Essential Oil Composition of Grindelia squarrosa from Southern Idaho.

Grindelia squarrosa is an arid lands herb that has been used in Native American traditional medicine, is a potential source of pharmacologically active compounds, and has been explored as a source of biofuel. The purpose of this work was to examine the essential oil composition of G. squarrosa from southern Idaho. Gas chromatographic methods revealed the essential oil of G. squarrosa var. serrulata to be rich in monoterpenoids, α-pinene (21.9%), limonene (17.1%), terpinolene (10.6%), and borneol (6.5%). The essential oil composition of G. squarrosa from Idaho is similar to that previously reported from specimens collected from Montana and confirms the volatile phytochemistry of plants growing in North America. The major essential oil components were screened for antimicrobial activity against respiratory and dermal pathogens. (-)-ß-Pinene showed strong antibacterial activity against Streptococcus pneumoniae (MIC 39.1 µg/mL) and (-)-borneol showed strong activity against Staphylococcus aureus (MIC 78.1 µg/mL).

The importance of nutrient ratios in determining elevations in geosmin synthase (geoA) and 2-MIB cyclase (mic) resulting in taste and odour events.

Geosmin synthase (geoA) and 2-MIB cyclase (mic) are key biosynthetic genes responsible for the production of taste and odour (T&O) compounds, geosmin and 2-MIB. These T&O compounds are becoming an increasing global problem for drinking water supplies. It is thought that geosmin and 2-MIB may be linked to, or exacerbated by, a variety of different environmental and nutrient triggers. However, to the best of our knowledge, no studies to date have evaluated the combined effects of seasonality, temperature, and nutrient concentrations on geoA and mic copy numbers in conjunction with T&O concentrations. In this study, environmental triggers behind geosmin and 2-MIB production were investigated in nine reservoirs across Wales, U.K. between July 2019 - August 2020. The abundance of geoA and mic were quantified through quantitative Polymerase Chain Reaction (qPCR). Temporal changes in geoA and geosmin concentrations revealed geoA to be an indicator of monthly geosmin concentrations, although only when geosmin concentrations exceeded 100 ng L-1. Model analysis of a reservoir with elevated geosmin concentrations revealed geoA to be significantly associated with mean temperature (p < 0.001) and the nutrients dissolved reactive silicate (p < 0.001), dissolved iron (p < 0.001), total inorganic nitrogen to phosphorous ratio (TIN:TP) (p < 0.001) and ammonium to nitrate ratio (NH4+:NO3-) (p < 0.001). Sulphate also demonstrated a significant positive linear relationship with geoA (p < 0.001). For mic analysis, NH4+:NO3- was significantly associated with mic (p < 0.05) and an association with dissolved reactive silicate was also observed (p = 0.084). Within this study we also report extreme variance in gene copy numbers between the study seasons. No consistent relationship could be determined for mic copy numbers mL-1 and 2-MIB (ng L-1). The findings from this study indicate that TIN:TP and NH4+:NO3- serve as good predictors for elevated geoA and mic, along with negative linear relationships observed for mean temperature and dissolved reactive silicate. Overall, our findings demonstrate the importance of nutrient concentrations, nutrient ratios and temperature for evidence based predictive capacity of taste and odour events in drinking water reservoirs.

Early warning of MIB episode based on gene abundance and expression in drinking water reservoirs.

Cellular 2-methylisoborneol (MIB) yield of cyanobacteria varies under different conditions according to culture studies and field investigations, the causal mechanism remains unclear and results in ineffective MIB prediction. Through an intensive field survey during an MIB episode produced by Pseudanabaena cinerea in QCS reservoir, we demonstrated that MIB synthesis (mic) gene abundance (DNA) and expression (RNA) might be useful as parameters for early warning of MIB production. It was found that the abundance of mic DNA and RNA peaked ahead of MIB concentrations by 10 and 7 days, respectively. In addition, the RNA abundance (R2 = 0.45, p < 0.01) showed a slightly higher correlation with MIB compared to DNA abundance (R2 = 0.37, p < 0.01), suggesting that the conditions for the growth of Pseudanabaena cinerea might be slightly different from those for mic gene expression, which was verified by a culture experiment. The highest cell growth was obtained under 36 µmol photons m-2 s-1, while the highest cellular MIB yield and mic gene expression level were obtained under 85 µmol photons m-2 s-1. Our results clearly supported that light intensity was the virtual regulator governing the mic gene expression within the controlled culture experiment and the actual MIB episode in the reservoir. Besides these results, we developed an early warning model using mic gene abundance as an indicator of MIB episodes, which was verified in two other reservoirs. Our findings highlight the effect of light intensity on mic gene expression and MIB synthesis and provide an early warning tool targeting MIB episode prediction, which therefore should be of importance for source water authorities.

Thirteen Dipterocarpoideae genomes provide insights into their evolution and borneol biosynthesis.

Dipterocarpoideae, the largest subfamily of the Dipterocarpaceae, is a dominant component of Southeast Asian rainforests and is widely used as a source of wood, damar resin, medicine, and essential oil. However, many Dipterocarpoideae species are currently on the IUCN Red List owing to severe degradation of their habitats under global climate change and human disturbance. Genetic information regarding these taxa has only recently been reported with the sequencing of four Dipterocarp genomes, providing clues to the function and evolution of these species. Here, we report on 13 high-quality Dipterocarpoideae genome assemblies, ranging in size from 302.6 to 494.8 Mb and representing the five most species-rich genera in Dipterocarpoideae. Molecular dating analyses support the Western Gondwanaland origin of Dipterocarpaceae. Based on evolutionary analysis, we propose a three-step chromosome evolution scenario to describe the karyotypic evolution from an ancestor with six chromosomes to present-day species with 11 and 7 chromosomes. We discovered an expansion of genes encoding cellulose synthase (CesA), which is essential for cellulose biosynthesis and secondary cell-wall formation. We functionally identified five bornyl diphosphate synthase (BPPS) genes, which specifically catalyze the biosynthesis of borneol, a natural medicinal compound extracted from damar resin and oils, thus providing a basis for large-scale production of natural borneol in vitro.

Gelatin-based nanofiber membranes loaded with curcumin and borneol as a sustainable wound dressing.

Infection is a huge obstacle to wound healing. Thus, to enhance the healing of infected wounds, wound dressings that permit the dual delivery of antimicrobials and antioxidants are highly desirable. In this study, a series of gelatin-based nanofiber membranes with different curcumin contents were fabricated via solution electrospinning. The obtained membranes were characterized in terms of their morphologies, in addition to their physical, mechanical, and in vitro properties. The results showed that the membranes maintained an integrated morphology, excellent water absorption capability, satisfactory mechanical properties, and a high dissolution rate of curcumin. The addition of curcumin and borneol conferred the membranes the ability to inhibit Staphylococcus aureus and eliminate free radicals. Furthermore, cytocompatibility testing using the L929 cell line confirmed the excellent biocompatibility of the membranes. These gelatin-based nanofiber membranes loaded with curcumin and borneol can therefore be considered as promising materials for dressing wounds. Moreover, the use of biodegradable polymers and environmentally sustainable production techniques in this system render it suitable for the commercial manufacture of composite membranes.

Low-Temperature Photothermal Therapy Based on Borneol-Containing Polymer-Modified MXene Nanosheets.

Noninvasive photothermal therapy (PTT) is an emerging strategy for eliminating multidrug-resistant (MDR) bacteria that achieve sterilization by generating temperatures above 50 °C; however, such a high temperature also causes collateral damage to healthy tissues. In this study, we developed a low-temperature PTT based on borneol-containing polymer-modified MXene nanosheets (BPM) with bacteria-targeting capabilities. BPM was fabricated through the electrostatic coassembly of negatively charged two-dimensional MXene nanosheets (2DM) and positively charged quaternized α-(+)-borneol-poly(N,N-dimethyl ethyl methacrylate) (BPQ) polymers. Integrating BPQ with 2DM improved the stability of 2DM in physiological environments and enabled the bacterial membrane to be targeted due to the presence of a borneol group and the partially positive charge of BPQ. With the aid of near-infrared irradiation, BPM was able to effectively eliminate methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli) through targeted photothermal hyperthermia. More importantly, BPM effectively eradicated more than 99.999% (>5 orders of magnitude) of MRSA by localized heating at a temperature that is safe for the human body (≤40 °C). Together, these findings suggest that BPM has good biocompatibility and that membrane-targeting low-temperature PTT could have great therapeutic potential against MDR infections.

[Comparison between macroscopic identification and DNA barcoding identification of Amomi Fructus].

This study aims to explore the consistency between macroscopic identification and DNA barcoding identification of Amomi Fructus. With the DNA barcoding identification results, we evaluated the reliability of identifying Amomi Fructus quality by combining macroscopic traits with main volatile chemical components. Thirteen batches of Amomi Fructus samples were collected for identification. Firstly, the morphological and sensory characteristics of each sample were observed and recorded according to the standard in Chinese Pharmacopoeia(2020 edition). The 100-fruit weight, longitudinal diameter, transverse diameter, and longitudinal diameter-to-transverse diameter ratio were measured, which correspond to large, solid, and full kernel representing good quality in the sensory evaluation. The odor value detected by electronic nose and major volatile components(borneol, camphor, limonene, and borneol acetate) correspond to the sensory evaluation of strong odor representing good quality. Secondly, DNA barcoding was employed to identify the 13 batches of samples. Finally, clustering analysis was performed for the main volatile components and macroscopic traits, and the identification results were compared with those of DNA barcoding. Except two batches of samples(No.6 and No.10), the macroscopic identification showed the results consistent with those of DNA barcoding, with an identification rate of 84.62%. The clustering results of the content of four volatile chemical components and macroscopic traits were also consistent with the DNA barcoding identification results. DNA barcoding can verify the results of macroscopic identification and provide a scientific basis for the inheritance and development of macroscopic identification. Moreover, the combination of macroscopic traits and chemical components demonstrates higher accuracy in the quality evaluation of Chinese medicinal materials.

Natural borneol enhances the anti-cerebral ischaemia efficacy of formononetin in MCAO/R rats by promoting its delivery in the brain.

Objectives Due to its high morbidity, high mortality, and high disability, stroke has been the first cause of death and the major cause of adult disability in China. Natural borneol has been widely utilized in Traditional Chinese Medicine to promote drug absorption. Formononetin is a natural isoflavonoid with potent neuroprotective activity but poor brain delivery. Methods This study aimed to screen the optimum proportion that natural borneol promotes formononetin entry into the brain, evaluate the anti-cerebral ischaemia efficacy of formononetin/natural borneol combination in middle cerebral artery occlusion/reperfusion model rats, and clarify the possible mechanism for natural borneol's promoting formononetin delivery in the brain. Key findings Our studies exhibited that natural borneol remarkably promoted formononetin entry into the brain when combined with formononetin in a 1 : 1 molar ratio and notably improved neuro-behavioural scores and reduced the infarct of middle cerebral artery occlusion/reperfusion model rats. This study further discovered that the enhanced anti-cerebral ischaemia effect resulted from natural borneol increasing the permeability of the blood-brain barrier to elevate formononetin concentration in the brain rather than the pharmacodynamic synergy or addition between formononetin and natural borneol. Conclusions The study provides a good strategy to screen drug combinations for the treatment of brain disease by combining natural borneol with other drugs.

d-Borneol enhances cisplatin sensitivity via autophagy dependent EMT signaling and NCOA4-mediated ferritinophagy.

BACKGROUND: d-Borneol has been widely used as a drug absorption enhancer, but there are few studies on the anti-resistance ability of d-borneol combined with cisplatin in cisplatin-resistant non-small cell lung cancer cells. Ferroptosis, autophagy and epithelial-mesenchymal transition (EMT) have been reported to be associated with drug resistance. PURPOSE: To investigate the molecular mechanisms and sensitizing effects of d-borneol combined with cisplatin to against drug cisplatin resistance from the perspective of ferroptosis, autophagy and EMT resistance. METHODS: H460/CDDP xenograft tumor model was established to verify the antitumor activity and safety in vivo. RNA sequencing was used to predict target molecules and signaling pathways. Reactive oxygen species (ROS) were used as marker of ferroptosis, and its level was determined by a dichlorodihydrofluorescein diacetate fluorescent probe and flow cytometry. Levels of glutathione (GSH), malondialdehyde (MDA), and antioxidants such as superoxide dismutase (SOD) and thioredoxin (Trx) involved in the balance of oxidative stress were measured by an assay kit or enzyme-linked immunosorbent assay. Western blotting and real-time polymerase chain reaction were used to assess the regulatory mechanism of EMT markers, autophagy, and ferroptosis signaling pathways. RESULTS: d-Borneol in combination with cisplatin reduced tumor volume and weight, enhanced tumor-inhibiting effects, and alleviated cisplatin-induced damage to the liver and kidney in vivo. RNA-sequencing showed that differentially expressed genes were enriched in ferroptosis. d-Borneol in combination with cisplatin promoted ROS accumulation, increased the content of MDA levels, and decreased GSH, SOD, Trx, and heme oxygenase-1 expression to induce oxidative damage. d-Borneol combination with cisplatin induced ferroptosis by promoting nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy and regulating intracellular iron ion transport via upregulating PRNP and downregulating PCBP2. In addition, d-borneol combined with cisplatin promoted autophagy by upregulating expression of LC3II/ATG5/Beclin-1 and inhibited the EMT by increasing the expression of epithelial marker E-cadherin and decreasing mesenchymal markers (N-cadherin and vimentin) and transcription factors (Snail and ZEB1). CONCLUSION: For the first time, our study implies that d-borneol enhanced cisplatin sensitivity by inducing ferroptosis, promoting autophagy and inhibiting EMT progression, thereby enhancing antitumor activity. It suggests that d-borneol could be developed as a novel chemosensitizers.

Terpene dispersion energy donor ligands in borane complexes.

Structural characterization of the complex [B(ß-pinane)3] (1) reveals non-covalent H⋯H contacts that are consistent with the generation of London dispersion energies involving the ß-pinane ligand frameworks. The homolytic fragmentations of 1, and camphane and sabinane analogues ([B(camphane)3] (2) and [B(sabinane)3] (3)) were studied computationally. Isodesmic exchange results showed that London dispersion interactions are highly dependent on the terpene's stereochemistry, with the ß-pinane framework providing the greatest dispersion free energy (ΔG = -7.9 kcal mol-1) with Grimme's dispersion correction (D3BJ) employed. PMe3 was used to coordinate to [B(ß-pinane)3], giving the complex [Me3P-B(ß-pinane)3] (4), which displayed a dynamic coordination equilibrium in solution. The association process was found to be slightly endergonic at 302 K (ΔG = +0.29 kcal mol-1).

Neutrophil Immunomodulatory Activity of (-)-Borneol, a Major Component of Essential Oils Extracted from Grindelia squarrosa.

Grindelia squarrosa (Pursh) Dunal is used in traditional medicine for treating various diseases; however, little is known about the immunomodulatory activity of essential oils from this plant. Thus, we isolated essential oils from the flowers (GEOFl) and leaves (GEOLv) of G. squarrosa and evaluated the chemical composition and innate immunomodulatory activity of these essential oils. Compositional analysis of these essential oils revealed that the main components were α-pinene (24.7 and 23.2% in GEOFl and GEOLv, respectively), limonene (10.0 and 14.7%), borneol (23.4 and 16.6%), p-cymen-8-ol (6.1 and 5.8%), ß-pinene (4.0 and 3.8%), bornyl acetate (3.0 and 5.1%), trans-pinocarveol (4.2 and 3.7%), spathulenol (3.0 and 2.0%), myrtenol (2.5 and 1.7%), and terpinolene (1.7 and 2.0%). Enantiomer analysis showed that α-pinene, ß-pinene, and borneol were present primarily as (-)-enantiomers (100% enantiomeric excess (ee) for (-)-α-pinene and (-)-borneol in both GEOFl and GEOLv; 82 and 78% ee for (-)-ß-pinene in GEOFl and GEOLv), while limonene was present primarily as the (+)-enantiomer (94 and 96 ee in GEOFl and GEOLv). Grindelia essential oils activated human neutrophils, resulting in increased [Ca2+]i (EC50 = 22.3 µg/mL for GEOFl and 19.4 µg/mL for GEOLv). In addition, one of the major enantiomeric components, (-)-borneol, activated human neutrophil [Ca2+]i (EC50 = 28.7 ± 2.6), whereas (+)-borneol was inactive. Since these treatments activated neutrophils, we also evaluated if they were able to down-regulate neutrophil responses to subsequent agonist activation and found that treatment with Grindelia essential oils inhibited activation of these cells by the N-formyl peptide receptor 1 (FPR1) agonist fMLF and the FPR2 agonist WKYMVM. Likewise, (-)-borneol inhibited FPR-agonist-induced Ca2+ influx in neutrophils. Grindelia leaf and flower essential oils, as well as (-)-borneol, also inhibited fMLF-induced chemotaxis of human neutrophils (IC50 = 4.1 ± 0.8 µg/mL, 5.0 ± 1.6 µg/mL, and 5.8 ± 1.4 µM, respectively). Thus, we identified (-)-borneol as a novel modulator of human neutrophil function.

Degradation of geosmin and 2-methylisoborneol in UV-based AOPs for photoreactors with reflective inner surfaces: Kinetics and transformation products.

Geosmin (GSM) and 2-methylisoborneol (2-MIB) are representative musty/earthy odor compounds commonly present in surface water. In present study, the degradation of GSM and 2-MIB subject to different UV-based advanced oxidation processes (AOPs), including UV/H2O2, UV/S2O82-, UV/chlorine, and UV/chloramine, in a phosphate-buffered saline (PBS) was conducted in a photoreactor with reflective inner surfaces and compared with that in an environmental water sample. A dynamic model to predict the degradation of GSM and 2-MIB in the photoreactor with reflective inner surfaces in the four UV-based AOPs was developed applying the second-order rate constants for the GSM and 2-MIB with primary reactive species (i.e., •OH, •Cl, and •SO4-) determined in this study. The model was proven to successfully simulate the degradation of GSM and 2-MIB. In addition, 8, 7, 8, and 11 degradation intermediates were detected from UV/H2O2, UV/S2O82-, UV/chlorine, and UV/chloramine in this study, and possible degradation pathways were proposed. This study is the first to report the degradation kinetics and formation products of GSM and 2-MIB in UV/chloramine. Research based on photoreactors with reflective inner surfaces may provide some guidance for eliminating GSM and 2-MIB in UV-based AOPs for full-scale engineering applications.

d-Borneol enhances cisplatin sensitivity via p21/p27-mediated S-phase arrest and cell apoptosis in non-small cell lung cancer cells and a murine xenograft model.

BACKGROUND: Cisplatin (CDDP) is commonly used to treat non-small cell lung cancer (NSCLC), but the appearance of drug resistance greatly hinders its efficacy. Borneol may promote drug absorption; however, synergism between borneol and CDDP in suppressing NSCLC is not clearly understood. Hence, we investigated borneol as a novel chemosensitizer to support chemotherapeutic efficacy and reduce side effects. METHODS: We compared viability after exposure to d-borneol, l-borneol, and synthetic borneol in two NSCLC cell lines, A549 and H460, and selected the most sensitive cells. We then assessed synergy between borneol forms and CDDP in cisplatin-resistant NSCLC cells, H460/CDDP. Next, we identified effective concentrations and exposure times. Subsequently, we evaluated cell migration via wound healing and cell proliferation via clone formation assay. Then, we focused on P-glycoprotein (P-gp) function, cell cycle, apoptosis, and RNA sequencing to elucidate underlying molecular mechanisms for synergy. Finally, we used an H460/CDDP xenograft tumor model to verify antitumor activity and safety in vivo. Data were examined using one-way analysis of variance (ANOVA) for multiple datasets or t-test for comparisons between two variables. RESULTS: d-Borneol was more effective in H460 than A549 cells. d-Borneol combined with CDDP showed greater inhibition of cell proliferation, migration, and clone formation in H460/CDDP cells than CDDP alone. RNA sequencing (RNA-seq) analysis identified differentially expressed genes enriched in cell cycle pathways. The impact of d-borneol on CDDP chemosensitivity involved arrest of the cell cycle at S phase via p27/p21-mediated cyclinA2/D3-CDK2/6 signaling and activation of intrinsic apoptosis via p21-mediated Bax/Bcl-2/caspase3 signaling. Further, d-borneol ameliorated drug resistance by suppressing levels and activity of P-gp. Cotreatment with d-borneol and CDDP inhibited tumor growth in vivo and reduced CDDP-caused liver and kidney toxicity. CONCLUSIONS: d-Borneol increased the efficacy of cisplatin and reduced its toxicity. This compound has the potential to become a useful chemosensitizer for drug-resistance NSCLC.

Potentiation of the Activity of Antibiotics against ATCC and MDR Bacterial Strains with (+)-α-Pinene and (-)-Borneol.

The increasing rates of antimicrobial resistance have demanded the development of new drugs as conventional antibiotics have become significantly less effective. Evidence has identified a variety of phytocompounds with the potential to be used in the combat of infections caused by multidrug-resistant (MDR) bacteria. Considering the verification that terpenes are promising antibacterial compounds, the present research aimed to evaluate the antibacterial and antibiotic-modulating activity of (+)-α-pinene and (-)-borneol against MDR bacterial strains. The broth microdilution method was used to determine the minimum inhibitory concentration (MIC) of the compounds and antibiotics and further evaluate the intrinsic and associated antibiotic activity. These analyses revealed that (+)-α-pinene showed significant antibacterial activity only against E. coli (MIC = 512 µg.mL-1), while no significant inhibition of S. aureus and P. aeruginosa growth was observed (MIC ≥ 1024 µg mL-1). However, when combined with antibiotics, this compound induced a significant improvement in the activity of conventional antibiotics, as observed for ciprofloxacin, amikacin, and gentamicin against Staphylococcus aureus, as well as for amikacin and gentamicin against Escherichia coli, and amikacin against Pseudomonas aeruginosa. On the other hand, (-)-borneol was found to inhibit the growth of E. coli and enhance the antibiotic activity of ciprofloxacin and gentamicin against S. aureus. The present findings indicate that (+)-α-pinene and (-)-borneol are phytocompounds with the potential to be used in the combat of antibacterial resistance.

Borneol Ester Derivatives as Entry Inhibitors of a Wide Spectrum of SARS-CoV-2 Viruses.

In the present work we studied the antiviral activity of the home library of monoterpenoid derivatives using the pseudoviral systems of our development, which have glycoproteins of the SARS-CoV-2 virus strains Wuhan and Delta on their surface. We found that borneol derivatives with a tertiary nitrogen atom can exhibit activity at the early stages of viral replication. In order to search for potential binding sites of ligands with glycoprotein, we carried out additional biological tests to study the inhibition of the re-receptor-binding domain of protein S. For the compounds that showed activity on the pseudoviral system, a study using three strains of the infectious SARS-CoV-2 virus was carried out. As a result, two leader compounds were found that showed activity on the Wuhan, Delta, and Omicron strains. Based on the biological results, we searched for the potential binding site of the leader compounds using molecular dynamics and molecular docking methods. We suggested that the compounds can bind in conserved regions of the central helices and/or heptad repeats of glycoprotein S of SARS-CoV-2 viruses.

LC-MS-based metabolomics reveals metabolic changes in short- and long-term administration of Compound Danshen Dripping Pills against acute myocardial infarction in rats.

BACKGROUND: Mild and systematically improving multiple metabolic disorders was a focused view for Compound Danshen Dripping Pills playing synergistic effects through multiple components and multiple targets. The difference in overall therapeutic effects and endogenous metabolic regulation between short- and long-term administration was still unclear. PURPOSE: This study aimed to explore the difference in endogenous metabolic regulation between short- and long-term Compound Danshen Dripping Pills (CDDP) administration against acute myocardial infarction (AMI). METHODS: The model of AMI was induced by ligating the left anterior descending coronary artery. The cardiac protection effects of CDDP were investigated by echocardiography, 1- or 2-week were defined as short- and long-term based on desirable efficacy variability. The entire metabolic changes between short- and long-term administration of CDDP were profiled by UPLC-Q-TOF-MS. In addition, the metabolic regulatory network of CDDP administration against myocardial infarction rats was also compared with those of a typical chemical drug isosorbide 5-mononitrate (ISMN). RESULTS: After 1- or 2-week continuous oral administration, CDDP could significantly alleviate AMI-induced cardiac dysfunction. By using LC-MS-based metabolomics analyses, we systematically investigated the metabolic profiles of plasma and heart tissue samples at fixed exposure time-points (2 h, 24 h) from AMI rats with CDDP treatment. Most interestingly, global endogenous metabolic changes were observed in cardiac samples collected at different stages post consecutive CDDP administration, fluctuating at 2 and 24 h after 1 week but stabilizing after 2 weeks. The disrupted metabolic pathways such as glycerophospholipid, amino acids, fatty acids, and arachidonic acid metabolism were reconstructed after both short- and long-term CDDP treatment, while taurine and hypotaurine metabolism and purine metabolism contributed to the whole efficacy after long-term CDDP administration. CONCLUSION: Long-term CDDP treatment plays prolonged and stable efficacy against AMI compared with short-term treatment by specifically regulating purine and taurine and hypotaurine metabolism and systematically redressing metabolic disorders.

A Study on the Mechanism of the Sedative-hypnotic Effect of Cinnamomum camphora chvar. Borneol Essential Oil Based on Network Pharmacology.

In this paper, we investigated the sedative-hypnotic effect of Cinnamomum camphora chvar. Borneol essential oil (BEO, 16.4% borneol), a by-product of steam distillation of Cinnamomum camphora chvar. Borneol, from which natural crystalline borneol (NCB, 98.4% borneol) is obtained. Using locomotor activity tests and pentobarbital sodium-induced sleep test, it was found that BEO significantly reduced locomotor activity (p < 0.05), shortened sleep latency (p < 0.0001), prolonged sleep duration (p < 0.05), and had a sedative-hypnotic effect. We constructed the "components-targets-signaling pathways" and "proteinprotein interaction" (PPI) network of BEO using network pharmacology. The results show that the 24 active components of BEO acted on 17 targets, mainly through response to alkaloid and catecholamine transport, and neuroactive ligand-receptor interaction. The PPI network identified 12 key proteins, mainly dopamine receptor (DR)D2, opioid receptor mu 1 (OPRM1), and opioid receptor kappa 1 (OPRK1), and we further analyzed the active components and targets of BEO through molecular docking. The results showed that the active components and targets obtained by network pharmacology analyses had good binding activity, which reflected their multi-component, multi-target, multi-pathway action characteristics. This paper provides a theoretical basis for further study of the mechanism of action of BEO in the treatment of insomnia.

Sniffing out camphor: the fine balance between hydrogen bonding and London dispersion in the chirality recognition with α-fenchol.

Binary complexes between the chiral monoterpenoids camphor and α-fenchol were explored with vibrational and rotational jet spectroscopy as well as density functional theory in order to explore how chirality can influence the binding preferences in gas-phase complexes. The global minimum structures of the two diastereomers were assigned. It is found that chirality recognition leads to different compromises in the fine balance between intermolecular interactions. While one isomer features a stronger hydrogen bond, the other one is more tightly arranged and stabilized by larger London dispersion interactions. These new spectroscopic results help understand the influence of chirality in molecular aggregation and unveil the kind of interactions involved between a chiral alcohol and a chiral ketone with large dispersion contributions.