Confocal image of three oxoaporphine alkaloids in cancer cell lines and their interaction with DNA by multispectroscopic and molecular docking techniques.

Dicentrinone (Di), liriodenine (Li) and lysicamine (Ly) are three natural oxoaporphine alkaloids (OAs), which revealed significant biological activity such as anticancer, anti-inflammatory and antimicrobial activities and were considered as potential lead compounds for the development of new clinical chemicals. In the present study, confocal laser scanning fluorescence microscopy observation demonstrated these three natural OAs could traverse inside of the nucleus and get an opportunity to interact with DNA. Their interaction properties with DNA were then investigated simultaneously by two spectral fluorescent probes of ethidium bromide (EB) and methyl green (MG), as well as UV-vis absorption and cyclic voltammetry measurements, and further verified by the molecular docking analysis. Results indicated Di and Li were distinctly classified as the intercalative molecules to DNA, however, Ly was confirmed with a mixed-mode binding of partial intercalation and groove affinity. Their binding ability was revealed as the follows: Di ≥ Li > Ly, which was correlated with their structural changes. Thermodynamic studies revealed the binding process of Li and Ly with ctDNA was all spontaneous, the hydrophobic interaction was the major binding force for Li-ctDNA complex, however, the interaction between Ly and ctDNA relied on both hydrophobic and hydrogen binding force. Molecular docking provided detailed computational interaction of Di, Li and Ly with DNA, which proved the intercalation binding of Li-DNA complex and Di-DNA complex stabilizing mainly by the π-π binding force, however, apart from a small quantity of π-π interaction, another binding force in the Ly-DNA complex mainly was supplied from the weaker Pi-Alkyl, hydrogen bond and Pi-Anion interactions.

Paucatalinone A from Paulownia Catalpifolia Gong Tong Elicits mitochondrial-mediated cancer cell death to combat osteosarcoma.

As the global cancer burden escalates, the search for alternative therapies becomes increasingly vital. Natural products, particularly plant-derived compounds, have emerged as promising alternatives to conventional cancer treatments due to their diverse bioactivities and favorable biosafety profiles. Here, we investigate Paucatalinone A, a newly discovered geranylated flavanone derived from the fruit of Paulownia Catalpifolia Gong Tong, notable for its significant anti-cancer properties. We revealed the capability of Paucatalinone A to induce apoptosis in osteosarcoma cells and deciphered its underlying mechanisms. Our findings demonstrate that Paucatalinone A substantially augments apoptosis, inhibits cell proliferation, and demonstrates a pronounced anti-tumor effect in a murine model of osteosarcoma. Mechanistically, Paucatalinone A disrupts calcium homeostasis and exacerbates intracellular reactive oxygen species accumulation, leading to mitochondrial impairment, cytoskeletal collapse, and caspase-dependent apoptotic cell death. This study underscores the potential of Paucatalinone A in initiating apoptosis in cancer cells and highlights the therapeutic efficacy of plant-derived agents in treating osteosarcoma, offering a viable approach for managing other intractable cancers.

New cyclic C-geranylflavanones isolated from Paulownia fortunei fruits with their anti-proliferative effects on three cancer cell lines.

Seven new C-geranylated flavanones, fortunones F - L (1-7), were isolated from the fresh mature fruits of Paulownia fortunei (Seem.) Hemsl. Their structures were determined by extensive spectroscopic data interpretation (UV, IR, HRMS, NMR, and CD). These new isolated compounds were all with a cyclic side chain modified from the geranyl group. Among them, compounds 1-3 all possessed a dicyclic geranyl modification, which was described firstly for Paulownia C-geranylated flavonoids. All the isolated compounds were subjected to the cytotoxic assay on human lung cancer cell A549, mouse prostate cancer cell RM1 and human bladder cancer cell T24, respectively. Results indicated A549 cell line was more sensitive to C-geranylated flavanones than the other two cancer cell lines and compounds 1, 7 and 8 exhibited potential anti-tumor effects (IC50 ˂ 10 µM). Further research revealed the effective C-geranylated flavanones could exert their anti-proliferative activity on A549 cells by inducing apoptosis and blocking cells in G1 phase.

Possible pharmaceutical applications can be developed from naturally occurring phenanthroindolizidine and phenanthroquinolizidine alkaloids.

Naturally occurring phenanthroindolizidine and phenanthroquinolizidine alkaloids (PIAs and PQAs) are two small groups of herbal metabolites sharing a similar pentacyclic structure with a highly oxygenated phenanthrene moiety fused with a saturated or an unsaturated N-heterocycle (indolizidine/quinolizidine moieties). Natural PIAs and PQAs only could be obtained from finite plant families (such as Asclepiadaceae, Lauraceae and Urticaceae families, etc.). Up to date, more than one hundred natural PIAs, while only nine natural PQAs had been described. PIA and PQA analogues have been applied to the development of potent anticancer agents all along because of their excellent cytotoxic activity. However, in the last two decades, other great biological properties, such as anti-inflammatory and antiviral activities were revealed successively by different pharmacological assays. Especially because of their potent antiviral activity against coronavirus (TGEV, SARS CoV and MHV) and tobacco mosaic virus, PIA and PQA analogues have attracted much pharmaceutical attention again, some of them have been used to present interesting targets for total or semi synthesis, and structure-activity relationship (SAR) study for the development of antiviral agents. In this review, natural PIA and PQA analogues obtained in the last two decades with their herbal origins, key spectroscopic characteristics for structural identification, biological activity with possible SARs and application prospects were systematically summarized. We hope this paper can stimulate further investigations on PIA and PQA analogues as an important source for potential drug discovery.

Paulownia C-geranylated flavonoids: their structural variety, biological activity and application prospects.

Paulownia species, especially their flowers and fruits, are traditionally used in Chinese herbal medicines for the treatment of infectious diseases. C-geranylated flavonoids were found to be the major special metabolites in Paulownia flowers and fruits, and 76 C-geranylated flavonoids had been isolated and characterized thus far. Structural variations in Paulownia C-geranylated flavonoids are mainly due to the complicated structural modifications in their geranyl substituents. These natural compounds have attracted much attention because of their various biological activities, including antioxidation, anti-inflammation, cytotoxic activity and various enzymatic inhibitions, etc. Among them, diplacone, a major Paulownia component, was considered to have promise for applications in medicine. This paper summarizes the information from current publications on Paulownia C-geranylated flavonoids, with a focus on their structural variety, key spectroscopic characteristics, biological activity with structure-activity relationships and application prospects. We hope that this paper will stimulate further investigations of Paulownia species and this kind of natural product.

Undescribed C-geranylflavonoids isolated from the fruit peel of Paulownia catalpifolia T. Gong ex D.Y. Hong with their protection on human umbilical vein endothelial cells injury induced by hydrogen peroxide.

Six undescribed C-geranylated flavonoids, including five C-geranylflavanones named as paucatalinones F - J, one C-geranylflavonol named as paucatalinone K, along with seven known geranylated flavanones, were isolated from the fruit peel of Paulownia catalpifolia T. Gong ex D.Y. Hong. Their structures were elucidated distinctly according to their UV, IR, MS, NMR, and CD data. Among them, two compounds were substituted with unusual modified geranyl groups, namely paucatalinone F with an oxygenated cyclogeranyl substituent and paucatalinone H with a terminal pyranoid geranyl substituent. Furthermore, the protective effects on human umbilical vein endothelial cells (HUVECs) injury induced by H2O2 were evaluated, and paucatalinone F showed the most potential activity. The bioactive results suggested that the geranyl substituent may be an important factor for restraining oxidative HUVECs damage and Paulownia C-geranylated flavonoids might have the potential for preventing cardiovascular complications.

Identification of C-geranylated flavonoids from Paulownia catalpifolia Gong Tong fruits by HPLC-DAD-ESI-MS/MS and their anti-aging effects on 2BS cells induced by H2O2.

The fruits of Paulownia catalpifolia Gong Tong are used as a Chinese folk herbal medicine for the treatment of enteritis, tonsillitis, bronchitis, and dysentery, etc. Our previous study has identified new C-geranylated flavanones with obvious anti-proliferative effects in lung cancer A549 cells. In the present study, a new C-geranylated flavone, paucatalinone C (1) and five known C-geranylated flavanones (2-6) were isolated. In addition, a total of 34 C-geranylated flavonoids were detected by HPLC-DAD-ESI-MS/MS coupling techniques from the CH2Cl2 extract of P. catalpifolia. Futhermore, anti-aging effects of isolated compounds were evaluated in vitro with premature senescent 2BS cells induced by H2O2. Phytochemical results indicated that P. catalpifolia was a natural resource of abundant C-geranylated flavonoids. Diplacone (3) and paucatalinone A (5) were the potent anti-aging agents in the premature senescent 2BS cells induced by H2O2 and the C-geranyl substituent may be an important factor because of its lipophilic character.

Development of Marker-Free Transgenic Potato Tubers Enriched in Caffeoylquinic Acids and Flavonols.

Potato (Solanum tuberosum L.) is a major crop worldwide that meets human economic and nutritional requirements. Potato has several advantages over other crops: easy to cultivate and store, cheap to consume, and rich in a variety of secondary metabolites. In this study, we generated three marker-free transgenic potato lines that expressed the Arabidopsis thaliana flavonol-specific transcriptional activator AtMYB12 driven by the tuber-specific promoter Patatin. Marker-free potato tubers displayed increased amounts of caffeoylquinic acids (CQAs) (3.35-fold increases on average) and flavonols (4.50-fold increase on average). Concentrations of these metabolites were associated with the enhanced expression of genes in the CQA and flavonol biosynthesis pathways. Accumulation of CQAs and flavonols resulted in 2-fold higher antioxidant capacity compared to wild-type potatoes. Tubers from these marker-free transgenic potatoes have therefore improved antioxidant properties.

[Study on Chemical Constituents of Strychnos nux-vomica].

Objective: To isolate and identify the chemical constituents from the seeds of Strychnos nux-vomica. Methods: Chromatographic separation techniques such as silica gel chromatography,ODS chromatography and Sephadex LH-20 chromatography were used for the isolation and purification. The structures of the chemical constituents were identified on the basis of mass spectrometry,NMR spectroscopy and so on. Results: 16 compounds were isolated and their structures were identified as: α-amyrin( 1), vomicine( 2), stearic acid( 3), ß-sitosterol( 4),vanillin( 5), ethyl gallate( 6),methyl gallate( 7),novacine( 8),strychnine( 9), daucosterol( 10),brucine chloromethochloride( 11),loganic acid( 12),strychnine chloromethochloride( 13),brucine( 14),geniposide( 15) and loganin( 16). Conclusion: Compounds 3,6,7 and 15 are isolated from this genus for the first time.

[Chemical Constituents of Paulownia tomentosa Fruits].

OBJECTIVE: To investigate the chemical constituents from the fruits of Paulownia tomentosa. METHODS: The compounds were isolated and purified by column chromatography and their structures were identified on the basis of physicochemical properties and spectral analyses. RESULTS: Seven compounds were isolated and their structures were identified as ursolic acid (1), sesamin(2),2α,3α, 19a-trihydroxyurs-12-en-28-oic acid(3), luteolin(4), tricin-7-O-ß-D-glucoside(5),3',4',5,7-tetrahydroxy-6-[7-hydroxy-3,7-dimethyl-2(E)-octenyl] flavanone(6) and stigmasterol(7). CONCLUSION: Compounds 3, 5 and 7 are isolated from Paulownia genus for the first time. Compound 2 is isolated from Paulownia tomentosa for the first time.

New geranylated flavanones from the fruits of Paulownia catalpifolia Gong Tong with their anti-proliferative activity on lung cancer cells A549.

Three new geranylated flavanones, named as paucatalinone A (1), B (2), and isopaucatalinone B (3), were isolated from the fruits of Paulownia catalpifolia Gong Tong (Scrophulariaceae). Their structures were well determined by means of IR, MS, 1D and 2D NMR, and CD techniques. Paucatalinone A (1) is the first sample as a dimeric geranylated flavanone derivative isolated from natural products. Paucatalinone A (1) displayed good antiproliferative effects on human lung cancer cells A549 and resulted in a clear increase of the percentage of cells in G1 phase and a decrease in the percentage of cells in S and G2/M phases in comparison with control cells.

Ultra-HPLC method for quality and adulterant assessment of steviol glycosides sweeteners - Stevia rebaudiana and stevia products.

Stevia products are advertised as a zero-calorie sweetener. Glucose should not be an intrinsic component of this product, but it has been identified from some of stevia products in a preliminary study. An UHPLC-UV method was developed for the quantitative determination of glucose from stevia products. After stevia products reacted with 1-phenyl-3-methyl-5-pyrazolone (PMP), PMP derivatives were analysed and glucose was found in seven out of 35 products in the range 0.3-91.5% (w/w). Two products, SPR-12 and SPR-27, showed remarkable amounts of glucose at 61.6% and 91.5%, respectively. In addition, an UHPLC-UV-evaporative light-scattering detector (ELSD) method was developed for the quantitative determination of rebaudioside A, stevioside, rebaudioside D, dulcoside A and steviolbioside from Stevia rebaudiana and related products. In a 12 min run, five steviol glycosides were baseline-separated. ELSD and ultraviolet (UV) detections showed comparable results. The LC methods were validated for linearity, repeatability, accuracy, limits of detection (LOD) and limits of quantification (LOQ). For steviol glycosides, the LODs and LOQs were found to be less than 10 and 30 µg ml(-1), respectively. The RSD for intra- and inter-day analyses was less than 2.5%, and the recovery was 90-94%. For PMP derivative of glucose, the LOD and LOQ were 0.01 and 0.05 µg ml(-1), respectively. Repeatability (RSD) was less than 2.6%; recovery was 98.6-101.7%. The methods are useful for the identification, quality assurance, and adulterant assessment of S. rebaudiana and steviol glycosides sweeteners (stevia products).

[Chemical constituents from root bark of Dictamnus dasycarpus].

OBJECTIVE: To isolate and identify the chemical constituents from the root bark of Dictamnus dasycarpus. METHODS: Silica gel, Sephadex LH-20, ODS and PTLC were employed for the isolation and purification of chemical constituents. The structures were identified on the basis of spectral data and physicochemical examination. RESULTS: Thirteen compounds were isolated and identified as follows: rutaevin (1), obacunone (2), fraxinellone (3), limonin (4), dictamnine (5), beta-sitosterol (6), 5-hydroxylmethylfuraldehyde (7), daucosterol (8), 3beta-hydroxy-cholesta-5-ene (9), fraxinellonone (10), rutin (11), quercetin (12) and scopoletin (13). CONCLUSION: Compounds 7 and 9 are isolated from this genus for the first time.

Antiviral spirooliganones A and B with unprecedented skeletons from the roots of Illicium oligandrum.

Two novel spirooliganones A (1) and (2), a pair of spiro carbon epimers, with a rare dioxaspiro skeleton were isolated from the roots of Illicium oligandrum. The structures were fully determined by spectroscopic analysis and chemical methods, especially modified Mosher's method, and X-ray diffraction analysis. Spirooliganone B was found to exhibit more potent activities against coxsackie virus B3 and influenza virus A (H3N2) (IC50 3.70-5.05 µM) than spirooliganone A. The biosynthetic pathway involving a hetero-Diels-Alder reaction of the epimers was proposed.

[Chemical constituents of Neoalsomitra integrifoliola].

OBJECTIVE: To study the chemical constituents of the n-BuOH fraction of 95% ethanolic extract of leaves of Neoalsomitra integrifoliola. METHOD: The compounds were isolated with kinds of column chromatography. The structures were determined by MS and NMR spectroscopic techniques. RESULT: Eight compounds were isolated from the n-BuOH fraction of 95% ethanolic extract and their structures were identified as 2-phenylethyl rutinoside (1), rutin (2), kaempferol-3-O-alpha-L-rhamnopyranosyl-(1-->6)-beta-D-glucopyranoside (3), isorhamnetin-3-O-alpha-L-rhamnopyranosyl-(1-->6)-beta-D-glucopyranoside (4), methyl chlorogenate (5), guanosine (6), adenosine (7), myo-inositol (8), respectively. CONCLUSION: All compounds were isolated from this genus for the first time.

[Study on chemical constituents from flowers of Ailanthus altissima].

OBJECTIVE: To isolate and identify the chemical constituents from the flowers of Ailanthus altissima. METHODS: Macroporous adsorptive resins (DM130), Silica gel, Sephadex LH-20, ODS were employed for the isolation and purification of chemical constituents. The structures were identified on the basis of spectral data and physicochemical examination. RESULTS: Eight compounds were isolated and identified as follows: brevifolin (1), brevifolin carboxylic acid (2), methyl brevifolin carboxylate (3), ellagic acid (4), diethyl-2,2',3,3',4,4'- hexahydroxybiphenyl-6,6'-dicarboxylate (5), rutin (6), gallic acid (7), ethyl gallate (8). CONCLUSION: Compounds 1 -5 are isolated from this genus for the first time.

Dimeric prenylated C6-C3 compounds from the stem bark of Illicium oligandrum.

Three new dimeric prenylated C6-C3 compounds, namely, illicidiones A (1), B (2), and C (3), were isolated from the stem bark of Illicium oligandrum. The structure and absolute configuration of these compounds were determined by extensive spectroscopic and chemical analyses, including NMR, modified Mosher method, and single-crystal X-ray study. Compounds 1-3 exhibited weak anti-inflammatory activities.

Four new phenolic diglycosides from the roots of Illicium oligandrum.

Four new phenolic diglycosides (1-4), named illoliganoside A-D, and three known glycosides (5-7), were isolated from the roots of Illicium oligandrum. The structures of the new diglycosides were determined on the basis of HRMS, NMR spectroscopic, and chemical methods. The anti-inflammatory and cytotoxic activities for 1-7 were evaluated.

Prenylated C6-C3 compounds with molecular diversity from the roots of Illicium oligandrum.

Eleven prenylated C(6)-C(3) compounds, illioliganpyranone A (1), illioliganfunone A-D (2-5), and illioliganone D-I (6-11), together with five known prenylated C(6)-C(3) compounds (12-16), were isolated from roots of Illicium oligandrum. The structures of 1-11 were elucidated by spectroscopic methods including 1D and 2D NMR, HRESIMS, and CD experiments. Possible biosynthetic pathways to compounds 1-16 derived from a common precursor of 5-allylbenzene-1,2,4-triol were postulated. All compounds were evaluated for cytotoxic activities against five human cancer cell lines (HCT-8, Bel-7402, BGC-823, A549 and A2780). Compound 15 exhibited significant cytotoxicity against HCT-8, BGC-823, A549, and A2780 cell lines with IC(50) values of 0.30-2.57 µM. Compound 16 showed moderate selective cytotoxicity against sensitive A2780 cells with IC(50) value of 1.38 µM.

New flavonoids with 2BS cell proliferation promoting effect from the seeds of Trigonella foenum-graecum L.

Ten flavonoids were isolated from the ethyl acetate-soluble fraction of the ethanolic extract of the seeds of Trigonella foenum-graecum and their structures were elucidated on the basis of spectroscopic methods to be 5,7,3'-trihydroxy-5'-methoxylisoflavone (1), biochanin A (2), formononetin (3), irilone (4), tricin (5), daidzein (6), calycosin (7), orientin-2''-O-p-trans-coumarate (8), vitexin-2''-O-p-trans-coumarate (9), and tricin-7-O-beta-D: -glucopyranoside (10). Compounds 1 and 8 are new flavonoids, and 8 and 9 strongly promoted 2BS cell proliferation induced by H(2)O(2).