Conessine is a steroidal alkaloid and a potent, selective histamine H3 receptor antagonist (pKi=8.27)[1-2]. Conessine is utilized in research areas such as antiviral, antibacterial resistance, and muscle atrophy[3-4].
In vitro, in A549 and RAW 264.7 cells, Conessine (1-40μM; 24h) significantly inhibited influenza A virus-induced cytopathic effects and viral plaque formation, and markedly reduced the expression of viral proteins (M2, NP, HA, NS1, PA, PB1)[5]. Pretreatment of A549, Huh7.5, and BHK21 cells with Conessine (10μM; 1h) upregulated intracellular cholesterol levels, increased the expression of cholesterol synthesis/metabolism-related genes (HMGCR, HMGCS1, INSIG1, MSMO1), and inhibited the replication of intracellular enveloped viruses[6].
In vivo,Swiss mice were treated with Conessine (0.1-10mg/kg; single subcutaneous injection), and 1 hour later, the mice received an intraperitoneal injection of ethanol (2g/kg). Conessine significantly enhanced ethanol-induced psychomotor excitation and prolonged the duration of hyperlocomotion. Conessine blocked ethanol's effects on dopaminergic and noradrenergic neurotransmission in the prefrontal cortex and reduced the levels of dopamine metabolites in the substantia nigra[7]. In ICR male mice treated with methamphetamine (3mg/kg; intraperitoneal injection), administration of Conessine (20mg/kg; single intraperitoneal injection) 30 minutes later significantly inhibited methamphetamine-induced hyperlocomotion. The effect of Conessine was mediated by blocking H3 receptors, thereby releasing histamine, which subsequently activated postsynaptic H1 receptors[8].
References:
[1] Kim H, Jang M, Park R, et al. Conessine treatment reduces dexamethasone-induced muscle atrophy by regulating MuRF1 and atrogin-1 expression. J Microbiol Biotechnol. 2018 Feb 1.
[2] Dua VK, Verma G, Singh B, et al. Anti-malarial property of steroidal alkaloid conessine isolated from the bark of Holarrhena antidysenterica. Malar J. 2013 Jun 10;12:194. doi: 10.1186/1475-2875-12-194.
[3] Kim H, Lee KI, Jang M, et al. Conessine Interferes with Oxidative Stress-Induced C2C12 Myoblast Cell Death through Inhibition of Autophagic Flux. PLoS One. 2016 Jun 3;11(6):e0157096.
[4] Jewboonchu J, Saetang J, Saeloh D, et al. Atomistic insight and modeled elucidation of conessine towards Pseudomonas aeruginosa efflux pump. J Biomol Struct Dyn. 2022 Mar;40(4):1480-1489.
[5] Cho WK, Ma JY. Anti-Viral Activity of Conessine Against Influenza A Virus. Int J Mol Sci. 2025 Aug 5;26(15):7572.
[6] Zhou S, Li J, Ling X, et al. Conessine inhibits enveloped viruses replication through up-regulating cholesterol level. Virus Res. 2023 Dec;338:199234.
[7] Morais-Silva G, Ferreira-Santos M, Marin MT. Conessine, an H3 receptor antagonist, alters behavioral and neurochemical effects of ethanol in mice. Behav Brain Res. 2016 May 15;305:100-7.
[8] Kitanaka J, Kitanaka N, Hall FS, et al. In vivo evaluation of effects of histamine H3 receptor antagonists on methamphetamine-induced hyperlocomotion in mice. Brain Res. 2020 Aug 1;1740:146873.
Conessine是一种甾体生物碱，作为强效、选择性的组胺H3受体拮抗剂（pKi=8.27）[1-2]。Conessine可用于抗病毒、抗菌耐药性和肌肉萎缩等相关研究[3-4]。
在体外，在A549、RAW 264.7细胞中，Conessine（1-40μM；24h）可显著抑制由流感A病毒（IAV）感染引起的细胞病变效应（CPE）和病毒噬斑形成，并能显著降低病毒蛋白（M2、NP、HA、NS1、PA、PB1）的表达[5]。Conessine（10μM；1h）预处理A549、Huh7.5和BHK21细胞，可上调细胞内的胆固醇水平，并增加与胆固醇合成/代谢相关基因（HMGCR、HMGCS1、INSIG1、MSMO1）的表达，并抑制胞内包膜病毒的复制[6]。
在体内，Conessine（0.1-10mg/kg；单次皮下注射）处理Swiss小鼠，1小时后小鼠接受腹腔注射乙醇（2g/kg）。Conessine显著增强了乙醇诱导的精神运动兴奋效应，并延长了高活动力持续时间。Conessine阻断了乙醇在额前皮质中对多巴胺能和去甲肾上腺素能神经传递的影响，并降低了黑质中多巴胺代谢物的水平[7]。在甲苯丙胺（3mg/kg；腹腔注射）处理ICR雄性小鼠30分钟后，Conessine（20mg/kg；单次腹腔注射）处理显著抑制了甲苯丙胺诱导的高活动力。Conessine通过阻断H3受体，释放组胺，进而激活突触后H1受体介导[8]。