Epirosmanol

Anti-Heliobacter pylori and Anti-Inflammatory Potential of Salvia officinalis Metabolites: In Vitro and In Silico Studies.[Pubmed:36677061]

Metabolites. 2023 Jan 16;13(1):136.

Due to its rising antibiotic resistance and associated inflammations, Helicobacter pylori poses a challenge in modern medicine. Salvia officinalis, a member of the Lamiaceae family, is a promising medicinal herb. In this regard, a phytochemical screening followed by GC-MS and LC-MS was done to evaluate the chemical profile of the total ethanolic extract (TES) and the essential oil, respectively. The anti-H. pylori and the anti-inflammatory activities were evaluated by a micro-well dilution technique and COX-2 inhibition assay. Potential anti-H. pylori inhibitors were determined by an in silico study. The results revealed that the main metabolites were flavonoids, sterols, volatile oil, saponins, and carbohydrates. The LC-MS negative ionization mode demonstrated 12 compounds, while GC-MS showed 21 compounds. Carnosic acid (37.66%), Epirosmanol (20.65%), carnosol1 (3.3%), and 12-O-methyl carnosol (6.15%) were predominated, while eucalyptol (50.04%) and camphor (17.75%) were dominant in LC-MS and GC-MS, respectively. TES exhibited the strongest anti-H. pylori activity (3.9 microg/mL) asymptotic to clarithromycin (0.43 microg/mL), followed by the oil (15.63 microg/mL). Carnosic acid has the best-fitting energy to inhibit H. pylori (-46.6769 Kcal/mol). TES showed the highest reduction in Cox-2 expression approaching celecoxib with IC(50) = 1.7 +/- 0.27 microg/mL, followed by the oil with IC(50) = 5.3 +/- 0.62 microg/mL. Our findings suggest that S. officinalis metabolites with anti-inflammatory capabilities could be useful in H. pylori management. Further in vivo studies are required to evaluate and assess its promising activity.

Screening active ingredients of rosemary based on spectrum-effect relationships between UPLC fingerprint and vasorelaxant activity using three chemometrics.[Pubmed:31785534]

J Chromatogr B Analyt Technol Biomed Life Sci. 2019 Dec 15;1134-1135:121854.

Rosmarinus officinalis L., rosemary, is traditionally used to treat headache and improve cardiovascular disease partly due to its vasorelaxant activity, while the vasorelaxant ingredients remain unclear. In this study, chemical spectrum-pharmacological effect relationship (spectrum-effect relationship) was utilized for efficiently discovering the main vasorelaxant ingredients of rosemary. Ten kinds of rosemary extracts were prepared by different extracting solvents and macroporous resin purification, and their chemical components were analyzed by UPLC. At the same time, the vasorelaxant activities of the 10 kinds of rosemary extracts were estimated on isolated rat thoracic aorta, and three chemometrics named partial least squares regression (PLSR), grey correlation analysis (GRA), and the least absolute shrinkage and selection operator (LASSO) were applied to construct spectrum-effect relationship between the UPLC fingerprints and vasorelaxant activity of rosemary extracts. As a result, most rosemary extracts showed dose-dependent increase in vasorelaxant activity and five kinds of ingredients, including carnosol, carnosic acid, Epirosmanol methyl ether, carnosol isomer, and augustic acid were screened as vasorelaxant ingredients. Further, the vasorelaxant activities of carnosic acid and carnosol were verified. Moreover, the increase of nitric oxide (NO) and the decrease of angiotensin-II (Ang-II) were thought to contribute to the vasorelaxant activity of rosemary.

Acetylcholine esterase inhibitors and melanin synthesis inhibitors from Salvia officinalis.[Pubmed:27444345]

Phytomedicine. 2016 Sep 15;23(10):1005-11.

BACKGROUND: Salvia officinalis is a traditionally used herb with a wide range of medicinal applications. Many phytoconstituents have been isolated from S. officinalis, mainly phenolic diterpenes, which possess many biological activities. PURPOSE: This study aimed to evaluate the ability of the phenolic diterpenes of S. officinalis to inhibit acetylcholine esterase (AChE) as well as their ability to inhibit melanin biosynthesis in B16 melanoma cells. METHODS: The phenolic diterpenes isolated from the aerial parts of S. officinalis were tested for their effect on melanin biosynthesis in B16 melanoma cell lines. They were also tested for their ability to inhibit AChE using Ellman's method. Moreover, a molecular docking experiment was used to investigate the binding affinity of the isolated phenolic diterpenes to the amino acid residues at the active sites of AChE. RESULTS: Seven phenolic diterpenes-sageone, 12-methylcarnosol, carnosol, 7b-methoxyrosmanol, 7a-methoxyrosmanol, isorosmanol and Epirosmanol-were isolated from the methanolic extract of the aerial parts of S. officinalis. Isorosmanol showed a melanin-inhibiting activity as potent as that of arbutin. Compounds 7a-methoxyrosmanol and isorosmanol inhibited AChE activity by 50% and 65%, respectively, at a concentration of 500 microM. CONCLUSIONS: The results suggest that isorosmanol is a promising natural compound for further studies on development of new medications which might be useful in ageing disorders such as the declining of cognitive functions and hyperpigmentation.

New terpenoid glycosides obtained from Rosmarinus officinalis L. aerial parts.[Pubmed:25200369]

Fitoterapia. 2014 Dec;99:78-85.

Five new terpenoid glycosides, named as officinoterpenosides A(1) (1), A(2) (2), B (3), C (4), and D (5), together with 11 known ones, (1S,4S,5S)-5-exo-hydrocamphor 5-O-beta-D-glucopyranoside (6), isorosmanol (7), rosmanol (8), 7-methoxyrosmanol (9), Epirosmanol (10), ursolic acid (11), micromeric acid (12), oleanolic acid (13), niga-ichigoside F(1) (14), glucosyl tormentate (15), and asteryunnanoside B (16), were obtained from the aerial parts of Rosmarinus officinalis L. Their structures were elucidated by chemical and spectroscopic methods (UV, IR, HRESI-TOF-MS, 1D and 2D NMR). Among the new ones, 1 and 2, 3 and 4 are diterpenoid and triterpenoid glycosides, respectively; and 5 is a normonoterpenoid. For the known ones, 6 was isolated from the Rosmarinus genus first, and 15, 16 were obtained from this species for the first time.

Structure activity relationship of phenolic diterpenes from Salvia officinalis as activators of the nuclear factor E2-related factor 2 pathway.[Pubmed:23507152]

Bioorg Med Chem. 2013 May 1;21(9):2618-22.

Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor known to activate cytoprotective genes which may be useful in the treatment of neurodegenerative disease. In order to better understand the structure activity relationship of phenolic diterpenes from Salvia officinalis L., we isolated carnosic acid, carnosol, Epirosmanol, rosmanol, 12-methoxy-carnosic acid, sageone, and carnosaldehyde using polyamide column, centrifugal partition chromatography, and semi-preparative high performance liquid chromatography. Isolated compounds were screened in vitro for their ability to active the Nrf2 and general cellular toxicity using mouse primary cortical cultures. All compounds except 12-methoxy-carnosic acid were able to activate the antioxidant response element. Furthermore both carnosol and carnoasldehyde were able to induce Nrf2-dependent gene expression as well as protect mouse primary cortical neuronal cultures from H(2)O(2) induced cell death.

Phenolic diterpenes derived from Hyptis incana induce apoptosis and G(2)/M arrest of neuroblastoma cells.[Pubmed:23155243]

Anticancer Res. 2012 Nov;32(11):4781-9.

BACKGROUND: Neuroblastoma is one of the most commonly encountered solid tumors in the pediatric age group, and the prognosis of patients with advanced neuroblastoma is very poor. In this study, the antitumor effects of five phenolic diterpenes derived from Hyptis incana (Lamiaceae), a Brazilian medicinal plant, were examined on neuroblastoma cells. MATERIALS AND METHODS: Cytotoxicity was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptotic nuclear shrinkage was monitored by Hoechst 33342 staining. The cell-cycle status was evaluated by flow cytometry and protein alterations were monitored by western blotting. Differentiated cells were photographed and counted in a randomized fashion. RESULTS: All of the examined compounds exhibited significant cytotoxicity towards the neuroblastoma cells. In particular, 7-ethoxyrosmanol had a high degree of efficacy. Nuclear condensation and degradation of procaspase-3 and -9 were observed after treatment of the cells with these compounds. Moreover, phenolic diterpenes induced cell-cycle arrest in the G(2)/M phase. Rosmanol and Epirosmanol tended to induce differentiation. CONCLUSION: Phenolic diterpenes isolated from H. incana have multiple antitumor effects on neuroblastoma cells.

Activation of the nuclear receptor PPARgamma by metabolites isolated from sage (Salvia officinalis L.).[Pubmed:20696231]

J Ethnopharmacol. 2010 Oct 28;132(1):127-33.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia officinalis has been used as a traditional remedy against diabetes in many countries and its glucose-lowering effects have been demonstrated in animal studies. The active compounds and their possible mode of action are still unknown although it has been suggested that diterpenes may be responsible for the anti-diabetic effect of Salvia officinalis. AIM OF THE STUDY: To investigate whether the reported anti-diabetic effects of Salvia officinalis are related to activation of the nuclear receptor peroxisome proliferator-activated receptor (PPAR)gamma and to identify the bioactive constituents. MATERIALS AND METHODS: From a dichloromethane extract of Salvia officinalis able to activate PPARgamma several major metabolites were isolated by chromatographic techniques. To assess bioactivity of the isolated metabolites a PPARgamma transactivation assay was used. RESULTS: Eight diterpenes were isolated and identified including a new abietane diterpene being the Epirosmanol ester of 12-O-methyl carnosic acid and 20-hydroxyferruginol, which was isolated from Salvia officinalis for the first time, as well as viridiflorol, oleanolic acid, and alpha-linolenic acid. 12-O-methyl carnosic acid and alpha-linolenic acid were able to significantly activate PPARgamma whereas the remaining metabolites were either unable to activate PPARgamma or yielded insignificant activation. CONCLUSIONS: Selected metabolites from Salvia officinalis were able to activate PPARgamma and hence, the anti-diabetic activity of this plant could in part be mediated through this nuclear receptor.

Development of a triple hyphenated HPLC-radical scavenging detection-DAD-SPE-NMR system for the rapid identification of antioxidants in complex plant extracts.[Pubmed:15941042]

J Chromatogr A. 2005 May 13;1074(1-2):81-8.

A rapid method for the simultaneous detection and identification of radical scavenging compounds in plant extracts was developed by combining an HPLC with on-line radical scavenging using DPPH* as a model radical and an HPLC-DAD-SPE-NMR system. Using this method a commercial rosemary extract was investigated. All major compounds present in the extract were collected on SPE cartridges after their separation. Advantages of on-line SPE peak trapping are the possibility to perform HPLC with non-deuterated solvents, a concentration effect and being able to record NMR spectra in pure 100% deuterated solvents. After comparing DAD and DPPH scavenging chromatograms, 1H NMR spectra of compounds having radical scavenging activities were recorded. Afterwards all compounds were collected and infused into an ESI-MS. The five main active compounds - carnosol, carnosic acid carnosaldehyde, 12-methoxycarnosic acid and epiisorosmanol could be identified from the combined UV, NMR and mass spectral data without actually isolating them. It was possible to record on-line an HMBC spectrum of carnosic acid. Also one compound was tentatively identified as Epirosmanol methyl ether.

Determination of phenolic antioxidant compounds produced by calli and cell suspensions of sage (Salvia officinalis L.).[Pubmed:14593803]

J Plant Physiol. 2003 Sep;160(9):1025-32.

Sage (Salvia officinalis L.) calli were established by culturing internodal segments, excised from aseptic seedlings, on MS basal medium gellied with agar and supplemented with 0.05 mg/L dichlorophenoxyacetic acid (2,4-D) in presence of benzyladenine (BA) or zeatin (ZEA) or kinetin (KIN), at 1.5 mg/L. Suspended cells were established by transferring one callus to 50 mL of liquid MS basal medium devoid of agar and containing the same type of hormonal supplementation used in respective calli growth. The highest growth of calli and suspensions occurred with 1.5 mg/L ZEA. However, with this cytokinin supplementation, as well as with 1.5 mg/L KIN, both in presence of 0.05 mg/L 2,4-D, suspensions differentiated small root shaped structures. Well shaped, majority single cell suspensions were formed under the effect of 0.05 mg/L 2,4-D and 0.5 mg/L KIN. Calli grown with 0.05 mg/L 2,4-D and 1.5 mg/L BA and suspended cells grown with 0.05 mg/L 2,4-D and ZEA or KIN at 1.5 mg/L, or KIN at 0.5 mg/L, were searched for phenolics production. Twelve phenolic compounds were identified in calli: gallic acid, 3-O-caffeoylquinic acid, 5-O-caffeoylquinic acid, caffeic acid, rosmarinic acid, hesperetin, Epirosmanol, hispidulin, genkwanin, carnosol, carnosic acid, and methyl carnosate. With the exception for genkwanin and Epirosmanol all of these phenolic compounds were also produced by the sage suspension cultures grown in the presence of 1.5 or 0.5 mg/L KIN. Genkwanin was the only phenolic absent in the suspensions grown with 1.5 ZEA. Suspended cells, grown with 0.5 mg/L KIN, and calli cultures showed the highest specific accumulation of the total phenolics, with rosmarinic acid representing 94-97%.

Semisynthesis of rosmanol and its derivatives. Easy access to abietatriene diterpenes isolated from the genus Salvia with biological activities.[Pubmed:12141857]

J Nat Prod. 2002 Jul;65(7):986-9.

The known diterpenes rosmanol (3), rosmaquinone (4), 7-methoxyrosmanol (5), 7-ethoxyrosmanol (6), galdosol (7), and Epirosmanol (8) have been obtained by partial synthesis from carnosol (2), an abundant natural product present in Salvia species. The physical and spectroscopic data of these semisynthetic diterpenes were identical to those of authentic natural samples and with data reported in the literature. These abietane diterpenes have very interesting biological activities and are present in the genus Salviain low quantities; thus, the semisynthetic approach described here represents an efficient alternative method to obtain these compounds. Additionally, the known diterpene 16-hydroxyrosmanol (10) and a new aromatic diterpene 11 were obtained from 16-hydroxycarnosol (9) by reaction with Ph3P/NBS in CH2Cl2. The structure of the new compound 11 was established from its spectroscopic data as 12,16-epoxycarnosol.

Antioxidant activity of chemical components from sage (Salvia officinalis L.) and thyme (Thymus vulgaris L.) measured by the oil stability index method.[Pubmed:11902922]

J Agric Food Chem. 2002 Mar 27;50(7):1845-51.

A new abietane diterpenoid, 12-O-methyl carnosol (2), was isolated from the leaves of sage (Salvia officinalis L.), together with 11 abietane diterpenoids, 3 apianane terpenoids, 1 anthraquinone, and 8 flavonoids. Antioxidant activity of these compounds along with 4 flavonoids isolated from thyme (Thymus vulgaris L.) was evaluated by the oil stability index method using a model substrate oil including methyl linoleate in silicone oil at 90 degrees C. Carnosol, rosmanol, Epirosmanol, isorosmanol, galdosol, and carnosic acid exhibited remarkably strong activity, which was comparable to that of alpha-tocopherol. The activity of miltirone, atuntzensin A, luteolin, 7-O-methyl luteolin, and eupafolin was comparable to that of butylated hydroxytoluene. The activity of these compounds was mainly due to the presence of ortho-dihydroxy groups. The 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity of these compounds showed the similar result.

Antioxidant properties of phenolic diterpenes from Rosmarinus officinalis.[Pubmed:11749806]

Acta Pharmacol Sin. 2001 Dec;22(12):1094-8.

AIM: To investigate the inhibition capacities of carnosol, rosmanol, and Epirosmanol, which are phenolic diterpenes from Rosmarinus officinalis, to oxidized low-density lipoprotein (LDL) formation in human blood and detect their scavenging activities to lipid free radical and superoxide anion in vitro. METHODS: The antioxidant activities which were expressed with the inhibilities to lipid free radicals in the membrane lipid of cell and oxidized LDL formation were evaluated by TBARS assay and ESR method. The inhibition on the Cu2+-mediated oxidization of apo B formation in LDL was investigated by fluorescence spectroscopy. RESULTS: Carnosol, rosmanol, and Epirosmanol had an inhibitory activity to lipid peroxidation and oxidized apo B formation in human bloods LDL. The IC50 were 7-10 micromol/L. The antioxidant mechanism was related to the scavenging activities to lipid free radical. CONCLUSION: carnosol, rosmanol, and Epirosmanol showed the activity in inhibiting LDL oxidation.

Apianane terpenoids from Salvia officinalis.[Pubmed:11738402]

Phytochemistry. 2001 Dec;58(8):1171-5.

Three apianane terpenoids, rel-(5S, 6S, 7S, 10R, 12S, 13R)-7-hydroxyapiana-8,14-diene-11,16-dion-(22,6)-olide, rel-(5S, 6S, 7R, 10R, 12S, 13R)-7-hydroxyapiana-8,14-diene-11,16-dion-(22,6)-olide and rel-(5S, 6S, 7S, 10R, 12R, 13S)-7-hydroxyapiana-8,14-diene-11,16-dion-(22,6)-olide were isolated from the leaves of Salvia officinalis, together with 15 known compounds, salvigenin, lupeol, beta-sitosterol, stigmasterol, physcion, carnosol, rosmadial, rosmanol, Epirosmanol, isorosmanol, columbaridione, atuntzensin A, miltirone, carnosic acid and 12-O-methyl carnosic acid. Their structures were established on the basis of spectral evidence.

Inhibition of lipid peroxidation and superoxide generation by diterpenoids from Rosmarinus officinalis.[Pubmed:7480180]

Planta Med. 1995 Aug;61(4):333-6.

Four diterpenoids, carnosic acid (1), carnosol (2), rosmanol (3), and Epirosmanol (4), were isolated as antioxidative agents from the leaves of Rosmarinus officinalis by bioassay-directed fractionation. These diterpenoids inhibited superoxide anion production in the xanthine/xanthine oxidase system. Mitochondrial and microsomal lipid peroxidation induced by NADH or NADPH oxidation were also completely inhibited by these diterpenes at the concentration of 3-30 microM. Furthermore, carnosic acid protected red cells against oxidative hemolysis. These phenolic diterpenes were shown to be effective to protect biological systems against oxidative stresses.