Chemical Composition and Antibacterial and Antiulcerative Colitis Activities of Essential Oil from Pruni Semen.

This study was sought to investigate the chemical composition and antibacterial and antiulcerative colitis (UC) effects of essential oil from Pruni Semen (PSEO). A GC-MS assay showed that the major compounds in PSEO were products of amygdalin hydrolysis, which possessed great antibacterial and anti-inflammatory potential. In vitro antibacterial experiments demonstrated that PSEO treatment inhibited activity of four kinds of intestinal pathogens probably by disrupting the cell wall. Further in vivo studies showed that PSEO administration significantly improved physiological indexes, attenuated histopathological characteristics, and inhibited proinflammatory cytokine production in dextran sulfate sodium (DSS)-induced UC mice. Network pharmacology and molecular docking results predicted that PSEO might prevent UC via regulating the PI3K/AKT pathway. Western blotting and immunofluorescence assays were further conducted for verification, and the results evidenced that PSEO intervention significantly regulated the PI3K/AKT pathway and the expression of its downstream proteins in DSS-induced mice. PSEO might provide a new dietary strategy for UC treatment.

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.

p-Synephrine ameliorates alloxan-induced diabetes mellitus through inhibiting oxidative stress and inflammation via suppressing the NF-kappa B and MAPK pathways.

Oxidative stress and inflammation play important roles in the development of diabetes mellitus. p-Synephrine, the primary pharmacologically active protoalkaloid in Citrus species, has been popularly consumed as a dietary supplement for weight loss management. However, the effects of p-synephrine on diabetes mellitus and the action mechanisms have not been clearly elucidated. In this study, the in vitro antioxidant effects of p-synephrine were evaluated. The data showed that p-synephrine treatment exhibited significant scavenging effects against DPPH, ABTS and OH radicals and showed high reducing power. Diabetic mice were developed by alloxan injection, followed by p-synephrine administration to investigate its hypoglycemic effects in vivo. The results showed that p-synephrine intervention significantly prevented alloxan-induced alteration in body weight, organ indexes, serum uric acid content and serum creatinine content. Meanwhile, p-synephrine application significantly improved the lipid profiles, superoxide dismutase (SOD) and catalase (CAT) activities and glutathione (GSH) contents in the serum and kidneys of diabetic mice and reduced the malondialdehyde (MDA) content in the serum of diabetic mice. Further assays suggested that p-synephrine treatment improved alloxan-induced decreases of glucose tolerance and insulin sensitivity. Also, p-synephrine supplementation altered histopathological changes in the kidneys and interscapular brown adipose tissues in diabetic mice. In addition, p-synephrine administration inhibited renal inflammation through suppressing tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) gene expression levels, as well as CD45 expression levels. The anti-inflammatory effects were probably involved in the regulation of nuclear factor-κB (NF-κB) activation and mitogen-activated protein kinase (MAPK) phosphorylation. In conclusion, p-synephrine application significantly ameliorated alloxan-induced diabetes mellitus by inhibiting oxidative stress via suppressing the NF-κB and MAPK pathways.

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.

Natural bioactive constituents from herbs and nutraceuticals promote browning of white adipose tissue.

Obesity is a significant public health problem worldwide that is characterized by abnormal or excessive fat accumulation. Unfortunately, the application of available weight-loss drugs has been restricted because of their serious adverse effects. Browning of white adipose tissue (WAT), which refers to the transformation of white adipocytes to beige adipocytes under certain stimulations, is regarded as a new strategy to solve the obesity problem. Numerous studies have recently evidenced that traditional Chinese medicine (TCM) could promote browning of WAT with multi-component and multi-target characteristics. This article summarizes natural constituents from TCM with stimulatory effects on browning of WAT in the past two decades. The active ingredients can be generally divided into polyphenols, saponins, alkaloids, terpenoids, phenylpropanoids and others, such as resveratrol, quercetin, curcumin, genistein, capsaicin, epigallocatechin gallate (EGCG), berberine, menthol, emodin and ginsenosides. Simultaneously, the chemical structures, source, model, efficacy and mechanism of these monomeric compounds are also described. And the mechanisms of these active ingredients are mainly involved in the regulation of PRDM16, PGC-1α, PPARγ, SIRT1, AMPK, ß3-adrenergic receptors, TRPV1 and TRPM8 channels, FGF21 and miRNAs. The present article opens opportunities for developing novel drugs or supplements from TCM with wide acceptability to prevent obesity progression and its associated metabolic disorders.

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.

Single-Cell Characterization of Malignant Phenotypes and Developmental Trajectories of Adrenal Neuroblastoma.

Neuroblastoma (NB), which is a subtype of neural-crest-derived malignancy, is the most common extracranial solid tumor occurring in childhood. Despite extensive research, the underlying developmental origin of NB remains unclear. Using single-cell RNA sequencing, we generate transcriptomes of adrenal NB from 160,910 cells of 16 patients and transcriptomes of putative developmental cells of origin of NB from 12,103 cells of early human embryos and fetal adrenal glands at relatively late development stages. We find that most adrenal NB tumor cells transcriptionally mirror noradrenergic chromaffin cells. Malignant states also recapitulate the proliferation/differentiation status of chromaffin cells in the process of normal development. Our findings provide insight into developmental trajectories and cellular states underlying human initiation and progression of NB.

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.

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.

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 Blossoms of Citrus aurantium L. var. amara Engl. Show Significant Anti-Complement and Anti-Inflammatory Effects.

Citrus aurantium L. var. amara Engl. (CAVA) was traditionally used as a digestant or expectorant in China. Crude polyphenols (CAVAP-W) extracted from blossoms of CAVA were mainly composed of eriocitrin/neoeriocitrin, eriocitrin/neoeriocitrin, rhoifolin, hesperidin, naringin, rutin, veronicastroside, neohesperidin, and hesperetin by LC-MS analysis. CAVAP-W showed significant anticomplement and anti-inflammatory effects. Due to the close relationship between anticomplement and anti-inflammatory activity, the anti-inflammatory effect was further investigated and the results showed that CAVAP-W significantly suppressed production of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß), and mRNA expression of inducible nitric oxide synthase (iNOS), IL-6, TNF-α, IL-1ß, and cyclooxygenase-2 (COX-2) in lipopolysaccharides-stimulated RAW264.7 cells. Furthermore, CAVAP-W inhibited mitogen-activated protein kinase (MAPK) phosphorylation and NF-κB activation through suppressing nuclear translocation of nuclear factor-kappa B (NF-κB) P65, degradation and phosphorylation of IκBα, phosphorylation of IκKα/ß, c-Jun N-terminal kinase (JNK), and P38, and activation of COX-2, thereby exerting the anti-inflammatory effects.

Anti-inflammatory Effect of Essential Oil from Citrus aurantium L. var. amara Engl.

Essential oil has been popularly used as an alternative for the treatment of inflammation. The bioactivities of essential oil from blossoms of Citrus aurantium L. var. amara Engl (CAVAO) showed greater anti-inflammation potential than that of antioxidant, anticancer, and 3T3-L1 proliferation inhibition. CAVAO (250 µg/mL) significantly inhibited production of nitric oxide (NO) (99.54 ± 2.81%), interleukin-6 (IL-6) (98.11 ± 1.62%), tumor necrosis factor-α (TNF-α) (41.84 ± 1.52%), and interleukin-1ß (IL-1ß) (56.09 ± 2.21%) as well as their gene expression level. CAVAO also markedly decreased the expression levels of cyclooxygenase-2 (COX-2) gene and protein. Furthermore, CAVAO inhibited nuclear factor-κB (NF-κB) activation, which was justified by the inhibitory effect on NF-κB nuclear translocation, IκBα phosphorylation and degradation, and phosphorylation-dependent IκB kinase activation in RAW264.7 cells stimulated with lipopolysaccharides. CAVAO also suppressed the phosphorylation of c-Jun N-terminal kinase (JNK) and p38, indicating that mitogen-activated protein kinase (MAPK) signaling pathways were also blocked. The major constituents of CAVAO were characterized as linalool (64.6 ± 0.04%), α-terpineol (7.61 ± 0.03%), (R)-limonene (6.15 ± 0.04%), and linalyl acetate (5.02 ± 0.03%), which might be responsible for its observed anti-inflammation activity. It is concluded that CAVAO has great potential to be developed into a functional food for the treatment of inflammatory-associated diseases.

Various Antioxidant Effects Were Attributed to Different Components in the Dried Blossoms of Citrus aurantium L. var. amara Engl.

Citrus aurantium L. var. amara Engl. (CAVA) was traditionally used as an edible and medicinal material in China. Total flavonoids (CAVAF), alkaloids (CAVAA), polysaccharides (CAVAP), coumarins (CAVAC), and neroli (CAVAO) were extracted from CAVA. Hesperidin, naringin, and neohesperidin composed 83.94% of CAVAF, and synephrine represented 50.56% of CAVAA. On the basis of 1,1-diphenyl-2-picrylhydrazyl radical (DPPH•), 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt radical cation (ABTS• +), hydroxyl radical (•OH), ferric-reducing antioxidant power (FRAP), and reducing power assays, the antioxidant activities of five components were comprehensively and comparatively investigated. CAVAF had a stronger DPPH• scavenging effect and FRAP and reducing power. CAVAP and CAVAA exhibited comparable •OH scavenging effects to vitamin C. CAVAA showed the highest ABTS• + scavenging activity. In conclusion, different constituents varied significantly toward different sources of free radicals and other oxidants. It is obvious that CAVA has various antioxidant effects, which are attributed to different components.

Immune enhancement effects and extraction optimization of polysaccharides from Citrus aurantium L. var. amara Engl.

The crude polysaccharides of Citrus aurantium L. var. amara Engl (CAVAPs) were extracted and their bioactivities including DPPH radical scavenging activity, cytotoxicity to human breast cancer cells, MCF-7, as well as lung cancer cells, HCC827, and their immune-enhancement activity were evaluated. Results showed that CAVAPs exhibited better immunoenhancement activity compared to the DPPH radical scavenging and anticancer activities. Subsequently, the immune enhancement activity of CAVAPs on RAW264.7 cells was further observed and the results displayed that CAVAPs could significantly stimulate the production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in RAW264.7 cells, and promote the mRNA expression levels of inducible nitric oxide synthase (iNOS), TNF-α, interleukin-1 beta (IL-1ß), and IL-6. Furthermore, western blot analysis demonstrated that the phosphorylated extracellular signal-regulated kinase (ERK), phosphorylated c-Jun N-terminal kinase (JNK), phosphorylated p38 and phosphorylated p65 were all remarkably increased in CAVAP-treated RAW264.7 cells. All these results indicated that CAVAPs might activate macrophages through the mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathway. Additionally, a three-level-three-factor Box-Behnken design (BBD) was performed to optimize the extraction process of CAVAPs for the purpose of application and further research. The maximum extraction yield reached 4.49 ± 0.25%.

Anti-inflammatory activities of essential oil isolated from the calyx of Hibiscus sabdariffa L.

Hibiscus sabdariffa Linn., belonging to the family of Malvaceae, is considered to be a plant with health care applications in China. The main purpose of this study was to analyze the composition of its essential oil and assess its potential therapeutic effect on anti-inflammatory activity. A water steam distillation method was used to extract the essential oil from H. Sabdariffa. The essential oil components were determined by gas chromatography/mass spectrometry (GC-MS) analysis and a total of 18 volatile constituents were identified, the majority of which were fatty acids and ester compounds. Biological activity showed that the essential oil extracted from H. Sabdariffa exhibited excellent anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated macrophage RAW 264.7 cells. The nitric oxide (NO) inhibition rate reached 67.46% when the concentration of the essential oil was 200 µg mL-1. Further analysis showed that the anti-inflammatory activity of the essential oil extracted from H. Sabdariffa might be exerted through inhibiting the activation of NF-κB and MAPK (JNK and ERK1/2) signaling pathways to decrease NO and pro-inflammatory cytokine (IL-1, IL-6, TNF-α, COX-2, and iNOS) production. Thus, the essential oil extracted from H. Sabdariffa is a good source of a natural product with a beneficial effect against inflammation, and it may be applied as a food supplement and/or functional ingredient.