Qualitative, Quantitative, In Vitro Antioxidant Activity and Chemical Profiling of Leptadenia pyrotechnica (Forssk.) Decne Using Advanced Analytical Techniques.

Leptadenia pyrotechnica Forssk. Decne (LP) is a medicinal herb from the Asclepiadaceae family with many advantageous properties. The goal of this research is to identify, quantify, and evaluate the antioxidant potential of LP to validate its remarkable therapeutic advantages. The hot soxhlet extraction method was employed to prepare different extracts of LP (stem and root). These extracts were evaluated physiochemically to check their impurity, purity, and quality; qualitatively to detect different phytochemicals; and quantitatively for phenol, saponin, tannin, flavonoid, and alkaloid contents. Then, the in vitro antioxidant potential was estimated by DPPH, NO, H2O2 scavenging assays, and MC and FRAP assays. The most prevalent phytochemicals of LP were then analysed by AAS, FT-IR, UV-visible, and GC-MS techniques. A higher extractive yield was shown by LPSE and LPRE (7.37 ± 0.11 and 5.70 ± 0.02). The LP stem showed better physicochemical and qualitative results than the root. The quantitative and in vitro antioxidant results indicated maximal phenols, tannins, and alkaloid contents in LPSE, which was further confirmed by UV-visible, FT-IR, and GC-MS results. The extraction methods (soxhlation or ultrasonication) were optimized by utilizing RSM to determine the impacts of multiple parameters. The study concluded that the plant has remarkable therapeutic advantages to promote additional clinical investigations and the mechanisms of its action.

Bioactive alkaloids from Nepalese Corydalis chaerophylla D.C. acting on the regulation of PCSK9 and LDL-R in vitro.

Four new alkaloids Chaeronepaline-A (1), Chaeronepaline-B (2), Chaeronepaline-C (3), and Chaeronepaline-D (4) were isolated from Corydalis chaerophylla D.C. collected from Nepal and their structures were elucidated by spectroscopic data, 1D, 2D NMR and mass spectrometry. The structures were established as 3,12- Dimethoxy-5,6-dihydroisoquinolino [2,1-b] isoquinolin- 7- ium- 2, 9- diol (1), 7-methyl-5, 6, 7, 8-tetrahydroisoquinoline- 2, 3- methylenedioxy- (8-> 9)- 10, 12- methylenedioxy- benzoic-16-acid (2), 7- methyl-5, 6, 7, 8- tetrahydro- 8H-spiro-9,14-dihydroxy-11,12-methylenedioxy-indane-isoquinoline (3) and 7- methyl-5, 6, 7, 8- tetrahydro- 8H-spiro-9,14-dihydroxy-11,12-methylenedioxy-indane-isoquinoline-N-oxide (4). The new alkaloids were tested in human hepatoma cell line to assess their ability to modulate the expression of low-density lipoprotein receptor (LDL-R), of proprotein convertase subtilisin/kexin 9 (PCSK9) and to affect cellular cholesterol biosynthesis with the aim to evaluate their potential hypocholesterolemic effect. Results indicated that compounds 2 and 3 upregulate the LDLR, and inhibited the cholesterol biosynthesis with compound 2, which also reduced the secretion of PCSK9 by Huh7 cells. These in vitro data indicated a potential hypocholesterolemic effect of compound 2 that requires further in vivo validation.

Examining the Long-Term Impacts of Ergot Alkaloids on Fetal Heifer Development and Subsequent Growth and Reproductive Performance.

Consumption of toxic endophyte-infected tall fescue results in poor reproductive performance in domestic livestock. In this study, the objective was to evaluate the effects of ergovaline exposure during mid-gestation (days 93 through 188 of gestation) on dam performance, the growing female fetus, and the subsequent growth and reproductive performance of the gestationally-exposed heifer calves. Pregnant Angus and Simmental-Angus cows were blocked by age (2 - 3, 4 - 7, and > 7 y), body weight (BW), and breed; and then randomly assigned to graze either novel (EN; <5% infection rate; n = 27 Year 1, n = 16 Year 2) or toxic endophyte-infected tall fescue (EI; 99% infection rate; n = 27 Year 1, n = 17 Year 2). Weekly BW, body condition scores (BCS), hair coat scores (HCS), hair shedding scores (HSS), and blood samples for progesterone (P4) analysis were collected from mid-April through July of 2017 (Year 1) and 2018 (Year 2). Gestation length, birth weight, placental characteristics, heifer calf growth, onset of puberty, ovarian characteristics, and artificial insemination (AI) pregnancy rates were measured. Data were analyzed using the MIXED procedure of SAS. Cows grazing EI pastures had reduced ADG, reduced BCS, greater HSS, and decreased P4 concentrations compared to cows on EN pasture (P < 0.01). Birth weights were decreased for heifers whose dams were exposed to EI pastures during their second trimester (P < 0.01). Heifer pregnancy rates were not impacted by EI pasture exposure during gestation for either year of the study. However, a treatment by year effect was seen for pregnancy rate for EI exposed heifers in Year 2; EI exposed heifers in Year 2 had increased pregnancy rates at two of the inseminations. Combined, these data reinforce that consumption of toxic endophyte-infected tall fescue during gestation can negatively impact both dam and offspring performance. More studies are needed to evaluate more parameters in an effort to elucidate the possible life-long impacts of ergovaline exposure during gestation.

Ramulus Mori (Sangzhi) Alkaloids Alleviate Diabetic Nephropathy through Improving Gut Microbiota Disorder.

Diabetic nephropathy (DN), one of the leading causes of end-stage kidney failure worldwide, is closely associated with high mortality in diabetic patients. However, therapeutic drugs for DN are still lacking. Ramulus Mori alkaloids (SZ-A), an effective component of alkaloids extracted from Ramulus Mori, have been found to improve glucose and lipid metabolism to mitigate diabetes and obesity; however, few studies have focused on their effects on DN progression. Thus, we investigated the protective role of SZ-A on DN through 16S rRNA sequencing, non-targeted metabolomics, and fecal microbiota transplantation (FMT) experiments. To address our hypothesis, we established the DN mouse model by combining a high-fat diet (HFD) with streptozotocin (STZ) injection. Herein, we demonstrated that SZ-A supplementation was recalcitrant to renal injury in DN mice, improving glomerular morphology, reversing the blood biochemistry parameters, and ameliorating podocyte injury. Importantly, the composition of the gut microbiota altered after SZ-A treatment, especially with the elevated abundance of Dubosiella and the increased level of serum pentadecanoic acid. FMT experiments further revealed that the gut microbiota exerted critical effects in mediating the beneficial roles of SZ-A. In vitro experiments proved that pentadecanoic acid administration improved podocyte apoptosis induced by AGEs. Taken together, SZ-A play a renoprotective role, possibly through regulating the gut microbiota and promoting pentadecanoic acid production. Our current study lends support to more extensive clinical applications of SZ-A.

Pyrrolizidine Alkaloids as Hazardous Toxins in Natural Products: Current Analytical Methods and Latest Legal Regulations.

Pyrrolizidine alkaloids (PAs) are toxic compounds that occur naturally in certain plants, however, there are many secondary pathways causing PA contamination of other plants, including medicinal herbs and plant-based food products, which pose a risk of human intoxication. It is proven that chronic exposure to PAs causes serious adverse health consequences resulting from their cytotoxicity and genotoxicity. This review briefly presents PA occurrence, structures, chemistry, and toxicity, as well as a set of analytical methods. Recently developed sensitive electrochemical and chromatographic methods for the determination of PAs in honey, teas, herbs, and spices were summarized. The main strategies for improving the analytical efficiency of PA determination are related to the use of mass spectrometric (MS) detection; therefore, this review focuses on advances in MS-based methods. Raising awareness of the potential health risks associated with the presence of PAs in food and herbal medicines requires ongoing research in this area, including the development of sensitive methods for PA determination and rigorous legal regulations of PA intake from herbal products. The maximum levels of PAs in certain products are regulated by the European Commission; however, the precise knowledge about which products contain trace but significant amounts of these alkaloids is still insufficient.

Tissue-Specific Natural Synthesis of Galanthaminein Zephyranthes Species and Its Accumulation in Different In Vitro-Grown Organs Following Methyl Jasmonate Treatment.

Galanthamine is an immensely valuable alkaloid exhibiting anti-cancer and antiviral activity. The cultivation of plant tissues in in vitro conditions is a good source for the synthesis and enrichment of secondary metabolites of commercial interest. In this study, the Amaryllidaceae alkaloid galanthamine was quantified in three Zephyranthes species, such as Zephyranthes candida, Zephyranthes grandiflora, and Zephyranthes citrina, and the impact of the methyl jasmonate (MJ) signaling molecule on galanthamine accumulation was monitored in in vitro-derived plant tissues. This is the first ever study of the MJ-regulated accumulation of galanthamine in in vitro-grown Zephyranthes tissues. Shoot regeneration was obtained in all three Zephyranthes species on Murashige and Skoog (MS) medium containing 2.0 mgL-1 benzylaminopurine (BAP) + 0.5 mgL-1 naphthalene acetic acid (NAA). The regenerated shoots were rooted on a medium containing 2.0 mgL-1 indole butyric acid (IBA). A GC-MS study of Zephyranthes extracts revealed the presence of 34 phyto-compounds of varied levels with therapeutic activities against diseases. The galanthamine content was quantified in plant parts of the three Zephyranthes species using high-performance thin layer chromatography (HPTLC); the maximum was found in Z. candida bulb (2.41 µg g-1 dry wt.), followed by Z. grandiflora (2.13 µg g-1 dry wt.), and then Z. citrina (2.02 µg g-1 dry wt.). The galanthamine content showed bulb > leaf > root source order. The in vitro-generated plantlets were treated with different MJ concentrations, and the galanthamine yield was measured in bulb, leaf, and root tissues. The highest galanthamine content was recorded in bulbs of Z. candida (3.97 µg g-1 dry wt.) treated with 150 µM MJ, showing an increase of 64.73% compared to the control. This accumulation may be attributed to MJ-induced stress, highlighting the potential commercial synthesis of galanthamine in vitro.

Conservation Potential Trough In Vitro Regeneration of Two Threatened Medicinal Plants Ungernia sewertzowii and U. victoris.

Ungernia sewertzowii (US) and U. victoris (UV) are medicinal plants and sources of biologically active compounds for pharmaceutical needs. The leaves of US contain 0.29-0.81% sum of alkaloids with a predominance of lycorine, which is 0.04-0.46% in leaves and 0.15-0.38% in bulbs. Lycorine is used to treat acute and chronic bronchitis. The leaves of UV contain 0.27-0.71% sum of alkaloids with a predominance of galanthamine-0.13-1.15%. Galanthamine is used to treat mild-to-moderate dementia (Alzheimer's disease). The natural populations of US and UV are in danger as sources of income for local people. To resolve this problem, two protocols for microclonal propagation were developed to replace natural raw materials with in vitro regenerated plants. Callusogenesis of US and UV was induced on Murashige and Skoog (MS) nutrient media with 2.4D (0.5 mg/L) in combination with BAP (0.5 mg/L), Kin (0.5 mg/L), or Zea (0.5 mg/L). Direct (for US) and indirect (for US and UN) organogenesis were observed on MS with BAP (0.5 mg/L) or Kin (0.5 mg/L) in combination with IAA (0.5 mg/L) or NAA (0.5 mg/L). Direct organogenesis resulted in 3-5 bulbs of US on one explant; indirect organogenesis resulted in up to 100-150 bulbs of US and UV on one explant within 6 months, or five to six subcultures after transferring the callus to the nutrient medium. The tissue cultures of US and UV were characterized by very low data on antioxidant activity based on IC50 values for DPPH and ABTS radical scavenging activities, whereas in vitro regenerated plants (leaves and bulbs) had higher data. We concluded that in vitro regenerated plants are valuable sources of lycorine and galanthamine, which allow the protection of the natural populations of these two species from extinction.

Lecanicillium psalliotae (Hypocreales: Cordycipitaceae) Exerts Ovicidal and Larvicidal Effects against the Sheep Blood-Feeding Nematode Haemonchus contortus through Its Liquid Culture Filtrates.

Nematophagous fungi (NF) form part of the soil microbiota and are natural enemies of nematodes, helping to regulate nematode populations. A verticillate NF isolated from soil from Tepalcingo, Mexico, was morphologically and molecularly characterised. This fungus was cultured in two different liquid media-Czapek-Dox broth (CzDoxB) and sweet potato dextrose broth (SPDB)-for 21 days. The ovicidal (OA) and larvicidal (LA) activities of fungal liquid culture filtrates (LCFs) were assessed in 96-well microtitre plates at different concentrations against Haemonchus contortus after 48 h. The morphological and molecular identification revealed the presence of Lecanicillium psalliotae. Additionally, the groups of compounds associated with nematocidal activity were determined from a qualitative chemical profile (QCP) using different reagents. The highest OA of the LCFs was obtained at 25 mg/mL from SPDB and CzDoxB and amounted to 97.2 and 99.06%, respectively. Meanwhile, the highest LA recorded with these LCFs at 100 mg/mL was 54.27% and 96.8%, respectively. The QCP revealed the presence of alkaloids and tannins in both LCFs that have previously been associated with nematocidal activity. Lecanicillium psalliotae exerted an important effect on H. contortus and could be of significance in future studies focused on the control and prevention of haemonchosis in small ruminants.

Identification of the cytochrome P450s responsible for the biosynthesis of two types of aporphine alkaloids and their de novo biosynthesis in yeast.

Aporphine alkaloids have diverse pharmacological activities; however, our understanding of their biosynthesis is relatively limited. Previous studies have classified aporphine alkaloids into two categories based on the configuration and number of substituents of the D-ring and have proposed preliminary biosynthetic pathways for each category. In this study, we identified two specific cytochrome P450 enzymes (CYP80G6 and CYP80Q5) with distinct activities toward (S)-configured and (R)-configured substrates from the herbaceous perennial vine Stephania tetrandra, shedding light on the biosynthetic mechanisms and stereochemical features of these two aporphine alkaloid categories. Additionally, we characterized two CYP719C enzymes (CYP719C3 and CYP719C4) that catalyzed the formation of the methylenedioxy bridge, an essential pharmacophoric group, on the A- and D-rings, respectively, of aporphine alkaloids. Leveraging the functional characterization of these crucial cytochrome P450 enzymes, we reconstructed the biosynthetic pathways for the two types of aporphine alkaloids in budding yeast (Saccharomyces cerevisiae) for the de novo production of compounds such as (R)-glaziovine, (S)-glaziovine, and magnoflorine. This study provides key insight into the biosynthesis of aporphine alkaloids and lays a foundation for producing these valuable compounds through synthetic biology.

Microbial allies: exploring fungal endophytes for biosynthesis of terpenoid indole alkaloids.

Terpenoid indole alkaloids (TIAs) are natural compounds found in medicinal plants that exhibit various therapeutic activities, such as antimicrobial, anti-inflammatory, antioxidant, anti-diabetic, anti-helminthic, and anti-tumor properties. However, the production of these alkaloids in plants is limited, and there is a high demand for them due to the increasing incidence of cancer cases. To address this research gap, researchers have focused on optimizing culture media, eliciting metabolic pathways, overexpressing genes, and searching for potential sources of TIAs in organisms other than plants. The insufficient number of essential genes and enzymes in the biosynthesis pathway is the reason behind the limited production of TIAs. As the field of natural product discovery from biological species continues to grow, endophytes are being investigated more and more as potential sources of bioactive metabolites with a variety of chemical structures. Endophytes are microorganisms (fungi, bacteria, archaea, and actinomycetes), that exert a significant influence on the metabolic pathways of both the host plants and the endophytic cells. Bio-prospection of fungal endophytes has shown the discovery of novel, high-value bioactive compounds of commercial significance. The discovery of therapeutically significant secondary metabolites has been made easier by endophytic entities' abundant but understudied diversity. It has been observed that fungal endophytes have better intermediate processing ability due to cellular compartmentation. This paper focuses on fungal endophytes and their metabolic ability to produce complex TIAs, recent advancements in this area, and addressing the limitations and future perspectives related to TIA production.

Molecular Targets of Plant-based Alkaloids and Polyphenolics in Liver and Breast Cancer- An Insight into Anticancer Drug Development.

Liver and Breast cancer are ranked as the most prevailing cancers that cause high cancer-related mortality. As cancer is a life-threatening disease that affects the human population globally, there is a need to develop novel therapies. Among the available treatment options include radiotherapy, chemotherapy, surgery, and immunotherapy. The most superlative modern method is the use of plant-derived anticancer drugs that target the cancerous cells and inhibit their proliferation. Plant-derived compounds are generally considered safer than synthetic drugs/traditional therapies and could serve as potential novel targets to treat liver and breast cancer to revolutionize cancer treatment. Alkaloids and Polyphenols have been shown to act as anticancer agents through molecular approaches. They disrupt various cellular mechanisms, inhibit the production of cyclins and CDKs to arrest the cell cycle, and activate the DNA repairing mechanism by upregulating p53, p21, and p38 expression. In severe cases, when no repair is possible, they induce apoptosis in liver and breast cancer cells by activating caspase-3, 8, and 9 and increasing the Bax/Bcl-2 ratio. They also deactivate several signaling pathways, such as PI3K/AKT/mTOR, STAT3, NF-kB, Shh, MAPK/ERK, and Wnt/ß-catenin pathways, to control cancer cell progression and metastasis. The highlights of this review are the regulation of specific protein expressions that are crucial in cancer, such as in HER2 over-expressing breast cancer cells; alkaloids and polyphenols have been reported to reduce HER2 as well as MMP expression. This study reviewed more than 40 of the plant-based alkaloids and polyphenols with specific molecular targets against liver and breast cancer. Among them, Oxymatrine, Hirsutine, Piperine, Solamargine, and Brucine are currently under clinical trials by qualifying as potent anticancer agents due to lesser side effects. As a lot of research is there on anticancer compounds, there is a desideratum to compile data to move towards clinical trials phase 4 and control the prevalence of liver and breast cancer.

Stereodivergent Total Synthesis of Tacaman Alkaloids.

This paper describes a concise, asymmetric and stereodivergent total synthesis of tacaman alkaloids. A key step in this synthesis is the biocatalytic Baeyer-Villiger oxidation of cyclohexanone, which was developed to produce seven-membered lactones and establish the required stereochemistry at the C14 position (92% yield, 99% ee, 500 mg scale). Cis- and trans-tetracyclic indoloquinolizidine scaffolds were rapidly synthesized through an acid-triggered, tunable acyl-Pictet-Spengler type cyclization cascade, serving as the pivotal reaction for building the alkaloid skeleton. Computational results revealed that hydrogen bonding was crucial in stabilizing intermediates and inducing different addition reactions during the acyl-Pictet-Spengler cyclization cascade. By strategically using these two reactions and the late-stage diversification of the functionalized indoloquinolizidine core, the asymmetric total syntheses of eight tacaman alkaloids were achieved. This study may potentially advance research related to the medicinal chemistry of tacaman alkaloids.

Heteryunine A, an amidated tryptophan-catechin-spiroketal hybrid with antifibrotic activity from Heterosmilax yunnanensis.

An unprecedented spiro-C-glycoside adduct, heteryunine A (1), along with two uncommon alkaloids featuring a 2,3-diketopiperazine skeleton, heterpyrazines A (2) and B (3), were discovered in the roots of Heterosmilax yunnanensis. The detailed spectroscopic analysis helped to clarify the planar structures of these compounds. Compound 1, containing 7 chiral centers, features a catechin fused with a spiroketal and connects with a tryptophan derivative by a CC bond. Its complex absolute configuration was elucidated by rotating frame overhauser enhancement spectroscopy (ROESY), specific rotation, and the 13C nuclear magnetic resonance (NMR) and electronic circular dichroism (ECD) calculation. The possible biosynthetic routes for 1 were deduced. Compounds 1 and 2 showed significant antifibrotic effects and further research revealed that they inhibited the activation, migration and proliferation of hepatic stellate cells (HSCs) through suppressing the activity of Ras homolog family member A (RhoA).

Spirobipyridine Ligand Enabled Iridium-Catalyzed Site-Selective C-H Activation via Non-Covalent Interactions.

The selective borylation of specific C-H bonds in organic synthesis remains a formidable challenge. In this study, we present a novel spirobipyridine ligand that features a binaphthyl backbone. This ligand facilitates the iridium-catalyzed selective C-H borylation of benzene derivatives. The ligand is designed with "side-arm-wall" substituents that allow vicinal di- or multi-substituted benzene derivatives to approach metal center and effectively block other reactive sites by non-covalent interactions with substrates. The effectiveness of this strategy is demonstrated by the successful selective distal C-H activation of various alkaloids and its broad compatibility with functional groups.

Comparative transcriptome profiling reveals distinct regulatory responses of secondary defensive metabolism in Datura species (Solanaceae) under plant development and herbivory-mediated stress.

Differential expression of genes is key to mediating developmental and stress-related plant responses. Here, we addressed the regulation of plant metabolic responses to biotic stress and the developmental variation of defense-related genes in four species of the genus Datura with variable patterns of metabolite accumulation and development. We combine transcriptome profiling with phylogenomic techniques to analyze gene expression and coexpression in plants subjected to damage by a specialist folivore insect. We found (1) common overall gene expression in species of similar chemical profiles, (2) species-specific responses of proteins involved in specialized metabolism, characterized by constant levels of gene expression coupled with transcriptional rearrangement, and (3) induction of transcriptional rearrangement of major terpene and tropane alkaloid genes upon herbivory. Our results indicate differential modulation of terpene and tropane metabolism linked to jasmonate signaling and specific transcription factors to regulate developmental variation and stress programs, and suggest plastic adaptive responses to cope with herbivory. The transcriptional profiles of specialized metabolism shown here reveal complex genetic control of plant metabolism and contribute to understanding the molecular basis of adaptations and the physiological variation of significant ecological traits.

New insights into the chemistry and anticancer activity of Ophiocordyceps xuefengensis.

Ophiocordyceps xuefengensis (O. xuefengensis), the sister taxon of Ophiocordyceps sinensis (O. sinensis), is consumed as a "tonic food" due to its health benefits. However, little is known regarding the chemistry and bioactivity of O. xuefengensis. In this study, we characterized 80 indole-based alkaloids in the ethyl acetate fraction of O. xuefengensis by high performance liquid chromatography-quadrupole time of flight mass spectrometry (HPLC-Q-TOF-MS/MS), of which 54 indole-based alkaloids were identified as possibly new compounds. Furthermore, 29 of these compounds were established as potential anti-cancer compounds by ligand fishing combined with HPLC-Q-TOF-MS/MS. Moreover, molecular docking identified the NH- and OH- groups of these compounds as the key active groups. The present study has expanded the knowledge on the characteristic indole-based alkaloids and anti-cancer activity of O. xuefengensis.

In-vitro hepatotoxic activity of mitragynine and paynantheine isolated from the leaves of Mitragyna speciosa Korth. (Kratom).

Mitragynine, a primary alkaloid found in kratom leaves has been reported to have a broad range of pharmacological and toxicological properties while its congener, paynatheine has comparatively less information available on these aspects. Mitragynine and its congener, paynantheine, were isolated from the ethanol kratom leaves extract using gravity column chromatography techniques. Our study evaluated the cytotoxicity potential of mitragynine and paynantheine on normal human liver cell line, HL-7702, and human hepatoma cell line, HepG2. Mitragynine exhibited a moderate inhibitory effect on the HepG2 cell line with IC50 value of 42.11 ± 1.31 µM in comparison with vinblastine (IC50: 15.45 ± 0.72 µM) while it showed non-cytotoxic properties towards the HL-7702 cell line with concentrations ranging below 200 µM. In contrast, paynantheine exhibited weak cytotoxic properties towards HepG2 and HL-7702 cell lines. Further comprehensive evaluations of both compounds are needed to establish more details on the cytotoxicity potential of kratom alkaloids.

Mechanisms of mitotic inhibition in human aorta endothelial cells: Molecular and morphological in vitro spectroscopic studies.

Mitotic inhibitors are drugs commonly used in chemotherapy, but their nonspecific and indiscriminate distribution throughout the body after intravenous administration can lead to serious side effects, particularly on the cardiovascular system. In this context, our investigation into the mechanism of the cytotoxic effects on endothelial cells of mitotic inhibitors widely used in cancer treatment, such as paclitaxel (also known as Taxol) and Vinca alkaloids, holds significant practical implications. Understanding these mechanisms can lead to more targeted and less harmful cancer treatments. Human aorta endothelial cells (HAECs) were incubated with selected mitotic inhibitors in a wide range of concentrations close to those in human plasma during anticancer therapy. The analysis of single cells imaged by Raman spectroscopy allowed for visualization of the nuclear, cytoplasmic, and perinuclear areas to assess biochemical changes induced by the drug's action. The results showed significant changes in the morphology and molecular composition of the nucleus. Moreover, an effect of a given drug on the cytoplasm was observed, which can be related to its mechanism of action (MoA). Raman data supported by fluorescence microscopy measurements identified unique changes in DNA form and proteins and revealed drug-induced inflammation of endothelial cells. The primary goal of mitotic inhibitors is based on the impairment of tubulin formation and the inhibition of the mitosis process. While all three drugs affect microtubules and disrupt cell division, they do so through different MoA, i.e., Vinca alkaloids inhibit microtubule formation, whereas paclitaxel stabilizes microtubules. To sum up, the work shows how a specific drug can interact with endothelial cells.

Diterpenoid alkaloids from Delphinium sherriffii.

Three new diterpenoid alkaloids (1, 2, 3) and seventeen known (4-20) compounds were isolated from the whole plant of Delphinium sherriffii Munz (Ranunculaceae). Their structures were elucidated by various spectroscopic analyses, including IR, HR-ESI-MS, 1D and 2D NMR spectra. All compounds were evaluated for the inhibitory activity of Sf9 cells and compound 5 exhibited the strongest cytotoxicity (IC50 = 8.97 µM) against Sf9 cell line.

Two new pregnane alkaloids from Pachysandra terminalis Sieb. et Zucc. and their cytotoxic activities.

Pactermines E and F (1 and 2), two new pregnane alkaloids were isolated from the whole plant of Pachysandra terminalis Sieb. et Zucc. Their structures were determined by physicochemical properties and spectroscopic methods including 1D, 2D NMR, IR, HR-ESI-MS data. Cytotoxic activities against three human cancer A549, HCT116 and SW620 cell lines of the isolated compounds were evaluated by CCK8 method. However, all compounds showed no significant activity against the three cancer cells (IC50>100 µM) except for compound 1, which showed inhibitory effects against HCT116 cells with IC50 values of 84.6 µM.