ABIETANE QUINONE DITERPENES WITH ANTITUBERCULOSIS ACTIVITY ISOLATED FROM THE GENUS SALVIA

. The name Salvia, the largest genus of Lamiaceae, derives from the Latin "salvere" (= to feel good, healthy). In the Mediterranean basin, S. officinalis has been used since the time of the ancient Egyptians for medicinal purposes. Pliny the Elder was the first known author to describe a plant called "Salvia" by the Romans. Recent scientific research has confirmed the antituberculosis properties of numerous species present in the traditional ethnobotany.

The genus Salvia is present spontaneously in all continents except Australia, with diffusion in the temperate and tropical regions of the two hemispheres.
The species of this genus, about 900, prefer forest or mountainous habitats, but also ruderal environments. Six geographical areas constitute the centers of biodiversity of this kind: Central-southern states of the U.S.A., Central America where the Mexican area is the area with the greatest presence of taxa, South America, Southern Africa, Eastern and Western Asia. This vast geographical and habitat distribution makes the genus Salvia the most numerous and complex in the family Lamiaceae. The area including the Mediterranean Basin has about 250 species [4].
Many oh them show interesting biological activities when tested both "in vitro" and "in vivo" [5,6,10]. Species of the genus Salvia have been studied as a potential resource of quinone diterpenes with antimicrobial and antituberculosis activity [3,17].  CURRENT ISSUES AND PROSPECTS FOR THE DEVELOPMENT OF SCIENTIFIC RESEARCH   280   genus Salvia were examined: about 54 compounds show different biological   activity, while many have not yet been tested or are inactive; out of 175 molecules,   151 have the structure of abietane and 24 have a structure different from abietic acid [4,15].
The first two groups include the compounds endowed with the abietanic skeleton with the quinone group in the -para or -ortho position; the third group includes compounds in which a ring of the abietanic skeleton is open or rearranged; the fourth group includes all compounds with a molecular structure other than abietic acid. Several studies evidenced that the most typical activity of all diterpene quinones is the anticancer and antimicrobial activity (including antituberculosis), which was demonstrated by 38% and 30% of the molecules tested, respectively [4]. Diterpenoids isolated from Lamiaceae have more than 50 different skeletons [15].
Diterpenoids can be isolated from all plant organs, but most of them are found in the roots (Fig. 2). Some diterpene quinones are very common in several species of the genus Salvia (mostly "Tashinones") ( Fig. 3). In that way, around 100 compounds are extremely uncommon and each has been found in only one species. All this can be explained by the fact that many species are still poorly studied or that some diterpene quinones are exclusive to certain species [4].  [15,19].
According to recent studies, many tanshinoni have been shown to be active in the treatment of tuberculosis. Tanshinones from Salvia miltiorrhiza (Fig. 4) inhibit      also appeared to be active against Mycobacterium tuberculosis, but much weaker than the above compounds (MIC 250 μg/ml) [14]. Fig.9. Hypargenin F Many authors hypothesize that the presence of the quinone group in abietane quinone diterpenes is responsible for their antibacterial and antituberculosis activity [7,8,9]. A prolonged toxicity study in rats demonstrated that administration of S. miltiorrhiza extract of 8000 mg / kg for 3 months was not associated with toxic effects, as was a single oral dose of 15 g / kg in mice [13].
The LD of the aqueous and methanolic extract of S. deserta administered to mice is 30-40 g / kg. The LD 50 of the ethanol extract of S. Przewalski, administered to mice orally, intraperitoneally and intramuscularly, is 2547.7, 780.8, and 901.3 mg / kg, respectively [15].
In conclusion, it seems that toxic effects are not particularly relevant for Salvia species containing quinine diterpenes [4,15]. Based on the above, it is possible to conclude that both the Salvia genus as a whole and its abietane diterpene quinones certainly deserve attention and require more careful and in-depth research from the scientific community.

I would like to express my gratitude and appreciation for Assunta Esposito
Ph.D, Associate Professor, University of Campania Luigi Vanvitelli, Caserta, Italy whose guidance, support and encouragement has been invaluable.