Metabolomic profiling and antidiabetic activity of Callerya speciosa.

Callerya speciosa is a perennial edible and medicinal plant belonging to the family Fabaceae. This study was to reveal the similarities and differences between phytochemicals in different parts of C. speciosa using a combination of ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS), principal component analysis (PCA) and orthogonal projection to latent structures discriminant analysis (OPLS-DA). In addition, the anti-diabetic activity of C. speciosa extracts was explored. A total of 141 compounds were identified and 34 robustly known chemical markers were marked. PCA and heat map analyses revealed that the stems, leaves and pods had similar phytochemical compounds, while compounds in roots and flowers differed from each other and from those in the above ground parts. In addition, extracts of C. speciosa roots and flowers exhibited anti-diabetic activity, which can be applied to the development of anti-diabetic drugs.

Systematic characterisation of the effective components of five Callicarpa species with UPLC-Q-TOF-MS and evaluation of their anti-hyperuricaemic activity.

Callicarpa kwangtungensis (C. Kw), C. macrophylla (C. Ma), C. nudiflora (C. Nu), C. formosana (C. Fo), and C. kochiana (C. Ko) were medicinal plant resource in China. In this study, the UPLC/Q-TOF-MS analysis was performed and 151 compounds were identified. PCA analysis metabolic profiles of C. Nu, C. Ko and C. Kw leaves differ significantly from the other two Callicarpa species, while C. Fo and C. Ma share similar chemical constituents. OPLS-DA highlight with an S-plot indicated that there are 14 robust known chemical markers enabling the differentiation between these five Callicarpa plants. C. Ma, C. Nu, and C. Fo leaves extracts treatment effectively reversed the body weight loss, uric acid and creatinine content, hepatic XOD activity, kidney, liver, and ankle tissues injury and inflammation induced by potassium oxonate in hyperuricemia mice. While Ko and C. Kw leaves extracts treatment showed less improvement in hyperuricemia mice.

The Anti-Inflammatory Effect of Callicarpa nudiflora Extract on H. Pylori-Infected GES-1 Cells through the Inhibition of ROS/NLRP3/Caspase-1/IL-1ß Signaling Axis.

Helicobacter pylori (H. pylori) is the main pathogenic factor of gastric cancer, chronic gastritis, and other gastric diseases. It has been found that Callicarpa nudiflora (CN) as an air-dried leaf extract has a broad-spectrum antibacterial effect. This study aims to examine the effect of CN on H. pylori-infected GES-1 cells in vitro and elucidate its underlying mechanism by extracting active ingredients from air-dried leaves. GES-1 cells were cocultured with HPSS1 at MOI = 100 : 1 and treated with different concentrations of CN (100 and 200 µg/ml). Results showed that CN can significantly reduce cellular LDH leakage and attenuate H. pylori-induced cell apoptosis and ROS production in GSE-1 cells, so as to protect gastric epithelial cells from damage by H. pylori. CN can also inhibit the secretion of inflammatory factors, such as TNF-α, IL-1ß, IL-6, and IL-8. After CN treatment, the expression levels of active caspase-1, PYCARD, and NLRP3 were remarkably decreased in the treatment groups compared with the model group. To sum up, CN is highly protective against H. pylori-induced cell damage and apoptosis; CN can depress NLRP3 inflammasome activation and ROS production via the ROS/NLRP3/caspase-1/IL-1ß signaling axis to suppress H. pylori-triggered inflammatory response and pyroptosis.

Flavonoid-enriched extract from Millettia speciosa Champ prevents obesity by regulating thermogenesis and lipid metabolism in high-fat diet-induced obese C57BL/6 mice.

Millettia speciosa (M. speciosa) Champ is a medicinal and edible plant. The roots are rich in flavonoids, which possess multiple biological activities, including lipid-lowering effects. This study aimed to explore the effect of flavonoid-enriched extract from M. speciosa (FMS) on obesity. The UPLC-Q-TOF-MS analysis and chromatographic analysis were adopted to identify flavonoid compounds in FMS. Male C57BL/6J mice were fed with a high-fat diet for 3 months and were then treated with FMS (50 or 100 mg/kg/d) or Orlistat (10 mg kg-1 d-1) for another 8 weeks. A total of 35 flavonoids were identified in the extract of M. speciosa root. FMS reduced body weight gain, liver weight gain, white adipose tissue, lipid accumulation, and blood glucose. The levels of TG, ALT, AST, and inflammatory-related adipokines (TNF-α and IL-6) in serum were also reduced by FMS. In addition, FMS promoted thermogenesis in brown adipose tissue and induced the activation of lipolysis, fatty acid oxidation, and oxidative phosphorylation in white adipose tissues. In summary, long-term administration of FMS could ameliorate high-fat diet-induced obesity by stimulating adipose thermogenesis and lipid metabolism.

[Advances of Akkermansia muciniphila in regulating host functions].

Akkermansia muciniphila, abbreviated as AKK and found in 2004, is an oval-shaped gram-negative bacterium isolated from a human feal. A. muciniphila is widely present in the intestinal tract of human. Its specialization in mucin degradation makes it a key organism at the mucosal interface between the lumen and host cells. More and more studies have shown that it can play the role of probiotics. Notably, declined levels of A. muciniphila have been observed in patients with diabetes, liver disease, cardiovascular disease, inflammatory bowel disease, neurodegenerative diseases, etc. In addition, A. muciniphila combined with traditional Chinese medicine, exhibited higher effect on regulating host functions, but the underlying mechanism was still unclear, requiring further in-depth research. Therefore, the aims of this review are to summarize the main effects of A. muciniphila on host health and its relationship with traditional Chinese medicine, summarize the main problems, and provide a reference for the further research of A. muciniphila and traditional Chinese medicine.

The Welwitschia genome reveals a unique biology underpinning extreme longevity in deserts.

The gymnosperm Welwitschia mirabilis belongs to the ancient, enigmatic gnetophyte lineage. It is a unique desert plant with extreme longevity and two ever-elongating leaves. We present a chromosome-level assembly of its genome (6.8 Gb/1 C) together with methylome and transcriptome data to explore its astonishing biology. We also present a refined, high-quality assembly of Gnetum montanum to enhance our understanding of gnetophyte genome evolution. The Welwitschia genome has been shaped by a lineage-specific ancient, whole genome duplication (~86 million years ago) and more recently (1-2 million years) by bursts of retrotransposon activity. High levels of cytosine methylation (particularly at CHH motifs) are associated with retrotransposons, whilst long-term deamination has resulted in an exceptionally GC-poor genome. Changes in copy number and/or expression of gene families and transcription factors (e.g. R2R3MYB, SAUR) controlling cell growth, differentiation and metabolism underpin the plant's longevity and tolerance to temperature, nutrient and water stress.

Metabolomic profiling of M. speciosa champ at different growth stages.

Millettia speciosa Champ (M. speciosa) is an edible food and folk medicine and extracts from its roots exhibit a hepatoprotective effect. However, its metabolic growth process and the best harvest time have not been reported. This study systematically evaluated the metabolomic profiling of M. speciosa root extracts at different growth stages through the UPLC-Q-TOF-MS, nuclear magnetic resonance (NMR) and An orthogonal partial least squares-discriminant analysis (OPLS-DA). The results revealed there were significant differences among extracts from six ages of M. speciosa, and 110 compounds were identified. Pharmacological studies showed that 5-year and 20-year old M. speciosa roots may exhibit higher fat-lowering effects, while 5-year-old (M.s-5Y) showed better hepatoprotective activity in high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) mice. Hence, our study suggested that M.s-5Y may have potent efficacy in ameliorating NAFLD, which might be useful in determining the optimum time to harvest M. speciosa.

Bioactivities and Structure-Activity Relationships of Natural Tetrahydroanthraquinone Compounds: A Review.

Tetrahydroanthraquinones are a kind of important microbial secondary metabolites with promising biological activities. Most of them were found in microorganisms, a few were derived from Chinese herbal medicine. In this review, aiming to provide basis for the further research and development of tetrahydroanthraquinone compounds, we summarized the physiological activities of natural tetrahydroanthraquinone compounds, including anti-cancer, anti-microbial, and antidiabetic activities. The source, structure, and action mechanisms of active tetrahydroanthraquinones are described in detail. Furthermore, this review firstly analyzed the structure-activity relationship of tetrahydroanthraquinones. Our study will serve as a valuable guideline for further research on the structural optimization, mechanism study, and development of tetrahydroanthraquinone as novel drugs. Aiming to provide references for further studies and development of tetrahydroanthraquinone compounds.

Two new phenolic glycosides from the seeds of Citrullus lanatus.

Two new phenolic glycosides, named lanatusosides C (1) and D (2), together with four known compounds (3-6), were isolated from the seeds of Citrullus lanatus. Among them, compounds 3 and 4 were isolated from Cucurbitaceae for the first time, and compound 5 was reported from this plant for the first time. Their structures were elucidated by means of extensive spectral analysis, including HR-ESI-MS, 1H and 13C NMR techniques. The isolated new compounds were evaluated for cytotoxic activity against HepG2 cell line, of which compound 1 demonstrated weak cytotoxicity against the tested cell line.

Advance in Tissue Differentiation and its Regulatory Mechanisms by Master Proteins of Nervous System during Weaning.

Weaning is a critical period for the growth and development of mammals, in which various physiological and biochemical indicators of the body have undergone great changes. The development, differentiation, and maturation of the nervous system are regulated by many proteins. Changes in related proteins affect the physiological functions of the nervous system. However, the regulation of selfrenewal and differentiation of the nervous system at this stage is still poorly understood. The mechanism of differentiation and regulation of the major proteins in the nervous system during this special period of weaning remains to be investigated. Therefore, this paper aims to summarize the alteration of the nervous system during weaning and provide the basis for subsequent research.

Comparison of Anthraquinones, Iridoid Glycosides and Triterpenoids in Morinda officinalis and Morinda citrifolia Using UPLC/Q-TOF-MS and Multivariate Statistical Analysis.

Roots of Morinda officinalis and Morinda citrifolia have been interchangeably used in traditional Chinese medicine. However, there is no experimental evidence to support this. In this study, a ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS)-based approach and a multivariate statistical analysis (MSA) were adopted to compare the difference in the chemical compounds present in the root extract of M. officinalis and M. citrifolia. There were 26 anthraquinones, 15 triterpenes, and 8 iridoid glycosides identified in the root extracts of M. officinalis, 30 anthraquinones, 1 triterpene, and 8 iridoid glycosides in the root extracts of M. citrifolia. Among these, 25 compounds presented in both plants. In addition, a principal component analysis (PCA) showed that these two herbs could be separated clearly. Furthermore, an orthogonal partial least squares-discriminant analysis (OPLS-DA) found 9 components that could be used as chemical markers to discrimination the root extracts of M. officinalis and M. citrifolia. In addition, the results of a Cell Counting Kit 8 (CCK-8) assay and cell colony formation assay indicated that methanol root extracts of M. officinalis and M. citrifolia showed no cell cytotoxicity to normal cells, even promoted the proliferation of normal liver cells. To our knowledge, this is the first time that the differences between the root extracts of M. officinalis and M. citrifolia (Hainan province) have been observed systematically at the chemistry level.

HG30, a tetrahydroanthraquinone compound isolated from the roots of Prismatomeris connate, induces apoptosis in human non-small cell lung cancer cells.

HG30, a tetrahydroanthraquinone compound isolated from the roots of Prismatomeris connate, was previously shown to inhibit the proliferation of A549 cells. The aim of this study was to evaluate the antitumor activity of HG30 in two non-small cell lung cancer cell lines, A549 and H1299, and to explore potential underlying mechanisms. In cell viability and colony formation assays, HG30 treatment suppressed the proliferation and number of colonies formed by A549 and H1299 cells. Western blot analysis further demonstrated that induction of apoptosis by HG30 in A549 and H1299 cells involves both caspase-dependent apoptosis pathways, including mitochondria- and death receptor-mediated pathways, and an apoptosis-inducing factor (AIF) -associated caspase-independent apoptosis pathway. Specifically, HG30 treatment affected Bcl-2 family proteins and inhibitor of apoptosis protein (IAP) family proteins by down-regulating of Mcl-1, survivin and XIAP and up-regulation of Bid, and Bim.

A review of the use of pteridophytes for treating human ailments.

The aim of this review was to explore the pharmacological activity of early tracheophytes (pteridophytes) as an alternative medicine for treating human ailments. As the first vascular plants, pteridophytes (aka, ferns and fern allies) are an ancient lineage, and human beings have been exploring and using taxa from this lineage for over 2000 years because of their beneficial properties. We have documented the medicinal uses of pteridophytes belonging to thirty different families. The lycophyte Selaginella sp. was shown in earlier studies to have multiple pharmacological activity, such as antioxidant, anti-inflammatory, anti-cancer, antidiabetic, antiviral, antimicrobial, and anti-Alzheimer properties. Among all the pteridophytes examined, taxa from the Pteridaceae, Polypodiaceae, and Adiantaceae exhibited significant medicinal activity. Based on our review, many pteridophytes have properties that could be used in alternative medicine for treatment of various human illnesses. Biotechnological tools can be used to preserve and even improve their bioactive molecules for the preparation of medicines against illness. Even though several studies have reported medicinal uses of ferns, the possible bioactive compounds of several pteridophytes have not been identified. Furthermore, their optimal dosage level and treatment strategies still need to be determined. Finally, the future direction of pteridophyte research is discussed.

Garcinone C exerts antitumor activity by modulating the expression of ATR/Stat3/4E­BP1 in nasopharyngeal carcinoma cells.

Nasopharyngeal carcinoma (NPC) is one of the most common head and neck malignancies and is typically treated with radiotherapy and chemotherapy. Garcinone C, a natural compound isolated from Garcinia oblongifolia Champ., is a xanthone derivative with potential cytotoxic effects on certain cancers. However, there are limited studies regarding its effects on NPC cells, and its mechanism of action in NPC remains unknown. In the present study, we found that garcinone C significantly inhibited cell viability of the human NPC cell lines CNE1, CNE2, HK1 and HONE1. This inhibition was exerted in a time­ and dose­dependent manner. Flow cytometry demonstrated that garcinone C arrested the cell cycle at the S phase. Moreover, with 10 µM of high­dose garcinone C treatment, the cells exhibited necrotic morphology changes including cell swelling, rough endoplasmic reticulum degranulation, endoplasmic reticulum dilatation, mitochondrial swelling and vacuolar degeneration. In addition, we found that garcinone C stimulated the expression levels of ATR and 4E­BP1, while efficiently inhibiting the expression levels of cyclin B1, cyclin D1, cyclin E2, cdc2, CDK7 and Stat3. Collectively, the ability of garcinone C to inhibit NPC in growth in vitro suggested that garcinone C may be a novel agent for the management of NPC.

Iridoid glycosides from Callicarpa nudiflora Hook.

Four new iridoid glycoside derivatives (1-4), along with ten known iridoid glycosides (5-14), were isolated from Callicarpa nudiflora Hook et Arn. The structure of the new iridoid glycosides was elucidated as 5″-methoxy-ampicoside (1), 6″-O-trans-caffeoylcatalpol (2), 6″-O-trans-feruloylcatalpol (3) and 3″-methoxy-agnucastoside C (4) on the basis of spectroscopic analysis. Compounds 1-11 were reported from this plant for the first time. The cytotoxic activity of the isolated compounds against human cervical carcinoma Hela cells and ovarian carcinoma HeyA8 cells was evaluated using the microculture tetrazolium assay. Compounds 4, 5, 8, 12 and 13 showed cytotoxic activity against the Hela cell line with IC50 values of 25.3, 48.1, 17.3, 38.3 and 28.2 µM, respectively. While only compound 8 showed cytotoxicity against the HeyA8 cell line, with an IC50 of 35.5 µM.

Protective effects of seed melon extract on CCl4-induced hepatic fibrosis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Citrullus lanatus ssp. vulgaris var. megalaspermus Lin et Chao, was also known as watermelon belongs to family Cucurbitaceae, variously used as healthy food and in the treatment of liver and lungs problems. Currently, Citrullus lanatus has become a major economic crop of medicinal and edible effects with regional characteristics. AIM: This study was designed to evaluate the hepatoprotective and antioxidant activity of the seed melon (Citrullus lanatus ssp. vulgaris var. megalaspermus Lin et Chao) extract (SME) against carbon tetrachloride (CCl4) induced hepatic fibrosis in mice. MATERIALS AND METHODS: In this study, mice were randomly divided into 7 groups, including normal control, model, silymarin tablets as the positive control, SME 100, 200, 400, and 800mg/kg. After 8 weeks, activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TG), hyaluronic acid (HA) and laminin (LN) were checked. The levels of antioxidant enzymes such as superoxide dismutase (SOD), glutataion (GSH) and glutathione peroxidase (GSH-Px) were determined after SME administration. The hydroxyproline (HYP) levels, malondialdehyde (MDA) levels and histopathologic examinations of hepatocyte fibrosis were also determined. Additionally, effects of SME on alpha-smooth muscle actin (α-SMA) and transforming growth factor beta-1(TGF-ß1) protein expressions were determined. RESULTS: We found that SME could significantly lower the serum levels of hepatic enzyme markers AST, ALT, HA and LN (P<0.01). Compared with the CCl4-only treatment group, levels of hepatic SOD and GSH-Px were significantly increased, and the MDA levels were remarkably decreased in mice treated by SME at medium dose (400mg/kg) and high dose (800mg/kg) (P<0.01). A histological examination of the liver showed that lesions, including necrosis, lymphocyte infiltration and fatty degeneration, were partially healed by treatment with SME. The results of protein expressions studies displayed that SME could inhibit α-SMA and TGF-ß1 protein expression (P<0.01). CONCLUSION: The present results suggested that protective effect of SME against CCl4-induced hepatic fibrosis may rely on its effect on reducing oxidative stress and improving drug metabolizing enzyme activity in liver.

Two New Anthraquinones from the Roots of Prismatomeris connata.

Two new anthraquinones, 4-hydroxy-1,2,3-trimethoxy-7-hydroxymethylanthracene-9,10-dione (1) and 1,2,3-trimethoxy-7-hydroxymethylanthracene-9,10- dione (2), were isolated from the roots of Prismatomeris connata, a Chinese medicinal herb. Their structures were elucidated by spectroscopic analysis. Compound 1 exhibited cytotoxicity against a panel of H1229, HTB 179, A549 and H520 lung tumor cell lines with IC50 values ranging from 12.3 to 20 µM.

Prisconnatanones A, a cytotoxic naphthoquinone from Prismatomeris connata, suppresses the proliferation of human laryngocarcinoma HEp-2 cells in vitro.

Prisconnatanones A (Priscon-A) is a rare tetrahydroanthraquinone isolated from herbal Prismatomeris connate. In this study, we examine its anti-tumour activity on human laryngocarcinoma HEp-2 cells in vitro. The CCK-8 assay was performed to evaluate its cytotoxicity. Cell cycle and apoptosis were analysed using flow cytometric analysis. Here, we showed Priscon-A inhibited the proliferation of HEp-2 cells in a dose-dependent manner, and at 5 µM it almost completely inhibited cell growth. Its cytotoxicity was associated with the cell cycle arrest at G2/M phase. The Annexin V-FITC/PI binding assay showed that the cell death induced by Priscon-A was associated with apoptosis. And, western blot analysis revealed that the levels of the apoptosis protein, cleaved caspase-3, PARP, p21 and Bax protein increased, while the level of anti-apoptosis protein Bcl-2 decreased.. These data demonstrated that Priscon-A significantly inhibited HEp-2 cell growth, induced the cell cycle arrest at the G2/M phase and efficiently induced cell apoptosis.

[Chemical constituents of ethyl acetate fraction from seed melon (Citrulluslanatus ssp. vulgaris var. megalaspermus)].

In this paper, the chemical composition of ethyl acetate parts of seed melon were studied by using ethanol re-flux method, extraction method, and isolated by column chromatography oversilica gel and Sephadex LH-20 and HPLC. The structures of the separated compounds were identified by physical-chemical methods and spectral data such as MS, ¹H-NMR, ¹³C-NMR, etc. 12 compounds were got from the plant including one new compound, 4-hydroxymet-hyl-2-methoxyphenyl 1-O-ß-D-[6'-O-(4″-hydroxybenzoyl)-glucopyranoside] (1) and 11 known compounds, uracil (2), thymine (3), 2'-deoxyuridine (4), 7,8-dimethylalloxazine (5), indole-3-carboxylic acid (6), ß-adenosine (7), 4-hydroxybenzoic acid (8), p-coumaric acid (9), cucumegastigmanesⅠ (10), 3'-methoxyl-quercetin-7-O-ß-D-glucopyranoside (11) and 3,3'-dimethyloxy-4,4'-dihydroxy-9,9'-monoepoxy lignan (12).

Seven New Tetrahydroanthraquinones from the Root of Prismatomeris connata and Their Cytotoxicity against Lung Tumor Cell Growth.

The root of Prismatomeris connata has been used in China for centuries as the medicinal herb "Huang Gen" (HG), but its phytochemicals or active ingredients are not well understood. In this study, we performed chemical analysis of the ethyl acetate fraction of a HG ethanol extract. We thus isolated seven new tetrahydroanthraquinones, prisconnatanones C-I (compounds 1-7) from the root of P. connata and identified their structures using spectroscopic analyses. Their absolute configurations were established by both modified Mosher's and Mo2OAc4 methods, and ORD techniques. Their cytotoxicity was tested in a panel of human lung tumor cells (H1229, HTB179, A549 and H520 cell lines). Prisconnatanone I (7) showed the highest activity, with an IC50 value ranging from 2.7 µM to 3.9 µM in the suppression of tumor cell growth, and the others with chelated phenolic hydroxyls exhibited relatively lower activity (IC50: 8-20 µM). In conclusion, these data suggest that some of the natural tetrahydroanthraquinones in HG are bioactive, and hydroxylation at C-1 significantly increases the cytotoxicity of these compounds against lung tumor cell growth.