New pimarane diterpenoids with antibacterial activity from fungus Arthrinium sp. ZS03.

A comprehensive chemical study of the endophytic fungus Arthrinium sp. ZS03, associated with Acorus tatarinowii Schott, yielded eleven pimarane diterpenoids (compounds 1-11), including seven novel compounds designated arthrinoids A-G (1-7). The determination of their structures and absolute configurations was achieved through extensive spectroscopic techniques, quantum chemical calculations of electronic circular dichroism (ECD), and single-crystal X-ray diffraction analysis. Furthermore, 7 demonstrated inhibitory activity against Klebsiella pneumoniae, comparable to the reference antibiotic amikacin, with a minimum inhibitory concentration (MIC) of 8 µg·mL-1.

Abietane diterpenoids with anti-neuroinflammation activity from Rosmarinus officinalis.

A total of 12 abietane diterpenoids were isolated and identified from Rosmarinus officinalis in which 6 ones were undescribed compounds. Their structures were illuminated by the HRESIMS, NMR, and ECD methods and named as rosmarinusin Q-V (1-6). It worthy mentioned that rosmarinusin Q was a novel abietane diterpenoid with 6/6/5 skeleton whose C ring was an α,ß-unsaturated five-element ketone. All the compounds and four compounds (13-16) reported in our previous paper were evaluated their anti-neuroinflammatory activities on the LPS-induced BV2 cells. Compounds 5, 8, 9, 11, and 15 displayed significant anti-neuroinflammatory activity at the concentration of 10, 20, and 40 µM respectively. These results confirmed that R. officinalis contained abundant abietane diterpenoids and these compounds showed potential values of anti-neuroinflammation which could be developed as neuroprotective agents for the treatment of nerve damage caused by inflammation.

Extraction Optimization and Qualitative/Quantitative Determination of Bioactive Abietane-Type Diterpenes from Three Salvia Species (Common Sage, Greek Sage and Rosemary) by 1H-qNMR.

The objective of this study was the optimization of the extraction process and the qualitative and quantitative determination of the bioactive metabolites: 12-O-methylcarnosic acid (12MCA), carnosic acid (CA), carnosol (CS), 7-O-methyl-epi-rosmanol (7MER) and rosmanol (RO) in infusions, decoctions, turbulent flow extracts, tinctures and oleolites from three Salvia species: Salvia officinalis L. (common sage, SO), Salvia fruticosa Mill. (Greek sage, SF) and Salvia rosmarinus Spenn (syn Rosmarinus officinalis L.) (rosemary, SR), using Quantitative Proton Nuclear Magnetic Resonance Spectroscopy (1H-qNMR). Regarding the aqueous extracts, decoctions appeared to be richer sources of the studied metabolites than infusions among the three plants. For SR, the turbulent flow extraction under heating was the most efficient one. The optimum time for the preparation of decoctions was found to be 5 min for SF and SO and 15 min for SR. It is noteworthy that SR tinctures were not stable in time due to decomposition of the abietane-type diterpenes CA and CS because of the polar solvent used for their preparation. Contrary to this finding, the oleolites of SR appeared to be very stable. Olive oil as a solvent for extraction was very protective for the contained abietane-type diterpenes. A preliminary stability study on the effect of the storage time of the SF on the abietane-type diterpenes content showed that the total quantity of abietanes decreased by 16.51% and 40.79% after 12 and 36 months, respectively. The results of this investigation also demonstrated that 1H-qNMR is very useful for the analysis of sensitive metabolites, like abietane-type diterpenes, that can be influenced by solvents used in chromatographic analysis.

Diverse diterpenoids and a triterpenoid from Euphorbia spinidens Bornm. ex Prokh.

Four previously unreported diterpenoids including three ent-atisanes (1-3) and one ent-abietane (4), along with one known linear triterpenoid (5) and five known diterpenoids including four myrsinanes (6-9), and one abietane (10) have been isolated from the roots of Euphorbia spinidens Bornm. ex Prokh. The structures were determined on the basis of extensive spectroscopic analyses including HR-ESI-MS, 1D and 2D NMR and comparison of the data with those reported in the literature. Antimicrobial potential of isolated compounds were also evaluated. Guionianol B (10) showed good antibacterial activity against Staphylococcus aureus and Bacillus subtilis with MIC value of 6.25 µg/mL.

Abietane diterpenoids and iridoids from Caryopteris mongolica.

Six new abietane diterpenoids (1-6) and five undescribed iridoids (7-11) have been isolated from the aerial parts of Caryopteris mongolica. The intricate structural characterization of these compounds was meticulously undertaken using an array of advanced spectroscopic techniques. This process was further enhanced by the application of DP4+ probability analyses and electronic circular dichroism (ECD) calculations. Following isolation and structural elucidation, the cytotoxicity of these compounds was evaluated. Among them, compound 3 stood out, displaying significant cytotoxic activity against HeLa cells with an IC50 value of 7.83 ± 1.28 µmol·L-1. Additionally, compounds 1, 2, 4, 9, and 10 manifested moderate cytotoxic effects on specific cell lines, with IC50 values ranging from 11.7 to 20.9 µmol·L-1.

The key phytochemistry of rosemary (Salvia rosmarinus) contributing to hair protection against UV.

Extracts from rosemary (Salvia Rosmarinus) are analysed for their phytochemistry using LC-MS and the phytochemistry identified. The same extracts were tested for their efficacy to act as antioxidants by both hydrogen-atom transfer (ORAC) and single electron transfer (FRAP). A correlation analysis was performed to identify the key phytochemistry responsible for antioxidant efficacy. The top performing extracts were then tested in a peptide model and in hair with the presence of UV to measure ability to protect against UV-induced peptide and protein damage. Polyphenols (e.g. rosmarinic acid, glycosides of selgin) and abietane diterpenes (e.g. carnosic acid) in rosemary were identified as the principal compounds which enables the extracts to protect hair from UV. OBJECTIVE: The objective of this work was to correlate the phytochemistry of rosemary (Salvia rosmarinus), a botanical with known antioxidant properties, to a UV protection benefit in hair. These data will give insights into mechanisms of UV damage, the ROS formed and their reactivity. METHODS: LC-MS was used to compare the compounds in 10 commercial extracts of rosemary. ORAC (oxygen radical antioxidant capacity) and FRAP (ferric reducing antioxidant power) were used to measure the antioxidant capacity of the rosemary extracts. The ORAC assay measures ability of an antioxidant to react with a peroxyl radical via hydrogen atom extraction and FRAP measures electron transfer through reduction of ferric iron (Fe3+ ) to ferrous iron (Fe2+ ) by antioxidants present in the samples. Correlation of extract composition with antioxidant measures was performed using principal component analysis. Selected extracts were assessed for their ability to protect hair from UV damage in a model peptide system and on hair. In addition, the same methods were used to test rosmarinic acid and carnosic acid, key phytochemistries in the rosemary extracts. The model system was a peptide and its decomposition on exposure to UV was monitored by LC-MS in the absence and presence of the rosemary extracts. Hair degradation in the presence of UV was measured by exposure of UV in an Atlas weatherometer followed by extraction of degraded protein in water. A fragment of the S100A3 protein was used as a marker of UV damage (m/z = 1278) and quantified via LC-MS. RESULTS: Ten rosemary extracts were assessed for antioxidant performance and correlated with their compositions. The phytochemistry in each extract varied widely with a total of 33 individual compounds identified. The differences were most likely driven by the solvent and extraction method used by the supplier with extracts varying in the proportion of polar or non-polar compounds. This did influence their reactivity in the ORAC and FRAP assays and their efficacy in preventing protein damage. Two of the key compounds identified were rosmarinic acid and carnosic acid, with rosmarinic acid dominating in extracts with mainly polar compounds and carnosic acid dominating in extracts with mainly nonpolar compounds. Extracts with higher rosmarinic acid correlated with ORAC and FRAP scores, with UV protection on hair and in the peptide model system. The extracts chosen for hair experiments showed hair protection. UV protection was also measured for rosmarinic and carnosic acid. CONCLUSIONS: Despite the variation in the profile of phytochemistries in the 10 rosemary extracts, likely driven by the chosen extraction method, all rosemary extracts had antioxidant activity measured. This study suggests that the polyphenols (e.g. rosmarinic acid, glycosides of selgin) and abietane diterpenes (e.g. carnosic acid) are the principal compounds which enables the extracts to protect hair from UV.

INTRODUCTION: Les extraits de romarin (Salvia Rosmarinus) sont analysés par LC-MS pour établir et identifier leur profil phytochimique. Les mêmes extraits ont été testés pour leur efficacité à agir comme antioxydants à la fois par transfert d'atome d'hydrogène (ORAC) et par transfert d'électrons uniques (FRAP). Une analyse de corrélation a été réalisée pour identifier les propriétés phytochimiques clés responsables de l'efficacité antioxydante. Les extraits les plus performants ont ensuite été testés dans un modèle peptidique et sur les cheveux en présences d'UV pour mesurer la capacité à protéger contre les dommages induits par les UV su les peptides et protéines. Les polyphénols (par ex. acide rosmarinique, glycosides de selgin) et les diterpènes d'abiétine (par ex. acide carnosique) dans le romarin ont été identifiés comme les principaux composés permettant aux extraits de protéger les cheveux des UV. OBJECTIF: L'objectif de ce travail était de mettre en corrélation la phytochimie du romarin (Salvia rosmarinus), une plante aux propriétés antioxydantes connues, et les bénéfices d'une protection contre les UV dans les cheveux. Ces données fourniront des informations sur les mécanismes des dommages causés par les UV, la formation du ROS et leur réactivité. MÉTHODES: La LC-MS a été utilisée pour comparer les composés de 10 extraits commerciaux de romarin. L'ORAC (Oxygen Radical Antioxidant Capacity/Capacité d'absorption des radicaux d'oxygène) et la FRAP (Ferric Reduction Antioxidant Power/Pouvoir antioxydant de réduction ferrique) ont été utilisés pour mesurer la capacité antioxydante des extraits de romarin. Le dosage ORAC mesure la capacité d'un antioxydant à réagir avec un radical peroxyl par extraction d'atome d'hydrogène et la FRAP mesure le transfert d'électrons par réduction du fer ferrique (Fe3+ ) en fer ferreux (Fe2+ ) par les antioxydants présents dans les échantillons. La corrélation entre la composition de l'extrait et les mesures des antioxydants a été effectuée en analysant les composants principaux. Les extraits sélectionnés ont été évalués pour leur capacité à protéger les cheveux des dommages causés par les UV dans un modèle de système peptidique et sur les cheveux. En outre, les mêmes méthodes ont été utilisées pour tester l'acide rosmarinique et l'acide carnosique, principales caractéristiques phytochimiques dans les extraits de romarin. Le système modèle était un peptide et sa décomposition à l'exposition aux UV a été suivie par LC-MS en l'absence et en présence des extraits de romarin. La dégradation des cheveux en présence d'UV a été mesurée par l'exposition aux UV dans un indicateur de désagrégation Atlas suivi de l'extraction de protéines dégradées dans l'eau. Un fragment de la protéine S100A3 a été utilisé comme marqueur de dommage UV (m/z = 1278) et quantifié par LC-MS. RÉSULTATS: Dix extraits de romarin ont été évalués en termes de performance antioxydante et mis en corrélation avec leurs compositions. La phytochimie de chaque extrait variait considérablement, avec un total de 33 composés individuels identifiés. Les différences étaient très probablement dues à la méthode du solvant et de l'extraction utilisée par le fournisseur avec des extraits variant dans la proportion de composés polaires ou non polaires. Cela a effectivement influencé leur réactivité dans les dosages ORAC et FRAP et leur efficacité dans la prévention des dommages protéiques. Deux des composés clés identifiés étaient l'acide rosmarinique et l'acide carnosique, l'acide rosmarinique dominant dans les extraits contenant principalement des composés polaires et l'acide carnosique dominant dans les extraits contenant principalement des composés non polaires. Les extraits avec un taux d'acide rosmarinique plus élevé étaient mis en corrélation avec les scores ORAC et FRAP, avec une protection UV sur les cheveux et dans le système de modèle peptidique. Les extraits choisis pour les expériences sur les cheveux ont montré une protection des cheveux. La protection contre les UV a également été mesurée pour l'acide rosmarinique et l'acide carnosique. CONCLUSIONS: Malgré la variation des profils phytochimiques dans les dix extraits de romarin, probablement induite par la méthode d'extraction choisie, l'activité antioxydante de tous les extraits de romarin a été mesurée. Les polyphénols (par ex. acide rosmarinique, glycosides de selgin) et les diterpènes d'abiétane (par ex. acide carnosique) dans le romarin ont été identifiés comme les principaux composés permettant aux extraits de protéger les cheveux contre les UV.

Functional Study and Efficient Catalytic Element Mining of CYP76AHs in Salvia Plants.

Salvia is a large genus with hundreds of species used in traditional Chinese medicine. Tanshinones are a highly representative class of exclusive compounds found in the Salvia genus that exhibit significant biological activity. Tanshinone components have been identified in 16 Salvia species. The CYP76AH subfamily (P450) is crucial for the synthesis of tanshinone due to its catalytic generation of polyhydroxy structures. In this study, a total of 420 CYP76AH genes were obtained, and phylogenetic analysis showed their clear clustering relationships. Fifteen CYP76AH genes from 10 Salvia species were cloned and studied from the perspectives of evolution and catalytic efficiency. Three CYP76AHs with significantly improved catalytic efficiency compared to SmCYP76AH3 were identified, providing efficient catalytic elements for the synthetic biological production of tanshinones. A structure-function relationship study revealed several conserved residues that might be related to the function of CYP76AHs and provided a new mutation direction for the study of the directed evolution of plant P450.

16,17-dinor-abietane diterpenoids from Casearia kurzii.

Eleven undescribed 16,17-dinor-abietane diterpenoids, caseazins A-K (1-11), and ten known diterpenoids (12-21) were isolated from the twigs and leaves of Casearia kurzii (Flacourtiaceae). Caseazins A-K were the first abietane -type dinorditerpenoids to have been isolated from the plant of Casearia kurzii. Their chemical structures were elucidated using a combination of 1D and 2D NMR spectroscopy and mass spectrometry. The absolute configurations of 5 and 10 were established by electronic circular dichroism calculations. Moreover, compounds 2, 3, 13, 14, and 18 exhibited anti-inflammatory activity with IC50 values of 0.17, 0.36, 6.55, 1.30, and 4.53 µM, respectively. IL-1ß and caspase-1 analyses suggested that compound 14 inhibited NLRP3 inflammasome activation and blocked macrophage pyroptosis.

A Pharmacological Review of Tanshinones, Naturally Occurring Monomers from Salvia miltiorrhiza for the Treatment of Cardiovascular Diseases.

Cardiovascular diseases (CVDs) are a set of heart and blood vessel disorders that include coronary heart disease (CHD), rheumatic heart disease, and other conditions. Traditional Chinese Medicine (TCM) has definite effects on CVDs due to its multitarget and multicomponent properties, which are gradually gaining national attention. Tanshinones, the major active chemical compounds extracted from Salvia miltiorrhiza, exhibit beneficial improvement on multiple diseases, especially CVDs. At the level of biological activities, they play significant roles, including anti-inflammation, anti-oxidation, anti-apoptosis and anti-necroptosis, anti-hypertrophy, vasodilation, angiogenesis, combat against proliferation and migration of smooth muscle cells (SMCs), as well as anti-myocardial fibrosis and ventricular remodeling, which are all effective strategies in preventing and treating CVDs. Additionally, at the cellular level, Tanshinones produce marked effects on cardiomyocytes, macrophages, endothelia, SMCs, and fibroblasts in myocardia. In this review, we have summarized a brief overview of the chemical structures and pharmacological effects of Tanshinones as a CVD treatment to expound on different pharmacological properties in various cell types in myocardia.

Chemical Stability and Bioactivity of tanshinone I, tanshinone IIA, cryptotanshinone and dihydrotanshinone in in vitro test systems.

Danshen Si Wu is a Traditional Chinese Medicine used for menopausal complains. Beside tanshinone IIA (Tan IIA), Danshen also contains tanshinone I (Tan I), cryptotanshinone (CT) and dihydrotanshinone (DT). The aim of this study was to compare the biological activity of these tanshinones and to determine their cytotoxicity and genotoxicity. Purities and stabilities of the substances were analyzed by LC-DAD and LC-MS analyses. DT and CT concentrations decreased rapidly in dimethylsulfoxide and were converted to Tan I and Tan IIA, respectively. In aqueous solution concentration of all tanshinones decreased after 24 h. Tan I and Tan IIA showed dose-dependent bioactivity mediated by ERα and ERß. No cytotoxic and genotoxic effects for Tan I and Tan IIA were detected. In a yeast transactivation assay Tan I and Tan IIA showed antiandrogenic activity. A significant anabolic activity in C2C12 cells could be detected for Tan I and Tan IIA. In conclusion our data provide evidence that Tan I and Tan IIA are the most relevant bioactive tanshinones in Danshen. Our finding that all tanshinones display a certain instability in aqueous solutions is relevant when discussing their potential therapeutic benefits in humans.

COX-2 and iNOS inhibitory abietane diterpenoids from Pinus yunnanensis exudates.

Pinuskesiols A-F (1-6), six new structurally diverse abietane diterpenoids were isolated from Pinus yunnanensis resins. Their structures including absolute configurations were characterized by using spectroscopic and computational methods. All the compounds bear a carbonyl functionality at C-4 with 1 and 2 behaving as a lactone thereof. The isopropyl group is attached to C-13 via O-atom in 3. In addition, the presence of a Δ5(6) double bond and a ketone at C-7 makes 2 a large conjugated system. Biological evaluation revealed that 1, 2, and 4 could concentration-dependently inhibit iNOS and COX-2 expression in lipopolysaccharide-induced RAW 264.7 cells with 2 to be the most active toward COX-2 inhibition.

Cytotoxic ent-abietane diterpenoids from the leaves of Croton lachnocarpus Benth.

A phytochemical investigation on the 90% ethanol extract of the leaves of Croton lachnocarpus Benth. led to three new ent-abietane diterpenoids, 7ß,15-dihydroxy-ent-abieta-8,11,13-trien-3-one (1), 2ß,15-dihydroxy-ent-abieta-8,11,13-triene (2), and 7ß,13α,15-trihydroxy-ent-abieta-8(14)-en-3-one (3). Structural elucidation of all the compounds were performed by spectral methods such as 1 D and 2 D (1H-1H COSY, HMQC, NOESY and HMBC) NMR spectroscopy, in addition to electronic circular dichroism (ECD) spectra. The isolated compounds were tested in vitro for cytotoxic activity against 6 tumor cell lines. As a result, compound 3 exhibited some cytotoxicities against all the tested tumor cell lines with IC50 value less than 30 µM.

Bioactive icetexane and abietane diterpenes from Isodon phyllopodus.

A new icetexane diterpenoid, 11, 12, 20α-trihydroxyl-7ß-methoxyicetexa-8, 11, 13-triene-19, 10-lactone [Phyllane A (1)], and a new abietane diterpenoid, 7ß, 20-epoxy-3ß, 17-acetoxy-abieta-8, 11, 13-teriene-11, 12-diol [phyllane B (2)], along with two known compounds (3 and 4) were isolated from the methanol (MeOH) extract of twigs and leaves of the folk medicinal Isodon phyllopodus. Their structures were determined by spectroscopic analyses including 2 D NMR spectral data, and further confirmed by X-ray single crystal diffraction. Moreover, the compounds were evaluated for their cytotoxicity and anti-HIV activities, and phyllane A showed anti-HIV activity with an IC50 value of 15.7 µM, but phyllane B was found to be cytotoxic to the A549 host cells with a CC50 value of 108.5 µM.

Biologically Active Diterpenoids in the Clerodendrum Genus-A Review.

One of the key areas of interest in pharmacognosy is that of the diterpenoids; many studies have been performed to identify new sources, their optimal isolation and biological properties. An important source of abietane-, pimarane-, clerodane-type diterpenoids and their derivatives are the members of the genus Clerodendrum, of the Lamiaceae. Due to their diverse chemical nature, and the type of plant material, a range of extraction techniques are needed with various temperatures, solvent types and extraction times, as well as the use of an ultrasound bath. The diterpenoids isolated from Clerodendrum demonstrate a range of cytotoxic, anti-proliferative, antibacterial, anti-parasitic and anti-inflammatory activities. This review describes the various biological activities of the diterpenoids isolated so far from species of Clerodendrum with the indication of the most active ones, as well as those from other plant sources, taking into account their structure in terms of their activity, and summarises the methods for their extraction.

Isolation and Bioinspired Total Synthesis of Rugosiformisin A, A Skeleton-Rearranged Abietane-Type Diterpenoid from Isodon rugosiformis.

Rugosiformisin A, a skeleton-rearranged abietane-type diterpenoid with a spiro[4.5]decane motif, was isolated from Isodon rugosiformis. Its structure was unambiguously established via NMR spectroscopic analysis and single-crystal X-ray diffraction. A bioinspired asymmetric synthesis of rugosiformisin A was achieved in 15 steps with 2.7% overall yield. The synthesis features an iridium-catalyzed asymmetric polyene cyclization and a semipinacol rearrangement.

Modified ent-Abietane Diterpenoids from the Leaves of Suregada zanzibariensis.

The leaf extract of Suregada zanzibariensis gave two new modified ent-abietane diterpenoids, zanzibariolides A (1) and B (2), and two known triterpenoids, simiarenol (3) and ß-amyrin (4). The structures of the isolated compounds were elucidated based on NMR and MS data analysis. Single-crystal X-ray diffraction was used to establish the absolute configurations of compounds 1 and 2. The crude leaf extract inhibited the infectivity of herpes simplex virus 2 (HSV-2, IC50 11.5 µg/mL) and showed toxicity on African green monkey kidney (GMK AH1) cells at CC50 52 µg/mL. The isolated compounds 1-3 showed no anti-HSV-2 activity and exhibited insignificant toxicity against GMK AH1 cells at ≥100 µM.

Phytochemical Study and Antiglioblastoma Activity Assessment of Plectranthus hadiensis (Forssk.) Schweinf. ex Sprenger var. hadiensis Stems.

Glioblastoma (GB) is the most malignant form of primary astrocytoma, accounting for more than 60% of all brain tumors in adults. Nowadays, due to the development of multidrug resistance causing relapses to the current treatments and the development of severe side effects resulting in reduced survival rates, new therapeutic approaches are needed. The genus Plectranthus belongs to the Lamiaceae family and is known to be rich in abietane-type diterpenes, which possess antitumor activity. Specifically, P. hadiensis (Forssk.) Schweinf. ex Sprenger has been documented for the use against brain tumors. Therefore, the aim of this work was to perform the bioguided isolation of compounds from the acetonic extract of P. hadiensis stems and to investigate the in vitro antiglioblastoma activity of the extract and its isolated constituents. After extraction, six fractions were obtained from the acetonic extract of P. hadiensis stems. In a preliminary biological screening, the fractions V and III showed the highest antioxidant and antimicrobial activities. None of the fractions were toxic in the Artemia salina assay. We obtained different abietane-type diterpenes such as 7α-acetoxy-6ß-hydroxyroyleanone (Roy) and 6ß,7ß-dihydroxyroyleanone (DiRoy), which was also in agreement with the HPLC-DAD profile of the extract. Furthermore, the antiproliferative activity was assessed in a glioma tumor cell line panel by the Alamar blue assay. After 48 h treatment, Roy exerted strong antiproliferative/cytotoxic effects against tumor cells with low IC50 values among the different cell lines. Finally, we synthesized a new fluorescence derivative in this study to evaluate the biodistribution of Roy. The uptake of BODIPY-7α-acetoxy-6ß-hydroxyroyleanone by GB cells was associated with increased intracellular fluorescence, supporting the antiproliferative effects of Roy. In conclusion, Roy is a promising natural compound that may serve as a lead compound for further derivatization to develop future therapeutic strategies against GB.

Cytotoxic diterpenoid dimer containing an intricately caged core from Euphorbia fischeriana.

Bislangduoids A and B, a novel class of dimeric diterpenoids based on ent-abietanes tethered by C-17-C-15' bridge, were identified as trace components from a traditional Chinese medicine Euphorbia fischeriana (Langdu). Bislangduoid A features a highly oxidized scaffold incorporating a cage-like pentacyclic core. Their structures were elucidated by extensive spectroscopic techniques, electronic circular dichroism, and NMR calculations. The biosynthetic pathway for the dimeric skeleton and the unique caged moiety via Michael and acetal-formation reactions was proposed. Bislangduoid A showed pronounced cytotoxicity against HepG2 cells through the mitochondria-dependent apoptosis pathway.

Tanshinones: Leading the way into Lamiaceae labdane-related diterpenoid biosynthesis.

Tanshinones are the bioactive diterpenoid constituents of the traditional Chinese medicinal herb Danshen (Salvia miltiorrhiza), and are examples of the phenolic abietanes widely found within the Lamiaceae plant family. Due to the significant interest in these labdane-related diterpenoid natural products, their biosynthesis has been intensively investigated. In addition to providing the basis for metabolic engineering efforts, this work further yielded pioneering insights into labdane-related diterpenoid biosynthesis in the Lamiaceae more broadly. This includes stereochemical foreshadowing of aromatization, with novel protein domain loss in the relevant diterpene synthase, as well as broader phylogenetic conservation of the relevant enzymes. Beyond such summary of more widespread metabolism, formation of the furan ring that characterizes the tanshinones also has been recently elucidated. Nevertheless, the biocatalysts for the pair of demethylations remain unknown, and the intriguing potential connection of these reactions to the further aromatization observed in the tanshinones are speculated upon here.

Marginols A‒H, unprecedented pimarane diterpenoids from Kaempferia marginata and their NO inhibitory activities.

Kaempferia marginata rhizomes are used as an herb in food and as traditional medicine for the treatment of inflammatory-related diseases in Asian countries. In contrast to the previously reported phytochemical investigation of Thai and Chinese K. marginata rhizomes, which demonstrated the presence of sandaracopimaradiene and ent-sandaracopimaradiene, our first investigation of Vietnamese K. marginata rhizomes led to the isolation of eight undescribed pimarane diterpenoids, marginols A‒H, along with 18 known pimarane diterpenoids. The structures of these compounds were elucidated by spectroscopic techniques, including 1D and 2D NMR, HRESIMS, and CD spectroscopy and/or by comparisons of their NMR data with previously reported data. Furthermore, evaluations of the NO production inhibitory activity against LPS-stimulated RAW264.7 cells revealed that the undescribed compounds, marginols B and D‒G, and the known compounds, sandaracopimaradien-6ß,9α-diol-1-one and 6-acetoxysandaracopimardien-9-ol-1-one, showed potent activities. These results provide insights into the chemodiversity of Vietnamese K. marginata rhizomes as well as their traditional usage from the viewpoint of their chemical constituents.