Botaceuticals

Red Sage roots x Cardiovascular health

1. INTRODUCTION

Red sage (Salvia miltiorrhiza) is a perennial plant of the lamiaceae family, native to eastern Asia. Also known as Danshen, the health properties of its roots has been praised in Asia for over two millenia. Traditional Chinese Medicine recommands it essentially for cardiovascular health but recent scientific data indicate that its therapeutical potential goes much futher. Indeed, red sage and its active constituents have been the subject of numerous studies, both in vitro and in vivo, during the last decade. The results tends to not only validate the traditional use of the plant but also to widen its scope of health applications.
2. MOLECULES OF INTEREST

2.1. Diterpenoids

Red sage contains a myriad of diterpenoids with a majority of specific molecules called tanshinones. Tanshinones are abietane diterpenoids mainly found in the roots of Salvia miltiorrhiza. There is a wide diversity of them: tanshinone I, tanshinone IIA, cryptotanshinone, dihydrotanshinones and tetrahydrotanshinones (also called trijuganones since they also can be found in Salvia trijuga). The great majority of studies are however focusing on the properties of two of them: tanshinone IIA and, most recently, Cryptotanshinone.
These molecules are liposoluble and therefore benefit from significant bioavailability (although rarely used in traditional medicine, the oily maceration of red sage root is therefore of great interest). Tanshinones are, however, pratically insoluble in water and therefore are not involved in Danshen tea benefits.

2.2. Phenolic acids

Danshen roots (Salvia miltiorrhiza) contains more than 30 different phenolic acids [1]. Among them, Salvianolic acids and Salvianic acids (also called Danshensu) are probably the most studied. Indeed, experimental data clearly indicates that those molecules are of high therapeutical value in various health issues. Unlike tanshinones, Salvianolic acids and Danshesu are partially soluble in water and can therefore be considered as the molecules of interest in danshen tea.
3. CARDIOVASCULAR HEALTH & SALVIA MILTIORRHIZA

Due to the presence of various active molecules wich are the subject of ever-increasing scientific studies, the therapeutic potential of Salvia miltiorrhiza roots appears particularly wide and seems to expand every day. However, its interest in cardiovascular health remains the most studied topic to date (the goal of those studies often being to identify the pharmacological mechanisms explaining the traditional indication in Chinese medicine). This first article will therefore focus on the data associated with the use of red sage in this context (Future articles will focus on other application of this fascinating root). As it is often the case with medicinal plants, the activity of red sage is not limited to a single molecular cascade but intervenes at various levels for a global positive effect.

3.1. Red sage & Atherosclerosis

Atherosclerosis is one of the most concerning cardiovascular pathology in the world and, since Salvia miltiorrhiza is considered to be beneficial cardiovascular health, the plant was traditionally considered to be of interest in this context [2-4], an assumption that experimental data seems to validate. However, not every Danshen extract are of equal potential.
For instance, if some data indicate a potential benefit of Salvianolic acid A [5] and Salvianolic acid B [6], those are not sufficient to confirm a beneficial impact. In fact, a randomized clinical trial highlighted that water extract of Salvia miltiorrhiza doesn't seem to be effective as anti-atherosclerosis treatment [7]. This is not surprising, since most scientific data highlighted tanshinone IIA and Cryptotanshinone as the main active substances in this context (not present in water extract) [8]. They both have multiple impact on inflammation cascades like inhibiting TNFalpha [9-11] & NF-κB [11-14].
This anti-inflammatory activity has a significant impact on atherosclerosis, like the inhibition of LOX-1 expression (Lectin-like oxidized LDL receptor-1) [14-15], a receptor involved in many aspects of the pathology like monocytes recruiting & Foam cell formation [16]. It should be noted that Dihydrotanshinone has been reported to have a similar effect on LOX-1 [17].

Moreover, tanshinone IIA has been highlighted as an inhibitor of Foam cell formation through the modulation macrophage lipid accumulation [18-19] and cholesterol efflux [20], as well as other positive influence on molecular cascades related to atherosclerosis [21-24].
If those results clearly invite to consider the use of red sage for health purpose, some precautions should be taken in a clinical context. Indeed, Salvia miltiorrhiza extract are already used as medicine in some asian countries and drug interactions has been highlighted between Danshen and different statins (notably atorvastatin [25] and rosuvastatins [26]).

3.2. Red sage & Platelet aggregation

Red sage is traditionnaly considered as blood thinning and numerous experimental studies tend to validate the anti-aggregation effect on platelets [27-28]. Those health properties can be attributed to both tanshinones (tanshinone IIA [28-31], Cryptotanshinone [31] and dihydrotanshinone [32]) and phenolic acids (Salvianolic acids [33-38] and Danshensu [39]). Like for atherosclerosis, mutiple molecular pathways seem involved but the great majority of them are related to inflammation (for more information on anti-inflammatory properties of red sage, see future article).
Once again, attention should be paid to potential drug interactions, notably with clopidogrel (a drug with wich active molecules of danshen seem to have similarities in their mode of action) [40] and warfarin [41]. In this last case, however, some studies on specific pharmaceutical galenic have shown no significant issues [42-43].

3.3. Red sage & Hypertension

Hypertension is one of the most common cardiovascular condition. Fufang Danshen, a traditional formula mainly composed of Salvia miltiorrhiza roots has been evaluated in hypertensive context in a clinical study, showing positive results [44]. However, even if some preliminary studies also show vasodilatative effects of tanshinones (Tanshinone IIA [45], Cryptotanshinone [46] and dihydrotanshinone [47]) and salvianolic acid [48], they are not yet sufficient to consider red sage roots as antihypertensive medicinal plant. Nonetheless, multiple experimental studies revealed a positive impact on structural alterations and remodeling processes related to hypertensive state. A good exemple is ventricular hypertrophy associated to hypertension where tanshinone IIA seems to have a very positive impact [49-52].

3.4. Red sage & Cardiovascular protection

Of all the physiological effects of red sage roots and its constituents, none has probably been more studied than the cardioprotective properties. It would be to long to enumerate each and every one of them but it seems relevant to point out that substantial scientific data have been obtained on the activity of many active molecules from Salvia miltiorrhiza. Among them, Tanshinone IIA [53-61] and Salvianolic acids [62-70] are probably the most studied. However, it's should be noted that Cryptotanshinone has also been the subject of multiple experiments for the inhibition of cardiac fibrosis [71-73].
4. CONCLUSION

With numerous scientific data now available, it is reasonable to consider Danshen roots (Salvia miltiorrhiza) and its active molecules, as a great opportunity for modern phytotherapy. If Eastern Medicine considers Danshen as a "go to" medicinal plant for cardiovascular health (an indication that scientific data corroborate), its potential go much futher with interesting data in various areas such as Arthritis, Psoriasis and even perspectives in Oncology (see future articles for more information). 

However, despite its great potential, the use of red sage roots stays very limited in western phytotherapy. This paradoxal phenomenon can be explained by the fact that sourcing of pure (no contamination & no adulteration) as well as consistently performant (stable molecular composition with high concentration of bioactive molecules) red sage roots, is extremely difficult. A challenge that the R&D team of BOTALYS has been taking up since many years now. Carefully selecting the best cultivars and meticulously discovering the ideal growing conditions (temperature, light, nutrients, elicitors, etc.) for the production of the purest and most bioactive red sage, using indoor vertical farming.
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