [both 1D and 2D] spectra.

Phytochemical profile and rosmarinic acid purification from two Peruvian Lepechinia Willd. species (Salviinae, Mentheae, Lamiaceae).

The phytochemical profile of Lepechinia meyenii (Walp.) Epling and Lepechina floribunda (Benth.) Epling obtained by liquid chromatography associated with high-resolution mass spectrometry is presented. Forty eight compounds were detected exhibiting a variety of salvianolic acids and abietane phenolic diterpenoids. A simple procedure by cold evaporative crystallization to purify rosmarinic acid from these botanical species was also shown.

Bioactivity-guided separation of potential α-glycosidase inhibitor from clerodendranthus spicatus based on HSCCC coupled with molecular docking.

Clerodendranthus Spicatus is a traditional Dais medi-edible plant and it has been proven to have good blood glucose-lowering efficacy. However, the material basis of Clerodendranthus Spicatus has not been clarified yet and therefore needs to be determined. In this paper, the effective ingredients of this medicine were purified by high-speed counter-current chromatography. Alongside, their potential hypoglycemic activity was determined by α-glucosidase inhibitory activities in vitro and molecular docking. Finally, five compounds were purified and identified as 2-caffeoyl-L-tartaric acid (1), N-(E)-caffeoyldopamine (2), rosmarinc acid (3), methyl rosmarinate (4), 6,7,8,3',4'-Pentamethoxyflavone (5). Examination of α-glucosidase inhibitory activity in vitro showed that 2-caffeoyl-L-tartaric acid and rosmarinic acid had a higher inhibitory activity than acarbose. Molecular docking indicated that the affinity energy of the identified compounds ranged from - 7.6 to - 8.6 kcal/mol, a more desirable result than acarbose (- 6.6 kcal/mol). Particularly, rosmarinc acid with the lowest affinity energy of - 8.6 kcal/mol was wrapped with 6 hydrogen bonds. Overall, α-glucosidase inhibitory activities and molecular docking suggested that rosmarinc acid was likely to be a promising hypoglycemic drug.

Studies on Adsorption Kinetics and Thermodynamics of Macroporous Resin for Rosmarinic Acid.

This experiment treated perilla seeds with different concentrations of NaCl solution to enrich and purify their rosmarinic acid (RosA). The results showed that low concentrations of salt (0-20 mmol/L) promoted seed germination, while high concentrations (> 20 mmol/L) inhibited germination. When the salt concentration was 20 mmol/L, the germination rate was the highest. The content of RosA in germinated perilla seeds was 3.5 mg/g, which was 3.5 times as much as that in the seeds without germination. The RosA was purified using NK-109 macroporous resin and its adsorption kinetics, isotherms and thermodynamics were determined. The adsorption kinetics showed that the adsorption behavior of RosA in NK-109 resin conformed to the pseudo-second-order kinetic model. The model for RosA in the NK-109 resin exhibited Langmuir adsorption based on a spontaneous exothermic process according to its adsorption thermodynamics, which included both physical and chemical adsorption. The optimized process conditions were as follows: the loading concentration of 0.04 mg/mL, loading volume of 40 mL, 70% methanol as the eluent with the volume of 60 mL, and the purity of RosA was 42.1%.

Study of the Cluster Thinning Grape as a Source of Phenolic Compounds and Evaluation of Its Antioxidant Potential.

Thinning is a common viticulture practice in warm climates, and it is applied to increase the quality of the harvest. Thinning clusters are usually discarded, and they are considered another oenological industry waste. To valorize this by-product, the phenolic content and antioxidant activity of three red varieties (Tempranillo, Cabernet Sauvignon, and Syrah), thinned at three different times between veraison and harvest, were studied: the first at the beginning of the veraison stage, in a low ripening stage; the second in an intermediate ripening stage; and, finally, the third sampling in the highest ripening stage. These by-products showed high values of total phenolic contents (10.66-11.75 mg gallic acid equivalent/g), which is of the same order as or even higher than that found in grape pomace. In thinned grape were identified 24 phenolic compounds, being the flavan-3-ols (catechin and epicatechin) of particular interest, with mean contents ranging from 105.1 to 516.4 mg/kg of thinned grape. Antioxidant activity similar to that of the vintage grape was found. It is concluded that thinned grape is a good source of phenolic compounds. Its content does not depend mainly on the grape variety; however, it has been possible to establish differences based on the maturity stage of the thinning grapes: the intermediate ripeness stage, with a Brix degree in the range of 15-16 for this area, would be the optimum collection time for cluster thinning. In this intermediate ripeness stage, thinning grapes present a higher antioxidant activity and there is also appreciable anthocyanin content, which is not found for the lowest ripeness stage, since these samples present an intermediate composition in all the families of determined phenolic compounds: anthocyanins, flavonols, flavan-3-ols, cinnamic acids, and benzoic acids. It is important to note that the experiments in this study have been carried out with whole tinned grapes, without separating the skin or the seeds.

Lapathoside A Isolated from Fagopyrum esculentum Induces Apoptosis in Human Pancreatic Cancer Cells.

BACKGROUND/AIM: Lapathoside A, a phenylpropanoid ester, was isolated from the roots of buckwheat by searching for bioactive compounds against human pancreatic cancer cells. MATERIALS AND METHODS: Buckwheat root extracts, prepared by 70% ethanol, were separated into n-hexane, methylene chloride, ethyl acetate, n-butanol, and water fraction by solvent partitioning. Seven fractions were obtained from the ethyl acetate fraction by liquid chromatography, and fraction No. 6 contained lapathoside A. The effects of lapathoside A on Panc-1 and SNU-213 human pancreatic cancer cell lines were examined. RESULTS: The structure of lapathoside A was determined by liquid chromatography-mass spectrometry, liquid chromatography-tandem mass spectrometry, and nuclear magnetic resonance analysis. Next, we investigated whether lapathoside A has anticancer activity in human pancreatic cancer cell lines (PANC-1 and SNU-213). After treatment with 25 µM lapathoside A, viability of PANC-1 and SNU-213 cells decreased to about 40 and 27%, respectively. In addition, lapathoside A treatment also increased apoptosis while affecting the expression levels of apoptotic proteins. CONCLUSION: The effect of lapathoside A on apoptosis was confirmed in pancreatic cancer cell lines, supporting the application of lapathoside A in the treatment of pancreatic cancer.

Sequential extraction of carnosic acid, rosmarinic acid and pigments (carotenoids and chlorophylls) from Rosemary by online supercritical fluid extraction-supercritical fluid chromatography.

A high degree of selectivity is required during the plant extraction process in order to obtain extracts enriched in specific compounds or to avoid the extraction of unwanted ones. Rosemary is well known for its antioxidant compounds (carnosic acid, carnosol and rosmarinic acid). The plant also contains pigments (i.e. carotenoids, chlorophylls) which may cause a colour problem during the use of the extract in cosmetic formulations, for example. Supercritical fluid extraction is considered as a selective technique for plant extraction. Due to the physico-chemical properties of supercritical fluids, related to pressure, temperature and modifier addition, it is possible to carry out sequential extraction with successive conditions to collect different fractions that are rich either in pigments or in bioactive compounds. The aim of this study was to selectively extract bioactive compounds (i.e. carnosic acid and rosmarinic acid) and pigments (carotenoids and chlorophylls) from rosemary using supercritical fluid extraction. The optimisation of the extraction method was carried out using supercritical fluid extraction online coupled with a supercritical fluid chromatography (SFE-SFC) system. Two columns of different polarities were coupled to achieve the separation of the targeted compounds every five minutes during the extraction. Four fractions were obtained: a first one rich in carotenoids obtained with pure CO2 (25°C and 20 MPa), a second rich in carnosic acid obtained with 3% polar modifier (EtOH:water 50/50 v/v), a third fraction rich in rosmarinic acid using 10% of the same modifier and a fourth fraction rich in chlorophylls with 30% of ethanol as modifier. These four samples were then analysed by UHPLC-DAD-ESI-QTOF-HRMS in order to identify other extracted compounds and to study how the selected conditions impacted their extraction.

Two new glucoside derivatives of truxinic and cinnamic acids from Lavandula angustifolia mill.

A phytochemical investigations on the n-butanol fraction of Lavandula angustifolia Mill. residues resulted in the isolation of ten compounds, including two new ones, 4,4'dimethoxy-2,2'di-O-ß-d-glucopyranosyl-truxinate (1) and 2-(ß-d-glucosyloxy)-trans-cinnamic acid butyl ester (2), along with eight known compounds. The structures of compounds were confirmed by NMR and HR-ESI-MS techniques and comparison with published data. The NMR data for 3 were attributed for the first time. Compound 2 was proofed to be a natural compound in plant rather than a butyl ester artifact formed by esterification reaction with butanol by comparative HPLC-DAD analysis with the ethanol extract which was obtained prior to the application of butanol. All isolated compounds were evaluated for their antioxidant and anti-hypoglycaemic activities. Among them, compounds 4 and 5 showed strong anti-oxidant activities against DPPH with IC50 values of 12.99 and 31.74 µM, respectively. Compound 5 exhibited moderate inhibitory activity against PTP1B with an IC50 value of 31.28 µM.

Hepatoprotective activity assessment of amino acids derivatives of picroside I and II.

Picrorhiza kurroa has a long medicinal history as a traditional medicinal plant in China and India that is widely used in clinical treatments. It is a common treatment for liver diseases, fever, diarrhoea, indigestion, and some other diseases. Modern pharmacological studies proved that P. kurroa rhizomes have high levels of picroside I and II, which were identified as main constituents with anti-inflammatory and hepatoprotective activities. In our study, we used picroside I and II as the lead compounds to generate derivatives by reactions with Boc-valine or Boc-proline, which underwent dehydration and condensation with the hydroxyl groups in the lead compounds in the presence of coupling reagent N,N'-dicyclohexylcarbodiimide. We synthesized 11 derivatives and examined their hepatoprotective effects in vitro by assessing the proliferation rates of H2 O2 -exposed HepG2 cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. We found that some derivatives promoted higher proliferation rates in HepG2 cells than the natural compounds before derivatization, suggesting that those derivatives possessed an improved hepatoprotective capacity. The novel derivatization strategy for picrosides had the additional benefit that the esterification of their hydroxyl groups created derivatives not only with increased stability but also with improved pharmacokinetic properties and potentially prolonged half-life.

Molecularly imprinted polymers for selective extraction of rosmarinic acid from Rosmarinus officinalis L.

This study provides a robust and reproducible approach for selective extraction of rosmarinic acid (RA) using molecularly imprinted polymers (MIPs). Computational modeling and UV spectroscopic analysis were performed to optimize MIP synthesis. Consequently, six different bulk and surface imprinted polymers were generated using RA as the template. Binding performance of the imprinted polymers was evaluated using static equilibrium and complementary dynamic rebinding experiments. Despite the high selectivity of thus generated surface imprinted polymers, the corresponding bulk polymers exhibited better binding performance when serving as sorbents during solid phase extraction (SPE). An optimized molecularly imprinted solid phase extraction (MISPE) protocol was developed in respect to loaded amount of RA, composition of the loading solution, washing solvent, and elution volume. Thereby, a remarkably selective extraction of RA from real-world Rosmarinus officinalis L. extract with a recovery rate and purity of 81.96 ± 6.33% and 80.59 ± 0.30%, respectively, was achieved.

Antidiabetic Effects and Mechanisms of Rosemary (Rosmarinus officinalis L.) and its Phenolic Components.

Diabetes mellitus is a chronic endocrine disease result from absolute or relative insulin secretion deficiency, insulin resistance, or both, and has become a major and growing public healthy menace worldwide. Currently, clinical antidiabetic drugs still have some limitations in efficacy and safety such as gastrointestinal side effects, hypoglycemia, or weight gain. Rosmarinus officinalis is an aromatic evergreen shrub used as a food additive and medicine, which has been extensively used to treat hyperglycemia, atherosclerosis, hypertension, and diabetic wounds. A great deal of pharmacological research showed that rosemary extract and its phenolic constituents, especially carnosic acid, rosmarinic acid, and carnosol, could significantly improve diabetes mellitus by regulating glucose metabolism, lipid metabolism, anti-inflammation, and anti-oxidation, exhibiting extremely high research value. Therefore, this review summarizes the pharmacological effects and underlying mechanisms of rosemary extract and its primary phenolic constituents on diabetes and relative complications both in vitro and in vivo studies from 2000 to 2020, to provide some scientific evidence and research ideas for its clinical application.