Deciphering the Anticancer Arsenal of Piper longum: Network Pharmacology and Molecular Docking Unveil Phytochemical Targets Against Lung Cancer.

Introduction: Lung cancer, characterized by uncontrolled cellular proliferation within the lung tissues, is the predominant cause of cancer-related fatalities worldwide. The traditional medicinal herb Piper longum has emerged as a significant contender in oncological research because of its documented anticancer attributes, suggesting its potential for novel therapeutic development. Methods: This study adopted network pharmacology and omics methodology to elucidate the anti-lung cancer potential of P. longum by identifying its bioactive constituents and their corresponding molecular targets. Results: Through a comprehensive literature review and the Integrated Medicinal Plant Phytochemistry and Therapeutics database (IMPPAT), we identified 33 bioactive molecules from P. longum. Subsequent analyses employing tools such as SwissTargetPrediction, SuperPred, and DIGEP-Pred facilitated the isolation of 676 potential targets, among which 72 intersected with 666 lung cancer-associated genetic markers identified through databases including the Therapeutic Target Database (TTD), Online Mendelian Inheritance in Man (OMIM), and GeneCards. Further validation through protein-protein interaction (PPI) networks, gene ontology, pathway analyses, boxplots, and overall survival metrics underscored the therapeutic potential of compounds such as 7-epi-eudesm-4(15)-ene-1ß, demethoxypiplartine, methyl 3,4,5-trimethoxycinnamate, 6-alpha-diol, and aristolodione. Notably, our findings reaffirm the relevance of lung cancer genes, such as CTNNB1, STAT3, HIF1A, HSP90AA1, and ERBB2, integral to various cellular processes and pivotal in cancer genesis and advancement. Molecular docking assessments revealed pronounced affinity between 6-alpha-diol and HIF1A, underscoring their potential as therapeutic agents for lung cancer. Conclusion: This study not only highlights the bioactive compounds of P. longum but also reinforces the molecular underpinnings of its anticancer mechanism, paving the way for future lung cancer therapeutics.

Adaptation and Validation of a Modified Broth Microdilution Method for Screening the Anti-Yeast Activity of Plant Phenolics in Apple and Orange Juice Models.

Yeasts are the usual contaminants in fruit juices and other beverages, responsible for the decrease in the quality and shelf-life of such products. Preservatives are principally added to these beverages to enhance their shelf-life. With the increasing consumer concern towards chemical food additives, plant-derived antimicrobials have attracted the attention of researchers as efficient and safer anti-yeast agents. However, the methods currently used for determining their anti-yeast activity are time- and material-consuming. In this study, the anti-yeast effect of plant phenolic compounds in apple and orange juice food models using microtiter plates has been evaluated in order to validate the modified broth microdilution method for screening the antimicrobial activity of juice preservative agents. Among the twelve compounds tested, four showed a significant in vitro growth-inhibitory effect against all tested yeasts (Saccharomyces cerevisiae, Zygosaccharomyces bailii, and Zygosaccharomyces rouxii) in both orange and apple juices. The best results were obtained for pterostilbene in both juices with minimum inhibitory concentrations (MICs) ranging from 32 to 128 µg/mL. Other compounds, namely oxyresveratrol, piceatannol, and ferulic acid, exhibited moderate inhibitory effects with MICs of 256-512 µg/mL. Furthermore, the results indicated that differences in the chemical structures of the compounds tested significantly affected the level of yeast inhibition, whereas stilbenes with methoxy and hydroxy groups produced the strongest effect. Furthermore, the innovative assay developed in this study can be used for screening the anti-yeast activity of juice preservative agents because it saves preparatory and analysis time, laboratory supplies, and manpower in comparison to the methods commonly used.

Natural Products for Preventing and Managing Anthracycline-Induced Cardiotoxicity: A Comprehensive Review.

Doxorubicin (DOX) is an anthracycline anticancer agent that is highly effective in the treatment of solid tumors. Given the multiplicity of mechanisms involved in doxorubicin-induced cardiotoxicity, it is difficult to identify a precise molecular target for toxicity. The findings of a literature review suggest that natural products may offer cardioprotective benefits against doxorubicin-induced cardiotoxicity, both in vitro and in vivo. However, further confirmatory studies are required to substantiate this claim. It is of the utmost importance to direct greater attention towards the intricate signaling networks that are of paramount importance for the survival and dysfunction of cardiomyocytes. Notwithstanding encouraging progress made in preclinical studies of natural products for the prevention of DOX-induced cardiotoxicity, these have not yet been translated for clinical use. One of the most significant obstacles hindering the development of cardioprotective adjuvants based on natural products is the lack of adequate bioavailability in humans. This review presents an overview of current knowledge on doxorubicin DOX-induced cardiotoxicity, with a focus on the potential benefits of natural compounds and herbal preparations in preventing this adverse effect. As literature search engines, the browsers in the Scopus, PubMed, Web of Science databases and the ClinicalTrials.gov register were used.

The anti-aromatase and anti-estrogenic activity of plant products in the treatment of estrogen receptor-positive breast cancer.

Despite being the focal point of decades of research, female breast cancer (BC) continues to be one of the most lethal cancers in the world. Given that 80 % of all diagnosed BC cases are estrogen receptor-positive (ER+) with carcinogenesis driven by estrogen-ERα signalling, current standard of care (SOC) hormone therapies are geared towards modulating the function and expression levels of estrogen and its receptors, ERα and ERß. Currently, aromatase inhibitors (AIs), selective ER modulators (SERMs) and selective ER degraders (SERDs) are clinically prescribed for the management and treatment of ER+ BC, with the anti-aromatase activity of AIs abrogating estrogen biosynthesis, while the anti-estrogenic SERMs and SERDs antagonise and degrade the ER, respectively. The use of SOC hormone therapies is, however, significantly hampered by the onset of severe side-effects and the development of resistance. Given that numerous studies have reported on the beneficial effects of plant compounds and/or extracts and the multiple pathways through which they target ER+ breast carcinogenesis, recent research has focused on the use of dietary chemopreventive agents for BC management. When combined with SOC treatments, several of these plant components and/or extracts have demonstrated improved efficacy and/or synergistic impact. Moreover, despite a lack of in vivo investigations, plant products are generally reported to have a lower side-effect profile than SOC therapies and are therefore thought to be a safer therapeutic choice. Thus, the current review summarizes the findings from the last five years regarding the anti-aromatase and anti-estrogenic activity of plant products, as well as their synergistic anti-ER+ BC effects in combination with SOC therapies.

Potential of Plant-Derived Compounds in Preventing and Reversing Organ Fibrosis and the Underlying Mechanisms.

Increased production of extracellular matrix is a necessary response to tissue damage and stress. In a normal healing process, the increase in extracellular matrix is transient. In some instances; however, the increase in extracellular matrix can persist as fibrosis, leading to deleterious alterations in organ structure, biomechanical properties, and function. Indeed, fibrosis is now appreciated to be an important cause of mortality and morbidity. Extensive research has illustrated that fibrosis can be slowed, arrested or even reversed; however, few drugs have been approved specifically for anti-fibrotic treatment. This is in part due to the complex pathways responsible for fibrogenesis and the undesirable side effects of drugs targeting these pathways. Natural products have been utilized for thousands of years as a major component of traditional medicine and currently account for almost one-third of drugs used clinically worldwide. A variety of plant-derived compounds have been demonstrated to have preventative or even reversal effects on fibrosis. This review will discuss the effects and the underlying mechanisms of some of the major plant-derived compounds that have been identified to impact fibrosis.

Computer-aided drug discovery of c-Abl kinase inhibitors from plant compounds against chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is a hematological malignancy characterized by the neoplastic transformation of hematopoietic stem cells, driven by the Philadelphia (Ph) chromosome resulting from a translocation between chromosomes 9 and 22. This Ph chromosome harbors the breakpoint cluster region (BCR) and the Abelson (ABL) oncogene (BCR-ABL1) which have a constitutive tyrosine kinase activity. However, the tyrosine kinase activity of BCR-ABL1 have been identified as a key player in CML initiation and maintenance through c-Abl kinase. Despite advancements in tyrosine kinase inhibitors, challenges such as efficacy, safety concerns, and recurring drug resistance persist. This study aims to discover potential c-Abl kinase inhibitors from plant compounds with anti-leukemic properties, employing drug-likeness assessment, molecular docking, in silico pharmacokinetics (ADMET) screening, density function theory (DFT), and molecular dynamics simulations (MDS). Out of 58 screened compounds for drug-likeness, 44 were docked against c-Abl kinase. The top hit compound (isovitexin) and nilotinib (control drug) were subjected to rigorous analyses, including ADMET profiling, DFT evaluation, and MDS for 100 ns. Isovitexin demonstrated a notable binding affinity (-15.492 kcal/mol), closely comparable to nilotinib (-16.826 kcal/mol), showcasing a similar binding pose and superior structural stability and reactivity. While these findings suggest isovitexin as a potential c-Abl kinase inhibitor, further validation through urgent in vitro and in vivo experiments is imperative. This research holds promise for providing an alternative avenue to address existing CML treatment and management challenges.Communicated by Ramaswamy H. Sarma.

Antibacterial activity of plant-derived compounds and cream formulations against canine skin bacteria.

An urgent need to find alternative antimicrobial compounds effective in the prevention and treatment of skin infections led us to study the inhibitory activity of eight plant-derived bioactive compounds (betulin, curcumin, glycyrrhizic acid, guaiazulene, piperine, quercetin, quinine, tannic acid) against 14 canine skin isolates (11 Gram-positive and three Gram-negative bacteria) selected based on antibiotic resistance and virulence features. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) were determined using the broth microdilution method. In detail, the results for the eight different plant compounds showed their inhibitory activity in the concentration range from 0.04 to more than 16 mg/ml (MIC) and from 0.25 to more than 16 mg/ml (MBC). The most potent compounds appear to be tannic acid, followed by quinine and curcumin (MIC 0.04-16.0 mg/ml). The most susceptible strain to the tested agents in general was Bacillus cereus AE13, while Enterococcus faecium AA14 was the most resistant strain (the highest MICs) among the tested bacteria. The two most potent plant-derived compounds (tannic acid and quinine) were tested in mixture in different ratios (1:1, 1:2, 2:1). The lowest MIC and MBC values were observed for the 1:2 ratio, which was used for preparation of creams with different cream bases. One of the cream formulations (cream F) was effective up to 63.0 mg/ml (MIC) with a microbial inactivation time of 1-6 h according to the tested strain. This study provides evidence that some plant-derived compounds could have an antimicrobial effect against canine skin bacteria, the strength of which is bacterial strain dependent.

Synergistic Effect of Plant Compounds in Combination with Conventional Antimicrobials against Biofilm of Staphylococcus aureus, Pseudomonas aeruginosa, and Candida spp.

Bacterial and fungal biofilm has increased antibiotic resistance and plays an essential role in many persistent diseases. Biofilm-associated chronic infections are difficult to treat and reduce the efficacy of medical devices. This global problem has prompted extensive research to find alternative strategies to fight microbial chronic infections. Plant bioactive metabolites with antibiofilm activity are known to be potential resources to alleviate this problem. The phytochemical screening of some medicinal plants showed different active groups, such as stilbenes, tannins, alkaloids, terpenes, polyphenolics, flavonoids, lignans, quinones, and coumarins. Synergistic effects can be observed in the interaction between plant compounds and conventional drugs. This review analyses and summarises the current knowledge on the synergistic effects of plant metabolites in combination with conventional antimicrobials against biofilms of Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. The synergism of conventional antimicrobials with plant compounds can modify and inhibit the mechanisms of acquired resistance, reduce undesirable effects, and obtain an appropriate therapeutic effect at lower doses. A deeper knowledge of these combinations and of their possible antibiofilm targets is needed to develop next-generation novel antimicrobials and/or improve current antimicrobials to fight drug-resistant infections attributed to biofilm.

Tart Cherry (Prunus cerasus L.) Pit Extracts Protect Human Skin Cells against Oxidative Stress: Unlocking Sustainable Uses for Food Industry Byproducts.

Industrial processing of tart cherries (Prunus cerasus L.) produces bioproducts like cherry pits (CP), which contribute to adverse environmental effects. To identify sustainable strategies to minimize the environmental impact of cherry processing, we investigated their potential value as antioxidants for prospective utilization within cosmeceutical applications. Untargeted metabolomic analyses of water and water: ethanol CP extracts using an eco-friendly technique revealed significant enrichment in coumaroyl derivatives and flavonoids with congruent metabolite representation regardless of the extraction solvent. The antioxidant activity of tart CP extracts was evaluated on human skin cells exposed to H2O2 or LPS, modeling environmentally induced oxidants. Notably, both CP extracts provide antioxidant activity by reducing H2O2 or LPS-induced ROS in human skin keratinocytes without affecting cell viability. The CP extracts increased the expression of CAT and SOD1 genes encoding antioxidant regulatory enzymes while decreasing the expression of NOS2, a pro-oxidant regulator. These findings reveal the antioxidant properties of tart CP, offering new opportunities to produce natural-based skin care products and adding economic value while providing sustainable options to reduce the environmental impact of food byproducts.

Red Kale (Brassica oleracea L. ssp. acephala L. var. sabellica) Induces Apoptosis in Human Colorectal Cancer Cells In Vitro.

This article presents the results of studies investigating the effect of red kale (Brassica oleracea L. ssp. acephala L. var. sabellica) extract on cancer cells (HT-29). The cytotoxicity of the red kale extract was assessed using MTT and LDH assays, while qRT-PCR was employed to analyze the expression of genes associated with the p53 signaling pathway to elucidate the effect of the extract on cancer cells. Furthermore, HPLC-ESI-QTOF-MS/MS was applied to identify bioactive compounds present in red kale. The obtained results indicated that red kale extract reduced the viability and suppressed the proliferation of HT-29 cells (the IC50 value of 60.8 µg/mL). Additionally, mRNA expression analysis revealed significant upregulation of several genes, i.e., casp9, mapk10, mapk11, fas, kat2 b, and ubd, suggesting the induction of cell apoptosis through the caspase-dependent pathway. Interestingly, the study revealed a decrease in the expression of genes including cdk2 and cdk4 encoding cell cycle-related proteins, which may lead to cell cycle arrest. Furthermore, the study identified certain bioactive compounds, such as sinigrin, spirostanol, hesperetin and usambarensine, which could potentially contribute to the apoptotic effect of red kale extracts. However, further investigations are necessary to elucidate the specific role of these individual compounds in the anti-cancer process.

Regeneration of Pancreatic Beta Cells by Modulation of Molecular Targets Using Plant-Derived Compounds: Pharmacological Mechanisms and Clinical Potential.

Type 2 diabetes (T2D) is characterized by pancreatic beta-cell dysfunction, increased cell death and loss of beta-cell mass despite chronic treatment. Consequently, there has been growing interest in developing beta cell-centered therapies. Beta-cell regeneration is mediated by augmented beta-cell proliferation, transdifferentiation of other islet cell types to functional beta-like cells or the reprograming of beta-cell progenitors into fully differentiated beta cells. This mediation is orchestrated by beta-cell differentiation transcription factors and the regulation of the cell cycle machinery. This review investigates the beta-cell regenerative potential of antidiabetic plant extracts and phytochemicals. Various preclinical studies, including in vitro, in vivo and ex vivo studies, are highlighted. Further, the potential regenerative mechanisms and the intra and extracellular mediators that are of significance are discussed. Also, the potential of phytochemicals to translate into regenerative therapies for T2D patients is highlighted, and some suggestions regarding future perspectives are made.

A promising natural anthraquinones mediated by photodynamic therapy for anti-cancer therapy.

BACKGROUND: Experimental studies emphasize the therapeutic potential of plant-derived photosensitizers used in photodynamic therapy. Moreover, several in vitro and in vivo research present the promising roles of less-known anthraquinones that can selectively target cancer cells and eliminate them after light irradiation. This literature review summarizes the current knowledge of chosen plant-based-photosensitizers in PDT to show the results of emodin, aloe-emodin, parietin, rubiadin, hypericin, and soranjidiol in photodynamic therapy of cancer treatment and describe the comprehensive perspective of their role as natural photosensitizers. METHODS: Literature searches of chosen anthraquinones were conducted on PubMed.gov with keywords: "emodin", "aloe-emodin", "hypericin", "parietin", "rubiadin", "soranjidiol" with "cancer" and "photodynamic therapy". RESULTS: According to literature data, this review concentrated on all existing in vitro and in vivo studies of emodin, aloe-emodin, parietin, rubiadin, soranjidiol used as natural photosensitizers emphasizing their effectiveness and detailed mechanism of action in anticancer therapy. Moreover, comprehensive preclinical and clinical studies on hypericin reveal that the above-described substances may be included in the phototoxic treatment of different cancers. CONCLUSIONS: Overall, this review presented less-known anthraquinones with their promising molecular mechanisms of action. It is expected that in the future they may be used as natural PSs in cancer treatment as well as hypericin.

Dietary Challenges for Parasitoid Wasps (Hymenoptera: Ichneumonoidea); Coping with Toxic Hosts, or Not?

Many insects defend themselves against predation by being distasteful or toxic. The chemicals involved may be sequestered from their diet or synthesized de novo in the insects' body tissues. Parasitoid wasps are a diverse group of insects that play a critical role in regulating their host insect populations such as lepidopteran caterpillars. The successful parasitization of caterpillars by parasitoid wasps is contingent upon their aptitude for locating and selecting suitable hosts, thereby determining their efficacy in parasitism. However, some hosts can be toxic to parasitoid wasps, which can pose challenges to their survival and reproduction. Caterpillars employ a varied array of defensive mechanisms to safeguard themselves against natural predators, particularly parasitoid wasps. These defenses are deployed pre-emptively, concurrently, or subsequently during encounters with such natural enemies. Caterpillars utilize a range of strategies to evade detection or deter and evade attackers. These tactics encompass both measures to prevent being noticed and mechanisms aimed at repelling or eluding potential threats. Post-attack strategies aim to eliminate or incapacitate the eggs or larvae of parasitoids. In this review, we investigate the dietary challenges faced by parasitoid wasps when encountering toxic hosts. We first summarize the known mechanisms through which insect hosts can be toxic to parasitoids and which protect caterpillars from parasitization. We then discuss the dietary adaptations and physiological mechanisms that parasitoid wasps have evolved to overcome these challenges, such as changes in feeding behavior, detoxification enzymes, and immune responses. We present new analyses of all published parasitoid-host records for the Ichneumonoidea that attack Lepidoptera caterpillars and show that classically toxic host groups are indeed hosts to significantly fewer species of parasitoid than most other lepidopteran groups.

Essential Oils for the Conservation of Paper Items.

Archival documents and artworks stored in libraries frequently undergo degradative processes promoted by the so-called "biodeteriogens" that inhabit these places. A renewed interest in plant-derived products has arisen in those research groups focusing on cultural heritage preservation and looking for new and safe disinfection techniques. In this view, essential oils (EOs) and their volatile organic constituents are very appealing thanks to their versatility of action. A literature survey of the scientific publications involving EOs and/or their major constituents related to the conservation of paper items of cultural heritage interest is presented here, aiming to reveal benefits and limitations of such peculiar plant-derived compounds.

Discovery of Terpenes as Novel HCV NS5B Polymerase Inhibitors via Molecular Docking.

Hepatitis C virus (HCV) is a dangerous virus that is responsible for a large number of infections and deaths worldwide. In the treatment of HCV, it is important that the drugs are effective and do not have additional hepatotoxic effects. The aim of this study was to test the in silico activity of 1893 terpenes against the HCV NS5B polymerase (PDB-ID: 3FQK). Two drugs, sofosbuvir and dasabuvir, were used as controls. The GOLD software (CCDC) and InstaDock were used for docking. By using the results obtained from PLP.Fitness (GOLD), pKi, and binding free energy (InstaDock), nine terpenes were finally selected based on their scores. The drug-likeness properties were calculated using Lipinski's rule of five. The ADMET values were studied using SwissADME and pkCSM servers. Ultimately, it was shown that nine terpenes have better docking results than sofosbuvir and dasabuvir. These were gniditrin, mulberrofuran G, cochlearine A, ingenol dibenzoate, mulberrofuran G, isogemichalcone C, pawhuskin B, 3-cinnamyl-4-oxoretinoic acid, DTXSID501019279, and mezerein. Each docked complex was submitted to 150 ns-long molecular dynamics simulations to ascertain the binding stability. The results show that mulberrofuran G, cochlearine A, and both stereoisomers of pawhuskin B form very stable interactions with the active site region where the reaction product should form and are, therefore, good candidates for use as effective competitive inhibitors. The other compounds identified in the docking screen either afford extremely weak (or even hardly any) binding (such as ingenol dibenzoate, gniditrin, and mezerein) or must first undergo preliminary movements in the active site before attaining their stable binding conformations, in a process which may take from 60 to 80 ns (for DTXSID501019279, 3-cinnamyl-4-oxoretinoic acid or isogemichalcone C).

Computer Analysis of the Inhibition of ACE2 by Flavonoids and Identification of Their Potential Antiviral Pharmacophore Site.

In the present study, we investigated the antiviral activities of 17 flavonoids as natural products. These derivatives were evaluated for their in vitro antiviral activities against HIV and SARS-CoV-2. Their antiviral activity was evaluated for the first time based on POM (Petra/Osiris/Molispiration) theory and docking analysis. POM calculation was used to analyze the atomic charge and geometric characteristics. The side effects, drug similarities, and drug scores were also assumed for the stable structure of each compound. These results correlated with the experimental values. The bioinformatics POM analyses of the relative antiviral activities of these derivatives are reported for the first time.

Anti-BVDV Activity of Traditional Chinese Medicine Monomers Targeting NS5B (RNA-Dependent RNA Polymerase) In Vitro and In Vivo.

Natural products have emerged as "rising stars" for treating viral diseases and useful chemical scaffolds for developing effective therapeutic agents. The nonstructural protein NS5B (RNA-dependent RNA polymerase) of NADL strain BVDV was used as the action target based on a molecular docking technique to screen herbal monomers for anti-BVDV viral activity. The in vivo and in vitro anti-BVDV virus activity studies screened the Chinese herbal monomers with significant anti-BVDV virus effects, and their antiviral mechanisms were initially explored. The molecular docking screening showed that daidzein, curcumin, artemisinine, and apigenin could interact with BVDV-NADL-NS5B with the best binding energy fraction. In vitro and in vivo tests demonstrated that none of the four herbal monomers significantly affected MDBK cell activity. Daidzein and apigenin affected BVDV virus replication mainly in the attachment and internalization phases, artemisinine mainly in the replication phase, and curcumin was active in the attachment, internalization, replication, and release phases. In vivo tests demonstrated that daidzein was the most effective in preventing and protecting BALB/C mice from BVDV infection, and artemisinine was the most effective in treating BVDV infection. This study lays the foundation for developing targeted Chinese pharmaceutical formulations against the BVDV virus.

Effect of Hypericin-Mediated Photodynamic Therapy on the Secretion of Soluble TNF Receptors by Oral Cancer Cells.

Squamous cell carcinoma is the most common cancer of the head and neck region. In addition to the classic surgical treatment method, alternative therapy methods are sought. One such method is photodynamic therapy (PDT). In addition to the direct cytotoxic effect, it is essential to determine the effect of PDT on persistent tumor cells. The study used the SCC-25 oral squamous cell carcinoma (OSCC) cell line and the HGF-1 healthy gingival fibroblast line. A compound of natural origin-hypericin (HY)-was used as a photosensitizer (PS) at concentrations of 0-1 µM. After two hours of incubation with the PS, the cells were irradiated with light doses of 0-20 J/cm2. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) test was used to determine sublethal doses of PDT. Cell supernatants subjected to sublethal PDT were assessed for soluble tumor necrosis alpha receptors (sTNF-R1, sTNF-R2). The phototoxic effect was observed starting with a light dose of 5 J/cm2 and amplified with the increase in HY concentration and light dose. A statistically significant increase in sTNF-R1 secretion by SCC-25 cells was demonstrated after the PDT with 0.5 µM HY and irradiation with 2 J/cm2 (sTNF-R1 concentration = 189.19 pg/mL ± 2.60) compared to the control without HY and irradiated with the same dose of light (sTNF-R1 concentration = 108.94 pg/mL ± 0.99). The baseline production of sTNF-R1 was lower for HGF-1 than for SCC-25, and secretion was not affected by the PDT. The PDT had no effect on the sTNF-R2 production in the SCC-25 or HGF-1 lines.

Parasites as ecosystem modulators: foliar pathogens suppress top-down effects of large herbivores.

Parasites can catalyze or inhibit interactions between their hosts and other species, but the ecosystem-level effects of such interaction modifications are poorly understood. We conducted a large-scale field experiment in temperate grasslands of China to understand how foliar fungal pathogens influenced top-down effects of cattle on plant diversity and productivity. When foliar pathogens were suppressed, cattle grazing strongly reduced biomass of the dominant grass, Leymus chinensis, generating competitive release that significantly increased community-level species richness and evenness. In the absence of grazing, pathogen attack on L. chinensis had no measurable effect on host biomass. However, pathogens disrupted top-down effects of herbivory by inhibiting grazing effects on plant biomass and species richness. Mechanistically, fungal pathogens were linked to increased alkaloid and reduced nitrogen levels in leaf tissue, which appeared to deter cattle grazing on L. chinensis. In conclusion, foliar pathogens can suppress top-down effects of large herbivores on grassland community composition and ecosystem function by modifying the strength of their host's interactions with dominant consumers. Parasites may act as modulators of ecosystem function when their direct effects on host abundance are overshadowed by powerful influences on host traits that modify their interactions with competitors, herbivores, or predators.

Medicinal plants as a source of antiparasitics: an overview of experimental studies.

Despite advances in modern human and veterinary medicine, gastrointestinal (GI) parasitic infections remain a significant health issue worldwide, mainly in developing countries. Increasing evidence of the multi-drug resistance of these parasites and the side effects of currently available synthetic drugs have led to increased research on alternative medicines to treat parasitic infections. The exploration of potential botanical antiparasitics, which are inexpensive and abundant, may be a promising alternative in this context. This study summarizes the in vitro/in vivo antiparasitic efficacy of different medicinal plants and their components against GI parasites. Published literature from 1990-2020 was retrieved from Google Scholar, Web of Science, PubMed and Scopus. A total of 68 plant species belonging to 32 families have been evaluated as antiparasitic agents against GI parasites worldwide. The majority of studies (70%) were conducted in vitro. Most plants were from the Fabaceae family (53%, n = 18). Methanol (37%, n = 35) was the most used solvent. Leaf (22%, n = 16) was the most used plant part, followed by seed and rhizome (each 12%, n = 9). These studies suggest that herbal medicines hold a great scope for new drug discoveries against parasitic diseases and that the derivatives of these plants are useful structures for drug synthesis and bioactivity optimization.