Background Geraniol is an acyclic monoterpene alcohol, which is extracted from the ethereal oils of aromatic plants. A systematic analysis of its mechanism of action has not yet been carried out. Methods In this study, the druggability of geraniol was assessed via Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), and the potential targets of geraniol were identified using the Comparative Toxicogenomics Database (CTD). Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using WebGestalt. Drug-target-pathway networks were constructed using Cytoscape to give a visual view. Results Our findings showed that geraniol has superb druggability with 38 putative identified target genes. GO, KEGG, and network analyses revealed that these targets were associated with cancer, inflammatory immunoreactions, and other physiological processes. Conclusion Geraniol is predicted to target multiple proteins and pathways that shape a network which can exert systematic pharmacological effects.

/pdf/systematic-elucidation-of-the-mechanism-of-geraniol-via-8xi3gbpqsw.pdf

Systematic elucidation of the mechanism of geraniol via network pharmacology.

Pain prevalence among adults in the United States has increased 25% over the past two decades, resulting in high health-care costs and impacts to patient quality of life. In the last 30 years, our understanding of pain circuits and (intra)cellular mechanisms has grown exponentially, but this understanding has not yet resulted in improved therapies. Options for pain management are limited. Many analgesics have poor efficacy and are accompanied by severe side effects such as addiction, resulting in a devastating opioid abuse and overdose epidemic. These problems have encouraged scientists to identify novel molecular targets and develop alternative pain therapeutics. Increasing preclinical and clinical evidence suggests that cannabis has several beneficial pharmacological activities, including pain relief. Cannabis sativa contains more than 500 chemical compounds, with two principle phytocannabinoids, Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). Beyond phytocannabinoids, more than 150 terpenes have been identified in different cannabis chemovars. Although the predominant cannabinoids, Δ9-THC and CBD, are thought to be the primary medicinal compounds, terpenes including the monoterpenes β-myrcene, α-pinene, limonene, and linalool, as well as the sesquiterpenes β-caryophyllene and α-humulene may contribute to many pharmacological properties of cannabis, including anti-inflammatory and antinociceptive effects. The aim of this review is to summarize our current knowledge about terpene compounds in cannabis and to analyze the available scientific evidence for a role of cannabis-derived terpenes in modern pain management. SIGNIFICANCE STATEMENT: Decades of research have improved our knowledge of cannabis polypharmacy and contributing phytochemicals, including terpenes. Reform of the legal status for cannabis possession and increased availability (medicinal and recreational) have resulted in cannabis use to combat the increasing prevalence of pain and may help to address the opioid crisis. Better understanding of the pharmacological effects of cannabis and its active components, including terpenes, may assist in identifying new therapeutic approaches and optimizing the use of cannabis and/or terpenes as analgesic agents.

https://pharmrev.aspetjournals.org/content/pharmrev/73/4/98.full.pdf

Analgesic Potential of Terpenes Derived from Cannabis sativa

Introduction Antibiotics wee widely used as feed additives in animal husbandry. With the increase of drug resistance of bacteria, there is an urgent need to find alternatives to antibiotics. Clinically, methicillin-resistant Staphylococcus aureus (MRSA) infections account for about 25% to 50% of Staphylococcus aureus infections worldwide. Similarly, it is also one of the pathogens that cause serious animal infections. Methods We established a mouse model of systemic infection of MRSA to study the preventive effect of geraniol on MRSA and the immunomodulatory effect of geraniol. The mice in the experiment were injected with geraniol by intramuscular injection and were fed intraperitoneally with minimum lethal dose of MRSA. Then, the survival rate, inflammatory cytokines, oxidative stress factors in serum were measured. These values were used to estimate the bacterial load in different organs and to assess histopathological changes in the lungs, liver and kidneys. Results The above-mentioned two ways of using geraniol could prevent MRSA infection in vivo in mice and showed a significant dose-response relationship. In other words, geraniol significantly decreased the concentrations of inflammatory cytokines and oxidative stress factors in MRSA-infected mice. At the same time, the level of glutathione peroxidase also increased in a dose-proportional relationship. In the group of mice treated with geraniol, their superoxide dismutase levels were significantly higher than those in the vancomycin. After treatment with geraniol, the burden of MRSA decreased. No obvious histopathological abnormalities were found in the liver and kidney of MRSA-infected mice. In addition, geraniol improved the inflammatory changes in the lungs. Conclusion The results indicated that geraniol was a natural substance that could be used as an anti-inflammatory, antioxidant and antibacterial substance to protect mice from MRSA systemic infection. Generally, the research shows that as a natural medicine, geraniol has broad potential in the development and application of antibiotic substitutes.

/pdf/the-inhibitory-efficiencies-of-geraniol-as-an-anti-1zso6rthfd.pdf

The Inhibitory Efficiencies of Geraniol as an Anti-Inflammatory, Antioxidant, and Antibacterial, Natural Agent Against Methicillin-Resistant Staphylococcus aureus Infection in vivo.

Chinese herbs such as Flos magnoliae (FM) and Centipeda minima (CM) can be effective in treating allergic rhinitis (AR). However, there is little research on the therapeutic mechanism of these two drugs acting on AR at the same time. In order to systematically understand the mechanism of action of two drugs acting on AR at the same time, we searched various databases to obtain 31 components and 289 target proteins of FM, 25 components and 465 target proteins of CM. The interaction networks of FM, CM, and AR proteins were constructed by Cytoscape-v3.2.1 software. The core protein of two network intersections was obtained by using Venny 2.1.0. The R platform was used for the core target protein gene ontology (GO) comment analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis. Thirteen common targets and seven acting pathways were obtained. The results of animal experiments showed that FM and CM volatile oil could effectively improve the symptoms of AR by regulating the common targets. In summary, this study successfully explained the potential therapeutic mechanism of FM and CM in the treatment of AR. At the same time, it indicates that the two drugs can be compatible as a new application.

Pharmacology mechanism of Flos magnoliae and Centipeda minima for treating allergic rhinitis based on pharmacology network.

// Na Shen 1 , Jing Peng 1 , Xiong Wang 1 , Yaowu Zhu 1 , Weiyong Liu 1 , Aiguo Liu 2 and Yanjun Lu 1 1 Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China 2 Department of Otorhinolaryngology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China Correspondence to: Aiguo Liu, email: aiguoliu309@163.com Yanjun Lu, email: junyanlu_2000@163.com Keywords: hearing loss (HL), GJB2 , p.V37I, pedigree analysis, meta-analysis Received: February 03, 2017      Accepted: March 19, 2017      Published: April 21, 2017 ABSTRACT Pathogenic variants in the gap junction protein beta-2 ( GJB2 ) gene are the most common cause of hearing loss. Of these, the p.V37I variant of GJB2 has a high allele frequency (up to 10%) in East Asians. Characterization of the phenotypic spectrum associated with p.V37I, as well as the role of this variant in the onset of hearing loss could have a remarkable effect on future diagnostic strategies. Here, we performed a pedigree analysis of unrelated families exhibiting various hearing phenotypes, and then conducted a meta-analysis to comprehensively assess the association between the p.V37I and the risk of hearing loss. Pedigree analyses showed that both homozygous p.V37I variants, as well as compound heterozygous p.V37I with other GJB2 pathogenic variants, contributed to various phenotypes of hearing loss. Meanwhile, meta-analysis demonstrated that, compared with those in the wild type group, both p.V37I homozygotes and compound heterozygous p.V37I variants were at significantly higher risk of developing hearing loss (odds ratios = 7.14 and 3.63; 95% confidence intervals = 3.01-16.95 and 1.38–9.54, respectively). Conversely, heterozygous p.V37I variants alone did not increase the risk of hearing loss. Given the high allele carriage rate of p.V37I (up to 10%) within the general population, our work not only provides information that might influence future genetic screening policies, but also offers insight into clinical risk evaluation and genetic counseling regarding hearing loss.

/pdf/association-between-the-p-v37i-variant-of-gjb2-and-hearing-3b14z0e4h5.pdf

Association between the p.V37I variant of GJB2 and hearing loss: a pedigree and meta-analysis.

The homozygote p.V27I/p.E114G variant of GJB2 is a putative indicator of nonsyndromic hearing loss in Chinese infants

* Equal contributors. Received July 25, 2015; Accepted October 16, 2015; Epub November 15, 2015; Published November 30, 2015 Abstract: GJB2 accounts for more than 80% of recessive forms of hereditary hearing loss (HL); however, the correla- tion between the p.V37I variant of GJB2 and hearing phenotype is controversial. This study aimed to investigate the clinical and epidemiological characteristics of the p.V37I variant in sensorineural hearing loss in Chinese infants (0-3 months). Hearing and gene tests were conducted in 300 infants (aged 0-3 months) with sensorineural hear- ing impairment and 484 normal infants (aged 0-3 months). Among the 300 hearing-impaired infants, 16 (5.33%) exhibited homozygous p.V37I variation and 7 (2.34%) showed a compound-heterozygous p.V37I variation, whereas no homozygous p.V37I (0%) or compound-heterozygous p.V37I (0%) condition was found among the 484 normal in- fants. The hearing impairment ranged from mild to profound in all patients exhibiting the homozygous p.V37I or the compound-heterozygous p.V37I condition, although most patients (61.54%) exhibit mild or moderate HL. Our results indicated that the p.V37I variation of GJB2 mutation is mainly associated with mild or moderate hearing impairment. Therefore, otolaryngologists should also screen the p.V37I variant of GJB2 in patients with mild or moderate HL.

https://www.ijcem.com/files/ijcem0013400.pdf

Original Article Prevalence of p.V37I variant of GJB2 among Chinese infants with mild or moderate hearing loss

Background Geraniol is a monoterpene alcohol that has anti-fungal, anti-cancer and anti-nociceptive properties, but its anti-allergic rhinitis (AR) property is unclear. Methods In this study, the anti-inflammatory role and its possible mechanisms of geraniol in human mast cell line (HMC-1) cells stimulated by inflammatory trigger phorbol 12-myristate 13-acetate plus A23187 (PMACI), as well as in ovalbumin (OVA)-induced AR mice models were investigated. Results PMACI results in a significant increase in the production of proinflammatory cytokines, such as TNF-α, IL-1β, MCP-1, IL-6 and as well as histamine. Geraniol was found to inhibit both TNF-α, IL-1β and IL-6 protein and mRNA expressions at concentrations of 40, 80, 160 μM. In OVA-induced AR models, geraniol treatment was able to suppress AR biomarkers (OVA-specific IgE and IL-1β as well as histamine) and nasal rub scores. Interestingly, p38, a member of the mitogen-activated protein kinase (MAPK) signaling family, was found to be increasingly hypophosphorylated as geraniol dose was increased. Similar decreases in the nuclear level of p65, a member of the nuclear factor kappa B (NF-κB) signaling pathway, were also observed. Conclusion Our data highlights that the anti-inflammatory properties of geraniol on AR-related markers in activated HCM-1 cells and OVA-induced AR models may be mediated through the regulation of the MAPK/NF-κB signaling pathway.

/pdf/geraniol-suppresses-proinflammatory-mediators-in-phorbol-12-4qt81crlq6.pdf

Geraniol suppresses proinflammatory mediators in phorbol 12-myristate 13-acetate with A23187-induced HMC-1 cells.

GJB2 accounts for more than 80% of recessive forms of hereditary hearing loss (HL); however, the correlation between the p.V37I variant of GJB2 and hearing phenotype is controversial. This study aimed to investigate the clinical and epidemiological characteristics of the p.V37I variant in sensorineural hearing loss in Chinese infants (0-3 months). Hearing and gene tests were conducted in 300 infants (aged 0-3 months) with sensorineural hearing impairment and 484 normal infants (aged 0-3 months). Among the 300 hearing-impaired infants, 16 (5.33%) exhibited homozygous p.V37I variation and 7 (2.34%) showed a compound-heterozygous p.V37I variation, whereas no homozygous p.V37I (0%) or compound-heterozygous p.V37I (0%) condition was found among the 484 normal infants. The hearing impairment ranged from mild to profound in all patients exhibiting the homozygous p.V37I or the compound-heterozygous p.V37I condition, although most patients (61.54%) exhibit mild or moderate HL. Our results indicated that the p.V37I variation of GJB2 mutation is mainly associated with mild or moderate hearing impairment. Therefore, otolaryngologists should also screen the p.V37I variant of GJB2 in patients with mild or moderate HL.

Prevalence of p.V37I variant of GJB2 among Chinese infants with mild or moderate hearing loss.

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The homozygote p.V27I/p.E114G variant of GJB2 is a putative indicator of nonsyndromic hearing loss in Chinese infants

Original Article Prevalence of p.V37I variant of GJB2 among Chinese infants with mild or moderate hearing loss

Geraniol suppresses proinflammatory mediators in phorbol 12-myristate 13-acetate with A23187-induced HMC-1 cells.

Prevalence of p.V37I variant of GJB2 among Chinese infants with mild or moderate hearing loss.