Essential Oil from Vietnamese Peperomia leptostachya Hook. & Arn. (Piperaceae): Chemical Composition, Antioxidant, Anti-Inflammatory, Cytotoxic Activities, and In Silico Analysis.

This study is the first to investigate the chemical composition and antioxidant, anti-inflammatory, and cytotoxic activities of Peperomia leptostachya leaf oil. A yellow oil was obtained through hydro-distillation, with a yield of 0.1% (w/w). The GC-MS analysis revealed 66 compounds, constituting 99.6% of the oil. Sesquiterpene hydrocarbons predominated (70.4%), followed by monoterpene hydrocarbons (13.2%), oxygenated sesquiterpenes (12.4%), non-terpenic compounds (2.0%), and oxygenated monoterpenes (1.6%). Major constituents included germacrene D (25.1%), (E)-caryophyllene (17.4%), bicyclogermacrene (6.6%), α-pinene (6.2%), and ß-pinene (4.7%). The assessment of antioxidant capacity via 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assay yielded a weak effect, with an IC50 value > 100 µg/mL. The inhibition of lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells was quantified using the MTT assay, showing an IC50 value of 15.15 ± 0.68 µg/mL. Furthermore, cytotoxic effects on SK-LU-1 cell line growth were evaluated using the sulforhodamine B assay, resulting in an IC50 value of 37.45 ± 2.43 µg/mL. The anti-inflammatory activity was notable among the analyzed bioactivities of this oil. By employing a computational model, the predominant secondary metabolites in the essential oil were selected as candidates for interaction analysis with cyclooxygenase-2, an enzyme implicated in the inflammatory response. Our findings suggest that P. leptostachya leaf oil could serve as a potential source of natural compounds with prospective therapeutic effects in treating inflammatory conditions.

Conarubins A-D: Four Monoterpene-Chalcone Conjugates from Conamomum rubidum and Their Anti-inflammatory and Cytotoxic Activities.

Four novel compounds, conarubins A-D (1-4), were isolated from the whole plants of Conamomum rubidum collected in Vietnam. Their structures were elucidated by extensive spectroscopic analyses and by quantum chemical calculations of NMR and ECD. Compounds 1 and 2 were the first examples of monoterpene-monoterpene-chalcone conjugates in nature, whereas compound 4 was an unprecedented monoterpene-substituted chalcone containing a 3,4,5-trioxygenated cyclohexa-2,5-diene-1-one ring. The anti-inflammatory and cytotoxic activities of all isolates were investigated.

Aspiletrein A Induces Apoptosis Cell Death via Increasing Reactive Oxygen Species Generation and AMPK Activation in Non-Small-Cell Lung Cancer Cells.

Lung cancer remains a leading cause of death in cancer patients, and deregulation of apoptosis is a serious concern in clinical practice, even though therapeutic intervention has been greatly improved. Plants are a versatile source of biologically active compounds for anticancer drug discovery, and aspiletrein A (AA) is a steroidal saponin isolated from Aspidistra letreae that has a potent cytotoxic effect on various cancer cell lines. In this study, we investigated and determined the underlying molecular mechanism by which AA induces apoptosis. AA strongly induced apoptosis in NSCLC cells by mediating ROS generation and thereby activating AMP-activated protein kinase (AMPK) signaling. Consequently, downstream signaling and levels of phosphorylated mTOR and Bcl-2 were significantly decreased. Pretreatment with either an antioxidant, N-acetylcysteine, or an AMPK inhibitor, compound C, could reverse the apoptosis-inducing effect and counteract the effect of AA on the AMPK signaling pathway. Decreased levels of Bcl-2 were due to AA-mediating Bcl-2 degradation via a ROS/AMPK/mTOR axis-dependent proteasomal mechanism. Consistently, the apoptotic-inducing effect of AA was also observed in patient-derived malignant lung cancer cells, and it suppressed an in vitro 3D-tumorigenesis. This study identified the underlying mechanism of AA on lung cancer apoptosis, thereby facilitating potential research and development of this compound for further clinical implications.

Antioxidant activity and α-glucosidase inhibitability of Distichochlamys citrea M.F. Newman rhizome fractionated extracts: in vitro and in silico screenings.

Distichochlamys citrea M.F. Newman (commonly known as "Black Ginger") is an endemic plant to Vietnam and has been extensively exploited by folk medication for treatments of infection-related diseases and diabetes. In this work, its rhizomes were subjected to fractionated extraction, phytochemical examination, evaluation of antioxidant effect by DDPH free radical neutralization, and inhibitory activity toward α-glucosidase. The compositional components were subjected to in silico screening, including density functional theory calculation, molecular docking simulation, physicochemical analysis, and pharmacokinetic regression. In the trials, EtOAc fraction is found as the bioactive part of most effectiveness, regarding both antioxidant effect (IC50 = 90.27 µg mL-1) and α-glucosidase inhibitory activity (IC50 = 115.75 µg mL-1). Chemical determination reveals there are 13 components of its composition. DFT-based calculations find no abnormal constraints in their structures. Docking-based simulation provides order of inhibitory effectiveness: 3-P53341 > 12-P53341 > 7-P53341 > 4-P53341 > 11-P53341 > 10-P53341. QSARIS-based investigations implicate their biocompatibility. ADMET-based regressions indicate that all candidates are generally safe for medicinal applications. The findings would contribute to the basis for further studies on the chemical compositions of Distichochlamys citrea and their biological activities. Supplementary Information: The online version contains supplementary material available at 10.1007/s11696-022-02273-2.

Antioxidant Activity of a New Xanthone Derivative from Aspidistra Letreae: In Vitro and In Silico Studies.

A new xanthone derivative, aspidxanthone A (1), and three known compounds ((2S)-1-(ß-D-galactopyranosyloxy)-3-(hexadecanoyloxy)propan-2-yl (9Z,12Z)-octadeca-9,12-dienoate (2), (25S)-spirostane-1ß,3α,5ß-triol (3), and asparenyldiol (4)) were isolated from the whole of the endemic species Aspidistra letreae in Vietnam. Their structures were elucidated by means of extensive spectroscopic analyses and comparison with published data. In this study, we report the isolation and structure elucidation of a new compound aspidxanthone A, antioxidant activities of the extract and isolates 1-4, and in silico molecular docking of aspidxanthone A. The ethyl acetate extract had good antioxidant activity with an IC50 value of 26.3 µg mL-1 . Among the isolates, aspidxanthone A exhibited DPPH reduction activity with an IC50 value of 11.2 µM, which is in the same range as that of the positive control, ascorbic acid. The mechanism of action of aspidxanthone A on the tyrosinase and xanthine oxidase proteins have been clarified by in silico studies.

chiro-Inositol Derivatives from Chisocheton paniculatus Showing Inhibition of Nitric Oxide Production.

Six new chiro-inositol derivatives (1-6) were isolated from the leaves of Chisocheton paniculatus collected in Vietnam. Their chemical structures were elucidated by 1D and 2D NMR and HRESIMS analyses. All isolated compounds were evaluated for their inhibitory activity against lipopolysaccharide-induced nitric oxide (NO) production in the RAW 264.7 macrophage cell line. Compound 4 exhibited potent inhibitory activity for NO production with an IC50 value of 7.1 µM.

Effects of Hippeastrum reticulatum on memory, spatial learning and object recognition in a scopolamine-induced animal model of Alzheimer's disease.

CONTEXT: The methanol extracts from Hippeastrum reticulatum (L'Hér.) Herb. (Amaryllidaceae) (HR) display acetylcholinesterase inhibitory (AChEI) activity. OBJECTIVE: AChEI of alkaloids isolated from HR bulbs and the ameliorating effects of the alkaloid fraction (AHR) on memory and cognitive dysfunction in scopolamine-treated mice were investigated. MATERIALS AND METHODS: Alkaloids were isolated by column chromatography and identified by spectroscopy. AChEI was evaluated using the modified Ellman's method. Sixty Swiss male mice were randomly divided into six groups, received samples for 15 days. Normal group received saline, scopolamine-treated group scopolamine (1.5 mg/kg, intraperitoneal injection). Test groups received AHR (5, 10 and 15 mg/kg, per os) and positive control group donepezil (5 mg/kg, per os), administered 1 h before the test, scopolamine was injected 30 min prior to testing. The cognitive-enhancing activity of AHR against scopolamine-induced memory impairments was investigated using Y-maze, the novel object recognition test (NORT) and the Morris water maze (MWM) test. RESULTS: Seven alkaloids were isolated for the first time from the genus Hippeastrum: trans-dihydronarciclasine (1), N-chloromethylnarcissidinium (2), narciprimin (3), narciclasine-4-O-ß-d-xylopyranoside (4), N-methyltyramine (5), 3ß,11α-dihydroxy-1,2-dehydrocrinane (6) and brunsvigine (7); three are new compounds (2, 5, 6). Among them, 2-3 and 5-6 showed AChEI in vitro with IC50 values of 29.1, 46.4, 70.1 and 104.5 µg/mL, respectively. The anti-AChEI of 2, 5 and 6 are reported for the first time. In in vivo test, AHR (15 mg/kg) significantly increased in spontaneous alternation performance in the Y-maze test (p < 0.01), it significantly increased the time spent exploring the novel object (p < 0.05) comparison with scopolamine-treated group. The administration of AHR at doses 10 and 15 mg/kg significantly decreased escapes latency and swimming distance to the platform on day 6 compared to these in day 1 (p < 0.01 and p < 0.05, respectively). CONCLUSIONS: AHR could be a potential candidate of future trials for treatment of memory and cognitive dysfunction in Alzheimer's disease.

Antibacterial activities of chemical constituents from the aerial parts of Hedyotis pilulifera.

CONTEXT: Hedyotis pilulifera (Pit.) T.N. Ninh (Rubiaceae) has been used in Vietnamese ethnomedicine; the methanol extract exhibited antibacterial activity in our preliminary screening. OBJECTIVES: In this study, compounds from H. pilulifera were isolated and their antibacterial activity in vitro was evaluated. MATERIALS AND METHODS: The aerial parts of H. pilulifera (1.4 kg) were extracted with MeOH, suspended in water and ethyl acetate extract was chromatographed on a silica gel column. The structures of isolated compounds were elucidated by the combination analyses of spectroscopy including 1D-, 2D-NMR, HRMS and in comparison with the reported NMR data in the literature. All isolated compounds were evaluated for inhibitory effect using the microdilution method toward Staphylococcus aureus, Bacillus subtilis and Mycobacterium smegmatis, and MIC values were determined. RESULTS: Twenty compounds were isolated, including five triterpenoids, two steroids, two aromatic compounds, three fatty acids, one quinone derivative, one lignan glycoside, one ceramide and five glycolipids. Among these, oleanolic acid showed significant antibacterial activity against M. smegmatis with the MIC value of 2.5 µg/mL. Remarkably, rotungenic acid showed strong activity against S. aureus, B. subtilis, M. smegmatis with MIC values of 2.5, 2.5 and 1.25 µg/mL, respectively. Rotundic acid exhibited significant antibacterial activity against B. subtilis with the MIC value of 5 µg/mL. To the best of our knowledge, the antibacterial activity of rotungenic acid, stigmast-4-ene-3,6-dione and (2S,3S,4R,2'R)-2-(2'-hydroxytetracosanoylamino) octadecane-1,3,4-triol was reported for the first time. CONCLUSIONS: Oleanolic acid, rotungenic acid, and rotundic acid were considered to be useful for developing new antimicrobial therapeutic agents for human.

A new polyoxygenated cyclohexene and a new megastigmane glycoside from Uvaria grandiflora.

A new polyoxygenated cyclohexene, (-)-3-O-debenzoylzeylenone (1), and a new megastigmane glycoside, grandionoside A (2), were isolated from the aerial parts of Uvaria grandiflora collected in Vietnam, together with ten known compounds including polyoxygenated cyclohexenes (3-6), a triterpenoid (7), an alkaloid (8), a long chain alcohol (9), hexenyl glycopyranoside (10), and saponins (11-12). Their chemical structures were elucidated by a combination of extensive NMR spectroscopy with X-ray crystallographic analysis for 1, and chemical conversion for 2. Compound 1 exhibited significant cytotoxicity against the LU-1 and SK-Mel-2 cell lines with IC50 values of 4.68 and 3.63 µM, respectively. Remarkably, the cytotoxicity of 12 against the LU-1, KB, Hep-G2, MKN-7, and SW-480 cell lines was comparable to that of ellipticine, the positive control, with IC50 values ranging from 1.24 to 1.60 µM.

Aspidiatas C and D, two new spirostanol saponins from Aspidistra triradiata and their cytotoxic activities.

Aspidiatas C and D (1 and 2), two new spirostanol saponins, were isolated along with two known compounds, (25 R*)-spirost-5-en-3ß-yl α-L-rhamnopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→4)-[α-L-rhamnopyranosyl-(1→2)]-ß-D-glucopyranoside (3), (25 R*)-spirost-5-en-3ß-yl α-L-rhamnopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→4)-ß-D-glucopyranoside (4) from the whole plant of Aspidistra triradiata collected in Vietnam. The chemical structures were determined by HRESIMS, 1D- and 2D-NMR analysis, and comparison with published data. Compound 3 exhibited potent cytotoxicity against MCF7, HepG2, SK-LU-1, and HT-29 human cancer cell lines with IC50 values ranging from 0.19 to 0.65 µM. Compounds 1, 2, and 4 displayed moderate cytotoxic effects with IC50 values ranging from 12.32 to 82.27 µM. Compounds 1-4 were isolated from the genus Aspidistra for the first time.

Homalolides C-D, two new sesquiterpenoids from the rhizomes of Homalomena pendula.

Two new sesquiterpenoids, homalolides C - D (1‒2), were co-isolated from the rhizomes of Homalomena pendula (Blume) Bakh.f collected in Vietnam with five known ones, aromadendrane-4α,10α-diol (3), bullatantriol (4), 1ß,4ß,6α-trihydroxy-eudesmane (5), 1ß,4ß,6ß-trihydroxyeudesmane (6), and 1ß,4ß,7α-trihydroxy-eudesmane (7). The structures and relative configuration of new compounds were elucidated by 1 D-/2D-NMR, IR, UV and HRESIMS analyses, and by comparisons to the reported data in the literature. Homalolide C presented an unprecedented skeleton with the 4/8 bicyclic system. All isolates did not exhibit appreciable inhibitory effects on LPS-induced NO production in the RAW 264.7 macrophage cell line and on the growth of human lung cancer cell line (SK-LU-1).

Conamonin A and dihydrochalcones from the whole plants of Conamomum rubidum (Lamxay & N.S.Lý) Skornick. & A.D. Poulsen showing anti-inflammatory and cytotoxic activities.

A new compound, conamonin A (1), was isolated from the whole plants of Conamomum rubidum with eight known dihydrochalcones (2-9). Their structures were elucidated by a combination of spectroscopic methods as well as by comparison with previously reported data. The absolute configuration of 1 was assigned by TDDFT-ECD method. Compounds 1 and 8 showed inhibitory activity against LPS-induced NO production in the RAW 264.7 cells, with IC50 values of 58.29 ± 2.88 and 81.77 ± 5.99 µM, respectively. Compounds 3/4 and 5/6 exhibited inhibitory effects, with IC50 values of 28.76 ± 1.16 and 29.89 ± 1.79 µg/mL, respectively. Compounds 2, 7-9 exhibited significant cytotoxic activity against human lung carcinoma (the SK-LU-1 cell line) with IC50 values ranging from 9.87 to 17.99 µM. This study offers valuable insights into the chemical constituents and biological activities of Conamomum rubidum, highlighting its potential as a source for discovering new anti-inflammatory and cytotoxic agents.

A green method to extract rutin from Sophora japonica L.

Sophora japonica L. contains high levels of rutin, which has great potential for use in pharmaceutical products for the treatment of diseases related to the cardiovascular and circulatory systems. We proposed a method of extracting rutin from S. japonica by using a green solvent.•Green deep eutectic solvents (DESs) of choline chloride and ethylene glycol (ChCl-Eth) showed the highest extraction efficiency of rutin from S. japonica.•Under optimal conditions, the extraction yield of ChCl-Eth was 1.34 times higher than that of methanol as solvent.•Rutin was recovered from the DES extracts using water as the antisolvent with a high recovery yield, and the DESs of ChCl-Eth could be productively recovered and reused at least 3 times.

Sesquiterpenoids from the rhizomes of Homalomena pendula and their anti-inflammatory activities.

Sixteen sesquiterpenoids including two new ones, homalolides A - B (1‒2), were firstly isolated from the methanolic extract of the rhizomes of Homalomena pendula collected in Vietnam. The structures and relative stereochemistry of new compounds were elucidated by 1D-/2D-NMR, IR, UV and HRESIMS analyses. The GCMS experiment demonstrated that homalolide A (1) is an artifact due to the methylation during methanolic extraction process. All isolates (1‒16) were tested for their inhibitory activities against lipopolysaccharide-induced nitric oxide production in the RAW 264.7 macrophage cell line. Compounds 1, 3, 6‒8, 10‒12 displayed moderate inhibitory effect on NO production with IC50 values ranging from 35.41 to 64.06 µM.

Chemical composition and biological activities of essential oil from Grewia bulot leaves.

This study focused on the chemical composition and biological activities of the essential oil derived from Grewia bulot, a plant species known for its medicinal properties. The analysis of Grewia bulot essential oil revealed the presence of 78 constituents. The major compounds were α-cadinol (13.5%), 1,8-cineole (12.7%), 1,10-di-epi-cubenol (9.8%), epi-α-cadinol (6.7%), (E,E)-α-farnesene (5.9%), (E)-citral (4.0%), selin-11-en-4-α-ol (4.0%), citronellol isobutanoate (3.9%), and geranic acid (3.7%). The essential oil exhibited promising antioxidant potential with an IC50 value of 452.65 ± 28.40 µg/mL in DPPH model. This oil did not show NO production inhibitory effect in RAW 264.7 cells. In addition, the essential oil exhibited significant cytotoxicity against KB, Hep-G2, MCF-7, and SK-LU-1 cancer cell lines, with IC50 values ranging from 44.04 ± 1.47 to 74.20 ± 3.71 µg/mL.

Chemical composition and acetylcholinesterase inhibitory activity of essential oil from the leaves of Mitrephora poilanei Weeras. & R.M.K. Saunders.

The present study provides the first information on the chemical composition and acetylcholinesterase inhibitory activity of the essential oil (EO) from the leaves of Mitrephora poilanei Weeras. & R.M.K.Saunders from Vietnam. Gas chromatography and gas chromatography-mass spectrometry analysis revealed that the main components of the M. poilanei EO were ß-caryophyllene (13.2%), α-humulene (10.5%), germacrene D (8.1%), ß-elemene (5.2%) and bicyclogermacrene (5.1%). The anti-acetylcholinesterase assay showed that the EO displayed moderate activity with IC50 value of 31.16 ± 3.06 µg/mL. These findings proposed that the plant can be exploited for its anti-acetylcholinestrate potential.

Structure revision and absolute configuration of 5,7-diepi-2α-hydroxyoplopanone and anti-osteoporotic activities of sesquiterpenoids from the rhizomes of Homalomena pendula.

Five sesquiterpenoids including 2α-hydroxyoplopanone (1), oplopanone (2), 1ß,4ß,6α-trihydroxy-eudesmane (3), 1ß,4ß,7α-trihydroxy-eudesmane (4) and bullatantriol (5) were isolated from Homalomena pendula. The structure of the previously reported compound, 5,7-diepi-2α-hydroxyoplopanone (1a), has been revised to 1 by the spectroscopic evidences (1D-/2D-NMR, IR, UV and HRESIMS) and by comparison between experimental and theoretical NMR data using DP4+ protocol. Furthermore, the absolute configuration of 1 was unambiguously assigned by ECD experiments. Compounds 2 and 4 displayed a potent ability to stimulate osteogenic differentiation of MC3T3-E1 cells at 4 µg/mL (by 123.74% and 131.07%, respectively) and 20 µg/mL (by 112.45% and 126.41%, respectively) whilst 3 and 5 did not show any activities. At 20 µg/mL, 4 and 5 significantly promoted the mineralization of MC3T3-E1 cells with values of 112.95% and 116.37%, respectively, whereas 2 and 3 were inactive. The results indicated that 4 could be an excellent component for anti-osteoporosis studies from the rhizomes of H. pendula.

Isolation, structural elucidation, and cytotoxic activity investigation of novel styryl-lactone derivatives from Goniothalamus elegans: in vitro and in silico studies.

Two styryl-lactone derivatives (1 and 2) were isolated from the aerial parts of Goniothalamus elegans. Compound 1 is a newly discovered natural product, and compound 2 is reported in this plant for the first time. The absolute configuration of 1 was determined based on the ECD spectrum. The two styryl-lactone derivatives were tested for cytotoxicity activity against five cancer cell lines and human embryonic kidney cells. The newly discovered compound demonstrated potent cytotoxicity, with IC50 values ranging from 2.05 to 3.96 µM. Computational methods were also applied to investigate the mechanism of the cytotoxic activity of the two compounds. Density functional theory and molecular mechanisms were used to assess the interaction between protein targets to compound 1 and 2, respectively, through the EGF/EGFR signaling pathway. The results indicated that 1 showed a strong binding affinity for two proteins EGFR and HER-2. Finally, ADMET predictions were used to validate the pharmacokinetics and toxicity of these compounds. The results showed that both compounds are likely to be absorbed in the gastrointestinal tract and penetrate the blood-brain barrier. Based on our findings, these compounds may have potential for further studies to be developed into active ingredients for cancer treatment.

Chemical constituents from the Knema globularia fruits and their in vitro cytotoxicity.

Two new compounds, designated as knecorticosanones A-B (1-2), along with three known compounds (3-5) were isolated from the fruits of Knema globularia. Their structures were elucidated by extensive spectroscopy analysis, including 1D- and 2D-NMR, UV, IR, and HRESIMS and by comparison with the reported data in the literature. Compounds 1-5 were evaluated for their cytotoxicity. Knecorticosanone B (2) and malabaricone D (5) exhibited moderate cytotoxic effect against Hep-G2, MCF-7 and SK-LU-1 cell lines with IC50 values ranging from 8.76 ± 1.02 to 18.74 ± 1.75 µM while knecorticosanone A (1), virolane (3) and 7-hydroxy-3',4'-methylenedioxyflavan (4) exhibited weak inhibitory effect against these cell lines with IC50 values ranging from 25.85 ± 2.75 to 66.75 ± 2.08 µM.

Antitumor activities of Aspiletrein A, a steroidal saponin from Aspidistra letreae, on non-small cell lung cancer cells.

BACKGROUND: Lung cancer is one of the leading causes of death worldwide due to its strong proliferative and metastatic capabilities. The suppression of these aggressive behaviors is of interest in anticancer drug research and discovery. In recent years, many plants have been explored in order to discover new bioactive secondary metabolites to treat cancers or enhance treatment efficiency. Aspiletrein A (AA) is a steroidal saponin isolated from the whole endemic species Aspidistra letreae in Vietnam. Previously, elucidation of the structure of AA and screening of its cytotoxic activity against several cancer cell lines were reported. However, the antitumor activities and mechanisms of action have not yet been elucidated. In this study, we demonstrated the anti-proliferative, anti-migrative and anti-invasive effects of AA on H460, H23 and A549 human lung cancer cells. METHODS: MTT, wound healing and Transwell invasion assays were used to evaluate the anti-proliferation, anti-migration and anti-invasion effects of AA, respectively. Moreover, the inhibitory effect of AA on the activity of protein kinase B (Akt), a central mediator of cancer properties, and apoptotic regulators in the Bcl-2 family proteins were investigated by Western blotting. RESULTS: AA exhibits antimetastatic effects in human lung cancer cells through the inhibition of the pAkt/Akt signaling pathway, which in turn resulted in a significant inhibitory effect of AA on the migration and invasion of the examined lung cancer cells. CONCLUSIONS: Aspiletrein A may be a potent inhibitor of protein kinase B (Akt). Hence, AA could be further explored as a potential antimetastatic lead compound.