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Amarisolide H and 15-epi-Amarisolide H, Two Diterpenoid Glucosides from Salvia circinnata
Abstract
The HPLC–PDA profiling of an acetone-soluble extract of the leaves of Salvia circinnata Cav. (Syn. Salvia amarissima Ortega), Lamiaceae, collected at Patzcuaro, Michoacan, Mexico, indicated this population corresponds to the chemotype “amarisolide A.” The phytochemical study of the extract led to the isolation of two new diterpenoid glucosides, amarisolide H and 15-epi-amarisolide H, which were obtained as an epimeric mixture, together with the known compounds amarisolides A, D, G, 16-epi-amarisolide G, and 5,6-dihydroxy-7,3′,4′-trimethoxyflavone. The structures of compounds amarisolide H and 15-epi-amarisolide H were determined by the analyses of their NMR and HRMS data. The cytotoxicity and anti-multidrug resistance (MDR) effects of compounds amarisolide H, 15-epi-amarisolide H, amarisolide A, amarisolide G, and 16-epi-amarisolide G in MCF-7 cancer cells sensible and resistant to vinblastine were essayed.
... This fact turns the plant into a "rare species" that is very vulnerable to extinction from its natural habitat (Rabinowitz 1981), so its collect must avoid be excessive and future studies should be consider the propagation of the plant. As part of our ongoing efforts to isolate and characterize novel bioactive specialized metabolites from the Mexican flora (Ortega et al. 2020;García-Nava et al. 2022;Sepúlveda-Cuellar et al. 2023) with antiprotozoal, cytotoxic, and MDR reversion activities (Bautista et al. 2015a(Bautista et al. , b, 2022, herein, we describe the first chemical study from the aerial parts of Decachaeta perornata (Klatt) R.M.King & H.Rob., Asteraceae, and the cytotoxicity of its major constituents, xerantholide (1) and ivalin (2), against three cancer cell lines. ...
Phytochemical study of a CH2Cl2-soluble extract from the leaves and flowers of Decachaeta perornata (Klatt) R.M.King & H.Rob., Asteraceae, led to the isolation of two sesquiterpene lactones, a guaianolide and an eudesmanolide. The structures of both compounds were established by the extensive analyses of their 1D/2D NMR and HRMS data as xerantholide and ivalin. The absolute configuration of guaianolide was determined by two methods: TD-DFT ECD calculations and single crystal X-ray diffraction. Eudesmanolide is noteworthy for its potential applications in the treatment of several types of carcinoma. An HPLC–PDA profiling of the extract was developed, and the amount of each isolate was quantified to subsequently assay the cytotoxicity of the extract and its isolates against three human cancer cell lines: MCF-7, HCT-116, and HeLa. Guaianolide and an eudesmanolide displayed significant cytotoxicity with IC50 values less than 5 µg/ml against the three cell lines assayed, highlighting their antitumor potential.
Salvia L. (Sage) is a therapeutically important plant genus with over 1000 species worldwide. They are a rich source of novel diterpenes. In this present study, we tried to review the chemistry and pharmacology of the Salvia diterpenes between 2016 and 2024. Therefore, we collected information from various scientific databases, including Scopus and PubMed, using key words “Salvia” AND “Diterpene” OR “Diterpenoid”. This updated review article discussed the phytochemistry and pharmacology of 258 undescribed diterpenes isolated from the Salvia genus between 2016 and October 2024. Studies showed that these diterpenes could be structurally divided into subclasses such as abietanes, clerodanes, icetexanes, labdanes, and fusicoccanes. The reported diterpenes have exhibited various pharmacological effects such as anticancer, antibacterial, antiviral, antiparasitic, anti-inflammatory, analgesic, anti-oxidant, antidiabetic, and neurotrophic activities. According to the results, these diterpenes of Salvia can be the lead compounds for drug discovery, especially for cancer and microbial diseases.
Graphical abstract
Background:
Salvia urica Epling is taxonomically and phylogenetically related to Salvia amarissima Ortega. The last species has pharmacological relevance by its contents of bioactive metabolites. Nowadays, Salvia urica has no reports about its chemical constituents and pharmacological activities.
Hypothesis:
Does the close relationship between S. amarissima and S. urica led both species produce similar specialized metabolites? Does Salvia urica display similar pharmacological effects as S. amarissima?
Studied species:
Salvia urica Epling (Lamiaceae).
Study site and dates:
The plant material was collected in Teopisca, Chiapas, Mexico, in December 2021.
Methods:
Metabolites of the acetone extract from Salvia urica were identified by GC-MS and HPLC-PDA profiling. In parallel, a phytochemical study was conducted, and the individual constituents purified, previously characterized by 1D NMR, were assayed on antihyperglycemic effect in diabetic mice and a charcoal-gum arabic-induced hyperperistalsis model in rats.
Results:
The volatile compounds identified by GC-MS were alkanes, aromatics and triterpenes. The principal constituents of the acetone extract of Salvia urica were amarissinin A and 5,6-dihydroxy-7,3',4'-trimethoxyflavone, which were also quantified by HPLC-PDA. The extract and both metabolites isolated showed an antihyperglycemic effect on streptozotocin-induced diabetic mice, suggesting a possible synergic effect. In addition, the compound 5,6-dihydroxy-7,3',4'-trimethoxyflavone (IC50 = 0.79 mg/kg) showed a better antipropulsive effect than loperamide (IC50 = 16.6 mg/kg).
Conclusions:
The phytochemical composition of an acetone extract of Salvia urica was determined by first time. The metabolites isolated from this plant support the phylogenetic relationship of S. urica with Salvia amarissima, and they showed antipropulsive and antihyperglycemic effects.
Salvia amarissima Ortega was evaluated to determinate its antihyperglycemic and lipid profile properties. Petroleum ether extract of fresh aerial parts of S. amarissima (PEfAPSa) and a secondary fraction (F6Sa) were evaluated to determine their antihyperglycemic activity in streptozo-cin-induced diabetic (STID) mice, in oral tolerance tests of sucrose, starch, and glucose (OSTT, OStTT, and OGTT, respectively), in terms of glycated hemoglobin (HbA1c), triglycerides (TG), and high-density lipoprotein (HDL). In acute assays at doses of 50 mg/kg body weight (b.w.), PEfAPSa and F6Sa showed a reduction in hyperglycemia in STID mice, at the first and fifth hour after of treatment, respectively, and were comparable with acarbose. In the sub-chronic test, PEfAPSa and F6Sa showed a reduction of glycemia since the first week, and the effect was greater than that of the acarbose control group. In relation to HbA1c, the treatments prevented the increase in HbA1c. In the case of TG and HDL, PEfAPSa and F6Sa showed a reduction in TG and an HDL increase from the second week. OSTT and OStTT showed that PEfAPSa and F6Sa significantly lowered the postprandial peak at 1 h after loading but only in sucrose or starch such as acarbose. The results suggest that S. amarissima activity may be mediated by the inhibition of disaccharide hydrolysis, which may be associated with an α-glucosidase inhibitory effect.
An infusion prepared from the aerial parts of Salvia amarissima Ortega inhibited the enzyme protein tyrosine phosphatase 1B (PTP-1B) (IC50~88 and 33 μg/mL, respectively). Phytochemical analysis of the infusion yielded amarisolide (1), 5,6,4′-trihydroxy-7,3′-dimethoxyflavone (2), 6-hydroxyluteolin (3), rutin (4), rosmarinic acid (5), isoquercitrin (6), pedalitin (7) and a new neo-clerodane type diterpenoid glucoside, named amarisolide G (8a,b). Compound 8a,b is a new natural product, and 2–6 are reported for the first time for the species. All compounds were tested for their inhibitory activity against PTP-1B; their IC50 values ranged from 62.0 to 514.2 μM. The activity was compared to that of ursolic acid (IC50 = 29.14 μM). The most active compound was pedalitin (7). Docking analysis predicted that compound 7 has higher affinity for the allosteric site of the enzyme. Gas chromatography coupled to mass spectrometry analyses of the essential oils prepared from dried and fresh materials revealed that germacrene D (15) and β-selinene (16), followed by β-caryophyllene (13) and spathulenol (17) were their major components. An ultra-high performance liquid chromatography coupled to mass spectrometry method was developed and validated to quantify amarisolide (1) in the ethyl acetate soluble fraction of the infusion of S. amarissima.
p align="left"> Background : Salvia circinata is an endemic species of Mexico used in the folk medicine of Santiago Huauclilla, Oaxaca, mainly as remedy for gastrointestinal diseases.
Hypothesis : If the extracts of Salvia circinata have secondary metabolites with antinociceptive activity, then the behavior of nociception in the model of “whriting” in mice will decrease.
Specie studied : Salvia circinata Cav. (Lamiaceae).
Study site and years of study : Salvia circinata was collected in Santiago Huauclilla, Oaxaca, in July 2014.
Methods : Firstly, the acute toxicity of S. circinata extracts was evaluated to calculate the LD50 with OECD method. Then, dose-response curves of the antinociceptive effect of S. circinata organic and aqueous extracts (1, 10, 30, 100, and 300 mg/kg) were obtained in the writhing test in mice. Furthermore, chromatographic techniques were applied to isolate the compounds and were identified by comparison of the values of 1H NMR, 13C NMR and ESIMS reported in the literature.
Results : Our data showed significant antinociceptive activity in all the tested extracts. Amarisolide A and pedalitin were isolated in the ethyl acetate and methanol extracts, respectively and assayed at doses of 1, 5 and 10 mg/kg, i.p. All the compounds decreased nociception in mice in at least 50 % from a minimal dosage of 1 mg/kg, i.p. and in a similar manner than the reference drug ketorolac (1 mg/kg, i.p.).
Conclusions : Our findings give evidence that Salvia circinata possesses antinociceptive activity depending on the presence of several known bioactive constituents, reinforcing its use in the Mexican traditional medicine to alleviate abdominal pain.</p
Antecedentes:
Lamiaceae es una de las familias con mayor riqueza de especies en México. Sin embargo, aún se carece de un estudio detallado sobre su diversidad en el país y de una revisión taxonómica global y actualizada. Como resultado, el aprovechamiento y conservación de los integrantes de esta familia es limitado.
Preguntas:
¿Qué avances se han logrado en el estudio y entendimiento de la riqueza, endemismo y distribución de las Lamiaceae mexicanas? ¿Qué estrategias deben ejecutarse para consolidar el conocimiento de la familia en el país?
Taxon:
Lamiaceae
Sitio de estudio:
México
Métodos:
Se hizo una revisión exhaustiva de las Lamiaceae mexicanas en la literatura, bases de datos y herbarios. Se sintetizó el estado de su conocimiento. Se aplicaron análisis cuantitativos para evaluar su riqueza, endemismo y distribución geográfica.
Resultados:
México cuenta con 33 géneros y 598 especies, de las cuales el 66.2 % son endémicas. El género más diverso es Salvia, con 306 especies. El estado más diverso es Oaxaca, mientras que Jalisco alberga el mayor número de especies endémicas.
Conclusiones:
En México, Lamiaceae es la octava familia más diversa y el número de sus especies representa el 5.5 % de la familia a nivel mundial, por lo que el país puede considerarse uno de los centros de diversificación más importante. Debido a lo anterior, y al endemismo elevado que presenta, México es crucial para la conservación in situ de la familia. Si bien se ha logrado un avance considerable de su conocimiento y en la actualidad hay un repunte en su estudio, es necesario diversificar los campos de investigación.
Eleven neo-clerodane diterpenoids (1–11) including the new analogues 1, 2, and 10, and 3′,5,6,7-tetrahydroxy-4′-methoxyflavone (12) were isolated from the aerial parts of Salvia polystachya. Polystachyne G (1) and 15-epi-polystachyne G (2) were isolated as an epimeric mixture, containing a 5-hydroxyfuran-2(5H)-one unit in the side chain at C-12 of the neo-clerodane framework. Polystachyne H (10) contains a 1(10),2-diene moiety and a tertiary C-4 hydroxy group. The structures of these compounds were established by analysis of their NMR spectroscopic and MS spectrometric data. The absolute configurations of compounds 3, 4, and 10 were determined through single-crystal X-ray diffraction analysis. The antibacterial, antifungal, and phytotoxic activities of the diterpenoids were determined. In addition, the stimulatory effect of the expression of extracellular matrix components of nine of the isolates (1–8 and 11) was assayed. Compounds 1–4, 8, and 11 increased the expression of the genes codifying for type I, type III, and type V collagens and for elastin.
A dried infusion prepared from the aerial parts of Salvia circinata did not provoke acute toxicity in mice (LD50 > 5 g/kg). This infusion showed poor hypoglycemic and antihyperglycemic effects (100–570 mg/kg) when tested in normal and hyperglycemic mice using acute and oral glucose tolerance tests, respectively. However, this infusion possessed antihyperglycemic action in vivo during an oral sucrose tolerance test (31.6–316 mg/kg), suggesting the presence of α-glucosidase inhibitors in S. circinata. Fractionation of a nonpolar extract of the aerial parts of the plant yielded a new biflavone (1) and four new neoclerodane diterpenoid glucosides (2–5) along with the known compounds amarisolide (6), pedalitin (7), apigenin-7-O-β-d-glucoside (8), and the flavone 2-(3,4-dimethoxyphenyl)-5,6-dihydroxy-7-methoxy-4H-chromen-4-one (9). Compounds 1 and 6–9 were active against mammalian α-glucosidases; 6 and 7 were also active against a recombinant α-glucosidase from Ruminococcus obeum and reduced significantly the postprandial peak during an oral sucrose tolerance test in healthy mice, consistent with their α-glucosidase inhibitory activity. Molecular docking and dynamic studies revealed that compounds 6 and 7 might bind to α-glucosidases at the catalytic center of the enzyme.
Teotihuacanin (1), an unusual rearranged clerodane diterpene with a new carbon skeleton containing a spiro-10/6 bicyclic system, was isolated from the leaves and flowers of Salvia amarissima. Its structure was determined through spectroscopic analyses. Its absolute configuration was established by single-crystal X-ray diffraction. Compound 1 showed potent modulatory activity of multidrug resistance in vinblastine-resistant MCF-7 cancer cell line (reversal fold, RFMCF-7/Vin+ > 10703) at 25 μg/mL.
La familia Lamiaceae es muy diversa en México y se distribuye con preferencia en las zonas templadas, aunque es posible encontrar géneros como Hyptis y Asterohyptis, que habitan en zonas secas y calientes; es una de las familias más diversas en el país, de la cual no se tenían datos actualizados sobre su diversidad y endemismo. En este trabajo se presenta una clave para identificar los géneros de la familia, las descripciones de los mismos, con comentarios acerca de su riqueza y endemismo, un mapa de distribución de la familia y un listado de especies presentes en el país; todo lo anterior a partir de una revisión de la bibliografía, de varios herbarios mexicanos (CHAPA, CHIP, ENCB, FCME, IEB, MEXU, OAX, SERO y UAMIZ) y de las colecciones y listados disponibles en Internet (F, K, MO y US). En México se encuentran 32 géneros nativos o naturalizados por largo tiempo y 591 especies que representan el 8.11% de la familia, con un endemismo de 65.82%.
Two new 5,10-seco-neo-clerodanes, salvimicrophyllins A and B (1 and 2), and two new neo-clerodanes, salvimicrophyllins C and D (3 and 4), were isolated from the leaves and flowers of Salvia microphylla. The structures of these compounds were elucidated mainly by analysis of their NMR spectroscopic and mass spectrometric data. The relative configurations of the salvimicrophyllins were determined by analysis of NOESY spectra and ECD curves, and the relative configuration of compound 2 was confirmed by single-crystal X-ray diffraction crystallography.
Ethnopharmacological relevance:
The species of Salvia subgenus Calosphace are used medicinally and ritually in numerous traditions of folk healing among indigenous cultures of North and South America with more than 500 species. These species contain numerous bioactive terpenes and terpenoids, some active at human opioid and GABA receptors, which may contribute to their effectiveness as folk medicines. Medicinal plant complexes contain species which share common names, morphological and/or aromatic properties, and medicinal uses; these complexes are found in traditional systems of medicine. Our research looks for complexes within Calosphace and the secondary metabolites they contain.
Materials and methods:
Several studies have combined molecular phylogenetics and ethnopharmacology to successfully target active medicinal species. In this paper, we have selected a monophyletic clade, Salvia subgenus Calosphace, and performed a literature search to identify medicinal plant complexes within it. We created a database from over 200 references, found using keywords, and herbarium sheets. To identify medicinal plant complexes within the database, all species with shared vernacular names were first grouped. If the species sharing common names had similar medicinal uses and morphological similarity, they were concluded to be a complex. In order to determine the accuracy and validity of this approach, the chia complex was used as control, and we more species than reported by all of the published references combined. After identifying complexes and species within each, we searched the phytochemical literature to identify all reported secondary metabolites for each.
Results:
We identify four previously unidentified complexes. Mirto (5 species) is used extensively in the treatment of the folk illness susto and other illnesses in Mexico, and is characterized by red flowers. Ñucchu (7 species) used as a symbolic element in religious processions and in the treatment of respiratory ailments in Peru and characterized by red flowers. Cantueso (2 species), with blue flowers, is used for respiratory ailments in Mexico, and Manga-paqui (3 species) is used for kidney and liver diseases in Ecuador. For the species of each complex we report all traditional preparations, other vernacular names, and known secondary metabolites. Among these complexes, Mirto and Ñucchu appear to have exceptional levels of cultural significance.
Conclusions:
Our results support our hypothesis that species within Salvia subgenus Calosphace will assort into complexes of medicinal plants that share common names, appearances, and medicinal uses. We have identified four new complexes within this monophyletic lineage, mirto, ñucchu, cantueso, and manga-paqui.
Reversal of multidrug resistance (MDR) by thirty resin glycosides from the morning glory family (Convolvulaceae) was evaluated in vinblastine-resistant human breast carcinoma cells (MCF-7/Vin). The effects of these amphipathic compounds on the cytotoxicity and P-glycoprotein (P-gp)-mediated MDR were estimated with the sulforhodamine B colorimetric assay. Active noncytotoxic compounds exerted a potentiation effect of vinblastine susceptibility by 1- to over 1906-fold at tested concentrations of 5 and 25 μg/mL. Murucoidin V (1) enhanced vinblastine activity 255-fold when incorporated at 25 μg/mL and also, based on flow cytometry, significantly increased the intracellular accumulation of rhodamine 123 with the use of reserpine as a positive control for a MDR reversal agent. Incubation of MCF-7/Vin cells with 1 caused an increase in uptake and notably lowered the efflux rate of rhodamine 123. Decreased expression of P-glycoprotein by compound 1 was detected by immunofluorescence flow cytometry after incubation with an anti-P-gp monoclonal antibody. These results suggest that resin glycosides represent potential efflux pump inhibitors for overcoming MDR in cancer therapy.
Salvia circinnata Cav. (Syn. S. amarissima Ortega), Lamiaceae, is a Mexican medicinal plant used in traditional medicine for the treatment of gastrointestinal illness, cancer, and diabetes. Samples of ten natural populations were analyzed by application of a systematic approach which involved the combination of DNA barcoding, GC–MS, HPLC–DAD, and HPLC-FLD for differentiation of their chemical profiles. Taxonomic and phylogenetic analyses indicated that all of them belong to the same analyzed plant species. The GC–MS analysis showed the presence of alkanes, amides, anthraquinones, and sesquiterpenoids in the volatile fraction of the extracts. HPLC–PDA and HPLC-FLD analyses indicated that at least four chemotypes exist for the analyzed species, diverging in the production of clerodane diterpenes: (i) an amarissinin A–rich population; (ii) another single population producer of amarisolide A; (iii) producing populations of teotihuacanin and amarissinin A, (iv) while another population only produced alkanes and sesquiterpenes as distinctive constituents not previously reported for this plant. The multivariate statistical analysis suggests that this chemical diversity depends on environmental factors.Graphical abstract
Ethnopharmacological relevance
Mexico is considered an ancestral center of diversity of Salvia species, however many of them lack scientific information. Salvia circinnata Cav. (syn. Salvia amarissima Ortega) is an endemic species used in traditional medicine to treat disorders attributed to a cold state like anxiety in the central nervous system, as well as gastrointestinal ailments and pain relief.
Aim of the study
To give preclinical evidence about the pharmacological properties of this species by investigating its antinociceptive and anti-inflammatory effects, the chemical nature of at least one metabolite, and a possible mechanism of action and adverse effects, using different experimental models of pain.
Material and methods
Different crude extracts of Salvia circinnata Cav. aerial parts were prepared using increasing polarity and evaluated in the formalin test in mice. This screening allowed to select and evaluate an ethyl acetate extract (EtOAc), as the most bioactive extract, and a metabolite. Antinociceptive and anti-inflammatory activities were confirmed using the plantar test and carrageenan-induced edema. The antinociceptive effects of the extracts were compared to that observed with morphine (1 mg/kg), tramadol (20 mg/kg) or indomethacin (20 mg/kg) as reference drugs. Participation of opioids and TRPV1 receptors was investigated, as well as acute toxicity and adverse effects of sedation and gastric damage.
Results
EtOAc (0.1–10 mg/kg) of S. circinnata Cav. showed a dose-dependent and significant antinociceptive activity, associated in part with the presence of a neo-clerodane glycoside amarisolide A (0.01–1 mg/kg), in the neurogenic and inflammatory phases of the formalin test. Central action of both treatments was corroborated in the plantar test, whereas anti-inflammatory effects were confirmed with the extract (1 and 10 mg/kg) and amarisolide A (1 mg/kg) in the carrageenan-induced edema test. An opioid mechanism in both treatments, and the TRPV1 receptor modulation in the extract were involved. No acute toxicity and adverse effects were noticed with the extract and pure compound in comparison to the reference drugs.
Conclusion
These results provide preclinical evidence of the ethnopharmacological antinociceptive S. circinnata Cav. properties, in which the neo-clerodane diterpene glycoside amarisolide A was partially responsible involving the participation of the opioid receptors, while TRPV1 receptor modulation was implicated in the anti-inflammatory activity may be because of the presence of other constituents. This information supports the use of this species in folk medicine for pain therapy.
Salvia circinata Cav., Lamiaceae, is commonly used in Mexican traditional medicine to treat gastrointestinal ailments, including diarrhea. An acetone-soluble extract from the aerial parts of S. circinata was suspended in a 9:1 methanol–water mixture and fractionated by partition with hexane and EtOAc. The hexane, EtOAc, and aqueous fractions were evaluated for their antiprotozoal activities, where the EtOAc-soluble fraction displayed the best antiprotozoal activity. Resolution of this fraction by chromatographic methods afforded the known diterpenoids amarissinins A–C (1–3), teotihuacanin (4), and amarisolide F (5), along with two flavones, apigenin (6) and 5,6-dihydroxy-7,3′,4′-trimethoxy flavone (7). Compound 7 was the most active one, with IC50 values of 0.05 μM and 0.13 μM against Entamoeba histolytica and Giardia lamblia, respectively. Interestingly, it was even more active than metronidazole and emetine, used as positive controls. Compounds 1–6 showed moderate antiprotozoal activity with IC50 values ranging from 23.9 to 67.8 μM against Entamoeba histolytica, and 39.4 to 127 μM against Giardia lamblia. These results provide evidence-based support for the traditional use of S. circinata, and suggest that the 5,6-dihydroxy-7,3′,4′-trimethoxy flavone (7) may have an important role in the antidiarrheal activity of the plant.
Graphical abstract
Phytochemical investigation of the leaves and flowers from Salvia hirsuta led to the isolation of the five microphyllane-type diterpenoids (1–5), and two flavones (6–7). Hirsutolides constituted new diterpenoids containing a 5-hydroxyfuran-2(5H)-one and were isolated as an epimeric mixture at C-3 and C-15. The structures of the isolated compounds were established through the analysis of their NMR spectroscopic and MS spectrometric data; and confirmed by single-crystal X-ray diffraction studies. Cytotoxic and MDR modulatory activities of compounds 1–5 were determined.
Nine terpenoids were isolated from the leaves and flowers of Salvia amarissima, including a new acylated diterpenoid glucoside, amarisolide F (1), a new neo-clerodane diterpenoid, amarissinin D (2), which was isolated as an acetyl derivative (2a), and four known diterpenoids. The structure of amarisolide F (1) was elucidated by NMR and MS data analyses, as well as its methanolysis products 7 and 8, which also constituted new diterpenoids, named amarissinin E and 8-epi-amarissinin E, respectively. The absolute configuration of compound 7 was established by single-crystal X-ray diffraction. The cytotoxicity and anti-MDR effect of 1 in three phenotypes of the MCF-7 cell lines were assayed. Compound 1 was 2-3.6-fold more active than amarissinins A (3) and B (4), but several orders of magnitude less active than teotihuacanin (6) and reserpine. © 2018 American Chemical Society and American Society of Pharmacognosy.
A series of neo-clerodane-type diterpenoids were isolated from the aerial parts of Salvia filipes, including the new compounds 4-epi-polystachyne A (1), salvifilines A (3), C (7), and D (8), and salvifiline B, which was isolated as the 15-O-methyl derivatives 4/5. In addition, the five known diterpenoids (2, 9-12), together with ursolic, oleanolic, and betulinic acids, and the flavone eupatorin were also isolated. The structures were determined by analysis of their spectroscopic data, mainly 1D and 2D NMR. The structure of salvifiline D was confirmed by X-ray analysis. The cytotoxic activities of the diterpenoids were evaluated, but all were inactive against a panel of six human cancer cell lines.
A new neo-clerodane glycoside, amarisolide, has been isolated from the aerial parts of Salvia amarissima. Its structure was established as 2β-O-β-D-glucopyranosyl neo-cleroda-3,13(16),14-trien-15,16-epoxy-18,19-olide by chemical and spectroscopic means.
The flavonoid fraction from the leaves of Lantana montevidensis Briq. (Verbenaceae) showed antiproliferative activity against human gastric adenocarcinoma (MK-1, GI50: 12 microg/ml), human uterus carcinoma (HeLa, 5 microg/ml), and murine melanoma (B16F10, 5 microg/ml) cells in vitro. Bioactivity-guided chemical investigation of the fraction has resulted in the isolation of apigenin (10) and ten 5,6,7-oxygenated flavones: cirsilineol (1), eupatorin (2), 5,4'-dihydroxy-6,7,3',5'-tetramethoxyflavone (3), 5,6-dihydroxy-7,3',4'-trimethoxyflavone (4), 5,6,4'-trihydroxy-7,3',5'-trimethoxyflavone (5), 5,6,3'-trihydroxy-7,4'-dimethoxyflavone (6), 5,3',4'-trihydroxy-6,7,5'-trimethoxyflavone (7), cirsiliol (8), hispidulin (9), and eupafolin (11). Antiproliferative activity of the isolated flavones, some other related flavones (luteolin, baicalein, 6-hydroxyluteolin, pectolinarigenin, jaceosidin, desmethoxycentaureidin, eupatilin, and chrysin) from other plant materials, and synthetic 6- and 7-methoxyflavones was evaluated, and the structure-activity relationships were examined.
The families and genera of vascular plants: Labiatae
- R M Harley
- S Atkins
- A L Budantsev
- P D Cantino
- B J Conn
- R Grayer
- M M Harley
- R De Kok
- T Krestovskaja
- R Morales
- A J Paton
- O Ryding
- T Upson
Harley RM, Atkins S, Budantsev AL, Cantino PD, Conn BJ, Grayer
R, Harley MM, de Kok R, Krestovskaja T, Morales R, Paton AJ,
Ryding O, Upson T (2005) The families and genera of vascular
plants: Labiatae. Springer 54:574. https:// doi. org/ 10. 2307/ 25065 407