Megastigmane Glucosides Research Articles

Chemical Profiling, Antioxidant, and Anti-Inflammatory Activities of Hyoseris radiata L., a Plant Used in the Phytoalimurgic Tradition.

Hyoseris radiata L. (Asteraceae), known as "wild chicory", is a perennial herbaceous plant native to the Mediterranean region, North Africa, and West Asia. Collected from the wild, the plant is largely used in Italy for culinary purposes and in popular medicine, so that it can be included in the list of phytoalimurgic plants. The present study aimed to investigate for the first time the plant's chemical profile, through a combined UHPLC-HR-ESI-Orbitrap/MS and NMR approach, and its potential healthy properties, focusing on antioxidant and anti-inflammatory activities. The LC-MS/MS analysis and the isolation through chromatographic techniques of the plant's hydroalcoholic extract allowed the authors to identify 48 compounds, including hydroxycinnamic acids, flavonoids, megastigmane glucosides, coumarins, and lignans, together with several unsaturated fatty acids. The quantitative analysis highlighted a relevant amount of flavonoids and hydroxycinnamic acids, with a total of 12.9 ± 0.4 mg/g DW. NMR-based chemical profiling revealed the presence of a good amount of amino acids and monosaccharides, and chicoric and chlorogenic acids as the most representative polyphenols. Finally, the antioxidant and anti-inflammatory activities of H. radiata were investigated through cell-free and cell-based assays, showing a good antioxidant potential for the plant extract and a significant reduction in COX-2 expression.

New Megastigmane and Polyphenolic Components of Henna Leaves and Their Tumor-Specific Cytotoxicity on Human Oral Squamous Carcinoma Cell Lines.

Polyphenols have a variety of phenolic hydroxyl and carbonyl functionalities that enable them to scavenge many oxidants, thereby preserving the human redox balance and preventing a number of oxidative stress-related chronic degenerative diseases. In our ongoing investigation of polyphenol-rich plants in search of novel molecules, we resumed the investigation of Lawsonia inermis L. (Lythraceae) or henna, a popular ancient plant with aesthetic and therapeutic benefits. The leaves' 70% aq acetone extract was fractionated on a Diaion HP-20 column with different ratios of H2O/an organic solvent. Multistep gel chromatographic fractionation and HPLC purification of the Diaion 75% aq MeOH and MeOH fractions led to a new compound (1) along with tannin-related metabolites, benzoic acid (2), benzyl 6'-O-galloyl-β-D-glucopyranoside (3), and ellagic acid (4), which are first isolated from henna. Repeating the procedures on the Diaion 50% aq MeOH eluate led to the first-time isolation of two O-glucosidic ellagitannins, heterophylliin A (5), and gemin D (6), in addition to four known C-glycosidic ellagitannins, lythracin D (7), pedunculagin (8), flosin B (9), and lagerstroemin (10). The compound structures were determined through intensive spectroscopic investigations, including HRESIMS, 1D (1H and 13C) and 2D (1H-1H COSY, HSQC, HMBC, and NOESY) NMR, UV, [α]D, and CD experiments. The new structure of 1 was determined to be a megastigmane glucoside gallate; its biosynthesis from gallic acid and a β-ionone, a degradative product of the common metabolite β-carotin, was highlighted. Cytotoxicity investigations of the abundant ellagitannins revealed that lythracin D2 (7) and pedunculagin (8) are obviously more cytotoxic (tumor specificity = 2.3 and 2.8, respectively) toward oral squamous cell carcinoma cell lines (HSC-2, HSC-4, and Ca9-22) than normal human oral cells (HGF, HPC, and HPLF). In summary, Lawsonia inermis is a rich source of anti-oral cancer ellagitannins. Also, the several discovered polyphenolics highlighted here emphasize the numerous biological benefits of henna and encourage further clinical studies to profit from their antioxidant properties against oxidative stress-related disorders.

Chemical composition and cardiotropic activity of Ziziphora clinopodioides subsp. bungeana (Juz.) Rech.f.

Ethnopharmacological relevanceZiziphora clinopodioides subsp. bungeana (Juz.) Rech.f. is a subshrub that is widely distributed in China, Kazakhstan, Kyrgyzstan, Mongolia, Russia, Tajikistan, Turkmenistan, and Uzbekistan. The species is used in traditional medicine for the relief of symptoms connected to cardiovascular diseases like coronary heart disease or hypertension. Aim of the studywas to validate traditional use of Z. clinopodioides subsp. bungeana for the treatment of coronary hearth diseases using in vivo models and to find active compounds responsible for the activity. Materials and methodsMultiple extracts were obtained from the aerial parts of Z. clinopodioides subsp. bungeana using maceration, liquid-liquid extraction, CO2 extraction and ultrasound-assisted extraction. Preliminary screening studies for the evaluation of the efficacy of Z. clinopodioides subsp. bungeana extracts on the model of hemic hypoxia were performed. The most effective samples were selected and included in the main study. Stage 2 of the study evaluated the cardiotropic activity of the selected extracts on a model of chronic heart failure. Preparations were administered to animals intragastrically once a day for 28 days. For the isolation of individual compounds plant material was extracted with 96% ethanol. The obtained crude extract was sequentially extracted with n-hexane and dichloromethane and separated by chromatography on a Diaion HP-20 column. The obtained fractions were further subjected to Sephadex LH-20 column chromatography and eluted isocratically with 96% ethanol (EtOH) to yield subfractions, which were further separated by preparative HPLC to obtain 13 individual compounds. ResultsExtracts obtained from Ziziphora clinopodioides subsp. bungeana (Juz.) Rech.f. herb were subjected to pharmacological screening for the evaluation of their efficacy on hemic hypoxia. Based on the obtained results, out of the sixteen tested extracts two (AR and US 60%) were selected for further evaluation of their cardiotropic activity. Modeling of chronic heart failure was carried out in accordance with the following stages: 1) anesthesia with chloral hydrate at a dose of 450 mg/kg, intraperitoneally, 2) artificial ventilation of the lungs, 3) thoracotomy, 4) modeling of permanent ischemic or ischemic-reperfusion damage. Both extracts effected the indicators of contraction and output, comparable to the reference drug - Monopril. Based on the extraction methods used to obtain RAF and US60 and data from the literature, it can be assumed that they contain compounds with medium polarity, including polyphenols and terpenoids. At the next stage three previously undescribed monoterpenoid derivatives – Ziziphoric acid (1), Ziziphoroside D (2) and 6′-malonylziziphoroside A (3), along with two previously described megastigmane glucosides – blumenol C glucoside (4), blumenol C 9-O-(6′-O-malonyl-beta-D-glucopyranoside (5) and two previously described monoterpenoids 7a-hydroxymintlactone (6), 7-hydroxypiperitone (7) together with six polyphenols – pinocembrine-7-O-rutinoside (8), chrysine-7-O-rutinoside (9), acacetin-7-O-rutinoside (10), luteolin-7-O-rutinoside (11), rutin (12) and rosmarinic acid (13) were isolated from Z. clinopodioides subsp. bungeana extracts. ConclusionOur results support the traditional use of Z. clinopodioides subsp. bungeana for the treatment of coronary diseases. As a result of Z. clinopodioides subsp. bungeana extracts screening in vivo, two extracts were selected as potential cardiotropic agents. Phytochemical analysis of the plant material led to the isolation of five terpenoid derivatives, two megastigmane glycosides, five flavonoids and one cinnamic acid derivative, which could be responsible for the reported biological activity. Future experiments are required to understand the mechanisms of action for the isolated compounds.

Chemical investigation of Buddleja officinalis leaves and localization of defensive triterpenoids to its glandular trichomes

Buddleja officinalis is a traditional Chinese medicinal plant covered with glandular and non-glandular trichomes on leaves. Phytochemical investigation of its leaves led to the identification of one undescribed tetranorcycloartane 3-oxo-25,26,27,29-tetranorcycloartan-24-oic acid (1) and one first identified natural product tetranorcycloartane 3-oxo-25,26,27,29-tetranorcycloartan-24-oic methyl ester (2), along with an undescribed megastigmane glucoside (3) and 14 known constituents (4–17). Structures of undescribed chemicals were elucidated by comprehensive 1D and 2D NMR, MS and CD analysis. Further chemical investigation resulted in six triterpenoids (4–9) being localized to the trichomes of B. officinalis. The major trichome components cycloeucalenone (4) and 24-oxo-29-norcycloartan-3-one (5) showed potent antifeedant activity against a generalist insect cotton bollworm (Helicoverpa armigera), but no obvious activity against the specialist herbivore Hyphasis inconstans. Compounds 4 and 7 also displayed inhibitory effects on seed germination of Arabidopsis thaliana. In addition, 1 and 4 exhibited moderate antibacterial activity toward three gram-positive bacteria.

First Occurrence of Megastigmane Glucosides in a Plant of Retama Genus.

Chemical investigation of Retama sphaerocarpa collected in Algeria resulted in the isolation of two megastigmane glucosides, compounds 1 and 2, along with a series of isoflavones and phenol derivatives. Compound 1, named retamoside, was new and its structure was determined by extensive application of spectroscopic methods, including HRMS, 1D and 2D NMR and CD. The anti-inflammatory properties of co-occurring main megastigmane, saurobaccioside B (2) and structurally related vomifoliol (3) on LPS-stimulated murine macrophages RAW 274.7 have been evaluated.

Megastigmane sesquiterpenoids from whole plants of Viola kunawurensis

Investigation on the chemical constituents of Viola kunawurensis resulted in the isolation of seven undescribed megastigmane sesquiterpenoids including four bicyclic megastigmane glucosides, kunawuronoside A-D, two megastigmane glucosides, kunawuronoside E-F, and a megastigmane, kunawurone A, together with ten known megastigmane sesquiterpenoids. Their structures were established by comprehensive 1D, 2D-NMR and HRESIMS analyses, and their absolute configurations were determined by comparing their calculated ECD data with the experimental ones. Evaluations of the anti-inflammatory activity revealed that kunawuronoside A-D and compounds 14–15 inhibited COX-2 expression with inhibition rates ranging from 36.7% to 58.5%, while the NO production induced by lipopolysaccharide (LPS) was suppressed by the kunawuronoside A-D in a dose-dependent manner in RAW264.7 macrophage cell line.

Four new glucosides from the aerial parts of Equisetum sylvaticum.

Two previously undescribed megastigmane glucosides, (3S)-3-hydroxy-4-oxo-7,8-dihydro-β-ionone-3-O-β-D-glucopyranoside (1), (3S)-3-hydroxy-4-oxo-β-ionone-3-O-β-D-glucopyranoside (2), an apocarotenoid glucoside named equiseoside A (3) and an unusual aromatic compound with a glucose-fused skeleton named equiseoside B (4), together with 35 known compounds (5-39) were isolated from the aerial parts of Equisetum sylvaticum. The structures of these compounds were elucidated by spectroscopic methods, including 1D and 2D NMR, IR, CD, and HR-MS.

PTP1B and α-glucosidase inhibitory activities of the chemical constituents from Hedera rhombea fruits: Kinetic analysis and molecular docking simulation

In this study, we present the first investigation of Hedera rhombea Bean fruit, which led to the isolation of six undescribed compounds including two megastigmane glucosides, two rare 1,4-dioxane neolignanes, and two quinic acid derivatives, together with 26 known compounds. Their structures and absolute configurations were elucidated by extensive analysis of NMR spectroscopic data, HRMS, and ECD calculations. This is the first report on the isolation of methyl 3-O-caffeoyl-5-O-p-coumaroylquinate from a natural source. Among the isolated compounds, falcarindiol and caffeoyltryptophan showed significant PTP1B inhibition with IC50 values of 7.32 and 16.99 μM, respectively, compared to those of the positive controls [sodium orthovanadate (IC50 = 17.96 μM) and ursolic acid (IC50 = 4.53 μM)]. These two compounds along with several other compounds displayed significant α-glucosidase inhibitions with IC50 values ranging from 12.88 to 91.89 μM, stronger than that of the positive control (acarbose, IC50 = 298.07 μM). Enzyme kinetic analysis indicated that caffeoyltryptophan and falcarindiol displayed competitive and mixed-type PTP1B inhibition, respectively, whereas the α-glucosidase inhibition type was mixed-type for caffeoyltryptophan and uncompetitive (rarely reported for a-glucosidase inhibitors) for falcarindiol. In addition, molecular docking results showed that these active compounds exhibited good binding affinities toward both PTP1B and α-glucosidase with negative binding energies. The results of the present study demonstrate that these active compounds might be beneficial in the treatment of type 2 diabetes.

Chemical Constituents from the Branches and Leaves of Alchornea trewioides.

Two new megastigmane glucosides namely trewiosides A (1) and B (2), along with 20α-hydroxypregn-4-en-3-one β-D-glucopyranoside (3), sugeroside (4), and schizandriside (5) were isolated from the branches and leaves of Alchornea trewioides. The structure elucidation was confirmed by extensive analysis of the one and two dimensional (1 and 2D) NMR, electronic circular dichroism (ECD) as well as high resolution electrospray ionization quadrupole time-of-flight (HR-ESI-QTOF) mass spectra. Noteworthily, the isolation of compounds 1 and 2 represents the second finding of megastigmane derivatives with a methoxycarbonyl group at C-5 to date. In addition, compound 3 showed weak cytotoxicity against three human cancer cell lines as A549 (lung carcinoma), HepG2 (hepatocarcinoma), and MCF7 (breast carcinoma). Besides, compounds 2 and 3 exhibited moderate inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells. Whereas, the remaining compounds 1, 4 and 5 showed weak inhibitory activity.

Chemical constituents from the branches and leaves of Alchornea annamica

Phytochemical investigation of the branches and leaves of Alchornea annamica led to isolation of ten secondary metabolites, including two new megastigmane glucosides alnamicosides A (1) and B (2). The structure elucidation was confirmed by 1 D and 2 D NMR, ECD as well as HR-QTOF-MS experiments. The megastigmane derivatives 1 − 3 exhibited inhibitory effects on LPS-induced NO production in RAW264.7 cells with IC50 values of 78.72 ± 1.90, 77.40 ± 9.40 and 82.16 ± 4.56 µM, respectively. This is the first report on chemical constituents and biological activity of the plant A. annamica.

Chemical constituents and absolute configuration of megastigmanes’ isolated from Sedum sarmentosum Bunge

Phytochemical investigation of a methanolic extract of Sedum sarmentosum collected from Vietnam resulted in the isolation of a new megastigmane glucoside, named sedumoside K (1), together with 17 previously reported compounds (2–18). Structural elucidation of the new compound was achieved by HRFABMS, NMR spectroscopic analysis, acid hydrolysis and quantum ECD calculations. The absolute configuration of compounds 2–6 has been revised. The major isolates were tested for cytotoxic activity against HeLa human cervical cancer cells, and all showed moderate activities.

Antioxidant compounds from Banisteriopsis argyrophylla leaves as α-amylase, α-glucosidase, lipase, and glycation inhibitors

Banisteriopsis argyrophylla belongs to the Malpighiaceae family, which is a species from Cerrado, also known as “cipó-prata” or “cipó-folha-de-prata.” Several species of this family present biological potential. This work reports the chemical identification of the ethanol extract (EE) and its fractions from B. argyrophylla leaves and shows the analysis of the antioxidant activity and inhibitory effects on activities of α-amylase, α-glucosidase and lipase, and non-enzymatic glycation. The ethyl acetate fraction (EAF) and n-butanol fraction (BF) showed antioxidant activity, with IC50 values of 4.1 ± 0.1 and 4.8 ± 0.1 μg mL−1, respectively, by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method, and IC50 values of 6046.3 ± 174.2 and 6264.2 ± 32.2 µmol Trolox eq g−1 by the oxygen radical absorbance capacity (ORAC) method. Furthermore, the DPPH method with these fractions presented electroactive species with antioxidant potential, as shown by the differential pulse voltammetry (DPV) method. The inhibitory effects of the EAF and BF were demonstrated by the following results: IC50 of 5.1 ± 0.3 and 2.5 ± 0.2 μg mL−1 for α-amylase, IC50 of 1093.5 ± 26.0 and 1250.8 ± 21.9 μg mL−1 for α-glucosidase, IC50 of 8.3 ± 4.1 and 4.4 ± 1.0 μg mL−1 for lipase, and IC50 of 1.3 ± 0.1 and 0.9 ± 0.1 μg mL−1 for glycation. Some bioactive compounds were identified by (–)-ESI-MS/MS, such as catechin, procyanidins, glycosylated flavonoids, kaempferol, and megastigmane glucosides. The antidiabetic activity of B.argyrophylla has been reported for the first time.

Attenuation of Inflammatory Symptoms by Icariside B2 in Carrageenan and LPS-Induced Inflammation Models via Regulation of MAPK/NF-κB Signaling Cascades.

Prolonged inflammatory responses can lead to the development of several chronic diseases, such as autoimmune disorders and the development of natural therapeutic agents is required. A murine model was used to assess the anti-inflammatory effects of the megastigmane glucoside, icariside B2 (ICSB), and the assessment was carried out in vitro, and in vivo. The in vitro anti-inflammatory effects of ICSB were tested using LPS-stimulated BV2 cells, and the protein expression levels of inflammatory genes and cytokines were assessed. Mice were subcutaneously injected with 1% carrageenan (CA) to induce acute phase inflammation in the paw. Inflammation was assessed by measuring paw volumes hourly; subsequently, the mice were euthanized and the right hind paw skin was expunged and processed for reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses. ICSB inhibits LPS-stimulated nitric oxide (NO) and prostaglandin E2 (PGE2) generation by reducing the expression of inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2). ICSB also inhibits the COX-2 enzyme with an IC50 value of 7.80 ± 0.26 µM. Molecular docking analysis revealed that ICSB had a strong binding affinity with both murine and human COX-2 proteins with binding energies of −8 kcal/mol and −7.4 kcal/mol, respectively. ICSB also reduces the manifestation of pro-inflammatory cytokines, such as TNF-α, IL-6, and IL-1β, at their transcriptional and translational level. ICSB hinders inhibitory protein κBα (IκBα) phosphorylation, thereby terminating the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) nuclear translocation. ICSB also represses the mitogen-activated protein kinases (MAPKs) signaling pathways. ICSB (50 mg/kg) showed an anti-edema effect in CA-induced mice and suppressed the CA-induced increases in iNOS and COX-2 protein levels. ICSB attenuated inflammatory responses by downregulating NF-κB expression through interference with extracellular signal-regulated kinase (ERK) and p38 phosphorylation, and by modulating the expression levels of iNOS, COX-2, TNF-α, IL-1β, and IL-6.

Megastigmane Derivatives from the Cladodes of Opuntia humifusa and Their Nitric Oxide Inhibitory Activities in Macrophages

Opuntia humifusa, known as the eastern prickly pear cactus and locally called "Cheonnyuncho" in Korea, is cultivated widely on Jeju Island, Korea. Phytochemical analysis of the methanolic extract of the cladodes of O. humifusa, for which previous research is relatively limited, was performed under the guidance of LC/MS-based analysis. As a result, one new megastigmane (1) and four new megastigmane glucosides (2-5) were isolated along with 18 known compounds (6-23). The structures of the new compounds were established by 1D and 2D NMR and HRESIMS, and their absolute configurations were established by chemical reactions, quantum chemical electronic circular dichroism calculations, and DP4+ analysis using the gauge-including atomic orbital NMR chemical shift calculations as well as the application of Snatzke's method. The isolated compounds (1-23) were tested for NO production inhibition in lipopolysaccharide (LPS)-induced RAW 264.7 cells to investigate their anti-inflammatory effects. Compounds 10 and 11 exhibited significant inhibitory effects on LPS-induced NO production in a dose-dependent manner. The potential mechanistic pathway of 10 and 11 was also investigated using Western blotting, indicating that compounds 10 and 11 inhibit NO through iNOS expression.

Structural Diversity of Chemical Constituents from Okinawan Plants

In our continuing search for secondary metabolites from plants, we investigated the chemical constituents of various Okinawan plants. From the stems and leaves of Croton cascarilloides (Euphorbiaceae), a great number of rare diterpenoids: crotofolanes; crotocascarins A-Q, and new diterpenoids; rearranged nor-crotofolanes: crotocascarins α-γ; a rearranged crotofolane: neocrotocascarin; and a new skeletal diterpenoid: isocrotofolane glucoside were isolated. Their structures were mainly elucidated from NMR spectroscopic evidence. In addition, absolute configurations of crotocascarins A, B, K and O, crotocascarin α and neocrotocascarin were determined by X-ray crystallographic analyses, chiral HPLC analyses of 2-methylbutyric acid in their molecules, application of the circular dichroism rule for the α,β-unsaturated γ-lactone ring, and the modified Mosher's method. The absolute structures of crotofolanes were reported for the first time, and a biosynthetic mechanism for the formation of crotocascarin α and neocrotocascarin from crotocascarin B was proposed. Other interesting compounds, namely diosmarioside H: a dimeric ent-kaurane glycoside from the leaves of Diospyros maritima, and melionosides A-C: megastigmane glucosides with a spiro-ring structure from the leaves of Meliosma lepidota ssp. squamulata were also isolated.

Chemical constituents of the Piper crocatum leaves and their chemotaxonomic significance

Chemical study of Piper crocatum leaves has led to isolation of a new megastigmane glucoside isomer (18), along with 23 known compounds including fifteen phenolic compounds (1–15), two monoterpenes (16 and 17), three sesquiterpenes (19–21), a phenolic amide glycoside (22), a neolignan (23), and a flavonoid C-glycoside (24). Structures of these compounds were identified via spectroscopic methods and compared with those reported in the literature. Seven compounds (7, 11, 13, 14, 17, 20, and 24) from the P. crocatum species and 17 others (1–6, 8–10, 12, 15–16, 18–19, and 21–23) from the Piper genus and Piperaceae family were isolated and reported for the first time. Furthermore, this study discusses chemotaxonomic relations between P. crocatum and other Piper species.

Megastigmane derivatives from Corispermum mongolicum and their anti-inflammatory activities

Phytochemical investigation of the ethanol extract of the whole plant of Corispermum mongolicum Iljin led to the isolation of a new megastigmane, (―)-(3R)-hydroxysulfonyloxy-β-ionone (1), a new megastigmane glucoside, (3S,6S,9R)-3,9,13-trihydroxymegastigman-4-ene-3-O-β-d-glucopyranoside (2), as well as four known compounds (3–6). The structures of these new compounds were elucidated mainly by using NMR, HR-ESI-MS, and modified Mosher’s method. The anti-inflammatory activities of the isolated megastigmane derivatives were evaluated by examining the secretion of inflammatory markers (NO, TNF-α, and IL-6) by LPS-stimulated RAW 264.7 cells. Compounds 1–2, 4 and 5 exhibited anti-inflammatory activities, and compound 2 was found to possess better inhibitory activity than the other compounds tested.

Bioactive megastigmane glucosides and monoterpenes from Lyonia ovalifolia

Three new megastigmane glucosides (1–3) and two new monoterpenes (4–5), together with 14 related known compounds (6–19) were isolated from the twigs and leaves of Lyonia ovalifolia. The structures of the new compounds were determined by extensive MS, NMR, CD experiments and chemical methods. Compounds 2, 6, and 18 displayed potent antiviral activity against Coxsackie B3, with IC50 values between 6.4 and 14.6 µM. Additionally, compounds 6, 10, and 11 exhibited noteworthy anti-inflammatory activities, with inhibition rates ranging from 54.55% to 83.33% under the concentration of 10−5 M.

Benzoxazinoid and indoxyl glycosides from Wrightia religiosa

A new class of secondary metabolites of the family Apocynaceae, benzoxazinoid, was reported for the first time from Wrightia religiosa. A new benzoxazinoid glycoside, (2S)-2-O-β-d-glucopyranosyl-2H-1,4-benzoxazin-3(4H)-one (2) and a new indole diglycoside, indoxyl 3-O-β-d-apiofuranosyl-(1 → 6)-β-d-glucopyranoside (4) were isolated, together with twelve known compounds, including benzoxazinoid glycosides (1, 3), simple aromatic glycosides (5–8), a lignan glycoside (9), flavonol glycosides (10–13) and a megastigmane glucoside (14). The structure elucidation of these compounds was based on analyses of physical and spectroscopic data including 1D and 2D NMR experiments. A benzoxazinoid with (2S)-configuration was isolated for the first time from natural source.

Polar Constituents of Salvia willeana (Holmboe) Hedge, Growing Wild in Cyprus.

Twenty compounds were isolated from the aerial parts of Salvia willeana (Holmboe) Hedge, growing wild in Cyprus. These compounds comprise one new and one known acetophenone, one megastigmane glucoside, five phenolic derivatives, two caffeic acid oligomers, three flavonoids, two lignans, two triterpene acids, one monoterpene glucoside, and two fatty acids. The structures of the isolated compounds were established by means of NMR [(Rotating-frame OverhauserEffect SpectroscopY) (1H-1H-COSY (COrrelation SpectroscopΥ), 1H-13C-HSQC (Heteronuclear Single Quantum Correlation), HMBC (Heteronuclear Multiple Bond Correlation), NOESY (Nuclear Overhauser Effect SpectroscopY), ROESY (Rotating-frame Overhauser Effect SpectroscopY)] and MS spectral analyses. This is the first report of the natural occurrence of 4-hydroxy-acetophenone 4-O-(3,5-dimethoxy-4-hydroxybenzoyl)-β-d-glucopyranoside. A chemical review on the non-volatile secondary metabolites has been carried out. Based on the literature data, the analysis revealed that the chemical profile of S. willeana is close to that of S. officinalis L.