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Chinese Journal of Natural Medicines Jun 2024Depression ranks among the most common neuropsychiatric disorders globally. Current studies examining the roles of inflammation and mitochondrial autophagy in the...
Depression ranks among the most common neuropsychiatric disorders globally. Current studies examining the roles of inflammation and mitochondrial autophagy in the antidepressant efficacy of paeoniflorin (PF) are sparse. This study aimed to elucidate PF's antidepressant mechanism by promoting autophagy and inhibiting NLRP3 inflammasome activation using chronic unpredictable mild stimulation (CUMS)-induced C57BL/6 mouse models in vivo and corticosterone (CORT)-induced HT22 cell models in vitro. Results demonstrated that PF enhanced the viability of HT22 cells following CORT exposure, restored mitochondrial membrane potential (MMP), reduced reactive oxygen species accumulation, increased LC3 fluorescence intensity, and suppressed inflammatory cytokine secretion and inflammation activation. Additionally, PF ameliorated depressive behaviors induced by CUMS and improved damage in hippocampal neurons. It also reduced the expression of NLRP3, ASC, Caspase-1, IL-1β, and the assembly of the NLRP3 inflammasome. Moreover, PF upregulated the expression of autophagy-related proteins in the hippocampus, facilitating the clearance of damaged mitochondria and enhancing autophagy. The role of autophagy in PF's antidepressant effects was further confirmed through the use of the autophagy inhibitor 3-methyladenine (3-MA), which reduced the efficacy of PF. In conclusion, PF effectively improved depressive behaviors in CUMS-induced mice and reduced NLRP3-mediated inflammation both in vivo and in vitro, likely via the induction of autophagy.
Topics: Animals; NLR Family, Pyrin Domain-Containing 3 Protein; Glucosides; Autophagy; Monoterpenes; Mice; Mitochondria; Mice, Inbred C57BL; Inflammasomes; Male; Depression; Antidepressive Agents; Hippocampus; Disease Models, Animal; Reactive Oxygen Species
PubMed: 38906599
DOI: 10.1016/S1875-5364(24)60654-0 -
Evidence that the cold- and menthol-sensing functions of the human TRPM8 channel evolved separately.Science Advances Jun 2024Transient receptor potential melastatin 8 (TRPM8) is a temperature- and menthol-sensitive ion channel that contributes to diverse physiological roles, including cold...
Transient receptor potential melastatin 8 (TRPM8) is a temperature- and menthol-sensitive ion channel that contributes to diverse physiological roles, including cold sensing and pain perception. Clinical trials targeting TRPM8 have faced repeated setbacks predominantly due to the knowledge gap in unraveling the molecular underpinnings governing polymodal activation. A better understanding of the molecular foundations between the TRPM8 activation modes may aid the development of mode-specific, thermal-neutral therapies. Ancestral sequence reconstruction was used to explore the origins of TRPM8 activation modes. By resurrecting key TRPM8 nodes along the human evolutionary trajectory, we gained valuable insights into the trafficking, stability, and function of these ancestral forms. Notably, this approach unveiled the differential emergence of cold and menthol sensitivity over evolutionary time, providing a fresh perspective on complex polymodal behavior. These studies provide a paradigm for understanding polymodal behavior in TRPM8 and other proteins with the potential to enhance our understanding of sensory receptor biology and pave the way for innovative therapeutic interventions.
Topics: TRPM Cation Channels; Humans; Menthol; Cold Temperature; Evolution, Molecular; Phylogeny; Thermosensing
PubMed: 38905339
DOI: 10.1126/sciadv.adm9228 -
Tree Physiology Jun 2024With climate warming and economic globalization, insect-microbe assemblages are becoming increasingly responsible for various devastating forest diseases worldwide....
With climate warming and economic globalization, insect-microbe assemblages are becoming increasingly responsible for various devastating forest diseases worldwide. Japanese larch (Larix kaempferi) is extensively cultivated in China because of its high survival rate, rapid maturation, and robust mechanical properties. Endoconidiophora fujiensis, an ophiostomatoid fungus associated with Ips subelongatus, has been identified as a lethal pathogen of L. kaempferi in Japan. However, there is a dearth of research on the pathogenicity of E. fujiensis in larches in China. Therefore, we investigated the pathogenicity of E. fujiensis in introduced L. kaempferi and indigenous larch (Larix olgensis) trees and compared the induced resistance responses to the pathogen in both tree species in terms of physiology and gene expression. Five-year-old saplings and 25-year-old adult trees of L. olgensis and L. kaempferi were inoculated in parallel during the same growing season. E. fujiensis exhibited high pathogenicity in both larch species, but particularly in L. kaempferi compared to L. olgensis adult trees; adult L. olgensis was more resistant to E. fujiensis than adult L. kaempferi, which was reflected in higher accumulation of defensive monoterpenes, such as myrcene, 3-carene, and limonene, and the earlier induction of defense genes catalase (CAT) and pathogenesis-related protein 1 (PR1). This study contributes to our understanding of the interactions between bark beetle-associated ophiostomatoid fungi and host larches, from phenotypic responses to alterations in secondary metabolites via defense- and metabolism-related gene activation, providing a valuable foundation for the management of larch diseases and pests in the future.
PubMed: 38905265
DOI: 10.1093/treephys/tpae069 -
The Science of the Total Environment Jun 2024Rubber trees emit a range of volatile organic compounds (VOCs), including isoprene, monoterpenes, and sesquiterpenes, as part of their natural metabolism. These VOCs can...
Rubber trees emit a range of volatile organic compounds (VOCs), including isoprene, monoterpenes, and sesquiterpenes, as part of their natural metabolism. These VOCs can significantly influence air quality through photochemical reactions that produce ozone and secondary organic aerosols (SOAs). This study examines the impact of VOCs detected in a rubber tree plantation in Northeastern Thailand on air quality, highlighting their role in atmospheric reactions that lead to the formation of ozone and SOAs. VOCs were collected at varying heights and seasons using Tenax-TA tubes paired with an atmospheric sampler pump and identified by gas chromatography-mass spectrometry. In total, 100 VOCs were identified, including alkanes, alkenes, terpenes, aromatics, and oxygenated VOCs. Principal Coordinate Analysis (PCoA) revealed distinct seasonal VOC profiles, with hydrocarbons, peaking in summer and terpenes in the rainy season. The Linear Mixed-Effects (LME) model indicates that VOC concentrations are more influenced by seasonal changes than by sampling heights. Secondary organic aerosol potential (SOAP) and ozone formation potential (OFP) of selected VOC species were also determined. The total SOAP ranged from 67.24 μg/m in summer to 17.87 μg/m in winter, while the total OFP ranged from 377.87 μg/m in summer to 139.39 μg/m in winter. Additionally, positive matrix factorization (PMF) analysis identified four main VOC sources: gasoline combustion (18.3 %), microbial activity (38.6 %), monoterpene emissions during latex production (15.0 %), and industrial sources (28.1 %). These findings provide essential information for managing air pollution in rubber tree plantations. By adopting focused air quality management strategies, plantation operators can mitigate the adverse effects of VOCs, promoting a healthier and more sustainable future.
PubMed: 38897456
DOI: 10.1016/j.scitotenv.2024.173984 -
Metabolic Engineering Jun 2024Monoterpene indole alkaloids (MIAs) are a group of plant-derived natural products with high-value medicinal properties. However, their availability for clinical...
Monoterpene indole alkaloids (MIAs) are a group of plant-derived natural products with high-value medicinal properties. However, their availability for clinical application is limited due to challenges in plant extraction. Microbial production has emerged as a promising strategy to meet the clinical demands for MIAs. The biosynthetic pathway of cis-trans nepetalactol, which serves as the universal iridoid scaffold for all MIAs, has been successfully identified and reconstituted. However, bottlenecks and challenges remain to construct a high-yielding platform strain for cis-trans nepetalactol production, which is vital for subsequent MIAs biosynthesis. In the present study, we focused on engineering of Pichia pastoris cell factories to enhance the production of geraniol, 8-hydroxygeraniol, and cis-trans nepetalactol. By targeting the biosynthetic pathway from acetyl-CoA to geraniol in both peroxisomes and cytoplasm, we achieved comparable geraniol titers in both compartments. Through protein engineering, we found that either G8H or CPR truncation increased the production of 8-hydroxygeraniol, with a 47.8-fold and 14.0-fold increase in the peroxisomal and cytosolic pathway strain, respectively. Furthermore, through a combination of dynamical control of ERG20, precursor and cofactor supply engineering, diploid engineering, and dual subcellular compartmentalization engineering, we achieved the highest ever reported production of cis-trans nepetalactol, with a titer of 4429.4 mg/L using fed-batch fermentation in a 5-L bioreactor. We anticipate our systematic metabolic engineering strategies to facilitate the development of P. pastoris cell factories for sustainable production of MIAs and other plant natural products.
PubMed: 38897449
DOI: 10.1016/j.ymben.2024.06.007 -
Phytomedicine : International Journal... Jun 2024Perillyl alcohol (POH) is a aroma monoterpene commonly obtained from various plants' essential oil. Recently, increasing researches have demonstrated that POH may be... (Review)
Review
BACKGROUND
Perillyl alcohol (POH) is a aroma monoterpene commonly obtained from various plants' essential oil. Recently, increasing researches have demonstrated that POH may be useful, not only as flavor compound, but also as bioactive molecule because of a variety of biological activities.
PURPOSE
The aim of this review is to summarize the production, pharmacological activities and molecular mechanism, active derivatives, toxicity and parmacokinetics, and industrial application of POH.
METHODS
A systematic search of published articles up to January 2024 in Web of Science, China Knowledge Network, and PubMed databases is conducted using the following keywords: POH, POH derivatives, biological or pharmacological, production or synthesis, pharmacokinetics, toxicity and application.
RESULTS
Biotechnological production is considered to be a potential alternative approach to generate POH. POH provides diverse pharmacological benefits, including anticancer, antimicrobial, insecticidal, antioxidant, anti-inflammatory, hypotensive, vasorelaxant, antinociceptive, antiasthmatic, hepatoprotective effects, etc. The underlying mechanisms of action include modulation of NF-κB, JNK/c-Jun, Notch, Akt/mTOR, PI3K/Akt/eNOS, STAT3, Nrf2 and ERS response pathways, mitigation of mitochondrial dysfunction and membrane integrity damage, and inhibition of ROS accumulation, pro-inflammatory cytokines release and NLRP3 activation. What's more, the proteins or genes influenced by POH against diseases refer to Bax, Bcl-2, cyclin D1, CDK, p21, p53, HIF-1α, AP-1, caspase-3, M6P/IGF2R, PARP, VEGF, etc. Some clinical studies report that intranasal delivery of POH is a safe and effective treatment for cancer, but further clinical investigations are needed to confirm other health benefits of POH in human healthy. Depending on these health-promoting properties together with desirable flavor and safety, POH can be employed as dietary supplement, preservative and flavor additive in food and cosmetic fields, as building block in synthesis fields, as anticancer drug in medicinal fields, and as pesticides and herbicides in agricultural fields.
CONCLUSION
This review systematically summarizes the recent advances in POH and highlights its therapeutic effects and potential mechanisms as well as the clinical settings, which is helpful to develop POH into functional food and new candidate drug for prevention and management of diseases. Future studies are needed to conduct more biological activity studies of POH and its derivatives, and check their clinical efficacy and potential side effects.
PubMed: 38897045
DOI: 10.1016/j.phymed.2024.155826 -
Journal of Ethnopharmacology Jun 2024In Brazilian popular medicine, Lippia alba leaves are used in teas to treat pain and inflammatory diseases.
ETHNOPHARMACOLOGICAL RELEVANCE
In Brazilian popular medicine, Lippia alba leaves are used in teas to treat pain and inflammatory diseases.
AIM OF THE STUDY
to evaluate the chemical composition, antinociceptive, and anti-inflammatory activities of Lippia alba essential oil and its major compound geraniol.
MATERIAL AND METHODS
Lippia alba leaves were collected in Pará state, Brazil. The leaf essential oil was obtained using a modified Clevenger-type extractor. Then, the oil was analyzed by GC and GC-MS analyses. To evaluate the toxicity of LaEO and geraniol, the doses of 50, 300, and 2000 mg/kg were used in a mouse model. For antinociception tests, abdominal contortion, hot plate, and formalin tests were used; all groups were treated with LaEO and geraniol at doses of 25, 50, and 100 mg/kg; and to evaluate inflammation using the ear edema model.
RESULTS
The constituents identified in the highest content were oxygenated monoterpenes: geraniol (37.5%), geranial (6.7%) and neral (3.8%). The animals treated with LaEO and geraniol demonstrated atypical behaviors with aspects of lethargy and drowsiness, characteristics of animals in a state of sedation; the relative weights showed no significant difference compared to the controls. In the abdominal contortion test, LaEO at 25 mg/kg, 50 mg/kg doses, and 100 mg/kg reduced the number of contortions, representing a percentage reduction of 84.64%, 81.23%, and 66.21% respectively. In the hot plate test, LaEO and geraniol increased the latency time at doses of 25, 50, and 100 mg/kg in all test periods; there was no statistical difference between LaEO and geraniol. In the first phase of the formalin test, only doses of 25 mg/kg and 100 mg/kg of LaEO showed significant activity, reducing the latency time by 53.40% and 58.90%. LaEO at doses of 25 mg/kg and 100 mg/kg reduced the size of the edema, demonstrating an anti-inflammatory activity of 59.38% (25 mg/kg) and 50% (100 mg/kg).
CONCLUSION
Lippia alba essential oil and geraniol showed central/peripheral analgesic and anti-inflammatory potential and can be used as an alternative or complementary treatment to conventional drugs. More studies are needed to evaluate its action mechanisms and its analgesic effects.
PubMed: 38897034
DOI: 10.1016/j.jep.2024.118459 -
Molecules (Basel, Switzerland) Jun 2024L. possesses abundant germplasm resources and holds significant value in terms of ornamental, edible, and medicinal aspects. However, the quality characteristics vary...
L. possesses abundant germplasm resources and holds significant value in terms of ornamental, edible, and medicinal aspects. However, the quality characteristics vary significantly depending on different varieties. Selection of a high-quality variety with a characteristic aroma can increase the economic value of flowers. The analytic hierarchy process (AHP) is an effective decision-making method for comparing and evaluating multiple characteristic dimensions. By applying AHP, the aromatic character of 60 varieties of flowers were analyzed and evaluated in the present study. Headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS) was employed to identify volatile components in flowers. Thirteen volatile components were found to contribute to the aroma of flowers, which helps in assessing their potential applications in essential oil, aromatherapy, and medical treatment. These components include 2-phenylethanol, geraniol, linalool, nonanal, decanal, (E)--ocimene, α-farnesene, indole, nerolidol, 3-furanmethanol, 3-carene, benzaldehyde and benzenemethanol. The varieties with better aromatic potential can be selected from a large amount of data using an AHP model. This study provides a comprehensive understanding of the characteristics of the aroma components in flowers, offers guidance for breeding, and enhances the economic value of flowers.
Topics: Gas Chromatography-Mass Spectrometry; Volatile Organic Compounds; Solid Phase Microextraction; Flowers; Odorants; Acyclic Monoterpenes; Oils, Volatile; Sesquiterpenes; Phenylethyl Alcohol; Alkenes; Indoles
PubMed: 38893586
DOI: 10.3390/molecules29112712 -
Molecules (Basel, Switzerland) May 2024Volatile oil serves as a traditional antipyretic component of Bupleuri Radix. var. (Wolff) Shan et Y. Li belongs to the genus and is distinguished for its high level...
Volatile oil serves as a traditional antipyretic component of Bupleuri Radix. var. (Wolff) Shan et Y. Li belongs to the genus and is distinguished for its high level of saikosaponins and volatile oils; nonetheless, prevailing evidence remains inconclusive regarding its viability as an alternative resource of other official species. This study aims to systematically compare the volatile oil components of both dried and fresh roots of var. and the four legally available species across their chemical, molecular, bionics, and anatomical structures. A total of 962 compounds were determined via GC-MS from the dried roots; var. showed the greatest differences from other species in terms of hydrocarbons, esters, and ketones, which was consistent with the results of fresh roots and the e-nose analysis. A large number of DEGs were identified from the key enzyme family of the monoterpene synthesis pathway in var. via transcriptome analysis. The microscopic observation results, using different staining methods, further showed the distinctive high proportion of phloem in var. , the structure which produces volatile oils. Together, these pieces of evidence hold substantial significance in guiding the judicious development and utilization of genus resources.
Topics: Oils, Volatile; Bupleurum; Plant Roots; Gas Chromatography-Mass Spectrometry; Plants, Medicinal
PubMed: 38893436
DOI: 10.3390/molecules29112561 -
International Journal of Molecular... Jun 2024Ferulic acid (Fer) and geraniol (Ger) are natural compounds whose antioxidant and anti-inflammatory activity confer beneficial properties, such as antibacterial,...
Ferulic acid (Fer) and geraniol (Ger) are natural compounds whose antioxidant and anti-inflammatory activity confer beneficial properties, such as antibacterial, anticancer, and neuroprotective effects. However, the short half-lives of these compounds impair their therapeutic activities after conventional administration. We propose, therefore, a new prodrug (Fer-Ger) obtained by a bio-catalyzed ester conjugation of Fer and Ger to enhance the loading of solid lipid microparticles (SLMs) designed as Fer-Ger delivery and targeting systems. SLMs were obtained by hot emulsion techniques without organic solvents. HPLC-UV analysis evidenced that Fer-Ger is hydrolyzed in human or rat whole blood and rat liver homogenates, with half-lives of 193.64 ± 20.93, 20.15 ± 0.75, and 3.94 ± 0.33 min, respectively, but not in rat brain homogenates. Studies on neuronal-differentiated mouse neuroblastoma N2a cells incubated with the reactive oxygen species (ROS) inductor HO evidenced the Fer-Ger ability to prevent oxidative injury, despite the fact that it appears ROS-promoting. The amounts of Fer-Ger encapsulated in tristearin SLMs, obtained in the absence or presence of glucose, were 1.5 ± 0.1%, allowing the control of the prodrug release (glucose absence) or to sensibly enhance its water dissolution rate (glucose presence). These new "green" carriers can potentially prolong the beneficial effects of Fer and Ger or induce neuroprotection as nasal formulations.
Topics: Prodrugs; Animals; Coumaric Acids; Rats; Mice; Humans; Hydrolysis; Acyclic Monoterpenes; Cell Line, Tumor; Esters; Terpenes; Reactive Oxygen Species; Antioxidants
PubMed: 38892454
DOI: 10.3390/ijms25116263