Pararorine A, isoindolinone alkaloid from the endophytic fungus Paramyrothecium roridum and its anti-tumor activity.

Pararorine A, a new isoindolinone alkaloid was isolated from Paramyrothecium roridum, an endophytic fungus from the medicinal plant Gynochthodes officinalis (F.C. How) Razafim. & B. Bremer. The structure of this compound was elucidated by extensive spectroscopic (UV, IR, MS, and NMR) analyses. In addition, the antitumor activity of pararorine A was evaluated against SF-268, MCF-7, HepG2, and A549 tumor cell lines. The results revealed that pararorine A exhibited potent antitumor activities with the IC50 values ranging from 1.69 to 8.95 µM. Moreover, the tumor cell inhibitory activity of pararorine A was evidenced by promoting cytochrome C release and cell cycle arrest as well as the induction of apoptosis by the up-regulation of the protein expressions of JNK and Bax through PARP-cleavage and caspase 3-cleavage.

Irpexols A-C, xanthone derivatives from the endophyte fungus Irpex laceratus A878.

Three new xanthone derivatives irpexols A-C (1-3) and five known xanthones including three dimeric ones were successfully isolated from Irpex laceratus A878, an endophytic fungus of the family Irpicaceae from the medicinal plant Pogostemon cablin (Blanco) Bentham (Lamiaceae). The structures of these compounds were elucidated by extensive spectroscopic analyses including ultraviolet-visible spectroscopy (UV), infrared spectroscopy (IR), mass spectrometry (MS), and nuclear magnetic resonance (NMR). All of the three new compounds (1-3) share a de-aromatic and highly­oxygenated xanthone skeleton. In addition, the cytotoxic activity of compounds 1-8 were evaluated against SF-268, MCF-7, HepG2, and A549 tumor cell lines. The results revealed that compound 6 showed moderate cytotoxic activity with the IC50 values ranging from 24.83 to 45.46 µM, while the IC50 values of the positive control adriamycin was ranging from 1.11 to 1.44 µM.

Rosemary: Unrevealing an old aromatic crop as a new source of promising functional food additive-A review.

Rosemary (Rosmarinus officinalis L.) is one of the most famous spice plants belonging to the Lamiaceae family as a remarkably beautiful horticultural plant and economically agricultural crop. The essential oil of rosemary has been enthusiastically welcome in the whole world for hundreds of years. Now, it is wildly prevailing as a promising functional food additive for human health. More importantly, due to its significant aroma, food, and nutritional value, rosemary also plays an essential role in the food/feed additive and food packaging industries. Modern industrial development and fundamental scientific research have extensively revealed its unique phytochemical constituents with biologically meaningful activities, which closely related to diverse human health functions. In this review, we provide a comprehensively systematic perspective on rosemary by summarizing the structures of various pharmacological and nutritional components, biologically functional activities and their molecular regulatory networks required in food developments, and the recent advances in their applications in the food industry. Finally, the temporary limitations and future research trends regarding the development of rosemary components are also discussed and prospected. Hence, the review covering the fundamental research advances and developing prospects of rosemary is a desirable demand to facilitate their better understanding, and it will also serve as a reference to provide many insights for the future promotion of the research and development of functional foods related to rosemary.

Peniciriols A and B, two new citrinin derivatives from an endophytic fungus Penicillum citrinum TJNZ-27.

Two undescribed citrinin derivatives, named peniciriols A-B (1-2), together with six known compounds were isolated from endophytic fungus Penicillum citrinum TJNZ-27. The structures of two new compounds were well established by the detail interpretation of NMR and HRESIMS data as well as ECD measurement powered by molecular calculation. Among them, compound 1 shared an unprecedented dimerized citrinin skeleton with the formation of an intriguing 9H-xanthene ring system, whereas compound 2 possess a highly substituted phenylacetic acid skeleton, which was rarely-occurring in natural secondary metabolites. Moreover, these novel compounds were tested for cytotoxic and antibacterial activities, whereas these novel compounds did not exhibit any noticeable cytotoxic or antibacterial activities.

Two new secondary metabolites isolated from the fungus Penicillium virgatum T49-A.

The extensively chemical investigation of the EtOAc extract of the soil fungus Penicillium virgatum T49-A has successfully led to the isolation of two undescribed secondary metabolites penivirtone A (1) and peniviramide B (2) together with six known compounds. Their chemical structures including the absolute configurations of the two new compounds were comprehensively established by extensive analyses of NMR and HRESIMS spectra as well as ECD powered by theoretical calculations. Moreover, the cytotoxic and antibacterial activities of compounds 1-2 were also evaluated, whereas the two novel compounds showed no notable cytotoxic and antibacterial activities.

Preparation, structural characterization, and bioactivities of polysaccharides from Psidium guajava: A review.

Psidium guajava L. is one of the most pivotal members belong to the Myrtaceae family, and it is an important tropical fruit with highly nutritional, healthy, and pharmacological values prevailing in worldwide for decades. The polysaccharides of P. guajava (PGPs) are served as one of the most active constituents, which possess a variety of biofunctionalities including anti-inflammatory, antidiarrheic, antihypertension, and antidiabetic properties. Hence, a systematic review aimed to comprehensively summarize the recent research advances of PGPs is necessary for facilitating their better understanding. The present review discussed current research progress on the PGPs, including extraction and purification methods, structural features, biological activities, and potential pharmacological mechanism. In addition, this review may also provide some valuable insights for further development and potential value in affording functionally useful agents in food industry or therapeutically effective medicine in the fields of P. guajava polysaccharides.

Cytospones E-J from the endophytic fungus Cytospora rhizophorae.

Cytospones E-J (1-6), six unreported α-pyrone derivatives, together with six known ones (7-12) were isolated from the solid culture of the endophytic fungus Cytospora rhizophorae A761, an endophytic fungus from Gynochthodes officinalis. The structures of the unreported compounds were unambiguously elucidated through spectroscopic analyses (1D, 2D NMR and HRESIMS), and their absolute configurations were assigned by single-crystal X-ray diffraction (Cu Kα) analyses. Furthermore, cytospones E-J were evaluated for anti-inflammatory and α-glucosidase inhibitory activities.

Light synergistically promotes the tea green leafhopper infestation-induced accumulation of linalool oxides and their glucosides in tea (Camellia sinensis).

Linalool, which is one of the most representative aroma substances in tea, is transformed into other aroma-related compounds, including linalool 3,6-oxides and linalool 3,7-oxides. The objective of this study was to elucidate the linalool oxide synthesis pathway and its response to stress in tea. By feeding experiment, chemical synthesis, and compound analysis, it was found that linalool can be transformed to linalool oxides via 6,7-epoxylinalool. The conversion rate from 6,7-epoxylinalool to linalool oxides was relatively high under acidic conditions. Four linalool oxide glucosides obtained from tea were structurally characterized. Additionally, tea green leafhopper infestation was observed to activate the whole metabolic flow from linalool into linalool oxides and their glucosides (p < 0.01). Moreover, light treatments further increased the accumulation of linalool oxides and their glucosides (p < 0.05). These results will be useful for elucidating the mechanism mediating linalool oxides content changes in response to stress in tea.

The Chinese medicine Fufang Zhenzhu Tiaozhi capsule protects against renal injury and inflammation in mice with diabetic kidney disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Zhenzhu Tiaozhi capsule (FTZ) is a patented preparation of Chinese herbal medicine that has been used to treat hyperlipidemia, nonalcoholic fatty liver disease, atherosclerosis, and other glucolipid metabolic diseases (GLMDs) in the clinic for almost 10 years. However, how FTZ reduces albuminuria and attenuates diabetic kidney disease (DKD) progression is unknown. AIM OF THE STUDY: To clarify the effects of FTZ on DKD mice model and to explore the underlying mechanisms. MATERIALS AND METHODS: We used streptozotocin (STZ) (40 mg/kg/d, i.p. for 5 days, consecutively) combined with a high-fat diet (HFD) to induce a DKD mouse model, followed by FTZ (1, 2 g/kg/d, i.g.) treatment for 12 weeks. Losartan (30 mg/kg/d, i.g.) was used as a positive control. Measurements of 24 h proteinuria, serum creatinine (SCr), fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), and low density lipoprotein cholesterol (LDL-C) levels and expression levels of fibronectin (FN), collagen IV, inflammatory cytokines, inflammatory cells, interleukin-17A (IL-17A) and the nuclear transcription factor-κB (NF-κB) signaling pathway in the kidney were examined. RESULTS: FTZ effectively decreased 24 h proteinuria, Scr, FBG, TC, TG, and LDL-C levels, inhibited mesangial cell expansion, reduced FN and collagen IV accumulation, and F4/80+ macrophage cell infiltration and Ly-6G+ neutrophil infiltration in glomerulus and tubulointerstitium. Furthermore, IL-17A production and the NF-κB signaling pathway were also downregulated after the administration of FTZ. CONCLUSION: FTZ might attenuate DKD progression, and inhibited kidney inflammation and fibrosis by inhibiting the expression of RORγT and IL-17A in vivo, offering novel insights for the clinical application of FTZ.

Cytotoxic diaporindene and tenellone derivatives from the fungus Phomopsis lithocarpus.

Nine new compounds, including five natural rarely-occurring 2, 3-dihydro-1H-indene derivatives named diaporindenes E-I (1-5), and four new benzophenone analogues named tenellones J-M (6-9) were isolated from the deep-sea sediment-derived fungus Phomopsis lithocarpus FS508. All the structures for these new compounds were fully characterized on the basis of spectroscopic data, NMR spectra, and ECD calculation and single-crystal X-ray diffraction analysis. The potential anti-tumor activities of compounds 1-9 against four tumor cell lines SF-268, MCF-7, HepG-2, and A549 were evaluated using the SRB method. Compound 7 exhibited cytotoxic activity against the SF-268 cell line with an IC50 value of 11.36 µmol·L-1.

Herbivore-Induced (Z)-3-Hexen-1-ol is an Airborne Signal That Promotes Direct and Indirect Defenses in Tea (Camellia sinensis) under Light.

Tea (Camellia sinensis) is the most popular nonalcoholic beverage worldwide. During cultivation, tea plants are susceptible to herbivores and pathogens, which can seriously affect tea yield and quality. A previous report showed that (Z)-3-hexenol is a potentially efficient defensive substance. However, the molecular mechanism mediating (Z)-3-hexenol signaling in tea plants and the resulting effects on plant defenses remain uncharacterized. To clarify the signaling mechanisms in which (Z)-3-hexenol and light are involved, the gene transcription and metabolite levels were assessed, respectively. This study demonstrated that tea plants rapidly and continuously release (Z)-3-hexen-1-ol in response to an insect infestation. (Z)-3-Hexen-1-ol absorbed by adjacent healthy plants would be converted into three insect defensive compounds: (Z)-3-hexenyl-glucoside, (Z)-3-hexenyl-primeveroside, and (Z)-3-hexenyl-vicianoside identified with laboratory-synthesized standards. Moreover, (Z)-3-hexen-1-ol also activates the synthesis of jasmonic acid to enhance the insect resistance of tea plants. Additionally, a continuous light treatment induces the accumulation of (Z)-3-hexenyl-glycosides. Hence, (Z)-3-hexenol serves as a light-regulated signaling molecule that activates the systemic defenses of adjacent plants. Our study reveals the molecular mechanisms by which biotic and abiotic factors synergistically regulate the signaling functions of herbivore-induced plant volatiles in plants, providing valuable information for future comprehensive analyses of the systemic defense mechanisms in plants.

Molecular Mechanism of Palmitic Acid on Myocardial Contractility in Hypertensive Rats and Its Relationship with Neural Nitric Oxide Synthase Protein in Cardiomyocytes.

OBJECTIVE: It is aimed at investigating the mechanism of palmitic acid (PA) on myocardial contractility in hypertensive rats and its relationship with myocardial neural nitric oxide synthase (nNOS) protein. METHODS: The rats were randomly divided into sham operation group and hypertensive group, with thirty rats in each group, to prepare angiotensin II-induced hypertensive model rats. The blood pressure of rats was measured by the multianimal multichannel tail cuff noninvasive blood pressure system of Kent Coda, USA. The Ionoptix single-cell contraction detection system was used to detect myocardial cells. ATP level of left ventricular cardiomyocytes was determined by luminescence method, and protein was measured by Western blot. RESULTS: Compared with the sham group, systolic blood pressure and diastolic blood pressure were increased in the hypertensive group over 4 weeks; PA increased the contractility of left ventricular cardiomyocytes in normal rats, but not in hypertensive rats, and PA increased the intracellular ATP level of rats in the sham group but not in the hypertension group. In the hypertension group, the expression of nNOS in the cardiomyocytes was significantly increased, and specific nNOS inhibitor S-methyl-L-thiocitrulline (SMTC) was found to restore the positive inotropic effect of PA in the myocardium of the hypertension group. PA was supplemented after using CPT-1 inhibitor etomoxir (ETO); it was found that ETO inhibited the positive inotropic effect of PA on left ventricular cardiomyocytes in the sham group, and PA was supplemented after using SMTC and ETO, it was found that SMTC + ETO could inhibit the positive inotropic effect of PA on left ventricular cardiomyocytes in myocardium of hypertensive rats. CONCLUSION: PA could increase the contractility of healthy cardiomyocytes, but had no obvious positive effect on the cardiomyocytes of hypertensive rats, PA enhanced the contractility of cardiomyocytes by increasing ATP level in them, and the inhibitory effect of PA on myocardial contractility in hypertensive rats may be related to the increased nNOS and CPT-1 in cardiomyocytes.

Molecular mechanism of Fufang Zhenzhu Tiaozhi capsule in the treatment of type 2 diabetes mellitus with nonalcoholic fatty liver disease based on network pharmacology and validation in minipigs.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Zhenzhu Tiaozhi formula (FTZ) of which a patented preparation of Chinese herbal medicine has been well documented with significant clinical curative effect for hyperglycemia and hyperlipidemia. Because of the complexity of the chemical constituents of Chinese herbal formulas, the holistic pharmacological mechanism of FTZ acting on type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) remains unclear. AIM OF THE STUDY: To investigate the pharmacological efficacy and mechanism of FTZ in the treatment of T2DM accompanied by NAFLD. MATERIALS AND METHODS: Network pharmacology and validation in minipigs were used in this study. First, potential bioactive compounds of FTZ were identified by the traditional Chinese medicine system pharmacology technology platform (TCMSP). Then, targets of compounds were gathered using DrugBank, SwissTargetPrediction and TCMSP, while targets for T2DM and NAFLD were collected from CTD (compounds-targets-diseases network) and GeneCards. Common targets were defined as direct therapeutic targets acting on T2DM with NAFLD. In addition, crucial targets were chosen by the protein-protein interaction (PPI) network and contribution to compound-therapeutic targets in T2DM with the NAFLD network. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the metabolism-related signaling pathways affected by FTZ. Candidate patterns selected by network pharmacology were tested in the minipigs model of T2DM with NAFLD. Measurements of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting insulin (FINS) and fasting blood glucose (FBG) in the blood and the expression levels of proteins, including PI3K-AKT and HIF-1α, in the livers of the minipigs were followed by the administration of FTZ. RESULTS: A total of 116 active compounds and 82 potential targets related to T2DM and NAFLD were found. Pathway and functional enrichment analysis showed that FTZ mainly regulates metabolism-related pathways, including PI3K-AKT, HIF-1α, TNFα and MAPK. Animal experiments showed that FTZ treatment significantly reduced the serum levels of TG, TC, LDL-C and FBG, increased serum levels of HDL-C, ameliorated systemic insulin resistance (IR), and attenuated liver damage in minipigs with T2DM and NAFLD. FTZ treatment has an obviously favorable influence on hepatic steatosis and liver lipid accumulation in the histopathologic features of HE, Oil red O staining, and electron microscopy. Mechanistically, FTZ improved liver metabolism by increasing the phosphorylation of PI3K-AKT and decreasing the expression of HIF-1α. CONCLUSION: Network pharmacology was supported by experimental studies, which indicated that FTZ has demonstrated therapeutic benefits in T2DM and NAFLD by regulating the PI3K-AKT and HIF-1α signaling pathways.

Trichothecene macrolides from the endophytic fungus Paramyrothecium roridum and their cytotoxic activity.

The chemical investigation of the secondary metabolites of Paramyrothecium roridum (homotypic synonym: Myrothecium roridum), an endophytic fungus isolated from the medicinal plant Morinda officinalis, led to the isolation of twelve cytotoxic trichothecene macrolides, including two new ones, named myrothecines H and I. The structures of the new macrolides were elucidated by extensive spectroscopic measurements analyses. In addition, the cytotoxic activities of these compounds were evaluated against SF-268, NCI-H460, and HepG-2 tumor cell lines, and all isolated compounds (1-12) exhibited significant cytotoxic activity with the IC50 ranging from 0.0002-16.2 µM. Moreover, the inhibitory activity of myrothecines H and I was evidenced by inducing phosphorylation of JNK (c-Jun N-terminal protein kinase) protein and the PARP (poly ADP-ribose polymerase) cleavage, and eventually induce apoptosis of HepG-2 cells. The results indicated that myrothecines H and I could be applied as chemotherapeutic agents.

Eutyscoparols A-G, polyketide derivatives from endophytic fungus Eutypella scoparia SCBG-8.

The chemical investigation on Eutypella scoparia SCBG-8, an endophytic fungus isolated from the leaves of Leptospermum brachyandrum, has resulted in the isolation of six new phenolic compounds eutyscoparols A-F (1-6) and one new natural product eutyscoparol G (7). The structures and absolute configurations of compounds 1-7 were determined by extensive chemical and spectroscopic analyses such as single crystal X-ray diffractions. Moreover, all compounds were evaluated for their antibacterial and cytotoxic activities in vitro.

Renshen Shouwu extract enhances neurogenesis and angiogenesis via inhibition of TLR4/NF-κB/NLRP3 signaling pathway following ischemic stroke in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Renshen Shouwu extract (RSSW) is a patented Traditional Chinese Medicine included in Chinese Pharmacopoeia for neurasthenia, forgetfulness, insomnia, inappetence and excessive fatigue. Our previous study had demonstrated the neuroprotective effect of RSSW against ischemic stroke in rats with middle cerebral artery occlusion (MCAO). However, its underlying mechanism remains unknown. AIM OF THE STUDY: In this study, we investigated the neurogenesis and angiogenesis effects of RSSW in ischemic stroke rats, and further revealed its underlying mechanism focused on TLR4/NF-κB/NLRP3 signaling pathway. MATERIALS AND METHODS: Firstly, active compounds of RSSW were determined by High Performance Liquid Chromatography (HPLC). Secondly, Middle cerebral artery occlusion (MCAO) was performed to induce ischemic stroke in rats and 2, 3, 5-Triphenyltetrazolium chloride (TTC) staining was employed to evaluate whether MCAO surgery was successfully established. Neurological deficit evaluation was conducted according to the Zea Longa' method. Then, we explored the neurogenesis and angiogenesis effects after oral administration of RSSW (50 mg/kg, 100 mg/kg) in MCAO-induced rats by Immunofluorescence Staining. Moreover, the proteins involved in TLR4/NF-κB/NLRP3 signaling pathway (TLR4, p-NF-κB p65, NF-κB p65, NLRP3, pro-IL-1ß, IL-1ß, pro-Caspase-1, Caspase-1) were determined by western blotting. RESULTS: It was observed that RSSW treatment significantly increased the number of newborn neurons and brain microvessel density (MVD) after ischemic stroke. What's more, RSSW treatment significantly downregulated TLR4, p-NF-κB p65/p65, NLRP3, pro-IL-1ß, IL-1ß, pro-Caspase-1, Caspase-1 proteins involved in TLR4/NF-κB/NLRP3 signaling pathway. CONCLUSIONS: RSSW enhances neurogenesis and angiogenesis via inhibition of TLR4/NF-κB/NLRP3 inflammatory signaling pathway following ischemic stroke in rats. Hence, RSSW may be a promising Chinese Medicine for the treatment of ischemic stroke.

Alternative Pathway to the Formation of trans-Cinnamic Acid Derived from l-Phenylalanine in Tea (Camellia sinensis) Plants and Other Plants.

trans-Cinnamic acid (CA) is a precursor of many phenylpropanoid compounds, including catechins and aroma compounds, in tea (Camellia sinensis) leaves and is derived from l-phenylalanine (l-Phe) deamination. We have discovered an alternative CA formation pathway from l-Phe via phenylpyruvic acid (PPA) and phenyllactic acid (PAA) in tea leaves through stable isotope-labeled precursor tracing and enzyme reaction evidence. Both PPA reductase genes (CsPPARs) involved in the PPA-to-PAA pathway were isolated from tea leaves and functionally characterized in vitro and in vivo. CsPPAR1 and CsPPAR2 transformed PPA into PAA and were both localized in the leaf cell cytoplasm. Rosa hybrida flowers (economic crop flower), Lycopersicon esculentum Mill. fruits (economic crop fruit), and Arabidopsis thaliana leaves (leaf model plant) also contained this alternative CA formation pathway, suggesting that it occurred in most plants, regardless of different tissues and species. These results improve our understanding of CA biosynthesis in tea plants and other plants.

Biochemical Pathway of Benzyl Nitrile Derived from l-Phenylalanine in Tea (Camellia sinensis) and Its Formation in Response to Postharvest Stresses.

Volatiles affect tea (Camellia sinensis) aroma quality and have roles in tea plant defense against stresses. Some volatiles defend against stresses through their toxicity, which might affect tea safety. Benzyl nitrile is a defense-related toxic volatile compound that accumulates in tea under stresses, but its formation mechanism in tea remains unknown. In this study, l-[2H8]phenylalanine feeding experiments and enzyme reactions showed that benzyl nitrile was generated from l-phenylalanine via phenylacetaldoxime in tea. CsCYP79D73 showed activity for converting l-phenylalanine into phenylacetaldoxime, while CsCYP71AT96s showed activity for converting phenylacetaldoxime into benzyl nitrile. Continuous wounding in the oolong tea process significantly enhanced the CsCYP79D73 expression level and phenylacetaldoxime and benzyl nitrile contents. Benzyl nitrile accumulation under continuous wounding stress was attributed to an increase in jasmonic acid, which activated CsCYP79D73 expression. This represents the first elucidation of the formation mechanism of benzyl nitrile in tea.

Increasing Temperature Changes Flux into Multiple Biosynthetic Pathways for 2-Phenylethanol in Model Systems of Tea (Camellia sinensis) and Other Plants.

2-Phenylethanol (2PE) is a representative aromatic aroma compound in tea (Camellia sinensis) leaves. However, its formation in tea remains unexplored. In our study, feeding experiments of [2H8]L-phenylalanine (Phe), [2H5]phenylpyruvic acid (PPA), or (E/Z)-phenylacetaldoxime (PAOx) showed that three biosynthesis pathways for 2PE derived from L-Phe occurred in tea leaves, namely, pathway I (via phenylacetaldehyde (PAld)), pathway II (via PPA and PAld), and pathway III (via (E/Z)-PAOx and PAld). Furthermore, increasing temperature resulted in increased flux into the pathway for 2PE from L-Phe via PPA and PAld. In addition, tomato fruits and petunia flowers also contained the 2PE biosynthetic pathway from L-Phe via PPA and PAld and increasing temperatures led to increased flux into this pathway, suggesting that such a phenomenon might be common among most plants containing 2PE. This represents a characteristic example of changes in flux into the biosynthesis pathways of volatile compounds in plants in response to stresses.

Four new metabolites from the endophytic fungus Diaporthe lithocarpus A740.

One new benzophenone derivative, named tenllone I (1), two new eremophilane derivatives lithocarins B (2) and C (3), and a new monoterpentoid lithocarin D (4), together with two know compounds (5 and 6) were isolated from the endophytic fungus Diaporthe lithocarpus A740. All of the structures for these new compounds were fully characterized and established on the basis of extensive spectroscopic interpretation. In addition, all the isolated compounds were evaluated in vitro for their cytotoxic activity. Compounds 2, 3, and 5 showed weak inhibitory activities against tumor cell lines.