Search Results (27)

Intercropping is a promising strategy for sustainable medicinal plant cultivation, but its impact on plant–microbe interactions remains poorly understood. This study investigated the influence that intercropping giant lily (Cardiocrinum giganteum) with bamboo (BG), Chinese fir (FG), and mixed forests (MG) had on the giant lily metabolome and microbiome compared to a monoculture control (GG). Metabolomic analysis revealed that BG significantly increased the accumulation of terpenoids (e.g., yucalexin B22, 19.39-fold), alkaloids (e.g., anabasine, 2.97-fold), and steroids (e.g., O-acetyl-lariciresinol, 4.49-fold), while MG induced the production of stress-related metabolites (e.g., aflatoxin G2, 128.62-fold), and FG enhanced nitrogen metabolism (e.g., putrescine, 2.47-fold). Intercropping altered the rhizosphere and endophytic microbial communities, with BG enriching beneficial bacteria (e.g., Acidobacteria and Alphaproteobacteria) and FG promoting symbiotic fungi (e.g., Serendipita and Xylariales). Network analysis revealed strong correlations between specific microbial taxa (e.g., Bacillus and Ceratobasidiaceae) and key metabolites (e.g., norpandamarilactonine A, methylgingerol), indicating their potential roles in shaping the metabolic profiles of giant lily. These findings highlight the complex interplay between intercropping systems, microbial communities, and medicinal plant metabolism and provide a basis for developing targeted cultivation strategies to enhance the production of bioactive compounds in giant lily and other medicinal plants. Full article

Wound healing stands as a paramount therapeutic pursuit, imposing significant challenges on healthcare, particularly for vulnerable populations. Cedrus brevifolia, a species endemic to Cyprus, thrives in the Tripylos region, commonly known as Cedar Valley, within the Paphos forest. Despite its endemism, this species exhibits negligible genetic divergence from its Mediterranean related species. This study aims to investigate the potential of C. brevifolia resin and bark extracts in promoting wound healing in a mouse model. Previous in vitro investigations have elucidated the antioxidant and anti-inflammatory potential of extracts and isolates derived from the title plant, warranting further exploration in an in vivo setting. This experimental design employed 40 male SKH-hr2 black and brown mice aged 2–4 months. Wounds measuring 1 cm² were meticulously induced in the anesthetized mice and the potential healing effect of the herbal hydrogel formulations was evaluated. The healing potential of the C. brevifolia extracts was rigorously assessed through the daily application of gel formulations containing resin concentrations of 5% and 10% w/w, alongside sapwood and heartwood extracts at concentrations of 0.5% and 1% w/w. The evaluation of the treatments encompassed a multifaceted approach, incorporating clinical observations, skin biophysical parameter assessments utilizing an Antera 3D camera, and FT-IR spectroscopy, in addition to histopathological examination. The chemical compositions were also investigated through NMR and bio-guided isolation. The most prominent herbal hydrogel preparation proved to be the 10% resin, followed by the sapwood at 1%. The chemical analysis unveiled abietic acid, manool, and lariciresinol derivatives that potentially contributed to the observed results. Bridging the gap between in vitro observations and in vivo outcomes attempts to shed light on the potential therapeutic benefits of C. brevifolia hydrogels in wound care. Full article

Currently, agroindustrial waste can be used to obtain bioactive compounds. The solid-state fermentation is an alternative for the valorization of these waste and to be able to release bioactive compounds that may be of interest to different industrial sectors. The aim of this study was to evaluate solid-state fermentation conditions using pineapple peel waste as the substrate with Aspergillus niger spp., to release bioactive compounds using a Plackett–Burman exploratory design. Temperature, humidity, inoculum, NaNO₃, MgSO₄, KCl, and KH₂PO₄ conditions in the fermentation process were evaluated. The antioxidant capacity was determined, and the main compounds of the fermentation extracts were identified. The results revealed that the Aspergillus niger HT3 strain reached a hydrolyzable tannin release of 10.00 mg/g, While Aspergillus niger Aa20 reached a condensed tannin release of 82.59 mg/g. The KH₂PO₄ affects the release of condensed tannins with A. niger Aa20, and MgSO₄ affects the release of hydrolyzable tannins with A. niger HT3. In addition, a positive antioxidant activity was demonstrated for the DPPH, ABTS, and FRAP technique. The main compounds in the fermented pineapple peel were 3-feruloylquinic acid, caffeic acid, lariciresinol, and 3-hydroxyphloretin 2′-O-xylosyl-glucoside, among others. The solid-state fermentation process is a biotechnological alternative for the release of bioactive compounds. Full article

Oxidative stress, a driver of liver pathology, remains a challenge in clinical management, necessitating innovative approaches. In this research, we delved into the therapeutic potential of polyphenols for oxidative liver injury using a multiscale network analysis framework. From the Phenol-Explorer database, we curated a list of polyphenols along with their corresponding PubChem IDs. Verified target information was then collated from multiple databases. We subsequently measured the propagative effects of these compounds and prioritized a ranking based on their correlation scores for oxidative liver injury. This result underwent evaluation to discern its effectiveness in differentiating between known and unknown polyphenols, demonstrating superior performance over chance level in distinguishing these compounds. We found that lariciresinol and isopimpinellin yielded high correlation scores in relation to oxidative liver injury without reported evidence. By analyzing the impact on a multiscale network, we found that lariciresinol and isopimpinellin were predicted to offer beneficial effects on the disease by directly acting on targets such as CASP3, NR1I2, and CYP3A4 or by modulating biological functions related to the apoptotic process and oxidative stress. This study not only corroborates the efficacy of identified polyphenols in liver health but also opens avenues for future investigations into their mechanistic actions. Full article

Lignans are widespread polyphenolic secondary plant metabolites possessing high biological activity. One of the most promising industrial-scale sources of such compounds is coniferous knotwood, containing a large number of polyphenolic compounds. Their use in pharmaceutical and other industries is limited by the difficulty in obtaining high-purity preparations from plant material and the requirement of advanced separation techniques. In this study, supercritical fluid chromatography on polar stationary phases was proposed for the efficient separation and identification of spruce, pine, fir, and larch knotwood extractives. Among the six tested sorbents, the best results were shown by silica with grafted diol and 2-ethylpyridine groups under conditions of gradient elution with a carbon dioxide–methanol mobile phase, which ensured the efficient retention and separation of analytes due to donor–acceptor interactions. Scaling up the method on a DIOL stationary phase provided a semi-preparative separation of extractives within 30 min to obtain 14 individual compounds with a purity of 90–99% and yields from 0.3 to 51% of the dry extract. These included eight lignans (nortrachelogenin, matairesinol, oxomatairesinol, α-conidendrin, 5-hydroxymatairesinol and its isomer, lariciresinol, and secoisolariciresinol), two oligolignans, three stilbenes (pinosylvin and its methyl ester, pterostilbene), and flavonoid taxifolin. The developed approach is distinguished with low operational costs, low consumption of organic solvents, environmental safety, and it is fully consistent with the principles of green chemistry. Full article

Abies alba Mill. (Pinaceae), silver fir, is a widespread gymnosperm species in Europe, important for its ecological, economic, social, and cultural significance, as well as for its use for food and bioremediation purposes. The various parts of the plant (leaves, branches, cones, wood, bark) are also of pharmaceutical interest due to their composition of active compounds. In the last three decades, an impressive amount of research has been dedicated to this species. The variability of the chemical composition of essential oils (whether they come from leaves, oleoresin from branches, or other parts of the plant) is impressive, even in the case of specimens collected from the same geographical area. For essential oils prepared from needles or twigs and branches, limonene, β-pinene, α-pinene, camphene, β-phellandrene, and bornyl acetate are the leading compounds, although their wide variations seem to correspond to multiple chemotypes. Both bark and wood are rich in lignans and phenolic compounds. Matairesinol is apparently the dominant lignan in bark, and secoisolariciresinol and lariciresinol are the dominant ones in wood samples. Pharmacological studies with promising results have evaluated the antioxidant effect (mainly due to essential oils), but also the antimicrobial, antitumor, probiotic, antidiabetic, anti-steatosis, and anti-psoriatic activities. Full article

Neuroblastoma can be accessed with compounds of larger sizes and wider polarities, which do not usually cross the blood–brain barrier. Clinical data indicate cases of spontaneous regression of neuroblastoma, suggesting a reversible point in the course of cell brain tumorigenesis. Dual specificity tyrosine-phosphorylation-regulated kinase2 (DYRK2) is a major molecular target in tumorigenesis, while curcumin was revealed to be a strong inhibitor of DYRK2 (PBD ID: 5ZTN). Methods: in silico studies by CLC Drug Discovery Workbench (CLC) and Molegro Virtual Docker (MVD) Software on 20 vegetal compounds from the human diet tested on 5ZTN against the native ligand curcumin, in comparison with anemonin. In vitro studies were conducted on two ethanolic extracts from Anemone nemorosa tested on normal and tumor human brain cell lines NHA and U87, compared with four phenolic acids (caffeic, ferulic, gentisic, and para-aminobenzoic/PABA). Conclusions: in silico studies revealed five dietary compounds (verbascoside, lariciresinol, pinoresinol, medioresinol, matairesinol) acting as stronger inhibitors of 5ZTN compared to the native ligand curcumin. In vitro studies indicated that caffeic acid has certain anti-proliferative effects on U87 and small benefits on NHA viability. A. nemorosa extracts indicated potential benefits on NHA viability, and likely dangerous effects on U87. Full article

Since chronic inflammation can be seen in severe, long-lasting diseases such as cancer, there is a high demand for effective methods to modulate inflammatory responses. Among many therapeutic candidates, lignans, absorbed from various plant sources, represent a type of phytoestrogen classified into secoisolariciresionol (Seco), pinoresinol (Pino), matairesinol (Mat), medioresinol (Med), sesamin (Ses), syringaresinol (Syr), and lariciresinol (Lari). Lignans consumed by humans can be further modified into END or ENL by the activities of gut microbiota. Lignans are known to exert antioxidant and anti-inflammatory activities, together with activity in estrogen receptor-dependent pathways. Lignans may have therapeutic potential for postmenopausal symptoms, including cardiovascular disease, osteoporosis, and psychological disorders. Moreover, the antitumor efficacy of lignans has been demonstrated in various cancer cell lines, including hormone-dependent breast cancer and prostate cancer, as well as colorectal cancer. Interestingly, the molecular mechanisms of lignans in these diseases involve the inhibition of inflammatory signals, including the nuclear factor (NF)-κB pathway. Therefore, we summarize the recent in vitro and in vivo studies evaluating the biological effects of various lignans, focusing on their values as effective anti-inflammatory agents. Full article

c-Jun N-terminal kinase 1 (JNK1) is currently considered a critical therapeutic target for type-2 diabetes. In recent years, there has been a great interest in naturopathic molecules, and the discovery of active ingredients from natural products for specific targets has received increasing attention. Based on the above background, this research aims to combine emerging Artificial Intelligence technologies with traditional Computer-Aided Drug Design methods to find natural products with JNK1 inhibitory activity. First, we constructed three machine learning models (Support Vector Machine, Random Forest, and Artificial Neural Network) and performed model fusion based on Voting and Stacking strategies. The integrated models with better performance (AUC of 0.906 and 0.908, respectively) were then employed for the virtual screening of 4112 natural products in the ZINC database. After further drug-likeness filtering, we calculated the binding free energy of 22 screened compounds using molecular docking and performed a consensus analysis of the two methodologies. Subsequently, we identified the three most promising candidates (Lariciresinol, Tricin, and 4′-Demethylepipodophyllotoxin) according to the obtained probability values and relevant reports, while their binding characteristics were preliminarily explored by molecular dynamics simulations. Finally, we performed in vitro biological validation of these three compounds, and the results showed that Tricin exhibited an acceptable inhibitory activity against JNK1 (IC₅₀ = 17.68 μM). This natural product can be used as a template molecule for the design of novel JNK1 inhibitors. Full article

Lignans are a group of natural polyphenols present in medicinal plants and in plants which are a part of the human diet for which more and more pharmacological activities, such as antimicrobial, anti-inflammatory, hypoglycemic, and cytoprotective, are being reported. However, it is their cytotoxic activities that are best understood and which have shed light on this group. Two anticancer drugs, etoposide, and teniposide, were derived from a potent cytotoxic agent—podophyllotoxin from the roots of Podophyllum peltatum. The evidence from clinical and observational studies suggests that human microbiota metabolites (enterolactone, enterodiol) of dietary lignans (secoisolariciresinol, pinoresinol, lariciresinol, matairesinol, syringaresinol, medioresinol, and sesamin) are associated with a reduced risk of some hormone-dependent cancers. The biological in vitro, pharmacological in vivo investigations, and clinical studies demand significant amounts of pure compounds, as well as the use of well-defined and standardized extracts. That is why proper extract preparation, optimization of lignan extraction, and identification are crucial steps in the development of lignan use in medicine. This review focuses on lignan extraction, purification, fractionation, separation, and isolation methods, as well as on chromatographic, spectrometric, and spectroscopic techniques for their qualitative and quantitative analysis. Full article

Chronic hepatitis induced by hepatitis B virus (HBV) infection is a serious public health problem, leading to hepatic cirrhosis and liver cancer. Although the currently approved medications can reliably decrease the virus load and prevent the development of hepatic diseases, they fail to induce durable off-drug control of HBV replication in the majority of patients. The roots of Isatis indigotica Fortune ex Lindl., a traditional Chinese medicine, were frequently used for the prevention of viral disease in China. In the present study, (−)-lariciresinol ((−)-LRSL), isolated from the roots of Isatis indigotica Fortune ex Lindl., was found to inhibit HBV DNA replication of both wild-type and nucleos(t)ide analogues (NUCs)-resistant strains in vitro. Mechanism studies revealed that (−)-LRSL could block RNA production after treatment, followed by viral proteins, and then viral particles and DNA. Promoter reporter assays and RNA decaying dynamic experiments indicated that (−)-LRSL mediated HBV RNA reduction was mainly due to transcriptional inhibition rather than degradation. Moreover, (−)-LRSL in a dose-dependent manner also inhibited other animal hepadnaviruses, including woodchuck hepatitis virus (WHV) and duck hepatitis B virus (DHBV). Combining the analysis of RNA-seq, we further found that the decrease in HBV transcriptional activity by (−)-LRSL may be related to hepatocyte nuclear factor 1α (HNF1α). Taken together, (−)-LRSL represents a novel chemical entity that inhibits HBV replication by regulating HNF1α mediated HBV transcription, which may provide a new perspective for HBV therapeutics. Full article

The study aims to examine the association of dietary intake of lignans with the risk of hip fractures in Chinese older adults. This was a 1:1 age- and gender- matched case–control study. Dietary survey was conducted by face-to-face interviews using a 79-item validated food frequency questionnaire. Habitual intake of total and individual lignans (matairesinol, secoisolariciresinol, pinoresinol, and lariciresinol) was estimated based on the available lignans databases. Conditional logistic regression was used to examine the relationship of dietary total and individual lignans, lignan-rich foods (vegetables, fruits, nuts, and cereals) and dietary fibers with the risk of hip fracture. A total of 1070 pairs of hip fracture incident cases and controls were recruited. Compared with the lowest quartile, the highest quartile group showed a reduced hip fracture risk by 76.3% (0.237, 95% CI: 0.103–0.544, P_trend < 0.001) for total lignans, and 62.5% (0.375, 95% CI: 0.194–0.724, P_trend = 0.001) for dietary fibers. Similar findings were observed for individual lignans, the estimated enterolactone level, as well as lignans from vegetables and nuts. We concluded that greater consumption of total and individual lignans, and lignan-rich foods were significantly associated with decreased risk of hip fracture. Full article

The chemical composition of the Cynophalla flexuosa hydroethanolic extract (CFHEE) was identified and its antioxidant, antifungal and antipleomorphic activities against C. albicans and C. tropicalis strains were evaluated. Phytochemical prospecting evidenced polyphenolic and triterpenoid compounds while UPLC-MS analysis revealed the presence of Isopropyl/n-propyl-GLS; Methylpropyl-GLS/butyl-GLS; Methylbutyl-GLS; Quercetin O-di-hexoside; Quercetin-pentosyl-hexoside; Rutin; Quercetin O-glucoside; Kaempferol O-rhamnosyl-hexoside; Kaempferol O-pentosyl-hexoside and Lariciresinol hexoside. The CFHEE inhibited the effect of the DPPH^● free radical, both when evaluated individually and in combination with the antifungal fluconazole. When associated with 256 μg/mL fluconazole, the extract, at concentrations from 128 μg/mL, reduced the effect of the DPPH^● free radical with values ranging from 37.7% to 95.8%. The extract’s antifungal effect was considered clinically irrelevant and its combination with the antifungal triggered an antagonistic effect against the two strains, thus indicating the popular use of bravo beans in the form of teas or infusions should not be combined with the intake of the drug Fluconazole as this may lead to a reduction of its clinical effect. The extract, however, inhibited morphological changes (pleomorphism) in Candida species, preventing the development of hyphae. The CFHEE possesses an antioxidant effect and a potential pharmacological activity for the inhibition of one of the Candida spp. virulence factors. Full article

The chemical composition of extractives in the sapwood (SW), heartwood (HW), knotwood (KW), and branchwood (BW of silver fir (Abies alba Mill.) was analyzed, and their antifungal and antioxidant properties were studied. In addition, the variability of extractives content in a centripetal direction, i.e., from the periphery of the stem towards the pith, was investigated. The extracts were analyzed chemically with gravimetry, spectrophotometry, and chromatography. The antifungal and antioxidative properties of the extracts were evaluated by the agar well diffusion method and the diphenyl picrylhydrazyl radical scavenging method. Average amounts of hydrophilic extractives were higher in KW (up to 210.4 mg/g) and BW (148.6 mg/g) than in HW (34.1 mg/g) and SW (14.8 mg/g). Extractives identified included lignans (isolariciresinol, lariciresinol, secoisolariciresinol, pinoresinol, matairesinol) phenolic acids (homovanillic acid, coumaric acid, ferulic acid), and flavonoids epicatechin, taxifolin, quercetin). Secoisolariciresinol was confirmed to be the predominant compound in the KW (29.8 mg/g) and BW (37.6 mg/g) extracts. The largest amount of phenolic compounds was extracted from parts of knots (281.7 mg/g) embedded in the sapwood and from parts of branches (258.9 mg/g) adjacent to the stem. HW contained more lignans in its older sections. Hydrophilic extracts from knots and branches inhibited the growth of wood-decaying fungi and molds. KW and BW extracts were better free radical scavengers than HW extracts. The results of the biological activity tests suggest that the protective function of phenolic extracts in silver fir wood can also be explained by their antioxidative properties. The results of this study describe BW as a potential source of phenolic extractives in silver fir. Full article

In vitro cultures of scarlet flax (Linum grandiflorum L.), an important ornamental flax, have been established as a new possible valuable resource of lignans and neolignans for antioxidant and anti-inflammatory applications. The callogenic potential at different concentrations of α-naphthalene acetic acid (NAA) and thidiazuron (TDZ), alone or in combinations, was evaluated using both L. grandiflorum hypocotyl and cotyledon explants. A higher callus induction frequency was observed on NAA than TDZ, especially for hypocotyl explants, with a maximum frequency (i.e., 95.2%) on 1.0 mg/L of NAA. The presence of NAA (1.0 mg/L) in conjunction with TDZ tended to increase the frequency of callogenesis relative to TDZ alone, but never reached the values observed with NAA alone, thereby indicating the lack of synergy between these two plant growth regulators (PGRs). Similarly, in terms of biomass, NAA was more effective than TDZ, with a maximum accumulation of biomass registered for medium supplemented with 1.0 mg/L of NAA using hypocotyls as initial explants (DW: 13.1 g). However, for biomass, a synergy between the two PGRs was observed, particularly for cotyledon-derived explants and for the lowest concentrations of TDZ. The influence of these two PGRs on callogenesis and biomass is discussed. The HPLC analysis confirmed the presence of lignans (secoisolariciresinol (SECO) and lariciresinol (LARI) and neolignan (dehydrodiconiferyl alcohol [DCA]) naturally accumulated in their glycoside forms. Furthermore, the antioxidant activities performed for both hypocotyl- and cotyledon-derived cultures were also found maximal (DPPH: 89.5%, FRAP 866: µM TEAC, ABTS: 456 µM TEAC) in hypocotyl-derived callus cultures as compared with callus obtained from cotyledon explants. Moreover, the anti-inflammatory activities revealed high inhibition (COX-1: 47.4% and COX-2: 51.1%) for extract of hypocotyl-derived callus cultures at 2.5 mg/L TDZ. The anti-inflammatory action against COX-1 and COX-2 was supported by the IC₅₀ values. This report provides a viable approach for enhanced biomass accumulation and efficient production of (neo)lignans in L. grandiflorum callus cultures. Full article