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Five new compounds, including two sesquiterpenoid glycosides (1 and 2), two monoterpenoid glycosides (3 and 4), and a quinovose ester (5), together with four known compounds (6–9) were isolated from branches and leaves of Pittosporum pulchrum Gagnep. Their structures were established by 1D and 2D NMR, HR-ESI-MS, IR and UV spectral analyses. This is the first time to investigate the chemical constituents of P. pulchrum. Subsequently, the anti-inflammatory and antioxidant activities of different solvent fractions of ethanol extract and isolated compounds were evaluated. Dichloromethane and ethyl acetate fractions dramatically inhibited the production of NO in a concentration-dependent manner in LPS-induced RAW264.7 cells. Ethyl acetate and n -butanol fractions showed excellent DPPH radical scavenging activities with IC 50 values of 24.31 μg/mL and 27.81 μg/mL, respectively. Compounds 7 and 8 might be potential natural antioxidants with IC 50 values of 16.13 μM and 24.81 μM, respectively. [Display omitted] • Chemical investigation on Pittosporum pulchrum Gagnep. was conducted firstly. • Five undescribed compounds were obtained from branches and leaves of P. pulchrum. • Anti-inflammatory and antioxidant effects of extract and isolates were evaluated. • Compounds 7 and 8 might be potential natural antioxidants with medicinal value. [ABSTRACT FROM AUTHOR]

A series of C-3 arylated huperzine A (HPA) derivatives (1 − 30) were designed and synthesized in good yields via palladium-catalyzed Suzuki cross-coupling reaction. Cholinesterase inhibitory and neuroprotective activities of all 30 derivatives were evaluated. Cholinesterase inhibition results revealed that derivatives 2 and 15 exhibited dual inhibitory activity against both acetylcholinesterase (AChE inhibition: 2 , IC 50 = 1.205 ± 0.395 μ M; 15 , IC 50 = 0.225 ± 0.062 μ M) and butyrylcholinesterase (BChE inhibition: 2 , IC 50 = 8.598 ± 3.605 μ M; 15 , IC 50 = 4.013 ± 0.068 μ M), a feature not observed in huperzine A. Molecular docking results indicated that the introduction of aryl groups enhanced the affinity of the derivatives for the acyl-binding pocket of BChE, thereby limiting the hydrolysis of acetyl choline. However, these derivatives exhibited poor performance in cytotoxicity and neuroprotection assays. [Display omitted] • Thirty C-3 arylated huperzine A derivatives (1 – 30) were designed and synthesized via palladium-catalyzed Suzuki cross-coupling reaction. • Derivative 2 and 15 exhibited dual inhibition activity against both AChE and BChE. • A molecular docking study were performed to elucidate the interaction between these derivatives and BChE. [ABSTRACT FROM AUTHOR]

The late-stage difunctionalization of diterpene oridonin by light-promoted direct oxyamination with various O -benzoylhydroxylamines was carried out to afford C16α- N -C17-OBz-oridonin derivatives (1 – 25) for the first time. Though as a radical reaction, it features high stereoselectivity to only produce C16α- N -C17-OBz-oridonins. The in vitro antiproliferative activity of these C16α- N -C17-OBz-oridonins against the human breast cancer cell lines (MCF-7) was evaluated by MTT assay, showing that most of the synthesized compounds possessed moderate anticancer activity against MCF-7 cell lines superior or similar to the parent compound oridonin. The derivative 25 with a N -methyl- N -(naphthalen-1-ylmethyl) substitution showed better cytotoxicity against MCF-7 cells (IC 50 value of 11.75 μM) than oridonin (IC 50 value of 17.95 μM). [Display omitted] [ABSTRACT FROM AUTHOR]

In order to develop antiviral drugs, we utilized pterodontic acid (Poa-1) as a lead compound and conducted various modifications, including oxidation, reduction, addition, esterification, and acylation, resulting in the synthesis of 29 derivatives, of which 25 were novel acylation derivatives. Cell-level validation demonstrated that 4 derivatives exhibited significant inhibitory effects on the influenza A virus (H1N1), with an IC 50 = 4.04–36.13 μM. Notably, four acylation derivatives (compounds IIE5 , IIE6 , IIE9 , and IIE17) exhibited specific antiviral activities against influenza A virus (H1N1) with low cytotoxicity, indicating favorable therapeutic indices (SI = 3.5–11.9). Structure-activity relationship studies indicated that C5–C6 olefins are essential groups for antiviral activity, C11–C12 conjugated olefins will not interfere with antiviral activity. Carboxylic acid is an essential group for activity. Moreover，Carboxylic acid acylation can improve antiviral activity, and the inclusion of guanidine, cyclic amine, and phenyl groups with electron-donating substituents could enhance the antiviral activity of the lead compound. Natural products structural modifications are capable of improving the biological activity of lead compounds, offering a rapid pathway for the development of potent new structures. [Display omitted] [ABSTRACT FROM AUTHOR]

A series of piperine derivatives were designed and successfully synthesized. The antitumor activities of these compounds against 293 T human normal cells, as well as MDA-MB-231 (breast) and Hela (cervical) cancer cell lines, were assessed through the MTT assay. Notably, compound H7 exhibited moderate activity, displaying reduced toxicity towards non-tumor 293 T cells while potently enhancing the antiproliferative effects in Hela and MDA-MB-231 cells. The IC 50 values were determined to be 147.45 ± 6.05 μM, 11.86 ± 0.32 μM, and 10.50 ± 3.74 μM for the respective cell lines. In subsequent mechanistic investigations, compound H7 demonstrated a dose-dependent inhibition of clone formation, migration, and adhesion in Hela cells. At a concentration of 15 μM, its inhibitory effect on Hela cell function surpassed that of both piperine and 5-Fu. Furthermore, compound H7 exhibited promising antitumor activity in vivo, as evidenced by significant inhibition of tumor angiogenesis and reduction in tumor weight in a chicken embryo model. These findings provide a valuable scientific foundation for the development of novel and efficacious antitumor agents, particularly highlighting the potential of compound H7 as a therapeutic candidate for cervical cancer and breast cancer. [Display omitted] [ABSTRACT FROM AUTHOR]

Phytochemical investigation on the extract of the seeds of Thevetia peruviana resulted in the isolation of six new cardiac glycosides, namely theveperosides A-F (1–6), including a rare 19-nor-cardenolide (1), together with seven known analogues (7–13). The chemical structures of these compounds were determined based on detailed spectroscopic analysis. The cytotoxic activities of 1–13 were evaluated against MCF-7, HCT-116, HeLa, and HepG2 cancer cell lines, and their structure-activity relationships (SARs) were investigated. Compound 3 exhibited the significant cytotoxic effects with IC 50 values ranging from 0.032 to 0.055 μΜ, which could induce HepG2 cells apoptosis in a dose-dependent manner. [Display omitted] • Six new cardiac glycosides (1–6) were isolated from the seeds of T. peruviana. • Compound 1 is a rare 19-nor-cardenolide. • Compound 3 induced HepG2 cells apoptosis in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

The Potentilla genus has long been used traditionally as food and a folklore medicine. In the present study, aerial parts of two Potentilla species, Potentilla fulgens and Potentilla atrosanguinea , of western Himalayan origin, were studied for their anti-breast cancer activity. Ethyl acetate (PAA-EA, PFA-EA), methanolic (PAA-ME, PFA-ME) and hydro-methanolic extract (PAA-HM, PFA-HM) of the plants were tested for their antiproliferative activities against MCF-7 and T-47D breast cancer cell lines. The extracts showed good antiproliferative activity against ER- α dominant breast cancer cell line T-47D, having IC 50 values 6.19 ± 0.01 to 33.23 ± 0.04 μg/ml. Eight compounds were isolated, characterized, and quantified from ethyl acetate and methanolic extracts by column chromatography, 1D, 2D-NMR, HRMS and TLC densitometric analysis. Two compounds (4 and 6) have shown better antiproliferative activity than standard bazedoxifene and were further evaluated for their ER- α binding affinity via—fluorescence polarization-based competitive binding assay. The antiestrogenic properties of both compounds were assessed using western blotting. Compounds 4 and 6 were found to have significant affinity for the ER- α and managed to decrease its expression by 38 and 54% respectively. Compounds 4 and 6 also had good stability and reactivity as measured by minimal fluctuations in molecular dynamic simulation analysis, a good dock score in molecular docking, and a respectable HOMO-LUMO energy gap in DFT calculations. Compounds 4 and 6 have shown reliable results and can be used in the development of natural product-based anti-breast cancer agents. [Display omitted] • Natural products are source of leads in cancer drug discovery. • P. atrosanguinea and P. fulgens are traditionally being used as food in India were studied for their anti-breast cancer potential. • Eight compounds were isolated and evaluated for their antiproliferative activity alongwith quantification by HPTLC. • Compounds 4 and 6 were found to possess significant antiproliferative activity, ER-α binding affinity, and anti-estrogenic activity. • These compounds have shown dynamic stability In silico via. DFT and MD simulation. [ABSTRACT FROM AUTHOR]

This study was designed to investigate chemical composition and biological activities of the Anthriscus cerefolium methanolic extract. Chemical characterization of the extracts was performed by LC–HRMS/MS analysis. Antimicrobial activities of the extract were investigated on six bacteria and eight fungi while antioxidant activity was assessed by six different assays. Anti-enzymatic activity of the methanolic extract was tested on five enzymes associated with therapy of neurodegenerative diseases and diabetes mellitus type 2. Cytotoxic properties of the extract were tested on human immortalized keratinocytes (HaCaT) and tumor cell lines (SiHa, MCF7, HepG2). Anti-inflammatory activity of the extract was assessed on bacteria mediated inflammation model using HaCaT cell line. Molecular docking studies of enzymes and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis were performed. The results showed that the obtained extract was rich in phenolic compounds (a total of seventy-two were identified), with malonyl-1,4- O -dicaffeoylquinic acid and 3,5- O -dicaffeoylquinic acid dominating in the sample. The extract expressed antimicrobial, antioxidant, anti-enzymatic, cytotoxic and anti-inflammatory properties. The identified compounds demonstrated strong binding to the acetylcholinesterase (AChE) and to a lesser extent, to the butyrylcholinesterase (BChE), glucosidase, amylase, and modestly, to tyrosinase. KEGG pathway analysis has shown that the certain phenolic compounds may be related to anti-tumor, anti-inflammatory and anti-microbial activities of the extract. The data obtained suggest that phenolic compounds of the extract and their mixtures should be considered for future research as ingredients in pharmaceutical and nutraceutical formulations. [Display omitted] [ABSTRACT FROM AUTHOR]

Euphorbia lathyris L. (EL) is a traditional poisonous herbal medicine used to treat dropsy, ascites, amenorrhea, anuria and constipation. Processing to reduce toxicity of EL is essential for its safe and effective application. However, there is little known regarding the molecular mechanism of reducing toxicity after EL processing. This research aimed to screen the differential markers for EL and PEL, explore the differential mechanisms of inflammatory injury induced by EL and processed EL (PEL) to expound the mechanism of alleviating toxicity after EL processing. The results showed that 15 potential biomarkers, mainly belonging to diterpenoids, were screened to distinguish EL from PEL. EL promoted the expressions of TLR4, NLRP3, NF-κB p65, IL-1β and TNF-α, increased lipid rafts abundance and promoted TLR4 positioning to lipid rafts. Meanwhile, EL decreased LXRα and ABCA1 expression, and reduced cholesterol efflux. In contrast to EL, the effects of PEL on these indicators were markedly weakened. In addition, Euphorbia factors L 1 , L 2 , and L 3 affected LXRα, ABCA1, TLR4, NLRP3, NF-κB p65, TNF-α and IL-1β expression, influenced cholesterol efflux and lipid rafts abundance, and interfered with the colocalization of TLR4 and lipid rafts. The inflammatory injury caused by processed EL was significantly weaker than that caused by crude EL, and reduction of Euphorbia factors L 1 , L 2 , and L 3 as well as attenuation of inflammatory injury participated in processing-based detoxification of EL. Our results provide valuable insights into the attenuated mechanism of EL processing and will guide future research on the processing mechanism of toxic traditional Chinese medicine. [Display omitted] • Euphorbia lathyris L. (EL) is a classic traditional herbal medicine with toxicity. • Processing to attenuate the toxicity of EL is important for its clinical use. • The detoxification of EL processing is related to Euphorbia factors L 1 , L 2 and L 3. • Attenuation of inflammatory injury participates in detoxification of EL processing. • Processed EL reduces inflammation via LXRα/ABCA1 and TLR4 recruitment to lipid raft. [ABSTRACT FROM AUTHOR]

Chrysosplenium axillare Maxim. is used in traditional Tibetan medicine for the treatment of various human diseases, such as fever, headache, cholecystitis, acute icterohepatitis and acute liver necrosis. In this study, five new cucurbitane triterpenoid derivatives, chrysosaxillins A-E (1–5), along with three known structurally related compounds (6–8) have been isolated from whole herb of C. axillare. Their structures were elucidated by spectroscopic methods, including 1D and 2D NMR, HRESIMS, UV, IR, ECD and single-crystal X-ray diffraction. All isolates were evaluated for cytotoxic activities against four tumor cell lines including PC-3, A549, MCF-7, and HepG2. The results discovered that compound 1 possessed the most potent cytotoxicity against A549 cells with IC 50 value of 0.05 μM, while compounds 2 and 4 have mild cytotoxicities against cells tested with IC 50 values ranging from 8.78 to 41.72 μM. Our study suggests that C. axillare might serve as a valuable source of cucurbitane triterpenoids potentially useful for the development of new anti-tumor agents and support its use as a crop benefits to local economic. [Display omitted] • Isolation and identification of five new cucurbitane triterpenoid derivatives. • The first report of compounds 7 and 8 from Chrysosplenium genus. • Potent cytotoxicity of compound 1 against A549 cells with IC 50 value of 0.05 μM. [ABSTRACT FROM AUTHOR]

Helicobacter pylori is a bacterium that is present in the stomach of about 50% of the global population and is associated with several gastric disorders, including cancer. Natural products with antimicrobial activity have been tested against H. pylori , among them Trichilia catigua (catuaba), which is widely distributed in Brazil. This study aimed to evaluate extracts of T. catigua bark against H. pylori via determination of the minimum inhibitory and bactericidal concentrations (MIC and MBC); evaluation of virulence factors by real-time PCR, synergism with standard antimicrobials and morphology by scanning electron microscopy and simulations of the mechanism of action by molecular docking. The ethyl acetate fraction provided the best results, with an MIC 50 of 250 μg/mL and a 42.34% reduction in urease activity, along with reduced expression of the CagA and VacA genes, which encode for the main virulence factors. This fraction presented synergistic activity with clarithromycin, reducing the MIC of the drug by four-fold. Docking simulations suggested that the extracts inhibit fatty acid synthesis by the FAS-II system, causing damage to the cell membrane. Therefore, T. catigua extracts have potential as an adjuvant to treatment and are promising for the development of new anti- H. pylori drugs. [Display omitted] • Helicobacter pylori is a bacterium associated with the development of stomach cancer. • Trichilia catigua extracts showed a synergistic effect with clarithromycin and amoxicillin. • The extracts caused a reduction in the gene expression of the main virulence factors. • Molecular Docking analysis suggested interference with the H. pylori cell membrane. [ABSTRACT FROM AUTHOR]

Novel coumarin-piperazine-2(5 H)-furanone hybrids 5a – l were efficiently synthesized by introducing a furanone scaffold into coumarin using piperazine as a linker. The cytotoxicity of all hybrids 5a – l were evaluated by MTT assay on human lung cancer A549 cells and normal human lung fibroblast WI-38 cells with cytarabine (CAR) as a positive control. Hybrid 5l (IC 50 = 11.28 μM) was the most toxic to A549 cells, 18-fold more toxic than the reference CAR (IC 50 = 202.57 μM). Moreover, hybrid 5l (IC 50 = 411.93 μM) was less toxic to WI-38 cells, with a much higher selectivity (5l , SI ≈ 37, WI-38/A549) than CAR (SI ≈ 2). Structure–activity relationship analysis showed that both the cytotoxicity against A549 cells and selectivity (WI-38/A549) were greatly improved when the bornyl group was incorporated in the hybrids (5c , 5f , 5i and 5l). Further, hybrid 5l was more toxic and selective against four types of human lung cancer cells (A549, Calu-1, PC-9 and H460; IC 50 = 5.72–45.46 μM; SI ≈ 9–72) than three other types of human cancer cells (SK-BR-3, 786-O and SK-OV-3, IC 50 = 39.07–130.82 μM; SI ≈ 0–2), showing remarkable specificity. In particular, hybrid 5l (IC 50 = 5.72 μM) showed the highest cytotoxicity against H460 cells with the highest selectivity of up to 72 (WI-38/H460). Flow cytometric analysis showed that hybrid 5l induced apoptosis in H460 cells in a concentration-dependent manner. Molecular docking studies revealed a high binding affinity of hybrid 5l with CDK2 protein. Hybrid 5l is expected to be a leading candidate for anti-lung cancer agents. [Display omitted] • Novel coumarin-piperazine-2(5 H)-furanone hybrids 5 were efficiently synthesized. • Bornyl moiety greatly enhanced both the cytotoxicity and selectivity of hybrids 5. • Hybrid 5l was 18-fold more toxic than the reference CAR to lung cancer A549 cells. • Selectivity of hybrid 5l (SI ≈ 37, WI-38/A549) was much higher than CAR (SI ≈ 2). • Hybrid 5l was selectively more toxic against lung cancer cells than other cells. [ABSTRACT FROM AUTHOR]

Four undescribed sesquiterpene compounds (1 – 4) and six known compounds (5 – 10) were isolated from A. mongolica. Furthermore, compound 5 was a new natural product previously synthesized. The LPS-stimulated BV2 cells were used as a model to evaluate the anti-inflammatory activity of the isolated compounds, among them, compounds 2 , 3 and 4 showed significant inhibition of NO levels with IC 50 values of 27.48, 27.39 and 24.96 μM, respectively. [Display omitted] [ABSTRACT FROM AUTHOR]

Brain edema after ischemic stroke could worsen cerebral injury in patients who received intravenous thrombolysis. Cornus officinalis Sieb. et Zucc. , a long-established traditional Chinese medicine, is beneficial to the treatment of neurodegenerative diseases including ischemic stroke. In particular, its major component, cornel iridoid glycoside (CIG), was evidenced to exhibit neuroprotective effects against cerebral ischemic/reperfusion injury (CIR/I). Aimed to explore the effects of the CIG on brain edema of the CIR/I rats, the CIG was analyzed with the main constituents by using HPLC. The molecular docking analysis was performed between the CIG constituents and AQP4-M23. TGN-020, an AQP4 inhibitor, was used as a comparison. In the in vivo experiments, the rats were pre-treated with the CIG and were injured by performing middle cerebral artery occlusion/reperfusion (MCAO/R). After 24 h, the rats were examined for neurological function, pathological changes, brain edema, and polarized Aqp4 expressions in the brain. The HPLC analysis indicated that the CIG was composed of morroniside and loganin. The molecular docking analysis showed that both morroniside and loganin displayed lower binding energies to AQP4-M23 than TGN-020. The CIG pre-treated rats exhibited fewer neurological function deficits, minimized brain swelling, and reduced lesion volumes compared to the MCAO/R rats. In the peri-infarct and infarct regions, the CIG pre-treatment restored the polarized Aqp4 expression which was lost in the MCAO/R rats. The results suggested that the CIG could attenuate brain edema of the cerebral ischemia/reperfusion rats by modulating the polarized Aqp4 through the interaction of AQP4-M23 with morroniside and loganin. [Display omitted] • Brain edema is one of the devastating events that occur in the cerebral ischemic /reperfusion injury (CIR/I). • The formation of brain edema is correlated to the polarized AQP4 expression. • Cornel iridoid glycoside (CIG) was composed of morroniside and loganin. • The CIG could attenuate brain edema of the cerebral ischemia/reperfusion rats. • The CIG could increase the polarized Aqp4 which was lost in the CIR/I rats. • There were interactions between AQP4-M23 and morroniside/loganin. [ABSTRACT FROM AUTHOR]

Two new ent -labdane diterpenoids, hypoestesins A-B (1 – 2) and five new labdane diterpenoids, hypopurolides H-L (3 – 7), were isolated from the aerial parts of Hypoestes purpurea. All of the structures were fully determined based on extensive analysis of 1H, 13C, 2D NMR, and HRESIMS data. The absolute configurations of 1 – 3 was established through comparing the experimental and calculated ECD curves and the structure of 5 was confirmed by single crystal X-ray diffraction experiment. Compounds 5 – 7 were unusual C23 labdane diterpenoids having a γ- acetonyl- α , β -unsaturated γ -lactone unit and each assigned as C-15 epimeric mixture. Furthermore, cytotoxic and anti-inflammatory activities of 3 – 7 were evaluated. The results showed that 3 had remarkable cytotoxic activity against HL-60, A549, SMMC-7721, MDA-MB-231, and SW480 cancer cell lines with IC 50 values ranging from 2.35 to 17.06 μ M. Compound 4 showed moderate cytotoxic activity against HL-60 and SMMC-7721 cancer cell lines with IC 50 values of 15.12 ± 0.53 and 12.92 ± 0.60 μ M, respectively. Furthermore, compound 4 was also found to exhibit inhibitory activity against NO production in RAW 264.7 macrophages with IC 50 values of 23.56 ± 0.99 μ M, compared to the positive control L-NMMA with an IC 50 value of 41.11 ± 1.34 μ M. [Display omitted] • Seven new diterpenoids were isolated from Hypoestes purpurea. • Hypopurolides J-L were unusual labdane diterpenoids with C23 skeleton. • Hypopurolides H and I exhibited potent cytotoxic activities. • Hypopurolide I also exhibit NO inhibitory activity. [ABSTRACT FROM AUTHOR]

This study aims to elucidate the potential targets and molecular mechanisms underlying the anticancer effects of Red fermented rice extract using molecular simulation techniques. The inhibitory effects of different elution fractions of Red fermented rice extract on A549 and MCF-7 cell proliferation were evaluated through CCK-8 assays. Liquid chromatography-mass spectrometry (LC-MS) was employed to elucidate the structural information of active components, while molecular simulation techniques aided in identifying target proteins based on small molecule structures. Protein immunoblotting was utilized to investigate the mechanisms of action of relevant targets. The study found that the petroleum ether-ethyl acetate and ethyl acetate elution fractions of Red fermented rice extract significantly inhibited A549 and MCF-7 cell proliferation, with stronger effects observed on A549 cells. LC-MS structural analysis identified 25 small molecule structures. Molecular simulations successfully revealed interaction between active elution fractions of Red fermented rice extract and the cancer-related protein FGFR1. Further investigation into the phosphorylation of FGFR1 and its downstream pathway targets PI3K/AKT demonstrated that the active elution fractions exerted their anticancer activity by inhibiting the phosphorylation of FGFR1, PI3K, and AKT proteins. This comprehensive study, integrating CCK-8 assays, LC-MS, molecular simulation techniques, and protein immunoblotting, provides a deep understanding of the anticancer mechanisms of Red fermented rice extract, guiding its further development and clinical application. [Display omitted] • Hongqu extract demonstrates significant anticancer activity against A549 and MCF-7 cell lines. • Petroleum ether-ethyl acetate and ethyl acetate elution fractions exhibit potent inhibitory effects. • Molecular simulation identifies interaction between active fractions and cancer-related protein FGFR1. • Investigation reveals inhibition of FGFR1 phosphorylation and downstream PI3K/AKT pathway. • Protein immunoblotting validates the mechanism, indicating suppression of tumor cell proliferation. • Comprehensive use of assays and techniques provides a deep understanding of Hongqu extract's anticancer mechanisms. • Findings offer valuable insights for the further development and clinical exploration of Hongqu extract. [ABSTRACT FROM AUTHOR]

Two new triterpenoids, ilexsaponin U (1) and ilexsaponin V (2) , and three new phenylpropanoids, pubescenoside S (3) , pubescenoside T (38), and pubescenoside U (39), along with thirty-four existing compounds were isolated from the roots of Ilex pubescens. The elucidation of their structures involved comprehensive spectroscopic techniques, including IR, UV, HR-ESI-MS, and NMR experiments. The anti-inflammatory effects of almost all the compounds were evaluated in LPS-induced RAW264.7 cells. Among these, compounds 1 , 4 , 8 , 11 , 12 , 26 , 27 , 29 and 33 exhibited varying degrees of inhibition of inflammatory factors. Notably, compounds 1 , 4 and 8 significantly inhibited the mRNA levels of iNOS, IL-6, IL-1 β and TNF α , comparable to or exceeding the effect of the positive control (dexamethasone, DEX). We also evaluated the cardioprotective effects of these compounds in OGD/R-induced H9c2 cells. The results revealed that compounds 2 , 3 , 7 , 8 , 26 , 35 , 36 and 37 at 20 μM significantly increased cell viability by 24.9 ± 3.4%, 28.0 ± 0.3%, 37.6 ± 0.2%, 44.86 ± 0.5%, 9.47 ± 2.1%, 23.9 ± 0.4%, 39.5 ± 3.1% and 28.2 ± 0.1%, respectively. Some of them exhibited effects equal to or greater than that of the positive control (diazoxide, DZ) at 100 μM, showing a 21.9 ± 3.0% increase. [Display omitted] • Two new triterpenoids and three new phenylpropanoids were isolated from the roots of Ilex pubescens. • Structures were elucidated by spectroscopic analysis. • Compounds 1 , 4 and 8 significantly inhibited the mRNA levels of iNOS, IL-6, IL-1 β and TNF α in LPS-induced RAW264.7 cells. • Compounds 7 , 8 and 36 significantly increased the cell viability in OGD/R-induced H9c2 cells. [ABSTRACT FROM AUTHOR]

Three undescribed seco -iridoid glycosides, one undescribed flavonoid glycoside, and three known glycosides were isolated and identified from Gentiana olivieri Griseb. The structures of these compounds were determined through spectroscopic analysis and ECD calculations. Olivierisecosides N P (1 – 3) were identified as aromatic conjugated seco -iridoid glucosides, among them olivierisecoside N was representing a particularly rare subtype known as the morroniside seco -iridoids. The compounds 2 , 3 , 5 , and 6 exhibited significant inhibition of COX-2 expression, particularly compound 5 which demonstrated the most pronounced inhibitory activity with IC 50 value of 23.33 ± 0.51 μM. This study provides evidence for the potential development and utilization of G. olivieri as a source of anti-inflammatory components. Four seco -iridoid glucosides were isolated from Gentiana olivieri Griseb, all compounds screened for their anti-inflammatory effects and compound 5 had the most significant inhibitory activity against COX-2. [Display omitted] • Four undescribed glucosides were isolated from the Gentiana olivieri Griseb. • Structures were elucidated by NMR, MS, and absolute configurations were established by ECD. • All the isolates screened for the anti-inflammatory activity by inhibition COX-2. [ABSTRACT FROM AUTHOR]

E. tournefortii has wound healing properties in folk medicine and 5% infusions are used for stomach ulcers. It is also used in colds, abdominal pain, digestive problems, as an appetite enhancer and antispasmodic. For this purpose, in the study biochemical and histopathological evaluation of the ulcer protective effect of the extract obtained from the E. tournefortii in the indomethacin-induced gastric ulcer model in rats was aimed to develop new strategies in the treatment of ulcers. The phytochemical profile of the plant was elucidated for the first time by LC-HRMS in this study. The results indicate that, in terms of TNF-α, IL-1β, IL-8, IL-6, PGE2, NF-κB, VEGF, NO, COX-1 and COX-2 biochemical parameters, E. tournefortii protects the gastric mucosa to the inflammation, and also modulates the PGE2 pathway, and has a similar effect or even a more positive effect than the reference substance lansoprazole. According to LC-HRMS analysis results, chlorogenic acid, genistein and quinic acid were the main constituents of E. tournefortii extract with 1397.081, 1014.177 and 992.527 μg/g extract, respectively. Considering the anti-inflammatory and antioxidant effects of these phenolic components, it is thought that the major components are responsible for the anti-ulcer activity of the E. tournefortii extract. [Display omitted] • E. tournefortii protects the gastric mucosa from the inflammation and modulates the PGE2 pathway. • E. tournefortii has a similar or even a more positive effect than lansoprazole. • High-dose of E. tournefortii is not preferable as a therapetiıcs efficency due to leading an increases in inflamation. • According to LC-HRMS; chlorogenic acid, genistein and quinic acid were the main constituents of E. tournefortii extract. [ABSTRACT FROM AUTHOR]

Three new spatane diterpenoids (1 – 3) were isolated from the brown alga Stoechospermum marginatum together with three known compounds (4 – 6). The structures of these compounds were determined by the detailed NMR spectroscopic and Mass spectrometric analyses. All the isolated compounds were screened for their cytotoxic potentials against a panel of four human cancer cell lines, which include DU145 (Prostate), B16F10 (Melanoma), MDA MB-231 (Breast), and HeLa (Cervical) along with a normal cell line (HEK). The screening results indicated that compounds 1 , 4 and 5 displayed significant activities against B16F10 [IC 50 , 6.21 ± 0.14, 5.88 ± 0.21, 5.31 ± 0.24 μM] and MDA MB-231 [9.25 ± 0.61, 4.59 ± 0.14, 4.19 ± 0.13 μM] cell lines, respectively. In view of their significant activity, these compounds 1 , 4 and 5 were further taken up for detailed fluorescence assays, scratch assay and flow cytometry analysis, which revealed that they diminished proliferation and arrested cell cycle in the S phase and G2/M phase, which induced cell death by apoptosis. Overall, based on their considerable results, these compounds could serve as lead molecules in the development of anticancer drug candidates. [Display omitted] [ABSTRACT FROM AUTHOR]

This study evaluates the antibacterial effectiveness of Origanum vulgare hydroethanolic extract, both independently and in combination with antibiotics, against Escherichia coli strains associated with avian colibacillosis—a significant concern for the poultry industry due to the rise of antibiotic-resistant E. coli. The urgent demand for new treatments is addressed by analyzing the extract's phytochemical makeup via High-Performance Liquid Chromatography (HPLC), which identified sixteen phenolic compounds. Antibacterial activity was determined through agar diffusion and the measurement of minimum inhibitory and bactericidal concentrations (MIC and MBC), showing moderate efficacy (MIC: 3.9 to 7.8 mg/mL, MBC: 31.2 to 62.4 mg/mL). Combining the extract with antibiotics like ampicillin and tetracycline amplified antibacterial activity, indicating a synergistic effect and highlighting the importance of combinatory treatments against resistant strains. Further analysis revealed the extract's mechanisms of action include disrupting bacterial cell membrane integrity and inhibiting ATPase/H+ proton pumps, essential for bacterial survival. Moreover, the extract effectively inhibited and eradicated biofilms, crucial for preventing bacterial colonization. Regarding cytotoxicity, the extract showed no hemolytic effect at 1 to 9 mg/mL concentrations. These results suggest Origanum vulgare extract, particularly when used with antibiotics, offers a promising strategy for managing avian colibacillosis, providing both direct antibacterial benefits and moderating antibiotic resistance, thus potentially reducing the economic impact of the disease on the poultry industry. [Display omitted] [ABSTRACT FROM AUTHOR]

Hypoxia-inducing factor-1α (HIF-1α) is overexpressed in variety of tumor patients and plays an important role in the regulation of hypoxia response in tumor cells. Therefore, its inhibitors have become one of the targets for the treatment of a variety of cancers. Two series of panaxadiol (PD) ester derivatives containing pyrazole (18a–j) and pyrrole (19a–n) moiety were synthesized and their HIF-1α inhibitory activities were evaluated. Among all the target compouds, compounds 18c , 19d , and 19n (IC 50 = 8.70 – 10.44 μM) showed better HIF-1α inhibitory activity than PD (IC 50 = 13.35 μM). None of these compounds showed cytotoxicity above 100 μM and inhibited HIF-1α transcription in a dose-dependent manner. These compounds showed good antitumor activity and provide lead compounds for further design and activity study of PD ester derivatives. [Display omitted] [ABSTRACT FROM AUTHOR]

Coptis teeta Wall., an endangered but valuable medicinal species having various folklore uses in Indian and Chinese Traditional system of medicine. Its distribution is restricted to India, China and Tibet. In India, C. teeta is traditionally used in joint disorders, urinary infections and inflammatory diseases, however the scientific validation is missing. Thus, the present study aims to validate the anti-lithiatic and anti-gout activity of C. teeta rhizome extract (CTME) through in-vitro biological assays. The metabolic fingerprinting of CTME through reverse phase-high performance liquid chromatography-photodiode array (RP-HPLC-PDA) showed the presence of five benzyl-isoquinoline alkaloids, namely berberine (2.59%), coptisine (0.746%) jatrorrhizine (0.133%), palmatine (0.03%) and tetrahydropalmatine (0.003%). The anti-gout potency analysed via in-vitro xanthine oxidase (XOD) inhibition assay, followed by HPTLC (High performance thin layer chromatography) mediated bio-autographic inhibition of XOD signifies that CTME exhibit strong inhibition of XOD (IC 50 : 3.014 μg/ml), insignificantly different (p > 0.05) from allopurinol (IC 50 : 2.47 μg/ml). The XOD bioautographic assay advocates that the efficacy is primarily due to berberine and coptisine alkaloids. The CTME has significant anti-lithiatic activity, and thereby limiting the progression of crystal nidus formation, mediated via inhibition of calcium oxalate crystals nucleation and aggregation. Additionally, the extract also exhibits potential effect on inhibition of oxidative stress associated inflammation, which plays crucial role in alleviating urolithiasis and gouty conditions. Validating the traditional claims of C. teeta will not only confirm its medicinal benefits for targeted pathological conditions but also enhance its industrial demand. [Display omitted] • Coptis teeta has several uses in Indian and Chinese traditional systems of medicine. • Alkaloids content varies from 0.003 to 2.59%, rich source of berberine and coptisine. • Promising invitro antilithiatic and antigout activities validates the traditional usage. • Coptisine, therapeutically at par with berberine but less toxic and may be used as its alternative. [ABSTRACT FROM AUTHOR]

Biotransformation of ursane-type triterpenoid ilexgenin A by endophytic fungi Lasiodiplodia sp. MQD-4 and Pestalotiopsis sp. ZZ-1, isolated from Ilex pubescences and Callicarpa kwangtungensis respectively, was investigated for the first time. Six previously undescribed metabolites (1 – 6) with 23-norursane triterpenoids skeleton were isolated and their structures were unambiguously established by the analysis of spectroscopic data and single-crystal X-ray crystallographic experiments. Decarboxylation, oxidation, and hydroxylation reactions were observed on the triterpenoid skeleton. Especially, the decarboxylation of C-23 provided definite evidence to understand the biogenetic process of 23-norursane triterpenoids. Moreover, the qualitative analysis of the extract of I. pubescences showed metabolites 1 , 3 , 4 , and 6 could be detected in the originated plant, indicating biotransformation by endophytic fungi is a practical strategy for the isolation of novel natural products. Finally, all isolates were evaluated for the protective activities against H 2 O 2 -induced HUVECs dysfunction in vitro. Compound 5 could improve the viability of endothelial cells and decrease the level of intracellular ROS. [Display omitted] [ABSTRACT FROM AUTHOR]

Notoginseng leaf triterpenes (PNGL), derived from the dried stems and leaves of P. notoginseng , is a phytoestrogen that exerts many neuroprotective effects in vivo and in vitro of ischemic stroke. However, its impact on neurological restoration specifically in relation to angiogenesis following ischemic stroke remains unexplored. The aim of this study was to assess the effects of PNGL on angiogenesis subsequent to ischemic stroke. Male Sprague-Dawley rats were utilized in this study and were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R). Post-ischemia, PNGL were administered through intraperitoneal (i.p.) injection. The high-performance liquid chromatography (HPLC) fingerprinting, triphenyltetrazolium chloride (TTC) staining, immunofluorescent staining, network pharmacology and western blot analyses were assessed to determine the therapeutical effect and molecular mechanisms of PNGL on cerebral ischemia/reperfusion injury. Our findings demonstrate that PNGL effectively reduced infarct volume, enhanced cerebral blood flow, and induced angiogenesis in rats subjected to MCAO/R. Notably, PNGL also facilitated neuronal proliferation and migration in HUMECs in vitro. The proangiogenic effects of PNGL were found to be linked to the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and the AMPK/SIRT1-mediated PGC-1/ERα axis, as well as the activation of neurological function. Our study provides evidence that PNGL hold promise as an active ingredient of inducing proangiogenic effects, potentially through the activation of the Nrf2 pathway and the AMPK/SIRT1-mediated PGC-1/ERα axis. These findings contribute to the understanding of novel mechanisms involved in the restoration of neurological function following PNGL treatment for ischemic stroke. [Display omitted] [ABSTRACT FROM AUTHOR]

Thymus daenensis Celak (Lamiaceae family), known as denaian thyme, is an Iranian endemic plant, commonly used for its carminative, expectorant, antibacterial and antifungal properties. Previous studies report the chemical profile of the essential oil of T. daenensis aerial parts, but little is known about its non volatile constituents. Herein, phytochemical and biological investigation of the polar extract of T. daenensis aerial parts to provide further insight into traditional use of this plant has been accomplished. High-performance liquid chromatography coupled to linear ion-trap and orbitrap high-resolution mass spectrometry (LC-ESI/LTQOrbitrap/MS/MS) analysis of MeOH extract was performed to guide the isolation of specialized metabolites and successive characterization by NMR analysis. MeOH extract displayed antioxidant activity evaluated by DPPH (EC 50 = 48.99 ± 1.47 μg/mL) and TEAC assay (1.37 mg/mL). Successively, the biofilm inhibitory activity of extract and isolated compounds against mature biofilms of Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, Listeria monocytogenes, and Staphylococcus aureus , and their influence on the metabolism of sessile bacterial cells were evaluated. Two previously unreported thymol derivatives have been identified. The biofilm inhibitory activity of isolated compounds highlighted a promising antimicrobial action for the tested compounds. In particular, vanillic acid, (3 S ,5 R ,6 R ,7E,9 S)-megastigm-7-ene-3,5,6,9-tetrol 3- O -β-D-glucopyranoside, thymoquinol-2- O -β-D-glucopyranoside and the never reported compound daenol resulted capable of exerting inhibitory activity vs all pathogenic strains. All compounds tested at a concentration of 10 μg/mL inhibited the metabolism of the sessile cells of E. coli at a percentage ranging between 37.7% and 77.39%, and of L. monocytogenes at a percentage ranging between 21.79% and 71.17%. [Display omitted] • A LC-MS profile of the MeOH extract of Thymus daenensis aerial parts was carried out. • Two previously undescribed thymol derivatives have been isolated and characterized by NMR analysis. • The inhibitory activity of extract and isolated compounds against mature biofilms of different bacteria has been tested. • The influence of extract and isolated compounds on the metabolism of sessile bacterial cells has also been evaluated. • Some compounds including the undescribed daenol were active in inhibiting mature biofilms of all tested strains. [ABSTRACT FROM AUTHOR]

Four pairs of undescribed enantiomeric guaiane sesquiterpenoids, (±)-alismaenols A-D (1a/1b, 3a/3b-5a/5b), together with a pair of known ones (2a/2b) were isolated from the rhizomes of Alisma plantago-aquatica. The structures and relative configurations of the isolates were established by analysis of their 1D, 2D-NMR and HRESIMS data. Their absolute configurations were determined by comparison of their experimental CD spectra and calculated electronic circular dichroism (ECD) spectra or by single-crystal X-ray diffraction analysis. All compounds (1a / 1b - 5a / 5b) were evaluated for their inhibitory effects on nitric oxide (NO) production in LPS-induced RAW 264.7 cells, and compound 1a exhibited stronger activity (IC 50 = 12.89 μ M) than indomethacin (IC 50 = 14.03 μ M). [Display omitted] [ABSTRACT FROM AUTHOR]

In this study, bioactive compounds were isolated and characterized from the leaves and root-barks extracts of S.latifolius , with subsequent in vitro experimental investigations for antihyperglycemic potentials on α-amylase and α-glucosidase enzymes. Thirteen bioactive compounds were identified, including 10-Hydroxystrictosamide (2) and Quinovic acid-3-O-α-L-rhamnosyl-28-O-β- d -glucopyranosyl ester (8), using chromatographic, nuclear magnetic resonance spectroscopy (NMR), and mass spectrometry (MS) techniques. Experimental assays revealed that compounds 1–4 exhibited potent inhibition of α-amylase and α-glucosidase, with compound 2 demonstrating the most potent α-amylase inhibition (IC 50 value of 0.52 ± 0.003 μg/mL). Compound 8 showed a lower IC 50 value (0.098 ± 0.016 μg/mL) against α-glucosidase compared to compound 2 and acarbose. Synergistic effects among the compounds could enhance their inhibitory actions on the enzymes, positioning them as potential anti-hyperglycemia agents. Compound 2 displayed the highest binding affinity (−7.970 kcal/mol) when docked against α-amylase (PDB ID: 2QV4), comparable to acarbose (−8.515 kcal/mol). It also ranked among the top ligands against α-glucosidase (PDB ID 3TOP), although compound 13 and acarbose had higher docking scores. All compounds exhibited ideal ADMET properties, suggesting good bioavailability and low toxicity. In conclusion, the isolated compounds exhibit promising antihyperglycemic potential and favourable safety profiles for further exploration. [Display omitted] [ABSTRACT FROM AUTHOR]

Six undescribed bicyclic sesquiterpene coumarins, kuhistanin A, ferukrin isovalerate, 9' β ,12' α - ferukrin isovalerate, (17′ E)- 9' α , 12' β - isomarcandin, (17′ Z)- 9' α , 12' β - isomarcandin and (17′ E) - isomarcandin, together with nine known ones were isolated from the roots of Ferula kuhistanica Korovin. The structures of them were elucidated using NMR and HRESIMS data analysis. The relative configurations of the isolates were confirmed by NOE correlations and NMR calculation. The absolute configurations of them were confirmed by X-ray diffraction analysis and ECD calculation. Anti-vitiligo, anti-inflammatory and cytotoxicity of the isolates were tested. Acetyl feselol, feselol, ferusingensine I and farnesiferol A significantly increased the melanin content at the concentration of 10 μM. (17′ E) - 9' α , 12' β - isomarcandin exhibited strong cytotoxicity against HT-29 cell line with IC 50 values of 8.94 ± 0.47 μM, and (17′ E) - isomarcandin demonstrated strong cytotoxicity against Hela, A549 and HT-29 cell lines with IC 50 values of 5.29 ± 0.25, 4.01 ± 0.20, and 4.16 ± 0.21 μM, respectively. This study concluded that, isolated compounds from F. kuhistanica demonstrated strong bioactivity towards anti-vitiligo and cytotoxicity and active compounds are suggested as anti-vitiligo and cytotoxicity agent for future drug development. Six undescribed sesquiterpene coumarins kuhistanin A, ferukrin isovalerate, 9' β ,12' α - ferukrin isovalerate, (17′ E)- 9' α , 12' β - isomarcandin, (17' Z)- 9' α , 12' β - isomarcandin and (17′ E) - isomarcandin, together with nine known ones were isolated from the roots of F. kuhistanica. The isolates were tested their anti-vitiligo, anti-inflammatory and cytotoxic activities. [Display omitted] • Six undescribed sesquiterpene coumarins were isolated from F. kuhistanica roots • The structural elucidation of these compounds was described. • Anti-vitiligo and cytotoxic activities of the isolates were tested. [ABSTRACT FROM AUTHOR]

Kaempferia galanga L. is an aromatic medicinal plant belonging to the Zingiberaceae family. Its rhizome has been widely used as traditional Chinese medicine and a flavor spice for a long time. In this study, six previously undescribed phenylpropanoids, including four [2+2] - cycloaddition-derived cyclobutane natural products (1 - 4), and two phenylpropanoids (5 - 6) were isolated from the rhizomes of K. galanga L. Their structures were elucidated by spectroscopic methods, single-crystal X-ray diffraction, NMR calculation, and ECD spectra calculation. These cyclobutane derivatives were isolated from K. galanga for the first time. Furthermore, compounds 1-6 were evaluated for the potential inhibitory activities on NO production and NF- κ B nuclear translocation in LPS-triggered RAW 264.7 macrophages. The results showed that the isolated compounds have a moderate anti-inflammatory activity measured on their potency to inhibit NO production and the expression of iNOS and COX-2. Additionally, compound 2 effectively suppressed NF- κ B nuclear translocation at a concentration of 40 μ M. [Display omitted] • Six new phenylpropanoids were isolated from the rhizome of Kaempferia galanga L. • The isolated phenylpropanoids showed moderate anti-inflammatory activity. • Compound 2 blocked NF- κ B nuclear translocation in RAW 264.7 cells. [ABSTRACT FROM AUTHOR]

Diterpenoids occupy an important slot of the natural products diversity space with wide ranges of bioactivities and complex structures, providing potential applications for the development of therapeutics. In this study, we reported four new abietane-type diterpenoids viroxocin B-E (1–4), a new totarane-type diterpenoid viroxocin F (5), and a new sempervirane-type diterpenoid viroxocin G (6) along with four known compounds (7 – 10), isolated and identified from a widely used Traditional Chinese Medicine, Isodon serra (I. serra). Their structures were established by spectroscopic data analysis, experimental and calculated electronic circular dichroism (ECD) data, as well as X-ray diffraction analysis. Compounds 2 , 5 , 7 , 8 and 10 exhibited promising anti-inflammatory activities in lipopolysaccharide (LPS)-induced RAW 267.4 cells, and their inhibition rates on NO production were more than 60% at 10 μM. Compound 7 showed cytotoxicity against human renal cell carcinoma 769P at 20 μM, the inhibition rate was 52.66%. [Display omitted] [ABSTRACT FROM AUTHOR]

Euphorbia himalayensis Boiss. is an alpine member of the Euphorbiaceae family. Its dried roots have been used to treat digestive problems and chest congestion in traditional Tibetan and Mongolian medicine. Despite thousands of years of use in medicine, the bioactive compounds of the root remain unknown. Herein, we isolated a novel aqueous-soluble polysaccharide (EHP2) from the E. himalayensis root and determined its structural characteristics via high-performance gel permeation chromatography, Fourier-transform infrared spectroscopy, gas chromatography–mass spectrometry, and nuclear magnetic resonance spectrometry. The homogeneous molecular weight of EHP2 was 23.6 kDa with narrow polydisperity (Mw/Mn = 1.4), and EHP2 mainly comprised of glucose (86.4%), galactose (11.9%) and mannose (1.7%). The major backbone of EHP2 was →4)-α-D-GalAp-(1 → 4)-α-D-Glcp-(1 → and the branch chain was α-D-Glcp-(1→. The antioxidant activity of the EHP2 was evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and superoxide anion radical scavenging assays, and antioxidant enzyme activity (SOD, GSH and MDA) was determined in human umbilical vein endothelial cells (HUVECs). The EHP2 demonstrated lower potential scavenging effects on DPPH and superoxide free radical scavenger than ascorbic acid, and in HUVECs, it led to increased SOD and GSH activities and decreased MDA levels. This study is the first to describe an E. himalayensis polysaccharide compound with potential antioxidant activity. [Display omitted] [ABSTRACT FROM AUTHOR]

In Brazil, latex from Euphorbia umbellata (African milk tree) has been increasingly used in folk medicine to treat several types of cancer, including melanoma. The effect of lyophilized latex (LL), its hydroethanolic extract (E80), triterpene (F-TRI)- and diterpene (F-DIT)-enriched fractions, along with six isolated phorbol esters from LL and phorbol 12-myristate 13-acetate (PMA) on J774A.1, THP-1, SK-MEL-28, and B16-F10 cell line viability were evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. The compounds were identified by 2D-NMR and HRESIMS. The effect of the LL, extract and fractions on cell viability was also assessed through a resazurin reduction assay. At 100 μg/ml, LL, and its fractions moderately inhibited J774A.1 (37.5–59.5%) and THP-1 (12.6–43.6%) metabolism. LL (IC 50 70 μg/ml) and F-TRI (IC 50 68 μg/ml) were barely more effective against B16-F10 cells, and only F-TRI exerted an inhibitory effect on SK-MEL-28 cells (IC 50 66–75 μg/ml). The samples did not effectively inhibit THP-1 growth (IC 50 69–87 μg/ml, assessed by MTT). B16-F10 was susceptible to PMA (IC 50 53 μM) and two 12-phenylacetate esters (IC 50 56–60 μM), while SK-MEL-28 growth was inhibited (IC 50 58 μM) by one of these kinds of esters with an additional 4β-deoxy structure. Synagrantol A (IC 50 39 μM) was as effective as PMA (IC 50 47 μM) in inhibiting J774A.1 growth in a dose-dependent manner. Furthermore, an in silico study with target receptors indicated a high interaction of the compounds with the PKC proteins. These results provide useful knowledge on the effect of tigliane-type diterpenes on tumor cell from the perspective of medicinal chemistry. [Display omitted] [ABSTRACT FROM AUTHOR]

In the present study, we have attempted a comprehensive assessment of the possible radioprotective efficacy of Pterocarpus santalinus aqueous extract (PSAE). All the studied models were gamma-irradiated with prior treatment with PSAE. First, the content of total phenols (4.061 μg/mg gallic acid equivalents), flavonoids (6.616 μg/mg quercetin equivalents), and tannins (0.008 mg/L of PSAE) were determined spectrophotometrically. Second, UHPLC-HRMS analysis was performed to identify the possible radioprotectors. Of those, santalins A & B are known for their usage as natural color in foods and alcoholic beverages identified in PSAE. Treatment was well tolerated with no side effects from PSAE. Later, it was shown that radiation-induced lethality significantly amended in PSAE-treated spleen lymphocytes as evidenced by reduced elevated levels of ROS and lipid peroxidation, restored total thiols and GSH: GSSG, inhibited DNA DSBs and cell death. Furthermore, an immunomodulation study was carried out because radiation exposure induces an inflammatory response. Our study shows that PSAE suppressed concanavalin A-induced T-cell proliferation as evidenced by CFSE dye dilution and CD69 antibody staining methods. Taken together, the current study explored the protective efficacy of PSAE from gamma radiation-inflicted injuries and hence we recommend PSAE as a potent radioprotective formulation. [Display omitted] • P. santalinus aqueous extract (PSAE) possesses in vitro radioprotective activity. • Quercetin, Rutin, and Apigenin were the major compounds detected in the PSAE. • PSAE protected spleen lymphocytes from DNA damage and cell death. • PSAE suppressed concanavalin A-induced T-cell proliferation. [ABSTRACT FROM AUTHOR]

The growing incidence of Clostridium difficile associated diarrhea (CDAD) underscores the urgency for potent treatments. This research delves into the therapeutic potential of Scutellaria baicalensis Georgi (Lamiaceae) root (SR) in addressing CDAD and its influence on gut microbiota. Using a CDAD mouse model and fidaxomicin as a control, SR's impact was measured through diarrhea symptoms, colonic histopathology, and C. difficile toxin levels. Employing the PacBio platform, 16S rRNA full-length gene sequencing analyzed the gut microbial composition and the effect of SR. Results revealed SR considerably alleviated diarrhea during treatment and restoration phases, with a marked decrease in colonic inflammation. C. difficile toxin levels dropped significantly with SR treatment (P < 0.001). While SR didn't augment gut microbiota's overall abundance, it enhanced its diversity. It restored levels of Proteobacteria and Bacteroidetes, reduced Akkermansia spp. and Enterococcus spp. proportions, and modulated specific bacterial species' abundance. In essence, SR effectively mitigates CDAD symptoms, curtails inflammatory reactions, and beneficially restructures gut microbiota, suggesting its potential in advanced CDAD clinical intervention. [Display omitted] [ABSTRACT FROM AUTHOR]

The traditional Chinese medicine Tetrastigma Hemsleyanum (TH) is employed in treating respiratory diseases; however, the aerial parts by which its total flavonoids alleviate acute lung injury (ALI) are still unknown. This study investigated the protective effect and mechanism of Tetrastigma Hemsleyanum flavonoids (THF) in lipopolysaccharide (LPS)-induced ALI in mice. Firstly, the total flavonoids from the above-ground part of TH were extracted. Subsequently, the composition of THF was analyzed using LC-MS. In vivo, the impact of THF on ALI mice was assessed through lung histopathology and the evaluation of various inflammatory factors' expression in mice. After treating RAW264.7 cells with THF in vitro, changes in inflammatory markers were examined upon LPS stimulation, and mRNA expression levels of inflammatory factors were detected using RT-qPCR. Finally, Western blot analysis was performed to determine TLR4/NF-κB pathway-associated proteins expression. In summary, a total of 24 flavonoids have been identified in THF. In vivo and vitro results show that THF effectively reduces the damage caused by LPS inflammation by blocking the expression and release of inflammatory factors. THF alleviates inflammatory injury by modulating the TLR4/NF-KB pathway. The results suggest that flavonoids exhibit a potent anti-inflammatory effect and effectively mitigate LPS-induced injury both in vivo and in vitro. We suggested that these flavonoids exert their therapeutic effects by modulating the TLR4/NF-KB pathway. In conclusion, the development of THF is anticipated to represent a promising new pharmaceutical for treatingALI. [Display omitted] • The aerial parts save medicinal resources than the underground part. • THF treat ALI through the TLR4/ NF-κB pathway. • THF effect is related to monomer composition. • THF monomer composition was detected by LC-MS. [ABSTRACT FROM AUTHOR]

Liver fibrosis is a wound-healing process. It can be induced by various chronic liver diseases. Liver fibrosis is characterized by the activation of hepatic stellate cells (HSCs), a key event. However, no effective treatment strategies to cure or alleviate liver fibrosis-induced pathologic changes have yet been developed. Traditional Chinese medicine (TCM) exhibits a good anti-fibrosis action, with few side effects. Gentiana decoction, a TCM also called Longdan Xiegan Tang (LXT), is used for purging the liver in clinical settings. However, the role of LXT in preventing liver fibrosis and the underlying regulatory mechanism have not yet been investigated. This study demonstrates that LXT treatment can protect the liver from the injuries resulting from CCl 4 -induced liver fibrosis in mice and suppress the activation of HSCs. The mice in the LXT group exhibit litter collagen I and HSC activation marker α-smooth muscle actin (α-SMA) expression. Transcriptome sequencing of the mouse liver tissue reveals that the level of Parkin, a mitophagy marker, decreased in CCl 4 -induced liver fibrosis. Further study shows that the injection of Parkin-overexpression adeno-associated virus (Parkin–AAV) via the tail vein can reduce CCl 4 -induced liver fibrogenesis in mice. We conducted a mechanistic study also, which suggests that LXT treatment suppresses the activation of HSCs by upregulating the expression of Parkin. Hence, it can be suggested that LXT inhibits liver fibrosis by activating the Parkin signaling pathway. [Display omitted] [ABSTRACT FROM AUTHOR]

Curcumae rhizoma (CR) is the dried rhizoma of Curcuma phaeocaulis Val (CP), Curcuma kwangsiensis S. G. Lee et C. F. Liang (CK) and Curcuma wenyujin Y. H. Chen et C. Ling (CW), used widely to treat blood stagnation in China. Currently, quality control indicators for CR are limited to chemical composition analysis. It is unclear whether the current quality standard of the multicomponent content of CR can reflect clinical effects, due to the lack of the evaluation of biological effects. A method of evaluating quality was developed called the effect-constituent index (ECI). By meticulously measuring and calibrating the key active components, the ECI offers a comprehensive assessment of the CR's biological effects, establishing a crucial link to clinical efficacy and safety. An analytical protocol employing high-performance liquid chromatography (HPLC) was devised to ascertain the presence and measure ten principal constituents within CR sourced from various species and the content of total volatile oil was also measured. An In vitro antiplatelet aggregation assay was developed to measure the antiplatelet aggregation biopotencies of thirty batches of CR and ten main components. Then, the calibration weights for each constituent in the ECI were determined based on the antiplatelet aggregation biopotency values of eight components with notable efficacy. The ECI calculation involved summing the products obtained by multiplying the content (Ci) of each component by its corresponding biopotency weight (Wi). Correlation analysis unveiled a the most robust correlation (R = 0.8579, p < 0.001) between ECI and antiplatelet aggregation biopotency of CR, when compared to individual components or volatile oil content. The devised ECI, synthesizing chemical and biological data pertinent to clinical effectiveness, facilitates a nuanced assessment of CR quality across various species in its efficacy in treating blood stagnation. This method addresses the challenge of guaranteeing effectiveness through chemical analysis alone. This study offers substantiation for the applicability of the ECI as a tool for assessing the quality of traditional Chinese medicine (TCM). [Display omitted] • Significant chemical profile variation among different origins of Curcumae rhizome. • Anti-platelet aggregation assay was constructed to measure Curcumae Rhizoma biopotency. • The ECI was established to reflect the biological effect of Curcumae Rhizoma. • The established ECI showed a high correlation with the biopotency of Curcumae Rhizoma. • The ECI provide a novel method for the quality control of TCM. [ABSTRACT FROM AUTHOR]

Phytochemical investigation on the leaves of Tibetan Leucosceptrum canum , a Chinese medicinal herb, led to the isolation of seven new leucosceptrane sesterterpenoids (1 – 7) and five known analogs (8 – 12). Comprehensive spectroscopic analysis (including 1D and 2D NMR, and HRMS), quantum chemistry computations, and single crystal X-ray crystallographic analysis were applied to elucidate their structures. Compounds 1 – 3 and 6 were the first examples of the leucosceptrane sesterterpenoids with rare C-2 oxidation. Compound 2 exhibited immunosuppressive activities via suppressing the secretion of cytokines IL-6 and TNF-α in LPS-induced macrophages RAW264.7 with IC 50 values of 13.39 and 19.34 μM, respectively. [Display omitted] • Seven new leucosceptrane sesterterpenoids were isolated from Leucosceptrum canum. • NMR, ECD and X-ray analyses were used to clarify the absolute configurations. • It was the 1st report of the leucosceptrane sesterterpenoids with C-2 oxidation. • Several compounds showed moderate immunosuppressive activity. [ABSTRACT FROM AUTHOR]

Forty-three diarylheptanoids were isolated from Alpinia officinarum rhizomes among them eight ones (1 – 6) were undescribed compounds whose structures were identified by UV, IR, HRESIMS, and NMR. The neuroprotective effects of these diarylheptanoids were evaluated on H 2 O 2 -damaged SH-SY5Y cells. Compounds 7 , 10 , 12 , 20 , 22 , 25 , 28 , 33 , 35 , 37 , and 42 presented significant neuroprotective effects than that of the positive control (EGCG) at the concentrations of 5, 10 or 20 μM. Compounds 10 , 22 , 25 , and 33 significantly reduced the ROS levels and inhibited the generations of MDA and NO in oxidative injured cells to display neuroprotective effects. This study lay the foundation for the application of Alpinia officinarum rhizomes. [Display omitted] [ABSTRACT FROM AUTHOR]

Molecular dereplication and drug-like discovery are important tools for exploring the chemical profile of metabolites in a complex mixture. In order to establish a workflow for discovering novel acetylcholinesterase (AChE) ligands, we performed the chemical study of Myrsine guianensis (Aubl.) Kuntze (Primulaceae). To carry out the bioprospection, nine extracts were obtained from different parts of the plant. Through the dereplication approaches, seventeen metabolites were annotated. In order to confirm the putative inferences, a HPLC preparative method was developed to isolate three known myrsinoic acids, A (1) , B (2) and C (3). Along with, we are reporting the obtention of two new congeners, G (5) and H (6) , which their structures were elucidated by NMR and HRMS data. Besides that, two extracts were submitted to affinity assays to accelerate the discovery of AChE ligands. Desorbates were analyzed through LC-HRMS for calculating the affinity ratio (AR). Thus, (1) presented AR = 4.59, therefore was considered a potential ligand. [ABSTRACT FROM AUTHOR]

In our quest to discover advanced glycation end products (AGEs) inhibitors from Clinacanthus nutans (Burm.f.) Lindau leaves, we conducted a bioactivity-based molecular networking. This approach integrates LC-MS2 profiling and in vitro antiglycation data to predict bioactive compounds. We began by screening three extracts: 100% ethanol, 70% ethanol and 100% water alongside the in vitro antioxidant activity, total phenolics content (TPC) and schaftoside content. Among these extracts, 100% ethanol extract exhibited the highest total AGEs inhibition effects (IC 50 = 80.18 ± 11.6 μg/mL), DPPH scavenging activity (IC 50 = 747.40 ± 10.30 μg/mL) and TPC (26.54 ± 2.09 μg GAE /mg extract). Intriguingly, 100% ethanol extract contained the lowest amount of schaftoside, suggesting the involvement of other phytochemicals in the antiglycation effects. The molecular networking and in silico structural annotations of 401 LC-MS features detected in the fractions from 100% ethanol extract predicted 21 bioactive compounds (p < 0.05, r > 0.90), including several C 40 carotenoids, alkaloids containing tetrapyrrole structures and fatty acids. On the contrary, all phenolics showed weak correlations with antiglycation effects. These predictions were further validated in vitro, where carotenoid lutein showed half maximal inhibitory concentration, IC 50 = 96 ± 8 μM and selected flavonoid- C -glycosides exhibited weaker inhibitions (IC 50 between 568 and 1922 μM). Notably, lutein content was higher in freeze-dried leaves (12.42 ± 0.82 mg/100 g) than oven-dried, although the former was associated with elevated mercury levels. In summary, C. nutans exhibited potential antiglycation and antioxidant activity, and lutein was identified as the main bioactive principle. [Display omitted] [ABSTRACT FROM AUTHOR]

Four undescribed amide alkaloids hongkongensines A-C and 1-(1-oxo-6-hydroxy-2 E ,4 E -dodecadienyl)-piperidine, five known amide alkaloids, and three known neolignans were isolated from the aerial part of Piper hongkongense. The planar structures of these compounds were determined by detailed analyses of HR-ESI-MS and NMR data. The absolute configurations of hongkongensines A-C were elucidated by single-crystal X-ray diffraction analysis and ECD calculations. Moreover, the inhibitory activities of PCSK9 expression in vitro for all compounds were assessed by PCSK9 AlphaLISA screening. Kadsurenone (10) displayed a significant inhibitory activity at 5 μM with an inhibition rate of 51.98%, compared with 55.55% of berberine (BBR 5 μM). [Display omitted] • Four undescribed amide alkaloids were isolated from Piper hongkongense. • Their absolute configurations were elucidated by single-crystal X-ray diffraction and ECD calculations. • Hongkongensine C (3) is a chlorine-containing natural product. • Kadsurenone (10) displayed a significant inhibitory activity of PCSK9 expression. [ABSTRACT FROM AUTHOR]

Employing an MS/MS-based molecular networking-guided strategy, three new eudesmane-type sesquiterpenes (1 – 3) and one undescribed pseudoguaianolide sesquiterpene (8), along with four known eudesmane-type sesquiterpene lactones (4 – 7) were extracted and purified from the herbs of Carpesium abrotanoides L. Structural elucidation encompassed comprehensive spectroscopic analysis, NMR calculations, DP4+ analysis, and ECD calculations. The cytotoxicity activity of all isolates was evaluated against two human hepatoma carcinoma cells (HepG2 and Hep3B) in vitro. It was demonstrated that compounds 2 and 4 showed moderate cytotoxic against HepG2 and Hep3B cells. Furthermore, all compounds were evaluated for their acetylcholinesterase (AChE) inhibitory activity. Particularly noteworthy is that, in comparison to the positive control, compound 1 demonstrated significant AChE inhibition with an inhibition rate of 77.86%. In addition, the inhibitory mechanism of compound 1 were investigated by in silico docking analyze and molecular dynamic simulation. [Display omitted] • Employing an MS/MS-based molecular networking-guided strategy, eight sesquiterpenes were isolated from Carpesium abrotanoides L. [ABSTRACT FROM AUTHOR]

Three new sorbicillinoids sorbicatechols E -G (1 – 3), along with seven known compounds 4 – 10 , were obtained from the ethanol extract of Penicillium sp. HS-11, a fungal endophyte of the medicinal plant Huperzia serrata. The structures of 1 – 3 were established by detailed interpretation of the spectroscopic data and their absolute configurations were established by comparative analyses of the ECD spectra. Sorbicatechol G (3) represented the first hybrid sorbicillinoid bearing a tetralone skeleton. In the in-vitro bioassay, trichodimerol (5) exhibited moderate inhibitory activity against the Escherichia coli β -glucuronidase (EcGUS) with an IC 50 value of 92.0 ± 9.4 μM. [Display omitted] [ABSTRACT FROM AUTHOR]

This study aims to clarify the specific anti-fatigue components of Schizophyllum commune (S.commune) and analyze its potential anti-fatigue mechanism. The main anti-fatigue active ingredient of S.commune was locked in n-butanol extract (SPE-n) by activity evaluation. Twelve compounds were identified by high performance liquid chromatography-electrospray tandem mass spectrometry (LC–ESI–MS/MS). The anti-fatigue effect of morusin is the most predominant among these 12 ingredients. The determination of biochemical indices showed that morusin could increase liver glycogen reserves, improve the activity of antioxidant enzymes in liver, and reduce reactive oxygen species (ROS) content in muscle tissue, thereby reducing myocyte damage. Further studies revealed that morusin could reduce the level of oxidative stress by activating Nrf2/HO-1 pathway, thus alleviating the fatigue of mice caused by exhaustive exercise. The current findings provide a theoretical basis for the development of natural anti-fatigue functional food. [Display omitted] • The anti-fatigue active components was mainly n-butanol extract of Schizophyllum commune through activity screening. • Morusin was identified as the major active anti-fatigue substance in Schizophyllum commune by LC–ESI–MS/MS. • Morusin could relieve fatigue by regulating the Nrf2/HO-1 pathway and down-regulating oxidative stress. [ABSTRACT FROM AUTHOR]

Misuse of synthetic pesticides and antimicrobials in agriculture and the food industry has resulted in food contamination, promoting resistant pests and pathogen strains and hazards for humanity and the environment. Therefore, ever-increasing concern about synthetic chemicals has stimulated interest in eco-friendly compounds. Ferulago angulata (Schltdl.) Boiss. and Ferula assa-foetida L., as medicinal species with restricted natural distribution and unknown biological potential, aimed at investigation of their essential oil (EO) biological properties, were subjected. Z -β-Ocimene and Z -1-Propenyl-sec-butyl disulfide molecules were identified as the major composition of the essential oil of the fruits of F. angulata and F. assa-foetida , respectively. In vitro antimicrobial activity and membrane destruction investigation by scanning electron microscopy imaging illustrated that F. angulata EO had potent antibacterial activity. Besides, the EOs of both plants exhibited significant anti-yeast activity against Candida albicans. In relation to insecticidal activity, both EOs indicated appropriate potential against Ephestia kuehniella ; however, the F. assa-foetida EO had more toxicity on the studied pest. Among several insecticidal-related targets, acetylcholinesterase was identified as the main target of EO based on the molecular docking approach. Hence, in line with in vitro results, in silico evaluation determined that F. assa-foetida has a higher potential for inhibiting acetylcholinesterase and, consequently, better insecticide properties. Overall, in addition to the antioxidant properties of both EO, F. angulata EO could serve as an effective prevention against microbial spoilage and foodborne pathogens, and F. assa-foetida EO holds promise as a multi-purpose and natural biocide for yeast contamination and pest management particularly against E. kuehniella. [Display omitted] [ABSTRACT FROM AUTHOR]

Achyranthes bidentata Blume (Amaranthaceae) is an annual or perennial herb widely used as ethnomedicine in Traditional Chinese Medicine for treating fever, cold, ulcers, mensural pain, dementia, and osteoporosis. In the current study, UPLC-IM-Q-TOF-MS/MS-based chemometric approach was adopted for the tentative identification of fifty-six compounds in the extract and fractions of A.bidentata seeds. Further, the chemometric-guided isolation led to the isolation of two previously undescribed oleanane-type triterpenoid saponins, named achyranosides A-B (27 and 30), along with three known compounds (31 , 44 , and 23) from water fraction of A. bidentata seeds. The structures of new compounds were elucidated based on the detailed analysis of NMR, HR-ESI-MS, FT-IR spectral data, and GC-FID techniques. The isolated compounds in vitro acetylcholinesterase inhibitory activity revealed the promising activity of chikusetsusaponin IVa (23) (IC 50 = 63.7 μM) with mixed type of AChE inhibition in enzyme kinetic studies. Additionally, in silico binding free energy of isolated compounds disclosed the greater stability of enzyme-ligand complex owing to underlying multiple H-bond interactions. Overall, the study demonstrates the effectiveness of a chemometric-guided approach for the phytochemical exploration and isolation of new oleanane-type triterpenoid saponins from A. bidentata seeds. [Display omitted] • Fifty-six compounds were tentatively identified in the extract and fractions of A. bidentata seeds using UPLC-IM-Q-TOF-MS/MS analysis. • Two previously undescribed triterpenoid saponins along with three known were isolated from water fraction using chemometric-guided isolation. • The extract, fractions and isolated saponins demonstrated encouraging in vitro acetylcholinesterase inhibitory potential and greater stability of enzyme-inhibitor complex in in silico studies. • Chikusetsusaponin IVa [(5); IC 50 : 63.72 μM] showed mixed type of AchE inhibition in the enzyme kinetic studies. [ABSTRACT FROM AUTHOR]

The OSMAC (one strain many compounds) concept is a cultivation-based approach to increase the diversity of secondary metabolites in microorganisms. In this study, we applied the OSMAC-approach to the endophytic fungus Trichocladium sp. by supplementation of the cultivation medium with 2.5% phenylalanine. This experiment yielded five new compounds, trichocladiol (1), trichocladic acid (2), colletodiolic acid (3), colletolactone (4) and colletolic acid (5), together with five previously described ones (6–10). The structures were elucidated via comprehensive spectroscopic measurements, and the absolute configurations of compound 1 was elucidated by using TDDFT-ECD calculations. For formation of compounds 3–5 , a pathway based on colletodiol biosynthesis is proposed. Compound 6 exhibited strong antibacterial activity against methicillin-resistant Staphylococcus aureus with a minimal inhibitory concentration (MIC) of 0.78 μM as well as a strong cytotoxic effect against the human monocytic cell line THP1 with an IC 50 of 0.7 μM. Compound 8 showed moderate antibacterial activity against Mycobacterium tuberculosis with a MIC of 25 μM and a weak cytotoxic effect against THP1 cells with an IC 50 of 42 μM. [Display omitted] [ABSTRACT FROM AUTHOR]

The aim of this work is to explore the effects of herbal medicine on secondary metabolites of microorganisms during fermentation. Clonostachys rogersoniana was found to metabolize only small amounts of polyketide glycosides rogerson B and C on fresh potatoes, but after replacing the medium to the medicinal plant Rubus delavayi Franch., the type and content of the metabolized polyketones showed significant changes. The sugars and glycosides in R. delavayi are probably responsible for the changes in secondary metabolites. Six polyketide glycosides including a new metabolite, rogerson F, and two potential antitumor compounds, TMC-151C and TMC-151D, were isolated from the extract of R. delavayi fermented by C. rogersoniana. In addition, 13C labeling experiments were used to trace the biosynthesis process of these compounds. TMC-151C and TMC-151D showed significant cytotoxic activity against PANC-1, K562 and HCT116 cancer cells but had no obvious cytotoxic activity against BEAS-2B human normal lung epithelial cells. The yields of TMC-151C and TMC-151D reached 14.37 ± 1.52 g/kg and 1.98 ± 0.43 g/kg, respectively, after fermentation at 28 °C for 30 days. This is the first study to confirm that herbal medicine can induce microbes to metabolize active compounds. And the technology of fermenting medicinal materials can bring more economic value to medicinal plants. [Display omitted] • Secondary metabolites of microorganisms can be affected by herbal medicine. • TMC-151 s were enriched by fermentation of R. delavayi with C. rogersoniana. • The yields of TMC-151C and TMC-151D reached 14.37 ± 1.52 and 1.98 ± 0.43 g/kg. • Biosynthetic pathways of TMC-151 s were predicted by 13C labeling experiments. [ABSTRACT FROM AUTHOR]