Search Results (703)

Rugulopteryx okamurae is an invasive brown alga that has colonised Mediterranean and northeastern Atlantic coastlines, posing significant ecological and economic challenges. Its biomass is rich in structurally diverse metabolites—including polysaccharides (alginate, fucoidan, laminaran), phlorotannins, diterpenoids, fatty acids, and peptides—many of which exhibit notable antioxidant, anti-inflammatory, antimicrobial, and anticancer activities. Comparative assessment of extraction yields, structural features, and bioactivity data highlights phlorotannins and diterpenoids as particularly promising, demonstrating low-micromolar potencies and favourable predicted interactions with key inflammatory and apoptotic targets. Algal polysaccharides exhibit various bioactivities but hold strong potential for scalable and sustainable industrial applications. Emerging compound classes such as fatty acids and peptides display niche bioactivities; however, their structural diversity and mechanisms of action remain insufficiently explored. Insights from in vitro and in silico studies suggest that phlorotannins may modulate NF-κB and MAPK signalling pathways, while diterpenoids are implicated in the induction of mitochondrial apoptosis. Despite these findings, inconsistent extraction methodologies and a lack of in vivo pharmacokinetic and efficacy data limit translational potential. To overcome these limitations, standardized extraction protocols, detailed structure–activity relationship (SAR) and pharmacokinetic studies, and robust in vivo models are urgently needed. Bioactivity-guided valorisation strategies, aligned with ecological management, could transform R. okamurae biomass into a sustainable source for functional foods, cosmetics, and pharmaceuticals applications. Full article

Daphne odora is an evergreen shrub belonging to the Thymelaeaceae family that is widely cultivated as an ornamental garden plant. Its roots, leaves, and flowers have traditionally been used in Chinese medicine to treat pain, skin diseases, and rheumatism. While previous phytochemical studies have reported the presence of phenols, coumarins, biflavonoids, lignans, and daphnane diterpenoids in D. odora, its flowers remain largely unexplored. In the present study, the first comprehensive investigation of daphnane diterpenoids contained in the flower buds and blooming flowers of D. odora was conducted using ultra-high-performance liquid chromatography coupled with Q-Exactive-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Exactive-Orbitrap MS). A total of 30 daphnane diterpenoids were identified, including 12 previously unreported compounds, through detailed analysis of their retention times and MS/MS fragmentation patterns. Comparative profiling revealed that flower buds contained a higher abundance and greater diversity of daphnane diterpenoids than flowers. Furthermore, LC–MS-guided isolation enabled the purification of a novel compound, daphneodorin I (16), and its structure was elucidated through extensive physicochemical and spectroscopic analyses. Compound 16 represents the first daphnane diterpenoid with a Z-configured phenolic acyl moiety isolated from plants of the Thymelaeaceae family. Full article

A chemical investigation of the EtOAc fraction from soft coral Clavularia viridis resulted in the isolation of 12 undescribed dolabellane-type diterpenoids, namely clavirolides W–Z (1–4), clavularols A–H (5–12), and three known analogs (13–15). Their structures were characterized by an extensive analysis of spectroscopic data, including X-ray diffraction and ECD calculations for the assignment of absolute configurations. The structures of 2 and 4–6 are feathered as peroxyl-substituted derivatives, while compounds 7–12 possess additional oxidative cyclization, including epoxide or furan that are rare in the dolabellane family. All these compounds were evaluated for activities on cytotoxic and anti-inflammatory models. Compound 10 exhibited most potential against NO production in the BV2 cell induced by LPS with an IC₅₀ value of 18.3 μM. Full article

Marine-derived fungi have proven to be a rich source of structurally diverse terpenoids with significant pharmacological potential. This systematic review of 119 studies (2020–2024) identifies 512 novel terpenoids, accounting for 87% of the total discoveries to 2020, from five major classes (monoterpenes, sesquiterpenes, diterpenes, sesterterpenes, and triterpenes) isolated from 104 fungal strains across 33 genera. Sesquiterpenoids and diterpenoids constitute the predominant chemical classes, with Trichoderma, Aspergillus, Eutypella, and Penicillium being the most productive genera. These fungi were primarily sourced from distinct marine niches, including deep sea sediments, algal associations, mangrove ecosystems, and invertebrate symbioses. Notably, 57% of the 266 tested compounds exhibited diverse biological activities, encompassing anti-inflammatory, antibacterial, antimicroalgal, antifungal, cytotoxic effects, etc. The chemical diversity and biological activities of these marine fungal terpenoids underscore their value as promising lead compounds for pharmaceutical development. Full article

Natural products, characterized by their structural novelty, multi-target capabilities, and favorable toxicity profiles, represent a prominent reservoir for the discovery of innovative anticancer therapeutics. In the current investigation, we identified ajuforrestin A, a diterpenoid compound extracted from Ajuga lupulina Maxim, as a potent agent against lung cancer. In vitro, this compound markedly curtailed the proliferation of A549 cells. Mechanistic explorations revealed that ajuforrestin A could arrest A549 cells in the G0/G1 phase of the cell cycle, provoke apoptosis in cancer cells, and impede their migration by modulating the STAT3 and FAK signaling cascades. Angiogenesis is indispensable for tumor formation, progression, and metastatic dissemination. Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 are established as crucial mediators in tumor neovascularization, a process fundamental to both the expansion of tumor cells and the development of new blood vessels within the tumor milieu. Through the combined application of a Tg(fli1:EGFP) zebrafish model and SPR experimentation, we furnished strong evidence for the ability of ajuforrestin A to obstruct tumor angiogenesis via selective engagement with VEGFR-2. Finally, a zebrafish xenograft tumor model demonstrated that ajuforrestin A could effectively restrain tumor growth and metastasis in vivo. Ajuforrestin A therefore shows considerable promise as a lead compound for the future development of therapies against non-small cell lung cancer (NSCLC). Full article

A previously undescribed cis-clerodane diterpenoid, diangelate solidagoic acid J (1), along with two known cis-clerodane diterpenoids, solidagoic acid C (2) and solidagoic acid D (3), as well as two known unsaturated monoacylglycerols, 1-linoleoyl glycerol (4) and 1-α-linolenoyl glycerol (5), were isolated and characterized from the n-hexane leaf extract of Solidago gigantea (giant goldenrod). Compounds 2–5 were identified first in this species, and compounds 4 and 5 are reported here for the first time in the Solidago genus. The bioassay-guided isolation procedure included thin-layer chromatography (TLC) coupled with a Bacillus subtilis antibacterial assay, preparative flash column chromatography, and TLC–mass spectrometry (MS). Their structures were elucidated via extensive spectroscopic and spectrometric techniques such as one- and two-dimensional nuclear magnetic resonance (NMR) spectroscopy and high-resolution tandem mass spectrometry (HRMS/MS). The antimicrobial activities of the isolated compounds were evaluated by a microdilution assay. All compounds exhibited weak to moderate antibacterial activity against the Gram-positive plant pathogen Clavibacter michiganensis, with MIC values ranging from 17 to 133 µg/mL, with compound 5 being the most potent. Only compound 1 was active against Curtobacterium flaccumfaciens pv. flaccumfaciens, while compound 3 demonstrated a weak antibacterial effect against B. subtilis and Rhodococcus fascians. Additionally, the growth of B. subtilis and R. fascians was moderately inhibited by compounds 1 and 5, respectively. None of the tested compounds showed antibacterial activity against Gram-negative Pseudomonas syringae pv. tomato and Xanthomonas arboricola pv. pruni. No bactericidal activity was observed against the tested microorganisms. Compounds 2 and 3 displayed weak antifungal activity against the crop pathogens Bipolaris sorokiniana and Fusarium graminearum. Our results demonstrate the efficacy of bioassay-guided strategies in facilitating the discovery of novel bioactive compounds. Full article

Tanshinones are a class of lipophilic diterpenoid quinones extracted from Salvia miltiorrhiza (Dan shen), a widely used herb in traditional Chinese medicine. These compounds, particularly tanshinone IIA (T-IIA) and sodium tanshinone sulfonate (STS), have been acknowledged for their broad spectrum of biological activities, including anti-inflammatory, antioxidant, anti-tumor, antiresorptive, and antimicrobial effects. Recent studies have highlighted the potential of tanshinones in the treatment of osteolytic diseases, characterized by excessive bone resorption, such as osteoporosis, rheumatoid arthritis, and periodontitis. The therapeutic effects of tanshinones in these diseases are primarily attributed to their ability to inhibit osteoclast differentiation and activity, suppress inflammatory cytokine production (e.g., tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, and IL-6), and modulate critical signaling pathways, including NF-kB, MAPK, PI3K/Akt, and the RANKL/RANK/OPG axis. Additionally, tanshinones promote osteoblast differentiation and mineralization by enhancing the expression of osteogenic markers such as Runx2, ALP, and OCN. Preclinical models have demonstrated that T-IIA and STS can significantly reduce bone destruction and inflammatory cell infiltration in arthritic joints and periodontal tissues while also enhancing bone microarchitecture in osteoporotic conditions. This review aims to provide a comprehensive overview of the pharmacological actions of tanshinones in osteolytic diseases, summarizing current experimental findings, elucidating underlying molecular mechanisms, and discussing the challenges and future directions for their clinical application as novel therapeutic agents in bone-related disorders, especially periodontitis. Despite promising in vitro and in vivo findings, clinical evidence remains limited, and further investigations are necessary to validate the efficacy, safety, and pharmacokinetics of tanshinones in human populations. Full article

The inhibition of steroid 5-alpha reductase (S5AR), a key mechanism for managing dihydrotestosterone-dependent conditions, has been demonstrated in teak (Tectona grandis L.f.) leaf extracts. Our recent clinical study confirmed the effectiveness of a hair growth formulation containing teak leaf extract in males with androgenic alopecia. However, significant variability in S5AR inhibitory activity among teak leaf samples from different regions underscores the need for quality control of raw materials. This study applied a metabolomics approach to investigate the influence of leaf age, harvesting period, and geographic origin on chemical composition and S5AR inhibitory activity, as well as to identify active S5AR inhibitors. Geographic origin emerged as the primary determinant of variations in chemical profiles and S5AR inhibitory activity. Using orthogonal partial least squares analysis, six diterpenoid S5AR inhibitors were identified, including four compounds reported for the first time as S5AR inhibitors: rhinocerotinoic acid, 7-oxo-8-labden-15-oic acid, 8-hydroxy-labd-13-en-15-oic acid, and a novel diterpene, 7-hydroxy-labd-8,13-dien-15-oic acid. These findings highlight the potential of metabolomics as a powerful tool for discovering bioactive compounds and optimizing raw material selection. By prioritizing proven geographic sources, consistent bioactivity can be achieved, supporting the therapeutic potential of teak leaves in managing S5AR-related conditions. Full article

The mycelia of Hericium erinaceus contain neuroprotective cyathane diterpenoids (e.g., erinacine A). There is evidence that cultivation of submerged mycelia with surfactants increases glucose uptake and biomass, but the impact on erinacine production is unknown. Here, we tested the impact of glucose and polysorbate 80 on the mycelial erinacine profiles of five Hericium strains cultivated under submergence, including those of Hericium erinaceus, Hericium americanum, and Hericium coralloides. Metabolite profiling confirmed that mycelial extracts contained 13% to 91% of the erinacines A, C and P in additive-free cultures of all strains, with the remainder secreted to the culture medium. Overall, erinacine P production was several orders of magnitude greater than that of the other erinacines, except for H. erinaceus (DAOMC 251029), where erinacine C was most evident. H. coralloides (DAOMC 251017) produced the greatest concentrations of erinacines A and P. For the most part mycelial erinacine concentrations were reduced in cultures co-supplemented with glucose and polysorbate 80. This treatment caused an 83–100% reduction in the concentrations of erinacines A, C, and P in the mycelial extracts of most strains. By contrast, there was evidence that glucose and polysorbate 80 had no effect on erinacine A production within mycelia of H. americanum, and erinacine P concentrations in H. erinaceus (DAOMC 251029) and H. americanum (DAOMC 251011). In most strains, the secretion of erinacines to the culture medium declined with glucose and polysorbate 80. Conversely, these additives increased the concentrations of erinacines C and P in the culture medium filtrate of H. americanum (DAOMC 21467) and yielded more secreted erinacine P in H. erinaceus (DAOMC 251029). The information provides feasible strategies to produce mycelia with unique erinacine profiles including those rich in erinacine P. Full article

Background/Objectives: Rhodococcus rhodochrous IEGM 107 cells exhibit pronounced catalytic activity toward mono- and diterpenoids. However, the genetics and enzymatic foundations underlying this activity remain poorly understood. Methods: Using new-generation sequencing, the R. rhodochrous IEGM 107 whole genome was sequenced. Bioinformatic analysis and PCR were employed to identify and characterize genes, with a focus on cytochromes P450 (CYP450s). Results: The catalytic potential of R rhodochrous IEGM 107 was revealed. Its CYP450 genes were detected and analyzed, providing information on the enzymatic base of the strain related to the biotransformation of terpenoids. Conclusions: These findings enhance the understanding of the molecular and genetic basis for terpenoid transformations in R. rhodochrous actinomycetes. The results provide a foundation for future studies on gene expression and enzyme characterization aimed at developing efficient and selective biocatalysts for mono- and diterpenoid transformations. Full article

Photosynthetic organisms such as cyanobacteria have the potential for the sustainable production of complex organic molecules due to their ability to use light as an energy source to fix CO₂ and assimilate inorganic nutrients. Over the past decade, large efforts have been put into the metabolic engineering of cyanobacteria to produce various compounds such as alcohols, isoprenoids, biopolymers, and recombinant proteins. Forskolin is a structurally complex labdane-type diterpenoid with eight chiral carbon atoms and is naturally produced in the root cork of the plant Plectranthus barbatus. Forskolin is a potent cAMP activator indicated as a pharmaceutical for a variety of diseases. In the plant, forskolin biosynthesis from geranylgeranyl diphosphate involves six enzymes: two terpene synthases, three cytochrome P450s, and a single acetyltransferase. In this work, we express all six biosynthetic genes from Plectranthus barbatus in Synechocystis sp. PCC. 6803 and demonstrate heterologous production of this complex diterpenoid in a phototroph cyanobacterium. Forskolin titers reached 25.0 ± 4.4 µg/L and the forskolin was entirely secreted into the media. The forskolin-producing Synechocystis strain and empty vector control were cultivated in a photobioreactor for 8 days. Both strains showed similar chlorophyll a contents, and the forskolin-producing strain reached a slightly higher OD₇₃₀ than the control. Forskolin began accumulating in the supernatant after 4 days and increased over time. These results indicate that forskolin production did not negatively impact cell growth. Full article

Salvia atropatana is a medicinal plant native to Middle Eastern countries. It has been traditionally used in Turkish and Iranian folk medicine to treat infections, wounds, inflammatory diseases, spastic conditions, and diabetes. Its therapeutic potential has been attributed to its essential oil, polyphenolic acid, flavonoid, and diterpenoid content. The aim of the study was to determine the optimal conditions of in vitro S. atropatana shoot culture to enhance proliferation and secondary metabolite production. It examined the effects of various cytokinins and culture duration on culture growth parameters and phenolic compound accumulation. Exogenous cytokinin supplementation significantly enhanced shoot proliferation, with the highest proliferation ratio (6.3) observed with 1 and 2 mg/L 6-benzylaminopurine (BAP). Biomass accumulation was the highest at 0.5 mg/L BAP, followed by 1 and 2 mg/L meta-toplin (mTOP). Phenolic profiling identified nine compounds, with rosmarinic acid (RA) as the dominant metabolite. The highest RA content (16 mg/g dry weight) was achieved with 1 and 2 mg/L BAP and 0.5 mg/L of its ryboside. The TOPSIS (Technique for Order of Preference by Similarity to Ideal Solution) method identified 1 mg/L BAP as the optimal treatment, balancing high proliferation, biomass, and polyphenol accumulation. Extending culture duration to 50 days increased biomass and phenolic content reaching 19.25 mg/g dry weight. However, morphological changes, including apical necrosis, were observed, and a significantly longer cultivation period was needed, questioning the value of the procedure. This study provides a basis for scalable in vitro production of bioactive compounds in S. atropatana. Full article

Cannabis sativa L. has been traditionally used for its therapeutic properties, particularly in treating various skin conditions. This study explores the in vitro anti-aging potential of five distinct parts of C. sativa L. (inflorescence, seed, leaf, stem, and root) by analyzing their bioactive compounds and biological activities. Ultrasound-assisted extraction was employed using ethyl acetate as an extracting solvent, followed by chemical characterization via gas chromatography-mass spectrometry (GC-MS/MS) and liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS/MS) analyses. The biological assessment included antioxidant, anti-inflammatory, anti-tyrosinase activities, and cytotoxicity evaluations. The inflorescence extract demonstrated the antioxidant activity, with a half-maximal inhibitory concentration (IC₅₀) value of 3,849.01 ± 5.25 µg/mL against DPPH radicals and 31.19 ± 0.96% inhibition of NO radicals at 1.25 mg/mL. Notably, the stem extract exhibited the highest anti-tyrosinase activity, with an IC₅₀ value of 0.01 ± 0.00 mg/mL, and significantly inhibited 5-lipoxygenase (5-LOX) activity with an IC₅₀ value of <0.024 µg/mL. All extracts showed no cytotoxicity on HaCaT cells at a concentration of 10 µg/mL, indicating their potential safety for dermatological applications. The stem extract was abundant in phytosterols, triterpenoids, diterpenoids, unsaturated fatty acids, and phenolic compounds, which likely contribute to its anti-inflammatory and anti-tyrosinase effects. These findings suggest that the stem, traditionally considered as waste, could be a valuable raw material for developing dermatological treatments with strong anti-inflammatory and skin-brightening effects. Full article

Isodon suzhouensis, also known as “Wangzaozi”, is an edible and medicinal plant belonging to the Lamiaceae family. Its main functional constituents are the tetracyclic diterpenoids known as wangzaozins. Wangzaozins have a strong structural similarity to gibberellins (GAs), which are synthesized via the diterpenoid biosynthetic pathway (map00904). The formation of the diterpenoid skeleton is regulated by copalyl diphosphate synthase (CPS) and kaurene synthase (KS). In order to identify and study the KS gene involved in wangzaozins biosynthesis, a transcriptomic and metabolomic analysis of Isodon suzhouensis was performed. The IsKS1 gene, which was highly expressed in leaves, was successfully cloned. The binding mode and sites of IsKS1 with its catalyzed substrate, ent-copalyl diphosphate (ent-CPP), were predicted using AutoDock. The docking results revealed hydrophobic interactions, hydrogen bonds, and salt bridges between them. Furthermore, overexpression of IsKS1 in Arabidopsis thaliana resulted in a significant increase in gibberellin content, as well as the up-regulation of GA2(KS) and GA3OX1 genes. These results suggest that the IsKS1 gene is involved in gibberellin biosynthesis and may potentially contribute to the biosynthesis of wangzaozins. Full article

The genus Clinopodium L. (Lamiaceae) comprises perennial herbaceous plants known for their diverse pharmacological properties. Clinically, these plants are mainly used for the treatment of various hemorrhagic disorders. This review systematically summarizes the research progress on the chemical composition, pharmacological activity, quality control, toxicity, and pharmacokinetics of the genus Clinopodium by searching Google Scholar, Scopus-Elsevier, Wiley, Springer, Taylor & Francis, Medline, Web of Science, CNKI, Weipu, Wanfang, and other academic databases over the last decade (March 2015–February 2025). To date, more than one hundred and thirty structurally diverse secondary metabolites have been isolated and identified from this genus, including flavonoids, triterpenoid saponins, diterpenoid glycosides, lignans, and phenylpropanoids. In addition, numerous volatile oil constituents have been identified in over forty species of the genus Clinopodium. Crude extracts and purified compounds exhibit a variety of pharmacological activities, including hemostatic, anti-myocardial cell injury, cardiovascular protective, anti-inflammatory, antimicrobial, antitumor, hypoglycemic, and insecticidal properties. However, current quality assessment protocols in the genus Clinopodium are limited to flavonoid- and saponin-based evaluations in C. chinense (Benth.) O. Kuntze and C. gracile (Benth.) O. Matsum. Further research is needed to elucidate the pharmacological mechanisms, toxicity, and possible interactions with other drugs. Therefore, the genus Clinopodium has a wide range of biologically active compounds with potential applications in drug development for hemostasis and cardiovascular protection. Nevertheless, there is also an urgent need to establish standardized methodologies to address uncertainties concerning the safety and efficacy of injectable extracts or compounds. Full article