Β-caryophyllene Oxide Research Articles

Chemical Composition and Biological Activities of St John’s Wort (Hypericum perforatum L.) Essential Oil from Bulgaria

Since ancient times, essential oils obtained from various aromatic plants have been utilized as bioactive ingredients in medicines, foods and cosmetics. The present study aimed to investigate the chemical composition and biological activities of St John’s Wort (Hypericum perforatum L.) essential oil (SJW EO) from Bulgaria, which is known to possess various biological properties. Gas chromatography and mass spectrometry (GC–MS) analysis, determination of antioxidant activity (by the ABTS method), an antimicrobial activity test and an in vitro anti-inflammatory activity test were performed. The main classes of compounds identified by GC–MS analysis were monoterpenes (43.55%), followed by sesquiterpenes (36.81%) and alkanes (16.92%). The predominant chemical components of SJW EO were α-pinene (27.52%), followed by β-pinene (10.08%), β-caryophyllene (6.77%), germacrene D (6.37%) and caryophyllene oxide (4.48%). The highest antibacterial activity was observed against the Gram-negative bacteria Klebsiella pneumoniae ATCC 13883 (inhibition zone of 12.0 mm) and Pseudomonas aeruginosa ATCC 9027 (inhibition zone of 11.0 mm). SJW EO exhibited significant in vitro anti-inflammatory activity, as the results demonstrated that its anti-inflammatory effect was stronger than those of the conventional anti-inflammatory drugs Prednisolon Cortico and acetylsalicylic acid (Aspirin), which were used as controls (all in concentration of 1 mg/mL). The obtained results demonstrated that Bulgarian SJW EO can be used as an active ingredient in the composition of new products for the pharmaceutical and cosmetic industries.

Selenium Improves the Nutritional and Antioxidant Properties of Oregano (Origanum vulgare L.) Grown in Hydroponics

Oregano (Origanum vulgare L.) is one of the most commercially popular aromatic spices which has long been used in folk medicine as a medicinal plant due to the presence of a wide group of bioactive secondary metabolites. The experimental data available to date indicate that plants of individual species within the Lamiaceae family implement different strategies for the absorption and distribution of selenium (Se) and differ in their metabolic response to Se treatment. In this regard, the present study investigated the effect of Se application (in the form of sodium selenate) at various concentrations (2.0, 5.0, 10.0, 20.0, and 40.0 μM) on the growth and accumulation of Se in oregano plant shoots and roots, as well as on nutritional components and secondary metabolites in shoots. The addition of Se to the nutrient solution at concentrations of 2–20 μM did not adversely affect the growth and accumulation of biomass in the oregano plants, which were characterized by a significant ability to transfer Se from roots to shoots (the translocation factor was >2). The Se treatment enhanced the nutritional proprieties of the oregano and, particularly, it stimulated the accumulation of carbohydrates and proteins (by 30 and 17%) and minerals (calcium and manganese). The total contents of phenolic compounds, flavonoids, hydroxycinnamic acids, luteolin-7-glucoside and its derivatives, catechin, 3,4-dihydroxybenzoic acid, rosmarinic acid and oleanolic and ursolic acids, as well as the percentage of essential oil, showed a dose-dependent increase in the oregano under the Se treatment. Changes in the relative content of the four main components of oregano essential oil (sabinene, germacrene D, β-caryophyllene, and (Z)-β-ocimene) under the Se treatment were not significant. The relative proportions of β-caryophyllene oxide and terpinen-4-ol increased with Se concentration augmentation in the nutrient solution. The obtained results indicate the prospect of using Se at 5–20 μM concentrations in nutrient solution in hydroponically grown oregano to produce Se-biofortified plants with higher levels of compounds beneficial to health and antioxidant activity without yield reduction.

Antimicrobial Profiling of Piper betle L. and Piper nigrum L. Against Methicillin-Resistant Staphylococcus aureus (MRSA): Integrative Analysis of Bioactive Compounds Based on FT-IR, GC-MS, and Molecular Docking Studies

This study explored the antimicrobial potential of Piper betle L. (PBL) and Piper nigrum L. (PNL) extracts against MRSA. Plant parts including stem, leaf, and fruit were extracted using aquadest, methanol, and hexane, resulting in 18 distinct extracts. FT-IR combined with cluster analysis (CA) categorized the extracts, and anti-MRSA activity was assessed through the paper disk diffusion method. The most potent extracts were further analyzed using GC-MS to identify bioactive compounds. Additionally, molecular docking studies were conducted for MRSA protein targets (4DKI, 6H5O, and 4CJN). The hexane extract of PNL and the aqueous extract of PBL fruit showed the strongest inhibitory effects. GC-MS identified piperine (14.22%) and diisooctyl phthalate (14.67%) as major compounds, with piperolein B, piperanine, β-caryophyllene oxide, and α-caryophylladienol as minor compounds in the hexane extract of PNL, while hydroxychavicol (81.89%) and chavibetol (12.01%) were predominant in the aquadest extract of PBL. Molecular docking revealed that piperolein B and piperine had strong binding affinities to MRSA proteins 4DKI, 6H5O, and 4CJN, comparable to ciprofloxacin. In conclusion, this study confirms the potential of PBL and PNL as sources of novel anti-MRSA agents, supporting further research to develop new therapies.

β-Caryophyllene oxide inhibits lysine acetylation of histones in Fusarium proliferatum to block ribosomal biosynthesis and function

The natural bicyclic sesquiterpene, β-Caryophyllene oxide (BCPO), has demonstrated inhibitory activity against Fusarium species. While previous studies have documented its antifungal properties through various biochemical mechanisms, the role of BCPO in modulating epigenetic modifications of DNA via histone deacetylases (HDACs) has received comparatively less attention. The study aims to elucidate how BCPO inhibits Fusarium proliferatum by affecting histone acetylation. Our results indicate that BCPO enhances FPRO_01165 (FpSIR2) enzyme activity to 6.01 ng/min/mg, representing a 55.30 % increase. Molecular docking analysis and molecular dynamics simulation confirmed the interaction between BCPO and FpSIR2. Furthermore, high concentrations (HC) of BCPO significantly inhibited the growth of F. proliferatum, resulting in marked reductions in H3K9ac and H3K27ac modification levels. We conducted chromatin immunoprecipitation sequencing (ChIP-seq) to identify enrichments of H3K9ac and H3K27ac, while also obtaining transcriptomic data from the HC treatment group. Combined analyses revealed that decreased levels of H3K9ac and H3K27ac primarily affected ribosomal pathways in F. proliferatum, leading to downregulation of several ribosomal genes and their corresponding proteins, such as RPL4, RPS19, and RPS16. Our findings suggest that BCPO stimulates both the production and activity of FpSIR2, which subsequently inhibits histone lysine acetylation in F. proliferatum. This inhibition suppresses ribosome biosynthesis and function as well as overall growth in this pathogen. The property of BCPO to reduce acetylation provides new insights for developing highly efficient yet low-toxicity antifungal agents.

In vivo and in silico anti-inflammatory activity of Artemisia vulgaris and β-caryophyllene oxide in carrageenan-induced paw edema in Wistar rats

This study is aimed to evaluate the impact of methanolic extract of Artemisia vulgaris and isolated plant compound, β-Caryophyllene oxide against carrageenan-induced paw edema in rat model and its therapeutic potential compared with reference drug, Indometacin. Methanolic extract of A. vulgaris was characterized using FTIR, LC-MS, NMR spectral studies. Paw edema was induced by sub-plantar injection of 100 µl of 1% carrageenan. Oxidative enzymes, such as super oxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR), lipid peroxidation and C-reactive protein levels were measured in paw tissue. In silico evaluation of anti-inflammatory activity of plant compounds was evaluated against the molecular targets of inflammation. C-reactive protein and lipid-peroxidation levels were significantly increased whereas the activity levels of oxidative enzymes were significantly decreased in inflammation-induced rats. The recovery of oxidative enzyme levels was seen in treated groups in a dose dependent manner. C-reactive protein and lipid-peroxidation levels were significantly decreased in treated groups, indicating the anti-inflammatory activity of the plant extract and the plant compound. Computational analysis rationalizes the inhibitory ability of plant derived compound possibly by altering the inflammatory signaling pathway.

Exploring the Mechanism of Cytotoxic Activity of β-Caryophyllene Oxide and its Potential to Enhance the Activity of Doxorubicin

Plant-derived compounds, including flavonoids, sesquiterpenes, and others, have been widely investigated for their role in cancer treatment. Here, we highlight the significance of some natural compounds (β-caryophyllene oxide) in enhancing doxorubicin's chemotherapeutic cytotoxicity. We also determined a novel mechanism of cytotoxicity for β-caryophyllene oxide by revealing its ability to bind with the DNA. This potentially causes its cytotoxicity when added alone and its ability to enhance doxorubicin's cytotoxicity. We also show that some natural compounds (epicatechin) may provide protection to cancer cells against doxorubicin's toxicity. This is most likely caused by their antioxidant behavior which potentially suppressed the doxorubicin-induced reactive oxygen species (ROS) resulting in a decrease in its cytotoxicity. Moreover, similar suppression in the cytotoxicity of β-caryophyllene oxide was noticed when incubated with the other flavonoids.

Bioinspired Semisynthesis and Structure Revisions of Chlorinated Norsesquiterpenoids Rumphellatins A-C.

The first synthesis of chlorine-containing hemiketals, rumphellatins A-C (1-3), previously inaccessible by means of total synthesis, was achieved starting from commercially available (-)-β-caryophyllene oxide (7). Structures of rumphellatins A (1) and C (3) were revised, while structures of rumphellatin B (2) and intermediate rumphellolide C (19) were confirmed. The study expands availability of exotic norsesquiterpenoids for profiling their biological activity as well as facilitates the elucidation of biosynthetic pathways of their formation.

Antileishmanial and Antifungal Activities of Volatile Oils from Cinnamomum Cassia Bark and Schinus Molle Leaves.

This study reports on the chemical composition and antileishmanial and anticandidal activities of volatile oils (VOs) of Schinus molle dried leaves (SM), Cinnamomum cassia branch bark (CC) and their blends. Major constituents of SM were spathulenol (26.93 %), β-caryophyllene (19.90 %), and caryophyllene oxide (12.69 %), whereas (E)-cinnamaldehyde (60.11 %), cinnamyl acetate (20.90 %) and cis-2-methoxycinnamic acid (10.37 %) were predominant in CC. SM (IC50=21.45 μg/mL) and CC (IC50=23.27 μg/mL) displayed good activity against L. amazonensis promastigotes, besides having good or moderate activity against nine Candida strains, with Minimum Inhibitory Concentration (MIC) values ranging from 31.25 to 250 μg/mL. While the three SM and CC blends were not more active than the VOs tested individually, they exhibited remarkably high antileishmanial activity, with IC50 values ranging between 3.12 and 7.04 μg/mL, which is very similar to the IC50 of amphotericin B (positive control).

Chemical compounds, anti-tumor and anti-neuropathic pain effect of hemp essential oil in vivo

Hemp (Cannabis sativa L.), an annual dioecious plant, has shown extensive application in the fields of fibers, food, oil, medicine, etc. Currently, most attention has been paid to the therapeutic properties of phytocannabinoids. However, the pharmaceutical research on essential oil from hemp is still lacking. In this study, hemp essential oil (HEO) was extracted from hemp flowers and leaves, and the components were analyzed by GC–MS. Quatitative analysis of three main compounds β-caryophyllene, β-caryophyllene oxide, α -humulene were determined by GC-FID. The anti-tumor and anti-neuropathic pain effects of HEO were evaluated. In the paclitaxel induced neuropathic mice model, HEO reduced the serum level of inflammatory cytokines TNF-α to achieve the analgesic effect, which was tested by evaluating mechanical and thermal hyperalgesia. Further investigation with cannabinoid receptor 2 (CB2 R) antagonist AM630 revealed the mechanism of reversing mechanical hyperalgesia may be related to CB2 R. In Lewis lung cancer grafted mice model, the tumor growth was significantly inhibited, the levels of tumor inflammatory cytokines TNF-α and IL-6 were downregulated, immune organ index was modified and immune-related CD4+, CD8+ T lymphocytes level, CD4+/CD8+ ratio were increased when administered with HEO. These results reveal that HEO plays a role not only in tumor chemotherapy induced peripheral neuropathy treatment, but also in anti-tumor treatment which offers key information for new strategies in cancer treatment and provides reference for the medicinal development of hemp.

Bioactives of the essential oil from the leaves of Eugenia pyriformis Cambess (Myrtaceae) on the effects of tobacco.

Lung cancer is the most commonly diagnosed and the main cause of cancer death, usually related to cigarette smoking. Furthermore, the microbiota of people exposed to cigarette smoke can be modified, making it difficult to eliminate opportunistic microorganisms. The leaves of Eugenia pyriformis are a by-product of fruit production and, to date, there have been no studies addressing the antiproliferative, anti-inflammatory, and antimicrobial activities. Investigate the antimicrobial, Nitric Oxide (NO)-production inhibition, and antiproliferative activities of the essential oil from E. pyriformis leaves and its possible effect on the treatment and prevention of damage caused by tobacco. The essential oil (EO) was obtained by hydrodistillation (3h). Its chemical composition was investigated by GC-MS. It was proposed to investigate antiproliferative activity against human tumor cell lines, namely, breast adenocarcinoma (MCF-7), lung (NCI-H460), cervical (HeLa), and hepatocellular (HepG2) carcinomas. A non-tumor primary culture from pig liver (PLP2) was also tested. The EO capacity to inhibit nitric oxide (NO) production was evaluated by a lipopolysaccharide stimulated murine macrophage cell line. Antibacterial and antifungal activities against opportunistic pathogens were investigated against seven strains of bacteria and eight fungi. The results indicated the presence of 23 compounds in the essential oil, the majority were spathulenol (45.63%) and β-caryophyllene oxide (12.72%). Leaf EO provided 50% inhibition of nitric oxide production at a concentration of 92.04µgmL-1. The EO also demonstrated antiproliferative activity against all human tumor cell lines studied, with GI50 values comprised between 270.86 and 337.25µgmL-1. The essential oil showed antimicrobial potential against the bacteria Listeria monocytogenes (Murray et al.) Pirie (NCTC 7973) and Salmonella Typhimurium ATCC 13311 (MIC 1870µgmL-1) and fungi Aspergillus versicolor ATCC 11730, Aspergillus ochraceus ATCC 12066, Penicillium ochrochloron ATCC 90288, Penicillium verrucosum var. cyclopium (Westling) Samson, Stolk & Hadlok (food isolate) (MIC 1870µgmL-1) and Trichoderma viride Pers. IAM 5061 (1,400µg mL-1). The demonstrated anti-inflammatory, antiproliferative, and antimicrobial activities in the leaves of E. pyriformis can add value to the production chain of this plant, being a possible option for preventing and combating cancer, including lung cancer.

Synergistic Antinociceptive Effect of β-Caryophyllene Oxide in Combination with Paracetamol, and the Corresponding Gastroprotective Activity.

Pain is the most frequent symptom of disease. In treating pain, a lower incidence of adverse effects is found for paracetamol versus other non-steroidal anti-inflammatory drugs. Nevertheless, paracetamol can trigger side effects when taken regularly. Combined therapy is a common way of lowering the dose of a drug and thus of reducing adverse reactions. Since β-caryophyllene oxide (a natural bicyclic sesquiterpene) is known to produce an analgesic effect, this study aimed to determine the anti-nociceptive and gastroprotective activity of administering the combination of paracetamol plus β-caryophyllene oxide to CD1 mice. Anti-nociception was evaluated with the formalin model and gastroprotection with the model of ethanol-induced gastric lesions. According to the isobolographic analysis, the anti-nociceptive interaction of paracetamol and β-caryophyllene oxide was synergistic. Various pain-related pathways were explored for their possible participation in the mechanism of action of the anti-nociceptive effect of β-caryophyllene oxide, finding that NO, opioid receptors, serotonin receptors, and K+ATP channels are not involved. The combined treatment showed gastroprotective activity against ethanol-induced gastric damage. Hence, the synergistic anti-nociceptive effect of combining paracetamol with β-caryophyllene oxide could be advantageous for the management of inflammatory pain, and the gastroprotective activity should help to protect against the adverse effects of chronic use.

Evaluation of cannabimimetic effects of selected minor cannabinoids and Terpenoids in mice

BackgroundThe cannabis plant contains several cannabinoids, and many terpenoids that give cannabis its distinctive flavoring and aroma. Δ9-Tetrahydrocannabinol (Δ9-THC) is the plant's primary psychoactive constituent. Given the abuse liability of Δ9-THC, assessment of the psychoactive effects of minor cannabinoids and other plant constituents is important, especially for compounds that may be used medicinally. This study sought to evaluate select minor cannabinoids and terpenes for Δ9-THC-like psychoactivity in mouse Δ9-THC drug discrimination and determine their binding affinities at CB1 and CB2 receptors. MethodsΔ9-THC, cannabidiol (CBD), cannabinol (CBN), cannabichromene (CBC), cannabichromenevarin (CBCV), Δ8-tetrahydrocannabinol (Δ8-THC), (6aR,9R)-Δ10-tetrahydrocannabinol [(6aR,9R)-Δ10-THC], Δ9-tetrahydrocannabinol varin (THCV), β-caryophyllene (BC), and β-caryophyllene oxide (BCO) were examined. ResultsAll minor cannabinoids showed measurable cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptor binding, with CBC, CBCV, and CBD, showing the weakest CB1 receptor binding affinity. BC and BCO exhibited negligible affinity for both CB1 and CB2 receptors. In drug discrimination, only Δ8-THC fully substituted for Δ9-THC, while CBN and (6aR,9R)-Δ10-THC partially substituted for Δ9-THC. THCV and BCO did not alter the discriminative stimulus effects of Δ9-THC. ConclusionIn summary, only some of myriad cannabinoids and other chemicals found in the cannabis plant bind potently to the identified cannabinoid receptors. Further, only four of the compounds tested herein [Δ9-THC, Δ8-THC, (6aR,9R)-Δ10-THC, and CBN] produced Δ9-THC-like discriminative stimulus effects, suggesting they may possess cannabimimetic subjective effects. Given that the medicinal properties of phytocannabinoids and terpenoids are being investigated scientifically, delineation of their potential adverse effects, including their ability to produce Δ9-THC-like intoxication, is crucial.

Sesquiterpenoids from the stem bark of Aglaia pachyphylla Miq (Meliaceae) and cytotoxic activity against MCF-7 Cancer Cell Line

Sesquiterpenoids are terpenoid-derived compounds formed from three isoprene units with diverse pharmacological activities. Sesquiterpenoids can be obtained from higher plants, such as the genus Aglaia from the Meliaceae family. This study aims to isolate and characterize the structure of sesquiterpenoidsfrom the n-hexane extract of Aglaia pachyphylla Miq stem bark and to determine their cytotoxic activity against MCF-7 breast cancer cells. The n-hexane extract was separated and purified by various chromatography techniques such as vacuum liquid chromatography, normal-phase chromatography, and reversed-phase chromatography to obtain three sesquiterpenoids. The chemical structures of sesquiterpenoids were identified by various spectroscopic analyses such as IR, MS, 1D-NMR, and 2D-NMR and compared with previously reported spectrum data. Three sesquiterpenoids were identified as β-caryophyllene oxide (1), 1β-Hydroxy-4(15),5-eudesmadiene (2), and spathulenol (3). The three compounds were tested against MCF-7 breast cancer cells using the PrestoBlue method. Compound 2 showed the highest cytotoxic activity with an IC50 value of 262,25 µM.

Sensitization of cholangiocarcinoma cells to chemotherapy through BCRP inhibition with β-caryophyllene oxide

Cholangiocarcinomas (CCAs) are cancers originated in the biliary tree, which are characterized by their high mortality and marked chemoresistance, partly due to the activity of ATP-binding cassette (ABC) export pumps, whose inhibition has been proposed as a strategy for enhancing the response to chemotherapy. We have previously shown that β-caryophyllene oxide (CRYO) acts as a chemosensitizer in hepatocellular carcinoma by inhibiting ABCB1, MRP1, and MRP2. Here, we have evaluated the usefulness of CRYO in inhibiting BCRP and improving the response of CCA to antitumor drugs. The TCGA-CHOL cohort (n = 36) was used for in silico analysis. BCRP expression (mRNA and protein) was assayed in samples from intrahepatic (iCCA) and extrahepatic (eCCA) tumors (n = 50) and CCA-derived cells (EGI-1 and TFK-1). In these cells, BCRP-dependent mitoxantrone transport was determined by flow cytometry. At non-toxic concentrations, CRYO inhibited BCRP function, which enhanced the cytostatic effect of drugs used in the treatment of CCA. The BCRP ability to confer resistance to a panel of antitumor drugs was determined in Chinese hamster ovary (CHO) cells with stable BCRP expression. At non-toxic concentrations, CRYO markedly reduced BCRP-induced resistance to known substrate drugs (mitoxantrone and SN-38) and cisplatin, gemcitabine, sorafenib, and 5-FU but not oxaliplatin. Neither CRYO nor cisplatin alone significantly affected the growth of BCRP-expressing tumors subcutaneously implanted in immunodeficient mice. In contrast, intratumor drug content was enhanced when administered together, and tumor growth was inhibited. In sum, the combined treatment of drugs exported by BCRP with CRYO can improve the response to chemotherapy in CCA patients.

Sesquiterpene-evoked phytochemical toxicity in PC12 neuronal cells reveals a variable degree of oxidative stress and alpha-tocopherol and glutathione-dependent protection

Phytochemicals are often promoted generally as antioxidants and demonstrate variable levels of reactive oxygen species (ROS) sequestration in vitro, which attributes to their neuroprotective bioactivity. Sesquiterpenes from cannabis and essential oils may demonstrate bifunctional properties towards cellular oxidative stress, possessing pro-oxidant activities by generating ROS or scavenging ROS directly. Sesquiterpenes can also oxidize forming sesquiterpene oxides, however the relative contribution they make to the bioactivity or cytotoxicity of complex botanical extracts more generally is unclear, while selected cannabis-prevalent terpenes such as β-caryophyllene may also activate cannabinoid receptors as part of their biological activity. In the present study, we investigated selected sesquiterpenes β-caryophyllene and humulene and their oxidized forms (β-caryophyllene oxide and zerumbone, respectively) against established antioxidants (ascorbic acid, α-tocopherol, and glutathione) and in the presence of cannabinoid receptor 1 and cannabinoid receptor 2 antagonists, to gain a better understanding of the molecular and cellular mechanisms of neuroprotection versus neurotoxicity in semi-differentiated rat neuronal phaeochromocytoma (PC12) cells. Our results demonstrate that the sesquiterpenes β-caryophyllene, humulene and zerumbone possess concentration-dependent neurotoxic effects in PC12 cells. Both β-caryophyllene- and humulene-evoked toxicity was unaffected by CB1 or CB2 receptor antagonism, demonstrating this occurred independently of cannabinoid receptors. Both glutathione and α-tocopherol were variably able to alleviate the concentration-dependent loss of PC12 cell viability from exposure to β-caryophyllene, humulene and zerumbone. During 4-hour exposure to sesquiterpenes only modest increases in ROS levels were noted in PC12 cells, with glutathione co-incubation significantly inhibiting intracellular ROS production. However, significant increases in ROS levels in PC12 cells were demonstrated during 24-hour incubation with either antioxidants or sesquiterpenes individually, and with additive toxicity exhibited in combination. Overall, the results highlight a concentration-dependent profile of sesquiterpene neurotoxicity independent of cannabinoid receptors and dissociated from the formation of reactive oxygen species as a marker or correlate to the loss of cell viability.

Stimulation of Hemolysis and Eryptosis by β-Caryophyllene Oxide.

Eryptosis stimulated by anticancer drugs can lead to anemia in patients. β-caryophyllene oxide (CPO) is an anticancer sesquiterpene present in various plants; however, its effect on the structure and function of human red blood cells (RBCs) remains unexplored. The aim of this study was to investigate the hemolytic and eryptotic activities and underlying molecular mechanisms of CPO in human RBCs. Cells were treated with 10-100 μM of CPO for 24 h at 37 °C, and hemolysis, LDH, AST, and AChE activities were photometrically assayed. Flow cytometry was employed to determine changes in cell volume from FSC, phosphatidylserine (PS) externalization by annexin-V-FITC, intracellular calcium by Fluo4/AM, and oxidative stress by 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA). Cells were also cotreated with CPO and specific signaling inhibitors and antihemolytic agents. Furthermore, whole blood was exposed to CPO to assess its toxicity to other peripheral blood cells. CPO induced concentration-responsive hemolysis with LDH and AST leakage, in addition to PS exposure, cell shrinkage, Ca2+ accumulation, oxidative stress, and reduced AChE activity. The toxicity of CPO was ameliorated by D4476, staurosporin, and necrosulfonamide. ATP and PEG 8000 protected the cells from hemolysis, while urea and isotonic sucrose had opposite effects. CPO stimulates hemolysis and eryptosis through energy depletion, Ca2+ buildup, oxidative stress, and the signaling mediators casein kinase 1α, protein kinase C, and mixed lineage kinase domain-like pseudokinase. Development of CPO as an anticancer therapeutic must be approached with prudence to mitigate adverse effects on RBCs using eryptosis inhibitors, Ca2+ channel blockers, and antioxidants.

Prediction analysis of quality markers and resource evaluation of Artemisiae Argyi Folium based on chemical composition and network pharmacology

This study is based on ultra-high-performance liquid chromatography(UPLC), gas chromatography-mass spectrometry(GC-MS), and network pharmacology methods to analyze and predict potential quality markers(Q-markers) of Artemisiae Argyi Folium. First, UPLC and GC-MS techniques were used to analyze the content of 12 non-volatile components and 8 volatile components in the leaves of 33 Artemisia argyi germplasm resources as candidate Q-markers. Subsequently, network pharmacology was employed to construct a "component-target-pathway-efficacy" network to screen out core Q-markers, and the biological activity of the markers was validated using molecular docking. Finally, cluster analysis and principal component analysis were performed on the content of Q-markers in the 33 A. argyi germplasm resources. The results showed that 18 candidate components, 60 targets, and 185 relationships were identified, which were associated with 72 pathways related to the treatment of 11 diseases and exhibited 5 other effects. Based on the combination of freedom and component specificity, six components, including eupatilin, cineole, β-caryophyllene, dinatin, jaceosidin, and caryophyllene oxide were selected as potential Q-markers for Artemisiae Argyi Folium. According to the content of these six markers, cluster analysis divided the 33 A. argyi germplasm resources into three groups, and principal component analysis identified S14 as having the highest overall quality. This study provides a reference for exploring Q-markers of Artemisiae Argyi Folium, establishing a quality evaluation system, further studying its pharmacological mechanisms, and breeding new varieties.

Synergistic Repellent and Irritant Effects of a Mixture of β-Caryophyllene Oxide and Vetiver Oil against Mosquito Vectors.

Repellents play a major role in reducing the risk of mosquito-borne diseases by preventing mosquito bites. The present study evaluated the mosquito-repellent activity of β-caryophyllene oxide 1% (BCO), vetiver oil 2.5% (VO), and their binary mixtures (BCO + VO (1:1), BCO + VO (2:1), BCO + VO (1:2)) against four laboratory-colonized mosquito species, Aedes aegypti (L.), Aedes albopictus (Skuse), Anopheles minimus Theobald, and Culex quinquefasciatus Say, using an excito-repellency assay system. In general, the compound mixtures produced a much stronger response in the mosquitoes than single compounds, regardless of the test conditions or species. The greatest synergetic effect was achieved with the combination of BCO + VO (1:2) in both contact and noncontact trials with An. minimus (74.07-78.18%) and Cx. quinquefasciatus (55.36-83.64%). Knockdown responses to the binary mixture of BCO + VO were observed for Ae. albopictus, An. minimus, and Cx. quinquefasciatus, in the range of 18.18-33.33%. The synergistic repellent activity of BCO and VO used in this study may support increased opportunities to develop safer alternatives to synthetic repellents for personal protection against mosquitoes.

Chemical composition and anti-Xanthomonas citri activities of essential oils from Schinus molle L. fresh and dry leaves and of its major constituent spathulenol

Citrus canker, which is caused by Xanthomonas citri, is a severe disease that affects citrus plants worldwide. This paper aimed to compare, for the first time, the chemical composition and anti-Xanthomonas citri activities of essential oils from Schinus molle fresh and dry leaves (EO-FL and EO-DL, respectively). Anti-X. citri activity of spathulenol, the major constituent of oils, was also evaluated. Activities were screened by the broth microdilution method on 96‐well culture plates. Three major constituents were identified in EO-FL and EO-DL by GC-MS and GC-FID: spathulenol, β-caryophyllene and caryophyllene oxide. EO-DL (MIC = 31.25 µg/mL), EO-FL (MIC = 62.5 µg/mL) and spathulenol (MIC = 100 µg/mL) were active against X. citri strains (resistant, tolerant and sensitive to copper). Even though results showed that in vitro potential of EO-FL, EO-DL and spathulenol against X. citri, further in vivo studies are needed to prove their applicability to the biocontrol of citrus canker.

Sesquiterpenes from two Compositae plants as promising inhibitors to nuclear hormone receptor 3 of Tribolium castaneum

Essential oils (EOs) and their volatile secondary metabolites have been proved to be effective on storage pests control, while restricted on the application due to unclear mechanism. Molecular dynamics (MD) simulations and binding free energies analysis provided an effective approach to reveal mechanism on conformational calculation. In this work, the insecticidal and repellent capacities of Praxelis clematidea and Ageratum houstonianum oils and their main components identified by gas chromatography–mass spectrometry (GC–MS) were scientifically measured. Interestingly, P. clematidea oil exhibited strong fumigant toxicity against Tribolium castaneum (LC50 = 7.07 mg/L air). Moreover, two EOs exhibited over 80% repellent rate against T. castaneum at the highest concentration of 78.63 nL/cm2. Furthermore, hundreds of enzymes related to the regulation of biological processes of T. castaneum were screened to explore the underlying molecular mechanism and develop promising insecticides. Besides, top hits were subjected to MD simulations and binding free energies analysis to elucidate complex inter-molecular stability and affinity over simulated time. The results demonstrated that isolongifolene, δ-cadinene, β-caryophyllene and caryophyllene oxide were prioritized as they were establishing conserved and stable interactions with residues of nuclear hormone receptor 3 (TcHR3) of T. castaneum, which suggested that the four sesquiterpenes have potential to be promising insecticides on storage pests control.