Choline Dehydrogenase Contributes to Salt Tolerance in Dunaliella through Betaine Synthesis.

In Dunaliella tertiolecta, a microalga renowned for its extraordinary tolerance to high salinity levels up to 4.5 M NaCl, the mechanisms underlying its stress response have largely remained a mystery. In a groundbreaking discovery, this study identifies a choline dehydrogenase enzyme, termed DtCHDH, capable of converting choline to betaine aldehyde. Remarkably, this is the first identification of such an enzyme not just in D. tertiolecta but across the entire Chlorophyta. A 3D model of DtCHDH was constructed, and molecular docking with choline was performed, revealing a potential binding site for the substrate. The enzyme was heterologously expressed in E. coli Rosetta (DE3) and subsequently purified, achieving enzyme activity of 672.2 U/mg. To elucidate the role of DtCHDH in the salt tolerance of D. tertiolecta, RNAi was employed to knock down DtCHDH gene expression. The results indicated that the Ri-12 strain exhibited compromised growth under both high and low salt conditions, along with consistent levels of DtCHDH gene expression and betaine content. Additionally, fatty acid analysis indicated that DtCHDH might also be a FAPs enzyme, catalyzing reactions with decarboxylase activity. This study not only illuminates the role of choline metabolism in D. tertiolecta's adaptation to high salinity but also identifies a novel target for enhancing the NaCl tolerance of microalgae in biotechnological applications.

Sedative and hypnotic effects of Polygala tenuifolia willd. saponins on insomnia mice and their targets.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygala tenuifolia Willd. has been widely used in the treatment of cancer, forgetfulness, depression and other diseases. AIM OF REVIEW: The purpose of this study was to investigate the sleep-enhancing effect and mechanism of P. tenuifolia saponins (PTS). MATERIALS AND METHODS: The total saponin (YZ-I) and purified saponin (YZ-II) fractions were extracted and ICR mice model of insomnia was established by p-chlorophenylalanine (PCPA) induction to observe anxiety and depression behaviors. Effects of YZ-I and YZ-II on the levels of neurotransmitters, hormones, and inflammation cytokines were detected by ELISA, RT-qPCR and western blotting. RESULTS: The results showed that YZ-I and YZ-II reduced the immobility time of mice and prolonged the sleep time of mice and significantly increased the concentrations of 5-HT, NE, PGD2, IL-1ß and TNF-α. YZ-I and YZ-II regulated GABAARα2, GABAARα3, GAD65/67, 5-HT1A and 5-HT2A, while regulated the levels of inflammatory cytokines such as DPR, PGD2, iNOS and TNF-α to exert sedative and hypnotic effects. CONCLUSION: PTS are mainly achieved sedative and hypnotic effects by altering serotonergic, GABAergic and immune systems, but the effects and mechanisms of action of YZ-I were different from YZ-II.

The Hypoglycemic Activities and Underlying Mechanisms of Two Saponins-Rich Components from Fried Ziziphus jujuba Mill. Kernel.

SCOPE: Dried Ziziphus jujuba Mill. kernel is a potential natural source of nutraceutical and therapeutic agents in China. Recent researches have shown that the saponins of dried Z. jujuba Mill. kernel (SZJs: SZJ-1 and SZJ-2) have various biological effects. However, the hypoglycemic activities and underlying mechanisms of SZJs remain obscure. METHOD AND RESULTS: In the current study, two saponins SZJ-1 and SZJ-2 mainly composed of betulinic acid, spinosin, jujuboside A, and jujuboside B are extracted and is olated from dried Z. jujuba Mill. kernel. The SZJ-1 and SZJ-2 could significantly inhibit the activities of digestion enzymes α-glucosidase and α-amylases. The hypoglycemic ability of SZJ-1 and SZJ-2 is further investigated and the results show that SZJ-1 and SZJ-2 can improve the hyperglycemic by increasing the glucose consumption, improving the superoxide dismutase (SOD), hexokinase (HK), pyruvate kinase (PK) activities, and decrease the MDA content of insulin resistant HepG2 cells. Furthermore, SZJ-1 and SZJ-2 can activate the phosphorated adenosine 5'-monophosphate (AMP)-activated protein kinase α (p-AMPK), phosphoinositide 3-kinase p110α (PI3K-p110α), and phosphorated glycogen synthase kinase-3ß (Ser9) (p-GSK3ß). CONCLUSION: These results indicating that the SZJ-1 and SZJ-2 might improve the insulin resistant symptoms by improving the energy metabolic level and increasing the glycogen synthase activity of HepG2 cells.

Potential anticancer activities of securinine and its molecular targets.

BACKGROUND: Securinine is an alkaloid identified from the roots and leaves of the shrub Flueggea suffruticosa (Pall.) Baill. The molecular structure of securinine consists of four rings, including three chiral centers. It has been suggested that securinine can be chemically synthesized from tyrosine and lysine. Securinine has long been used to treat central nervous system diseases. In recent years, more and more evidence shows that securinine also has anticancer activity, which has not been systematically discussed and analyzed. PURPOSE: This study aims to propose an overall framework to describe the molecular targets of securinine in different signal pathways, and discuss the current status and prospects of each pathway, so as to provide a theoretical basis for the development securinine as an effective anticancer drug. METHODS: The research databases on the anticancer activity of securinine from PubMed, Scopus, Web of Science and ScienceDirect to 2021 were systematically searched. This paper follows the Preferred Reporting Items and Meta-Analysis guidelines. RESULTS: Securinine has the ability to kill a variety of human cancer cells, including, leukemia as well as prostate, cervical, breast, lung, and colon cancer cells. It can regulate the signal pathways of phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin, Wnt and Janus kinase-signal transducer and activator of transcription, promote cancer cell apoptosis and autophagy, and inhibit cancer cell metastasis. Securinine also has the activity of inducing leukemia cell differentiation. CONCLUSION: Although there has been some experimental evidence indicating the anticancer effect of securinine and its possible pharmacology, in order to design more effective anticancer drugs, it is necessary to study the synergy of intracellular signaling pathways. More in vivo experiments and even clinical studies are needed, and the synergy between securinine and other drugs is also worth studying.

Role of polyphenols from Polygonum multiflorum Caulis in obesity-related disorders.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygoni Multiflori Caulis (PMC) has been widely consumed as folk medicine in China for anti-obesity, sleep-enhancing and many other pharmacological effects. However, the material basis and underlying mechanism of PMC on obesity-related disorders were still not clear. AIM OF THE STUDY: To screen active constituents from PMC and explore their multitarget mechanisms in the treatment of obesity and its associated disorders. MATERIALS AND METHODS: Several major constituents were extracted from PMC and LC-MS assay were used to identify the compounds. The lipase inhibitory activity and lipid accumulation in 3T3-L1 preadipocytes were determined. Furthermore, Caenorhabditis elegans (C. elegans) and high-fat diet (HFD)-induced mice were established to explore the potential pharmacological functions and related mechanisms using kits, RT-qPCR and biochemical analysis. RESULTS: Regarding the lipase inhibitory activity, the inhibition rate of EA and n-Bu extracts at 4 mg/mL reached over 80%. Effects on 3T3-L1 preadipocytes proliferation and differentiation were also obvious, indicating that EA and n-Bu extracts might exert potential anti-obesity functions. LC-MS assay further showed that polyphenols including emodin and physcion comprised majority of EA and n-Bu extracts. EA and n-Bu extracts treatment could significantly modulate the antioxidant response and lipid accumulation in C. elegans, as evidenced by increased SOD and CAT contents, reduced MDA levels, higher TG contents and changes of related mRNA expression levels. In HFD-induced mice, the inhibition ratio of body weight as well as the histological and biochemical indexes of liver, plasma and epididymal adipose tissues were also reversed by EA and n-Bu extracts treatment. Moreover, EA and n-Bu extracts administration increased the microbial diversity, reshaped the microbiota structure and enhanced the relative abundance of Bifidobacterium. CONCLUSIONS: This study demonstrated the multicomponent and multitarget characteristics of PMC in preventing obesity related disorders. The results provided novel insights for the development and utilization of PMC.

Anticancer Effects and Molecular Target of Theaflavins from Black Tea Fermentation in Vitro and in Vivo.

Black tea is one of the most popular beverages in the world, and numerous epidemiological studies have shown that drinking black tea is good for health. As a natural tea pigment formed during the fermentation of black tea, the content of theaflavins accounts for only 2-6% of the dry weight of black tea, but they have a great impact on the color and taste of black tea soup. Recently, a large number of studies have shown that theaflavins have a significant anticancer effect. In this Perspective, we first state the physical and chemical properties, separation and purification methods, and biological formation pathways of theaflavins and analyze their safety and oral bioavailability and the structure-activity relationship of their antioxidant and anticancer activities; then, we describe in detail their anticancer effect in vitro and in vivo and highlight their various molecular targets involved in cancer inhibition. The anticancer molecular targets of theaflavins are mainly cell-cycle regulatory proteins, apoptosis-related proteins, cell-migration-related proteins, and growth transcription factors. Finally, the possibility of developing new health-care food based on theaflavins is discussed. This Perspective is expected to provide a theoretical basis for the anticancer application of theaflavins in the future.

Structural characterization of novel arabinoxylan and galactoarabinan from citron with potential antitumor and immunostimulatory activities.

This study aimed to extract polysaccharides from citron and analyze their structures and potential bioactivities. Two novel polysaccharides CM-1 and CM-2 were purified from citron by DEAE-Sepharose Fast Flow and Sephadex G-100 column chromatography. Monosaccharide composition, linkage and NMR data were used to infer their sugar chains composition. The anti-breast cancer cells and immunoregulatory activities of CM-1 and CM-2 were investigated. Results indicated that CM-1 (Mw = 21,520 Da), composed of arabinose, xylose, mannose and glucose in a molar ratio of 10.78:11.53:1.00:1.70, was arabinoxylan (AX) with (1 â†’ 4)-linked ß-d-Xylp skeleton monosubstituted with α-l-Araf units at O-3 position. While CM-2 (Mw = 22,303 Da), composed of arabinose, mannose, glucose and galactose in a molar ratio of 25.46:1.45:1.00:6.57, was galactoarabinan (GA) with (1 â†’ 5)-linked α-l-Araf backbone substituted by ß-d-Galp units at O-2 and/or O-3 positions. Both polysaccharides exhibited potential inhibiting cancer and immunostimulatory activities in vitro, especially CM-1. These results provide a basis for further research on citron polysaccharides.

Bergaptol from blossoms of Citrus aurantium L. var. amara Engl inhibits LPS-induced inflammatory responses and ox-LDL-induced lipid deposition.

Aberrant activation of inflammation and excess accumulation of lipids play pivotal roles in atherosclerosis (AS) progression. Constituents from Citrus aurantium Linn variant amara Engl (CAVA) were effectively investigated for their various bioactivities, especially anti-inflammation. Bergaptol (BER) is particularly abundant in Citrus products. Accumulating studies have confirmed its predominant anti-cancer and antioxidant functions, whereas few studies focused on its antiatherogenic functions. In the current study, BER was isolated from CAVA for the first time. Macrophages were stimulated with lipopolysaccharides (LPSs) or oxidized low-density lipoproteins (ox-LDL) to mimic inflammatory responses and AS development. BER treatment significantly inhibited LPS-induced production of nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and gene expression of inducible nitric oxide synthase (iNOS), IL-6, TNF-α, interleukin-1 beta (IL-1ß) and cyclooxygenase-2 (COX-2). BER also potently blocked LPS-induced mitogen-activated protein kinase (MAPK) phosphorylation and nuclear factor-kappa B (NF-κB) activation, as evidenced by the inhibitory effects on c-Jun N-terminal kinase (JNK), P38, P65, IκBα and IκKα/ß phosphorylation, and NF-κB nuclear translocation. Furthermore, BER treatment markedly mitigated ox-LDL-induced foam cell formation by inhibiting scavenger receptor class A type I (SRA1) and cluster of differentiation 36 (CD36)-dependent cholesterol uptake. In conclusion, BER might be a novel therapeutic agent for AS prevention through inhibiting inflammatory responses and cholesterol uptake.

Potential roles of dietary flavonoids from Citrus aurantium L. var. amara Engl. in atherosclerosis development.

Dietary consumption of flavonoids correlated positively with lower risk of cardiovascular disease. However, the precise roles of flavonoids from the blossoms of Citrus aurantium Linn variant amara Engl (CAVA) in atherosclerosis (AS) are still poorly understood. This study aimed to find novel flavonoid-type skeletons with protection against AS. Total flavonoids (CAVAF), homoeriodictyol (HE) and hesperetin-7-O-ß-d-glucopyranoside (HG) were isolated from the blossoms of Citrus aurantium Linn variant amara Engl. by chromatography. Their suppressive effects on lipopolysaccharide (LPS)-induced inflammatory responses and ox-LDL-induced foam cell formation were systematically and comparatively investigated using macrophage RAW264.7 cells. HE was more powerful than HG in inhibiting LPS-induced production of nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1ß) and gene expression in RAW264.7 cells. HE and HG showed different responses to extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinases (JNK), P38, P65, IκBα, IκKα/ß phosphorylation, and nuclear factor-kappa B (NF-κB) nuclear translocation. HE and HG also differentially decreased oxidized low-density lipoprotein (ox-LDL)-induced foam cell formation by regulating peroxisome proliferator-activated receptor-gamma (PPARγ), phospholipid ATP-binding cassette transporter A1 (ABCA1), phospholipid ATP-binding cassette transporter G1 (ABCG1), scavenger receptor class B type I (SRB1), scavenger receptor class A type I (SRA1) and cluster of differentiation 36 (CD36) expression at gene and protein levels in RAW264.7 cells. HG showed weaker potential than HE in preventing AS development. Their chemical differences might partially explain the discrepancy in their bioactivity. In conclusion, HE and HG might be developed into novel therapeutic agents against inflammation and AS-associated diseases.

Effects of diosgenin and its derivatives on atherosclerosis.

Atherosclerosis is one of the leading causes of death in patients with cardiovascular diseases worldwide. Although some progress has been made in the treatment of cardiovascular diseases, the morbidity and mortality of cardiovascular diseases still continue to rise. At present, it is an important topic for researchers to develop safe and effective drugs from natural products to prevent and treat cardiovascular diseases. Diosgenin (DSG) is a plant sterol saponin mainly found in natural medicinal plants such as fenugreek seeds and wild yam tubers. More and more studies have reported that DSG has significant pharmacological activities such as anticancer, cardiovascular protection, hypolipidemic, anti-inflammatory, and neuroprotection. Furthermore, diosgenin is also an important basic raw material for the preparation of steroids and contraceptives in the pharmaceutical industry. Numerous preclinical studies have shown that DSG has great potential in the treatment of various cardiovascular diseases in vivo and in vitro, especially in atherosclerosis. This review mainly discusses the effects of DSG on endothelial dysfunction, lipid profile, and macrophage foam cell formation, VSMC viability, thrombosis and inflammation during the formation of atherosclerosis. Also, the mechanism of DSG on atherosclerosis was elaborated in detail. It is noteworthy that newly synthesized DSG derivatives and DSG delivery systems have good antithrombotic activity and pharmacokinetic characteristics.

Comparative antitumor and anti-inflammatory effects of flavonoids, saponins, polysaccharides, essential oil, coumarin and alkaloids from Cirsium japonicum DC.

Cirsium japonicum DC (Asteraceae) is a perennial thistle widely distributed in Asia, it is also consumed as functional food and herb in China. To analyze the health effects of C. japonicum, flavonoids, saponins, polysaccharides, essential oil, coumarin and alkaloids were extracted from C. japonicum, and their cytotoxicity to normal cells, anti-inflammatory effect against LPS-induced RAW 264.7 macrophages, antiproliferative effects against human lung adenocarcinoma cell A549 and anti-atherosclerosis activities in ox-LDL-stimulated RAW 264.7 cell were investigated. Results showed that coumarins exhibited strongest cell toxicity (IC50 = 162.7 µg/ml), and alkaloids showed slightly cytotoxicity at high concentration. Saponin could significantly inhibit cancer cell proliferation, especially for A549 cell and the inhibition rate reached to 47.0% at concentration of 200 µg/ml, which might result from the promotion of ROS generation in cancer cell. Saponin, essential oil and flavonoids could dose-dependently inhibit NO production in LPS-induced RAW 264.7 macrophages, whose inhibition rates were 65.4%, 73.0% and 80.4% at concentration of 50 µg/ml, respectively. Besides, saponin, essential oil and flavonoids also decreased lipid accumulation in ox-LDL-induced RAW 264.7 cell, which might be beneficial for cardiovascular health. These results indicated that different components from C. japonicum exhibited different bioactivities, providing useful information to better use thistle resources.

Identification of narciclasine from Lycoris radiata (L'Her.) Herb. and its inhibitory effect on LPS-induced inflammatory responses in macrophages.

Lycoris radiata (L'Her.) Herb. (L. radiata) was traditionally used as a folk medicine in China for treatment of Alzheimer's disease. However, the specific component responsible for its considerable toxicity remained unclear thus restricting its clinical trials. Narciclasine (NCS) was isolated from L. radiata and treatment of NCS for 72 h exhibited significant antiproliferative effects against L02, Hep G2, HT-29 and RAW264.7 cells. However, what needs to be emphasized is that at safe working concentrations of 0.001-0.016 µM, administration of NCS for 24 h inhibited the mRNA expression of inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-ɑ), interleukin-1beta (IL-1ß) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced macrophages thereby suppressing production of nitric oxide (NO), IL-6, TNF-ɑ and IL-1ß. NCS supplementation also inhibited nuclear factor-kappa B (NF-κB) activation by suppressing NF-κB P65 phosphorylation and nuclear translocation, IκBɑ degradation and phosphorylation, and IκKɑ/ß phosphorylation. The phosphorylation of c-Jun N-terminal kinase (JNK) and P38, and expression of COX-2 was also attenuated by NCS. These results suggested that NCS might exert anti-inflammatory effects through inhibiting NF-κB and mitogen-activated protein kinase (MAPK) pathways even at very low doses.

Anti-fatigue Effects of Active Ingredients from Traditional Chinese Medicine: A Review.

BACKGROUND: The application of traditional Chinese medicine (TCM) in the treatment of fatigue has long been practiced in clinical and showed significant effects. OBJECTIVE: This article summarizes the work done on the natural products from TCM that are reported to have effects of treating fatigue, in the past two decades. METHOD: Research status, sources, models, efficacy and mechanisms of active ingredients and their monomer in the treatment of fatigue are discussed. RESULTS: Pharmacological research shows that active ingredients of polysaccharide can significantly improve body's resistance through promoting glycogen synthesis, reducing sports metabolites and increasing hypoxia tolerance; Alkaloids have been proven to be effective in promoting the reserving of various glucogen substances, improving exercise endurance and speeding up the metabolism of body's urea nitrogen in mice; With the increase of glycosides amount, up goes the sport endurance, liver glycogen content and the ability of clear lactate index in mice, indicating that saponin has clear, dose-dependent anti-fatigue effect; Polyphenols have also functions of resisting fatigue, where they reduce free radicals accumulated and thus slow down the rapid declination of exercise capacity when doing sports; There are other active ingredients of TCM that have biological activities, like some proteins, anthraquinones, terpenes, unsaturated fatty acid monomer compounds; And research has found that tonic medicine can promote the elimination of fatigue and improve athletic ability. CONCLUSION: It is hoped that the data summarized in this review will be beneficial to the screening of new nature-derived drugs with the ability of relieving and improving fatigue.

Health functions and structure-activity relationships of natural anthraquinones from plants.

Anthraquinone compounds with the anthraquinone ring structure are widely found in traditional Chinese medicines and they are attracting a lot of attention due to their good pharmacological activity. Diversities of anthraquinones depend on their chemical structures, such as the number of anthraquinone rings and the substituents; what's more, the difference in chemical structure determines the difference in physiological activity. Based on results of previous studies, this review summarizes several natural anthraquinones identified from Chinese herbal medicines and their physiological activities including anti-cancer, anti-pathogenic microorganisms, anti-inflammatory, anti-oxidation, anti-osteoporosis, anti-depression, and anti-constipation. The source, effect, model, and action mechanism of the active anthraquinones are described in detail, from which their structure-activity relationship is summarized. By analyzing the relationship between anthraquinone structure and function, we found that, on the whole structure, the anthraquinone ring and anthraquinone glycosides have significant anticancer activity and anti-constipation activity, while for their substituents, anthraquinones substituted by alizarin have significant antioxidant activity and the polarity of the substituents is closely related to their antibacterial activities.

Comparison of the Effects and Inhibitory Pathways of the Constituents from Gynostemma pentaphyllum against LPS-Induced Inflammatory Response.

Saponins, the primary phytochemicals contributing to the health properties of G. pentaphyllum were frequently studied. However, compounds responsible for its bioactivities were still poorly understood. The saponin-rich fraction (GPMS), 3- O-[2G-( E)-Coumaroyl-3G- O-ß-d-glucosyl-3R- O-ß-d-glucosylrutinoside] (KCGG), gypenoside XLVI and gypenoside L were obtained by purification of G. pentaphyllum. The compounds were examined and compared with GPMS for their inhibitory effects on LPS-induced nitric oxide (NO) production. GPMS and KCGG differed in their inhibitory capacities against pro-inflammatory cytokines secretion. GPMS exhibited strong inhibition on inducible nitric oxide synthase (iNOS) and interleukin-6 (IL-6) mRNA expression but weak inhibition on tumor necrosis factor-α (TNF-α) and interleukin-1ß mRNA expression. KCGG was better at inhibiting iNOS, IL-6, TNF-α, and cyclooxygenase-2 (COX-2) mRNA expression. GPMS showed similar inhibitory potency on mitogen-activated protein kinase phosphorylation and nuclear factor-κB (NF-κB) activation, as evidenced by their regulatory effects on LPS-induced P65 phosphorylation, NF-κB nuclear translocation, IκBα phosphorylation and degradation, IκKα/ß phosphorylation, c-Jun N-terminal kinase phosphorylation, P38 phosphorylation, and COX-2 expression. KCGG was more powerful in inhibiting the NF-κB pathway, suggesting that KCGG might be used in the management of inflammatory-associated diseases in which NF-κB played pivotal roles. Furthermore, KCGG might be mainly responsible for the predominant effects of GPMS.

Polyphenols from Ilex latifolia Thunb. (a Chinese bitter tea) exert anti-atherosclerotic activity through suppressing NF-κB activation and phosphorylation of ERK1/2 in macrophages.

Ilex latifolia Thunb is a kind of herbal tea and widely consumed as a functional tea beverage in Asian countries. In this study, polyphenols were extracted from I. latifolia and the major compounds were identified by liquid chromatography-mass spectrometry (LC-MS), then the effect on oxidized low-density lipoprotein (ox-LDL)-induced macrophage foam cell formation was investigated. Results showed that the polyphenols could significantly inhibit ox-LDL-induced macrophage foam cell formation and suppress lipid droplet accumulation and cholesterol uptake in RAW 264.7 cells. Additionally, the secretion of pro-inflammatory cytokines, such as tumor necrosis factor (TNF-α), interleukin (IL)-1ß, IL-6 and inducible nitric oxide synthase (iNOS), was significantly inhibited. Moreover, the polyphenols could suppress the expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and clusters of differentiation 36 (CD 36), which were receptors for ox-LDL. Mechanistically, I. latifolia polyphenols could inhibit macrophage foam cell formation by suppressing NF-κB activation and phosphorylation of ERK1/2.

Pharmacological and Nutritional Effects of Natural Coumarins and Their Structure-Activity Relationships.

Coumarins are fused benzene and pyrone ring systems with a wide spectrum of bioactivities, including antitumor, anti-inflammation, antiviral, and antibacterial effects. In this paper, the current development of coumarin-based drugs is introduced, and their structure-activity relationship is discussed by reviewing the relevant literature published in the past 20 years. Coumarin molecules can be customized by the target site to prevent systemic side effects by virtue of structural modification. The ortho-phenolic hydroxyl on the benzene ring has remarkable antioxidant and antitumor activities. Coumarins with aryl groups at the C-4 position have good activities in anti-HIV, antitumor, anti-inflammation, and analgesia. C-3 phenylcoumarins have strong anti-HIV and antioxidant effects. Tetracycline pyranocoumarins can significantly inhibit HIV; osthol structural analogues have antimicrobial activity. Praeruptorin C and its derivatives play an important role in lowering blood pressure and dilating coronary arteries, and khellactone derivatives have significant inhibitory effects on AIDS, cancer, and cardiovascular diseases. It is concluded that the specific site on the core structure of coumarin exhibits one or more activities due to the electronic or steric effects of the substituents. This review is intended to be conducive to rational design and development of more active and less toxic agents with a coumarin scaffold.

Bioassay-guided isolation and identification of anticancer and antioxidant compounds from Gynostemma pentaphyllum (Thunb.) Makino.

Gynostemma pentaphyllum (Thunb.) Makino is a medicinal and edible plant in China whose buds and leaves are used for making a popular kind of tea drink. The anticancer and antioxidant properties of the ethyl acetate (EA) and n-butanol (n-Bu) fractions provide a basis for conducting experiments for isolation and identification of key compounds that may be responsible for the aforementioned properties of G. pentaphyllum. Four compounds were isolated from the two fractions using ODS packing column, silica gel column, polyamide column, Sephadex LH-20 gel column and HPLC. With the aid of 1H, 13C NMR and mass spectrometry, they were identified as 3,4-dihydroxy phenyl-O-ß-d-glucoside, gypenoside XLVI, gypenoside L and ginsenoside Rd. 3,4-Dihydroxy phenyl-O-ß-d-glucoside showed the strongest DPPH (97.23%) and ABTS (101.37%) scavenging effect and ferric ion reducing power (FRAP value 0.8846), which may be closely related to the hydrogen atoms of phenolic hydroxyls. Gypenoside L and ginsenoside Rd displayed the highest inhibition of tumor cell proliferation of A549 and MCF-7 cell lines, which had to do with the chemical structure of the compounds bearing glycosylated parts and free hydroxyls at the 20th or 21st carbon atom of dammarane-type saponin.

Antioxidant and anti-inflammatory effects of polyphenols extracted from Ilex latifolia Thunb.

To promote the rational and effective application of Ilex latifolia Thunb., a Chinese bitter tea widely consumed as a health beverage, polyphenols were extracted from its leaves and their cellular antioxidant activity (CAA) and anti-inflammatory effect against mouse macrophage RAW 264.7 cells were analyzed. Results showed that the antioxidant capacity of polyphenols was high, and their CAA values in PBS wash and no PBS wash protocols were 6871.42 ± 85.56 and 25161.61 ± 583.55 µmol QE (quercetin equivalents)/100 g phenolic extracts, respectively. In addition, polyphenols from I. latifolia displayed strong inhibition on LPS-induced NO-production in RAW 264.7 cells. Polyphenol treatment inhibited the release of pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6) induced by LPS in a dose-dependent manner by ELISA and mRNA expression analysis. Western blot results showed that the anti-inflammatory activity of polyphenols from I. latifolia might be exerted through inhibiting the activation of MAPKs (ERK and JNK) and NF-κB to decrease NO, COX-2 and pro-inflammatory cytokines production. Thus, the polyphenol enriched extracts from I. latifolia are a good source of natural antioxidants with a beneficial effect against inflammation, and they may be applied as a food supplement and/or functional ingredient.

Identification of bioactives from Astragalus chinensis L.f. and their antioxidant, anti-inflammatory and anti-proliferative effects.

This work was designed to obtain the valuable compounds with antioxidant, anti-proliferative and anti-inflammatory activities from Astragalus chinensis. Ethyl acetate fraction obtained from A. chinensis L.f. had significant antioxidant, anti-proliferative and anti-inflammatory activities. Subsequently, five single compounds were separated and purified, which were identified as formononetin (1), rhamnocitrin (2), calycosin (3), ß-daucosterol (4), rhamnocitrin-3-O-ß-d-glucoside (5). The results displayed that formononetin and rhamnocitrin exhibited significant cytotoxicity actions against tumor cell lines. Calycosin exerted the strongest anti-inflammatory effect of inhibition effects on NO production in macrophages.