Article

Anticancer Activity of Linalool Terpenoid: Apoptosis Induction and Cell Cycle Arrest in Prostate Cancer Cells

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Abstract

Purpose: To evaluate the anticancer activity of linalool against human prostate cancer (DU145) cells. Methods: The anticancer activity of linalool against DU145 cancer cells was evaluated by 3-(4, 5- dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Flow cytometry, using propidium iodide and Annexin V-FITC, was applied to study apoptosis and cell cycle phase distribution. Inverted light microscopy was used to study the effect of linalool on cell morphology and apoptotic body formation in DU145 cells while gel electrophoresis was employed to evaluate the effect of linalool on DNA fragmentation. Results: Linalool induced a dose-dependent as well as time-dependent growth inhibitory effect on DU145 prostate cancer cells. It induced sub-G1 phase growth arrest which led to increase in sub-G0/G1 cell population after treatment with increasing doses of linalool. DNA ladder appeared to be more evident with increasing linalool concentration. However, no DNA fragments were observed in the control groups. It was observed that 4.36, 11.54, 21.88 and 15.54 % of the cells underwent early apoptosis after treatment with 0 (no linalool treatment), 20, 40, and 80 μM of linalool, respectively. Compared to control cells, linalool treatment resulted in the appearance of cell shrinkage along with membrane blebbing which are characteristic features of cell apoptosis. Conclusion: The findings of this study indicate that linalool can be developed as a plant-based chemotherapeutic agent against prostate cancer © Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. All rights reserved.

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... The pharmacological activities of this 10-carbon isoprenoid were evaluated both in vitro and in vivo and were found having sedative, analgesic, anti-inflammatory, antioxidant, antimicrobial, and antitumor properties among others [17,18]. Linalool was reported to induce cell cycle arrest and/or apoptosis in a wide variety of human cancer cells such as prostate [19], leukemia [20,21], cervical [21], breast [22], sarcoma [23] and epithelial ovarian cancer cells [24], however no reports for HCC cells are available to this respect and the mechanisms by which these effects are produced are not completely understood. We have previously shown the ability of linalool to inhibit the mevalonate pathway and cell growth in HepG2 and A549 cells [25], suggesting that its anticancer activity could be due to the inhibition of Ras prenylation, which is essential to promote tumorigenesis [26]. ...
... Linalool has been investigated as a promising chemopreventive and chemotherapeutic agent in several in vitro and in vivo models including liver [25], lung [25], prostate [19], leukemia [20], cervical [21], breast [22], human cancer cells and in tumor-bearing mice [23]. It has been evaluated as a mono-drug agent or combined with conventional drugs, and it was found that antiproliferative concentrations were strongly dependent on cell line in the micro- [19][20][21][22] or milimolar [23][24][25] range. ...
... Linalool has been investigated as a promising chemopreventive and chemotherapeutic agent in several in vitro and in vivo models including liver [25], lung [25], prostate [19], leukemia [20], cervical [21], breast [22], human cancer cells and in tumor-bearing mice [23]. It has been evaluated as a mono-drug agent or combined with conventional drugs, and it was found that antiproliferative concentrations were strongly dependent on cell line in the micro- [19][20][21][22] or milimolar [23][24][25] range. However, the mechanisms by which linalool exerts its antiproliferative effects in HCC cells are not completely understood. ...
Article
Aims: Linalool is a plant-derived monoterpene with anticancer activity, however its mechanisms of action remain poorly understood. The aim of this work was to elucidate the anticancer mechanisms of action of linalool in hepatocellular carcinoma (HCC) HepG2 cells. Main methods: Cell viability and proliferation were determined by WST-1 assay and BrdU incorporation, respectively. Cell cycle analysis was assessed through flow cytometry (FC) and western blot (WB). Apoptosis was determined by caspase-3 activity, TUNEL assay and WB. Reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were analyzed by FC and fluorescence microscopy. Expression of Ras, MAPKs (ERK, JNK and p38) and Akt/mTOR pathways were evaluated by WB. Key findings: Linalool (0-2.5 mM) dose-dependently inhibited cell proliferation by inducing G0/G1 cell cycle arrest, through Cdk4 and cyclin A downregulation, p21 and p27 upregulation, and apoptosis, characterized by MMP loss, caspase-3 activation, PARP cleavage and DNA fragmentation. Low concentrations of linalool (1.0 mM) reduced membrane-bound Ras and Akt activity whereas higher amounts (2.0 mM) triggered mTOR inhibition and ROS generation, in correlation with MAPKs activation and Akt phosphorylation. ROS scavenger N-acetyl-L-cysteine partially rescued HepG2 cell growth and prevented MPP depolarization, ERK and JNK activation. Moreover, specific ERK and Akt phosphorylation inhibitors potentiated linalool anti-cancer activity, pointing Akt and ERK activation as pro-survival mechanisms in response to higher concentrations of linalool. Significance: This report reveals that linalool induces G0/G1 arrest and apoptosis in HepG2 cells involving Ras, MAPKs and Akt/mTOR pathways and suggests that linalool is a promising anticancer agent for HCC therapy.
... Linalool and 1,8-cineole have been evaluated as potential chemopreventive and chemotherapeutic molecules as mono-drug agents or combined with conventional drugs. Numerous in vitro and in vivo studies demonstrated the anticancer potential of these monoterpenes in lung [28], liver [16,28,33], breast [23], ovarian [34], skin [35], cervical [36,37], colon [38,39], sarcoma [40], glioma [41], leukemia [36,42,43], prostate [44,45], oral [46] and gastric [47] cancer cells. Nevertheless, to our knowledge, the mechanisms by which linalool and 1,8-cineole impair the proliferation of NSCLC A549 cells remain unexplored. ...
... In this study, we show that linalool (1.0-2.0 mM) and 1,8-cineole (4.0-8.0 mM) significantly inhibited A549 cell viability without showing inhibitory effects on normal lung WI-38 cells. The effective concentrations of linalool and 1,8cineole reported to inhibit in vitro cancer cell proliferation vary from micromolar (μM) [35,36,39,42,43,45,47] to millimolar (mM) [16,33,34,37,38,40,44,46]. This heterogeneity in sensitivity depends on the cancer cell type but also each cell line evaluated. ...
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Linalool and 1,8-cineole are plant-derived isoprenoids with anticancer activities in lung cancer cells, nevertheless, the cellular and molecular mechanisms of action remain poorly understood. The purpose of this study was to determine the anticancer mechanisms of action of linalool and 1,8-cineole in lung adenocarcinoma A549 cells. Linalool (0–2.0 mM) and 1,8-cineole (0–8.0 mM) inhibited cell proliferation by inducing G0/G1 and/or G2/M cell cycle arrest without affecting cell viability of normal lung WI-38 cells. None of the two monoterpenes were able to induce apoptosis, as observed by the lack of caspase-3 and caspase-9 activation, PARP cleavage, and DNA fragmentation. Linalool, but not 1,8-cineole, increased reactive oxygen species production and mitochondrial membrane potential depolarization. Reactive oxygen species were involved in cell growth inhibition and mitochondrial depolarization induced by linalool since the antioxidant N-acetyl-L-cysteine prevented both effects. Besides, linalool (2.0 mM) and 1,8-cineole (8.0 mM) inhibited A549 cell migration. The combination of each monoterpene with simvastatin increased the G0/G1 cell cycle arrest and sensitized cells to apoptosis compared with simvastatin alone. Our results showed that both monoterpenes might be promising anticancer agents with antiproliferative, anti-metastatic, and sensitizer properties for lung cancer therapy.
... Linalool induces cell cycle arrest in certain cancer types. In human prostate cancer cells (DU145), the use of the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay by Sun et al. [43] demonstrated that linalool at 20, 40 and 80 μM concentrations induced sub-G1 cell cycle arrest and, consequently, DNA damage. Similarly, Chang, Shieh, Chen, Yeh and Dong [49] demonstrated that, in U937 myeloid leukemia cell line, linalool induces cell cycle arrest at G0/G1 phase, which causes a replication suspension, and consequently leads to the accumulation of damaged DNA and activation of tumor suppression mechanisms. ...
... [63] Activation of the Nrf2/HO-1 signaling pathway [64,65] Inhibition of NO production [66] Anticancer and Anti-proliferative Cell cycle arrest [42,43,49] Apoptosis induction [45,47,48,51,52] Activation of immune cells (T helper cells) [44] Prevention of the overexpression of angiogenic factors (VEGF and TGF-β1) ...
Article
The medicinal properties of essential oils from aromatic plants are known since antiquity. Currently, the technological innovation enabled the reinvention of the ancient plant knowledge leading to the identification and extraction of organic compounds present in essential oils. These organic compounds belong mainly to the terpene group and are accountable for the wide range of bioactive properties attributed to essential oils. Linalool (C10H18O), so-called 3,7-dimethyl-1,6-octadien-3-ol, is a monoterpene alcohol broadly present as a major constituent of plant essential oils, particularly lavender and coriander. Linalool per se is non-toxic and, according to recent in vitro and in vivo scientific studies, it has demonstrated to have a comprehensive range of bioactive properties, which can be exploited for pharmaceutic and cosmetic applications. The present review focuses on the anti-inflammatory, anticancer, anti-hyperlipidemic, antimicrobial, antinoceptive, analgesic, anxiolytic, antidepressive and neuroprotective properties of linalool. The advantages of the loading in nanotechnology-based drug delivery systems, with the purpose of enhancing its bioactive properties are also discussed.
... Sun et al. 129 proved that linalool can be an effective anticancer agent to prostate cancer. Using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, they ascertained that linalool exerted a strong cytotoxicity in human prostate cancer cells (DU145). ...
... DNA damage induced after treatment with various concentrations of linalool (0, 20, 40, and 80 μM); cell shrinkage and membrane blebbing observed by inverted light microscopy revealed that linalool induced apoptosis in DU145 cells. The findings of Sun et al. 129 suggested that linalool exerted an anticancer activity in prostate cancer cells by inducing cell cycle arrest and apoptosis in a dose and time dependent manner. In fact in a more recent paper, the activity of L. angustifolia essential oil and linalool on prostate cancer cell models was also researched. ...
... Numerous studies have reported the diverse biological activities of LIN (27)(28)(29)(30)(31). While most of these studies were conducted in vitro or in animal models using different administration methods (i.e. ...
... Alkaloids, on the other hand, exhibit various apoptotic inductions, impacting the delicate balance between pro-apoptotic and anti-apoptotic signals within cancer cells [56]. Moreover, terpenoids exert their effects through multiple mechanisms, including interference with cell cycle progression, induction of oxidative stress, and the modulation of signaling pathways associated with apoptosis [57,58]. ...
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Please cite this article as: Foroughi-Gilvaee M. R., Martirosyan D., Mashayekhnia M. J., Maadi M. A., Sarvendani M. R. R., Maghsoumi M. Exploring the potential of bioactive compounds in preventing cancer growth and progression: A comprehensive review. ABSTRACT Cancer stands as a prominent global cause of mortality, with a noteworthy surge in related deaths in recent years. Over the past decade, several bioactive compounds have emerged as potent agents in impeding the relentless advance of cancer. Notably, numerous studies highlight the efficacy of natural plant-derived bioactive compounds in augmenting chemotherapy outcomes and mitigating adverse drug effects associated with chemotherapeutic agents. This comprehensive review investigates the anticancer effects of three types of bioactive compounds: polyphenols, alkaloids, and terpenoids. It elucidates their mechanisms of action and consolidates evidence from preclinical studies. Furthermore, this review delves into the molecular mechanisms through which these active compounds may manifest their anticancer properties, drawing insights from cell and animal-based studies.
... Research shows plant secondary metabolites are proved to be good anti-cancer agents in in-vitro condition, either independently or synergistically with other compounds through regulation of metabolic and signaling pathways, inhibition of enzymes vital for cancer progression, angiogenesis, microtubule assembly and inducing apoptosis [42,43]. Terpenoids  Induces apoptosis and arrest cell cycle regulation in prostate cancer cell [44] Flavonoids  Induces cell cycle arrest, induction of apoptosis and differentiation, inhibition of angiogenesis [47] Glycosides  Demonstrated potent Cytotoxic effects against various cancer cell lines in initial preclinical studies [49] Quinones  Acts as anti-mitotic agents and tubulin polymerization inhibitor and exhibits cytotoxicity [50] ...
Chapter
Chemical, Material Sciences & Nano technology book series aims to bring together leading academic scientists, researchers and research scholars to exchange and share their experiences and research results on all aspects of Chemical, Material Sciences & Nano technology. The field of advanced and applied Chemical, Material Sciences & Nano technology has not only helped the development in various fields in Science and Technology but also contributes the improvement of the quality of human life to a great extent. The focus of the book would be on state-of-the-art technologies and advances in Chemical, Material Sciences & Nano technology and to provides a remarkable opportunity for the academic, research and industrial communities to address new challenges and share solutions. The content of the book is as follows
... Linalool exhibited anti-cancer properties against several cancer cells, including DU145 (Sun et al., 2015) and HepG2, A549, SW620, T-47D (Chang & Shen, 2014), RPMI 7932 (Cerchiara et al., 2015), HeLa and U937 (Chang et al., 2015). Moreover, This compound has been reported to have anti-inflammatory activities in LPS-stimulated RAW 264.6 cells (Huo et al., 2013) and BV2 microglia cells . ...
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In the present study, the differences between the chemical compositions of the essential oils obtained from the leaves and flowers of two cultivars of M. cajuputi collected from Moc Hoa district, Long An province. By using Gas Chromatography-Mass Spectrometry, a total of 105 components have been identified in the essential oils of four samples of two M. cajuputi cultivars such as “Tràm gió” leaves, “Tràm gió” flowers, “Tràm cừ” leaves and “Tràm cừ” flowers. The Agglomerative Hierarchical Cluster (AHC) and Principal Component Analysis (PCA) were performed to show the similarities/dissimilarities in chemical compositions among the four studied samples. As a result, the components of the essential oils of four studied samples were divided into two clusters. Cluster I included two samples such as “Tràm gió” leaf and “Tràm gió” flower with high presence of 1,8-cineole (35.12 and 17.69%), linalool (3.31 and 5.03%), (R)-α-terpinyl acetate (9.17 and 8.1%). Cluster II comprised “Tràm cừ” leaf and “Tràm cừ” flower with the high concentration of α-pinene (9.87 and 12.19%), γ-terpinene (10.48 and 11.3%), p-mentha-2,4(8)-diene (8.8 and 12.7%).
... Previously, apoptotic effect of linalool on breast (MCF-7 and MDA-MB-231) and prostate (22Rv1 and DU145) cancer cell line was reported [27][28][29]. Therefore, not only linalool but also combination of linalool and linalool acetate is an apoptotic inducer in cancer cells. ...
Article
Grapefruit mint (Mentha suaveolens × piperita) is a hybrid, perennial, and aromatic plant widely cultivated all over the world and used in the food, cosmetics, and pharmaceutical industries mostly for its valuable essential oil. Herein, we evaluated the anticancer activity of the grapefruit mint essential oil, cultivated in Iran. For the chemical composition analysis of essential oil, GC-MS was used. MTT assay was utilized for assessing the cytotoxic activity of the essential oil. The type of cell death was determined by annexin V/PI staining. Essential oil effect on the expression of maternally expressed gene 3 (MEG3), a regulatory lncRNA involved in cell growth, proliferation, and metastasis, was studied using qRT-PCR. Linalool (43.9%) and linalool acetate (40.1%) were identified as the dominant compounds of essential oil. Compared with MCF-7, the MDA-MB-231 cells were more sensitive to essential oil (IC50 = 7.6 µg/ml in MCF-7 and 5.9 µg/ml in MDA-MB-231 after 48 h). Essential oil induced cell death by apoptosis. Wound healing scratch assay confirmed the anti-invasive effect of essential oil. In addition, essential oil upregulated the tumor suppressor MEG3 in breast cancer cells. These results provide new insights into grapefruit mint essential oil potential application as an anticancer adjuvant in combination treatments for breast cancer patients.
... Numerous therapeutic approaches, either through positively controlling/regulating compounds against Jab1, were conducted using CB Dock and Patch Dock. Terpenoids have received more attention as a result of their ability to induce apoptosis in cancer cells of LNCaP (prostate male cancer cells), human breast cancer (MDAMB231) cells, and HT-29 (human colon cancer cells) [34][35][36] . Although screened terpenoids are widely established for their anticancer properties in HeLa cells, their Jab1 inhibitory potential in breast cancer cells is unknown. ...
Article
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Jab1 (c-Jun activation domain-binding protein-1) overexpression has been extensively linked to cancer development (or metastasis) in various malignancies by positively regulating cancer cell proliferation or inactivating several tumor suppressors. Recent research has focused on utilizing plant products to target crucial elements of dysregulated signaling pathways to elucidate a potent cancer therapeutic approach. Terpenoids have shown significant anti-inflammatory and anti-cancerous properties in a broader range of carcinomas by inducing apoptosis. Through an extensive literature search, we have selected only those terpenoids (from the NPACT database) that have not been explored against Jab1 (CSN5, COP9 signalosome subunit 5) in breast cancer for our research study. We have used two docking servers, PATCH DOCK, and CB DOCK, to find the binding interaction between selected terpenoids and Jab1. Further, we have also used SWISS ADME to investigate the pharmacokinetics of selected ligands. Amongst all selected ligands, lutein (belongs to the xanthophylls class) has displayed maximum binding energy in both CB Dock and Patch Dock analysis. Hence, our preliminary in silico results have shown lutein as the potent lead candidate for developing a better drug against breast cancer. However, more in silico and in vitro studies are still needed to validate the inhibitory potential of lutein terpenoid against Jab1 in breast cancer.
... Iwasaki et al. (2016) show that linalool induces apoptosis of human colon cancer cells via cancer-specific oxidative stress. In prostate cancer cells, linalool treatment result in the appearance of cell shrinkage and membrane blebbing, which are characteristic features of cell apoptosis (Sun et al. 2015). Repellent activity of linalool was evaluated by Müller et al. (2009). ...
Article
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Lavender essential oil is economically important and widely used in aromatherapy perfumery, food industry and pharmacy. Bulgaria is a global leader in lavender cultivation overtaking countries such as France, UK, China, India, and Spain during the last few years. The aim of this research is: 1) to characterize a lavender essential oil sample obtained from agricultural plantation near Pomorie, Bulgaria; 2) to perform descriptive statistical test based on a data set of 13 samples available in 4 publications, 3) to compare the varieties regarding the quantity of the most important components such as linalool and linalyl acetate 4) to summarize the pharmacological effects of the main components. As a result of GS/MS analysis of the essential oil sample obtained from agricultural plantation near Pomorie, we identified 44 compounds. The major constituents were linalyl acetate (27.5%) linalool (24.1%), E -β-ocimene (7.0%), terpinen-4-ol (5.1%) caryophyllene (4.5%), carvacrol (4.4%), lavandulyl acetate (3.5%), Z -β-farnesene (3.3%), and - Z -β-ocimene (3.2%). Linalool and linalyl acetate are the main ingredients based on which the quality of the essential oil is evaluated. In the studied samples they fluctuated between varieties depending on the year of extraction and the locations of origin in Bulgaria. Some varieties were characterized by a more stable ratio of linalool – linalyl acetate, compared to others. The main other components of our sample as well as the other examined Bulgarian samples fit the standards according to the requirements of ISO (2002) and the of European Pharmacopoeia (10 th edn., Council of Europe 2020) with few exceptions. Lavender oil has numerous pharmacological applications based on its anxiolytic, sedative, antioxidant, anti-inflammatory, antitumor and antimicrobial activities. Although linalool and linalyl acetate largely contribute to these effects, the overall efficacy of lavender oil is proven to be due synergistic relationships between the components.
... Several studies in vitro and in vivo have shown that thymol and carvacrol induced apoptosis, cytotoxicity, cell cycle arrest, and antimetastatic activity, and also displayed different antiproliferative effects and inhibition of signalling pathways (Sampaio et al. 2021;Islam et al. 2019;Fan et al. 2015). Linalool, a monoterpene found in many aromatic plants, has also demonstrated a high potential as an antitumoural compound since it promotes autophagy and apoptosis of tumour cells (prostate, breast, colorectal, and liver) either in mice or in vitro using different cell lines Iwasaki et al. 2016;Pan and Zhang 2019;Chang and Shen 2014;Cerchiara et al. 2015;Xiu-Bin et al. 2015). In addition to its antitumoural effects, linalool and its derivatives also have anti-inflammatory activity since they can relieve the symptoms of inflammation by affecting the nuclear translocation of NF-κB and related pathways (Petrović et al. 2019;Ma et al. 2015). ...
Chapter
Terpenes are the largest and most diverse group of naturally occurring compounds found in plants. They can be classified according to the number of isoprene units, the most common being monoterpenes (C10), sesquiterpenes (C15), diterpenes (C20), and triterpenes (C30). Besides being the principal constituents of essential oils and playing fundamental roles in plants, many terpenes are extensively used in pharmaceutical and industrial applications ranging from flavours to fragrances and medicines. Several studies have already demonstrated the diversity of terpenes’ biological properties, including cancer chemopreventive effects, antimicrobial, antiviral, analgesic, anti-inflammatory, antifungal, antiparasitic, and other activities. This chapter compiles the various terpenes isolated from plants, their sources, biological activities and beneficial health effects, mechanism of action, extraction and applications, and the future perspective for using the terpenes as lead molecules in several areas of the industry.
... Previous studies have indicated that β-pinene and eucalyptol exert significant cytotoxic effects on different tumor cells [21,22]. However, it should not be ruled out that other dominant compounds such as terpinolene and linalool have also demonstrated strong anticancer effects in in vitro cancerous cells thereby indicating potential synergies among essential oil components [23,24]. ...
Article
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Hedychium spicatum is an essential oil bearing plant extensively used in the traditional system of medicine in several countries. Previous research has revealed H. spicatum essential oil (HSEO) to exhibit anti-tumor activity, although the mechanism of action is still unknown. Therefore, the current study was designed to carry out a comprehensive characterization of HSEO and evaluate the chemotherapeutic potential of HSEO against cancerous cells. The volatile constituents of HSEO was determined by one-dimensional gas chromatography with time-of-flight mass spectrometry (GC-TOFMS) and two-dimensional gas chromatography with time-of-flight mass spectrometry (GCxGC-TOFMS). In total, 193 phytocompounds could be detected, out of which 140 were identified for the first time. The major phytoconstituents detected by GCxGC-TOFMS were β-pinene (10.94%), eucalyptol (6.45%), sabinene (5.48%) and trans-isolimonene (5.00%). GCxGC-TOFMS analysis showed two and half fold increase in the constituents over GC-TOFMS due to better chromatographic separation of constituents in the 2nd dimensional column. HSEO was tested for in vitro cytotoxic activity against cancerous (PC-3, HCT-116 and A-549) and normal (3T3-L1) cell, with HSEO being most selective for prostate cancer cell (PC-3) over non-tumorigenic fibroblast (3T3-L1) cell. HSEO treatment inhibited the colony formation ability of PC-3 cells. HSEO treatment caused apoptotic cell death and cell cycle arrest at G2/M and S phase in PC-3 cells. HSEO induced apoptosis via intracellular ROS accumulation, mitochondria depolarization and increased caspase-3, 8, and 9 levels in PC-3 cells. Additionally, HSEO treatment led to a decrease of Bcl-2 and Bcl-xL and increase of Bax and Bak protein levels. Overall, results from this study highlighted the anticancer potential of H. spicatum essential oil, which could be considered as a new agent for treating prostate cancer.
... Cheng et al., 2017;Zhao et al., 2017;Marzali, 2017). Dalam penelitian Marzali (2017) dan Sun et al. (2015) disebutkan bahwa senyawa linalool menunjukkan aktivitas antikanker pada sel kanker prostat pada manusia bergantung pada dosis linalool yang dikonsumsi (Tabel 5). ...
Article
Ketumbar (Coriandrum sativum L.) merupakan salah satu tanaman rempah yang telah banyak dimanfaatkan sebagai penyedap dalam makanan, parfum, dan obat tradisional. Di indonesia, biji ketumbar banyak dimanfaatkan namun produktivitasnya sangat rendah. Bagian daunnya belum banyak digunakan dalam bidang pangan dan hanya sebagai salad, saus, atau hiasan sehingga perlu pemanfaatan lebih luas dan kajian lebih lanjut mengenai potensi pada daun ketumbar sebagai bagian tanaman ketumbar yang ekonomis, mudah didapatkan, memiliki sifat fungsional, dan belum banyak dimanfaatkan di masyarakat. Metode yang digunakan yaitu kajian literatur dengan pencarian jurnal pada database jurnal terindeks dan institusi terpercaya. Kajian literatur ini bertujuan untuk mempelajari potensi yang terdapat pada minyak atsiri daun ketumbar sebagai pendukung pangan fungsional sehingga dapat dimanfaatkan secara lebih luas di masyarakat. Minyak atsiri daun ketumbar memiliki potensi untuk dikembangkan sebagai pendukung pangan fungsional seperti permen jeli, cookies, dan jus buah. Kandungan senyawa bioaktif minyak atsiri daun ketumbar seperti linalool memiliki manfaat sebagai antidiabetes, antikolesterol, antikanker, dan antimikroba sehingga minyak atsiri daun ketumbar dapat dimanfaatkan secara luas di masyarakat.
... Linalool, another geranium component, can also cause cell cycle halt in certain cancers,186 demonstrated that linalool at 20, 40, and 80 μM concentrations triggered sub-G1 cell cycle arrest, resulting in DNA damage, in human prostate cancer cells (DU145) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Likewise, a recent article confirmed linalool's lethal activity in DU145 and PC-3 (human Caucasian prostate cancer) prostate cancer cells.187 ...
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Pelargonium graveolens (PG) is a popular medicinal plant, widely used in Africa for centuries to treat various diseases. Because of its wide exploitation, the therapeutic studies of P. graveolens keep penetrating. This research engulfs a comprehension of all previous studies related to this medicinal herb, where it summaries and evaluates the traditional uses, the botany, the phytochemistry, the pharmacology, and the toxicology of P. graveolens. A literature review was conducted through the classic books of herbs, medicine, PhD papers, and online scientific databases, searching up to January 2022. This review analyzes all literature on the research subject. Our main findings are: (1) more than 290 biochemical components have been identified from P. graveolens, counting terpenoids, flavonoids, steroids, alkaloids and other composites. (2) Terpenoids are the most significant biologically active matter detected in this plant. (3) Extracts and compounds of P. graveolens exert a wide range of pharmacological effects. Study of the plant’s toxicological effects has also been restricted as well. P. graveolens has potential in the treatment of numerous ailments, particularly cancers and diabetes. Current investigations confirmed that much traditional uses of P. graveolens has been corroborated by current studies. However, contemporary reports on its pharmacological impacts are not deep enough, and its underlying mechanisms for the cure of tumours and diabetes should be further elucidated.
... These results confirmed the compounds mentioned above as the main constituents of laurel hydrolate [64,93] and essential oil [94,95] in varying amounts. It is considered that methyl eugenol is a limiting factor that allows the use of laurel essential oil in food applications [96] and, along with linalool, exhibits antioxidant, antimicrobial, anti-inflammatory and anticancer properties [94,[97][98][99][100][101][102] and various effects on the central nervous system [98,103,104]. These compounds are the primary compounds responsible for the aroma of laurel leaves [105]. ...
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Functional beverages based on herbal extracts are highly demanded products due to the presence of bioactives with promising health benefits and interesting and characteristic sensory properties. Mediterranean medicinal and aromatic herbs contain a wide range of bioactives (non-volatile polyphenols, volatile terpenes) that are important constituents of herbal extracts and essential oils. The antioxidant capacity and potential health benefits of these bioactives could be associated with their synergistic effects. Therefore, this study aimed to characterize the non-volatile and volatile bioactives of sage (Salvia officinalis L.), wild thyme (Thymus serpyllum L.) and laurel (Laurus nobilis L.) aqueous extracts and their two- and three-component mixtures as well as their antioxidant capacity. The content of total phenols, flavonoids, hydroxycinnamic acids and flavonols was determined spectrophotometrically. Individual polyphenols were analyzed by LC-MS/MS, the volatiles were analyzed by HS-SPME/GC-MS, and the antioxidant capacity was analyzed by ORAC and DPPH assays. The results showed that aqueous extracts of all examined herbs and their mixtures contained a high content of phenolic compounds ranging from 0.97 to 2.79 g L−1 of the sample, among which the most common were flavonols. At the same time, mono- and sesquiterpenes were the main volatiles. All extracts showed high antioxidant capacity, especially L. nobilis (781.62 ± 5.19 μmol TE mL−1 of the sample in the DPPH assay; 1896.10 ± 8.77 μmol TE mL−1 of the sample in the ORAC assay) and the two-component mixture of L. nobilis and T. serpyllum (679.12 ± 5.19 μmol TE mL−1 in the DPPH assay; 1913.38 ± 8.77 μmol TE mL−1 in the ORAC assay). Mixtures of herbal extracts have been shown to possess additive or synergistic effects, consequently contributing to higher antioxidant capacity. Therefore, two-component mixtures of herbal extracts showed promising potential for the production of functional beverages.
... Using an in vitro cell culture assay, Cherng and colleagues also demonstrated anti-proliferative activity of linalool towards bladder (J82), lung (H661 and H520), cervix (HeLa), stomach (AGS), skin (BCC-1/KMC), bone (U2OS), mouth (OSCC-1/KMC), and kidney (RTCC-1/KMC) carcinoma cell lines [54]. Furthermore, linalool treatment was also found able to suppress the growth of breast (T-47D), colorectal (SW620), liver (Hep G2), lung (A549), and prostate (DU145, 22Rv1) cancer cell lines [55][56][57]. In addition to M. alba, linalool is also found present in several other plants. ...
Article
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Michelia × alba (M. alba) is a flowering tree best known for its essential oil, which has long been used as a fragrance ingredient for perfume and cosmetics. In addition, the plant has been used in traditional medicine in Asia and dates back hundreds of years. To date, there is a limited number of publications on the bioactivities of M. alba, which focused on its tyrosinase inhibition, antimicrobial, antidiabetic, anti-inflammatory, and antioxidant activities. Nevertheless, M. alba may have additional unexplored bioactivities associated with its bioactive compounds such as linalool (72.8% in flower oil and 80.1% in leaf oil), α-terpineol (6.04% flower oil), phenylethyl alcohol (2.58% flower oil), β-pinene (2.39% flower oil), and geraniol (1.23% flower oil). Notably, these compounds have previously been reported to exhibit therapeutic activities such as anti-cancer, anti-inflammation, anti-depression, anti-ulcer, anti-hypertriglyceridemia, and anti-hypertensive activities. In this review paper, we examine and discuss the scientific evidence on the phytochemistry, bioactivities, and traditional uses of M. alba. Here, we report a total of 168 M. alba biological compounds and highlight the therapeutic potential of its key bioactive compounds. This review may provide insights into the therapeutic potential of M. alba and its biologically active components for the prevention and treatment of diseases and management of human health and wellness.
... Taxol is a terpenoid used to treat ovarian and breast cancer [70] and thus has become essential in the medical field. Linalool, a terpenoid found in many plants, especially in flowers and spices, has been reported to show anticancer activity in DU145 cell lines by arresting the cell cycle at sub-G1 phase and by inducing apoptosis at IC 50 value 10.5 µM at 24 hours exposure [71]. On the other hand, the plant Capparis decidua ( Table 1) of desert region has induced cytotoxicity in A549 cancer cells at a very low IC 50 value of 1 µM. ...
Article
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Cancer a death havoc is increasing at an alarming pace globally. There is a need to explore novel chemicals having anticancerous potential for its treatment with minimal side effects. Natural compounds obtained from plants have less toxic properties and can be proved as a better medication against this lethal disease. Thus, the secondary metabolites having anticancer properties found in plants, fruits, and vegetables are being persistently evaluated for research in cancer treatment like anticancer drugs- vinblastine, vincristine and taxol which are derived from plants. This review summarizes the anticancer properties of chemical repertoires of plants inhabiting the hot arid regions present in India against various cancer cell lines like HepG2, MCF7, PC3, HT116 etc. The mechanism of action of flavonoids in the induction of apoptosis through suppression/promotion of various factors including Ras-ERK and PI3K-Akt signaling pathways and genes mainly such as Bax, Bcl-2, p53 involved in the proliferation of cancer cells play emphatically in combating the extent of the disease by promoting apoptosis in cancer cells. The insight about the reported mechanisms will open further avenues of the anticancer potential of novel secondary metabolites.
... In addition, the GC-MS analysis revealed that several terpenes presented on Tagetes extracts have been reported with attractive anticancer properties. Considering the monoterpenes, the linalool exhibited an antiproliferative effect on human melanoma cells (RPMI 7932) at [45,46] and the geraniol and geranyl acetate were reported due to their ability to trigger apoptosis, DNA damage and cell cycle arrest on colon cancer cells (Colo-205) at IC 50 values of 20 and 30 μM, respectively. [47] Similarly, the sesquiterpenes as spathulenol were disclosed effective against the ovarian cancer cell line (OVCAR-3) at CI 50 = 49.30 ...
... At doses of 20, 40 and 80 mM, the compound induced sub-G1 cell cycle arrest, and therefore DNA damage. 169 Furthermore, linalool has been demonstrated to possess potential anti-cancer properties against some cancer cell lines, including HepG2 (IC 50 156 Finally, Dlimonene has been proven to have bioactivity against breast cancer. Aer limonene intervention, cyclin D1 expression was reduced by 22% in tumor tissue, while its effect was hardly found in Ki67 tissue, cleaved caspase-3 expression, serum leptin, adiponectin, TGF-b1, insulin-like growth factor binding protein-3 (IGFBP-3) and interleukin-6 (IL-6) levels. ...
Article
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Alpinia Roxb. is the largest genus of the Zingiberaceae family. A large number of Alpinia species has been used as food and traditional medicines. Alpinia essential oils have been studied for their chemical profiles, in which 1,8-cineole, b-pinene, a-pinene, b-myrcene, camphor, g-terpinene, p-cymene, geraniol, a-fenchyl acetate, ocimene, methyl cinnamate, and b-caryophyllene have been found to be the major compounds. Essential oils isolated from Alpinia plants have been reported to have antimicrobial, cytotoxic, antioxidant, anti-inflammatory, anti-asthmatic, tyrosinase inhibitory, insecticidal, and larvicidal activities and slimming aromatherapy. In this review, the comprehensive information regarding the volatile components of various Alpinia plants, the bioactivities of Alpinia essential oils and their major compounds are provided.
... Nature is the big source of natural medicine and compounds derived from plants, animals, marines, and microbes [13][14][15][16][17][18]. Among them, plants provide many novel anticancer compounds [19] such as alkaloids [20,21], flavonoids [22,23], glycosides [24], saponins, tannins [25], and terpenoids [26] which are found from a plant having antioxidant and anticancer properties in a various cancer cell line, especially in a liver cancer cell line. HCC development is a multistep process that may include the alteration in host gene expression, DNA methylation, loss of heterozygosity, and point mutation, but still, we are lacking to determine the rate limiting step for initiation and progression of HCC [27]. ...
Article
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Hepatocellular carcinoma (HCC) is due to poor prognosis and lack of availability of effective treatment. Novel therapeutic strategies will be the fine tuning of intracellular ROS signaling to effectively deprive cells of ROS-induced tumor-promoting events. This review discusses the generation of ROS, the major signaling their modulation in therapeutics. We explore some of the major pathways involved in HCC, which include the VEGF, MAPK/ERK, mTOR, FGF, and Ser/Thr kinase pathways. In this review, we study cornerstone on natural bioactive compounds with their effect on hepatocarcinomas. Furthermore, we focus on oxidative stress and FDA-approved signaling pathway inhibitors, along with chemotherapy and radiotherapy enhancers which with early evidence of success. While more in vivo testing is required to confirm the findings presented here, our findings will aid future nonclinical, preclinical, and clinical studies with these compounds, as well as inspire medicinal chemistry scientists to conduct appropriate research on this promising natural compound and their derivatives.
... Arora et al. (2016) have also reported fungal extractinduced sub-G1 phase arrest. Interestingly, anticancer agents (linalool and subamolide E) also induce cell death by leading to the activation of DNA damage checkpoints and sub-G1 phase cell cycle arrest (Wang et al., 2011;Sun et al., 2015). The fungal secondary metabolic profiling remains uncharacterized to recognize the bioactive compounds contributing to the cytotoxic and apoptotic activities exhibited by BpME and BpCE from B. petrensis. ...
Article
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Hypersaline environments are known to support diverse fungal species from various orders. The production of secondary metabolites is one of the strategies that fungi adopt to thrive under such extreme environments, bringing up the stress tolerance response. Some such unique secondary metabolites also exhibit clinical significance. The increasing prevalence of drug resistance in cancer therapy demands further exploration of these novel bioactive compounds as cancer therapeutics. In the present study, a total of 31 endophytic fungi harboring inside red, green, and brown marine algae have been isolated and identified. The maximum likelihood analysis and diversity indices of fungal endophytes revealed the phylogenetic relationship and species richness. The genus Aspergillus was found to be the dominating fungus, followed by Cladosporium spp. All the isolated endophytic fungal extracts were tested for their cytotoxicity against HeLa and A431 cancer cell lines. Nine isolates were further analyzed for their cytotoxic activity from the culture filtrate and mycelia extract. Among these isolates, Biscogniauxia petrensis showed potential cytotoxicity with CC 50 values of 18.04 and 24.85 μg/ml against HeLa and A431 cells, respectively. Furthermore, the media and solvent extraction optimization revealed the highest cytotoxic active compounds in ethyl acetate extract from the potato dextrose yeast extract broth medium. The compound-induced cell death via apoptosis was 50–60 and 45% when assayed using propidium iodide-live/dead and loss of mitochondrial membrane potential assay, respectively, in HeLa cells. Four bioactive fractions (bioassay-based) were obtained and analyzed using chromatography and spectroscopy. This study reports, for the first time, the cytotoxic activity of an endophytic fungal community that was isolated from marine macro-algae in the Rameswaram coastal region of Tamil Nadu, India. In addition, B. petrensis is a prominent apoptotic agent, which can be used in pharmaceutical applications as a therapeutic.
... Linalool essential oil is prepared through chemical synthesis. 6 Several studies have suggested the anticancer activity of linalool against a wide range of cell lines; 7,8 however, its use is restricted by the high toxicity of the essential oil. 9 Recently, glutathione (GSH) has emerged as s popular biodegradable polymer that is used in the preparation of GSH-coated nanoparticles. ...
Article
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Background Linalool is a monoterpene compound with various potential therapeutic applications in several medical fields. Previous studies have indicated the activity of linalool against cell lines; however, its high level of toxicity restricts its use. The aim of this study was to design and manufacture compounds with a novel structure that can be used for loading linalool, to reduce its toxicity and improve its reachable ability. Methods We synthesized and characterized a new molecule for loading linalool onto gold nanoparticles (GNPs) capped with glutathione and conjugated with a CALNN peptide. Linalool was loaded onto the GNPs via the reaction of the surface groups of both linalool and the GNPs. Moreover, the target peptide could be loaded onto the surface of the GNPs via a chemical reaction. The cytotoxic effects of linalool–GNP (LG) and linalool–GNP–CALNN peptide (LGC) conjugates against ovarian cancer cells were investigated, as were the possible mechanisms underlying the induction of apoptosis. Results Our findings illustrated the significant antiproliferative effect of LG and LGC on SKOV-3 cells. The cytotoxicity assay demonstrated that LG and LGC were selectively toxic in cancer cells and induced apoptosis by activating caspase-8, the p53 protein, and various proteins involved in apoptosis. The present data demonstrated that LG and LGC have a high therapeutic potential and should be given particular consideration as anticancer drug-delivery systems, as LG and LGC were remarkably more cytotoxic against a cancer cell line than were linalool and GNPs alone. Conclusion We concluded that LG and LGC are promising compounds that can be used for treating ovarian cancer (SKOV-3) cells via the induction of apoptosis through extrinsic and intrinsic pathways.
... Other than this, another study demonstrated that 29 protected against CS-induced lung inflammation through inhibiting CS-induced NF-κB activation [37]. e anticancer activity of linalool (29) against human prostate cancer (DU145) cells was evaluated by the MTT assay and it was observed that 4.36%, 11.54%, 21.88%, and 15.54% of the cells underwent early apoptosis after treatment with 0, 20, 40, and 80 μM of 29, respectively [38]. In addition, Okumura et al. confirmed that terpinolene (10) could markedly reduce the expression of protein kinase AKT, which can mediate cell proliferation and survival signals, and contribute to cancer progression [39]. ...
Article
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Cinnamomum is a genus of the family Lauraceae, which has been recognized worldwide as an important genus due to its beneficial uses. A great deal of research on its phytochemistry and pharmacological effects has been conducted. It is noteworthy that terpenoids are the characteristic of Cinnamomum due to the peculiar structures and significant biological effects. For a more in-depth study and the better use of Cinnamomum plants in the future, the chemical structures and biological effects of terpenoids obtained from Cinnamomum were summarized in the present study. To date, a total of 181 terpenoids with various skeletons have been isolated from Cinnamomum . These compounds have been demonstrated to play an important role in immunomodulatory, anti-inflammatory, antimicrobial, antioxidant, and anticancer activities. However, studies on the bioactive components from Cinnamomum plants have only focused on a dozen species. Hence, further studies on the potential pharmacological effects need to be conducted in the future.
... Considering the close relationship between DNA damage and cancer development, the combination of antigenotoxic with cytotoxic activities of the mastic water constituents would suggest their potential anti-cancer properties and application in anticancer medicinal treatments. Indeed, several mastic extracts or mastic constituents have been shown to exert anti-cancer activities, such as reduced proliferation (cells)/growth (tumors), increased apoptosis, blockage in G1 phase of the cell cycle, and suppressed NF-κB activity, in vitro and in vivo against different tumors or cancer cells [35][36][37][38][39][40][41][42][43][44][45] . ...
Article
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Chios mastic products are well-known for their broad applications in food industry, cosmetics, and healthcare since the antiquity. Given our recent finding that Chios mastic water (CMW) exerts antigenotoxic action, in the present study, we evaluated the genotoxic as well as the antigenotoxic potential of the four major compounds of CMW, namely, verbenone, α-terpineol, linalool, and trans-pinocarveol. The cytokinesis block micronucleus (CBMN) assay in cultured human lymphocytes and the Drosophila Somatic Mutation And Recombination Test (SMART), also known as the wing spot test, were employed. None of the four major CMW's constituents or their mixtures showed genotoxic or recombinogenic activity in either of the assays used. Co-treatment of each of the constituents with MMC revealed that all except trans-pinocarveol exerted antigenotoxic potential. Moreover, co-administration of verbenone with linalool or α-terpineol presented statistically significant reduction of MMC-induced mutagenicity. In conclusion, the major CMW constituents were shown to be free of genotoxic effects, while some exerted antigenotoxic activity either alone or in combinations, suggesting synergistic phenomena. Our results provide evidence on the key antigenotoxicity effectors of the plant extract CMW.
... Linalool, the major alcohol in leaf oil (23.25 %), could be responsible for the oil's strong cytotoxic activity, where it was previously reported to have a potent cytotoxic effect against human prostate cancer (DU145) cells 30 , leukemia cells, cervical cancer cells 31 and breast carcinoma 32 . In addition, terpinen-4-ol, present at 8.33 % in the leaf oil, was also previously reported to have cytotoxic effects against colorectal, pancreatic, prostate and gastric cancer cells 33 , lung cancer cells 34 and human M14 melanoma cells 35 . ...
Article
The chemical composition of essential oils extracted by hydro-distillation of leaves, unripe and ripe fruit peels of Citrus reshni hort. ex Tanaka was studied using GC-MS analysis. The antiviral activity against avian influenza A (H5N1) was tested using Plaque reduction assay. Limonene was the major component in fruit peel oils whereas sabinene followed by linalool were the major components of the leaf oil. Percentage of limonene in fruit peel oil increased by ripening which influenced the biological activity of the oil. The peel oils (unripe and ripe) showed moderate inhibition of (H5N1) virus at concentration (2.5 μl/ml) where the ripe peel oil showed a higher selectivity index (8.716), on the other hand the leaf oil showed weak inhibition of (H5N1) virus and displayed high cytotoxicity which suggests other medicinal uses. The antiviral activity could be attributed to a synergistic effect between limonene; major component in peel oil, and other minor components. This study was the first to investigate the antiviral activity of C. reshni essential oils, as well as, the changes in composition of C. reshni peel oil during ripening and its effect on biological activity.
... Linalool possesses an anti-angiogenic activity thus having a role in treating or even preventing the progression of cancer cells [75]. It has been shown to be a promising agent against prostate cancer [76], endothelial ovarian carcinoma [77], colon cancer [78], leukaemia and cervical cancer [79]. Moreover, Ravizza, Gariboldi [80] reported that linalool reverses the doxorubicin resistance in human breast adenocarcinoma cells via enhancing the sensitivity of these carcinogenic cells towards the cytotoxic activity of doxorubicin. ...
Thesis
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The replacement of synthetic conventional compounds by natural ingredients; whether in medicine, food, or cosmetics; has been increasingly requested by consumers, especially since the last decade. Terpenes in general and monoterpenes in particular are secondary metabolites in plants, and they may be a promising natural alternative. Monoterpenes, the main constituents of plants’ essential oils, are odorous compounds that play a significant ecological role in plant evolution. They are primarily utilized by the flavour and fragrance industries due to their characteristic aroma. In addition, a series of representatives belonging to this substance class are antimicrobial, anti-inflammatory, antiseptic, and anticancer agents; or elicit other therapeutic effects. Thereby, acyclic monoterpene alcohols, mainly linalool, geraniol, nerol, and citronellol, are primarily in the focus of scientific research. Besides their aromatic character and their role in aromatherapy, they induce a series of pharmacological and physiological effects. In view of the latter, their metabolic pathways have been previously investigated in both plants and animals. Linalool and geraniol, for example, are metabolized giving 8-hydroxy and 8-carboxy derivatives; i.e. undergoing oxidation at C-8. However, these metabolites have not been tested in terms of odour or other physiological activities. Furthermore, no studies are at hand elucidating which structural features of these substances are responsible for specific odour qualities and potencies of these monoterpenes. In the frame of this doctoral thesis, a comparison between chemical structure and odour character of selected monoterpenes relating to linalool, geraniol, nerol, and β- citronellol has been conducted, complemented by investigations on their acetate derivatives and previously identified oxygenated metabolites. To achieve this aim, a series of oxygenated derivatives, bearing an aldehyde, an alcohol, or an acid functional group at C-8, were synthesized from the aforementioned terpene alcohols and acetates yielding 24 compounds, yielding a comprehensive substance library for future elucidation of the substances’ presence in nature and evaluation of their further potential physiological properties. Within this study, however, the focus lies on a comprehensive characterization of the compounds’ olfactory properties. Accordingly, all compounds were tested in relation to their odour qualities and relative odour thresholds (OTs) in air, as well as potential inter-individual variations in sensory perception for each single substance. Overall, the results show that v almost all investigated parent monoterpene alcohols and their acetates exhibited closely related odour characters; ranging between citrus-like, fresh, fruity, floral-sweet, and fatty. Amongst others, linalool was demonstrated to be the most potent monoterpene of the group of investigated compounds, eliciting an OT of 3.2 ng/Lair. According to this study, the presence of an OH group at C-3 in the linalool basic structure is the main contributor to its characteristic odour quality and high potency. On the other hand, the occurrence of this OH at C-1 in geraniol, nerol, and citronellol does not alter their odour quality but increases their odour threshold levels, with values of 40, 60 and 10 ng/Lair, respectively. Esterification of this OH-group to the respective acetate barely affected the odour quality, but provoked a decline in odour potency. Substitution at C-8 of either the parent monoterpeneols or their acetates by another OH-group retained the smell of the parent compounds but led to a dramatic decrease in the potency. However, the smell potency was only retained when replacing the alcoholic group at C-8 by an aldehyde or an acid group. It is worth mentioning that among the acetate derivatives 8-oxolinalyl acetate elicits similar smell impressions as linalool, thus exhibiting a citrus-like, fresh odour with an OT of 5.9 ng/Lair. Apart from that, further oxidation of C-8 of linalool, geraniol, citronellol, and citronellyl acetate to their corresponding acids led to a total odour loss.
... Some examples of recently explored molecules are: i) oleanane, which has been proved to inhibit mTor and Akt in PC-3 cells at extremely low concentrations (0.62 to 10 μM) 86,87 ; ii) tirucallic acid, which inhibits Akt/ mTOR signaling and induces simultaneous oxidative stress and apoptosis in PC-3 88 ; iii) curcubitacin, which has antiproliferative activity and is a potent inhibitor of cell growth in vitro (PC-3 and LNCaP cells), an effect related to disruption of cytoskeletal integrity by actin aggregation and cofilin-actin rod formation leading cell cycle arrest, cytokinesis failure and mitochondrial ROS production with consequent cellular apoptosis 89,90 ; iv) capilliposide (a novel oleanane triterpenoid saponin) has been demonstrated to have a role as cytotoxic and anti-tumor effects over PC-3 cells, associated with the release of cytochrome c from mitochondria and by the activation of caspase pathways 91 ; v) Linalool (monoterpenoid) induces sub-G1 cell cycle arrest with a significant increase of apoptotic cells. The results showed that treatment with different concentrations of linalool for 48 h led to an increase in the population of prostate cancer cells in the sub-G0/G1 phase (apoptotic population) (p< 0.01) 92 . Mechanistically, all the compounds described here have been implicated in a wide range of biological pathways and processes; thus, these compounds are potential candidates for anti-cancer agents. ...
Article
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Prostate cancer is one of the neoplastic diseases with the highest morbidity and mortality in the world. The diversity of available treatments and side effects related to therapeutic treatments are severe and affect a patient's quality of life. Thus, to creating new therapeutic alternatives to reduce morbidity and creating safe and effective therapies is a constant challenge. Recently, the use of traditional medicine and chemoprevention has gained importance. Several clinical and epidemiological studies suggest that a high-terpenoid compound-based diet is associated with a reduced risk of prostate cancer. This review is focused on the anti-proliferative effects of different terpenoids isolated from natural sources on human prostate cancer cells, with the aim of setting the basis to use these compounds as phytotherapeutic, nutraceutical and functional ingredients.
... Santonin, a sesquiterpene lactone and caryophyllene oxide are well known compound of family Asteraceae (Sakipova et al., 2017). Similar kinds of terpenoids, sesquiterpenes lactone, coumarin and phenols were also identified in a number of other plant extracts and reported to possess strong anticancer activities (Murata et al., 2013;Sun et al., 2015;Takasaki et al., 1999aTakasaki et al., , 1999b. But cytotoxicity of artemorin has never been reported. ...
Article
Ethnopharmacological relevance: Medicinal plants used in traditional medicines are affordable, easily accessible, safer, less toxic and considered as a rich or efficient source of bioactive molecules for modern therapeutics. Artemisia nilagirica (AR) has a long history of use in Indian traditional medicine to combat a wide variety of diseases including cancer. Aim of the study: Considering the vast potential of traditional healing plants to deliver safer, less toxic and efficient chemotherapeutics, we have examined anticancer activity of ethanolic extract, bioactive fractions and sub-fractions of AR against different human cancer cell lines along with their phytochemical analysis to understand the insights of novel anticancer activities for further preclinical studies. Materials and methods: Fresh plant material of AR was procured from the wild, dried and ground. The grinded materials was extracted in ethanol (AR-01) and fractionated into butanol (AR-02), ethyl acetate (AR-03), hexane (AR-04) and water (AR-05). The cytotoxicity was evaluated against three different human cancer cell lines, i.e. colon (DLD-1), lung (A-549), and breast (MCF-7) using Sulforhodamine B (SRB) assay along with non-cancerous VERO cells as control and doxorubicin (DOX) as positive control. As we observed strong cytotoxicity of AR-03 and AR-04 fractions against tested cells and marked cytotoxic effects particularly in colon cancer cell lines, we further re-fractionated, AR-03 into (AR-03A, AR-03B, AR-03C, AR-03D, AR-03E) and AR-04 into (AR-04A, AR-04B, AR-04C) sub-fractions by column chromatography and investigated against the same panel of cell lines in addition to one more colon cancer cell line (HT-29). Phytochemical analysis was performed through HPLC-ESI-QTOF-MS/MS fragmentation. Results: Ethyl acetate (AR-03) and hexane (AR-04) fractions were found to be the most cytotoxic against all the tested cell lines. Further, AR-03E and AR-04A sub-fractions were found more specific cytotoxic selectively against DLD-1 cancer cell lines at 100µg/ml concentration. HPLC-ESI-QTOF-MS/MS determination revealed the presence of 17 compounds in AR-01. Among them, 4 compounds were reported for the first time in this species. However, 3 identified compounds (artemorin, β-santonin and caryophyllene oxide) in AR-03E sub-fraction were commonly present in each bioactive fraction and may be considered as potential and safest cytotoxic agents for anticancer activity. Conclusions: Experimental evidences reported in this paper for anticancer activity validate the traditional wisdom of Artemisia nilagirica as an anticancer herbal drug. To our knowledge, this is our first novel observation of cytotoxicity and selectivity of ethyl acetate and hexane sub-fraction of AR-01 i.e. AR-03E and AR-04A respectively against DLD-1 human cancer cell lines. HPLC-ESI-QTOF-MS/MS determination attributes the identification of cytotoxic compounds which may be used for further preclinical studies.
... In the current reports revealed that the cell cycle arrest was taken place in the G0 and M phase and most of the cytokinetic and pharmacological research was also shows accurate cell cycle analysis [35]. Other report revealed that cell cycle arrest leads to increase in sub-G0/G1cell population after treatment with increasing doses of linalool terpenoid [36]. Phlorotanninsenriched extract of brown alga of H. grandifolius exhibited cytotoxicity against tumor cell line including Hep-2 and promoting cell death trough apoptosis mechanisms [34]. ...
Article
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Background Cancer causes leading death in the world population due to exposure of various carcinogenic/mutagenic agents, radiation and life style. There are 2.6 million new cases diagnosed each year. Therefore, the objective is aimed to study the antibacterial and antioxidant activities of solvent fractions of ethanolic extract of T. conoides and its anticancer activity also evaluated by analyzing cytotoxicity, cell cycle arrest and apoptosis in HepG2 cell line. Methods Antibacterial activity was done by disc diffusion method and expressed as in millimeter diameter of zone inhibition. Antioxidant activity was done by ABTS radical assay, superoxide radical assay, iron chelation and uric acid formation inhibitory assays. The cytotoxicity efficacy was estimated using MTT assay. Annexin-V FITC kit was used to estimate the apoptosis and cell cycle arrest by flowcytometer. Morphological changes of cell through alteration of nuclear content and mitochondrial membrane potential were also examined using Hoechst and JC1 stains under fluorescence microscopy, respectively. ResultsHighest antibacterial activity, TAA and RAA were found in EAF followed by DMF, HF and AF. Cytotoxicity of EAF was found to be 67% at 24 h and 83% at 48 h over the standard of quercetin (86% at 48 h). The cancer cells were found to be significantly (p < 0.05) higher in the proliferative G0/G1 phase where as significantly decreased in the S phase. Hence, treatment with T. conoides fraction showed statistically (p < 0.05) significant increase of apoptotic cells than that of quercetin standard (32%, 80 μg/mL). The apoptotic cell formation might be due to the change of nuclear content and mitochondrial membrane potential were further confirmed in HepG2 cells under fluorescence microscopy. Conclusion Ethyl acetate fraction of T. conoides showed highest antibacterial, antioxidant and anticancer activity through exhibiting synergistic effects over the respective standard compounds.
Article
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The aim of this review is to evaluate the potential of Hyssopus officinalis L., commonly known as hyssop, in addressing specific dermatological concerns based on existing research evidence. The review presents an analysis of the composition of essential oils and extracts derived from Hyssopus officinalis L. It encompasses a comprehensive examination of the pharmacological activities associated with hyssop herb essential oils/extracts, particularly in the context of dermatological concerns. Existing studies suggest promising potential for hyssop essential oil/extracts in addressing various skin conditions, including microbial skin infections, inflammatory diseases and oxidative stress-related skin damage. There are also data on potential cytotoxic, antigenotoxic and antimelanogenic effects. Furthermore, this review highlights the predominant compounds present in hyssop essential oil and extracts, elucidating their role as potential carriers of pharmacological activity. In the conclusion, the key findings of the review are summarized, emphasizing the promising attributes of Hyssopus officinalis L. for skin health. However, it also underscores the importance of addressing existing gaps in research and conducting clinical trials and additional studies to ensure the efficacy and safety of hyssop herb in dermatological applications.
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This comprehensive review endeavors to illuminate the nuanced facets of linalool, a prominent monoterpene found abundantly in essential oils, constituting a massive portion of their composition. The biomedical relevance of linalool is a key focus, highlighting its therapeutic attributes observed through anti-nociceptive effects, anxiolytic properties, and behavioral modulation in individuals affected by dementia. These findings underscore the compound's potential application in biomedical applications. This review further explores contemporary formulations, delineating the adaptability of linalool in nano-emulsions, microemulsions, bio-capsules, and various topical formulations, including topical gels and lotions. This review covers published and granted patents between 2018–2024 and sheds light on the evolving landscape of linalool applications, revealing advancements in dermatological, anti-inflammatory, and antimicrobial domains.
Chapter
Herbs and derived medicines are traditionally practiced in many regions worldwide. The components present in the plant are known as secondary metabolites that have many effective properties against several diseases. Herbal medicines are the complex of the components of the herbs that are prepared and used in alleviating infections in the diseases. Leukemia is a type of blood cancer that develops in the blood-forming tissues such as bone marrow and is found to be in forms such as lymphocytic leukemia and myeloid leukemia. This blood-related disorder develops in the blood-forming tissues by the accumulation of improperly differentiated cells and may spread to other related areas in treatment delay. The conventional treatment for this disease is effective but at a cost. So herbal medicines can be one of the effective treatments for leukemia. Therefore, the following chapter is going to be about the herbs and herbal medicine and its usage for leukemia. It will also focus on the medicinal properties such as apoptotic, anti-inflammation, and others, and their future perspectives.
Research
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After formulating the gel with the appropriate gel base for the intended use, the efficacy of the gel is evaluated for each therapeutic purpose, namely anticancer, antimicrobial, antifungal, antiviral, antihyperglycemic, analgesic, anti-inflammatory, anti-Plasmodal and antiparasitic effects. To determine the concentration Optimization of each terpenoid in the gel for maximum therapeutic benefit, in vitro permeation release by permeation chamber to use a suitable permeation chamber or diffusion cell to study the permeation of terpenoids from the gel through a membrane that mimics skin or affected tissue, Sampling by taking samples at predetermined time intervals to measure the amount of terpenoids that have permeated the membrane Analysis by sampling using appropriate techniques such as high performance liquid chromatography (HPLC) or gas chromatography (GC) to quantify the permeated terpenoids optimization of the gel formulation by adjusting the gel formulation based on the results of in vitro permeation studies to increase the penetration and delivery of terpenoids to the target tissue. Safety and toxicity testing by conducting safety and toxicity studies to ensure the gel is safe to use. This may include cytotoxicity testing, skin irritation tests and other relevant evaluations, final product development by optimizing the gel formulation and safety after validation, with the aim of developing the final product for commercial use, regulatory compliance by ensuring that the gel formulation meets regulatory requirements for pharmaceutical or cosmetic products, depending on their intended use.
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Bu çalışmada Türkiye'de hasat edilen 5 farklı narenciye (mandalina, greyfurt, portakal, kumkuat ve limon) kalitatif ve kantitatif olarak incelenmiştir. Bu amaçla Clevenger aparatı ile uçucu yağlar elde edilmiştir. Uçucu yağ bileşenleri GC-MS yardımıyla belirlendi. Limonen en düşükten en yükseğe doğru tüm meyve kabuklarında ortak bileşen olarak clementine mandalinada yaklaşık %24, portakalda %28 ve limonda %76, greyfurtta %98, kumkuatta %100 ortak bileşen olarak belirlenmiştir. Linalool, portakal ve mandalinanın ana bileşeni olarak belirlendi. Kabukların kuru maddesi ve külü belirlendi. Ayrıca kabuklarda bulunan elementler sem-edx yardımıyla belirlenmiştir. Sem-edx sonuçlarına göre kabuklar kalsiyum ve potasyum açısından oldukça zengindir.
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Significant metabolic pathways have been linked to AKR1B1 and AKR1B10. These enzymes are crucial biological targets in the therapy of colon cancer. In the past several decades, drug repurposing has gained appeal as a time and cost-efficient strategy for providing new indications for existing drugs. The structural properties of the plant-based alkaloidal drugs theobromine and theophylline were examined using density functional theory (DFT) computations, where the B3LYP/SVP method was used to quantify the dipole moment, polarizability, and optimization energy. Optimized structures obtained through DFT studies were docked inside the active pocket of target proteins to evaluate their inhibitory potential. Moreover, molecular dynamic simulation provides significant insight into a dynamic view of molecular interactions. The findings of current revealed theobromine and theophylline as strong AKR1B1 and AKR1B10 inhibitors, respectively. In addition, the anti-cancer potential of theophylline and theobromine was validated by targeting various tumor proteins, i.e. NF-κB, cellular tumor antigen P53 and caspase-3 using a molecular docking approach. Theobromine was found to be strongly interacted with NF-κB and caspase-3, whereas theophylline potentially inhibited cellular tumor antigen P53. In addition, the ADMET characteristics of theobromine and theophylline were identified, confirming their drug-like capabilities. These results should open the way for further experimental validation and structure-based drug design/repurposing of AKR1B1/AKR1B10 inhibitors for the treatment of colon cancer and associated malignancies. Communicated by Ramaswamy H. Sarma
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Curcuma aromatica Salisb. (C. aromatica) is commonly known as wild turmeric. Curcuma aromatica is an essential herbal plant and it has been extensively used in traditional medicine for centuries. It has been used for the treatment of gastrointestinal ailments, arthritic pain, inflammatory conditions, wounds, skin infections, and insect bites. This article aims to review the phytochemical and pharmacological aspects of C. aromatica and to provide a guide and insight for further studies. Electronic repositories, including Web of Science, Google Scholar, ProQuest, Science Direct, Scopus, and PubMed, were searched until December 2019 to identify studies relating to C. aromatica. A systematic analysis of the literature on pharmacognostical, physicochemical, and nutritional contents, bioactive compounds, and biological activities of C. aromatica was carried out, and ideas for future studies were also coined. A total of 157 articles concerning in vitro or in vivo (or both) researches on C. aromatica have been evaluated. Analyses of the data showed that C. aromatica consists of various classes of compounds, including alkaloids, flavonoids, curcuminoids, tannins, and terpenoids, that formed the bases of its pharmacological activities. The reviewed data also revealed that C. aromatica possessed the pharmacological effect of anticancer, antidiabetic, antioxidant, anti-inflammatory, antimicrobial, antitussive, antiepileptic, analgesic, wound healing, and insect repellent activities. This review has systematically compiled and summarized the literature related to the nutritional values and bioactive compounds, as well as the biological activities of C. aromatica. To the best of our knowledge, this is the most comprehensive review reported on C. aromatica.
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The use of complementary and alternative medicine (CAM) has been used since antiquity for the relief of symptoms related to many diseases including urologic ailments. CAM is typically defined as those healing philsophies, approaches and therapies that are generally not taught in medical schools and are not usually reimbursed by medical insurance companies. Complementary and alternative medicine therapies are distinguished as those used alone (alternative) or in addition to conventional therapies (complementary). Few studies have focused on the urologic population. In this article, we summarize recent studies assessing the prevalence rate of CAM use with special emphasis in prostate cancer patients.
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The use of complementary and alternative medicine (CAM) has been used since antiquity for the relief of symptoms related to many diseases including urologic ailments. CAM is typically defined as those healing philsophies, approaches and therapies that are generally not taught in medical schools and are not usually reimbursed by medical insurance companies. Complementary and alternative medicine therapies are distinguished as those used alone (alternative) or in addition to conventional therapies (complementary). Few studies have focused on the urologic population. In this article, we summarize recent studies assessing the prevalence rate of CAM use with special emphasis in prostate cancer patients.
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Prostate cancer mortality rates in the United States declined sharply after 1991 in white men and declined after 1992 in black men. The current study was conducted to investigate possible mechanisms for the declining prostate cancer mortality rates in the United States. The authors examined and compared patterns of prostate cancer incidence, survival rates, and mortality rates among black men and white men in the United States using the 1969-1999 U.S. prostate cancer mortality rates and the 1975-1999 prostate cancer incidence, survival, and incidence-based mortality rates from the Surveillance, Epidemiology, and End Results (SEER) Program for the U.S. population. The SEER data represent approximately 10% of the U.S. population. Prostate cancer incidence and mortality rates showed transient increases after 1986, when the U.S. Food and Drug Administration approved the use of prostate specific antigen (PSA) testing. The age-adjusted prostate cancer mortality rates for men age 50-84 years, however, have dropped below the rate in 1986 since 1995 for white men and since 1997 for black men. In fact, for white men ages 50-79 years, the 1998 and 1999 rates were the lowest observed since 1950. Incidence-based mortality rates by disease stage revealed that the recent declines were due to declines in distant disease mortality. Moreover, the decrease in distant disease mortality was due to a decline in distant disease incidence, and not to improved survival of patients with distant disease. Similar incidence, survival, and mortality rate patterns are seen in black men and white men in the United States, although with differences in the timing and magnitude of recent rate decreases. Increased detection of prostate cancer before it becomes metastatic, possibly reflecting increased use of PSA testing after 1986, may explain much of the recent mortality decrease in both white men and black men.
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This review is an updated and expanded version of a paper that was published in this journal in 1997. The time frame has been extended in both directions to include the 22 years from 1981 to 2002, and a new secondary subdivision related to the natural product source but applied to formally synthetic compounds has been introduced, using the concept of a "natural product mimic" or "NM" to join the original primary divisions. From the data presented, the utility of natural products as sources of novel structures, but not necessarily the final drug entity, is still alive and well. Thus, in the area of cancer, the percentage of small molecule, new chemical entities that are nonsynthetic has remained at 62% averaged over the whole time frame. In other areas, the influence of natural product structures is quite marked, particularly in the antihypertensive area, where of the 74 formally synthetic drugs, 48 can be traced to natural product structures/mimics. Similarly, with the 10 antimigraine drugs, seven are based on the serotonin molecule or derivatives thereof. Finally, although combinatorial techniques have succeeded as methods of optimizing structures and have, in fact, been used in the optimization of a number of recently approved agents, we have not been able to identify a de novo combinatorial compound approved as a drug in this time frame.
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Each year, the American Cancer Society (ACS) estimates the number of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute, Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. This report considers incidence data through 2003 and mortality data through 2004. Incidence and death rates are age-standardized to the 2000 US standard million population. A total of 1,444,920 new cancer cases and 559,650 deaths for cancers are projected to occur in the United States in 2007. Notable trends in cancer incidence and mortality rates include stabilization of the age-standardized, delay-adjusted incidence rates for all cancers combined in men from 1995 through 2003; a continuing increase in the incidence rate by 0.3% per year in women; and a 13.6% total decrease in age-standardized cancer death rates among men and women combined between 1991 and 2004. This report also examines cancer incidence, mortality, and survival by site, sex, race/ethnicity, geographic area, and calendar year, as well as the proportionate contribution of selected sites to the overall trends. While the absolute number of cancer deaths decreased for the second consecutive year in the United States (by more than 3,000 from 2003 to 2004) and much progress has been made in reducing mortality rates and improving survival, cancer still accounts for more deaths than heart disease in persons under age 85 years. Further progress can be accelerated by supporting new discoveries and by applying existing cancer control knowledge across all segments of the population.