Sanchez-Ramos JR. The rise and fall of tobacco as a botanical medicine. J Herb Med. 2020;22:100374.

Article  PubMed  PubMed Central  Google Scholar 

Berlowitz I, Torres EG, Walt H, Wolf U, Maake C, Martin-Soelch C. “Tobacco Is the Chief Medicinal Plant in My Work”: Therapeutic Uses of Tobacco in Peruvian Amazonian Medicine Exemplified by the Work of a Maestro Tabaquero. Front Pharmacol. 2020;11:594591.

Article  PubMed  PubMed Central  Google Scholar 

Charlton A. Medicinal uses of tobacco in history. J R Soc Med. 2004;97(6):292–6.

Article  PubMed  PubMed Central  Google Scholar 

Maehle AH. “Receptive substances”: John Newport Langley (1852–1925) and his path to a receptor theory of drug action. Med Hist. 2004;48(2):153–74.

Article  PubMed  PubMed Central  Google Scholar 

Miwa JM, Freedman R, Lester HA. Neural systems governed by nicotinic acetylcholine receptors: emerging hypotheses. Neuron. 2011;70(1):20–33.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hone AJ, McIntosh JM. Nicotinic acetylcholine receptors in neuropathic and inflammatory pain. FEBS Lett. 2018;592(7):1045–62.

Article  CAS  PubMed  Google Scholar 

Rosas-Ballina M, Olofsson PS, Ochani M, Valdes-Ferrer SI, Levine YA, Reardon C, et al. Acetylcholine-Synthesizing T Cells Relay Neural Signals in a Vagus Nerve Circuit. Science. 2011;334(6052):98–101.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang H, Yu M, Ochani M, Amella CA, Tanovic M, Susarla S, et al. Nicotinic acetylcholine receptor alpha 7 subunit is an essential regulator of inflammation. Nature. 2003;421(6921):384–8.

Article  CAS  PubMed  Google Scholar 

Gautron L, Rutkowski JM, Burton MD, Wei W, Wan Y, Elmquist JK. Neuronal and nonneuronal cholinergic structures in the mouse gastrointestinal tract and spleen. J Comp Neurol. 2013;521(16):3741–67.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dhanasobhon D, Medrano MC, Becker LJ, Moreno-Lopez Y, Kavraal S, Bichara C, et al. Enhanced analgesic cholinergic tone in the spinal cord in a mouse model of neuropathic pain. Neurobiol Dis. 2021;155:105363.

Article  CAS  PubMed  Google Scholar 

Chiari A, Tobin JR, Pan HL, Hood DD, Eisenach JC. Sex differences in cholinergic analgesia I: a supplemental nicotinic mechanism in normal females. Anesthesiology. 1999;91(5):1447–54.

Article  CAS  PubMed  Google Scholar 

Chen SR, Pan HL. Spinal GABAB receptors mediate antinociceptive actions of cholinergic agents in normal and diabetic rats. Brain Res. 2003;965(1–2):67–74.

Article  CAS  PubMed  Google Scholar 

Omare MO, Kibet JK, Cherutoi JK, Kengara FO. A review of tobacco abuse and its epidemiological consequences. J Public Health. 2022;30:1485–500.

Saito Y, Takizawa H, Konishi S, Yoshida D, Mizusaki S. Identification of cembratriene-4,6-diol as antitumor-promoting agent from cigarette smoke condensate. Carcinogenesis. 1985;6(8):1189–94.

Article  CAS  PubMed  Google Scholar 

Ferchmin P, Lukas R, Hann R, Fryer J, Eaton J, Pagan O, et al. Tobacco cembranoids block behavioral sensitization to nicotine and inhibit neuronal acetylcholine receptor function. J Neurosci Res. 2001;64(1):18–25.

Article  CAS  PubMed  Google Scholar 

Roberts DL, Rowland RL. Macrocyclic Diterpenes. a- and /3–4,8,13-Duvatriene-l,3-diols from Tobacco. J Org Chem. 1962;27(11):3989–95.

Article  CAS  Google Scholar 

Yan N, Du Y, Liu X, Zhang H, Liu Y, Zhang Z. A Review on Bioactivities of Tobacco Cembranoid Diterpenes. Biomolecules. 2019;9(1):30.

Article  PubMed  PubMed Central  Google Scholar 

Mudhish EA, Siddique AB, Ebrahim HY, Abdelwahed KS, King JA, El Sayed KA. The Tobacco beta-Cembrenediol: A prostate cancer recurrence suppressor lead and prospective scaffold via modulation of indoleamine 2,3-dioxygenase and tryptophan dioxygenase. Nutrients. 2022;14(7):1505.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fu H, Wang J, Wang J, Liu L, Jiang J, Hao J. 4R-cembranoid protects neuronal cells from oxygen-glucose deprivation by modulating microglial cell activation. Brain Res Bull. 2022;179:74–82.

Article  CAS  PubMed  Google Scholar 

Martins AH, Hu J, Xu Z, Mu C, Alvarez P, Ford BD, et al. Neuroprotective activity of (1S,2E,4R,6R,-7E,11E)-2,7,11-cembratriene-4,6-diol (4R) in vitro and in vivo in rodent models of brain ischemia. Neuroscience. 2015;291:250–9.

Article  CAS  PubMed  Google Scholar 

Eterovic VA, Del Valle-Rodriguez A, Perez D, Carrasco M, Khanfar MA, El Sayed KA, et al. Protective activity of (1S,2E,4R,6R,7E,11E)-2,7,11-cembratriene-4,6-diol analogues against diisopropylfluorophosphate neurotoxicity: preliminary structure-activity relationship and pharmacophore modeling. Bioorg Med Chem. 2013;21(15):4678–86.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Eaton MJ, Ospina CA, Rodriguez AD, Eterovic VA. Differential inhibition of nicotine- and acetylcholine-evoked currents through alpha4beta2 neuronal nicotinic receptors by tobacco cembranoids in Xenopus oocytes. Neurosci Lett. 2004;366(1):97–102.

Article  CAS  PubMed  Google Scholar 

Ferchmin PA, Hao J, Perez D, Penzo M, Maldonado HM, Gonzalez MT, et al. Tobacco cembranoids protect the function of acute hippocampal slices against NMDA by a mechanism mediated by alpha4beta2 nicotinic receptors. J Neurosci Res. 2005;82(5):631–41.

Article  CAS  PubMed  Google Scholar 

Eterovic VA, Perez D, Martins AH, Cuadrado BL, Carrasco M, Ferchmin PA. A cembranoid protects acute hippocampal slices against paraoxon neurotoxicity. Toxicol In Vitro. 2011;25(7):1468–74.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ferchmin PA, Andino M, Reyes Salaman R, Alves J, Velez-Roman J, Cuadrado B, et al. 4R-cembranoid protects against diisopropylfluorophosphate-mediated neurodegeneration. Neurotoxicology. 2014;44:80–90.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ferchmin PA, Perez D, Cuadrado BL, Carrasco M, Martins AH, Eterovic VA. Neuroprotection against diisopropylfluorophosphate in acute hippocampal slices. Neurochem Res. 2015;40(10):2143–51.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Olsson E, Holth A, Kumlin E, Bohlin L, Wahlberg I. Structure-related inhibiting activity of some tobacco cembranoids on the prostaglandin synthesis in vitro. Planta Med. 1993;59(4):293–5.

Article  CAS  PubMed  Google Scholar 

Ferchmin PA, Pagan OR, Ulrich H, Szeto AC, Hann RM, Eterovic VA. Actions of octocoral and tobacco cembranoids on nicotinic receptors. Toxicon. 2009;54(8):1174–82.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhu S, Huang S, Xia G, Wu J, Shen Y, Wang Y, et al. Anti-inflammatory effects of alpha7-nicotinic ACh receptors are exerted through interactions with adenylyl cyclase-6. Br J Pharmacol. 2021;178(11):2324–38.

Article  CAS  PubMed  Google Scholar 

Hone AJ, McIntosh JM. Nicotinic acetylcholine receptors in neuropathic and inflammatory pain. FEBS Lett. 2018;592(7):1045–62.

Article  CAS  PubMed  Google Scholar 

Umana IC, Daniele CA, McGehee DS. Neuronal nicotinic receptors as analgesic targets: It’s a winding road. Biochem Pharmacol. 2013;86(8):1208–14.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wu YJ, Wang L, Ji CF, Gu SF, Yin Q, Zuo J. The role of alpha7nAChR-mediated cholinergic anti-inflammatory pathway in immune cells. Inflammation. 2021;44(3):821–34.

Article  CAS  PubMed  Google Scholar 

Umana IC, Daniele CA, Miller BA, Abburi C, Gallagher K, Brown MA, et al. Nicotinic modulation of descending pain control circuitry. Pain. 2017;158(10):1938–50.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kageyama-Yahara N, Suehiro Y, Yamamoto T, Kadowaki M. IgE-induced degranulation of mucosal mast cells is negatively regulated via nicotinic acetylcholine receptors. Biochem Biophys Res Commun. 2008;377(1):321–5.

Article  CAS  PubMed  Google Scholar 

de Lucas-Cerrillo AM, Maldifassi MC, Arnalich F, Renart J, Atienza G, Serantes R, et al. Function of partially duplicated human α77 nicotinic receptor subunit CHRFAM7A gene: potential implications for the cholinergic anti-inflammatory response. J Biol Chem. 2011;286(1):594–606.

Article  PubMed