1. General Characteristics of the Salvia Genus
Comprising 900 species, the
Salvia genus is the largest in the Lamiaceae family. The main centers of species diversity are Central and South America (500) and the Mediterranean with Central Asia (250) and East Asia (more than 90 species)
[7,19][1][2]. The diversity of
Salvia in Central Asia is understudied: the first detailed summary of the Central Asian variations is presented by S.N. Kudryashov (1937)
[20][3], indicating 19 species of sage.
A.M. Makhmedov (1984, 1987)
[21][4] gives a significantly expanded composition of species, 34 species, including 20 endemics. According to the latest floristic checklists by Khassanov (2015) and Li et al. (2020)
[22[5][6],
23], there are 41 native
Salvia species in the flora of Central Asia (24 of which are endemic), and 13 species are found on the territory of Kazakhstan:
S. abrotanoides (Kar.) Sytsma,
S. aethiopis L.,
S. deserta Schangin.,
S. dumetorum Andrz.,
S. macrosiphon Boiss.,
S. karelinii J.B. Walker,
S. korolkowii Regel & Schmalh.,
S. nemorosa L.,
S. spinosa L.,
S. sclarea L.,
S. virgata Jacq., and
S. verticillata L., with
S. trautvetteri Regel being endemic to the flora of Kazakhstan
[23][6].
Sage has long been used as a flavoring agent in food, aromatics and cosmetics. Some species are known from a wide variety of applications in traditional medicine
[24][7] and might be recommended as a safe and effective remedy for treatment of many diseases. All species of sage are valuable to humans, displaying a wide range of pharmacological activity, including antitumor, anti-inflammatory, antinociceptive, antioxidant, antimicrobial, antimutagenic, anti-dementia, hypoglycemic and hypolipidemic effects. Each species is individual in terms of the content of essential oil (EO), phenolic acids, flavonoids and terpenic compounds. Characteristics of some of them are presented below.
S. deserta Schang. (desert sage) is a herbaceous perennial plant with 35–90 cm long stems. The stems are several, rarely single, longer than the inflorescence, branched in the upper part, and pubescent from the very base. The leaves are small, basal and dry up early. Inflorescences are simple, with 1–2(3) pairs of lateral branches. The corolla is dark purple and short pubescent on the outside. The fruit is dark brown, triangular–spherical nuts. The plant blooms in June–August and bears fruit in August–September. In general, it can be met in the mountains of Central Asia, Caucasus, Western Siberia and China
[25,26][8][9]. The aerial part of
S. deserta contains 0.02% of EO and the seeds contain 23% fatty acids
[25][8]. The aerial part of
S. deserta contains triterpenoids (ursane, oleanane and lupine derivatives)
[26][9], while diterpenes (royleanone, ferruginol, taxodione) and caffeic acid derivatives (rosmarinic acid, lithospermic acid B and the steroid daucosterol) are mostly found in the roots
[27][10]. Chemical constituents of
S. deserta are scarcely presented in the literature data with studies focused on its antimicrobial, antileishmanial and antithrombotic activities
[25,28][8][11].
S. sclarea L. (clary or musk sage) is a perennial plant with a straight stem covered with fine hairs, and it has bright inflorescences. The leaves can reach 30–35 cm in length and up to 20 cm in width. They are egg-shaped with fine wrinkles, pointed at the ends, and located on elongated petioles. The bush can bloom all summer. As a weed, it grows on any soil: rocky, clay, sandy. Growing mainly on arable land and mountain slopes, it reaches a height of 1 m or slightly higher under favorable conditions. Sage blooms in June–July, and its fruits ripen in June–August
[25][8]. Clary sage is rich in EO, containing 45–87% linalyl acetate, 0.3–3.2% geranyl acetate, and small amounts of neryl acetate and bornyl acetate. The content of monoterpene alcohols is significant, including linalool, geraniol, nerol, a minimum of citronellol, and terpineol. Monoterpenes (α- and β-pinene, camphene, β-myrcene, cis- and transocymene, limonene), sesquiterpenes and their derivatives (germacrene D, β-caryophyllene, α-copaene, β-element, β-bourbonene, δ-kadinen, β-eudesmol, α-humulene and α-bisabolol) and oxides (1,8-cineolkaryophyllene oxide) are present in insignificant amounts. Clary sage EO has antioxidant, antibacterial, antifungal, anti-inflammatory and antiviral activity as well as high wound-healing ability. Sage oil is used in the treatment of burns and long-lasting ulcers, stomatitis and gingivitis
[15,16][12][13].
S. stepposa Des.-Shost. (steppe sage) is a perennial plant with stems 35–60 cm high. The stem in the lower part is glabrous or pubescent with sparse short hairs. The corolla is blue–purple, 13–18 mm long, the basal rosette of the leaves is not pronounced, and the inflorescence is sparse, with 4–6 flower heads. The calyx is pubescent with glandular hairs. It blooms in June–July, and the fruits ripen in June–August
[25][8]. In traditional medicine, dried sage leaves are used (usually infusion) as an astringent, disinfectant, anti-inflammatory and aromatic means for rinsing the mouth and throat, with advantages against gum inflammation, stomatitis, bleeding from the gums, and diseases of the teeth and throat
[15][12].
S. officinalis L. (common or medicinal sage) is a perennial herbaceous plant or semi-shrub 20–80 cm tall. The stems are numerous, branched, tetrahedral, densely deciduous, and woody at the base, and the young ones are gray from numerous covering hairs. The leaves are opposite, gray–green, and densely pubescent. Its homeland is the Mediterranean, but it is cultivated all over the world
[25][8]. Diverse uses in traditional medicine are recorded
[29][14].
S. nemorosa L. (woodland sage, blue sage or wild sage) is a herbaceous perennial plant native to a wide area of central Europe and western Asia
[25][8]. The flowers contain 0.02–0.04% EO, the composition of which has not been studied. The seeds contain up to 19% of the fat-drying oil
[30][15]. Di- and triterpenes (like nemorone, nemorosin, horminone, 7-acetylhorminone, and salvinemorol), megastigmane glycosides (salvionosides A, B and C), pachystazone, salvipisone, α-amyrin, ursolic and oleanolic acids, stigmast-7-en-3-one, 24-methylenecycloartanol, stigmast-4-en-3-one, β-sitosterol, and stigmast-7-enol, as well as flavone aglycones apigenin, luteolin, eupatilin and salvigenin, have been isolated from its aerial parts
[31][16].
S. verticillata L. (lilac sage) contains a variety of polyphenols, volatile oils, and diterpenoids. Monoterpenes display protective effects against pentylenetetrazole-, picrotoxin- and N-methyl-D-aspartate-induced convulsions. Flavonoids of
S. verticillata are known to bind to the γ-aminobutyric acid (GABA)-type A-benzodiazepine site and may enhance the receptor sensitivity for endogenous GABA, which is a desired effect in the treatment of epilepsy
[32][17]. Extracts of aerial parts showed cytotoxic activity on human cancer cell lines along with antimicrobial activity
[33][18].
S. aethiopis (Mediterranean sage or African sage) is a perennial plant native to Eurasia. Morphologically, it is 50–120 cm high, with a thick, ribbed, shaggy pubescent, simple stem, and strongly branching only in the inflorescence; the inflorescence is strongly branched, with numerous, 6–10-flowered whorls; the corolla is white and medium-sized. It blooms in May–June and bears fruit in July–August. Diterpenes and sesterpenes were noted as major chemical constituents of
S. aethiopis [34,35,36][19][20][21].
Kazakhstani Species of Sage
A large number of Lamiaceae species (e.g.,
Lamium album,
Nepeta cataria,
Melissa officinalis,
Origanum vulgare) can be found almost everywhere in Kazakhstan with the widest representation in the mountain areas of Western Tyan Shan, Tarbagatai, Kyrgyz and Ile Alatau, Karatau, which is followed by Balkash and the western, central and northern parts of Kazakhstan. At the same time, endemic species, such as
Salvia trautvetteri and
Thymus altaicus, grow on limited territories (in Karatau; Altai, Saur and Soongari Alatau, correspondingly). More than 10 species of
Salvia (
S.) grow in Kazakhstan, with
S. deserta growing on steppes, forest edges, river banks, weed, near housing and in crops,
S. sclarea common in the foothill and foothill steppes of southern Kazakhstan (Karatau, Talas Alatau) and Dzhambul regions,
S. stepposa widely distributed in central (Turgay, western Melkosopochnik), northern (Tobolsk-Ishim, Irtysh, Kokchetav districts), Western (Caspian, Aktobe districts, Mugodzhary) and eastern (Semipalatinsk borovoi, Altai, eastern Melkosopochnik) Kazakhstan,
S. nemorosa widely distributed in all regions of Kazakhstan, but most abundantly in the south, within the southern Kazakhstan, Dzhambul and Almaty regions, and
S. aethiopis distributed in the Almaty, western Kazakhstan, Zhambyl and Turkestan regions
[25,35,36,37,38,39,40,41,42,43,44][8][20][21][22][23][24][25][26][27][28][29].
According to the study of Y.K. Levaya and G.A. Atazhanova, it was found that about 86 sage-containing drugs are available on the Kazakhstani market, of which most are presented in solid dosage forms
[45][30]. Sadly, only 13% of those drugs are produced locally
[46][31]. In Kazakhstan, the volume of the locally produced medications covers only 17–20% of the country’s pharmaceutical market, out of which the prevailing number are generics
[47][32]. At the same time, in Kazakhstan, the medicinal flora is represented by 1406 species belonging to 134 families of higher flowering plants, out of which at least 50 species are pharmacopeial
[42,43][27][28].
2. Nephroprotective Properties of the Salvia Genus
Decoction extract from the flowers of
S. officinalis exerted a protective effect against ethanol-induced injury in the rat liver and kidney by plasma transaminases activity and preservation of the hepatic tissue structure
[179][33].
A study by Ahn et al.
[180][34] showed that the chronic oral administration of Tanshinone IIA can improve renal dysfunction related to chronic kidney disease. Moreover, tanshinone IIA has renoprotective effects against the progression of diabetic nephropathy.
S. miltiorrhiza decreased urine protein excretion by 65% in streptozotocin-induced diabetic nephropathy
[181][35].
The in vivo results revealed that
S. officinalis aqueous extract (SOE) mitigated disturbances and histological alterations in the liver and kidney tissue in rats treated by CdCl
2. The kidney sections of the rats treated with SOE revealed renal tissue with a normal tubular and glomerular structure. Moreover, SOE administration induced a loss of body weight and a notable elevation in liver and kidney indices, NO, cholesterol, triglycerides, LDL, serum cytokines, hepatic and renal malondialdehyde, mRNA expression of
Bax gene accompanied by a significant decrease in HDL, hepatic and renal antioxidant enzymes and their mRNA gene expression
[182][36].
The nephroprotective effect of EO from the aerial parts of
S. officinalis seems to be related to a high content of β-caryophyllene, limonene, carvacrol, caryophyllene, borneol, α-pinene, and α-thujene. The administration of EO from this species significantly restored biochemical markers and pathological lesions on renal nephrotoxicity induced by vanadium in rats
[183,184][37][38]. Hosivandi et al. studied the protective effects of
S. macrosiphon methanolic extract on renal ischemia reperfusion, which was shown to significantly reduce the level of urea and creatinine
[185][39].
Kim et al. discovered that the extract of
S. plebeia inhibited the activity of xanthine oxidase, which is the main enzyme producing uric acid in the liver. In an animal model of hyperuricemia,
S. plebeia extract reduced serum urate to the levels observed in control animals. The urate-lowering effect of
S. plebeia extract in vivo was supported by the identification of compounds (nepetin, scutellarein, and luteolin) inhibiting xanthine oxidase enzyme activity in vitro
[186][40]. Lithospermic acid isolated from the extract of
S. miltiorrhiza roots had marked in vivo hypouricemic and anti-inflammatory effects on rats
[187][41].
The study of Zhang et al. demonstrated the uricosuric and nephroprotective effects of the ethyl acetate extract of
S. miltiorrhiza (EASM) and tanshinone IIA (Tan-IIA) on uric acid nephropathy. After treatment, decreased serum uric acid and creatinine levels were observed in experimental mice. Both EASM and Tan-IIA demonstrated inhibitory effects on uric acid nephropathy through the downregulating of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), relieving NOX4-mediated oxidative stress and suppressing MAPK pathways activation
[188][42].
The EO of
S. officinalis leaves inhibited xanthine oxidase (XOD), which catalyzes the generation of uric acid. This inhibitory activity might be associated with the presence of α-thujone, β-thujone, α-pinene, β-pinene, β-caryophyllene and myrcene
[116][43].
A study carried out by Bahadori et al. demonstrated that
S. spinosa was a potentially effective xanthine oxidase inhibitor (IC50 = 38.7 ± 0.5 mg/L), which may be related to the presence of caryophyllene and spathulenol
[189][44]. Moreover, the methanolic extract of
S. spinosa showed an XO inhibitory activity of 71.5%
[190][45].