Abietane diterpenoids from Caryopteris incana (Thunb.) Miq. And their HIF-2α inhibitory activities in vitro.

Eleven previously undescribed abietane-type diterpenoids, named caryopincanoids A-K (1-11), together with five known compounds, were isolated from the EtOH extract of the aerial parts of Caryopteris incana (Thunb.) Miq. Their structures were elucidated on the basis of comprehensive spectroscopic data, NMR calculations, and ECD calculations. The inhibitory activities of all compounds against HIF-2α gene expression in 786-O cells were tested by luciferase assay. Compounds 7, 9, 15, and 16 showed significant inhibitory effects with IC50 values ranging from 12.73 to 23.80 µM. The preliminary structure-activity relationship of these compounds was also discussed.

Salvia miltiorrhiza Bunge extract and Przewalskin ameliorate Bleomycin-induced pulmonary fibrosis by inhibition of apoptosis, oxidative stress and collagen deposition via the TGF-ß1 pathway.

BACKGROUND: Salvia miltiorrhiza Bunge (Labiatae) (DS) is a key part of the traditional Chinese medicine, whose roots are used to remove blood stasis, relieve pain, eliminate carbuncle and calm the nerves. Our research team found that the DS extract could significantly reverse LPS-induced lung injury, and five new diterpenoid quinones in DS extract with excellent lung protective activity for the first time. However, the material basis and mechanism of DS on pulmonary fibrosis (PF) needs to be explored in depth. OBJECTIVE: Bleomycin (BLM) was employed to establish the PF model, and Transcriptome and Surface plasmon resonance (SPR) ligand fishing technology were used to explore the material basis and mechanism of DS on PF, and provided theoretical research for clinical treatment of PF. METHODS: DS extract (24.58 or 49.16 mg/kg, i.g.) was administered daily from Day 8 to Day 28, followed by intratracheal BLM drip (5 mg/kg) to induce PF. Data about the influences of DS on PF were collected by transcriptome sequencing technology. Pulmonary ultrasound, airway responsiveness, lung damage, collagen deposition, and the levels of TNF-α, IL-1ß, apoptosis, oxidative stress (OS), immune cells, TGF-ß1, α-SMA, E-Cadherin and Collage Ⅰ were examined. The affinity component (Przewalskin) in DS extract targeted by TGF-ß1 was fished by SPR ligand fishing technology. Furthermore, an in vivo PF mouse model and an in vitro TGF-ß1 induced BEAS-2B cell model were established, to explore the mechanism of Przewalskin on PF from the apoptosis, OS and epithelial mesenchymal transformation pathway. RESULTS: DS extract improved pulmonary ultrasound, reduced lung damage and collagen deposition, downregulated TNF-α, IL-1ß, apoptosis, OS, TGF-ß1, α-SMA, E-Cadherin and Collage Ⅰ, transformed immune cells following Bleomycin challenge. Furthermore, affinity component (Przewalskin) also improved pulmonary ultrasound and airway responsiveness, reduced lung damage and collagen deposition, downregulated TNF-α, IL-1ß, apoptosis, OS in vivo and in vitro. CONCLUSION: Analysis using a mouse model revealed that DS extract and Przewalskin can relieve clinical symptoms of PF, reduce lung injury and improve lung function. Meanwhile, DS extract and Przewalskin can improve BLM-induced PF by inhibition of, OS, apoptosis and collagen deposition might via the TGF-ß1 pathway. This study provides references to identification of novel therapeutic targets, thereby facilitating drug development for PF.

Anti-inflammatory labdane diterpenoids from the aerial parts of Leonurus sibiricus.

Eleven undescribed labdane diterpenoids, sibiricusins K-U, and seven known analogues were obtained from the MeOH extract of the aerial parts of Leonurus sibiricus. The structures of the compounds were established by detailed spectroscopic data analysis, single-crystal X-ray diffraction analysis and ECD calculations. Among them, sibiricusins L-N featured a rare α, ß-unsaturated-γ-lactam moiety. Fourteen of the isolates were evaluated for their anti-inflammatory effect on the production of NO in LPS-induced RAW264.7 cells through Griess assay. Sibiricusin O displayed the strongest activity with an IC50 value of 9.0 ± 1.7 µM.

Salviamilthone A-O, diterpenoid quinones from Salvia miltiorrhiza.

Fifteen undescribed diterpenoid quinones salviamilthone A-O (1-15), together with three known diterpenoid quinones (16-18), were isolated from the roots of Salvia miltiorrhiza Bunge. Their structures were elucidated using 1D and 2D NMR data, while the relative and absolute configurations were confirmed by NOESY correlations and comparison between experimental and calculated ECD spectra. In the evaluation of bioactivities, salviamilthone J (10), salviamone (18) (10 µM) significantly increased cell viability and decreased the expression of IL-1ß in lipopolysaccharide-induced BEAS-2B cells. These data provide the molecular justification for the usage of Salvia miltiorrhiza in treating acute lung injury.

Structure-diversified terpenoids from Salvia prattii and their protective activity against alcoholic liver diseases.

Eleven previously unreported compounds (1-11), including five diterpenoids (1-5) and six sesquiterpenoids (6-11), together with two known diterpenoids (12-13), have been isolated from the roots of Salvia prattii. Their structures were comprehensively elucidated through spectroscopic methods, and their configurations were established using computational 13C nuclear magnetic resonance and electronic circular dichroism. Compound 1 was found to be an abietane-type diterpenoid with a novel rearrangement generated from the cleavage of the C-4/5 chemical bond, 20-methyl shift, and the rearrangement of the C-10 side chain. Compounds 2-3 were the third and fourth examples of arrangement seco-norabietanes with a spiro-lactone ring. We evaluated all compounds for their protective effects against alcoholic liver diseases (ALD). Compound 2 exhibited potential protective activity and hence can be used as a novel anti-ALD candidate.

Labdane and ent-halimane diterpenoids with STAT3-inhibitory activity from Leonurus sibiricus.

Nine undescribed labdane diterpenoids (1-9) and one undescribed ent-halimane diterpenoid (10) were isolated from the aerial parts of Leonurus sibiricus, together with four known analogues (11-14) during our searching for naturally occurring antitumor agents. Their structures were established by detailed spectroscopic analyses and electronic circular dichroism analysis. Compound 4 possessed a rare 10-epi labdane scaffold. All compounds except 5 were evaluated for their inhibitory activities against interleukin (IL)-6-stimulated signal transducer and activator of transcription (STAT3) expression using a luciferase reporter assay. Compound 1 showed the most inhibitory effect with the IC50 value 20.31 µM. Compound 1 inhibited the activation of JAK2/STAT3 signal pathway through binding to Gln326 of STAT3 in CNE cells. The antiproliferative evaluation of compound 1 against CNE, CAL-27, A549 and PANC-1 cells demonstrated that CNE cells were the most sensitive to 1. Furthermore, compound 1 showed moderate efficacy in inhibiting cell migration, invasion, and epithelial-mesenchymal transition in CNE cells. In addition, compound 1 also promoted ferroptosis in CNE cells in a dose-dependent manner. These results suggest that compound 1 might be a potential candidate lead for treating nasopharyngeal carcinoma.

The tanshinones from the plant of Salvia miltiorrhiza.

Six undescribed tanshinones, (+)-2-Cl-tanshindiol C (1), (-)-2-Cl-tanshindiol C (2), (+)-tanshinoic acid D (3), (-)-tanshinoic acid D (4), (-)-tanshinoic acid E (5), and (+)-tanshinoic acid E (6), were isolated from the rhizome of Salvia miltiorrhiza Bunge. Their structures were elucidated based on the spectroscopic data (UV, IR, HR-ESI-MS, and NMR). The bioactive assays of all these compounds for the antioxidant activities in cardiomyocytes upon hypoxia stimulation were evaluated. The results suggested that compounds 5 and 6 exhibited good antioxidant activities in cardiomyocytes and the cell survival rates were 46.3% and 57.9% (10-5 mol/L), respectively.

Anti-inflammatory labdane diterpenoids from the aerial parts of Leonurus japonicus.

Twenty-two labdane-type diterpenoids, including ten pairs of 15-epimers and a pair of 13,15-epimers, were obtained from the aerial parts of a well-known medicinal plant Leonurus japonicus Houtt. While these epimers were separated by chiral HPLC, their structures were established mainly via spectroscopic methods especially NMR, X-ray crystallography and ECD techniques. Among them, seventeen compounds, encompassing three pairs of solvolysis artefacts likely due to the use of ethanol as extracting solvent, were reported for the first time in the current work. Our preliminary anti-inflammatory screening demonstrated that seven diterpenoids displayed noteworthy inhibitory effect on the NO production in LPS-induced RAW264.7 cells. In addition, the release of pro-inflammatory factors TNF-α, IL-1ß and IL-6, as well as the expression of iNOS and COX-2 proteins, was also suppressed by the unreported 15,16-epoxy-6ß-hydroxy-15α-methoxy-7,16-dioxolabd-8,13-diene. Further investigation into the preliminary anti-inflammatory mechanism of this compound indicated that it could block the activation of NF-κB signaling pathway.

Pentacyclic triterpenoids from spikes of Prunella vulgaris L. with thyroid tumour cell cytostatic bioactivities.

Five new triterpenoids, including four ursane types (1-4) and one oleanane type (5), together with 15 known ursane types pentacyclic triterpenoids (6-20) were isolated from the fruit spikes of Prunella vulgaris L., a traditional Chinese herbal medicine. Their structures were elucidated based on IR, HR-ESI-MS, and NMR spectroscopic data. The SW579 cell line was used to evaluate anti-thyroid cancer activities of (1-20). The results indicated that (7-9), (16), and (19) exhibited apparent inhibitory activity with IC50 values of 25.73-71.41 µM (cisplatin as positive control, IC50 14.49 ± 0.97 µM). Network pharmacology and molecular docking were also used for the prediction of the synergistic actions and the underlying mechanisms. Accordingly, four potential targets have been characterized.

New natural furfural derivatives from the leaves and stems of Pogostemon cablin.

A new furfural derivative, pogoscafuran A (1), a new natural product, HMF levulinate (2), together with four known compounds (3-6) were isolated from an extract of the leaves and stems of Pogostemon cablin (Blanco) Benth. Their structures were elucidated on the basis of extensive spectroscopic analyses and single-crystal X-ray crystallography. Compound 1 was the first example of natural furfural derivative with a unique C5-C1' linkage between a molecule of furfural and 3-methyl-2-cyclopentenone moiety. The plausible biogenetic pathway for the new compound 1 was proposed. All these isolated compounds were tested for their inhibitory effects on the nitric oxide (NO) production induced by lipopolysaccharide in RAW264.7 cells, and only compound 1 exhibited weak inhibitory activity.

Comparison monoterpene and sesquiterpene, herbage yield of Satureja hortensis, Thymus vulgaris, and Salvia officinalis from the Fars province of Iran.

Recently, numerous side effects of synthetic drugs have led to using medicinal plants as a reliable source of new therapy. Pain is a global public health problem with a high impact on life quality and a huge economic implication, becoming one of the most important enemies in modern medicine. The medicinal use of plants as analgesic or antinociceptive drugs in traditional therapy is estimated to be about 80% of the world population. The lamiaceae family, one of the most important herbal families, incorporates a wide variety of plants with biological and medical applications. In this study, the main active compounds of Thymus vulgaris (thymol (51.59%), p-cymene (15.41%), carvacrol (4.52%) and γ-terpinene (12.63%), Salvia officinalis; cis-thujone (38.05%), camphor (16.08%), 1,8-cineole (11.97%), trans-thujone (5.88%), camphene (4.79%), α -pinene (4.69%) and carvacrol (50.68%), γ-terpinene (34.44%) and α-terpinene (3.72%) in Satureja hortensis was determined. The highest EO contents (w/w %) was obtained in the plants of summer savory (2.05%), followed by the garden thyme (1.83%) and common sage (0.55%). It is necessary to identify the most effective compounds in order to extract or synthesise in pure form for future use in the pharmaceutical industry. Also, might be used for isolation of potentially active compounds from some of these medicinal plants in future and formulation of commercial therapeutic agents.

Nomenclatural notes on Menthinae (Mentheae - Lamiaceae) native to Brazil.

Menthinae, one of the five subtribes of Mentheae (Lamiaceae), with ca. 735 species, is represented in Brazil by a wide range of herbs and shrubs. During an investigation of the taxonomic history of the group for the Flora e Funga do Brasil project, several nomenclatural issues with typifications in the group have been identified. This study attempts to resolve them, making suggestions of new types and re-evaluation of synonyms. Thirteen lectotypifications and one neotypification are being proposed, along with the recognition of Thymus selloi Spreng. ex J.A.Schmidt as a nomen nudum. Most of the suggested changes are due to the loss of many of Sellow's types at B during WWII, lack of specific herbaria references and collector numbers in the protologues, or to existence of designated syntypes in the referred collections. Our study is a contribution to the nomenclatural and taxonomic knowledge of Menthinae, providing a stable foundation for future study of its taxonomy, biogeography, and evolution.

Novel Plant Extract Ameliorates Metabolic Disorder through Activation of Brown Adipose Tissue in High-Fat Diet-Induced Obese Mice.

Obesity is characterized by excessive body fat accumulation due to unbalanced energy intake and expenditure. Potential therapeutic targets for anti-obesity include the inhibition of white adipose tissue (WAT) hypertrophy and hyperplasia and the activation of brown adipose tissue (BAT). Not only the activation of BAT but also the browning of WAT have gained increasing attention in research fields as an alternative method in the prevention and treatment of obesity. Here, we investigated possible mechanisms underlying the anti-obesity effect of Phlomis umbrosa Turcz. root ethanol extract (PUE) in an obesogenic animal model. PUE treatment can reduce diet-induced obesity and modulate obesity-associated metabolic disorders, including insulin resistance, hepatic steatosis, and inflammation. In the liver, PUE improved hepatic steatosis by suppressing hepatic lipogenesis and lipid absorption while increasing biliary sterol excretion and hepatic fatty acid oxidation compared to the high-fat group. Moreover, PUE increased energy expenditure and regulated fecal lipid excretion, leading to reduced body weight gain. In particular, PUE remarkably activated the browning of subWAT via upregulation of the browning-related protein and gene expression and promoted BAT activation. In conclusion, these findings provide the potential therapeutic usefulness into the effects of PUE in the treatment of obesity and metabolic disorders. Furthermore, it suggests that PUE treatment can regulate energy metabolism via activating BAT and browning subWAT.

Ten undescribed diterpenoid quinones derived from the Salvia miltiorrhiza.

This study aimed to report the structure elucidation of the compounds isolated from Salvia miltiorrhiza, and their biological evaluations. Ten undescribed diterpenoid quinones and 10 known analogues were isolated from the dried roots of S. miltiorrhiza. Their structures were elucidated by extensive analysis, including nuclear magnetic resonance, high-resolution mass spectra, and ultraviolet and infrared spectra. Their absolute configurations were determined by comparing the experimental and calculated electronic circular dichroism spectra. In the evaluation of bioactivities, Salvianolactone acid I, epi-danshenspiroketallactone F, danshinspiroketallactone, grandifolia G, and 2H-Naphtho [1,8-bc]furan (10 µM) significantly increased cell viability and decreased the nuclear transport of p-P65 in lipopolysaccharide-induced bronchial epithelial cells. It was concluded that the diterpenoid quinones might belong to potent targeted lung-protective agents.

Radioprotective Effects of Plants from the Lamiaceae Family.

BACKGROUND: Edible and medicinal plants are still an interesting source of promising biologically active substances for drug discovery and development. At a time of increasing cancer incidence in the world, alleviating the bothersome side effects of radiotherapy in debilitated cancer patients is becoming an important challenge. OBJECTIVE: The aim of the study was to overview the literature data concerning the radioprotective activity of extracts, essential oils, and some chemical compounds obtained from 12 species belonging to the Lamiaceae family, gathering of numerous spice and medicinal plants rich in valuable phytochemicals. RESULTS: The analysis of available publications showed radioprotective effectiveness of essential oils and complex extracts containing phenolic acids and flavonoids in various in vitro and in vivo models. Relatively welldocumented preventive properties exhibited the following species: Mentha × piperita, Ocimum tenuiflorum, Origanum vulgare, and Rosmarinus officinalis. However, few plants such as Lavandula angustifolia, Mentha arvensis, M. spicata, Plectranthus amboinicus, Salvia miltiorrhiza, S. officinalis, Scutellaria baicalensis, and Zataria multiflora should be more investigated in the future. Among the mechanisms of radioprotective effects of well-studied extracts and phytochemicals, it can be mentioned mainly the protection against chromosomal damage, scavenging free radicals, decreasing of lipid peroxidation and elevating of glutathione, superoxide dismutase, catalase, and alkaline phosphatase enzyme levels as well as the reduction of the cell death. The plant substances protected the gastrointestinal tract, bone marrow and lung fibroblasts. CONCLUSION: The studied species of Lamiaceae family and their active chemical compounds are potent in alleviating the side effects of radiotherapy and should be considered as a complementary therapy.

A new prenylated 3-benzoxepin derivative with anti-influenza A virus activity from Elsholtzia penduliflora.

A new prenylated 3-benzoxepin derivative, elsholtzioxin (1), together with fifteen known compounds (2-16) were isolated from the whole parts of Elsholtzia penduliflora. Their structures were elucidated on the basis of various spectroscopic techniques and chemical evidences. The antiviral activities of these compounds were evaluated in vitro. The new compound (1) exhibited potential anti-influenza virus activity against strain A/WSN/33/2009 (H1N1) with inhibition rate of 47.19%. Compounds 2, 9 and 12 exhibited significant inhibitory activities with IC50 value of 26.16, 34.66 and 20.81 µM, respectively.

The effect of time and temperature on shelf life of essential oil composition of Teucrium polium L.

Teucrium polium has been used to treat gastrointestinal disorders, inflammation, diabetes and rheumatism. This plant has beneficial therapeutic properties. In this research the changes in the composition of essential oils from the aerial parts of Teucrium polium were determined at different temperatures and times. The essential oil of air-dried samples was obtained by hydro distillation and analyzed by gas chromatography/mass spectrometry (GC/MS). Changes in essential oils compositions were detected during storage for 3 months in refrigerator, freezer, and at room temperature. The results indicated that at room temperature, the proportions of the compounds with lower boiling temperatures such as Cis-Verbenol (2.11-1.78%) and Germacrene D (1.56-0.94%) were decreased significantly. Furthermore, the essential oil composition showed the least alterations and Teucrium polium L. kept its primary quality when stored at low temperatures, particularly in refrigerator and freezer (Except: α-Pinene, ß-Pinene and Limonene).

Antiproliferative potential of moluccella laevis L. aerial parts family lamiaceae (labiatae), supported by phytochemical investigation and molecular docking study.

The current biologically guided study aimed the in vitro investigation of cytotoxic activity, identification of the phytochemical content of Moluccella laevis L. aerial parts and supporting this activity by a molecular docking study. Aqueous fraction demonstrated the most potent cytotoxic effect against CACO-2 with IC50 = 0.067 ± 0.01 µg/mL. Furthermore, EtOAc fraction showed a remarkable cytotoxic activity against MCF-7 cell line with IC50 = 0.35 ± 0.02 µg/mL. Consequently, total ethanolic extract (TEE) and its fractions were subjected to LC-HR-ESI-MS metabolic profiling to discover the constituents that possibly underlie their cytotoxicity. Twenty compounds were tentatively identified from metabolic analysis. Furthermore, eight compounds were isolated. In silico docking study revealed that stachydrine is more likely to account for the antiproliferative activity of both EtOAc and aqueous fractions, probably via its moderate inhibition of receptor tyrosine kinases. [Formula: see text].

Species conservation profile and revision of Salviakorolkowii (Lamiaceae, Lamiales), a narrow endemic of the Western Tian-Shan.

Background: Salviakorolkowii (Lamiaceae) has been considered a species of highest conservation priority due to its narrow distribution and isolated taxonomic position. The species has been known from Uzbekistan and, questionably, Kyrgyzstan and treated as endemic to the Western Tian-Shan. Its modern conservation status according to the IUCN Criteria has not been established. New information: The taxonomic position of Salviakorolkowii is evaluated; the species is treated as the sole member of S.sect.Odontochilus (Pobed.) Sennikov, comb. nov. because of its morphological differences and phylogenetic isolation. The herbarium collections are completely revised and the species is proven to occur mainly in Uzbekistan with a single locality (new country record) in Kazakhstan; its former report from Kyrgyzstan (one locality) is confirmed and documented by herbarium specimens. The species occurrences are mapped and its conservation status is assessed as Vulnerable due to the restricted size and continuous decline of its populations because of the ongoing degradation and destruction of its primary habitat (variegated outcrops) at lower elevations. This study highlights the importance of a thorough revision of herbarium collections in Central Asia for conservation purposes.

Complete chloroplast genome of Lamiophlomis rotata: comparative genome analysis and phylogenetic analysis.

Lamiophlomis rotata, the only species within the genus Lamiophlomis (family Labiatae), exhibits a broad geographical distribution in elevated highland areas in Qinghai-Tibetan Plateau and possesses significant therapeutic properties. Numerous chemical compositions and putative phylogenetic affiliations of this species have been documented in prior research. Nevertheless, there is a scarcity of accessible publications regarding the genomic data of L. rotata, particularly its chloroplast genome. This dearth of knowledge hampers the comprehensive investigation of its phylogenetic placement within the Labiatae family. In this study, we present a comprehensive analysis of the plastid genome of L. rotata. The plastid genome has a length of 151,837 base pairs (bp) and a GC content of 38.5%. Within this genome, a total of 135 genes were identified, including 90 protein-coding genes, 37 transfer RNA (tRNA) genes, and eight ribosomal RNA (rRNA) genes. By employing phylogenetic analysis, the taxonomic position of L. rotata within the family Labiatae is elucidated, highlighting a close relationship between the genus Lamiophlomis and the genus Phlomis. Notably, extensive genetic variations were uncovered between L. rotata and other Phlomis species. This study could provide significant insights for understanding the phylogenetic relationships of taxa within Labiatae.