Nitrogenous compounds from Aesculus wilsonii seeds.

Eight nitrogenous compounds including five undescribed ones, aeswilnitrousol A (1), aeswilnitrousosides BD (2-4), and 6-(2-hydroxy-3-methylbutylamino)-8-oxoadenine (5) were isolated from the seeds of Aesculus wilsonii. Their structures and absolute configurations were established based on spectroscopic determination, calculated electronic circular dichroism (ECD) analysis, as well as chemical reaction methods. Among the three known compounds, 7 and 8 were obtained from the Aesculus genus for the first time, and 6 was gained from this plant initially. The 13C NMR data of 7 and 8 were reported for the first time. Moreover, the inhibitory effect of all the isolates against LPS-induced nitric oxide production in RAW264.7 macrophages was evaluated. As a result, compounds 2 and 8 exhibited anti-inflammatory activity in a concentration-dependent manner at 10, 25, and 50 µM.

Aromatic compounds from the seeds of Dolichos lablab L. with anti-inflammatory activity.

Twenty-four aromatic compounds including five novel ones, dolilabphenosides A (1), B1 (2), B2 (3), C1 (4), and C2 (5) were obtained from the seeds of Dolichos lablab L. Their structures were established based on spectroscopic analyses and chemical reactions. Among the known compounds, 9, 10, 14, 17, 19, and 22-24 were gained from the family Leguminosae for the first time, and 6, 8, 11-13, 15, 16, 18, 20, as well as 21 were firstly identified from Dolichos genus. Moreover, the inhibitory effect evaluation of all the isolates against LPS-induced nitric oxide (NO) production in RAW264.7 macrophages suggested that compounds 1-3, 6, 7, 11-15, 17, 20, 21, 23, 24 exhibited anti-inflammatory activity in a concentration-dependent manner. Moreover, the novel compounds, dolilabphenosides A (1), B1 (2), B2 (3) were found to inhibit the secretion of inflammatory cytokine IL-1ß.

Bioactive triterpenes of jujube in the prevention of colorectal cancer and their molecular mechanism research.

BACKGROUND: Jujube, a popular fruit from the Rhamnaceae family, relieves colorectal inflammation caused by spleen deficiency and has been used in many formulas in clinical for decades to treat colorectal cancer (CRC). As of yet, the therapeutic substances and mechanism of their action are unknown. PURPOSE: The purpose of this study is to define the therapeutic substances of jujube and its mechanism of action in treating CRC. METHODS: The pharmacological effects of jujube extract and its fractions were evaluated in vivo using a CRC mouse model induced by AOM/DSS. The DAI value, colon length, mortality, tumor burden, and histological tumor size of the treated animals were compared. To explore the potential therapeutic substances, LC-MS analysis was conducted to characterize the serum migration components. A network pharmacology experiment was carried out for potential molecular targets. To verify the therapeutic substances as well as the molecular mechanism of jujube intervening CRC, cellular MTT assay of the serum migration components, Western blot and IHC tests were conducted. RESULTS: The in vivo pharmacological studies showed that compared to AOM/DSS treated mice, the mortality and DAI value, tumor burden, and histological tumor size of jujube extract and its fat-soluble fraction (mainly contained triterpenes) treated mice were significantly reduced, and their colon lengths were obviously longer than AOM/DSS treated mice. The targeted-LC/MS analysis supposed triterpenes 3, 7, 9, 11, 12, 14, 17 - 21, and 25 - 28 to be the serum migration components, which might be the potential therapeutic substances. In the network pharmacology experiment, the GO annotation and enrichment analysis of the KEGG pathway indicated that PI3K-Akt pathway and inflammatory reaction were important factors for jujube inhibiting CRC. Cellular MTT assay of serum migration components indicated that the potential effective substances from fat-soluble fraction to be triterpenes 3, 7, 17, 19, 20, and 25. The Western blot and IHC assays implied that the jujube extract, its fat-soluble fraction, and triterpenes 7, 17, and 20 showed inhibition on the expression of PI3K/Akt/NF-κB signaling pathway-related proteins. Additionally, it was noted in the pharmacodynamic experiment that ZJL's effectiveness was more apparent than ZJH and SQL in tumor burden rate, colon length, and spleen weight, which indicated that the efficacy of ZJ is contributed from CD and SQ, and they may have a synergistic effect on anti-CRC. CONCLUSION: These results for the first time provide evidence that jujube triterpenes possess an anti-CRC effect, their mechanism was involving the control of the PI3K/Akt/NF-κB signaling pathway. What's more, the potential synergistic effect of the fat-soluble and water-soluble components found in this study provided a solid foundation for our deep understanding of how jujube can ameliorate CRC.

Targeting autophagy in atherosclerosis: Advances and therapeutic potential of natural bioactive compounds from herbal medicines and natural products.

Atherosclerosis (AS) is the most common causes of cardiovascular disease characterized by the formation of atherosclerotic plaques in the arterial wall, and it has become a dominant public health problem that seriously threaten people worldwide. Autophagy is a cellular self-catabolism process, which is critical to protect cellular homeostasis against harmful conditions. Emerging evidence suggest that dysregulated autophagy is involved in the development of AS. Therefore, pharmacological interventions have been developed to inhibit the AS via autophagy induction. Among various AS treating methods, herbal medicines and natural products have been applied as effective complementary and alternative medicines to ameliorate AS and its associated cardiovascular disease. Recently, mounting evidence revealed that natural bioactive compounds from herbs and natural products could induce autophagy to suppress the occurrence and development of AS, by promoting cholesterol efflux, reducing plaque inflammation, and inhibiting apoptosis or senescence. In the present review, we highlight recent findings regarding possible effects and molecular mechanism of natural compounds in autophagy-targeted mitigation of atherosclerosis, aiming to provide new potential therapeutic strategies for the atherosclerosis treatment preclinically and clinically.

The phenolic acids from Oplopanax elatus Nakai stems and their potential photo-damage prevention activity.

25 phenolic acids, including four new isolates, eurylophenosides A-D (1-4) and 21 known ones (5-25) were isolated and identified from the stems of Oplopanax elatus Nakai. Among the known compounds 5-9, 11-13, 16, 18-25 were isolated from the genus for the first time; 17 was first obtained from the plant; and the NMR data of 22 was reported here first. Meanwhile, the UVB-induced photodamage model of HaCaT cells was used to study the prevent-photodamage abilities of compounds 1-2, 4-8, 11-13 and 15-25 with a nontoxic concentration at 50 µM. Moreover, a dose-dependent experiment was conducted for active compounds at the concentration of 10, 25, and 50 µM, respectively. Consequently, pretreatment with compounds 1, 16, 17, 19, 20, 22, 24 and 25 could suppress the cell viability decreasing induced by UVB irradiation in a concentration-dependent manner. These results indicated that phenolic acids were one kind of material basis with prevent-photodamage activity of O. elatus.

Constituents of Morus alba var. multicaulis leaf improve lipid metabolism by activating the AMPK signaling pathway in HepG2 cells.

One new compound, 3Z-1-O-ß-D-glucopyranosyl-3-hexene-1,5-diol (1), together with 26 known isolates (2-27) were obtained from the leaf of Morus alba var. multicaulis. Among the known compounds, 7, 11, 12, 14, 15, 18, 19, 23, and 24 were firstly obtained from the Morus genus; 2-5, 8, 10, 13, and 20 were firstly isolated from M. alba. var. multlcaulis. Meanwhile, the NMR data of 20 and 23 have been reported here for the first time. Moreover, compounds 1-11, 13, 21, and 23-27 showed inhibitory effects on triglyceride (TG) accumulation in HepG2 cells. In mechanism, compound 1 could activate the phosphorylation of AMP-activated protein kinase α (AMPKα) to accelerate the ß-oxidation of fatty acids via promoting the phosphorylation of acetyl-CoA carboxylase 1 and up-regulating carnitine palmitoyl-transferase 1A. Besides, compound 1 exerted lipolysis effect by activating hormone-sensitive lipase. In brief, compound 1 might play a role by up-regulating phosphorylation of AMPKα, enhancing the fatty acid ß-oxidation and lipolysis. 27 compounds were obtained from the leaf of Morus alba var. multicaulis. Among them, 18 showed inhibitory effects on TG accumulation in HepG2 cells. Moreover, the new compound, 3Z-1-O-ß-D-glucopyranosyl-3-hexene-1,5-diol (1), was found to play a role by up-regulating phosphorylation of AMPKα, enhancing the fatty acids ß-oxidation and lipolysis.

Bioactive flavonoids and stilbenes from the leaf of Morus alba var. multicaulis.

Twenty-two flavonoids and stilbenes (1-22) were obtained from the leaf of Morus alba var. multicaulis. Among them, morusalbanosides A (1), B1 (2), and B2 (3) were new compounds. Moreover, compounds 1, 3, 4-11, 15-18, and 22 displayed inhibitory effects on triglyceride (TG) accumulation in HepG2 cells in a concentration dependent manner. Furthermore, compounds 1, 3, 11, and 22 could activate the phosphorylation of AMP-activated protein kinase α (AMPKα), reduce the synthesis of TG by inhibiting the expression of fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD1). While, only compounds 1 and 11 could promote the phosphorylation of acetyl-CoA carboxylase 1 (ACC1) and accelerate the oxidation of fatty acids by up-regulating carnitine palmitoyltransferase 1A (CPT1A). In brief, this study found that most of the researched flavonoids and stilbenes could regulate TG metabolism in vitro. They might play the role by up-regulating phosphorylation of AMPKα, inhibiting TG biosynthesis, and promoting the oxidation of fatty acids.

Structurally diverse triterpenes obtained from the fruits of Ziziphus jujuba Mill. as inflammation inhibitors by NF-κB signaling pathway.

Twenty-nine triterpenes were obtained from the fruits of Ziziphus jujuba Mill. through various chromatography methods, and their stereo-structures were confirmed by spectroscopic methods. Among them, 2α,3ß,20-trihydroxylupane-28-oic acid (1) was identified as a new compound, and the 1H and 13C NMR data of 7, 8 and 23, as well as the 13C NMR data of 17 are reported here for the first time. Meanwhile, the nitric oxide (NO) inhibitory activities of all compounds were examined in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. As results, compounds 2, 7, 10-13, 15, 16, 18-21, 26-29 were found to play important roles in suppressing NO production at 5 µM. The structure-activity relationships (SARs) on NO inhibition indicated that the ursolic and oleanolic acid skeletons, p-coumaroyl group substitution, six-membered A ring, and deoxygenation (loss of C[double bond, length as m-dash]O) in the C ring showed a more positive effect on the NO inhibitory activity of triterpenes, while the reduction of the A ring C[double bond, length as m-dash]O to OH was a negative factor. Moreover, it was found that compounds 15 and 19 could suppress the phosphorylation of IκBα and NF-κB/p65 to prevent it from shifting into the nucleus and downregulate the expression of inflammatory factors, such as iNOS, IL-6 and TNF-α. Our investigations revealed that the NO inhibitory effects of the active triterpenes obtained from Z. jujuba were mediated, at least in part, through the NF-κB signaling pathway.

Identification and Structural Analysis of Spirostanol Saponin from Yucca schidigera by Integrating Silica Gel Column Chromatography and Liquid Chromatography/Mass Spectrometry Analysis.

Yucca schidigera Roezl (Mojave), a kind of ornamental plant belonging to the Yucca genus (Agavaceae), whose extract exhibits important roles in food, beverage, cosmetic and feed additives owing to its rich spirostanol saponins. To provide a comprehensive chemical profiling of the spirostanol saponins in it, this study was performed by using a multi-phase liquid chromatography method combining a reversed phase chromatography T3 column with a normal phase chromatography silica column for the separation and an ESI-Q-Exactive-Orbitrap MS in positive ion mode as the detector. By comparing the retention time and ion fragments with standards, thirty-one spirostanol saponins were identified. In addition, according to the summary of the chromatographic retention behaviors and the MS/MS cleavage patterns and biosynthetic pathway, another seventy-nine spirostanol saponins were speculatively identified, forty ones of which were potentially new ones. Moreover, ten novel spirostanol saponins (three pairs of (25R/S)-spirostanol saponin isomer mixtures) were targeted for isolation to verify the speculation. Then, the comprehensive chemical profiling of spirostanol saponins from Y. schidigera was reported here firstly.

Anti-inflammatory canthin-6-one alkaloids from the roots of Thailand Eurycoma longifolia Jack.

Two new canthin-6-one alkaloids, 4,9-dimethoxy-5-hydroxycanthin-6-one (1) and 9-methoxy-(R/S)-5-(1-hydroxyethyl)-canthin-6-one (2), together with fifteen known ones were isolated from the roots of Thailand Eurycoma longifolia Jack. Among the known canthin-6-one alkaloids, compounds 9 and 16 were isolated from the Eurycoma genus for the first time. Meanwhile, the nitric oxide (NO) inhibitory activities of all isolates were examined in lipopolysaccharide (LPS)-stimulated RAW264.7 cells at 50 µM. Moreover, a dose-dependent experiment was conducted for active compounds 1, 2, 4, 6, 7, 10, 12-17 at the concentration of 10, 25, and 50 µM, respectively. Consequently, compounds 1, 4, 6, 7, 12, 14, 15, as well as 17 were found to inhibit NO release from RAW264.7 cells in a dose-dependent manner. Two new canthin-6-one alkaloids, 4,9-dimethoxy-5-hydroxycanthin-6-one (1) and 9-methoxy-(R/S)-5-(1-hydroxyethyl)-canthin-6-one (2), together with fifteen known ones were isolated from the roots of Thailand Eurycoma longifolia Jack. Among them, 1, 4, 6, 7, 12, 14, 15, as well as 17 were found to inhibit NO release from RAW264.7 cells in a dose-dependent manner at the concentration of 10, 25, and 50 µM.

Correction to: The structure-activity relationship review of the main bioactive constituents of Morus genus plants.

The article The structure-activity relationship review of the main bioactive constituents of Morus genus plants, written by Jiejing Yan, Jingya Ruan, Peijian Huang, Fan Sun, Dandan Zheng, Yi Zhang and Tao Wang was originally published Online First without Open Access.

Phytochemistry and Comprehensive Chemical Profiling Study of Flavonoids and Phenolic Acids in the Aerial Parts of Allium Mongolicum Regel and Their Intestinal Motility Evaluation.

To clarify whether flavonoids and phenols in Allium mongolicum Regel have the effect of improving gastrointestinal function and analyze its quality, this study was designed to isolate and identify them from the aerial parts of A. mongolicum by using various chromatographic and spectrophotometric methods, a bioassay on motility of mouse isolated intestine tissue, as well as qualitative analysis using liquid chromatography/mass spectrometry (LC-MS) analysis. As a result, 31 flavonoids and phenolic acids were obtained and identified, including six new flavonoid glycosides, mongoflavonosides A1 (1), A2 (2), A3 (3), A4 (4), B1 (5), B2 (6), and four new phenolic acid glycosides, mongophenosides A1 (7), A2 (8), A3 (9), B (10). Among them, eleven flavonoids and three phenolic acids showed significant increase in the height of mouse small intestinal muscle. It was a first systematic bioactive constituents' study for A. mongolicum on gastrointestinal tract. Furthermore, according to the retention time (tR) and the exact mass-to-charge ratio (m/z), thirty-one compounds were unambiguously identified by comparing to the standard references by using LC-MS. Then, on the basis of generalized rules of MS/MS fragmentation pattern, chromatographic behaviors, as well as biosynthetic laws of the 31 isolates, five flavonoid glycosides and one phenolic acid glycoside were tentatively speculated. On the basis of the study, a fast analysis method for flavonoids and phenolic acids in A. mongolicum was established.

NMR and MS data for novel bioactive constituents from Pugionium cornutum L. Gaertn.

The data presented in this article are associated with the research article entitled "Bioactive Constituents Study of Pugionium cornutum L. Gaertn on Intestinal Motility" [1]. The aim of this data was to provide the 1D, 2D NMR and MS spectrum of novel bioactive compounds from P. cornutum.

The structure-activity relationship review of the main bioactive constituents of Morus genus plants.

Morus genus plants are mainly distributed in the temperate to tropical areas over the world and include 17 species and two subspecies. Due to their excellent pharmacological activity, security in food additives and high value in the national economy, Morus genus plants have drawn more and more attention in recent years. In the light of the references published over the last few decades, flavonoids, benzofurans, stilbenes, and Diels-Alder adducts have been reported to be the main bioactive constituents of Morus genus plants. This review summarizes the compounds with excellent bioactivities isolated from Morus genus plants as well as their structure-activity relationships (SARs), which might be useful for the further research and development of Morus genus plants. The aromatic heterocycles with excellent bioactivities isolated from Morus genus plants as well as their structure-activity relationships (SARs) were summarized.

Isoprenoids obtained from Cortex Dictamni and their nitric oxide inhibitory activities.

Nine new isoprenoids, named as dictamtrinor-guaianols A (1), B (2), C (3), D (4), and E (5), dictamnorsesquiterpenol A (6), dictamnorsesquiterpenosides B (7) and C (8), as well as dictamtriterpenol A (9), along with eight known compounds (10-17) were obtained from 70% EtOH extract of Cortex Dictamni. Their structures were ascertained based on the extensive spectroscopic methods and ECD data analysis. Moreover, LC-MS analysis result suggested compounds 2 and 3 were natural products. Furthermore, lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage model were used to evaluate nitric oxide production inhibitory activities of them, and compounds 2, 3, 5, 6, 8-11, as well as 15-17 displayed significant activities at 40 µM.

Bioactive constituents study of Pugionium cornutum L. Gaertn on intestinal motility.

Thirty-one compounds were obtained and identified from the dried roots of Mongolian medicinal and edible plant, Pugionium cornutum L. Gaertn. Eight of them were new ones, and named as pugcornols A (1), B (2), C (3), and D (4), pugcornosides A (5), B (6), C (7), and D (8), respectively. Among them, 1-4 were rare naturally occurring thiohydantoin derivatives. Meanwhile, all the isolates were determined for their activities on isolated mice jejunum contraction, and ten of them increased height of the spontaneous contractions. Moreover, we partly clarified the mechanism of 5-(methylsulfinyl)-pentanenitrile (9), a characteristic compound in P. cornutum by using different kinds of inhibitor.

Comprehensive Chemical Profiling in the Ethanol Extract of Pluchea indica Aerial Parts by Liquid Chromatography/Mass Spectrometry Analysis of Its Silica Gel Column Chromatography Fractions.

Pluchea indica Less. is a medicine and food dual-use plant, which belongs to the Pluchea genus, Asteraceae family. Its main constituents are quinic acids, flavonoids, thiophenes, phenolic acids, as well as sesquiterpenes. In order to provide a comprehensive chemical profiling of P. indica, an orthogonal chromatography combining reverse-phase chromatography BEHC18 column with a normal-phase chromatography silica column as the separation system and a ESI-Q-Orbitrap MS as the detector in both positive and negative ion modes were used. According to the retention time (tR) and the exact mass-to-charge ratio (m/z), 67 compounds were unambiguously identified by comparing to the standard references. Moreover, 47 compounds were tentatively speculated on the basis of the rules of MS/MS fragmentation pattern and chromatographic elution order generalized from the above-mentioned reference standards. Among them, 10 of them were potentially novel.

Effects of Benzophenones from Mango Leaves on Lipid Metabolism.

The mango tree (Mangifera indica L.) is a tropical, perennial, woody evergreen plant belonging to the Anacardiaceae. In traditional medicine, dried mango tree leaves were considered useful in treating diabetes and respiratory infections. In this paper, we review the phytochemical research on mango leaves and the mechanisms of benzophenones in lipid metabolism regulation. Thirty-six benzophenones have been isolated from mango leaves; among them, mangiferin is the major compound. Structure-activity relationships of benzophenones in lipid accumulation and the mechanisms of action of mangiferin in lipid metabolism are summarized. After oral administration, mangiferin is partly converted to its active metabolite, northyariol, which contributes to the activation of sirtuin-1 and liver kinase B1 and increases the intracellular AMP level and AMP/adenosine triphosphate ratio, followed by AMP-activated protein kinase phosphorylation, leading to increased phosphorylation of sterol regulatory element-binding protein-1c. Current evidence supports ethnopharmacological uses of mango leaves in diabetes and points toward potential future applications.

Anti-inflammatory constituents from Cortex Dictamni.

Eight new compounds named as dictamalkosides A (1), B (2), C (3), dictamphenosides A (4), B (5), C (6), D (7) and E (8), as well as 23 known ones were obtained from the 70% EtOH extract of Cortex Dictamni. Their structures were ascertained based on the spectroscopic evidences. Among the known compounds, 14, 17-23, 25-28, and 31 were isolated from Dictamnus genus for the first time; 16 and 24 were firstly isolated from this plant. And the 13C NMR data of 14 was reported here for the first time. Moreover, compounds 1-8, 12, 18-21, 27 and 31 were found to exhibit potential inhibitory effect on LPS-induced NO production at 40 µM for RAW 264.7 macrophages, which suggested alkaloids and phenolic acids might be anti-inflammation therapeutic substance in Cortex Dictamni.

Bioactive constituents obtained from the fruits of Citrus aurantium.

Three new compounds, citrusauranosides A (1), B (2), and C (3), along with 22 known compounds (4-25) were obtained from the 70% ethanol-water extract of the fruits of Citrus aurantium L.. Their structures were identified by spectroscopic methods. Among the known compounds, 14, 15, 17 and 23 were firstly obtained from Citrus genus, and the NMR data of 17 is reported here for the first time. Moreover, inhibitory effects of all compounds on motility of mouse isolated intestine tissue were determined. As a result, 1, 4-8, and 11 displayed significant inhibitory effects on contraction tension.