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The roots of Salvia rhytidea: a rich source of biologically active diterpenoids
Abstract
Sahandinone (1), 12-deoxysalvipisone (2), miltirone (3), 7α-acetoxyroyleanone (4), and labda-7,14-dien-13-ol (5) were isolated from the roots of Salvia rhytidea Benth. (Lamiaceae). Their structures were elucidated by a combination of spectroscopic analyses including EIMS and NMR. The 13C NMR spectroscopic data were revised for the quaternary carbons of both 1 and 3 with the help of HMBC spectra in respect to the spectral data previously reported in the literature. Compounds 1 and 3, two very potent anticancer agents, were isolated in high yields from the roots of the plant. The biological activities of the plants’ constituents were reported in the literature as antimicrobial, cytotoxic and antimalarial are discussed in this article.The major anticancer agents from Salvia rhytidea.
... There are 61 Salvia species naturally growing in Iran, seventeen of them are endemic (Jamzad, 2012). Several species of Salvia are pharmacologically active and have been widely used in folk medicine (Wu et al., 2013;Firuzi et al., 2013;Jassbi et al., 2017). Bioassay-guided purification of chemical constituents of Salvia species has resulted in the isolation of many bioactive phytochemicals such as flavonoids, phenolics, terpenoids and steroids (Jassbi et al., 2017). ...
... Several species of Salvia are pharmacologically active and have been widely used in folk medicine (Wu et al., 2013;Firuzi et al., 2013;Jassbi et al., 2017). Bioassay-guided purification of chemical constituents of Salvia species has resulted in the isolation of many bioactive phytochemicals such as flavonoids, phenolics, terpenoids and steroids (Jassbi et al., 2017). Among them, more than 550 diterpenoids have been reported from different Salvia species (Kabouche and Kabouche, 2008), most of which have shown a broad spectrum of interesting biological activities and ecological roles, that include antimicrobial, anticancer, antiviral, antioxidant and anti-inflammatory activities (González, 2015;Jassbi et al., 2017). ...
... Bioassay-guided purification of chemical constituents of Salvia species has resulted in the isolation of many bioactive phytochemicals such as flavonoids, phenolics, terpenoids and steroids (Jassbi et al., 2017). Among them, more than 550 diterpenoids have been reported from different Salvia species (Kabouche and Kabouche, 2008), most of which have shown a broad spectrum of interesting biological activities and ecological roles, that include antimicrobial, anticancer, antiviral, antioxidant and anti-inflammatory activities (González, 2015;Jassbi et al., 2017). Among different classes of anticancer drugs, natural products remain a main source of potential drugs to treat human tumors. ...
Salvia lachnocalyx Hedge, Lamiaceae, is an endemic sage which grows naturally in the Fars Province of Iran. The phytochemical analyses of the roots of S. lachnocalyx led to the isolation of five known diterpenoids: ferruginol (1), taxodione (2), sahandinone (3), 4-dehydrosalvilimbinol (4) and labda-7,14-dien-13-ol (5). Their chemical structures were elucidated using one (¹H and ¹³C) and two dimensional (COSY, HSQC and HMBC) NMR spectroscopic data as well as electron impact mass spectra. The cytotoxicity of the purified compounds was evaluated against three human cancer cell lines; MOLT-4 (acute lymphoblastic leukemia), HT-29 (colorectal adenocarcinoma) and MCF7 (breast adenocarcinoma) and all of the isolated compounds showed considerable cytotoxic activity against these cell lines. Compounds 2 and 3 (IC50 range: 0.41–3.87μg/ml) with endocyclic α,β-unsaturated carbonyl functional group, exhibited the highest cytotoxic activities compared to the other compounds (IC50 range: 6.85–17.23μg/ml). In conclusion, compounds 2 and 3 are presented as compounds that deserve further investigation of their biological activities.
... Punica granatum [135] Pomegranate Lythraceae Africa, Asia Whole plant Flavonoids, anthocyanins 139 Quassia amara [136] Bitter ash wood Simaroubaceae Africa Leaves Quassinoids 140 ...
... Salvia rhytidea [139] Persian sage Lamiaceae Iran, Afghanistan ...
... Royleanones 1 to 3 and 7 have been isolated from different genera of the Lamiaceae family, 4-6 while 2 has also been described from species of the Taxodiaceae family. 7,8 Some of these compounds exhibit antibacterial, [9][10][11] cytotoxic, 12 antiviral, 13 gastroprotective, 14 and antiparasitic 15,16 activities. ...
... H-2β, H-6β, and Me-18, respectively. The H-5α signal at δ1. 16 showed correlation with that at δ 0.92 thereby assigning Me-19. Some coupling constant values which can directly be extracted from the spectra are given in Table 3. ...
... Royleanones 1 to 3 and 7 have been isolated from different genera of the Lamiaceae family, 4-6 while 2 has also been described from species of the Taxodiaceae family. 7,8 Some of these compounds exhibit antibacterial, [9][10][11] cytotoxic, 12 antiviral, 13 gastroprotective, 14 and antiparasitic 15,16 activities. ...
... H-2β, H-6β, and Me-18, respectively. The H-5α signal at δ1. 16 showed correlation with that at δ 0.92 thereby assigning Me-19. Some coupling constant values which can directly be extracted from the spectra are given in Table 3. ...
The known diterpenoids horminone (1) and taxoquinone (2) as a mixture, and pure 6,7-dehydroroyleanone (7) were isolated from the aerial parts of not yet studied Salvia concolor Lamb. Although 1 and 2 are known, the ¹ H Nuclear Magnetic Resonance (NMR) data of their acetyl derivatives 4 to 6 are only partially described. Moreover, the ¹³ C NMR data assignments for 4 and 6 show some inconsistencies and reveal better agreement with those we obtained for diastereoisomeric 3 and 5. Since stereochemical aspects were in doubt, it was considered as mandatory to unambiguously determine the absolute configuration of 3 to 6 using vibrational circular dichroism spectroscopy, which then allowed the complete ¹ H and ¹³ C NMR chemical shift assignments of 4 to 6.
... Most of the Salvia species are pharmacologically active and have been widely used in folk medicine for more than 60 different ailments ranging from aches to epilepsy. Target treatments include colds, bronchitis, tuberculosis, obesity, diabetes, depression, dementia and menstrual disorders [4][5][6][7]. Salvia species are renowned for their abundance of flavonoids, phenolics, terpenoids and steroids, most of which have a broad spectrum of biological activity including antimicrobial, antioxidant, antiinflammatory, anticancer and antiviral activities [7][8][9]. ...
... Target treatments include colds, bronchitis, tuberculosis, obesity, diabetes, depression, dementia and menstrual disorders [4][5][6][7]. Salvia species are renowned for their abundance of flavonoids, phenolics, terpenoids and steroids, most of which have a broad spectrum of biological activity including antimicrobial, antioxidant, antiinflammatory, anticancer and antiviral activities [7][8][9]. ...
Diterpenoids salvimulticanol (1) and salvimulticaoic acid (2) together with known diterpenoid (3-6) were isolated from Salvia multicaulis. Structures were elucidated by spectroscopic techniques including HRESIMS as well as 1D-, and 2D-NMR. In-vitro cytotoxicity was assayed against human cancer cell lines. As several metabolites exhibited activity against drug-resistance lines, compounds were screened against a panel of human drug-sensitive and multidrug-resistant cancer lines. A proposed biosynthetic pathway for these new diterpenoids (1-2) as well as the cytotoxic structure-activity relationship of all identified compounds were discussed. Compound 1 and 6 showed the most potent cytotoxicity with IC50 11.58 and 4.13 towards leukemia cell lines CCRF-CEM and CEM-ADR5000, respectively.
... This genus includes nearly 1000 species which are widely distributed all over the world. Genus Salvia is a rich source of essential oils, flavonoids and terpenoids (Al-Aboudi et al. 2015;Hussain et al. 2016;Jassbi et al. 2016;Salimikia et al. 2016;Tabatabaei et al. 2017). This genus is reported for antioxidant, antimicrobial and antiviral activities (Jassbi et al. 2016;Moridi Farimani & Abbas-Mohammadi 2016). ...
... Genus Salvia is a rich source of essential oils, flavonoids and terpenoids (Al-Aboudi et al. 2015;Hussain et al. 2016;Jassbi et al. 2016;Salimikia et al. 2016;Tabatabaei et al. 2017). This genus is reported for antioxidant, antimicrobial and antiviral activities (Jassbi et al. 2016;Moridi Farimani & Abbas-Mohammadi 2016). Plants belonging to genus Salvia are well known in folk medicine to treat epilepsy, aches, colds, bronchitis and menstrual disorders (Velickovic et al. 2002;Tajbakhsh et al. 2007;Güllüce et al. 2006). ...
Salvia aethiopis is a perennial plant native to Eurasia and known by the common names Mediterranean sage or African sage. This plant has been used in Iranian medicine as a carminative and tonic. The ethanolic extract of aerial part of S. aethiopis exhibited moderate to weak activity towards delta and kappa opioid receptors (46.3 and 45.3% displacement, respectively). Chromatographic purification of the ethanolic extract on silica gel column led to isolation of one new: 3α-hydroxy-8α-acetoxy-13,14,15,16-tetranorlabdan-12-oic acid (I) and three known compounds: sesquiterpene spathulenol (II), β-sitosterol (III) and β-sitosterol-3-O-glucoside (IV). The structures of all isolated compounds were elucidated by their NMR (1D and 2D) and MS spectral data. All the fractions and isolated compounds were tested for cannabinoid and opioid receptor binding assays.
... Among the abietane diterpenoids, those with orthoor paraquinone-quinol functionality at C-11/C12 or C-11/C-14 constitute a very important type of terpenoids in the roots of Salvia species (Bisio et al. 2019). Phytochemical and biological investigation on the roots of S. sahendica, S. rhytidea, S. lachnocalyx and S. hydrangea resulted in isolation of several abietane and rearranged abietane or abeo-abietane diterpenoids with antimicrobial, antileishmanial and cytotoxic activities (Jassbi et al. 2006;Hadavand Mirzaei et al. 2017;Jassbi et al. 2017). We report here the occurrence of ferruginol (1) and five quinone abietanes diterpenoids; taxodione (2), 12-deoxy-6-hydroxy-6,7-dehydroroyleanone (3), 14-deoxycoleon U (4), 15-deoxyfuerstione (5) and taxodone (6) in the roots of S. spinosa for the first time and provide cytotoxicity data of the identified compounds. ...
The roots of Salvia spinosa L. (Lamiaceae) were extracted with hexane, dichloromethane (DCM) and ethyl acetate. The DCM extract exhibited cytotoxic activity (IC50 32.7 µg/mL) against MFC-7 breast cancer cell line in MTT colorimetric bioassay. Ferruginol (1), taxodione (2), 12-deoxy-6-hydroxy-6,7-dehydroroyleanone (3), 14-deoxycoleon U (4), 15-deoxyfuerstione (5) and taxodone (6) were isolated from the DCM roots extract. Their structures were elucidated by a combination of spectroscopic analyses including EIMS and 1H- and 13C NMR spectra. The cytotoxicity of compound 3 was determined against MCF-7 and K562 cell lines and compared with the other compounds. A pharmacophore model was built based on potent input compounds to resolve important pharmacophore features responsible for cytotoxic activity of the isolated compounds.
... The biological activities of the plants' constituents were reported in the literature as antimicrobial, cytotoxic and antimalarial. [40] Also the methanolic extract of S. rhytidea Benth. was rich in flavonoids and tannins. ...
... Leriifoliol (63), leriifolione (64), salvialeriicone (65), salvialeriol (66) were identified in root of S. leriifolia (Choudhary et al., 2013;Farimani et al., 2018;Hussain et al., 2016). Additionally, sahandinone (67), 12-deoxysalvipisone (68), miltirone (69), 7α-acetoxyroyleanone (70), and 1-deoxo aurocadiol (71) were isolated from root of S. rhytidea (Eghtesadi et al., 2016;Jassbi et al., 2017). The aerial parts and roots of S. multicaulis was reported to contain salvimulticanol (72), salvimulticaoic acid (73), 3-oxo-12-methoxy-14-hydroxyabieta-8,11,13-triene (74), 6-oxo-12-peroxyabieta-8,11,13-triene (75), multicaulin (76), 12-demethylmulticauline (77), multiorthoquinone (78) and 12-demethylmultiorthoquinone (79) (Hegazy et al., 2018;Ulubelen et al., 1997bUlubelen et al., , 1998. ...
Salvia is the largest genus of the Lamiaceae family, with over 900 species in the world which about 60 species are distributed in Iran, 17 of them are endemic. In Iran, Salvia species have been used to treat various diseases with a wide spectrum of pharmacological activity in vitro and in vivo. The present review summarizes the phytochemistry and pharmacology of medicinal Iranian Salvia species in order to describe their therapeutic potential for a range of diseases. . Phytochemical investigations reveal that the Iranian Salvia has a varied range of metabolites including terpenoids, flavonoids and phenolic acids. The most important pharmacological activities are antidiabetic, antioxidant, antimicrobial, cytotoxic and anti-inflammatory. Iranian Salvia traditionally used as carminatives, analgesics, digestive aids, antiseptics, sedative, anxiolytic, hypnotic, pain reduction and antidiabetic. Among the endemic species, the most interesting for human health are treating a variety of diseases.
... [34], S. rhytidea Benth. [35] and S. reuterana Boiss [36] which grow in Europe or the Middle East. This is the first time that labdane type diterpenoids have been isolated from a sage of the subgenus Calospahce. ...
The aerial parts of Salvia cinnabarina afforded two undescribed labdane diterpenoids 1 and 2 (malonylcommunol and 6β-hydroxy-trans-communic acid) along with two known labdane diterpenoids, trans-communic acid (3) and trans-communol (4). Additionally, seven known metabolites were also isolated; two isopimarane diterpenoids 5 and 6, two sesquiterpenoids identified as β-eudesmol (7) and cryptomeridiol (8), and three aromatic compounds identified as phthalic acid (9), a mixture of tyrosol fatty acid esters (10) and the flavone salvigenine (11). While compounds compounds 1–3 showed significant inhibition of yeast α-glucosidase, compounds 2, 3 and 7 had no anti-inflammatory activity in the edema model induced by TPA. This paper is not only the first report on a wild population of Salvia cinnabarina, but also of the presence of labdane-type diterpenoids in a Mexican Salvia sp.
... In addition, S. sahendica is used in Iranian folk medicine as an antibacterial and antifungal herb, and also for the treatment of dyspepsia (Esmaeili et al., 2009). Salvia species are rich in triterpenoids (Ballesta-Acosta et al., 2002), polyphenols (Lu and Foo, 2000), and diterpenoids (Xu et al., 2006;Fan et al., 2017;Venditti et al., 2017) exerting a variety of biological activities, such as antioxidant (Kabouche et al., 2007), antifeedant (Fraga et al., 2005), antibacterial (Kawahara et al., 2004), antimutagenic (Amaro-Luis et al., 1998), anti-inflammatory (Baricevic et al., 2001), cytotoxic (Guerrero et al., 2006;Jassbi et al., 2017;Beladjila et al., 2018), anti-HIV (Zhang et al., 2008), lipase inhibitory (Marrelli et al., 2019), and antiplatelet aggregation activities (Liu et al., 2011). ...
Ten undescribed neo-clerodane diterpenoids, named hispanins A-J, together with six known ones, were isolated from the aerial parts of Salvia hispanica L. Their structures were established by extensive spectroscopic analysis. The absolute configurations of the undescribed compounds were determined by the ECD data and single crystal X-ray diffraction analysis. Hispanins B and C represented the first neo-clerodane diterpenoids with a unique oxygen bridge between C-19 and C-20. All isolated compounds were evaluated for their protective effects against H2O2-induced cardiomyocyte injury. Five of these compounds showed significant cardioprotective effects.
... Salvipisone (132), a 11,14-p-12-hydroxyquinone diterpene, obtained from the roots of S. aethiopis L., collected in Spain, was one of the first isolated compounds belonging to 4,5-seco-5,l0-friedo-abietane group ( Rodríguez et al. 1984). Its 12-deoxy derivative (133) was obtained from the aerial parts of S. rytidea Benth. in 2016 ( Jassbi et al. 2017). The roots of S. sclarea yielded a new acetyl derivative of salvipisone (134) ( Ulubelen et al. 1997a). ...
A total of 175 abietane quinone diterpenes with ortho- or para-quinone chromophore, namely 11,12-ortho-quinone abietane, 11,14-para-quinone abietane, seco-abietane and abeo-abietanes quinones were surveyed from 130 species of Salvia of central Asia/Mediterranean area, eastern Asia, and Central and South America. An organized information on the phytochemistry and the biological activities, i.e. anti-cancer, antioxidant, anxiolytic and antidepressant, anti-obesity, antinflammatory, as well as antimicrobial and toxicological aspects of these compounds was provided. Due to the many nomenclatural mistakes caused by the abundance of data, and the need to provide the plant knowledge for further chemotaxonomic studies, the results about the botany and the taxonomy of the plant source of these compounds were also summarized.
... In our ongoing search for the bioactive phytochemicals from Iranian sage species (Farjam et al., 2013;Jassbi et al., 2012Jassbi et al., , 2017Jassbi et al., 2006;Mirzaei et al., 2017), we report here on the analysis of the constituents of S. ceratophylla roots. ...
Two previously undescribed rearranged abietanes, ceratol (1) and ceratodiol (2), and three known abietane-diterpenoids, including 1-ketoaethiopinone (3), ferruginol (4) and 12-deoxysalvipisone (5), were isolated from roots of Salvia ceratophylla. The structures of the purified compounds (1–5) were characterized based on analyses of their spectroscopic data, including 1D and 2D NMR and high-resolution electrospray mass spectra. The analytical data were then compared with those reported in the literature. Cytotoxicity of the isolated compounds was examined against two human cancer cell lines, MOLT-4 (human lymphoblastic leukemia) and MCF-7 (human breast adenocarcinoma), using the MTT reduction assay. Whereas compound 2 showed cytotoxicity against both cancer cells, 1 showed weak toxicity against MOLT-4 cells and no toxicity against MCF-7 cells. Compound 3 and compound 5, both of which had an α, β-unsaturated carbonyl function, showed the highest cytotoxic activities among the tested compounds.
... Salvia species have been used extensively in Turkey for herbal tea. Owing to the secretion of varied secondary metabolites, many Salvia species display a large variety of biological activities, such as anticancer (Jassbi et al. 2017;Ulubelen et al. 1999), anti-inflammatory, cardioprotective (Kolak et al. 2001;Ulubelen et al. 2002). The phytochemical investigation on Salvia cryptantha mainly based on extract activity such as antiviral (Civra et al. 2017), antitumor ( € Ozer et al. 2013). ...
Salvia absconditiflora Greuter & Burdet (Synonym Salvia cryptantha Montbret & Aucher ex Benth) has been used extensively for traditional medicine. The aerial of plant material was boiled in water then filtrated. The filtrate was partitioned with ethyl acetate and n-butanol sequentially to yield the ethyl acetate and n-butanol extract. A sample of water was lyophilized to yield the water extract. Ethyl acetate extract revealed the highest antioxidant activity and included the most phenolic compounds among the extracts. Hence, ethyl acetate extract was subjected to chromatographic techniques. Ursolic acid (1), crismaritin (2), luteolin (3), rosmarinic acid methyl ester (4), 3,4-dihydroxyl benzaldehyde (protocatechuic aldehyde) (5), caffeic acid (6), apigenin-7-O-β-glucoside (7), rosmarinic acid (8) and luteolin-7-O-β-glucoside (9) were isolated and the structures were elucidated by spectroscopic methods including 1D, 2D NMR, and LC-TOF/MS. Cirsimaritin (2), luteolin (3), rosmarinic acid methyl ester (4), rosmarinic acid (8), luteolin-7-O-β-glucoside (9) displayed the considerable antioxidant activity.
... Salvia genus is also a source of anti-cancer compounds. There are several reports on the isolation of cytotoxic and genotoxic metabolites from Salvia species (Akaberi et al., 2015;Jassbi et al., 2016;Topçu, 2006;Zhang et al., 2012). ...
... Further purification by a combination of silica gel CC, and preparative and semipreparative RP-HPLC afforded 17 abietane, icetexane, and isopimarane diterpenoids. Fourteen of them were identified as known compounds, including 12-hydroxy-20-norabieta-8,11,13-triene (1) [21], carnosol (3) [22], 7α-ethoxyrosmanol (4) [23], miltirone (5) [24], Δ 9 -dehydro-ferruginol (7) [25], ferruginol (8) [26], miltiodiol (10), 1-oxomiltirone (11) [27], barbatusol (12) [28], 11,12-dihydroxy-20-norabieta-5(10),8,11,13-tetraen-1-one (13) [29], ent-isopimara-8,15-diene-18-ol (14) [30], rosmanol (15), epi-rosmanol (16) [22], and galdosol (17) [23] (▶ Fig. 1). Compounds 3 and 15 have been reported from the aerial parts [31] of P. abrotanoides, while 11 has been previously isolated from the roots [2]. ...
As part of a screening for new antiparasitic natural products from Iranian plants, n-hexane and ethyl acetate extracts from the aerial parts of Perovskia abrotanoides were found to exhibit strong inhibitory activity against Trypanosoma brucei rhodesiense and Leishmania donovani. The activity was tracked by high-performance liquid chromatography (HPLC)-based activity profiling. Preparative isolation by a combination of silica gel column chromatography and HPLC afforded 17 diterpenoids (1–17), including 14 abietane-, two icetexane-, and one isopimarane-type derivatives. Among these, (5R,10S)-11-hydroxy-12-methoxy-20-norabieta-8,11,13-triene (2), 12-hydroxy-norabieta-1(10),8,11,13-tetraene-1,11-furan (6), and 12-methoxybarbatusol (9) were new compounds, the structure of which was established by comprehensive spectroscopic data analysis (one- and two-dimensional nuclear magnetic resonance, high-resolution electrospray ionization mass spectrometry, electronic circular dichroism). The antiprotozoal activity of the isolated compounds was evaluated against T. b. rhodesiense, Trypanosoma cruzi, L. donovani, and Plasmodium falciparum. Selectivity indexes (SI) were calculated in comparison to cytotoxicity on rat myoblast (L6) cells. Particularly active were 7α-ethoxyrosmanol (4) with an IC50 of 0.8 µM against T. b. rhodesiense (SI 14.9) and an IC50 of 1.8 µM (SI 6.9) against L. donovani, ferruginol (8) with an IC50 of 2.9 µM (SI 19.2) against P. falciparum, and miltiodiol (10) with an IC50 of 0.5 µM (SI 10.5) against T. b. rhodesiense. None of the compounds exhibited selective toxicity against T. cruzi (SI ≤ 1.6).
... It is represented in the Iranian flora by 58 species, of which 17 are endemic (Mozaffarian 2010). Some of these species have been used as medicinal, aromatic and ornamental plants (Habibi et al. 2000;Naghibi et al. 2010;Al-Aboudi et al. 2015;Hussain et al. 2016;Jassbi et al. 2016;Moridi Farimani & Abbas-Mohammadi 2016;Salimikia et al. 2016). A broad spectrum of biological activities has been reported for Salvia species, such as antioxidant, antimicrobial, anti-inflammatory, cytotoxic and antiplasmodial properties (Kamatou et al. 2008). ...
Phytochemical investigation of n-hexane extract of Salvia sahendica by normal phase column chromatography resulted in the isolation of six compounds. Structures were established by 1D and 2D NMR spectroscopy, and HRMS, as a new norditerpene 1, and known terpenoids, sclareol (2), oleanolic acid (3), β-sitosterol (4), salvigenin (5) and 3α-hydroxy-11α,12α-epoxyoleanan-28,13β-olide (6). The absolute configuration of 1 was confirmed by a combination of X-ray single crystal analysis and electronic circular dichroism spectroscopy. In vitro cytotoxic activity on breast cancer cell line (MDA-MB-231) and also the antimicrobial activity of the pure compounds were tested against Staphylococcus aureus, Bacilus cereus and Escherichia coli.
... practices (Walker et al. 2004). Some of the species possess antimicrobial, antimalarial, antioxidant and antiproliferative activities (Loizzo et al. 2014;Russo et al. 2015;Jassbi et al. 2016;Moridi Farimani & Abbas-Mohammadi 2016). Salvia apiana, commonly known as white sage, can be found scattered throughout southwestern North America, with the highest concentration in Southern California (Borek et al. 2006). ...
Salvia apiana (white sage, Lamiaceae family) plant is native to southern California and parts of Mexico. Some Native American tribes local to this region consider S. apiana to be sacred and burn the leaves as incense for purification ceremonies. The plant has been used to treat sore throats, coughs, chest colds, upper respiratory infections and poison oak rashes. The aqueous ethanolic extract of S. apiana showed moderate CB1 activity (58.3% displacement). Chromatographic purification of the ethanolic extract on silica gel column led to isolation of nine compounds: rosmadial (I), carnosol (II), 16-hydroxycarnosol (III), sageone (IV), cirsimaritin (V), salvigenin (VI), oleanolic acid (VII), 3β,28-dihydroxy-urs-12-ene (VIII), and ursolic acid (IX). The structures of the isolated compounds were determined by their 1D, 2D NMR and MS spectral data. All the fractions and isolated compounds were tested for cannabinoid and opioid receptor binding.
... The genus Salvia L. (Lamiaceae) contains more than 1000 species of herbs, subshrubs and shrubs with many of the species commonly used in cosmetics and in local folk medical practices (Walker et al. 2004). Some of the species possess antimicrobial, antimalarial, antioxidant and antiproliferative activities (Loizzo et al. 2014;Russo et al. 2015;Jassbi et al. 2016;Moridi Farimani & Abbas-Mohammadi 2016). Salvia apiana, commonly known as white sage, can be found scattered throughout southwestern North America, with the highest concentration in Southern California (Borek et al. 2006). ...
Salvia apiana (white sage, Lamiaceae family) plant is native to California. Indian tribes consider S. apiana to be sacred and burn the leaves as incense for purification ceremonies [1]. The plant has been used to treat sore throats, coughs, chest colds, upper respiratory infections, systemic poison oak rashes and acute candidal vaginitis. Native Americans widely used this plant in traditional Chumash healing [2]. Infusion of the leaves is used as a diaphoretic or diuretic [3]. The aqueous ethanolic extract of S. apiana showed moderate CB1 activity (58.3% displacement). The extract was fractionated on silica gel column chromatography using hexanes-acetone gradient to yield 15 fractions. Repeated column chromatography led to isolation of ten compounds, which were identified to be four diterpenes: rosmadial (I), carnosol (II), 16-hydroxycarnosol (III) & sageone (IV), two flavonoids: cirsimaritin (V), & salvigenin (VI), three triterpenes: oleanolic acid, erythrodiol, ursolic acid and a fatty acid: montanic acid. All the fractions and isolated compounds were submitted for biological studies to check for cannabinoid and opioid receptor binding. Acknowledgements: The project was supported by Award Number P20GM104932 from the National Institute of General Medical Sciences and in part by NCNPR. References: [1] Ali A, et al. (2015) Journal of Agriculture and Food Chemistry, 63: 447 – 456. [2]. Takeoka GR, et al. (2010) Journal of Essential Oil Research. 22: 241 – 244. [3]. Luis JG, et al. (1996) Tetrahedron Letters, 37: 4213 – 4216,
Crystals of previously described para-naphthoquinone abietane diterpenoids 12,16-dideoxy-aegyptinone B and 12-deoxy-salvipisone were obtained from Zhumeria majdae Rech.f. & Wendelbo. However, single-crystal X-ray diffraction analysis followed by reinterpretation of their NMR data revealed that their structures require revision, and they should be revised to the two ortho-naphthoquinones, zhumerianone C and aethiopinone, respectively. Interestingly, a further search through literature revealed that there were more of such cases, in which differentiation between the ortho-/para-orientation had not been carried out correctly in the structure elucidation of naphthalene containing abietane diterpenoids. Therefore, in the current study, we pointed out some 1D and 2D NMR generalizations that would help the unambiguous deduction of the ortho-/para-orientation of naphthalene containing abietanes and revised the structure of some previously described compounds accordingly. Based on these generalizations, structures of sibiriquinone A and B, sahandinone, and sahandone were revised to the known structures 1,2-didehydromiltirone, miltirone, saprorthoquinones, and sahandone B, respectively. Moreover, structures of tebesinone B, arucadiol, and sahandol II were revised to three undescribed structures. It was also proposed that structures of palmitoyl arucadiol and compounds with the salvifolane skeleton need revision. Furthermore, these structure revisions shed light on the structure-activity relationship of the quinone diterpenoids, approving that the ortho-quinone is the critical structural component for cytotoxicity in these compounds.
Two novel icetexane diterpenes were isolated from Salvia przewalskii Maxim., namely Salprzesides A (1) and B (2), together with two known abietane-type diterpenes respectively identified as sahandinone (3) and miltirone (4). The structures of isolated compounds were determined by UV, IR, HR-ESI-MS, 1D and 2D NMR analysis. The in vitro antiangiogenic activities of compounds 1–4 were studied against human umbilical vascular endothelial cells (HUVECs). The IC50 values of compounds 1–4 ranged from 4.22 ± 1.07 to 39.31 ± 2.17 μM against HUVECs.
Further investigations on phytochemical constituents of dichloromethane extract from roots of Salvia lachnocalyx (S. lachnocalyx) led to the isolation and identification of eight known diterpenoids from this plant for the first time. The chemical structures of the purified compounds were elucidated using spectroscopic analyses including EI-MS, 1 H and 13 C NMR and by comparison of the resulting spectra with those reported in the literature. Then, the cytotoxic activity of identified compounds was examined against two human cancer cell lines MCF-7 (human breast adenocarcinoma) and K562 (human chronic myelogenous leukemia). Molecular docking of promising cytotoxic compounds were performed by AutoDock Tools 1.5.4 program in the active site of Topoisomerase I. Eight known diterpenoids; 12-hydroxysapriparaquinone (1), 15-deoxyfuerstione (2), horminon (3), 7α-acetoxyroyleanone (4), 11β-hydroxymanoyl oxide (5), 2 microstegiol (6), 1-keto-aethiopinone (7) and 14-deoxycoleon U (8) were isolated of dichloromethane extract from roots of salvia lachnocalyx. Compounds 2, 3, 6, and 8 showed cytotoxic activity against MCF-7 (human breast adenocarcinoma) and K562 (human chronic myelogenous leukemia) cell lines with IC50 values in the range of 2.63-11.83 µg/mL. The inhibition of" topoisomerase I" was suggested by molecular docking calculations as the mechanism of cytotoxicity of the tested compounds. According to cytotoxic assay and docking results, it is suggested that compounds 2, 3, 6, and 8 have good potential as anticancer agents.
زمینه و هدف: از دیرباز استفاده از گیاهان دارویی برای درمان بیماریها رایج بوده است. مطالعه حاضر به بررسی فعالیتهای ضدمیکروبی، آنتیاکسیدانی و اندازهگیری ترکیبات فنولی و فلاونوئیدی کل سه عصارهی متانولی، اتانولی و آبی پنج گونه مختلف گیاهان دارویی: Withania somnifera L. Dunal، Salvia rhytidea Bent، Levisticum officinale L.، Seidlitzia rosmarinus L. و Achillea wilhelmsii L. میپردازد.
مواد و روشها: پس از تهیه عصارهها به روش ماسراسیون، فعالیتهای آنتیاکسیدانی با دو روش DPPH و FRAP و ضدمیکروبی علیه باکتریهای استافیلوکوکوس اورئوس، باسیلوس سرئوس، اشرشیا کلی و قارچهای آسپرژیلوس نایجر و کاندیدا آلبیکنس به روش دیسک دیفیوژن و محتوای فنولی و فلاونوئیدی کل به ترتیب با روشهای معرف فولین-سیوکالتیو و رنگسنجی کلرید آلومینیوم، سنجیده شده است.
نتایج: نتایج نشان دادند عصاره متانولی گونهی پنیرباد دارای بیشترین میزان ترکیبات فنولی (mgGAE/gExtract 64/4±45/41) و فلاونوئیدی (mgQUE/gExtract 54/2±21/35) و فعالیت آنتیاکسیدانی (µg/ml 36/1±12/8 IC50= و mMFe2+/mgExtract 68/1±19/58) و فعالیت ضدمیکروبی علیه باکتری استافیلوکوکوس اورئوس و قارچ کاندیدا آلبیکنس با قطر هاله عدم رشد به ترتیب 06/1±29 و 00/1±27 میلیمتر بوده است. در مقابل عصارهی آبی گونهی انجدان رومی دارای کمترین میزان ترکیبات فنولی (mg GAE/gSample 93/1±12/17) و فلاونوئیدی (mg QUE/gExtract 06/2±61/12) و فعالیت آنتیاکسیدانی (µg/ml 36/3±43/121 IC50= و mM Fe2+/mgExtract 52/2±74/13) و فعالیت ضدمیکروبی علیه باکتری باسیلوس سرئوس و قارچ آسپرژیلوس نایجر با قطر هاله عدم رشد به ترتیب 57/0±4 و 00/1±5 میلیمتر بوده است.
نتیجهگیری: بهطورکلی بر اساس نتایج بهدستآمده، گیاهان مورد مطالعه میتوانند کاندیدای خوبی جهت درمان بیماریهای ناشی از استرسهای اکسیداتیوی و بیماریهای ناشی از میکروبهای بیماریزا قرار گیرند.
Covering January to December 2017; previous review Nat. Prod. Rep., 2017, 34, 1233–1243.
This review covers the isolation and chemistry of diterpenoids from terrestrial as opposed to marine sources and includes labdanes, clerodanes, abietanes, pimaranes, kauranes, cembranes and their cyclization products. There are 228 references.
A new adduct of abietane-type diterpene, salvialeriicone (1), was isolated from Salvia leriifolia Benth., along with a new chemical entity nor-abietane diterpene, 2-isopropyl-8,8-dimethyl-7,8-dihydrophenanthrene-1,4,5(6H)-trione (2). Their structures were determined using mass spectrometry, and 1D- and 2D-NMR spectroscopy.
Three new seco-ursadiene triterpenoids 1–3 together with 11 known compounds were isolated from Salvia syriaca of Jordanian origin. The compounds were identified by using NMR spectroscopy including extensive 2D NMR experiments and mass spectrometry. The structure of compound 3 was confirmed by X-ray crystallography, and the information thus obtained was used to confirm the stereochemistry of compounds 1 and 2. This is the second report of 17,22-seco-17(28),12-ursadien-22-oic acids
The essential oils obtained by hydrodistillation of the aerial parts of Salvia persepolitana Benth., which is endemic to Iran, and Salvia rhytidea Benth. were analyzed by GC and GC/MS.Manool (37.3%) was the main component among the twenty-three constituents characterized in the oil of S. persepolitana representing 90.0% of the total components detected.The oil of S. rhytidea was characterized by higher amounts of terpinolene (27.0%), sabinene (17.5%) and limonene (14.9%) which were among the twenty-two components comprising 98.3% of the total oil detected.
In a screening of Iranian plants for antiprotozoal activity, an n-hexane extract of the roots of Salvia sahendica potently inhibited the growth of Plasmodium falciparum K1 strain. Subsequent HPLC-based activity profiling led to the identification of seven known and one new abietane-type diterpenoid. Structure elucidation was achieved by analysis of spectroscopic data including 1D and 2D NMR. The absolute configuration of sahandol (7) and sahandone (8) were assigned by comparison of experimental ECD spectra with calculated ECD data, using time-dependent density functional theory and methanol as the solvent. In vitro biological activity against P. falciparum and Trypanosoma brucei rhodesiense STIB 900 strain and cytotoxicity in rat myoblast (L6) cells were determined. The IC50 values of the compounds ranged from 0.8 µM to over 8.8 µM against P. falciparum, and from 1.8 µM to over 32.3 µM against T. brucei rhodesiense. The cytotoxic IC50 values ranged from 0.5-15.5 µM. Selectivity indices for P. falciparum were 0.1 to 18.2, and 0.1 to 1.2 for T. brucei rhodesiense.
The 13S compound 13-epiisomanool
(labda-8,14-dien-13β-ol) has been synthesized and its optical rotation
compared with that of the 13R isomer (isomanool) in
order to correct errors in the literature.
Diterpenoids are a class of compounds that derive from the condensation of four isoprene units that leads to a wide variety of complex chemical structures, including acyclic bi-, tri-and tetra-cyclic compounds; in Salvia species, only bi-, tri-and tetra-cyclic compounds have been found. This review covers a wide range of biological activities and mode of action of diterpenoids isolated from Salvia species that might raise some pharmacological and pharmaceutical interest.
We have produced a synoptic table where the biological activities of the main active principles are summarized. Our analysis emphasizes that diterpenoids from Salvia species continue to be a plant defence system since their antimicrobic activity. Experimental studies show that most of diterpenoids considered have cytotoxic and / or antiproliferative activity. Some of them have also cardiovascular and central effects. In a less extended manner, diterpenoids from Salvia species show gastrointestinal, urinary, antinflammatory, antidiabetic, ipolipidemic and antiaggregating effects.
In the last decade, several clinical trials have been developed in order to investigate the real value of Salvia extracts treatment; results obtained are promising and confer scientific basis in the use of medicinal plants from folk medicine.
Antibacterial bioassay guided fractionation of acetone extracts of Astragalus brachystachys resulted in isolation of sclareol and two related labdane-type diterpenoids, 14R-epoxysclareol and 6beta-hydroxysclareol. The antibacterial activity of the isolated compounds was measured and it was deduced that the epoxidation at the double bond of sclareol or hydroxylation at C-6 decreased the activity of the resulting compounds. Salvigenin (5-hydroxy-4',6,7-trimethoxyflavone) was also separated from this plant for the first time.
Chemical composition of volatile compounds from Salvia rhytidea Benth. was analyzed, for the first time, by gas chromatography/mass spectrometry. The volatiles were isolated from dried aerial parts of the plant by hydrodistillation. A total yield of 2.0 mg of essential oil per g of plant dry mass was obtained and sixty compounds were identified, representing 98.2% of total volatiles. The essential oil was characterized by a high content of hydrocarbon and oxygenated monoterpenes. The main constituents were p-cymene-8-ol (11.9%), spathulenol (7.3%), pulegone (6.4%), sabinene (5.8%), terpinen-4-ol (5.5%) and alpha-copaene (5.3%).
From roots of Hyptis martiusii Benth. two tanshinone diterpenes were isolated, the new 7beta-hydroxy-11,14-dioxoabieta-8,12-diene (1) in addition to the known 7alpha-acetoxy-12-hydroxy-11,14-dioxoabieta-8,12-diene (7alpha-acetoxyroyleanone) (2). Structures of 1 and 2 were established by spectroscopic means. The cytotoxic activity against five cancer cell lines was evaluated. Compounds 1 and 2 displayed considerable cytotoxic activity against several cancer cell lines with IC50 values in the range of 3.1 to 11.5 microg/ml and 0.9 to 7.6 microg/ml, respectively. The cytotoxic activity seemed to be related to inhibition of DNA synthesis, as revealed by the reduction of 5-bromo-2'-deoxyuridine incorporation and induction of apoptosis, as indicated by the acridine orange/ethidium bromide assay and morphological changes after 24 h of incubation in leukemic cells.
The cure from cancer is still not a reality for all patients, which is mainly due to the limitations of chemotherapy (e.g., drug resistance and toxicity). Apart from the high-throughput screening of synthetic chemical libraries, natural products represent attractive alternatives for drug development. We have done a systematic bioactivity-based screening of natural products derived from medicinal plants used in traditional Chinese medicine. Plant extracts with growth-inhibitory activity against tumor cells have been fractionated by chromatographic techniques. We have isolated the bioactive compounds and elucidated the chemical structures by nuclear magnetic resonance and mass spectrometry. By this strategy, we identified 25-O-acetyl-23,24-dihydro-cucurbitacin F as a cytotoxic constituent of Quisqualis indica. Another promising compound identified by this approach was miltirone from Salvia miltiorrhiza. The IC50 values for miltirone of 60 National Cancer Institute cell lines were associated with the microarray-based expression of 9,706 genes. By COMPARE and hierarchical cluster analyses, candidate genes were identified, which significantly predicted sensitivity or resistance of cell lines to miltirone.
The plants of the genus Salvia L. are important medicinal herbs of the Lamiaceae family and some of them such as S. officinalis (sage), S. miltiorrhiza (red sage, Danshen) and S. sclarea (clary sage) have been used as medicinal plants in the folk medicine of several countries. In this review, we discuss the reports that have examined Salvia species with the aim of isolation of pure compounds with different biological activities. The phytochemical analyses of various sage plants have reported 10 monoterpenoids (1–10), 1 sesquiterpenoid (11), 8 labdane (13–20), 15 ent-kaurane (21–35), 82 abietane, rearranged abietane and tanshinone (36–117), 3 icetexane (118–120), 43 clerodane (121–163), and 3 pimarane (164–166) diterpenoids with cytotoxic and antimicrobial, antiprotozoal, antioxidant, phytotoxic and insecticide effects. The other heavier terpenoids, including 3 sesterterpenes (167–169), 10 triterpenoids and β-sitosterol (170–180) have been introduced as minor bioactive compounds in the sage plants. Sahandinone (107), 6,7-dehydroroyleanone, 7-α-acetoxyroyleanone (40), and tanshinone like diterpenoids have been isolated from the roots’ extracts of different Salvia species. On the other hand, several radical scavenger phenolic compounds like simple phenolics and caffeic acid derivatives (181–201) including rosmarinic acid, flavonoids (202–217) as well as phenolic diterpenoids, such as carnosol and carnosic acid have been isolated from the aerial parts of these plants. One pyrrole (218) and 3 antimicrobial oxylipins (219–221) are among the other less detected constituents in the members of Salvias. Furthermore, sages also synthesize antifungal, antileishmanial and antimalarial phytochemicals in their roots and shoots, which are reviewed in this paper. We also examine the allelopathic phenomena and the ecologically important phytochemicals identified in different parts of the sage plants. Finally, antifeedant and insecticide phenomena, which are due to the presence of volatile monoterpenes and clerodane diterpenes in these plants, are discussed. Considering the presence of diverse biologically active phytochemicals in the sage plants, they can be suggested as suitable candidates for the formulation of valuable natural medicines.
Phytochemical investigation of the roots of Salvia chloroleuca led to the isolation and identification of a new rearranged abietane diterpenoid (1). Its structure was elucidated by interpretation of the 1D and 2D NMR spectra and completed by the analysis of the HR-ESI-MS data. Compound 1 is the secondly reported compound on a rearranged tricyclic abietane (4,5-seco-5,10-friedo-abietane) diterpenoid with a ketal functionality between C-2 and C-11. A plausible biosynthetic pathway of 1 was also proposed.
Two diterpenoids, (+)‐labda‐7,14‐dien‐13‐ol and (+)‐manoyl oxide, and one bis(bibenzyl) compound, isomarchantin C, were isolated as the major components from the Taiwanese liverwort Mylia nuda. The spectral evidence is discussed in this paper. In addition, several monoterpenes and sesquiterpenes were also identified by GC/MS.
The composition of the essential oils from aerial parts of three Salvia species: S. rhytidea Benth., S. limbata C. A. Mey. and S. palaestina Benth. have been analyzed by a combination of GC and GC/MS. During the fowering period, two oils (S. rhytidea and S. limbata) consisted mainly of monoterpenes, while in S. palaestina oil sesquiterpenes predominated over monoterpenes. The major components of the oil of S. rhytidea were β-phellandrene (22.7%) and sabinene (13.5%). In the oil of S. limbata, α-pinene (23.7%), β-pinene (18.7%) and sabinene (14.5%) were found to be the major constituents. β-Caryophyllene (36.4%) was the predominant compound in the oil of S. palaestina.
Salvia deserta SCHANG. (Lamiaceae) is a plant grown in Xinjiang province in China, and its dried roots are called Xinjiang-Danshen. This plant has not been used as a medicine or a food, but recently it was reported that Xinjiang-Danshen is mixed in Danshen (roots of S. miltiorhiza Bunge), a well- known Chinese crude drug, at Xinjiang province when latter was in short supply. We examined the constituents of the roots of S. deserta (Xinjiang- Danshen) and identified a new caffeic acid trimer [salvianolic acid K (1)], along with two known caffeic acid dimers [salviaflaside (2), rosmarinic acid (3)], a known caffeic acid tetramer [lithospermic acid B (4)], seven known abietane-type diterpenes [6,7-dehydroroyleanone (5), royleanone (6), taxodione (7), ferruginol (8), 7-O-methylhorminone (9), 7-O-acetylhorminone (10), horminone (11)], and a known steroid [daucosterol (12)]. Five of the diterpenes (5, 6, 9-11) were 'royleanones' and the main caffeic acid derivative was the trimer 1. These differed from the constituents of roots of S. miltiorhiza, which contains 'tanshinones' as diterpenes and magnesium lithospermate B as the main caffeic acid derivative. Thus, the mixing of Xinjiang-Danshen with Danshen is not appropriate and two should be considered different drugs.
A new diterpenoid quinone has been isolated and characterized on the basis of the chemical and spectroscopic properties.
The essential oils of eight Salvia species collected from different localities in Iran were analyzed by gas chromatography/mass spectrometry (GC/MS). The analytical results were compared with those previously published for related Iranian sage species in order to identify chemical markers for these species. Salvia eremophila, S. hypoleuca, and S. reuteriana are endemic, while S. atropatana, S. chloroleuca, S. santolinifolia, S. aegyptiaca, and S. macrosiphon also grow wild in neighboring countries. We categorized the Iranian Salvia species into four main chemotypes according to their essential-oil constituents: those which are dominated by 1) monoterpenes, 2) mono- and sesquiterpenes, or 3) sesquiterpenes as the major constituents, and 4) those containing low-molecular-weight acids, aldehydes, and esters, and green-leaf volatiles (GLVs). Likely due to the chemical diversity of different Salvia chemotypes, this categorization was supported by principal component analysis (PCA) for the group sampled here, but not for the values reported in the literature. We identified the following chemical markers: α-pinene, β-pinene, 1,8-cineol, linalool, and borneol in monoterpene-rich species, or β-caryophyllene, germacrene D, bicyclogermacrene, spathulenol, and caryophyllene oxide in sesquiterpene-rich species. Among these, α-pinene, β-caryophyllene, and germacrene D are the most common and abundant in the Salvia species investigated. In accordance with their close biological taxonomy, the chemical similarity of the essential oils of S. santolinifolia and S. eremophila is so high that we may consider them chemically identical.
A new diterpene, named rosmariquinone, was isolated from the leaves ofRosmarinus officinalis L. The leaves were first extracted using methanol and, upon further purification, this extract yielded rosmariquinone. Structure
elucidation of the antioxidant was done using IR, MS,1H-NMR and13C-NMR.
Phytochemical investigations of the n-hexane extract from the roots of Peltodon longipes (Lamiaceae) resulted in the isolation of 12 known abietane diterpenes (1-12). Structures were established on the basis of one and two dimensional nuclear magnetic resonance spectroscopic data ((1)H and (13)C, COSY, HSQC and HMBC), electron ionization mass spectrometric analysis (EIMS) as well as comparison with data from literature. These compounds, as well as eight known diterpenes (13-19) from Salvia miltiorrhiza, and two from Salvia sahendica (20 and 21) were evaluated for their cytotoxic effects in human pancreatic (MIAPaCa-2) and melanoma (MV-3) tumor cell lines using the MTT assay. Tanshinone IIa (13), 7α-acetoxyroyleanone (1), 1,2-dihydrotanshinone (16) and cryptotanshinone (14) had the highest cytotoxic effects in MIAPaCa-2, displaying IC(50) of 1.9, 4.7, 5.6, and 5.8 μM, respectively. Structure-activity relationships of abietane diterpenoid quinones are discussed.
Two naphthoquinone diterpenoids, 1 and 2, one tricyclic, and one tetracyclic rearranged abietane ('4,5-seco-10,5-friedo-abietane') diterpenoids, 3 and 4, respectively, together with horminone (5) have been isolated from the roots of Salvia sahendica. Compounds 2 and 3 are new, and the 13C-NMR assignment for compound 4 was modified using ' Heteronuclear Multiple-Bond Correlation' (HMBC) spectroscopic data. The structures of the compounds have been established by using different spectral data including 1D- and 2D-NMR, IR, UV, and MS. The elemental composition for the major peaks of 3 and 4 were determined by ' High-Resolution Electron Impact Mass Spectrometry' (HR-EI-MS). The relative configurations of the new compounds were determined by 1H-NMR and 'Rotating-Frame NOES' (ROESY) spectroscopy. Compounds 1, 2, and 5 showed antifungal activities when tested on Blakeslea trispora. Lapachol, a prelynated naphthoquinone, was used as a positive control. The biological activities of the related naphthoquinones and abietane diterpenoids were discussed.
Constituents of roots of Salvia deserta SCHANG. (Xinjiang-Danshen)
- Y Tezuka
- R Kasimu
- J X Li
- P Basnet
- K Tanaka
- T Namba
- S Kadota