Plant Natural Products Research Articles

Resveratrol: Protective Agent Against Alzheimer's Disease.

Resveratrol is a biologically active natural phenolic plant product. It has several properties which make them useful to treat the disease. In this review, we have highlighted the neuroprotective effects of resveratrol. Several available animal models have been proven to help understand the disease pathway and mechanism of action by resveratrol. In this review, we have highlighted the neuroprotective activity of resveratrol in AD, which effectively counter the neurodegenerative disease by decreasing the formation of plaques. Resveratrol is a natural plant product that is easily available, cost-effective, and possesses neuroprotective activity, which is useful for treating neurodegenerative diseases. Resveratrol presents a promising avenue for AD treatment due to its diverse neuroprotective mechanisms. Given the ongoing global challenge in treating AD, researchers have increasingly focused on exploring the therapeutic potential of resveratrol.

Chromosome-Scale Genome of the Fern Cibotium barometz Unveils a Genetic Resource of Medicinal Value

Ferns represent the second-largest group of vascular plants, yet their genomic resources lag far behind. Here, we present a chromosome-scale genome assembly of Cibotium barometz (L.) J. Sm., a medicinally important fern species. The 3.49 Gb genome, assembled into 66 chromosomes with 99.41% sequence anchorage, revealed an exceptionally high proportion (83.93%) of repetitive elements, dominated by recently expanded LTR retrotransposons. We identified 30,616 protein-coding genes, providing insights into fern-specific gene families. Genomic analyses uncover the evolutionary dynamics of 513 key biosynthetic genes, particularly those involved in terpenoid and flavonoid production. Expression profiling across tissues revealed tissue-specific regulation of these pathways, with notable upregulation of chalcone synthase genes in roots. Our structural analysis of 1-deoxy-d-xylulose-5-phosphate synthase, a key enzyme in terpenoid biosynthesis, demonstrated high conservation across land plants while highlighting fern-specific adaptations. The identification of multiple isoforms for key enzymes points to potential gene-duplication events or the evolution of fern-specific variants. This genome provides a foundation for understanding fern biology, evolution, and the molecular basis of their medicinal properties. It also offers valuable resources for conservation efforts and pharmacological research, paving the way for sustainable utilization of this valuable medicinal plant and advancing our understanding of plant diversity and natural product biosynthesis.

Structure and Function of Sabinene Synthase, a Monoterpene Cyclase That Generates a Highly Strained [3.1.0] Bicyclic Product.

Sabinene is a plant natural product with a distinctive strained [3.1.0] bicyclic ring system that is used commercially as a spicy and pine-like fragrance with citrus undertones. This unusual monoterpene has also been studied as an antifungal and anti-inflammatory agent as well as a next-generation biofuel. In order to understand the molecular determinants of [3.1.0] bicyclic ring formation in sabinene biosynthesis, we now report three X-ray crystal structures of sabinene synthase from Western red cedar, Thuja plicata (TpSS), with open and partially closed active site conformations at 2.21-2.72 Å resolution. We additionally report the complete biochemical characterization of sabinene synthase, including steady-state kinetics, active site mutagenesis, and product array profiling. The catalytic metal ion requirement is unexpectedly broad for a class I terpene cyclase: optimal catalytic activity was measured using Mn2+ or Co2+, with more modest activity observed using Mg2+ or Ni2+. Kinetic parameters were determined for both full-length TpSS and a deletion variant lacking the putative N-terminal plastidial targeting sequence, designated ΔTpSS. Monoterpene product profiles for both indicated similar product arrays independent of the catalytic metal ion used, with sabinene comprising nearly 90% of the total products generated. Site-directed mutagenesis was utilized to probe the function of active site residues, and several mutants yielded altered product arrays. Most notably, the G458A substitution converted ΔTpSS into a high-activity α-pinene synthase. α-Pinene contains a bicyclic [3.1.1] ring system; structural and mechanistic analyses suggest a molecular rationale for the reprogrammed transannulation reaction, leading to the alternative bicyclic product.

Identification of Secondary Metabolites by Multi-Omics Methods

Plant natural products, also known as plant specialized metabolites (SMs) due to their lineage-specific distribution, are small molecules synthesized by plants to adapt to changing environments [...]

Whole-pathway stimulation of anthocyanin biosynthesis by UDP-glycose: flavonoid glycosyltransferase gene (UFGT) providing new insights into natural product development based on plant cell factory

Anthocyanins are a type of plant natural products (PNPs) that play a crucial role in various fields, including food, medicine, cosmetics, and dyes. However, their primary source is plant extraction, leading to significant ecological damage and resource wastage issues. To address the challenge of achieving ecologically sustainable high-throughput anthocyanin production, this study proposes a plant cell factory (PCF) strategy based on suspension cell culture (SCC). In this study, the key gene VdUFGT involved in anthocyanin biosynthesis was cloned from Vitis davidii, and gene overexpression was conducted using Agrobacterium-mediated methods. Notably, the vgt3 transgenic cell line exhibited 4.4-fold increase in anthocyanin content, reaching 286.9 μg/g (FW) in solid medium, along with enhanced levels of flavonoids and proanthocyanidins. Integrative analysis of transcriptomics and metabolomics demonstrated that VdUFGT significantly promoted the expression of genes involved in anthocyanin biosynthesis, leading to the enhanced accumulation of various flavonoids, including anthocyanins. A small-scale plant cell factory was established, achieving an impressive production of 4.11 mg/g (DW) of anthocyanin within just 12 days, which is 8.5 times higher than that of the WT cell line, with the yield of purified freeze-dried anthocyanin powder reaching 3.17%. The plant cell factory, employing genetic engineering and suspension cell culture, offers a safe, ecological, economical, and efficient approach for the high-throughput production of plant natural products such as anthocyanins.

Ionic Liquid-Based Green Solvents for Extraction and Purification of Natural Plant Products

Introduction: This research paper explores the environmental sustainability of ionic liquid-based green solvents in the extraction and purification of natural plant products, with a focus on their entire life cycle. The objectives of the study were to assess the environmental impact of ionic liquid synthesis, energy consumption, water usage, emissions, recycling rates, policy effects, and stakeholder perceptions. Methods: Methodologically, we conducted a comprehensive Life Cycle Assessment (LCA) that involved primary data collection through field surveys and interviews with key stakeholders in the ionic liquid production and usage industry across various regions in India. The data were analyzed using specialized LCA software tools to quantify environmental impacts. Key findings include the identification of synthesis as a major contributor to environmental impact, emphasizing the need for greener synthesis methods. Results: The study revealed the significant carbon footprint, energy consumption, and water usage during production, highlighting opportunities for improvement. Emissions data underscored the importance of emission control measures, particularly for greenhouse gases and volatile organic compounds. Recycling and reuse were identified as environmentally friendly disposal methods. Policy compliance varied among stakeholders, indicating room for stricter regulations. Stakeholder perceptions varied, with researchers having the most positive outlook. Implications of the findings extend to sustainable chemistry practices, emphasizing interdisciplinary collaboration and the importance of considering the entire life cycle of chemical processes. Conclusion: This research contributes to a deeper understanding of green solvents and provides a foundation for promoting sustainable practices in industrial processes in India and globally.

Gene-Directed In Vitro Mining Uncovers the Insect-Repellent Constituent from Mugwort (Artemisia argyi).

Plants contain a vast array of natural products yet to be discovered, particularly those minor bioactive constituents. Identification of these constituents requires a significant amount of plant material, presenting considerable technical challenges. Mugwort (Artemisia argyi) is a widely recognized insect repellent herb, particularly renowned for its extensive usage during the Dragon Boat Festival in China, but the specific constituent responsible for its repellent activity remains unknown. Here, we employed a gene-directed in vitro mining approach to characterize mugwort terpene synthases (TPSs) systematically in a yeast expression system. Based on the establishment of "Terpene synthase-standard library", we have successfully identified 54 terpene products, including a novel compound designated as cyclosantalol. Through activity screening, we have identified that (+)-intermedeol, which presents in trace amount in plants, exhibits significant repellent activity against mosquitoes and ticks. After establishing its safety and efficacy, we then achieved its biosynthetic production in a yeast chassis, with an initial yield of 2.34 g/L. The methodology employed in this study not only identified a highly effective, safe, and commercially viable insect repellent derived from mugwort but also holds promise for uncovering and producing other valuable plant natural products in future research endeavors.

Research work of Prof. De-Eknamkul, including the mechanistic synergy of hair growth promotion by the Avicennia marina extract and its active constituent (avicequinone C) in dermal papilla cells isolated from androgenic alopecia patients

Androgenetic alopecia (AGA) is a genetically-predetermined disorder that affects many people around the world, leading to progressive hair loss. This baldness can negatively impact people’s perceptions of themselves and scientists are searching for a cure. There are only two US Food and Drug Administration-approved drugs used to treat AGA and they both have side effects. If a natural anti-AGA product could be developed with the ability to be effective minus negative side effects, this could be a game-changer for people with AGA. Professor Wanchai De-Eknamkul, Department of Pharmacognosy and Pharmaceutical Botany, Chulalongkorn University, Thailand, an expert in plant natural product biotechnology, is working to develop a natural anti-AGA product. He is a professor at the University’s Natural Product Biotechnology Research Unit, where research is underway to: elucidate the biosynthesis of bioactive natural products by searching for enzymes and genes involved in their biosynthetic pathways; discover bioactive natural compounds from medicinal plants by either enzyme-based or cell-based screening followed by studying their mechanism of actions; and develop high-performance thin-layer chromatography (HPTLC) as a tool for quick screening and identification of bioactive compounds. De-Eknamkul have been working to shed light on the genes and enzymes involved in the biosynthesis of the diterpenoid ‘plaunotol’ in Croton stellatopilosus. In another line of investigation, they are searching for natural compounds with anti-AGA and anti-grey hair activities and a further area of focus is the development of a technique for direct detection of compounds with anti-diabetes, anti-gonorrhoea and anti-AGA activities.

Ethnotaxonomy and Ethnobotanical Studies of Honey and Resinous Plants in the Tchamba Prefecture in Togo

Natural plant products have gained increasing attention, but climate change and human activities have led to the degradation of ecosystems and loss of biodiversity. This study aims to contribute to the preservation of local knowledge related to the classification and use of honey-producing and resinous plants in the Tchamba prefecture, Togo. Ethnotaxonomic and ethnobotanical data were collected through semi-directed interview and focus groups in the four localities, involving 92 respondents. A total of 96 plants of beekeeping were identified, classified into 88 genera, 33 families, and 22 orders, with 16 ethnotaxonomic criteria used for classification. The most common criteria were "plant use" and "plant habit". The study highlights the rich local knowledge of plant uses for food, medicine, and rituals, emphasizing the importance of conserving both biodiversity and cultural heritage. These findings contribute to understanding how indigenous knowledge can support conservation and sustainable use of plant resources.

Semi-Preparation and X-ray Single-Crystal Structures of Sophocarpine-Based Isoxazoline Derivatives and Their Pesticidal Effects and Toxicology Study.

Recently, research and development of novel pesticides from natural plant products have received much attention. To accelerate the application of sophocarpine as the agrochemical candidate, a series of novel sophocarpine-based isoxazoline derivatives were prepared by the 1,3-dipolar [2 + 3] cycloaddition reaction of sophocarpine with different chloroximes. Their structures were well characterized by high-resolution mass spectra, infrared spectra, and proton/carbon-13 nuclear magnetic resonance spectra. Eight steric configurations of compounds 5a, 5e', 5f, 5g, 5h, 5i, 5r, and 5u' were further determined by X-ray single-crystallography. Against Aphis citricola Van der Goot, compounds 5n (LD50: 0.032 μg/nymph) and 5o (LD50: 0.024 μg/nymph) exhibited greater than 3.7- and 4.9-fold potent aphicidal activity compared to sophocarpine (LD50: 0.118 μg/nymph). Against Tetranychus cinnabarinus Boisduval, derivative 5g displayed the most promising acaricidal activity with the LC50 value of 0.247 mg/mL, which was 14.2-fold that of sophocarpine. Compounds 5d and 5g also exhibited good control efficacy against T. cinnabarinus. Scanning electron microscopy images indicated that compound 5g can destroy the mite cuticle layer. These results will provide the foundation for the structural modification and use of sophocarpine derivatives as agrochemicals in the future.

The Effect of Natural Plant Products in the Management of Autoimmune Diseases Along with Photodynamic Therapy

The Effect of Natural Plant Products in the Management of Autoimmune Diseases Along with Photodynamic Therapy

Plant natural products as effective options for inhibiting foodborne pathogens: A comprehensive review of their activities, mechanisms, and applications in food preservation

Plant natural products as effective options for inhibiting foodborne pathogens: A comprehensive review of their activities, mechanisms, and applications in food preservation

Evolution of aromatic amino acid metabolism in plants: a key driving force behind plant chemical diversity in aromatic natural products.

A diverse array of plant aromatic compounds contributes to the tremendous chemical diversity in the plant kingdom that cannot be seen in microbes or animals. Such chemodiversity of aromatic natural products has emerged, occasionally in a lineage-specific manner, to adopt to challenging environmental niches, as various aromatic specialized metabolites play indispensable roles in plant development and stress responses (e.g. lignin, phytohormones, pigments and defence compounds). These aromatic natural products are synthesized from aromatic amino acids (AAAs), l-tyrosine, l-phenylalanine and l-tryptophan. While amino acid metabolism is generally assumed to be conserved between animals, microbes and plants, recent phylogenomic, biochemical and metabolomic studies have revealed the diversity of the AAA metabolism that supports efficient carbon allocation to downstream biosynthetic pathways of AAA-derived metabolites in plants. This review showcases the intra- and inter-kingdom diversification and origin of committed enzymes involved in plant AAA biosynthesis and catabolism and their potential application as genetic tools for plant metabolic engineering. I also discuss evolutionary trends in the diversification of plant AAA metabolism that expands the chemical diversity of AAA-derived aromatic natural products in plants. This article is part of the theme issue 'The evolution of plant metabolism'.

Environmental Impact Assessment of a Plant Cell-Based Bio-Manufacturing Process for Producing Plant Natural Product Ingredients

Purpose: This study employed a Life Cycle Assessment (LCA) methodology to evaluate the environmental impacts of a novel plant cell-based biomanufacturing process for producing plant natural product ingredients. The primary purpose was to assess the relative sustainability of the process and to provide insights into potential areas of improvement in the biomanufacturing process. Method: The LCA method used an MS Excel (Ver. 2407) -based approach with a cradle-to-gate system boundary covering raw material sourcing (A1), raw material transportation (A2), and product extract manufacturing (A3) stages. Energy use and material inventory data are presented for different unit operations, and environmental impact factors were obtained from the Ecoinvent database. The study included a Material Circularity Index (MCI) calculation to assess the circularity of the biomanufacturing process for the production of saponin emulsifiers that are normally extracted from the woody tissue of the Chilean soapbark tree (Quillaja saponaria). Comparative analyses were performed against a wild-harvest approach for plant tannin extraction from spruce (Picea abies) tree bark. Key Results: The environmental impact assessment focused on determining relative Global Warming Potential (GWP), Acidification Potential (AP), Freshwater Eutrophication (FE), Particulate Matter Formation (PMF), and Ozone Depletion Potential (ODP). Results indicated that the extract manufacturing stage (A3) contributed significantly to adverse environmental impacts, with varying levels of effects based on the energy source used. Comparative analysis with the wild harvest approach highlights the lower environmental impact of the alternative biomanufacturing process. The biomanufacturing process showed a 23% reduction in GWP, AP, and FE and a 25% reduction in PMF and ODP relative to the wild harvest approach. However, the MCI for the biomanufacturing process was estimated to be 0.186, indicating a low material circularity. Conclusions: The results revealed that the extract manufacturing stage, particularly energy consumption, significantly influences the relative environmental impacts of the alternative production processes. Different energy sources exhibit varying effects, with renewable energy sources showing lower environmental impacts. The Material Circularity Index indicated a low circularity for the biomanufacturing process, suggesting opportunities for improvement, such as incorporating recycled or reused materials. Compared with the tannin extraction process, the plant cell-based biomanufacturing process demonstrated lower environmental impacts, emphasising the importance of sustainable practices and the use of renewable energy sources in future plant natural product sourcing. Recommendations include implementing more sustainable practices, optimising raw material choices, and extending product life spans to enhance circularity and overall environmental benefits.

LC-MS-Based Targeted Metabolite Profiling and Atomic Absorption Spectrophotmeter Based Mineral Analysis of Methanol Extract of Terminalia bellerica (Gaertn.) Leaves

Aim: Natural products in medicinal plants are one of the important sources for modern drug discovery. Plant-based formulations play an important role in management of numerous diseases. To discover the medical potential of natural products, it is important to understand the bioactive compounds present in medicinal plants. Hence the aim of the study is to identify the volatile compounds by LC –MS analysis and minerals by AAS assay present in the leaves of Terminalia bellerica. Study Design: This study investigates metabolites present in leaves of Terminalia bellerica have been studied by AAS and LC-MS techniques. Results: The AAS assay showed that the leaves of T. bellerica are particularly rich in iron (260 mg/kg) compared to their zinc, manganese, and copper content. Meanwhile, the LC-MS analysis identified chebulinic acid, chebulagic acid, punicafolin, myricetin, rutin, and galloyl punicalagin as being present in the highest concentrations. Conclusion: Results highlighted presence of considerable amount of iron and other minerals in methanolic extract of the leaves of T. bellerica, it may be used in the development of health supplements. The results also revealed that bioactive compounds in the methanolic extracts of T. bellerica leave used for drug design and making it safe to human health.

Plant natural products: A lead for nephroprotection

An extremely dangerous side effect of type I and type II diabetes is diabetic nephropathy (DN). From the early microproteinuria to end-stage renal failure, it progresses. About one in three diabetics in the US suffer from diabetic nephropathy. Chronic hyperglycemia is the primary cause of diabetic ketoacidosis. Hyperglycemia (HG) has the potential to cause humoral mediators and cytokines to be produced by both resident and non-resident renal cells. These substances may interfere with cell growth, alter renal cell and tissue phenotype and function, interact with proteins, produce advanced glycation end products (AGEs), damage tubules and glomeruli, and ultimately cause kidney disease. Poor blood glucose management is thus a significant risk factor for the onset of DN. An alternate course of treatment for DN may use extracts from herbal remedies. Medicinal plants' bioactive components stop DN from progressing. Attention has to be paid to the role that traditional herbs and medications play in the treatment of diabetic nephropathy, particularly in India where several fruits and herbs are believed to provide health benefits. Natural compounds influence the KEAP1/Nrf2/ARE and NFB pathways in addition to having antioxidant and anti-inflammatory properties. The efficacy of entire herbs, plants, or seeds, together with their active components, in treating diabetic nephropathy was investigated in preclinical research. Natural compounds are biologically active substances that come from natural sources and are beneficial for treating specific illnesses. Numerous natural substances, such as glycosides, polysaccharides, terpenoids, alkaloids, flavonoids, and polyphenols, have been shown to enhance DN. The exorbitant expenses associated with contemporary medications suggest that other approaches are necessary for improved DN treatment. Future research on herbal remedies may provide a natural key to open a pharmacy for diabetologists. Keywords: Diabetic nephropathy; nephroprotective plant; herbal compounds, bioactive compound

Phytochemical, antioxidant and antibacterial studies of extracts and chromatographic fractions of <i>Gmelina arborea</i> Roxb (Lamiaceae)

Antimicrobial resistance and oxidative stress are increasing and researchers are being encouraged to search the natural plant products, due to their popular usage in ethno-medicine, for alternative source of antimicrobial and antioxidant compounds. Gmelina arborea used in West-Africa and Ayurveda folkloric medicine to cure several diseases was therefore investigated for phytochemical, antioxidant and antimicrobial activities. Extracts and chromatographic fractions of the root-bark tested for antibacterial activity with the MIC determined on seven selected bacteria using agar dilution method. The antioxidant capacity of the crude extracts was determined by six (6) methods: total flavonoid content, total phenolic content, ferric reducing power, total antioxidant capacity, Trolox equivalent antioxidant capacity and DPPH (2,2-diphenyl-1-picryhydrazyl) properties. Phytochemical screening indicated the presence of saponins, tannins, flavonoids, terpenoids anthraquinones, phenols and alkaloids. The methanol and ethyl-acetate extracts of the plant showed good antibacterial activities (18 mm inhibitory zones and MIC and MBC 12.5–100 mg/mL) against P. aeruginosa ATCC 27853 and S. aureus ATCC 6571. Antioxidant study of the extracts revealed that both ethyl acetate and methanol extracts have good antioxidant capacity comparable to that of ascorbic acid standard. Therefore, Gmelina arborea could prove a valuable source of developing new antimicrobial and antioxidant compounds for therapeutic uses.

Novel Pesticide Candidates Inspired by Natural Neolignan: Preparation and Insecticidal Investigation of Honokiol Analogs Containing 2-Aminobenzoxazole-Fused Core Scaffold.

As a continuation of our efforts to develop new agrochemicals with typical architecture and efficient bioactivity from plant natural products, natural neolignan honokiol was used as a lead compound to prepare novel analogs bearing the core 2-aminobenzoxazole scaffold. Their insecticidal potency against two representative agricultural pests, Plutella xylostella Linnaeus and Mythimna separata (Walker), were evaluated in vivo. The pesticide bioassay results revealed that compounds 7″a, 9, 10d, and 10j exhibited prominent larvicidal activity against the larvae of P. xylostella (LC50 = 7.95, 11.85, 15.51, and 12.06 μg/mL, respectively), superior to the precursor honokiol (LC50 = 43.35 μg/mL) and two botanical insecticides, toosendanin (LC50 = 26.20 μg/mL) and rotenone (LC50 = 23.65 μg/mL). Compounds 7d, 10d, and 10j displayed a more pronounced nonchoice antifeedant effect (AFC50 = 9.48, 9.14, and 12.41 μg/mL, respectively) than honokiol (AFC50 = 54.81 μg/mL) on P. xylostella. Moreover, compounds 7b, 7″a, 9, 10d, 10f, and 10j showed better growth inhibitory activity against M. separata (LC50 = 0.36, 0.34, 0.28, 0.16, 0.26, and 0.11 mg/mL, respectively) than honokiol, toosendanin, and rotenone (LC50 = 1.48, 0.53, and 0.46 mg/mL, respectively). A potted plant assay under greenhouse conditions illustrated that compounds 10d and 10j continued to provide good control efficacy against P. xylostella and an apparent protective effect on plants. Further cytotoxicity assay revealed that the aforementioned potent compounds showed relatively moderate toxicity and a good safety profile for non-target mammalian cells. Overall, the current work provides valuable insight into the agrochemical innovation of honokiol-derived analogs for use as natural-inspired pesticides in agricultural pest management.

Evaluation of antifungal activity of natural plant products against fungal contaminants isolated from Ngari (a fermented fish product of Manipur)

Evaluation of antifungal activity of natural plant products against fungal contaminants isolated from Ngari (a fermented fish product of Manipur)

Evaluation of the Therapeutic Potential of Traditionally-Used Natural Plant Extracts to Inhibit Proliferation of a HeLa Cell Cancer Line and Replication of Human Respiratory Syncytial Virus (hRSV).

Traditional approaches employing natural plant products to treat a wide array of ailments have been documented and described for thousands of years. However, there remains limited scientific study of the therapeutic potential or effectiveness of ethnobotanical applications. Increases in the incidence of cancer and emerging infectious diseases demonstrate a growing need for advances in the development of therapeutic options. In this study, we evaluate the therapeutic potential of aqueous extracts prepared from four plants, purple aster (Symphyotrichum novae-angliae (L.) Nemsom), common sage (Salvia lyrata (L.)), northern spicebush (Lindera benzoin (L.) Blume), and lamb's ear (Stachys byzantina (K.) Koch)) traditionally used in Native American medicine in Indiana, USA. Using a combination of cytotoxicity assays, immunofluorescence microscopy, and antiviral assays, we found that sage and spicebush extracts exhibit cytotoxic and antiproliferative effects on HeLa cell proliferation and that sage, spicebush, and aster extracts were capable of significantly inhibiting human respiratory syncytial virus (hRSV), a major respiratory pathogen of infants and the elderly. Chemical analysis of the four extracts identified four major compounds which were subsequently evaluated to identify the responsible constituents in the extracts. While none of the identified compounds were shown to induce significant impacts on HeLa cell proliferation, two of the compounds, (1S)-(-)-Borneol and 5-(hydroxymethyl)-furfural, identified in sage and spicebush, respectively, were shown to have antiviral activities. Our data suggest that several of the extracts tested exhibited either anti-proliferative or antiviral activity supporting future further analysis.