リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

大学・研究所にある論文を検索できる 「Sedative activities of essential oils from Beninese medicinal plants via inhalation administration and structure-activity relationships of their active compounds」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

コピーが完了しました

URLをコピーしました

論文の公開元へ論文の公開元へ
書き出し

Sedative activities of essential oils from Beninese medicinal plants via inhalation administration and structure-activity relationships of their active compounds

DOUGNON, GODFRIED TCHETONNOUGBO 京都大学 DOI:10.14989/doctor.k23831

2022.03.23

概要

In evolutionary terms, humans have greatly benefited from plants and their secondary metabolites. Since the dawn of humanity, plants have served as a source of food for human and animals, fibers for clothes and medication for human ailments. In the great diversity of the plant kingdom, essential oils have particularly attracted much attention recently. They are complex mixtures of hydrocarbons and oxygenated hydrocarbons produced by glandular trichomes and other secretory structures, principally found in leaves and flowers. They have served for a long time in many traditional healing systems and recent studies have proved their antioxidant, antibacterial, antimicrobial, anti-inflammatory, anticancer, sedative, anxiolytic and antidepressant activities. Africa is rich in many plant species, and especially in towns and rural villages of the Republic of Benin, traditional healers and market herbalists believe that fragrant species can be of interest through their sedative or sleep promoting activity. However, these species are still undocumented and the scientific evidence of their activity remains unclear.

In the present study, we have investigated the essential oils from 3 plant species collected in the Republic of Benin, namely Lantana camara L., Dysphania ambrosioides (L.) Mosyakin & Clemants and Chromolaena odorata (L.) R.M.King & H.Rob., for their sedative, anxiolytic or antidepressant activities when administered via inhalation to mice. In addition, the chemical composition of each essential oil was investigated and the compounds responsible for activities were identified. Further, we conducted a quantitative structure activity relationships activity analysis of selected sesquiterpenes using their absorption, distribution, metabolism, excretion and toxicity (ADMET) properties to predict their sedative activity on the CNS.

In Chapter 1, we present the sleep promoting effects of 3 plant species from the Republic of Benin. First, we investigated the chemical composition of essential oil from the leaves of L. camara (LCEO), evaluated its sedative effects in mice via inhalation administration, and identified the compounds responsible for activity. The results indicated that via inhalation administration, sabinene (38.81%) and 1,8-cineole (28.90%) were the main compounds in cause for the sedative activity of LCEO. Thus, they could be considered as promising candidates for the management CNS-associated diseases. Second, we analyzed the chemical composition of the essential oil from the leaves of D. ambrosioides (DAEO), and its sleep-promoting effects via inhalation administration in ddY mice. Ascaridole (35.52%) and p-cymene (47.16%) were the major components, and both compounds were evaluated for sedative activity by using the caffeine-treated excitatory mouse model. They were highly effective in decreasing locomotor activity of excited mice by more than 50%. Further investigations indicated that the GABAergic system mediates the sedative effect. The results further extend the knowledge on their use as potential, promising natural products for the management of sleep disorders and CNS-related ailments. Last, essential oil from the leaves of C. odorata (COEO) was investigated for its sedative activity in mice. The results showed that COEO significantly reduced mice locomotor activity and analysis of chemical composition of the oil indicated that caryophyllene oxide (43.75%) was the major compound. In order to understand the action mechanisms, caryophyllene oxide was tested for its effects on the CNS by using a caffeine pre-excited mice test and a pentobarbital sleeping-induced test in mice. The results demonstrated that caryophyllene oxide is a CNS-depressant; however, it does not operate via the GABAergic receptor system. Its precursor, β-caryophyllene, was also investigated and it demonstrated a similar pattern of sedative activity. We believe these results further extend actual knowledge on these naturally occurring sesquiterpenes.

In Chapter 2, we wanted to further understand the activities of monoterpene 1,8-cineole identified in L. camara, which demonstrated a novel double U-shaped curve pattern of sedative activity, as described in Chapter 1. Therefore, we present here the anxiolytic and antidepressant activities of naturally occurring monoterpene 1,8-cineole and its structural isomer 1,4-cineole. Anxiety-like behaviors were evaluated by using the light–dark box test (LDB) and marble-burying test (MBT) and depression-like symptoms were tested by using the forced swimming test (FST) and tail suspension test (TST). The results demonstrated that 1,8-cineole and 1,4-cineole both possessed an anxiolytic and antidepressant effect. Further, the role of the GABAA/benzodiazepine receptor system in the anxiolytic effects of 1,8- and 1,4-cineole was investigated through co-administration of flumazenil, a GABAergic system antagonist. The results suggested that only 1,8-cineole affects the GABAA/benzodiazepine receptors. In this chapter, we demonstrated that inhaled 1,8- and 1,4-cineole prevented anxiety and depressive-like symptoms in classic mice models.

Sesquiterpene compounds such as caryophyllene oxide, were previously demonstrated in Chapter 1, to be sedative even at low doses. A previous work has investigated QSAR study of monoterpene compounds. However, sesquiterpenes which are more complex and possess stronger odor in plants are not yet studied for possible QSAR or SAR analysis. Therefore, in Chapter 3, as a part of our endeavor to shed light on the effects of sesquiterpenes on the CNS, a detailed study on the properties of selected sesquiterpenes was performed by using their ADMET properties. From an initial list of one hundred and fourteen sesquiterpenes, a rigorous selection of eighteen sesquiterpenes was conducted, and these compounds were further divided into two groups: training set and external validation set of nine sesquiterpenes each. The training set was evaluated for sedative activity in mice via inhalation and the results demonstrated that all compounds were sedative, except for one compound, curzerene. QSAR study was performed using simple regression and multiple regression models, and a multiple regression model was the best fit to predict sedative activity of the sesquiterpenes. Further, molecular determinants were analyzed to find the key parameters needed for sedative activity. Molar refractivity and the number of hydrogen bonds acceptors were suggested to be statistically important in predicting more than 82% of the sedative activity. Therefore, in this chapter, we suggest novel QSAR models that could be useful in predicting sedative activity of sesquiterpenes, thus accelerating the process of drug development.

この論文で使われている画像

参考文献

[1] Takemoto H, Ito M, Shiraki T, Yagura T, Honda G. Sedative effects of vapor inhalation of agarwood oil and spikenard extract and identification of their active components. 2008; 62: 41–46

[2] Tankam JM, Ito M. Sedative, anxiolytic and antidepressant-like effects of inhalation of the essential oil of Ocimum gratissimum L . from Cameroon in mice. J Pharmacogn Phytochem 2014; 2: 1–9

[3] Ogawa K, Yabe H, Kitayama T, Ito M. Locomotor-reducing activity of sesquiterpenes related to Zingiber zerumbet essential oil and hexahydrozerumbone derivatives. Biol Pharm Bull 2016; 39: 1077–1080

[4] Karimi AG, Ito M. Sedative effect of vapor inhalation of essential oil from Heracleum afghanicum Kitamura seeds. J Essent Oil Res 2012; 24: 571–577

[5] Miyoshi T, Ito M, Kitayama T, Isomori S, Yamashita F. Sedative effects of inhaled benzylacetone and structural features contributing to its activity. Biol Pharm Bull 2013; 36: 1474–1481

[6] Tankam JM, Ito M. Inhalation of the essential oil of Piper guineense from Cameroon shows sedative and anxiolytic-like effects in mice. Biol Pharm Bull 2013; 36: 1608–1614

[7] Takemoto H, Ito M, Asada Y, Kobayashi Y. Inhalation administration of the sesquiterpenoid aristolen1(10)-en-9-ol from Nardostachys chinensis has a sedative effect via the GABAergic system. Planta Med 2015; 81: 343–347

[8] Ito K, Akahoshi Y, Ito M, Kaneko S. Sedative effects of inhaled essential oil components of traditional fragrance Pogostemon cablin leaves and their structure-activity relationships. J Tradit Complement Med 2016; 6: 140–145

[9] Ito K, Ito M. Sedative effects of vapor inhalation of the essential oil of Microtoena patchoulii and its related compounds. J Nat Med 2011; 65: 336–343

[10] Sharma OP, Dawra RK, Pattabhi V. Molecular structure, polymorphism, and toxicity of lantadene a, the pentacyclic triterpenoid from the hepatotoxic plant Lantana camara. J Biochem Toxicol 1991; 6: 57–63

[11] Khan M, Mahmood A, Alkhathlan HZ. Characterization of leaves and flowers volatile constituents of Lantana camara growing in central region of Saudi Arabia. Arab J Chem 2016; 9: 764–774

[12] Oluwadayo Sonibare O, Effiong I. Antibacterial activity and cytotoxicity of essential oil of Lantana camara L. leaves from Nigeria. African J Biotechnol 2008; 7: 2618–2620

[13] Weenen H, Nkunya MH, Bray DH, Mwasumbi LB, Kinabo LS, Kilimali VA. Antimalarial activity of Tanzanian medicinal plants. Planta Med 1990; 56: 368–370

[14] Deena MJ, Thoppil JE. Antimicrobial activity of the essential oil of Lantana camara. Fitoterapia 2000; 71: 453–455

[15] Alitonou G, Avlessi F, Bokossa I, Ahoussi E, Dangou J, Sohounhloué DCK. Chemical composition and biological activities of essential oil from Lantana camara Linn. Comptes rendus Chim 2004; 7: 1101–1105

[16] Fujiwara Y, Ito M. Synergistic effect of fragrant herbs in japanese scent sachets. Planta Med 2015; 81: 193– 199

[17] Sinha D, Efron D. Complementary and alternative medicine use in children with attention deficit 117 hyperactivity disorder. J Paediatr Child Health 2005; 41: 23–26

[18] Ogawa K, Miyoshi T, Kitayama T, Ito M. Locomotor-reducing effects and structural characteristics of inhaled zerumbone and tetrahydrozerumbone derivatives. Biol Pharm Bull 2014; 37: 1559–1563

[19] Noudogbessi JP, Chalard P, Figueredo G, Alitonou GA, Agbangnan P, Osseni A, Avlessi F, Chalchat JC, Sohounhloue DCK. Chemical compositions and physical characteristics of volatile extracts of leaves of Psidium guajava Linn and Lantana camara Linn of Benin. Res J Pharm Biol Chem Sci 2013; 4: 28–37

[20] Ngassoum MB, Yonkeu S, Jirovetz L, Buchbauer G, Schmaus G, Hammerschmidt FJ. Chemical composition of essential oils of Lantana camara leaves and flowers from Cameroon and Madagascar. Flavour Fragr J 1999; 14: 245–250

[21] Dua VK, Pandey AC, Dash AP. Adulticidal activity of essential oil of Lantana camara leaves against mosquitoes. Indian J Med Res 2010; 131: 434–439

[22] Pino JA, Marbot R, Rosado A, Romeu C, Martí MP. Chemical composition of the essential oil of Lantana camara L. From Cuba. J Essent Oil Res 2004; 16: 216–218

[23] Jawonisi IO, Adoga GI. Chemical Constituents of Essential Oil of Lantana camara L. Leaves. Br J Pharmacol Toxicol 2013; 4: 155–157

[24] Kasali AA, Ekundayo O, Paul C, Eshilokun AO, Yadua P. Essential oil of Lantana camara L. var. aculeata from Nigeria. J Essent Oil Res 2004; 16: 582–584

[25] da Silva M, Andrade E, Zoghbi M, Luz AI, da Silva J, Maia JG. The essential oils of Lantana camara L. occurring in North Brazil. Flavour Fragr J 1999; 14: 208–210

[26] Sousa EO, Colares AV, Rodrigues FFG, Campos AR, Lima SG, Costa JGM. Effect of collection time on essential oil composition of Lantana camara Linn (Verbenaceae) growing in Brazil Northeastern. Rec Nat Prod 2010; 4: 31–37

[27] Saleh M. Gas chromatographic analysis of the essential oil of Lantana camara L. varieties. Planta Med 1974; 25: 373–375

[28] Sundufu AJ, Shoushan H. Chemical composition of the essential oils of Lantana camara L. occuring in South China. Flavour Fragr J 2004; 19: 229–232

[29] Randrianalijaona JA, Ramanoelina PAR, Rasoarahona JRE, Gaydou EM. Seasonal and chemotype influences on the chemical composition of Lantana camara L. essential oils from Madagascar. Anal Chim Acta 2005; 545: 46–52

[30] Shah SMM, Ullah F, Shah SMH, Zahoor M, Sadiq A. Analysis of chemical constituents and antinociceptive potential of essential oil of Teucrium stocksianum Bioss collected from the North West of Pakistan. BMC Complement Altern Med 2012; 12: 1200

[31] Harraz FM, Hammoda HM, El-Ghazouly MG, Farag MA, El-Aswad AF, Bassam SM. Chemical composition, antimicrobial and insecticidal activities of the essential oils of Conyza linifolia and Chenopodium ambrosioides. Nat Prod Res 2015; 29: 879–882

[32] Xu J, Hu ZQ, Wang C, Yin ZQ, Wei Q, Zhou LJ, Li L, Du YH, Jia RY, Li M, Fan QJ, Liang XX, He CL, Yin LZ. Acute and subacute toxicity study of 1,8-cineole in mice. Int J Clin Exp Pathol 2014; 7: 1495–1501

[33] Tisserand R. Essential oil safety I. Int J Aromather 1996; 7: 28–32

[34] De Sousa DP, Nóbrega FFF, De Morais LCSL, De Almeida RN. Evaluation of the anticonvulsant activity of terpinen-4-ol. Zeitschrift fur Naturforsch - Sect C J Biosci 2009; 64: 1–5

[35] Becker AG, Parodi T V., Heldwein CG, Zeppenfeld CC, Heinzmann BM, Baldisserotto B. Transportation of silver catfish, Rhamdia quelen, in water with eugenol and the essential oil of Lippia alba. Fish Physiol Biochem 2012; 38: 789–796

[36] Ash M. Handbook of green chemicals. Washington. 2004

[37] Pakkirisamy M, Kalakandan SK, Ravichandran K. Phytochemical screening, GC-MS, FT-IR analysis of methanolic extract of Curcuma caesia roxb (black turmeric). Pharmacogn J 2014; 9: 952–956

[38] Zamyad M, Abasnejad M, Esmaeili-Mahani S, Mostafavi A. Alpha-Pinene as the Main Component of Ducrosia anethifolia Boiss Essential Oil is Responsible for its Effect on Locomotor Activity in Rats. Avicenna J Neuro Psych Physiol 2016; 3: 1–6

[39] Yang H, Woo J, Pae AN, Um MY, Cho NC, Park KD, Yoon M, Kim J, Lee CJ, Cho S. α-pinene, a major constituent of pine tree oils, enhances non-rapid eye movement sleep in mice through GABAAbenzodiazepine receptors. Mol Pharmacol 2016; 90: 530–539

[40] Bahi A, Al Mansouri S, Al Memari E, Al Ameri M, Nurulain SM, Ojha S. β-Caryophyllene, a CB2 receptor agonist produces multiple behavioral changes relevant to anxiety and depression in mice. Physiol Behav 2014; 135: 119–124

[41] Hirai M, Ito M. Sedative effects of the essential oil and headspace air of Ocimum basilicum by inhalation in mice. J Nat Med 2019; 73: 283–288

[42] Muchtaridi, Subarnas A, Apriyantono A, Mustarichie R. Identification of compounds in the essential oil of nutmeg seeds (Myristica fragrans Houtt.) that inhibit locomotor activity in mice. Int J Mol Sci 2010; 11: 4771–4781

[43] Yao QS, Chiou GCY. Inhibition of crystallins-induced inflammation in rabbit eyes with five phytogenic compounds. Acta Pharmacol Sin 1993; 14: 13–17

[44] Kirchner K, Wisniewski A, Cruz AB, Biavatti MW, Netz DJA. Chemical composition and antimicrobial activity of Hedyosmum brasiliense Miq., Chloranthaceae, essential oil. Rev Bras Farmacogn 2010; 20: 692– 699

[45] Coelho-De-Souza LN, Leal-Cardoso JH, De Abreu Matos FJ, Lahlou S, Magalhães PJC. Relaxant effects of the essential oil of Eucalyptus tereticornis and its main constituent 1,8-cineole on guinea-pig tracheal smooth muscle. Planta Med 2005; 71: 1173–1175

[46] Santos FA, Rao VSN. Antiinflammatory and antinociceptive effects of 1,8-cineole a terpenoid oxide present in many plant essential oils. Phyther Res 2000; 14: 240–244

[47] Teixeira GFD, Lima RCP, Silveira ER, Freitas MO, Campos AR. Sedative effect of Eucalyptus urophylla and E. brassiana in mice. Nat Prod Commun 2008; 3: 1539–1542

[48] Galindo LA, De Moraes Pultrini A, Costa M. Biological effects of Ocimum gratissimum L. are due to synergic action among multiple compounds present in essential oil. J Nat Med 2010; 64: 436–441

[49] Oh DR, Kim Y, Jo A, Choi EJ, Oh KN, Kim J, Kang H, Kim YR, Choi CY. Sedative and hypnotic effects of Vaccinium bracteatum Thunb. through the regulation of serotonegic and GABAA-ergic systems: Involvement of 5-HT1A receptor agonistic activity. Biomed Pharmacother 2019; 109: 2218–2227

[50] Bhaskar S, Hemavathy D, Prasad S. Prevalence of chronic insomnia in adult patients and its correlation with medical comorbidities. J Fam Med Prim Care 2016; 5: 780–784

[51] Sateia MJ, Sherrill WC, Winter-Rosenberg C, Heald JL. Payer perspective of the American academy of sleep medicine clinical practice guideline for the pharmacologic treatment of chronic insomnia. J Clin Sleep Med 2017; 13: 155–157

[52] Orzeł-Gryglewska J. Consequences of sleep deprivation. Int J Occup Med Environ Health 2010; 23: 95–114

[53] Felson S. Common sleeping pills: 9 medications that can help you sleep. WebMD Med 2020; Available at https://www.webmd.com/sleep-disorders/insomnia-medications. Accessed 01.06.2020

[54] Schreiner L, Bauer J, Ortner E, Buettner A. Structure–odor activity studies on derivatives of aromatic and oxygenated monoterpenoids synthesized by modifying p-cymene. J Nat Prod 2020; 83: 834–842

[55] Chekem MSG, Lunga PK, Tamokou JD, Kuiate JR, Tane P, Vilarem G, Cerny M. Antifungal properties of Chenopodium ambrosioides essential oil against Candida species. Pharmaceuticals 2010; 3: 2900–2909

[56] Almeida Bezerra JW, Rodrigues Costa A, de Freitas MA, Rodrigues FC, de Souza MA, da Silva ARP, dos Santos ATL, Vieiralves Linhares K, Melo Coutinho HD, de Lima Silva JR, Bezerra Morais-Braga MF. Chemical composition, antimicrobial, modulator and antioxidant activity of essential oil of Dysphania ambrosioides (L.) Mosyakin & Clemants. Comp Immunol Microbiol Infect Dis 2019; 65: 58–64

[57] de Sousa DP, de Almeida Soares Hocayen P, Andrade LN, Andreatini R. A systematic review of the anxiolytic-like effects of essential oils in animal models. Molecules 2015; 20: 18620–18660

[58] Askari VR, Rahimi VB, Ghorbani A, Rakhshandeh H. Hypnotic effect of Ocimum basilicum on pentobarbital-induced sleep in mice. Iran Red Crescent Med J 2016; 18

[59] do Vale TG, Furtado EC, Santos JG, Viana GSB. Central effects of citral, myrcene and limonene, constituents of essential oil chemotypes from Lippia alba (mill.) N.E. Brown. Phytomedicine 2002; 9: 709– 714

[60] Sugawara Y, Hara C, Tamura K, Fujii T, Nakamura K, Masujima T, Aoki T. Sedative effect on humans of inhalation of essential oil of linalool. Anal Chim Acta 1998; 365: 293–299

[61] Sayorwan W, Siripornpanich V, Piriyapunyaporn T, Hongratanaworakit T, Kotchabhakdi N, Ruangrungsi N. The effects of lavender oil inhalation on emotional states, autonomic nervous system, and brain electrical activity. J Med Assoc Thail 2012; 95: 598–606

[62] Bagci E, Aydin E, Mihasan M, Maniu C, Hritcu L. Anxiolytic and antidepressant-like effects of Ferulago angulata essential oil in the scopolamine rat model of Alzheimer’s disease. Flavour Fragr J 2016; 31: 70–80

[63] Alitonou GA, Sessou P, Tchobo FP, Noudogbessi JP, Avlessi F, Ou BY, Menut C, Villeneuve P, Sohounhloue DCK. Chemical composition and biological activities of essential oils of Chenopodium ambrosioides L. collected in two areas of Benin. Int J Biosci 2012; 2: 58–66

[64] Cavalli JF, Tomi F, Bernardini AF, Casanova J. Combined analysis of the essential oil of Chenopodium ambrosioides by GC, GC-MS and 13C-NMR spectroscopy: quantitative determination of ascaridole, a heatsensitive compound. Phytochem Anal 2004; 15: 275–279

[65] Jaramillo CBE, Duarte RE, Delgado W. Bioactivity of essential oil from Colombian Chenopodium ambrosioides. Rev Cuba Plantas Med 2012; 17: 54–64

[66] Cruz GVB, Pereira PVS, Patrício FJ, Costa GC, Sousa SM, Frazão JB, Aragão-Filho WC, Maciel MCG, 120 Silva LA, Amaral FMM, Barroqueiro ESB, Guerra RNM, Nascimento FRF. Increase of cellular recruitment, phagocytosis ability and nitric oxide production induced by hydroalcoholic extract from Chenopodium ambrosioides leaves. J Ethnopharmacol 2007; 111: 148–154

[67] Calado GP, Lopes AJ, Costa Junior LM, Lima F, Silva LA, Pereira WS, do Amaral FM, Garcia JB, Nascimento FRF. Chenopodium ambrosioides L. reduces synovial inflammation and pain in experimental osteoarthritis. PLoS One 2015; 10: e0141886

[68] Jardim CM, Jham GN, Dhingra OD, Freire MM. Composition and antifungal activity of the essential oil of the Brazilian Chenopodium ambrosioides L. J Chem Ecol 2008; 34: 1213–1218

[69] Singh HP, Batish DR, Kohli RK, Mittal S, Yadav S. Chemical composition of essential oil from leaves of Chenopodium ambrosioides from Chandigarh, India. Chem Nat Compd 2008; 44: 378–379

[70] Dougnon G, Ito M. Medicinal uses, thin-layer chromatography and high-performance liquid chromatography profiles of plant species from Abomey-Calavi and Dantokpa Market in the Republic of Benin. J Nat Med 2020; 74: 311–322

[71] Sahli F, Sousa SE, Vileno B, Lichter J, Lepoittevin JP, Blömeke B, Giménez-Arnau E. Understanding the skin sensitization capacity of ascaridole : a combined study of chemical reactivity and activation of the innate immune system (dendritic cells) in the epidermal environment. Arch Toxicol 2019; 93: 1337–1347

[72] Koba K, Catherine G, Raynaud C, Chaumont J-P, Sanda K, Laurence N. Chemical composition and cytotoxic activity of Chenopodium ambrosioides L. essential oil from Togo. Bangladesh J Sci Ind Res 1970; 44: 435–440

[73] Monzote L, Nance MR, García M, Scull R, Setzer WN. Comparative chemical, cytotoxicity and antileishmanial properties of essential oils from Chenopodium ambrosioides. Nat Prod Commun 2011; 6: 281–286

[74] Pavela R, Maggi F, Lupidi G, Mbuntcha H, Woguem V, Womeni HM, Barboni L, Tapondjou LA, Benelli G. Clausena anisata and Dysphania ambrosioides essential oils: From ethno-medicine to modern uses as effective insecticides. Environ Sci Pollut Res 2018; 25: 10493–10503

[75] Arena JS, Omarini AB, Zunino MP, Peschiutta ML, Defagó MT, Zygadlo JA. Essential oils from Dysphania ambrosioides and Tagetes minuta enhance the toxicity of a conventional insecticide against Alphitobius diaperinus. Ind Crops Prod 2018; 122: 190–194

[76] Stappen I, Tabanca N, Ali A, Wanner J, Lal B, Jaitak V, Wedge DE, Kaul VK, Schmidt E, Jirovetz L. Antifungal and repellent activities of the essential oils from three aromatic herbs from western Himalaya. Open Chem 2018; 16: 306–316

[77] Bai CQ, Liu ZL, Liu QZ. Nematicidal constituents from the essential oil of Chenopodium ambrosioides aerial parts. E-Journal Chem 2011; 8: S143–S148

[78] Dembitsky V, Shkrob I, Hanus LO. Ascaridole and related peroxides from the genus Chenopodium. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2008; 152: 209–215

[79] Al-Badani RN, da Silva JKR, Mansi I, Muharam BA, Setzer WN, Awadh NA. Chemical composition and biological activity of Lavandula pubescens essential oil from Yemen. J Essent Oil-Bearing Plants 2017; 20: 509–515

[80] Soares MH, Dias HJ, Vieira TM, de Souza MGM, Cruz AFF, Badoco FR, Nicolella HD, Cunha WR, Groppo M, Martins CHG, Tavares DC, Magalhães LG, Crotti AEM. Chemical composition, antibacterial, schistosomicidal, and cytotoxic activities of the essential oil of Dysphania ambrosioides (L.) Mosyakin & 121 Clemants (Chenopodiaceae). Chem Biodivers 2017; 14: e1700149

[81] Gupta D, Charles R, Mehta VK, Garg SN, Kumar S. Chemical examination of the essential oil of Chenopodium ambrosioides L. from the southern hills of India. J Essent Oil Res 2002; 14: 93–94

[82] Santiago JA, Cardoso MDG, Batista LR, de Castro EM, Teixeira ML, Pires MF. Essential oil from Chenopodium ambrosioides L.: secretory structures, antibacterial and antioxidant activities. Acta Sci Biol Sci 2016; 38: 139

[83] Tapondjou LA, Adler C, Bouda H, Fontem DA. Bioefficacité des poudres et des huiles essentielles des feuilles de Chenopodium ambrosioides et Eucalyptus saligna à l’égard de la bruche du niébé, Callosobruchus maculatus Fab. (Coleoptera, Bruchidae). Cah Agric 2003; 12: 401–407

[84] Blanckaert I, Paredes-Flores M, Espinosa-García FJ, Piñero D, Lira R. Ethnobotanical, morphological, phytochemical and molecular evidence for the incipient domestication of epazote (Chenopodium ambrosioides L.: Chenopodiaceae) in a semi-arid region of Mexico. Genet Resour Crop Evol 2012; 59: 557– 573

[85] Owolabi MS, Lajide L, Oladimeji MO, Setzer WN, Palazzo MC, Olowu RA, Ogundajo A. Volatile constituents and antibacterial screening of the essential oil of Chenopodium ambrosioides L. growing in Nigeria. Nat Prod Commun 2009; 4: 989–992

[86] Chu SS, Feng Hu J, Liu ZL. Composition of essential oil of Chinese Chenopodium ambrosioides and insecticidal activity against maize weevil, Sitophilus zeamais. Pest Manag Sci 2011; 67: 714–718

[87] Boutkhil S, El Idrissi M, Amechrouq A, Chbicheb A, Chakir S, El Badaoui K. Chemical composition and antimicrobial activity of crude, aqueous, ethanol extracts and essential oils of Dysphania ambrosioides (L.) Mosyakin & Clemants. Acta Bot Gall 2009; 156: 201–209

[88] Dougnon G, Ito M. Sedative effects of the essential oil from the leaves of Lantana camara occurring in the Republic of Benin via inhalation in mice. J Nat Med 2020; 74: 159–169

[89] Takemoto H, Omameuda Y, Ito M, Fukuda T, Kaneko S, Akaike A, Kobayashi Y. Inhalation administration of valerena-4,7(11)-diene from Nardostachys chinensis roots ameliorates restraint stress-induced changes in murine behavior and stress-related factors. Biol Pharm Bull 2014; 37: 1050–1055

[90] Patel DK. Ascaridole: a phytochemical of modern medicinal perspective. J Coast Life Med 2017; 5: 88–94

[91] Pollack Y, Segal R, Golenser J. The effect of ascaridole on the in vitro development of Plasmodium falciparum. Parasitol Res 1990; 76: 570–572

[92] Pastor J, García M, Steinbauer S, Setzer WN, Scull R, Gille L, Monzote L. Combinations of ascaridole, carvacrol, and caryophyllene oxide against Leishmania. Acta Trop 2015; 145: 31–38

[93] Okuyama E, Umeyama K, Saito Y, Yamazaki M, Satake M. Ascaridole as a pharmacologically active principle of “Paico”, a medicinal peruvian plant. Chem Pharm Bull 1993; 41: 1309–1311

[94] Abbas MA, Jaffal SM, Al-Najjar BO. Analgesic and anxiolytic activities of Achillea Biebersteinii: evidence for the involvement of GABAergic systems. Orient J Chem 2019; 35: 1433–1442

[95] Donatello NN, Emer AA, Salm DC, Ludtke DD, Bordignon SASR, Ferreira JK, Salgado ASI, Venzke D, Bretanha LC, Micke GA, Martins DF. Lavandula angustifolia essential oil inhalation reduces mechanical hyperalgesia in a model of inflammatory and neuropathic pain: the involvement of opioid and cannabinoid receptors. J Neuroimmunol 2020; 340: 577145

[96] Abdelhakim AM, Hussein AS, Doheim MF, Sayed AK. The effect of inhalation aromatherapy in patients undergoing cardiac surgery: a systematic review and meta-analysis of randomized controlled trials. Complement Ther Med 2020; 48: 102256

[97] da Silva PHN, dos Santos MSD, de Andrade SAM, da Silva CCE, de Oliveira CMÂ, Jensen L, da Silva VFL, Sena FMM, de Sousa BA, Veras MRH, Baldisserotto B. Sedative and anesthetic potential of the essential oil and hydrolate from the fruit of Protium heptaphyllum and their isolated compounds in Colossoma macropomum juveniles. Aquaculture 2020; 529: 735629

[98] Dougnon G, Ito M. Inhalation administration of the bicyclic ethers 1,8- and 1,4-cineole prevent anxiety and depressive-like behaviours in mice. Molecules 2020; 25: 1884

[99] Joglekar MM, Panaskar SN, Arvindekar AU. Inhibition of advanced glycation end product formation by cymene – A common food constituent. J Funct Foods 2014; 6: 107–115

[100] Code of Federal Regulations (CFR). Code of Federal Regulations Title 21. Code Fed Regul 2019; 3. Available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=172.515. Accessed 19.08.2020

[101] Mechergui K, Jaouadi W, Coelho JP, Khouja ML. Effect of harvest year on production, chemical composition and antioxidant activities of essential oil of oregano (Origanum vulgare subsp glandulosum (Desf.) Ietswaart) growing in North Africa. Ind Crops Prod 2016; 90: 32–37

[102] Asbaghian S, Shafaghat A, Zarea K, Kasimov F, Salimi F. Comparison of volatile constituents, and antioxidant and antibacterial activities of the essential oils of Thymus caucasicus, T. kotschyanus and T. vulgaris. Nat Prod Commun 2011; 6: 137–140

[103] de Santana MF, Guimarães AG, Chaves DO, Silva JC, Bonjardim LR, de Lucca Júnior W, Ferro JN, Barreto EO, dos Santos FE, Soares MB, Villarreal CF, Quintans JS, Quintans-Júnior LJ. The anti-hyperalgesic and anti-inflammatory profiles of p-cymene: evidence for the involvement of opioid system and cytokines. Pharm Biol 2015; 53: 1583–1590

[104] Bonjardim LR, Cunha ES, Guimarães AG, Santana MF, Oliveira MGB, Serafini MR, Araújo AAS, Antoniolli AR, Cavalcanti SCH, Santos MRV, Quintans-Júnior LJ. Evaluation of the anti-inflammatory and antinociceptive properties of p-cymene in mice. Zeitschrift fur Naturforsch - Sect C J Biosci 2012; 67: 15– 21

[105] Shang X, Wang Y, Zhou X, Guo X, Dong S, Wang D, Zhang J, Pan H, Zhang Y, Miao X. Acaricidal activity of oregano oil and its major component, carvacrol, thymol and p-cymene against Psoroptes cuniculi in vitro and in vivo. Vet Parasitol 2016; 226: 93–96

[106] Rao A, Zhang Y, Muend S, Rao R. Mechanism of antifungal activity of terpenoid phenols resembles calcium stress and inhibition of the TOR pathway. Antimicrob Agents Chemother 2010; 54: 5062–5069

[107] de Oliveira TM, de Carvalho RBF, da Costa IHF, de Oliveira GAL, de Souza AA, de Lima SG, de Freitas RM. Evaluation of p-cymene, a natural antioxidant. Pharm Biol 2015; 53: 423–428

[108] Marchese A, Arciola CR, Barbieri R, Silva AS, Nabavi SF, Tsetegho Sokeng AJ, Izadi M, Jafari NJ, Suntar I, Daglia M, Nabavi SM. Update on monoterpenes as antimicrobial agents: A particular focus on p-cymene. Materials (Basel) 2017; 10: 947–962

[109] Hotta M, Nakata R, Katsukawa M, Hori K, Takahashi S, Inoue H. Carvacrol, a component of thyme oil, activates PPARα and γ and suppresses COX-2 expression. J Lipid Res 2010; 51: 132–139

[110] Bianchini AE, Garlet QI, da Cunha JA, Bandeira JG, Brusque ICM, Salbego J, Heinzmann BM, 123 Baldisserotto B. Monoterpenoids (thymol, carvacrol and S-(+)-linalool) with anesthetic activity in silver catfish (Rhamdia quelen): evaluation of acetylcholinesterase and GABAergic activity. Brazilian J Med Biol Res 2017; 50

[111] Flood JF, Hernandez EN, Morley JE. Modulation of memory processing by neuropeptide Y. Brain Res 1987; 421: 280–290

[112] Kuzmin A V., Gerrits MAFM, Van Ree JM, Zvartau EE. Naloxone inhibits the reinforcing and motivational aspects of cocaine addiction in mice. Life Sci 1997; 60: PL257–PL264

[113] Matsuoka N, Maeda N, Yamazaki M, Ohkubo Y, Yamaguchi I. Effect of FR121196, a novel cognitive enhancer, on the memory impairment of rats in passive avoidance and radial arm maze tasks. J Pharmacol Exp Ther 1992; 263: 436–444

[114] Momose K, Inui A, Asakawa A, Ueno N, Nakajima M, Kasuga M. Anxiolytic effect of motilin and reversal with GM-109, a motilin antagonist, in mice. Peptides 1998; 19: 1739–1742

[115] Cvrčková F, Luštinec J, Žárský V. Complex, non-monotonic dose-response curves with multiple maxima: do we (ever) sample densely enough? Plant Signal Behav 2015; 10

[116] Kohn MC, Melnick RL. Biochemical origins of the non-monotonic receptor-mediated dose-response. J Mol Endocrinol 2002; 29: 113–123

[117] Federation of American Societies for Experimental Biology. Federation of American Societies for Experimental Biology. Nature 1941; 148: 658

[118] Jenner PM, Hagan EC, Taylor JM, Cook EL, Fitzhugh OG. Food flavourings and compounds of related structure I. Acute oral toxicity. Food Cosmet Toxicol 1964; 2: 327–343

[119] Hu X, Chu Y, Ma G, Li W, Wang X, Mo H, Yin Q, Guo J, Ma X, Zhou S. Simultaneous determination of ascaridole, p-cymene and α-terpinene in rat plasma after oral administration of Chenopodium ambrosioides L. by GC-MS. Biomed Chromatogr 2015; 29: 1682–1686

[120] Kagawa D, Jokura H, Ochiai R, Tokimitsu I, Tsubone H. The sedative effects and mechanism of action of cedrol inhalation with behavioral pharmacological evaluation. Planta Med 2003; 69: 637–641

[121] Çiçek SS. Structure-dependent activity of natural GABA(A) receptor modulators. Molecules 2018; 23: 1512

[122] Can OD, Demir Ozkay U, Kiyan HT, Demirci B. Psychopharmacological profile of Chamomile (Matricaria recutita L.) essential oil in mice. Phytomedicine 2012; 19: 306–310

[123] da Silva ER, de Oliveira DR, Fernandes PD, Bizzo HR, Leitaõ SG. Ethnopharmacological evaluation of Breu essential oils from Protium species administered by inhalation. Evidence-based Complement Altern Med 2017; 2017: 1–10

[124] Zhang J-H, Sun H-L, Chen S-Y, Zeng L, Wang T-T. Anti-fungal activity, mechanism studies on αPhellandrene and Nonanal against Penicillium cyclopium. Bot Stud 2017; 58: 1–9

[125] Dougnon G, Ito M. Role of Ascaridole and p-Cymene in the Sleep-Promoting Effects of Dysphania ambrosioides Essential Oil via the GABAergic System in a ddY Mouse Inhalation Model. J Nat Prod 2021; 84: 91–100

[126] Muniappan R, Reddy GVP, Raman A. Biological control of tropical weeds using arthropods. 2009

[127] Zahara M. Description of Chromolaena odorata L. R.M King and H. Robinson as medicinal plant: A 124 Review. IOP Conf Ser Mater Sci Eng 2019; 506

[128] Phan TT, Hughes MA, Cherry GW. Enhanced proliferation of fibroblasts and endothelial cells treated with an extract of the leaves of Chromolaena odorata (Eupolin), an herbal remedy for treating wounds. Plast Reconstr Surg 1998; 101: 756–765

[129] Akinmoladun AC, Ibukun EO, Dan-Ologe IA. Phytochemical constituents and antioxidant properties of extracts from the leaves of Chromolaena odorata. Sci Res Essays 2007; 2: 191–194

[130] Idu M, Onyibe HI. Medicinal Plants of Edo State, Nigeria. Res J Med Plant 2007; 1: 32–41

[131] Nanadini N, Nagababu P, Rao U, Venugopal N. Phytochemical, antimicrobial and antioxidant properties of an invasive weed Chromolaena odorata (L.) King & Robinson. Int J Phytomedicine 2014; 6: 286–292

[132] Lamaty G, Menut C, Zollo PHA, Kuiate JR, Bessiere JM, Ouamba JM, Silou T. Aromatic plants of tropical central africa IV. Essential oils of Eupatorium odoratum L. from Cameroon and Congo. J Essent Oil Res 1992; 4: 101–105

[133] Gogoi R, Sarma N, Begum T, Pandey SK, Lal M. North-East Indian Chromolaena odorata (L. King Robinson) Aerial Part Essential Oil Chemical Composition, Pharmacological Activities - Neurodegenerative Inhibitory and Toxicity Study. J Essent Oil-Bearing Plants 2020; 23: 1173–1191

[134] Tonzibo ZF, Wognin E, Chalchat JC, N’Guessan YT. Chemical Investigation of Chromolaena odorata L. King Robinson from Ivory Coast. J Essent Oil-Bearing Plants 2007; 10: 94–100

[135] Judzentiene A, Budiene J, Butkiene R, Kupcinskiene E, Laffont-Schwob I, Masotti V. Caryophyllene oxiderich essential oils of lithuanian Artemisia campestris ssp. campestris and their toxicity. Nat Prod Commun 2010; 5: 1981–1984

[136] Farag RS, Shalaby AS, El-Baroty GA, Ibrahim NA, Ali MA, Hassan EM. Chemical and Biological Evaluation of the Essential Oils of Different Melaleuca Species. Phyther Res 2004; 18: 30–35

[137] de Lima LS, da Silva DT, Garlet QI, Cunha MA, Mallmann CA, Baldisserotto B, Longhi SJ, Pereira AMS, Heinzmann BM. Anesthetic activity of Brazilian native plants in silver catfish (Rhamdia quelen). Neotrop Ichthyol 2013; 11: 443–451

[138] Oshima T, Ito M. Sedative effects of l-menthol, d-camphor, phenylethyl alcohol, and geraniol. J Nat Med 2021; 75: 319–325

[139] Ascari J, Sens SL, Nunes DS, Wisniewski A, Arbo MD, Linck VM, Lunardi P, Leal MB, Elisabetsky E. Sedative effects of essential oils obtained from Baccharis uncinella. Pharm Biol 2012; 50: 113–119

[140] Benovit SC, Silva LL, Salbego J, Loro VL, Mallmann CA, Baldisserotto B, Flores EMM, Heinzmann BM. Anesthetic activity and bioguided fractionation of the essential oil of Aloysia Gratissima (Gillies & Hook.) Tronc. in silver catfish Rhamdia quelen. An Acad Bras Cienc 2015; 87: 1675–1689

[141] Parodi TV, Gressler LT, Silva L de L, Becker AG, Schmidt D, Caron BO, Heinzmann BM, Baldisserotto B. Chemical composition of the essential oil of Aloysia triphylla under seasonal influence and its anaesthetic activity in fish. Aquac Res 2020; 51: 2515–2524

[142] Hammami S, Jmii H, Mokni R El, Khmiri A, Faidi K, Dhaouadi H, Aouni MH El, Aouni M, Joshi RK. Antiviral activities of Teucrium pseudochamaepitys growing spontaneously in Tunisia. Molecules 2015; 20: 20426–20433

[143] Zheng GQ, Kenney PM, Lam LKT. Sesquiterpenes from clove (Eugenia caryophyllata) as potential 125 anticarcinogenic agents. J Nat Prod 1992; 55: 999–1003

[144] Fidyt K, Fiedorowicz A, Strządała L, Szumny A. β-caryophyllene and β-caryophyllene oxide—natural compounds of anticancer and analgesic properties. Cancer Med 2016; 5: 3007–3017

[145] Stahl E, Kunde R. Die Leitsubstanzen der Haschisch-Suchhunde (Leading substances for hashish narcotic dogs). Kriminalistik 1973; 27: 385–389

[146] Meckes M, Calzada F, Tortoriello J, Gonzalez JL, Martínez M. Terpenoids isolated from Psidium guajava hexane extract with depressant activity on central nervous system. Phyther Res 1996; 10: 600–603

[147] Oppong-Damoah A, Blough BE, Makriyannis A, Murnane KS. The sesquiterpene beta-caryophyllene oxide attenuates ethanol drinking and place conditioning in mice. Heliyon 2019; 5: e01915

[148] The Good Scents Company. Caryophyllene, 13877-93-5. . Available at http://www.thegoodscentscompany.com/data/rw1011551.html#tosafty. Accessed 30.04.2021

[149] The Good Scents Company. Beta-caryophyllene oxide, 1139-30-6. . Available at http://www.thegoodscentscompany.com/data/rw1023631.html#tonotes. Accessed 30.04.2021

[150] Dewick PM. Medicinal Natural Products: A Biosynthetic Approach. John Wiley & Sons; 2002

[151] Sharma C, Al Kaabi JM, Nurulain SM, Goyal SN, Amjad KM, Ojha S. Polypharmacological Properties and Therapeutic Potential of β-Caryophyllene: A Dietary Phytocannabinoid of Pharmaceutical Promise. Curr Pharm Des 2016; 22: 3237–3264

[152] Klauke AL, Racz I, Pradier B, Markert A, Zimmer AM, Gertsch J, Zimmer A. The cannabinoid CB2 receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain. Eur Neuropsychopharmacol 2014; 24: 608–620

[153] Sabulal B, Dan M, J AJ, Kurup R, Pradeep NS, Valsamma RK, George V. Caryophyllene-rich rhizome oil of Zingiber nimmonii from South India: Chemical characterization and antimicrobial activity. Phytochemistry 2006; 67: 2469–2473

[154] Medeiros R, Passos GF, Vitor CE, Koepp J, Mazzuco TL, Pianowski LF, Campos MM, Calixto JB. Effect of two active compounds obtained from the essential oil of Cordia verbenacea on the acute inflammatory responses elicited by LPS in the rat paw. Br J Pharmacol 2007; 151: 618–627

[155] Galdino PM, Nascimento MVM, Florentino IF, Lino RC, Fajemiroye JO, Chaibub BA, de Paula JR, de Lima TCM, Costa EA. The anxiolytic-like effect of an essential oil derived from Spiranthera odoratissima A. St. Hil. leaves and its major component, β-caryophyllene, in male mice. Prog NeuroPsychopharmacology Biol Psychiatry 2012; 38: 276–284

[156] Marco EM, García-Gutiérrez MS, Bermúdez-Silva FJ, Moreira FA, Guimarães F, Manzanares J, Viveros MP. Endocannabinoid system and psychiatry: In search of a neurobiological basis for detrimental and potential therapeutic effects. Front Behav Neurosci 2011; 5

[157] The Jmol Team. Jmol: an open-source Java viewer for chemical structures in 3D. URL:www.jmol.sourceforgenet.net 2007; Available at http://jmol.sourceforge.net/. Accessed 30.04.2021

[158] Grundmann O, Nakajima JI, Kamata K, Seo S, Butterweck V. Kaempferol from the leaves of Apocynum venetum possesses anxiolytic activities in the elevated plus maze test in mice. Phytomedicine 2009; 16: 295– 302

[159] Buller R, Legrand V. Novel treatments for anxiety and depression: Hurdles in bringing them to the market. 126 Drug Discov Today 2001; 6: 1220–1230

[160] Majnooni MB, Mohammadi-Farani A, Gholivand MB, Nikbakht MR, Bahrami GR. Chemical composition and anxiolytic evaluation of Achillea wilhelmsii C. Koch essential oil in rat. Res Pharm Sci 2013; 8: 269– 275

[161] Abdelhalim A, Karim N, Chebib M, Aburjai T, Khan I, Johnston GAR, Hanrahan JR. Antidepressant, anxiolytic and antinociceptive activities of constituents from Rosmarinus officinalis. J Pharm Pharm Sci 2015; 18: 448–459

[162] Lahlou S, Figueiredo AF, Magalhães PJC, Leal-Cardoso JH. Cardiovascular effects of 1,8-cineole, a terpenoid oxide present in many plant essential oils, in normotensive rats. Can J Physiol Pharmacol 2002; 80: 1125–1131

[163] Gomes PB, Feitosa ML, Silva MIG, Noronha EC, Moura BA, Venâncio ET, Rios ERV, de Sousa DP, de Vasconcelos SMM, Fonteles MM de F, de Sousa FCF. Anxiolytic-like effect of the monoterpene 1,4-cineole in mice. Pharmacol Biochem Behav 2010; 96: 287–293

[164] Rosazza JPN, Steffens JJ, Sariaslani FS, Goswami A, Beale JM, Reeg S, Chapman R. Microbial Hydroxylation of 1,4-Cineole. Appl Environ Microbiol 1987; 53: 2482–2486

[165] Taheri MA, Fayaz S, Hoseini SM. Effects of dietary 1,8-cineole supplementation on serum stress and antioxidant markers of common carp (Cyprinus carpio) acutely exposed to ambient ammonia. Aquaculture 2019; 509: 8–15

[166] Zheng X, Zhang Y, Li Q, Liu Y, Wang X, Yang B, Zhu G, Zhou C, Gao Y, Liu Z. Effects of 1,8-cineole on neuropathic pain mediated by P2X2 receptor in the spinal cord dorsal horn. Sci Rep 2019; 9: 7909

[167] de Almeida AAC, da Costa JP, de Carvalho RBF, de Sousa DP, de Freitas RM. Evaluation of acute toxicity of a natural compound (+)-limonene epoxide and its anxiolytic-like action. Brain Res 2012; 1448: 56–62

[168] Ceremuga TE, Helmrick K, Kufahl Z, Kelley J, Keller B, Philippe F, Golder J, Padrón G. Investigation of the anxiolytic and antidepressant effects of curcumin, a compound from turmeric (Curcuma longa), in the adult male sprague-dawley rat. Holist Nurs Pract 2017; 31: 193–203

[169] Pires LF, Costa LM, Silva OA, De Almeida AAC, Cerqueira GS, De Sousa DP, De Freitas RM. Anxiolyticlike effects of carvacryl acetate, a derivative of carvacrol, in mice. Pharmacol Biochem Behav 2013; 112: 42–48

[170] Bourin M, Hascoët M. The mouse light/dark box test. Eur J Pharmacol 2003; 463: 55–65

[171] Porsolt RD, Anton G, Blavet N, Jalfre M. Behavioural despair in rats: A new model sensitive to antidepressant treatments. Eur J Pharmacol 1978; 47: 379–391

[172] Steru L, Chermat R, Thierry B, Simon P. The tail suspension test: A new method for screening antidepressants in mice. Psychopharmacology (Berl) 1985; 85: 367–370

[173] Radulovic̈ NS, Miltojevic̈ AB, Randjelovic̈ PJ, Stojanovic̈ NM, Boylan F. Effects of methyl and isopropyl N-methylanthranilates from Choisya ternata Kunth (Rutaceae) on experimental anxiety and depression in mice. Phyther Res 2013; 27: 1334–1338

[174] Poling A, Cleary J, Monaghan M. Burying by rats in response to aversive and nonaversive stimuli. J Exp Anal Behav 1981; 35: 31–44

[175] Bonetti EP, Pieri L, Cumin R, Schaffner R, Pieri M, Gamzu ER, Müller RKM, Haefely W. Benzodiazepine 127 antagonist Ro 15-1788: Neurological and behavioral effects. Psychopharmacology (Berl) 1982; 78: 8–18

[176] Porsolt RD, Bertin A, Jalfre M. Behavioral despair in mice: A primary screening test for antidepressants. Arch Int Pharmacodyn Ther 1977; 229: 327–336

[177] de Moraes PA, de Almeida GL, Costa M. Anxiolytic and sedative effects of extracts and essential oil from Citrus aurantium L. Biol Pharm Bull 2002; 25: 1629–1633

[178] Ajao MY, Akindele AJ. Anxiolytic and sedative properties of hydroethanolic extract of Telfairia occidentalis leaves in mice. Rev Bras Farmacogn 2013; 23: 301–309

[179] Kim KY, Seo HJ, Min SS, Park M, Seol GH. The effect of 1,8-cineole inhalation on preoperative anxiety: A randomized clinical trial. Evidence-based Complement Altern Med 2014; 2014: 1–7

[180] Tabari MA, Tehrani MAB. Evidence for the involvement of the GABAergic, but not serotonergic transmission in the anxiolytic-like effect of bisabolol in the mouse elevated plus maze. Naunyn Schmiedebergs Arch Pharmacol 2017; 390: 1041–1046

[181] Jung JW, Lee S. Anxiolytic Effects of Quercetin: Involvement of GABAergic System. J Life Sci 2014; 24: 290–296

[182] Quílez AM, Saenz MT, García GMD. Uncaria tomentosa (Willd. ex. Roem. & Schult.) DC. and Eucalyptus globulus Labill. interactions when administered with diazepam. Phyther Res 2012; 26: 458–461

[183] de Moura LV, da Silva AL, Figueiró M, Luis PÂ, Paula HA, Dupont BF, Bastos CE, Sávio ND, Moreno PRH, Elisabetsky E. Inhaled linalool-induced sedation in mice. Phytomedicine 2009; 16: 303–307

[184] Marques THC, Marques, Maria Leonildes Boavista Gomes CB, dos Santos LD, Siqueira HDS, Neto JDN, Branco M do SB, de Souza AA, de Sousa DP, de Freitas RM. Evaluation of the neuropharmacological properties of nerol in mice. World J Neurosci 2013; 03: 32–38

[185] Opdyke D. 1,4-Cineole. Food Chem Toxicol 1988; 26: 291

[186] Machado DG, Cunha MP, Neis VB, Balen GO, Colla A, Bettio LEB, Oliveira Á, Pazini FL, Dalmarco JB, Simionatto EL, Pizzolatti MG, Rodrigues ALS. Antidepressant-like effects of fractions, essential oil, carnosol and betulinic acid isolated from Rosmarinus officinalis L. Food Chem 2013; 136: 999–1005

[187] de Sousa DP, Raphael E, Brocksom U, Brocksom TJ. Sedative effect of monoterpene alcohols in mice: A preliminary screening. Zeitschrift fur Naturforsch - Sect C J Biosci 2007; 62: 563–566

[188] Abbasi-Maleki S, Kadkhoda Z, Taghizad-Farid R. The antidepressant-like effects of Origanum majorana essential oil on mice through monoaminergic modulation using the forced swimming test. J Tradit Complement Med 2020; 10: 327–335

[189] Guzmán-Gutiérrez SL, Gómez-Cansino R, García-Zebadúa JC, Jiménez-Pérez NC, Reyes-Chilpa R. Antidepressant activity of Litsea glaucescens essential oil: Identification of β-pinene and linalool as active principles. J Ethnopharmacol 2012; 143: 673–679

[190] Farahbod H, Johnson BA, Minami SS, Leon M. Chemotopic representations of aromatic odorants in the rat olfactory bulb. J Comp Neurol 2006; 497: 350–366

[191] Romagni JG, Allen SN, Dayan FE. Allelopathic effects of volatile cineoles on two weedy plant species. J Chem Ecol 2000; 26: 303–313

[192] Agorastos A, Chrousos GP. The neuroendocrinology of stress: the stress-related continuum of chronic 128 disease development. Mol Psychiatry 2021; 1–12

[193] Shiner B, Westgate CL, Bernardy NC, Schnurr PP, Watts B. Trends in Opioid Use Disorder Diagnoses and Medication Treatment Among Veterans With Posttraumatic Stress Disorder. J Dual Diagn 2017; 13: 201– 212

[194] Berlin HA. Antiepileptic drugs for the treatment of post-traumatic stress disorder. Curr Psychiatry Rep 2007; 9: 291–300

[195] Guina J, Merrill B. Benzodiazepines I: Upping the care on downers: The evidence of risks, benefits and alternatives. J Clin Med 2018; 7: 17

[196] Buckle J. Basic Plant Taxonomy, Basic Essential Oil Chemistry, Extraction, Biosynthesis, and Analysis. In: Clinical Aromatherapy. Churchill Livingstone; 2015: 37–72

[197] Abe AE, de Oliveira CE, Dalboni TM, Chagas-Paula DA, Rocha BA, de Oliveira RB, Gasparoto TH, da Costa FB, Campanelli AP. Anti-inflammatory sesquiterpene lactones from Tithonia diversifolia trigger different effects on human neutrophils. Rev Bras Farmacogn 2015; 25: 111–116

[198] Recio MC, Giner RM, Máñez S, Ríos JL, Cerdá M. In vivo activity of pseudoguaianolide sesquiterpene lactones in acute and chronic inflammation. Life Sci 2000; 66: 2509–2518

[199] Espinoza J, Urzúa A, Sanhueza L, Walter M, Fincheira P, Muñoz P, Mendoza L, Wilkens M. Essential oil, extracts, and sesquiterpenes obtained from the heartwood of Pilgerodendron uviferum act as potential inhibitors of the Staphylococcus aureus NorA multidrug efflux pump. Front Microbiol 2019; 10: 337

[200] Cho JY, Kim AR, Jung JH, Chun T, Rhee MH, Yoo ES. Cytotoxic and pro-apoptotic activities of cynaropicrin, a sesquiterpene lactone, on the viability of leukocyte cancer cell lines. Eur J Pharmacol 2004; 492: 85–94

[201] Olajide OA, Heiss EH, Schachner D, Wright CW, Vollmar AM, Dirsch VM. Synthetic cryptolepine inhibits DNA binding of NF-κB. Bioorg Med Chem 2007; 15: 43–49

[202] Huang GC, Chien TY, Chen LG, Wang CC. Antitumor effects of zerumbone from Zingiber zerumbet in P388D1 cells in vitro and in vivo. Planta Med 2005; 71: 219–224

[203] Burim RV, Canalle R, Lopes JLC, Vichnewski W, Takahashi CS. Genotoxic action of the sesquiterpene lactone centratherin on mammalian cells in vitro and in vivo. Teratog Carcinog Mutagen 2001; 21: 383–393

[204] Dougnon G, Ito M. Essential oil from the leaves of Chromolaena odorata, and sesquiterpene caryophyllene oxide induce sedative activity in mice. Pharmaceuticals 2021; 14: 651

[205] Wishart DS. Improving early drug discovery through ADME modelling: An overview. Drugs R D 2007; 8: 349–362

[206] Dunkin CM, Pokorny A, Almeida PF, Lee HS. Molecular Dynamics Studies of Transportan 10 (Tp10) Interacting with a POPC Lipid Bilayer. J Phys Chem B 2010; 115: 1188–1198

[207] Horn JN, Romo TD, Grossfield A. Simulating the Mechanism of Antimicrobial Lipopeptides with All-Atom Molecular Dynamics. Biochemistry 2013; 52: 5604–5610

[208] Duncavage EJ, Abel HJ, Pfeifer JD. In Silico Proficiency Testing for Clinical Next-Generation Sequencing. J Mol Diagnostics 2017; 19: 35–42

[209] Hartati FK, Djauhari AB, Viol KD. Evaluation of pharmacokinetic properties, toxicity, and bioactive 129 cytotoxic activity of black rice (Oryza sativa L.) as candidates for Diabetes mellitus drugs by in silico. Biointerface Res Appl Chem 2021; 11: 12301–12311

[210] Harley BK, Amponsah IK, Ben IO, Adongo DW, Mireku-Gyimah NA, Baah MK, Mensah AY, Fleischer TC. Myrianthus libericus: Possible mechanisms of hypoglycaemic action and in silico prediction of pharmacokinetics and toxicity profile of its bioactive metabolite, friedelan-3-one. Biomed Pharmacother 2021; 137: 111379

[211] Li Z, Howell K, Fang Z, Zhang P. Sesquiterpenes in grapes and wines: Occurrence, biosynthesis, functionality, and influence of winemaking processes. Compr Rev Food Sci Food Saf 2020; 19: 247–281

[212] Bayala B, Bassole IHN, Scifo R, Gnoula C, Morel L, Lobaccaro JMA, Simpore J. Anticancer activity of essential oils and their chemical components - A review. Am J Cancer Res 2014; 4: 591–607

[213] Eggersdorfer M. Terpenes. In: Ullmann’s Encyclopedia of Industrial Chemistry. American Cancer Society; 2000: 29–45

[214] Zafar F, Gupta A, Thangavel K, Khatana K, Sani AA, Ghosal A, Tandon P, Nishat N. Physicochemical and Pharmacokinetic Analysis of Anacardic Acid Derivatives. ACS Omega 2020; 5: 6021–6030

[215] Takemoto H, Yagura T, Ito M. Evaluation of volatile components from spikenard: Valerena-4,7(11)-diene is a highly active sedative compound. J Nat Med 2009; 63: 380–385

[216] Takemoto H, Ito M, Shiraki T, Yagura T, Honda G. Sedative effects of vapor inhalation of agarwood oil and spikenard extract and identification of their active components. J Nat Med 2008; 62: 41–46

[217] Toropov AA, Leszczynska D, Leszczynski J. Predicting water solubility and octanol water partition coefficient for carbon nanotubes based on the chiral vector. Comput Biol Chem 2007; 31: 127–128

[218] Judge V, Narasimhan B, Ahuja M, Sriram D, Yogeeswari P, De Clercq E, Pannecouque C, Balzarini J. Synthesis, antimycobacterial, antiviral, antimicrobial activities, and QSAR studies of isonicotinic acid-1- (substituted phenyl)-ethylidene/cycloheptylidene hydrazides. Med Chem Res 2012; 21: 1935–1952

[219] Mahajan S, Kamath V, Nayak S, Vaidya S. QSAR Analysis of Benzophenone Derivatives as Antimalarial Agents. Indian J Pharm Sci 2012; 74: 41

[220] Hamzeh-Mivehroud M, Rahmani S, Rashidi MR, Hosseinpour Feizi MA, Dastmalchi S. Structure-based investigation of rat aldehyde oxidase inhibition by flavonoids. 2013; 43: 661–670

[221] Hamzeh-Mivehroud M, Rahmani S, Rashidi MR, Dastmalchi S. Structural features of guinea pig aldehyde oxidase inhibitory activities of flavonoids explored using QSAR and molecular modeling studies. Med Chem Res 2016; 25: 2773–2786

[222] Ravichandran V, Jain PK, Mourya VK, Agrawal RK. QSAR study on some arylsulfonamides as anti-HIV agents. Med Chem Res 2007; 16: 342–351

[223] Puzyn T, Mostrag A, Falandysz J, Kholod Y, Leszczynski J. Predicting water solubility of congeners: Chloronaphthalenes—A case study. J Hazard Mater 2009; 170: 1014–1022

[224] Puzyn T, Rasulev B, Gajewicz A, Hu X, Dasari TP, Michalkova A, Hwang HM, Toropov A, Leszczynska D, Leszczynski J. Using nano-QSAR to predict the cytotoxicity of metal oxide nanoparticles. Nat Nanotechnol 2011 63 2011; 6: 175–178

[225] Daina A, Michielin O, Zoete V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 2017; 7: 1–13

[226] Zoete V, Daina A, Bovigny C, Michielin O. SwissSimilarity: A Web Tool for Low to Ultra High Throughput Ligand-Based Virtual Screening. J Chem Inf Model 2016; 56: 1399–1404

[227] Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 2012; 64: 4– 17 [228] Veber DF, Johnson SR, Cheng HY, Smith BR, Ward KW, Kopple KD. Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem 2002; 45: 2615–2623

[229] Ghose AK, Viswanadhan VN, Wendoloski JJ. A knowledge-based approach in designing combinatorial or medicinal chemistry libraries for drug discovery. 1. A qualitative and quantitative characterization of known drug databases. J Comb Chem 1999; 1: 55–68

[230] Santana K, do Nascimento LD, Lima e Lima A, Damasceno V, Nahum C, Braga RC, Lameira J. Applications of Virtual Screening in Bioprospecting: Facts, Shifts, and Perspectives to Explore the ChemoStructural Diversity of Natural Products. Front Chem 2021; 9: 155

[231] Naylor MR, Bockus AT, Blanco MJ, Lokey RS. Cyclic peptide natural products chart the frontier of oral bioavailability in the pursuit of undruggable targets. Curr Opin Chem Biol 2017; 38: 141–147

[232] Rossi SM, Doak BC, Backlund M, Poongavanam V, Over B, Ermondi G, Caron G, Matsson P, Kihlberg J. Impact of Dynamically Exposed Polarity on Permeability and Solubility of Chameleonic Drugs beyond the Rule of 5. J Med Chem 2018; 61: 4189–4202

[233] de Oliveira ECL, Santana K, Josino L, Lima e Lima AH, de Souza de Sales Júnior C. Predicting cellpenetrating peptides using machine learning algorithms and navigating in their chemical space. Sci Reports 2021 111 2021; 11: 1–15

[234] Doak BC, Over B, Giordanetto F, Kihlberg J. Oral Druggable Space beyond the Rule of 5: Insights from Drugs and Clinical Candidates. Chem Biol 2014; 21: 1115–1142

[235] Sander T, Freyss J, Von Korff M, Rufener C. DataWarrior: An open-source program for chemistry aware data visualization and analysis. J Chem Inf Model 2015; 55: 460–473

[236] Li X, Zhang Y, Chen H, Li H, Zhao Y. Insights into the Molecular Basis of the Acute Contact Toxicity of Diverse Organic Chemicals in the Honey Bee. J Chem Inf Model 2017; 57: 2948–2957

[237] Yap CW. PaDEL-descriptor: An open source software to calculate molecular descriptors and fingerprints. J Comput Chem 2011; 32: 1466–1474

[238] Golbraikh A, Tropsha A. Beware of q2! J Mol Graph Model 2002; 20: 269–276

[239] Ravichandran V, Rohini K, Harish R, Parasuraman S, Sureshkumar K. Insights into the key structural features of triazolothienopyrimidines as anti-HIV agents using QSAR, molecular docking, and pharmacophore modeling. Struct Chem 2019; 30: 1471–1484

[240] Ravichandran V, Rajak H. Qsar studies on neuraminidase inhibitors as anti-influenza agents. Turkish J Pharm Sci 2021; 18: 151–156

[241] Wold S, Eriksson L, Clementi S. Statistical Validation of QSAR Results. Chemom Methods Mol Des 2008; 2: 309–338

[242] Ravichandran V, Rajak H, Jain A, Sivadasan S, Varghese CP, Agrawal RK. Validation of QSAR Models - Strategies and Importance. Int J Drug Des Discov 2011; 2: 511–519 131

[243] Roy K, Das RN, Ambure P, Aher RB. Be aware of error measures. Further studies on validation of predictive QSAR models. Chemom Intell Lab Syst 2016; 152: 18–33

[244] Flores-Sumoza M, Alcázar JJ, Márquez E, Mora JR, Lezama J, Puello E. Classical QSAR and docking simulation of 4-pyridone derivatives for their antimalarial activity. Molecules 2018; 23: 3166

[245] Ravichandran V, Shalini S, Sundram K, Sokkalingam AD. QSAR study of substituted 1,3,4-oxadiazole naphthyridines as HIV-1 integrase inhibitors. Eur J Med Chem 2010; 45: 2791–2797

[246] Abdullahi M, Shallangwa GA, Uzairu A. In silico QSAR and molecular docking simulation of some novel aryl sulfonamide derivatives as inhibitors of H5N1 influenza A virus subtype. Beni-Suef Univ J Basic Appl Sci 2020; 9: 1–12

[247] Imamura K, Mataga N, Mori K. Coding of odor molecules by mitral/tufted cells in rabbit olfactory bulb. I. Aliphatic compounds. J Neurophysiol 1992; 68: 1986–2002

[248] Araneda RC, Kini AD, Firestein S. The molecular receptive range of an odorant receptor. Nat Neurosci 2000; 3: 1248–1255

[249] Yang NJ, Hinner MJ. Getting Across the Cell Membrane: An Overview for Small Molecules, Peptides, and Proteins. Methods Mol Biol 2015; 1266: 29

[250] Topliss JG, Edwards RP. Chance Factors in Studies of Quantitative Structure-Activity Relationships. J Med Chem 1979; 22: 1238–1244

参考文献をもっと見る

全国の大学の
卒論・修論・学位論文

一発検索!

この論文の関連論文を見る