Totarol (Synonyms: NSC 299936, (+)-Totarol, trans-Totarol)

Totarol is a diterpene originally isolated from P. totara that has diverse biological activities, including antibacterial, antioxidant, and neuroprotective properties.[1] It is active against Gram-positive bacteria, including P. acnes, S. mutans, B. subtilis, and B. ammoniagenes (MICs = 0.39, 0.78, 1.56, and 0.78 µg/ml, respectively), as well as penicillin-resistant and -susceptible strains of S. aureus (MICs = 0.78 and 1.56 µg/ml, respectively).[2] It inhibits mitochondrial respiration in P. aeruginosa, inhibiting NADH-cytochrome c, NADH-DPIP, and NADH-coenzyme Q reductases but not cytochrome c oxidase.[3] Totarol inhibits Fe(III)-ADP/NADPH-induced lipid oxidation in rat liver microsomes and mitochondria (IC50s = 4.79 and 0.47 µM, respectively) and autooxidation of linoleic acid with an IC50 value of 9.8 µM.[4] In rat primary cerebellar granule cells, totarol increases Akt and GSK-3β phosphorylation when used at a concentration of 5 µM and prevents neuronal death induced by glutamate or oxygen and glucose deprivation.[5] It also reduces infarct volume in a rat model of acute cerebral ischemic injury when administered at doses of 1 and 10 microgram/kg.

Reference:
[1]. Short, W.F., and Stromberg, H. Totarol. Part I. J. Chem. Soc. 0, 516-520 (1937).
[2]. Kubo, I., Muroi, H., and Himehima, M. Antibacterial activity of totarol and its potentiation. J. Nat. Prod. 55(10), 1436-1440 (1992).
[3]. Haraguchi, H., Oike, S., Muroi, H., et al. Mode of antibacterial action of totarol, a diterpene from Podocarpus nagi. Planta Med. 62(2), 122-125 (1996).
[4]. Haraguchi, H., Ishikawa, H., and Kubo, I. Antioxidative action of diterpenoids from Podocarpus nagi. Planta Med. 63(3), 213-215 (1997).
[5]. Gao, Y., Xu, X., Chang, S., et al. Totarol prevents neuronal injury in vitro and ameliorates brain ischemic stroke: Potential roles of Akt activation and HO-1 induction. Toxicol. Appl. Pharmacol. 289(2), 142-154 (2015).