Anti-inflammatory monomeric sorbicillinoids from the marine-fish-derived fungus Trichoderma sp. G13.

Four new monomeric sorbicillinoids, trichillinoids A - D (1-4), along with two known dimeric sorbicillinoids (5 and 6), and five known monomeric sorbicillinoids (7-11), were obtained from the marine-fish-derived fungus Trichoderma sp. G13. They were structurally characterized on the basis of comprehensive spectroscopic investigations (NMR, HRESIMS, and ECD). Compounds 1-4 displayed moderate anti-inflammatory activities, according to inhibiting the production of NO in RAW264.7 cells activated with IC50 values ranging from 14 to 20 µM.

Chromatographic and mass spectrometric technologies for chemical analysis of Euodiae fructus: A review.

INTRODUCTION: Euodiae fructus, also known as Evodiae fructus, is a popular Chinese herbal medicine derived from the dried, nearly ripe fruits of Tetradium ruticarpum (A. Juss.) T. G. Hartley. The main bioactive constituents of Euodiae fructus are alkaloids, limonoids, flavonoids, and anthraquinones. The contents of these compounds vary greatly between different plant species, geographic locations, and harvest times, which thus affect the therapeutic effects. OBJECTIVES: We aimed to summarize the chromatographic and mass spectrometric technologies applied for chemical analysis and quality evaluation of Euodiae fructus. Moreover, we aimed to emphasize the diverse soft ionization techniques and mass analyzers of LC-MS methods for assessment of Euodiae fructus. METHODOLOGY: A literature study was carried out by retrieving articles published between January 1988 and December 2021 from well-known databases, including PubMed, ASC, Elsevier, ScienceDirect, J·STAGE, Thieme, Taylor & Francis, Springer Link, Wiley Online Library, and CNKI. The chemical analysis methods were described in several categories in accordance with the used analytical techniques, including thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), high-performance liquid chromatography-mass spectrometry (HPLC-MS), gas chromatography-mass spectrometry (GC-MS), capillary electrophoresis (CE), and counter-current chromatography (CCC). RESULTS: This review systematically summarizes the achievements in chemical analysis and quality evaluation of Euodiae fructus published in over three decades, covering the various chromatographic and mass spectrometric technologies applied for identification and quantification of phytochemical constituents. CONCLUSION: The summary serves as an important basis for future phytochemical research and implementation of quality control methods in order to ensure the efficacy and safety of Euodiae fructus.

Comprehensive transcriptional variability analysis reveals gene networks regulating seed oil content of Brassica napus.

BACKGROUND: Regulation of gene expression plays an essential role in controlling the phenotypes of plants. Brassica napus (B. napus) is an important source for the vegetable oil in the world, and the seed oil content is an important trait of B. napus. RESULTS: We perform a comprehensive analysis of the transcriptional variability in the seeds of B. napus at two developmental stages, 20 and 40 days after flowering (DAF). We detect 53,759 and 53,550 independent expression quantitative trait loci (eQTLs) for 79,605 and 76,713 expressed genes at 20 and 40 DAF, respectively. Among them, the local eQTLs are mapped to the adjacent genes more frequently. The adjacent gene pairs are regulated by local eQTLs with the same open chromatin state and show a stronger mode of expression piggybacking. Inter-subgenomic analysis indicates that there is a feedback regulation for the homoeologous gene pairs to maintain partial expression dosage. We also identify 141 eQTL hotspots and find that hotspot87-88 co-localizes with a QTL for the seed oil content. To further resolve the regulatory network of this eQTL hotspot, we construct the XGBoost model using 856 RNA-seq datasets and the Basenji model using 59 ATAC-seq datasets. Using these two models, we predict the mechanisms affecting the seed oil content regulated by hotspot87-88 and experimentally validate that the transcription factors, NAC13 and SCL31, positively regulate the seed oil content. CONCLUSIONS: We comprehensively characterize the gene regulatory features in the seeds of B. napus and reveal the gene networks regulating the seed oil content of B. napus.

Old fusidane-type antibiotics for new challenges: Chemistry and biology.

The spread of antibiotic-resistant bacteria and exhausted drug leads render some infections untreatable now and in the future. To deal with these "new challenges", scientists tend to re-pick up "old antibiotics". Fusidane-type antibiotics have been known for nearly 80 years as potent antibacterial agents against gram-positive bacteria, especially Staphylococci, and represent the only triterpene-derived antibiotic class in clinical setting. These attractive characteristics have drawn renewed attention on fusidane-type antibiotics in recent decades. Isolation, characterization, biological evaluation, as well as chemical modifications of fusidane-type antibiotics are increasingly being reported. Combinatorial biosynthesis of this type of antibiotics has been successfully utilized not only for elucidating the biosynthetic pathways, but also for expanding their structural diversity. Some isolated and synthetic compounds exhibit comparable or even more potent biological activity than fusidic acid. This review provides an overview of progress on the studies of structure and biology of fusidane-type antibiotics from 1943 to April 2021. The informative structure-activity relationship is also highlighted.

The alleviative effect of flavonol-type Nrf2 activator rhamnazin from Physalis alkekengi L. var. franchetii (Mast.) Makino on pulmonary disorders.

Rhamnazin (RN) is a flavonol isolated from the calyxes and fruits of Physalis alkekengi L. var. franchetii (Mast.) Makino, which has been used for treating pulmonary diseases in traditional Chinese medicine. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a therapeutic target for pulmonary diseases. In the present study, the underlying mechanism and pharmacological effect of RN against pulmonary disorders are investigated. Human lung epithelial Beas-2B cell and RAW 264.7 murine macrophage-based cell models, and a cigarette smoke (CS)-induced pulmonary impairment mice model are adopted for investigation in vitro and in vivo. RN is identified to be an Nrf2 activator, which promotes Nrf2 dissociation from Keap1 via reacting with the Cys151 cysteine residue of Keap1, and suppresses Nrf2 ubiquitination. In addition, RN is able to attenuate toxicant-stimulated oxidative stress and inflammatory response in vitro. Importantly, RN significantly relieves CS-induced oxidative insult and inflammation, and RN-induced inhibition of inflammation is related to inhibition of nuclear transcription factor-κB (NF-κB) and induction of cell autophagy. In conclusion, our data indicate that RN is an activator of the Nrf2 pathway and evidently alleviates pulmonary disorders via restricting NF-κB activation and promoting autophagy. RN is a promising candidate for the therapy of pulmonary disorders.

Lignans from Euphorbia hirta L.

Five new lignans, euphorhirtins A-D (1-4), 5-methoxyvirgatusin (5), three artefacts, 7S-ethoxyisolintetralin (6), 7R-ethoxyisolintetralin (7), and 7R-ethoxy-3-methoxyisolintetralin (8), together with 13 known ones (9-21) were isolated from the medicinal plant Euphorbia hirta L. The structures of the compounds were elucidated by means of extensive spectroscopic analysis, including 1D and 2D NMR and HR-ESI-MS experiments. The absolute configurations of compound 1 was determined by ECD calculation. The isolates were evaluated for their inhibitory effects against the proliferation of the cancer cell lines (Hep G2, A549, and DU145) and compounds 14 and 18 showed inhibitory activity against the Hep G2 cells with IC50 values 7.2 ± 0.17 and 8.5 ± 0.36 µM.

Thesium chinense Turcz.: An ethnomedical, phytochemical and pharmacological review.

ETHNOPHARMACOLOGICAL RELEVANCE: Thesium chinense Turcz. has been used to treat mastitis, pulmonitis, tonsillitis, iaryngopharyngitis and upper respiratory tract infections in the indigenous medicine of China for a long history. Presently, several pharmaceutics prepared by this medical herb have been clinically used for the therapy of infectious diseases. AIM OF THE REVIEW: This review aims to comprehensively summarize the current researches on the ethnomedical, phytochemical and pharmacological aspects of T. chinense, and discuss their possible opportunities for the future research. MATERIALS AND METHODS: Extensive database searches, including Web of Science, SciFinder, Google Scholar and China Knowledge Resource Integrated, were performed using keywords such as 'Thesium chinense', 'Bai Rui Cao', and their chemical constituents. In addition, local classic herbal literature on ethnopharmacology and relevant textbooks were consulted to provide a comprehensive survey of this ethnomedicine. RESULTS: Thirty four chemical constituents, including flavonoids, alkaloids, and terpenoids, have been identified from T. chinense. Of which, flavonoids are the predominant and characteristic constituents. The crude extracts, the purified constituents, and commercial available pharmaceutics have displayed diverse in vitro and in vivo pharmacological functions (e.g. anti-inflammation, antimicrobial activity, analgesic effect, hepaprotection), and are particularly useful as a potential therapeutic agent against inflammation-related diseases. CONCLUSIONS: T. chinense is an important ethnomedical medicine and possesses a satisfying effect for treating inflammation, microbial infection, and upper respiratory diseases. It has received plenty of researches on its phytochemical and pharmacological aspects since 1970s. These findings definitely establish the link between chemical composition and pharmacological application, and support the ethnomedical use of T. chinense in the indigenous medicine of China. However, chemical composition of this plant and the molecular mechanisms of purified constituents have not been comprehensively investigated, and thus the trace constituents and the therapeutic targets of bioactive constituents deserve a further exploration. Collectively, the researchers should pay more attention to a better understanding and application of this ethnomedical plant.

Synthesis of nature product kinsenoside analogues with anti-inflammatory activity.

Kinsenoside is the major bioactive component from herbal medicine with a broad range of pharmacological functions. Goodyeroside A, an epimer of kinsenoside, remains less explored. In this report we chemically synthesized kinsenoside, goodyeroside A and their analogues with glycan variation, chirality inversion at chiral center(s), and bioisosteric replacement of lactone with lactam. Among these compounds, goodyeroside A and its mannosyl counterpart demonstrated superior anti-inflammatory efficacy. Furthermore, goodyeroside A was found to suppresses inflammatory through inhibiting NF-κB signal pathway, effectively. Structure-activity relationship is also explored for further development of more promising kinsenoside analogues as drug candidates.

New terpenoids and triketides from culture of the fungus Botrysphaeria laricina.

Three new isopimarane-type diterpenoids, botrysphins G-I (1-3), a new muurolane-type sesquiterpenoid, 11,12-dihydroxylentideusether (4), and two new triketides, 4-dechlorobotrysphone C (5) and 4,5-dihydroxy-3-methoxy-6-undecanoyloxy-2-cyclohexen-1-one (6), together with one known diterpenoid, sphaeropsidin A (7), one sesquiterpenoid, lentideusether (8), and one triketide sphaeropsidone (9), were isolated from culture of the fungus Botrysphaeria laricina associated with the moss Rhodobryum umgiganteum. The structures of the new compounds were established on the basis of extensive spectroscopic techniques including HRMS and 1D and 2D NMR data. Compounds 1 and 2 exhibited NO inhibitory activity with IC50 values of 13.9 µM and 41.9 µM, respectively. At the same time, these two compounds showed quinone reductase inducing activity with 2.7-fold of induction for 1 at 12.5 µM and 1.6-fold for 2 at 25.0 µM.

Chemical Constituents from Physalis Calyx seu Fructus and Their Inhibitory Effects against Oxidative Stress and Inflammatory Response.

Physalis Calyx seu Fructus, a traditional Chinese medicine consisting of the calyxes and fruits of Physalis alkekengi var. franchetii, has been used as therapy for inflammation-related respiratory diseases such as excessive phlegm, cough, sore throat, and pharyngitis for a long history in China. The aim of the present study was to investigate the chemical constituents of Physalis Calyx seu Fructus and identify the bioactive constituents responsible for its traditional application as therapy for inflammation-related diseases. In the present study, one new phenylpropanoid (1: ), two new steroids (17: and 18: ), together with 55 known constituents have been purified from the EtOH extract of Physalis Calyx seu Fructus. Among them, seven and twelve known constituents were isolated for the first time from Physalis Calyx seu Fructus and the genus Physalis, respectively. Fourteen constituents, including steroids [physalins (5:  - 9, 12:  - 14: , and 15: ) and ergostane (21: )], a sesquiterpenoid (35: ), alkaloids (36: and 37: ), and a flavonoid (44: ), showed inhibitory effects against oxidative stress. Ten constituents, including steroids (5, 6, 8, 13: , and 15: ), sesquiterpenoids (34: and 35: ), alkaloids (37: and 41: ), and a flavonoid (43: ), were found be potential anti-inflammatory constituents of this medicinal plant. The inhibition of oxidative stress and inflammatory response may be related to the regulation of Nrf2 and nuclear factor-κB pathways. The ethnomedical use of Physalis Calyx seu Fructus as a treatment for respiratory diseases might be attributed to the combined inhibitory effects of steroids, alkaloids, sesquiterpenoids, and flavonoids against oxidative stress and inflammatory response.

Novel secondary metabolites from the endobryophytic fungus Botrysphaeria laricina and their biological activity.

One novel polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) hybrid metabolite, laricinin A (1), two new meroterpenoids, tricycloalternarenes X and Y (2 and 3), one new coumarin, 3,4,7-trihydroxy-6-methylcoumarin (4), together with the known ethyl acetylorsellinate (5), diorcinol K (6), and tricycloalternarenes C and D (7 and 8) were obtained from culture of the fungus Botrysphaeria laricina isolated from the moss Rhodobryum umgiganteum. The structures of the new compounds were elucidated based on extensive spectroscopic techniques including HRMS and 1D and 2D NMR measurements. The absolute configuration of compound 1 was determined by ECD calculation and it was the first example of a novel group of PKS-NRPS hybrids possessing an unprecedented methyldihydropyran-isobutylpyrrolidinone skeleton. Compounds 2, 7, and 8 showed significant quinone reductase inducing activity in Hepa 1c1c7 cells.

Two pairs of diastereoisomeric isoflavone glucosides from the roots of Pueraria lobata.

Phytochemical investigation of the roots of Pueraria lobata led to the isolation of two pairs of new isoflavone glucosides, 3'-hydroxyneopuerarin A/B (1-2) and 3'-methoxyneopuerarin A/B (3-4). A pair of known compounds (5-6), which possess a very similar structure, were obtained together. Their structures were elucidated on the basis of spectroscopic data interpretation. Compounds 3-6 dose-dependently blocked the production of TNF-α and IL-6 in LPS-stimulated RAW264.7 cells, which indicated the potential anti-inflammatory effect of these compounds.

Three new triterpenoids from Mallotus macrostachyus.

Three new triterpenoids, mallomacrostins A-C (1-3), and 11 known ones (4-14) were obtained from the twigs and leaves of Mallotus macrostachyus. Mallomacrostin A possessed a new trinor-D:B-friedobaccharane skeleton. The structures of the new compounds were elucidated on the basis of extensive spectroscopic techniques including HR-ESIMS and NMR and the structure of 1 was confirmed by single crystal X-ray diffraction analysis. Spectroscopic data of the known compound 4 were provided for the first time. Compounds 2 and 10 exhibited significant anti-inflammatory activity by inhibiting LPS-induced release of nitric oxide with IC50 of 70.0 µM and 14.0 µM, respectively.

Fupyrones A and B, two new α-pyrones from an endophytic fungus, Fusarium sp. F20.

Two new α-pyrones, fupyrones A and B (1 and 2) and a biosynthetically related known α-pyrone, 4-methyl-5,6-dihydro-2H-pyran-2-one (3), were isolated from an endophytic fungus, Fusarium sp. F20, harbored in the stems of the Chinese medicinal plant Mahonia fortunei. Their structures were determined on the basis of spectroscopic data including MS and NMR. The antibacterial efficacies of compounds 1-3 were evaluated against four selected Gram-positive and Gram-negative bacteria, and their quorum sensing inhibitory activity was also investigated against the test organism, Chromobacterium violaceum.

Acrepyrone A, a new γ-pyrone derivative from an endophytic fungus, Acremonium citrinum SS-g13.

A new γ-pyrone derivative, acrepyrone A (1), and three known sorbicillinoids, trichodimerol (2), dihydrotrichodimerol (3) and tetrahydrotrichodimerol (4) were isolated from an endophytic fungus, Acremonium citrinum SS-g13, harboured in the roots of the Chinese medicinal plant Fructus mori. Their structures were determined by analysing MS, NMR, and ECD data. Compound 1 was evaluated for its cytotoxic effect, antibacterial activity and quorum sensing inhibitory potential.

Withanolides from the genus Physalis: a review on their phytochemical and pharmacological aspects.

OBJECTIVES: Withanolides are a group of modified C28 ergostane-type steroids with a C-22, C-26 δ-lactone side chain or a C-23, C-26 γ-lactone side chain. They enjoy a limited distribution in the plant kingdom and predominantly occur in several genera of Solanaceae. Of which, the genus Physalis is an important resource for this type of natural molecules. The present review aims to comprehensively illustrate the structural characteristics and classification of withanolides, and particularly focus on the progression on phytochemical and pharmacological aspects of withanolides from Physalis ranging from January 2015 to June 2019. KEY FINDINGS: Approximately 351 natural withanolides with novel and unique structures have so far been identified from genus Physalis, mainly isolated from the species of P. angulata and P. peruviana. Withanolides demonstrated diverse biological activity, such as anticancer, anti-inflammatory, antimicrobial, immunoregulatory, trypanocidal and leishmanicidal activity. Their observed pharmacological functions supported the uses of Physalis species in traditional or folk medicines. SUMMARY: Due to their unique structure skeleton and potent bioactivities, withanolides are regarded to be promising drug candidates, particularly for developing anticancer and anti-inflammatory agents. Further investigations for discovering novel withanolides of genus Physalis, exploiting their pharmacological values and evaluating their potency as therapeutic agents are significant work.

Chamiside A, a Cytochalasan with a Tricyclic Core Skeleton from the Endophytic Fungus Chaetomium nigricolor F5.

Chamiside A (1), a novel cytochalasan with a new 6/6/5-fused tricyclic core skeleton, was isolated from an endophytic fungus, Chaetomium nigricolor F5, harbored in the medicinal plant Mahonia fortunei. Its structure was unambiguously determined by extensive spectroscopic analyses, measurement of single-crystal X-ray diffraction, and electronic circular dichroism calculation. A biosynthetic pathway for the unique ring system in 1 was proposed. Compound 1 exhibited moderate antibacterial activity against Staphylococcus aureus.

New coumarins and monoterpene galloylglycoside from the stem bark of Sapium baccatum.

Sapium baccatum has been traditionally used as therapeutic remedies. To support its medicinal benefits, our current phytochemical investigation attempted to further discover novel bioactive compounds from S. baccatum. Eight new phenolic compounds, namely, seven coumarins (1-7) and one monoterpene galloylglycoside (8), together with 23 (9-31) known compounds were isolated. Their structures were determined by extensive spectroscopic methods and comparison with literatures. The three pairs of enantiomers of 1, 2 and 7 were confirmed on the basis of HPLC chiral analysis, electronic circular dichroism data and optical rotations. Two coumarins (1-2) were proven to be artifacts through HPLC analysis. The inhibitory effects on TNF-α secretion were examined biologically in LPS-induced BV2 microglia cells and all of the tested compounds exhibited significant inhibitory activity, especially new compound 1 possessed stronger inhibitory effects compared to the positive control quercetin. In addition, compounds 14 and 15 showed weak antifungal activity against Candida albicans SC5314 with MIC values both at 64 µg/mL. The results laid a solid foundation for additional research on S.baccatum related to its anti-inflammatory and antifungal medicinal value.

Two natural molecules preferentially inhibit azole-resistant Candida albicans with MDR1 hyperactivation.

Antifungal drug resistance is a significant clinical problem, and antifungal agents that can evade resistance are urgently needed. In infective niches, resistant organisms often co-existed with sensitive ones, or a subpopulation of antibiotic-susceptible organisms may evolve into resistant ones during antibiotic treatment and eventually dominate the whole population. In this study, we established a co-culture assay in which an azole-resistant Candida albicans strain was mixed with a susceptible strain labeled with green fluorescent protein to mimic in vivo conditions and screen for antifungal drugs. Fluconazole was used as a positive control to verify the validity of this co-culture assay. Five natural molecules exhibited antifungal activity against both susceptible and resistant C. albicans. Two of these compounds, retigeric acid B (RAB) and riccardin D (RD), preferentially inhibited C. albicans strains in which the efflux pump MDR1 was activated. This selectivity was attributed to greater intracellular accumulation of the drugs in the resistant strains. Changes in sterol and lipid compositions were observed in the resistant strains compared to the susceptible strain, and might increase cell permeability to RAB and RD. In addition, RAB and RD interfered with the sterol pathway, further aggregating the decrease in ergosterol in the sterol synthesis pathway in the MDR1-activated strains. Our findings here provide an alternative for combating resistant pathogenic fungi.

Induced production of steroids by co-cultivation of two endophytes from Mahonia fortunei.

A new ergosterol derivative, 23R-hydroxy-(20Z,24R)-ergosta-4,6,8(14),20(22)-tetraen-3-one (1), and a biosynthetically related known compound, (22E,24R)-ergosta-4,6,8(14),22-tetraen-3-one (2), were isolated from the co-culture between endophytic fungus Pleosporales sp. F46 and endophytic bacterium Bacillus wiedmannii Com1 both inhibiting in the medicinal plant Mahonia fortunei. The structure of the new compound 1 was determined by extensive spectroscopic analysis using HRMS and NMR, together with the modified Mosher's ester method. This is the first example of isolation of a ergosterol derivative with a Δ20(22)-double bond in the side chain. Compound 1 exhibited moderate antibacterial efficacy against Staphylococcus aureus and no obvious cytotoxic activities against the cancer cell lines A549, MDA-MB-231 and Hct116. Our results not only reveal that compound 1 is a potent antibacterial lead compound, but also highlight the powder of co-cultivation for inducing the production of cryptic natural products from endophytes derived from the same host plant.