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Phytochemical investigation of Staehelina uniflosculosa Sibth. & Sm. resulted in the isolation of twenty-two natural products: eleven sesquiterpene lactones, artemorin (1), tamirin (2), tanachin (3), reynosin (4), baynol C (5), desacetyl-β-cyclopyrethrosin (6), 1β-hydroxy-4α-methoxy-5α,7α,6β-eudesm-11(13)-en-6,12-olide (7), 1β,4α,6α-trihydroxyeudesm-11-en-8α,12-olide (8), 1β-hydroxy-arbusculin A (9), methyl-1β,4α,6α-trihydroxy-5α,7αH-eudesm-11(13)-en-12-oate (10) and methyl-1β,6α,8α-trihydroxy-5α,7αH-eudesma-4(15),11(13)-dien-12-oate (11); one lignan, pinoresinol (12); one norisoprenoid, loliolide (13); six flavonoids (four genins and two glycosides), hispidulin (14), nepetin (15), jaceosidin (16), eriodictyol (17), eriodictyol-3′-O-β-D-glucoside (18) and eriodictyol-7-O-β-D-glucuronide (19); and three phenolic derivatives (one phenolic acid and two phenolic glucosides), protocatechuic acid (20), arbutin (21) and nebrodenside A (22). From the isolated compounds, only nepetin (15) has been reported previously from the Staehelina genus and, to the best of our knowledge, it is the first time that compound (18) has been identified in Asteraceae. A number of these substances were tested for (a) inhibition of lipoxygenase and acetylocholinesterase, (b) their antioxidant activity using the DPPH (1,1-Diphenyl-2-picrylhydrazyl) method or/and (c) inhibition of lipid peroxidation. The tested components exhibited low antioxidant activity with the exception of 5 and 22, while the effectiveness of these compounds in the inhibition of acetylocholinesterase is limited. Furthermore, Molinspiration, an online computer tool, was used to determine the bioactivity ratings of the isolated secondary metabolites. The compounds' bioactivity ratings for potential therapeutic targets were very promising. [ABSTRACT FROM AUTHOR]

Ginkgo biloba is an ancient plant that has survived up until the present day. Gingko biloba is a rich source of valuable secondary metabolites, particularly terpene trilactones (TTLs) such as ginkgolides and bilobalides, which are obtained from the leaves and seeds of the plant. TTLs have pharmacological properties, including anticancer, anti-dementia, antidepressant, antidiabetic, anti-inflammatory, anti-hypertensive, antiplatelet, immunomodulatory, and neuroprotective effects. However, ginkgo is a very-slow-growing tree that takes approximately 30 years to reach maturity. In addition, the accumulation of TTLs in these plants is affected by age, sex, and seasonal and geographical variations. Therefore, plant cell cultures have been established in ginkgo to produce TTLs. Extensive investigations have been conducted to optimize the culture media, growth regulators, nutrients, immobilization, elicitation, and precursor-feeding strategies for the production of TTLs in vitro. In addition, metabolic engineering and synthetic biology methods have been used for the heterologous production of TTLs. In this review, we present the research strategies applied to cell cultures for the production of TTLs. [ABSTRACT FROM AUTHOR]

To understand the flavor and metabolite differences between the three commercial dried jujube cultivars Huizao (HZ), Hamazao 1 (HMZ), and Qiyuexian (QYX), their soluble sugars, organic acids, volatiles, and metabolites were systematically investigated. The results show that sucrose and malic acid were the main soluble sugar and organic acids contained in these dried jujubes, respectively. Sucrose (573.89 mg/g DW) had the highest presence in HZ, and the total sugar content (898.33 mg/g DW) was the highest in QYX. Both of these had a low total acid content, resulting in relatively high sugar–acid ratios (105.49 and 127.86, respectively) compared to that of HMZ (51.50). Additionally, 66 volatile components were detected in the 3 jujubes. These mainly included acids, aldehydes, esters, and ketones (90.5–96.49%). Among them, (E)-2-nonenal, (E)-2-decenal, heptanal, decanal, nonanal, and octanal were identified as the key aromatic substances of the dried jujubes, and their contents were the highest in HMZ. Moreover, 454 metabolites were identified, including alkaloids, amino acids, flavonoids, lipids, nucleotides, and terpenoids. The highest contents of flavonoids (5.6%) and lipids (24.9%) were detected in HMZ, the highest contents of nucleotides (10.2%) and alkaloids (27%) were found in QYX, and the contents of saccharides (5.7%) and amino acids (23.6%) were high in HZ. Overall, HZ, HMZ, and QYX significantly differ in their flavor and nutrition. HZ tastes better, HMZ is more fragrant, and QYX and HMZ possess higher nutritional values. [ABSTRACT FROM AUTHOR]

Ardisiae Crenatae Radix is an ethnic medicinal herb with good anti-inflammatory activity. Ardisiacrispin B is one of the main components in Ardisiae Crenatae Radix extract, with a content of up to 16.27%, and it may be one of the pharmacological components through which Ardisiae Crenatae Radix exerts anti-inflammatory activity. At present, reports on ardisiacrispin B mainly focus on anti-tumor effects, and there have been no reports on anti-inflammatory activities. As a triterpenoid saponin, due to its large molecular weight and complex structure, the composition of substances that function in the body may include other forms after metabolism, in addition to compounds with original structures. Exploring the anti-inflammatory effects on the prototypes and metabolites of the compound may provide a more comprehensive response to the characteristics of ardisiacrispin B's anti-inflammatory action. In this study, ardisiacrispin B was analyzed for metabolites to explore its metabolic processes in vivo. Subsequently, the anti-inflammatory effects of the prototypes and metabolites were further analyzed through network pharmacology, with the expectation of discovering the signaling metabolic pathways through which they may act. Finally, the anti-inflammatory effects of ardisiacrispin B in vitro and the effects on key signaling pathways at the protein level were explored. The results of this study showed that the isolated compounds were confirmed to be ardisiacrispin B. After the metabolite analysis, a total of 26 metabolites were analyzed, and the metabolism process in rats mainly involves oxidation, dehydration, glucuronide conjugation, and others. Speculation as to the anti-inflammatory molecular mechanisms of the prototypes and metabolites of ardisiacrispin B revealed that it may exert its anti-inflammatory effects mainly by affecting the PI3K-AKT pathway. Further anti-inflammatory mechanisms demonstrated that ardisiacrispin B had a good anti-inflammatory effect on LPS-induced RAW264.7 cells and a strong inhibitory effect on NO, TNF-α, and IL-1β release in cells. Furthermore, it had significant inhibitory effects on the expression of PI3K, P-PI3K, AKT, and P-AKT. This study supplements the gaps in the knowledge on the in vivo metabolic process of ardisiacrispin B and explores its anti-inflammatory mechanism, providing an experimental basis for the development and utilization of pentacyclic triterpenoids. [ABSTRACT FROM AUTHOR]

Flavonoids and their derivatives play important roles in plants, such as exerting protective activity against biotic and abiotic stresses, functioning in visual signaling to attract pollinators, and regulating phytohormone activity. They are also important secondary metabolites that are beneficial to humans. Ginkgo biloba L. is a well-known relict plant considered to be a "living fossil". Flavonoids present in ginkgo leaves have antioxidant and anti-aging capacities and show good therapeutic effects on a variety of neurological diseases. To date, studies on flavonoids have mainly focused on their extraction, pharmacological effects, and component analysis and on the expression levels of the key genes involved. However, a systematic review summarizing the biosynthesis and regulatory mechanisms of ginkgo flavonoids is still lacking. Thus, this review was conducted to comprehensively introduce the biological characteristics, value, and utilization status of ginkgo; summarize the effects, biosynthetic pathways, and transcriptional regulation of flavonoids; and finally, discuss the factors (ecological factors, hormones, etc.) that regulate the biosynthesis of flavonoids in ginkgo. This review will provide a reference basis for future research on the biosynthesis and efficient utilization of flavonoids in ginkgo. [ABSTRACT FROM AUTHOR]

α-Glucosidase inhibitors are essential in the treatment of diabetes mellitus. Plant-derived drugs are promising sources of new compounds with glucosidase-inhibiting ability. The Geum aleppicum Jacq. and Sibbaldianthe bifurca (L.) Kurtto & T.Erikss. herbs are used in many traditional medical systems to treat diabetes. In this study, metabolites of the G. aleppicum and S. bifurca herbs in active growth, flowering, and fruiting stages were investigated using high-performance liquid chromatography with photodiode array and electrospray ionization triple quadrupole mass spectrometric detection (HPLC-PDA-ESI-tQ-MS/MS). In total, 29 compounds in G. aleppicum and 41 components in S. bifurca were identified including carbohydrates, organic acids, benzoic and ellagic acid derivatives, ellagitannins, flavonoids, and triterpenoids. Gemin A, miquelianin, niga-ichigoside F1, and 3,4-dihydroxybenzoic acid 4-O-glucoside were the dominant compounds in the G. aleppicum herb, while guaiaverin, miquelianin, tellimagrandin II2, casuarictin, and glucose were prevailing compounds in the S. bifurca herb. On the basis of HPLC activity-based profiling of the G. aleppicum herb extract, the most pronounced inhibition of α-glucosidase was observed for gemin A and quercetin-3-O-glucuronide. The latter compound and quercetin-3-O-arabinoside demonstrated maximal inhibition of α-glucosidase in the S. bifurca herb extract. The obtained results confirm the prospects of using these plant compounds as possible sources of hypoglycemic nutraceuticals. [ABSTRACT FROM AUTHOR]

Actinomycetes are essential sources of numerous bioactive secondary metabolites with diverse chemical and bioactive properties. Lichen ecosystems have piqued the interest of the research community due to their distinct characteristics. Lichen is a symbiont of fungi and algae or cyanobacteria. This review focuses on the novel taxa and diverse bioactive secondary metabolites identified between 1995 and 2022 from cultivable actinomycetota associated with lichens. A total of 25 novel actinomycetota species were reported following studies of lichens. The chemical structures and biological activities of 114 compounds derived from the lichen-associated actinomycetota are also summarized. These secondary metabolites were classified into aromatic amides and amines, diketopiperazines, furanones, indole, isoflavonoids, linear esters and macrolides, peptides, phenolic derivatives, pyridine derivatives, pyrrole derivatives, quinones, and sterols. Their biological activities included anti-inflammatory, antimicrobial, anticancer, cytotoxic, and enzyme-inhibitory actions. In addition, the biosynthetic pathways of several potent bioactive compounds are summarized. Thus, lichen actinomycetes demonstrate exceptional abilities in the discovery of new drug candidates. [ABSTRACT FROM AUTHOR]

Phytochemical investigation of the aerial parts of Artemisia heptapotamica Poljak led to the isolation of ten known compounds, including four alkyl p-coumarates: octadecyl trans-p-coumarate (1), icosy trans-p-coumarate (2), docosyl trans-p-coumarate (3), and tetracosyl trans-p-coumarate (4), one sesquiterpene lactone: santonin (5), four flavonoids; axillarin (6), quercetin 3-O-methyl ether (7), luteolin (8), and quercetin (9), and one phenolic acid derivative: p-coumaric acid (10). The structures of the isolated compounds were identified by various spectroscopic analyses. Additionally, the antimicrobial activity of the total extract and different fractions was screened, and they exhibited no inhibition of the growth of Candida albicans, C. neoformans, Aspergillus fumigatus, methicillin-resistant Staphylococcus aureus (MRS), E. coli, Pseudomonas aeruginosa, Klebsiella pneumonia, and Vancomycin-resistant Enterococci (VRE) at the tested concentrations ranging from 8 to 200 μg/mL. The identification and tentative characterization of the secondary metabolites were conducted using LC-QToF analysis. This method helps in the putative characterization of sesquiterpene lactones, flavonoids, coumarate derivatives, and aliphatic compounds. The developed method identified 43 compounds, of which the majority were sesquiterpene lactones, such as eudesmanolides, germacranolides, and guaianolide derivatives, followed by flavonoids. The proposed LC-QToF method helps develop dereplication strategies and understand the major class of chemicals before proceeding with the isolation of compounds. [ABSTRACT FROM AUTHOR]

To compare the chemical distinctions of Panax ginseng Meyer in different growth environments and explore the effects of growth-environment factors on P. ginseng growth, an ultra-performance liquid chromatography–tandem triple quadrupole time-of-flight mass spectrometry (UPLC-Triple-TOF-MS/MS) was used to characterize the ginsenosides obtained by ultrasonic extraction from P. ginseng grown in different growing environments. Sixty-three ginsenosides were used as reference standards for accurate qualitative analysis. Cluster analysis was used to analyze the differences in main components and clarified the influence of growth environment factors on P. ginseng compounds. A total of 312 ginsenosides were identified in four types of P. ginseng, among which 75 were potential new ginsenosides. The number of ginsenosides in L15 was the highest, and the number of ginsenosides in the other three groups was similar, but it was a great difference in specie of ginsenosides. The study confirmed that different growing environments had a great influence on the constituents of P. ginseng, and provided a new breakthrough for the further study of the potential compounds in P. ginseng. [ABSTRACT FROM AUTHOR]

Minor genera actinomycetes are considered a promising source of new secondary metabolites. The strain Kribbella sp. CA-293567 produces sandramycin and kribbellichelins A & B In this work, we describe the complete genome sequencing of this strain and the in silico identification of biosynthetic gene clusters (BGCs), focusing on the pathways encoding sandramycin and kribbellichelins A–B. We also present a comparative analysis of the biosynthetic potential of 38 publicly available genomes from Kribbella strains. [ABSTRACT FROM AUTHOR]

Phenols are major compounds produced by plant species as a peripheral stimulus or as a regulatory defense mechanism under different environmental biotic stresses. These secondary metabolites are generated from shikimic and acetic acid metabolic pathways. The aromatic benzene ring compound plays an important role in plant development, especially in the defense forefront. They provide structural integrity and support to the plants. Phenolic phytoalexins released by pathogen/arthropod-attacked or wounded plants nullify or repel organisms for the advantage of the host. The allelopathic potential of phenolic compounds is observed in both natural and managed ecosystems. The global impacts of climatic variabilities such as drought, increased carbon dioxide, or greenhouse gas emissions alter the quantitative response of plant phenols. This review primarily discusses the different aspects of phenolic interactions concerning health, antioxidant properties, and insect-plant interaction as a nexus of soil and plant relations in response to variable climatic conditions. [ABSTRACT FROM AUTHOR]

A balanced gut microbiota and their metabolites are necessary for the maintenance of the host's health. The antibiotic-induced dysbiosis can cause the disturbance of the microbial community, influence the immune homeostasis and induce susceptibility to metabolic- or immune-mediated disorders and diseases. The Lactobacillus and their metabolites or components affect the function of the host's immune system and result in microbiota-mediated restoration. Recent data have indicated that, by altering the composition and functions of gut microbiota, antibiotic exposure can also lead to a number of specific pathologies, hence, understanding the potential mechanisms of the interactions between gut microbiota dysbiosis and immunological homeostasis is very important. The Lactobacillus strategies for detecting the associations between the restoration of the relatively imbalanced microbiome and gut diseases are provided in this discussion. In this review, we discuss the recently discovered connections between microbial communities and metabolites in the Lactobacillus treatment of β-lactam antibiotic-induced dysbiosis, and establish the relationship between commensal bacteria and host immunity under this imbalanced homeostasis of the gut microbiota. [ABSTRACT FROM AUTHOR]

Betulinic acid (BA) has been extensively studied in recent years mainly for its antiproliferative and antitumor effect in various types of cancers. Limited data are available regarding the pharmacokinetic profile of BA, particularly its metabolic transformation in vivo. In this study, we present the screening and structural investigations by ESI Orbitrap MS in the negative ion mode and CID MS/MS of phase I and phase II metabolites detected in mouse plasma after the intraperitoneal administration of a nanoemulsion containing BA in SKH 1 female mice. Obtained results indicate that the main phase I metabolic reactions that BA undergoes are monohydroxylation, dihydroxylation, oxidation and hydrogenation, while phase II reactions involved sulfation, glucuronidation and methylation. The fragmentation pathway for BA and its plasma metabolites were elucidated by sequencing of the precursor ions by CID MS MS experiments. [ABSTRACT FROM AUTHOR]

The roots of Sophora tonkinensis Gagnep., a traditional Chinese medicine, is known as Shan Dou Gen in the Miao ethnopharmacy. A large number of previous studies have suggested the usage of S. tonkinensis in the folk treatment of lung, stomach, and throat diseases, and the roots of S. tonkinensis have been produced as Chinese patent medicines to treat related diseases. Existing phytochemical works reported more than 300 compounds from different parts and the endophytic fungi of S. tonkinensis. Some of the isolated extracts and monomer compounds from S. tonkinensis have been proved to exhibit diverse biological activities, including anti-tumor, anti-inflammatory, antibacterial, antiviral, and so on. The research progress on the phytochemistry and pharmacological activities of S. tonkinensis have been systematically summarized, which may be useful for its further research. [ABSTRACT FROM AUTHOR]

Plants thrive under abiotic and biotic stress conditions with the changes in phytohormones like salicylic acid (SA), resulting in the synthesis of secondary metabolites. The present study determines the response of plants in producing secondary metabolites towards different SA concentrations at varying time intervals. Liquid chromatography-mass spectrometry-based metabolomics studies in Aphanamixis polystachya (Wall.) Parker seedlings are grown at 10 mM, 50 mM, and 100 mM SA concentrations, showed the differential expression of metabolites towards the stress. Alkaloids like amaranthin showed a 15-fold increase on the second day, and analog of androvinblastin showed a 20-fold increase on the sixth day in 10 mM SA compared with other groups. Flavanoid cyanidin 3-3 glucosyl was found to be with a 22-fold increment along with terpenoids betavulgaroside (18-fold), asiaticoside (17-fold), mubenin B (20-fold), and deslanoside (22-fold) increment in 50 mM SA on the sixth day. The shock exerted by 100 mM was too harsh, and the lowered metabolite production level was insufficient for the seedlings to survive at this higher SA condition. Arrangement of stressed groups using Pearson correlation studies, principal component analysis, and partial least square analysis placed 10 mM SA and controlled group closer and 50 mM SA and 100 mM SA groups closer to each other. The study observed that SA regulates metabolites that mediate biotic stress responses at low concentrations, and higher concentrations regulate abiotic stress regulating metabolites. [ABSTRACT FROM AUTHOR]

This study aimed to determine the chemical composition of different types of tissue of Cedrus brevifolia Henry (Pinaceae) methanolic extracts, namely needles, twigs, branches, and bark. Cedrus brevifolia is a narrow endemic coniferous tree species of Cyprus, growing in a sole population in the mountainous area of Paphos Forest. Chemical analysis of the extracts was performed using liquid chromatography combined with time-of-flight high-resolution mass spectrometry (LC/Q-TOF/HRMS). The majority of the 36 compounds tentatively identified belonged to the flavonoids family. The extract of needles was the richest extract in terms of secondary metabolites. The extracts were studied for their antioxidant activity using the DPPH free radical scavenging assay. Additionally, the antibacterial activity was evaluated by determining both the minimum inhibitory concentration and the minimum bactericidal concentration against Staphylococcus aureus and Escherichia coli. All extracts demonstrated antioxidant property, while bark gave the highest antioxidant capacity (IC50 value of 0.011 mg/mL) compared to the other tissues. Antibacterial activity was observed against both types of bacteria, with the extract of branches presenting the strongest activity against S. aureus (MIC, 0.097 mg/mL and MBC, 0.195 mg/mL). This is the first time that extracts of needles, twigs, branches, and bark of C. brevifolia are compared regarding their chemical composition as well as their antimicrobial and antioxidant properties. [ABSTRACT FROM AUTHOR]

The compounds 11,12,13-tri-nor-sesquiterpenes are degraded sesquiterpenoids which have lost the C3 unit of isopropyl or isopropenyl at C-7 of the sesquiterpene skeleton. The irregular C-backbone originates from the oxidative removal of a C3 side chain from the C15 sesquiterpene, which arises from farnesyl diphosphate (FDP). The C12-framework is generated, generally, in all families of sesquiterpenes by oxidative cleavage of the C3 substituent, with the simultaneous introduction of a double bond. This article reviews the isolation, biosynthesis and biological activity of this special class of sesquiterpenes, the 11,12,13-tri-nor-sesquiterpenes. [ABSTRACT FROM AUTHOR]

The genus Pseudonocardia belongs to a group of Actinomycetes, and is a member of the family Pseudonocardiacea. The members of this genus are aerobic, Gram‐positive, non‐motile bacteria that are commonly found in soil, plant and environment. Although this genus has a low clinical significance; however, it has an important role in biotechnology due to the production of secondary metabolites, some of which have anti‐bacterial, anti‐fungal and anti‐tumour effects. The use of phenotypic tests, such as gelatinase activity, starch hydrolysis, catalase and oxidase tests, as well as molecular methods, such as polymerase chain reaction, are necessary for Pseudonocardia identification at the genus and species levels. [ABSTRACT FROM AUTHOR]

1. Iris tectorum Maxim is a traditional herbal medicine that has been used to treat cancer, abdominal distension, hepatic cirrhosis, and inflammatory diseases. How I. tectorum Maxim is metabolised and the mechanistic basis for its pharmacological activity remain to be defined. 2. This study was designed to clarify the metabolism of I. tectorum Maxim and to explore the mechanistic basis for its pharmacological activity. 3. In the present study, 51 metabolites were identified via mass spectrometry in samples of bile, urine, and faeces from Wistar rats. Metabolites were mainly formed by glucuronidation, sulphation, methylation, and amino acid conjugation. 4. Tectoridin, tectorigenin, irigenin, iristectorigenin A, iristectorigenin B, and 6-hydroxygenistein were identified as potentially be bioactive candidate metabolites for which 36 putative targets and 90 interactions were detected through a network pharmacology analysis. Gene set enrichment analyses and compound-disease networks revealed the targets of these metabolites to regulate important proteins associated with cancer as well as cardiovascular, urogenital, and digestive system diseases. 5. Molecular docking confirmed the interactions of these six candidate bioactive metabolites with carbonic anhydrase IV, VII, and XII. 6. Overall, these data offer new insights into the metabolism and pharmacological activity of I. tectorum Maxim in vivo. [ABSTRACT FROM AUTHOR]

Sepsis is the dysregulated host response to an infection which leads to life-threatening organ dysfunction. Metabolomic profiling in bio-fluid or tissue is vital for elucidating the pathogenesis of sepsis and evaluating therapeutic effects of medication. In this study, an untargeted metabolomics approach was applied to study the metabolic changes in lung tissue of septic rats induced by cecal ligation and puncture (CLP) and investigate the treatment effects of Xubijing injection (XBJ). Metabolomics analyses were performed on ultra-high performance liquid chromatography-Q Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry (UHPLC-Q-Orbitrap-HRMS) together with multivariate statistical analysis. A total of 26 differential metabolites between CLP and sham-operated group were identified. The altered metabolic pathways included energy metabolism, amino metabolism, lipid metabolism, fatty acid metabolism and hormone metabolism. Among the 26-varied metabolites, 15 were significantly regulated after XBJ treatment. The metabolic pathway network of sepsis was drawn to interpret the pathological feature of lung damage caused by sepsis and the underlying regulating mechanism of XBJ on the molecular levels. Our findings display that LC-MS-based metabolomics is a useful tool for uncovering the underlying molecular mechanism of sepsis, and XBJ may exert therapeutic effect by regulating multiple metabolic pathways. [ABSTRACT FROM AUTHOR]

Sesquiterpene lactones (SL), characterized by their high prevalence in the Asteraceae family, are one of the major groups of secondary metabolites found in plants. Researchers from distinct research fields, including pharmacology, medicine, and agriculture, are interested in their biological potential. With new SL discovered in the last years, new biological activities have been tested, different action mechanisms (synergistic and/or antagonistic effects), as well as molecular structure–activity relationships described. The review identifies the main sesquiterpene lactones with interconnections between immune responses and anti-inflammatory actions, within different cellular models as well in in vivo studies. Bioaccessibility and bioavailability, as well as molecular structure–activity relationships are addressed. Additionally, plant metabolic engineering, and the impact of sesquiterpene lactone extraction methodologies are presented, with the perspective of biological activity enhancement. Sesquiterpene lactones derivatives are also addressed. This review summarizes the current knowledge regarding the therapeutic potential of sesquiterpene lactones within immune and inflammatory activities, highlighting trends and opportunities for their pharmaceutical/clinical use. [ABSTRACT FROM AUTHOR]

Polygala species are frequently used worldwide in the treatment of various diseases, such as inflammatory and autoimmune disorders as well as metabolic and neurodegenerative diseases, due to the large number of secondary metabolites they contain. The present study was performed on Polygala inexpectata, which is a narrow endemic species for the flora of Turkey, and resulted in the isolation of nine known compounds, 6,3′-disinapoyl-sucrose (1), 6-O-sinapoyl,3′-O-trimethoxy-cinnamoyl-sucrose (tenuifoliside C) (2), 3′-O-(O-methyl-feruloyl)-sucrose (3), 3′-O-(sinapoyl)-sucrose (4), 3′-O-trimethoxy-cinnamoyl-sucrose (glomeratose) (5), 3′-O-feruloyl-sucrose (sibiricose A5) (6), sinapyl alcohol 4-O-glucoside (syringin or eleutheroside B) (7), liriodendrin (8), and 7,4′-di-O-methylquercetin-3-O-β-rutinoside (ombuin 3-O-rutinoside or ombuoside) (9). The structures of the compounds were determined by the spectroscopic methods including 1D-NMR (1H NMR, 13C NMR, DEPT-135), 2D-NMR (COSY, NOESY, HSQC, HMBC), and HRMS. The isolated compounds were shown in an in silico setting to be accommodated well within the inhibitor-binding pockets of myeloperoxidase and inducible nitric oxide synthase and anchored mainly through hydrogen-bonding interactions and π-effects. It is therefore plausible to suggest that the previously established anti-inflammatory properties of some Polygala-derived phytochemicals may be due, in part, to the modulation of pro-inflammatory enzyme activities. [ABSTRACT FROM AUTHOR]

The chromone and flavonoid alkaloids represent an unusual group of structurally diverse secondary metabolites, derived from the convergence of multiple biosynthetic pathways that are widely distributed through the plant and animal kingdoms. Many of them have been discovered through bioassay-guided chemical investigations of traditional medicines, suggesting potential therapeutic significance. Their unique structures and varied pharmacological activities may provide important new leads for the discovery of drugs with novel mechanisms of action. Potential therapeutic indications are as diverse as cancer and viral infections, inflammation and immunomodulation, neurological and psychiatric conditions, and diabetes. [ABSTRACT FROM AUTHOR]

A metabonomics method using 1H nuclear magnetic resonance spectroscopy (¹HNMR) was applied to obtain a systematic view of the development and progression of postmenopausal osteoporosis. Using partial least squares discriminant analysis (PLS-DA), 26 and 34 characteristic resonances were found respectively in urine and plasma of ovariectomized rats (Variable importance, VIP value ≥1.0), and the significant altered metabolites identified in the plasma and urine were 10 and 9, respectively. Changes in these metabolites were related to the pathways of lipid, energy and amino acid metabolism, some of which involved the oxidative system. The described method was also used to analyze the therapeutic effects of Er-Xian Decoction (EXD), a traditional Chinese medicine widely used in the clinical treatment of osteoporosis in China. The results showed that EXD administration could provide satisfactory effects on osteoporosis through partially regulating the perturbed pathways of lipid, energy and amino acid metabolism and improving the anti-oxidative ability. [ABSTRACT FROM AUTHOR]

Chromone glycosides comprise an important group of secondary metabolites. They are widely distributed in plants and, to a lesser extent, in fungi and bacteria. Significant biological activities, including antiviral, anti-inflammatory, antitumor, antimicrobial, etc., have been discovered for chromone glycosides, suggesting their potential as drug leads. This review compiles 192 naturally occurring chromone glycosides along with their sources, classification, biological activities, and spectroscopic features. Detailed biosynthetic pathways and chemotaxonomic studies are also described. Extensive spectroscopic features for this class of compounds have been thoroughly discussed, and detailed 13C-NMR data of compounds 1–192, have been added, except for those that have no reported 13C-NMR data. [ABSTRACT FROM AUTHOR]

In the search for novel anti-infectives from natural sources, fungi, in particular basidiomycetes, have proven to still harbor so much potential in terms of secondary metabolites diversity. There have been numerous reports on isolating numerous secondary metabolites from genus Laetiporus. This study reports on two new triterpenoids, laetiporins C and D, and four known triterpenes from the fruiting body of L. sulphureus. The structures of the isolated compounds were elucidated based on their 1D and 2D nuclear magnetic resonance (NMR) spectroscopic data in combination with high-resolution electrospray mass spectrometric (HR-ESIMS) data. Laetiporin C exhibited weak antifungal activity against Mucor hiemalis. Furthermore, the compounds showed weak antiproliferative activity against the mouse fibroblast L929 and human cancer cell lines, including KB-3-1, A431, MCF-7, PC-3 and A549. [ABSTRACT FROM AUTHOR]

The metabolites profile of a plant is greatly influenced by geographical factors and the ecological environment. Various studies focused on artemisinin and its derivates for their antiparasitic and antitumoral effects. However, after the isolation and purification stage, their pharmaceutical potential is limited due to their low bioavailability, permeability and lifetime. The antibacterial activity of essential oils has been another topic of interest for many studies on this plant. Nevertheless, only a few studies investigate other metabolites in Artemisia annua. Considering that secondary metabolites act synergistically in a plant, the existence of other metabolites with antitumor and high immunomodulating activity is even more important. Novel nano-carrier systems obtained by loading herbs into magnetic nanoparticles ensures the increase in the antitumor effect, but also, overcoming the barriers related to permeability, localization. This study reported the first complete metabolic profile from wild grown Romanian Artemisia annua. A total of 103 metabolites were identified under mass spectra (MS) positive mode from 13 secondary metabolite categories: amino acids, terpenoids, steroids, coumarins, flavonoids, organic acids, fatty acids, phenolic acids, carbohydrates, glycosides, aldehydes, hydrocarbons, etc. In addition, the biological activity of each class of metabolites was discussed. We further developed a simple and inexpensive nano-carrier system with the intention to capitalize on the beneficial properties of both components. Evaluation of the nano-carrier system's morpho-structural and magnetic properties was performed. [ABSTRACT FROM AUTHOR]

Ageratina adenophora is one of the major invasive weeds that causes instability of the ecosystem. Research has reported that A. adenophora produces allelochemicals that inhibit the growth and development of food crops, and also contain some toxic compounds that cause toxicity to animals that consume it. Over the past decades, studies on the identification of major toxic compounds of A. adenophora and their toxic molecular mechanisms have been reported. In addition, weed control interventions, such as herbicides application, was employed to reduce the spread of A. adenophora. However, the development of therapeutic and prophylactic measures to treat the various A. adenophora—induced toxicities, such as hepatotoxicity, splenotoxicity and other related disorders, have not been established to date. The main toxic pathogenesis of A. adenophora is oxidative stress and inflammation. However, numerous studies have verified that some extracts and secondary metabolites isolated from A. adenophora possess anti-oxidation and anti-inflammation activities, which implies that these extracts can relieve toxicity and aid in the development of drug or feed supplements to treat poisoning-related disorders caused by A. adenophora. Furthermore, beneficial bacteria isolated from rumen microbes and A. adenophora can degrade major toxic compounds in A. adenophora so as to be developed into microbial feed additives to help ameliorate toxicity mediated by A. adenophora. This review presents an overview of the toxic mechanisms of A. adenophora, provides possible therapeutic strategies that are available to mitigate the toxicity of A. adenophora and introduces relevant information on identifying novel prophylactic and therapeutic measures against A. adenophora—induced toxicity. [ABSTRACT FROM AUTHOR]

The metabolism of scutellarein was investigated in rats. Four metabolites (M1-M4) together with scutellarein were detected and identified as scutellarein-glucuronides in rat plasma by HPLC-DAD, HPLC-MS, and HPLC-MS/MS. [ABSTRACT FROM AUTHOR]

Xanthones are secondary metabolites found in plants, fungi, lichens, and bacteria from a variety of families and genera, with the majority found in the Gentianaceae, Polygalaceae, and Clusiaceae. They have a diverse range of bioactivities, including anti-oxidant, anti-bacterial, anti-malarial, anti-tuberculosis, and cytotoxic properties. Xanthone glucosides are a significant branch of xanthones. After glycosylation, xanthones may have improved characteristics (such as solubility and pharmacological activity). Currently, no critical review of xanthone glucosides has been published. A literature survey including reports of naturally occurring xanthone glucosides is included in this review. The isolation, structure, bioactivity, and synthesis of these compounds were all explored in depth. [ABSTRACT FROM AUTHOR]

Natural disesquiterpenoids represent a small group of secondary metabolites characterized by complex molecular scaffolds and interesting pharmacological profiles. In the last decade, more than 400 new disesquiterpenoids have been discovered and fully characterized, pointing out once more the "magic touch" of nature in the design of new compounds. The perfect blend of complex and unique architectures and biological activity has made sesquiterpene dimers an attractive and challenging synthetic target, inspiring organic chemists to find new and biomimetic approaches to replicate the efficiency and the selectivity of natural processes under laboratory conditions. In this work, we present a review covering the literature from 2010 to 2020 reporting all the efforts made in the total synthesis of complex natural disesquiterpenoids. [ABSTRACT FROM AUTHOR]

The objective of the present study was to characterize chemical composition of hitherto unexamined aerial parts of Lactuca sativa var. angustana cv. Grüner Stern. In contrast to leafy and head varieties of the lettuces, asparagus lettuce grown in Europe is much less studied. Fractionation of a methanolic extract from leaves of L. sativa cv. Grüner Stern, supported with HPLC/DAD and 1H NMR analysis, led to the isolation and/or identification of numerous terpenoid and phenolic compounds, including five apocarotenoids—(-)-loliolide, (+)-dehydrovomifoliol, blumenol A, (6S,9S)-vomifoliol, and corchoionoside C; three sesquiterpene lactones; two lignans—((+)-syringaresinol and its 4-O-β-glucoside); five caffeic acid derivatives; and three flavonoids. Some of the compounds, to the best of our knowledge, have never been isolated from L. sativa before. Moreover, monolignols, phenolic acids and a tryptophan-derived alkaloid were found in the analyzed plant material. Stems, leaves and shoot tips of the asparagus lettuce were examined to assess their phenolics and sesquiterpene lactone content as well as DPPH scavenging activity. Another stem lettuce—L. sativa var. angustana cv. Karola, two cultivars of leafy lettuces and one species of wild lettuce—L. serriola, were also examined as a reference material using HPLC/DAD. The results have been discussed regarding our previous studies and the literature data available. [ABSTRACT FROM AUTHOR]

Natural toxic contaminants have been recognized as threats to human health. Ustiloxins are the toxic secondary metabolites of fungus generated from rice false smut disease, which are harmful to animal/human reproduction and growth. However, there are rare researches on the control and reduction of ustiloxins through physical, chemical and biological ways. Herein, we demonstrated that photocatalysis of semiconductor nanomaterials could be as a potential way to degrade or mitigate the contamination of ustiloxin A. A kind of wormlike graphitic carbon nitride (g-C3N4) was facilely prepared from modified dicyandiamide precursor via pyrolysis method and characterized by X-ray diffraction, high-resolution transmission electron microscope and X-ray photoelectron spectroscopy etc. It was found that g-C3N4 from modified dicyandiamide precursor showed better activity for ustiloxin A degradation under visible light irradiation than that of pristine g-C3N4. This was ascribed to the lager specific surface area, more uniform microstructure, better photogenerated charges separation and transformation of wormlike g-C3N4 compared with pristine g-C3N4. Most important, the structure of degradation intermediates and the possible pathway were proposed based on the results of high-performance liquid chromatography-mass spectrometry after 80 min photoreaction treatment. Our findings may provide a green, efficient way for ustiloxins mitigation and useful information for future study. [ABSTRACT FROM AUTHOR]

The edible and medicinal part of Inula nervosa Wall. (Xiaoheiyao) is confined to its root without sufficient phytochemical and biological investigation. In this study, the secondary metabolites of root, stem, leaf, and flower of I. nervosa Wall. were visualized using Global Natural Products Social Molecular Networking (GNPS), MolNetEnhancer, XCMS(xcmsonline.scripps.edu) analysis, and 'ili mapping based on high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) data to reveal their chemical differences. Among the 11 kinds of chemical repertoires annotated by MolNetEnhancer and 16 hits against the GNPS library, 10-isobutyryloxy-8,9-epoxythymol isobutyrate (1) was revealed as the most dominant and responsible marker between the roots and the other parts. Moreover, a battery of unique MS features as well as differential markers were discovered from different parts of the plant. The chemical differences contribute to the bioactivity differences, which presented in the 2,2-diphenyl-1-picryl-hydrazyl (DPPH)assay and H2O2-insulted HepG2 cells and were in significant correlations with the contents of 1. real-time reverse transcription polymerase chain reaction (RT-PCR)results demonstrated that I. nervosa Wall. extracts upregulated the mRNA expression of nuclear factor E2-related factor 2(Nrf2), heme oxygenase 1(HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1), manganese superoxide dismutase (MnSOD), and glutamate-cysteine ligase catalytic subunit (GCLC) actors involved in antioxidative response in H2O2-challenged HepG2 cells. These findings support the roots of I. nervosa Wall. as active parts of Xiaoheiyao, and also indicate the potential antioxidant activities of other parts. [ABSTRACT FROM AUTHOR]

Phytopathogenic fungi, causing significant economic and production losses, are becoming a serious threat to global food security. Due to an increase in fungal resistance and the hazardous effects of chemical fungicides to human and environmental health, scientists are now engaged to explore alternate non-chemical and ecofriendly management strategies. The use of biocontrol agents and their secondary metabolites (SMs) is one of the potential approaches used today. Trichoderma spp. are well known biocontrol agents used globally. Many Trichoderma species are the most prominent producers of SMs with antimicrobial activity against phytopathogenic fungi. Detailed information about these secondary metabolites, when grouped together, enhances the understanding of their efficient utilization and further exploration of new bioactive compounds for the management of plant pathogenic fungi. The current literature provides the information about SMs of Trichoderma spp. in a different context. In this review, we summarize and group different antifungal SMs of Trichoderma spp. against phytopathogenic fungi along with a comprehensive overview of some aspects related to their chemistry and biosynthesis. Moreover, a brief overview of the biosynthesis pathway, action mechanism, and different approaches for the analysis of SMs and the factors affecting the regulation of SMs in Trichoderma is also discussed. [ABSTRACT FROM AUTHOR]

Nitrogenous sesquiterpenoids fromnatural sourcesare rare, so unsurprisingly neither the potentially valuable bioactivity nor thebroad structural diversity of nitrogenous sesquiterpenoids has been reviewed before. This report covers the progressduring the decade from 2010 to February 2020 on the isolation, identification, and bioactivity of 391 nitrogen-containing natural sesquiterpenes from terrestrial plant, marine organisms, and microorganisms. This complete and in-depth reviewshouldbe helpful for discovering and developing new drugs of medicinal valuerelated to natural nitrogenous sesquiterpenoids. [ABSTRACT FROM AUTHOR]

A simultaneous analytical method for the organophosphorus insecticide fenthion and its five metabolites (fenthion oxon, fenthion oxon sulfoxide, fenthion oxon sulfone, fenthion sulfoxide, and fenthion sulfone) was developed based on ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Five matrices (brown rice, chili pepper, orange, potato, and soybean) were selected to validate the method. The target compounds were analyzed using positive electrospray ionization in the multiple reaction monitoring mode. For the best sensitivity in regard to the detector response, water and methanol containing formic acid (0.1%) were selected as the mobile phase. The optimum extraction efficiency was obtained through a citrate-buffered QuEChERS (quick, easy, cheap, effective, rugged, and safe) method. Recovery tests were carried out at three spiking levels (n = 3). At all fortification levels, the accuracy and precision results were between 70% and 120% with a relative standard deviation of ≤15%. The limit of quantitation was 0.01 mg/kg, and the correlation coefficients (r2) of the matrix-matched calibration curves were >0.99. Significant signal suppression in the detector responses were observed for all matrices, suggesting that a compensation method, such as matrix-matched calibration, is required to provide accurate quantitative results. The applicability of the presented method was confirmed for the simultaneous analysis of fenthion and its metabolites in various crops. [ABSTRACT FROM AUTHOR]

Bacopa monnieri has been used as a reputed drug in the Indian traditional ayurvedic system for centuries. This medicinal herb with important phytopharmaceuticals has been popularly known as "Brahmi". In recent years, B. monnieri has been extensively studied for its bioactive constituents, constituents responsible for memory enhancing effect, and also its diverse other useful effects. It possesses many pharmacological activities such as antioxidant, gastrointestinal, endocrine, antimicrobial, anti-inflammatory etc. The plant has been also used for the treatment of neurological and neuropsychiatric diseases. Due to its multipurpose therapeutic potential, micropropagation using axillary meristems and de novo organogenesis has been extensively studied in the species and is being reviewed. High frequency direct shoot organogenesis can be induced in excised leaf and internode explants in the absence of exogenous phytohormones and the rate of induction is enhanced in the presence of exogenous cytokinins, supplements, growth regulators, etc. Using explants from tissue culture raised plants, direct shoot regeneration leading to production of more than 100 rooted plants/explant within 8–12 weeks period with 85%–100% survival in the field after acclimatization can be expected following optimized protocols. Bioreactor based micropropagation was found to increase the multiplication rate of shoot cultures for the commercial propagation of B. monnieri plants. The maximum content of bacosides has been recorded in shoot biomass using an airlift bioreactor system. Further studies for the biosynthesis of bacosides and other secondary metabolites need to be conducted in the species utilizing untransformed shoot cultures in bioreactors. [ABSTRACT FROM AUTHOR]

Like flavonoids, biflavonoids, dimeric flavonoids, and polyphenolic plant secondary metabolites have antioxidant, antibacterial, antiviral, anti-inflammatory, and anti-cancer properties. However, there is limited data on their effects on cytochrome P450 (P450) and uridine 5′-diphosphoglucuronosyl transferase (UGT) enzyme activities. In this study we evaluate the inhibitory potential of five biflavonoids against nine P450 activities (P450s1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A) in human liver microsomes (HLMs) using cocktail incubation and liquid chromatography-tandem mass spectrometry (LC–MS/MS). The most strongly inhibited P450 activity was CYP2C8-mediated amodiaquine N-dealkylation with IC50 ranges of 0.019~0.123 μM. In addition, the biflavonoids—selamariscina A, amentoflavone, robustaflavone, cupressuflavone, and taiwaniaflavone—noncompetitively inhibited CYP2C8 activity with respective Ki values of 0.018, 0.083, 0.084, 0.103, and 0.142 μM. As selamariscina A showed the strongest effects, we then evaluated it against six UGT isoforms, where it showed weaker inhibition (UGTs1A1, 1A3, 1A4, 1A6, 1A9, and 2B7, IC50 > 1.7 μM). Returning to the P450 activities, selamariscina A inhibited CYP2C9-mediated diclofenac hydroxylation and tolbutamide hydroxylation with respective Ki values of 0.032 and 0.065 μM in a competitive and noncompetitive manner. However, it only weakly inhibited CYP1A2, CYP2B6, and CYP3A with respective Ki values of 3.1, 7.9, and 4.5 μM. We conclude that selamariscina A has selective and strong inhibitory effects on the CYP2C8 and CYP2C9 isoforms. This information might be useful in predicting herb-drug interaction potential between biflavonoids and co-administered drugs mainly metabolized by CYP2C8 and CYP2C9. In addition, selamariscina A might be used as a strong CYP2C8 and CYP2C9 inhibitor in P450 reaction-phenotyping studies to identify drug-metabolizing enzymes responsible for the metabolism of new chemicals. [ABSTRACT FROM AUTHOR]

Iridoids are a class of active compounds that widely exist in the plant kingdom. In recent years, with advances in phytochemical research, many compounds with novel structure and outstanding activity have been identified. Iridoid compounds have been confirmed to mainly exist as the prototype and aglycone and Ι and II metabolites, by biological transformation. These metabolites have been shown to have neuroprotective, hepatoprotective, anti-inflammatory, antitumor, hypoglycemic, and hypolipidemic activities. This review summarizes the new structures and activities of iridoids identified locally and globally, and explains their pharmacokinetics from the aspects of absorption, distribution, metabolism, and excretion according to the differences in their structures, thus providing a theoretical basis for further rational development and utilization of iridoids and their metabolites. [ABSTRACT FROM AUTHOR]

The growing incidence of microorganisms that resist antimicrobials is a constant concern for the scientific community, while the development of new antimicrobials from new chemical entities has become more and more expensive, time-consuming, and exacerbated by emerging drug-resistant strains. In this regard, many scientists are conducting research on plants aiming to discover possible antimicrobial compounds. The secondary metabolites contained in plants are a source of chemical entities having pharmacological activities and intended to be used for the treatment of different diseases. These chemical entities have the potential to be used as an effective antioxidant, antimutagenic, anticarcinogenic and antimicrobial agents. Among these pharmacologically active entities are the alkaloids which are classified into a number of classes, including pyrrolizidines, pyrrolidines, quinolizidines, indoles, tropanes, piperidines, purines, imidazoles, and isoquinolines. Alkaloids that have antioxidant properties are capable of preventing a variety of degenerative diseases through capturing free radicals, or through binding to catalysts involved indifferent oxidation processes occurring within the human body. Furthermore, these entities are capable of inhibiting the activity of bacteria, fungi, protozoan and etc. The unique properties of these secondary metabolites are the main reason for their utilization by the pharmaceutical companies for the treatment of different diseases. Generally, these alkaloids are extracted from plants, animals and fungi. Penicillin is the most famous natural drug discovery deriving from fungus. Similarly, marines have been used as a source for thousands of bioactive marine natural products. In this review, we cover the medical use of natural alkaloids isolated from a variety of plants and utilized by humans as antibacterial, antiviral, antifungal and anticancer agents. An example for such alkaloids is berberine, an isoquinoline alkaloid, found in roots and stem-bark of Berberis asculin P. Renault plant and used to kill a variety of microorganisms. [ABSTRACT FROM AUTHOR]

Characterization and determination of metabolites to monitor metabolic pathways play a paramount role in evaluating the efficacy and safety of medicines. However, the separation and quantification of metabolites are rather difficult due to their limited contents in vivo, especially in the case of Chinese medicine, due to its complexity. In this study, an effective and convenient method was developed to simultaneously quantify bufalin and its nine metabolites (semi-quantitation) in rat plasma after an oral administration of 10 mg/kg to rats. The prototype and metabolites that were identified were subsequently quantified using positive electrospray ionization in multiple reaction monitoring (MRM) mode with transitions of m/z 387.4→369.6 and 387.4→351.3 for bufalin, m/z 513.7→145.3 for IS, and 387.4→369.6, 419.2→365.2, and 403.2→349.2 for the main metabolites (3-epi-bufalin, dihydroxylated bufalin, and hydroxylated bufalin, respectively). The method was validated over the calibration curve range of 1.00–100 ng/mL with a limit of quantitation (LOQ) of 1 ng/mL for bufalin. No obvious matrix effect was observed, and the intra- and inter-day precisions, as well as accuracy, were all within the acceptable criteria in this method. Then, this method was successfully applied in metabolic profiling and a pharmacokinetic study of bufalin after an oral administration of 10 mg/kg to rats. The method of simultaneous determination of bufalin and its nine metabolites in rat plasma could be useful for pharmacokinetic–pharmacodynamic relationship research of bufalin, providing experimental evidence for explaining the occurrence of some adverse effects of Venenum Bufonis and its related preparations. [ABSTRACT FROM AUTHOR]

An imbalance in the production of reactive oxygen species in the body can cause an increase of oxidative stress that leads to oxidative damage to cells and tissues, which culminates in the development or aggravation of some chronic diseases, such as inflammation, diabetes mellitus, cancer, cardiovascular disease, and obesity. Secondary metabolites from Inula species can play an important role in the prevention and treatment of the oxidative stress-related diseases mentioned above. The databases Scopus, PubMed, and Web of Science and the combining terms Inula, antioxidant and secondary metabolites were used in the research for this review. More than 120 articles are reviewed, highlighting the most active compounds with special emphasis on the elucidation of their antioxidative-stress mechanism of action, which increases the knowledge about their potential in the fight against inflammation, cancer, neurodegeneration, and diabetes. Alantolactone is the most polyvalent compound, reporting interesting EC50 values for several bioactivities, while 1-O-acetylbritannilactone can be pointed out as a promising lead compound for the development of analogues with interesting properties. The Inula genus is a good bet as source of structurally diverse compounds with antioxidant activity that can act via different mechanisms to fight several oxidative stress-related human diseases, being useful for development of new drugs. [ABSTRACT FROM AUTHOR]

Ammonia is one of the major toxic components of metabolites in blood and tissues of high-producing dairy cows and could affect the health of bovine mammary glands. Bovine mammary epithelial cells are sensitive to oxidative stress induced by intensive cell metabolism. In our previous study, we found that ammonia could induce oxidative stress, apoptosis and inflammatory responses in bovine mammary epithelial cells. In the present study, the cytoprotective effects of astragaloside IV against ammonia in vitro were explored. The results demonstrated that pretreatment of MAC-T cells with astragaloside IV could potently suppress the increase in the level of intracellular reactive oxygen species (ROS) and the rate of cell apoptosis, inhibit the ammonia-induced inflammatory responses, and rescue the decrease of cell viability. Astragaloside IV prevented ammonia-induced endoplasmic reticulum stress. Astragaloside IV also significantly suppressed the levels of BAX, caspase 3 and p53 phosphorylation in ammonia-induced MAC-T cells. Nuclear factor erythroid 2-related factor 2(Nrf2) was essential for cytoprotective effects of astragaloside IV in MAC-T cells, as knockdown of Nrf2 dramatically abolished the prosurvival effects of astragaloside IV on treated cells. Furthermore, the PI3K/AKT and ERK/MAPK pathways were responsible for the induction of Nrf2 by astragaloside IV. In conclusion, astragaloside IV played a beneficial role against ammonia-induced damage of MAC-T cells. This provides a cue for future study to use astragaloside IV as a protective and curative agent against ammonia exposure of mammary glands in dairy cows. [ABSTRACT FROM AUTHOR]