Search For Natural Products Research Articles

An evaluative review on Stryphnodendron adstringens extract composition: Current and future perspectives on extraction and application

The search for natural products as an alternative to synthetic products has increased. This trend is mainly due to the health concerns of people searching for a better quality of life. In this context, obtaining bioactive compounds from vegetable matrices is a promising strategy for industrial applications like pharmaceuticals and food. Stryphnodendron adstringens (Mart.) Coville (popularly known as Barbatimão in Brazil) is a tree used in folk medicine due to its anti-inflammatory, analgesic, antiseptic, and wound healing properties. Its barks and leaves present a wide range of bioactive compounds, mainly phenolic acids , flavonoids , and tannins . The extraction of such compounds can be performed using various methods. However, specific knowledge to select the technique to obtain and concentrate the compounds is essential to obtain an extract of high purity. In addition, there is a current necessity to describe the whole production chain as sustainable. Therefore, this review aims to bring updated information on current research with Barbatimão extracts. The biological activities of the extracts are related to the extract composition. Additionally, the extraction techniques used for different parts of Barbatimão , as well as their chemical composition, are also discussed. Finally, future perspectives are provided to demonstrate the current gaps in scientific research with Barbatimão and encourage future investigations to open possibilities for the use of this species. • The main phenolic compounds were highlighted for the Stryphnodendron adstringens . • Extraction techniques that have already been used were described. • Possible applications of Barbatimão extracts were presented. • Gaps in the application of emerging extraction techniques are pointed out. • Barbatimão has potential for studies aimed at medicinal applications.

Further investigation of blockade effects and binding affinities of selected natural compounds to immune checkpoint PD-1/PD-L1.

The breakthrough in the discovery of immune checkpoint PD-1/PD-L1 inhibitors, such as the series of Bristol Myers Squibb synthetic compounds, boosted the research of small molecules with blockade effects on the interaction of PD-1/PD-L1. However, the search for natural products derived PD-1/PD-L1 inhibitors can be impeded by the false positive and/or negative results from the screening assays. Herein, we combined a PD-1/PD-L1 blockade assay (pair ELISA) and a PD-L1/PD-L1 binding assay (surface plasmon resonance; SPR) to evaluate a panel of natural compounds previously reported to show anti-PD-1/PD-L1 activity. The test compounds included kaempferol, cosmosiin, tannic acid, pentagalloyl glucose, ellagic acid, resveratrol, urolithin A, and rifubutin. Based on the analyses of their responses to the combined screening assays, these compounds were categorized into four groups: I) PD-1/PD-L1 inhibitors that can bind to PD-1 and PD-L1; II) PD-1/PD-L1 inhibitors selectively bind to PD-L1 protein; III) PD-1/PD-L1 inhibitors without binding capacity, and IV) PD-1/PD-L1 binders without blockade effect. Discrimination of positive responders in the PD-1/PD-L1 blockade and binding assays can provide useful insights to avoid false outcomes. Examples demonstrated in this study suggest that it is crucial to adopt proper evaluation methods (including using multiple-facet functional assays and target binding techniques) for the search for natural products derived PD-1/PD-L1 inhibitors.

Pharmacological effects of an aqueous leaf extract of Lophira lanceolata (Ochnaceae) on blood pressure and electrocardiogram in anesthetized rabbits

Arterial hypertension is a cardiovascular disease prevalent in black African countries. Its prevalence is 5 to 20% in sub-Sahara African countries and 20% in Côte d'Ivoire. Despite the variety of antihypertensive drugs available in modern medicine, the disease persists. Hence the search for natural products with potential anti-hypertensive properties is ongoing. This study focused on the effects of aqueous leaf extract of Lophira lanceolata on the arterial blood pressure (BP) and electrocardiography (ECG) in rabbits. Phytochemical analysis was carried out in order to determine the phytoconstituents contained in the extract. Varied L. lanceolata macerate doses (0.5 to 50 mg/kg bw) were administered to anesthetized rabbits intravenously. The carotid artery was intubated using a catheter connected to Ludwig's mercury manometer for BP measurement. The recording of the ECG was performed using an electrocardiograph. The phytochemical screening revealed the presence of phytoconstituents including polyphenols, flavonoids and alkaloids in L. lanceolata. The results showed that L. lanceolata induced a dose-dependent hypotension with a fifty percent effective dose (ED50) equal to 5.36 mg/kg bw. in normotensive rabbits. The hypotension induced by the extract was significantly (p<0.01) reduced up to 60% by atropine, an acetylcholine muscarinic receptor antagonist. In addition, the extract significantly (p<0.001) decreased the hypertension induced in rabbits with adrenaline up to 70%. On the ECG, the extract caused significant decreases (p<0.001) of the amplitudes of the P waves, T waves, the QRS complex and the PQ and QT intervals. However, the heart rate increased significantly (p<0.001). The usefulness of L. lanceolata in traditional medicine for the treatment of hypertension is potentiated. It is therefore important to encourage its use.

Plasmopara viticola the Causal Agent of Downy Mildew of Grapevine: From Its Taxonomy to Disease Management.

Plasmopara viticola (P. viticola, Berk. & M. A. Curtis; Berl. & De Toni) causing grapevine downy mildew is one of the most damaging pathogens to viticulture worldwide. Since its recognition in the middle of nineteenth century, this disease has spread from America to Europe and then to all grapevine-growing countries, leading to significant economic losses due to the lack of efficient disease control. In 1885 copper was found to suppress many pathogens, and is still the most effective way to control downy mildews. During the twentieth century, contact and penetrating single-site fungicides have been developed for use against plant pathogens including downy mildews, but wide application has led to the appearance of pathogenic strains resistant to these treatments. Additionally, due to the negative environmental impact of chemical pesticides, the European Union restricted their use, triggering a rush to develop alternative tools such as resistant cultivars breeding, creation of new active ingredients, search for natural products and biocontrol agents that can be applied alone or in combination to kill the pathogen or mitigate its effect. This review summarizes data about the history, distribution, epidemiology, taxonomy, morphology, reproduction and infection mechanisms, symptoms, host-pathogen interactions, host resistance and control of the P. viticola, with a focus on sustainable methods, especially the use of biocontrol agents.

Anti-Inflammatory Effect of Vanillin Protects the Stomach against Ulcer Formation.

Gastric ulcer is one of the most frequent gastrointestinal disorders, and there is an increasing search for natural products that can heal ulcers and avoid their recurrence. We aimed to evaluate the gastroprotective activity of vanillin, including the investigation of anti-inflammatory activity and the modulation of gene expression. Wistar rats were orally treated with vehicle, carbenoxolone, or vanillin (25, 50, or 100 mg/kg) and orally received absolute ethanol to develop gastric ulcers. We analyzed the ulcer area, conducted histological analysis, and measured the levels of the inflammatory cytokines TNF-α, IL-6, IL-1β, and IFN-γ, and anti-inflammatory cytokine IL-10 by ELISA. We analyzed mRNA expression for NF-κB, TNF-α, and Il-10. We measured NOx levels using the Griess reaction. Our results showed similar gastroprotection for the three doses. Vanillin increased mucus production and preserved gastric mucosa integrity. The gastroprotective effect was linked to anti-inflammatory activity as a result of decreasing the levels of TNF-α, IL-6, IL-1β, and IFN-γ and increasing IL-10 levels. Vanillin downregulated the mRNA expression of NF-κB and TNF-α, upregulated the mRNA expression of Il-10, and increased NOx levels in the stomach. The gastroprotective activity of vanillin is related to the maintenance of gastric mucus and the local inflammatory response modulation.

Epigenetic Strategies to Discover Novel Fungal Secondary Metabolites

Natural product search is an enduring revitalization upon the exploration of a huge already exotic potential for Secondary Metabolite (SM) production obscure in microbial genomes. Filamentous fungi genomes have an immense number of “orphan” SM gene clusters. Current evaluation indicates that only 5% of extant fungal species have been explored, thus the apparent for the disclosure of novel metabolites in fungi is extensive. In this situation, fungi burgeoning in severe environments are of special interest since they are distinguished producers of astonishing chemical structures. Genome mining strategies, more specifically epigenetic strategies are playing an important role in natural product discovery. This review has been organized and written to focus on available epigenetic approaches, targeting on DNA methyltransferase and histone deacetylase inhibitors along with reported novel secondary metabolites. To the best of our knowledge, this review article is the first attempt to incorporate the facts regarding DNA methyltransferase inhibitors and histone deacetylase inhibitors along with reported novel secondary metabolites with their recorded bioactivities.

Neural Signature of Buying Decisions in Real-World Online Shopping Scenarios - An Exploratory Electroencephalography Study Series.

The neural underpinnings of decision-making are critical to understanding and predicting human behavior. However, findings from decision neuroscience are limited in their practical applicability due to the gap between experimental decision-making paradigms and real-world choices. The present manuscript investigates the neural markers of buying decisions in a fully natural purchase setting: participants are asked to use their favorite online shopping applications to buy common goods they are currently in need of. Their electroencephalography (EEG) is recorded while they view the product page for each item. EEG responses to pages for products that are eventually bought are compared to those that are discarded. Study 1 repeats this procedure in three batches with different participants, product types, and time periods. In an explorative analysis, two neural markers for buying compared to no-buying decisions are discovered over all three batches: frontal alpha asymmetry peak and frontal theta power peak. Occipital alpha power at alpha asymmetry peaks differs in only one of the three batches. No further significant markers are found. Study 2 compares the natural product search to a design in which subjects are told which product pages to view. In both settings, the frontal alpha asymmetry peak is increased for buying decisions. Frontal theta peak increase is replicated only when subjects search through product pages by themselves. The present study series represents an attempt to find neural markers of real-world decisions in a fully natural environment and explore how those markers can change due to small adjustments for the sake of experimental control. Limitations and practical applicability of the real-world approach to studying decision-making are discussed.

Himalayan Ethnobotanical Exploration: An Overview of Selected Studies of Kangra District in Himachal Pradesh

Ethnobotany gives an understanding of interrelationships between people and plants. It deals with the documentation of the indigenous traditional knowledge of plants possessed by ethnic people and primitive communities who also are the custodians of this knowledge. They practice the traditional way of treatment for various ailments. Now, this knowledge holds both cultural as well as scientific value. The ethnobotanical knowledge also provides the source for the discovery of many drugs. Usage of Himalayan plant species for food and medicine has been well known for a long time. This knowledge is depleting rapidly in recent times due to globalization and modernization. This investigation provides ethnobotanical information from selected studies that truly focuses on the traditional medicinal plants used by the local people of the Kangra district. Information for the present study was collected through publications available on the ethnobotanical studies of the area. These studies provide relevant literature and inventories of useful plants. As the search for natural products and new drugs from plants is an important element, it becomes important to create awareness about biodiversity conservation as well as their role in healthcare. Measures are needed to support biodiversity prospecting and for conserving useful plants which are harvested only from the wild. Paying special attention to sustainable use of the ethnomedicinal plants found in the area may help lessen the impact of harvesting specific plant resources.

Short Overview of Some Assays for the Measurement of Antioxidant Activity of Natural Products and Their Relevance in Dermatology

Impaired systemic redox homeostasis is implicated in the onset and development of various diseases, including skin diseases. Therefore, continuous search for natural products with antioxidant bioactivities applicable in biomedicine is attractive topic of general interest. Research efforts aiming to validate antioxidant potentials of natural products has led to the development of several assays based on various test principles. Hence, understanding the advantages and limitations of various assays is important for selection of assays useful to study antioxidant and related bioactivities of natural products of biomedical interest. This review paper gives a short overview on some chemical and cellular bioassays used to estimate the antioxidant activity of chosen natural products together with a brief overview on the use of natural products with antioxidant activities as adjuvant medicinal remedies in dermatology.

Fungal Biofilms as a Valuable Target for the Discovery of Natural Products That Cope with the Resistance of Medically Important Fungi-Latest Findings.

The development of new antifungal agents that target biofilms is an urgent need. Natural products, mainly from the plant kingdom, represent an invaluable source of these entities. The present review provides an update (2017–May 2021) on the available information on essential oils, propolis, extracts from plants, algae, lichens and microorganisms, compounds from different natural sources and nanosystems containing natural products with the capacity to in vitro or in vivo modulate fungal biofilms. The search yielded 42 articles; seven involved essential oils, two Brazilian propolis, six plant extracts and one of each, extracts from lichens and algae/cyanobacteria. Twenty articles deal with the antibiofilm effect of pure natural compounds, with 10 of them including studies of the mechanism of action and five dealing with natural compounds included in nanosystems. Thirty-seven manuscripts evaluated Candida spp. biofilms and two tested Fusarium and Cryptococcus spp. Only one manuscript involved Aspergillus fumigatus. From the data presented here, it is clear that the search of natural products with activity against fungal biofilms has been a highly active area of research in recent years. However, it also reveals the necessity of deepening the studies by (i) evaluating the effect of natural products on biofilms formed by the newly emerged and worrisome health-care associated fungi, C. auris, as well as on other non-albicans Candida spp., Cryptococcus sp. and filamentous fungi; (ii) elucidating the mechanisms of action of the most active natural products; (iii) increasing the in vivo testing.

Therapeutic Applications of Terpenes on Inflammatory Diseases.

In the last decades, the search for natural products with biological applications as alternative treatments for several inflammatory diseases has increased. In this respect, terpenes are a family of organic compounds obtained mainly from plants and trees, such as tea, cannabis, thyme, and citrus fruits like lemon or mandarin. These molecules present attractive biological properties such as analgesic and anticonvulsant activities. Furthermore, several studies have demonstrated that certain terpenes could reduce inflammation symptoms by decreasing the release of pro-inflammatory cytokines for example, the nuclear transcription factor-kappa B, interleukin 1, and the tumor necrosis factor-alpha. Thus, due to various anti-inflammatory drugs provoking side effects, the search and analysis of novel therapeutics treatments are attractive. In this review, the analysis of terpenes’ chemical structure and their mechanisms in anti-inflammatory functions are addressed. Additionally, we present a general analysis of recent investigations about their applications as an alternative treatment for inflammatory diseases. Furthermore, we focus on terpenes-based nanoformulations and employed dosages to offer a global perspective of the state-of-the-art.

Application of microalgae and microalgal bioactive compounds in skin regeneration

The search for natural products with benefits for skin regeneration has gained a much broader interest worldwide. Microalgae represent a natural source of interesting bioactive compounds with an impact on wound-healing applications. The potential beneficial effects of microalgal carotenoids, polyunsaturated fatty acids, polysaccharides, and crude extracts have been reported in wound-healing applications due to their different biological activities, namely: i) the quenching of reactive oxygen species; ii) the suppression of the production of inflammatory cytokines and transduction cascades, and iii) the prevention of the microbial growth at the wound site. Wound dressings based on microalgae, and their bioactive compounds, which are aimed at being used in the treatment of skin injuries, are reviewed. Finally, the emerging strategies in the production of live microalgae-based photosynthetic scaffolds for skin regeneration are also outlined.

Citrullus colocynthis Seeds: A Potential Natural Immune Modulator Source for Broiler Reared under Chronic Heat Stress.

Simple SummaryChronic heat-stress exposure directly affects broiler immune response. Immunosuppression was demonstrated in broiler exposed to chronic heat stress with deterioration in humoral and cell-mediated immune responses. Natural immune modulator material is considered as a safe material for human consumption of poultry products. Citrullus colocynthis (CC) is a natural herb plant that has traditionally been used in folk remediation. Anti-diabetic, antioxidant, and anti-inflammatory attributes are some of the CC medical properties. The present study aims to investigate the immune modulator potentials of CC seeds supplementation to chronically heat- stressed-exposed broilers. Results demonstrated that CC seeds supplementation to heat-stressed broilers was able to alleviate the negative impacts of heat stress on broiler immune responses and antioxidant status. Thus, CC seeds are suggested to be added to broilers reared under heat stress in order to improve the immune response and consequently ameliorate productivity.There is an extensive search for natural products that can be introduced to broiler rations to improve performance, especially during the unfavorable breeding conditions. Under heat-stress conditions, the immune response seriously deteriorates, which consequently impairs broiler production performance. Thus, the present study aimed to investigate the potentials of Citrullus colocynthis seeds (CCs) supplementation to modulate the immune response of broilers subjected to chronic heat stress. A total of 300 Cobb-500 male broiler chickens aged 21 days were randomly divided into two equal groups and reared under either thermo-neutral condition (24 ± 1 °C) or subjected to cyclic heat stress (34 ± 1 °C for 8 h). Each group was further divided into two groups (5 replicate × 15 chicks) and was fed either the basal diet or the basal diet with 0.1% CCs supplementation. The results showed that heat stress impaired the production performance by lowering the final body weight and feed intake as well as impairing feed conversion. The levels of stress markers (i.e., malondialdehyde, tumor necrosis factor-α and corticosterone) increased (p < 0.05), whereas the activity of antioxidant enzymes decreased in broilers exposed to heat stress. Further, heat stress caused direct suppression of broiler humoral and cell-mediated immune responses. The stimulating index of T and B lymphocytes proliferation, as well as the antibody titer against sheep red blood cells, were significantly (p < 0.05) reduced by heat-stress exposure. However, CCs supplementation to broilers subjected to heat stress improved (p < 0.05) the final body weight, feed intake, and feed conversion ratio (FCR), compared to the non-supplemented stressed group. The cellular and cell-mediated immune response indicators significantly enhanced (p < 0.05) with CCs supplementation. Supplementation of CCs to broilers reared under similar environmental conditions elevated the total white blood cells (TWBCs) count and the broiler stimulating index of T and B lymphocytes. It can be concluded that CC seeds can be effectively used to stimulate the immune response and improve the production performance of broilers reared under heat-stress condition.

Chemical Inhibition of the Macrophage Inhibitor Factor (MIF) Induces Cell Cycle Arrest and Apoptosis in Lymphoid and Myeloid Leukemia

More selective and less toxic chemotherapeutic agents are needed as frontline treatments in high-risk patients and as salvage agents in relapse disease. In a search for natural products with anti-cancer activity, we previously reported that the isothiocyanate sulforaphane has anti-leukemic properties in pediatric T- and B-cell acute lymphoblastic leukemia by inducing G2/M cell cycle arrest and apoptosis (PLOS ONE, 2012). We hypothesized that sulforaphane forms adducts in leukemia cells resulting in the inactivation of proteins required for survival. Here we report that the macrophage inhibitor factor (MIF) is targeted by sulforaphane in lymphoid leukemia cells. Taking advantage of the electrophilic carbon of isothiocyanate (N=C=S) group in sulforaphane that spontaneously forms thionacyl adducts with sulfhydryl groups of cellular proteins, we performed a cell displacement assay by competition of a biotinylated derivative isothiocyanate with an excess (100 μM) of sulforaphane. Immunoblots showed loss of the biotin label in the macrophage inhibitor factor (MIF) by pre-incubation with sulforaphane in Nalm-6 (B-ALL) and KOPTK1 (T-ALL) cell lines. Although MIF has been targeted in colon cancer, gallbladder cancer, thyroid and squamous carcinomas, the anti-leukemic properties of MIF inhibition in blood cancers have not been explored yet. Prior to testing the effect of MIF inhibition with small molecules, we confirmed that MIF and its receptor CD74 are expressed in a panel of lymphoid (Nalm-6, REH, RS4, Jurkat, DND41, KOPTK-1) and myeloid (K562, HL60, U937, Kasumi, HEL) cell lines. The selective MIF inhibitor 4-iodo-6-phenylpyrimidine (4-IPP) induced cell death in a dose-dependent manner in myeloid and lymphoid cell lines but not significantly in LCL lymphoblastoid cells used as non-leukemic control; acute lymphoblastic leukemia cell lines were more sensitive to 4-IPP inhibition than myeloid leukemia cell lines. Annexin V staining showed increased apoptosis upon treatment with 4-IPP and analysis of DNA content by propidium iodide staining revealed a dose dependent arrest in S-phase. In contrast to sulforaphane and consistent with a cell cycle deregulation, immunoblot analysis showed increased cyclin E1 and a reduction of Cyclin B1. Finally, the capacity of 4-IPP to control leukemia burden in vivo will be evaluated in a cell-based xenograft model. Altogether, MIF emerges as a novel therapeutic target in leukemia that can be targeted with small molecule inhibitors. DisclosuresNo relevant conflicts of interest to declare.

Metabolomics Technologies for the Identification and Quantification of Dietary Phenolic Compound Metabolites: An Overview.

In the search for natural products with properties that may protect against or slow down chronic and degenerative diseases (e.g., cancer, and cardiovascular and neurodegenerative conditions), phenolic compounds (PC) with benefits for human health have been identified. The biological effects of PC in vivo depend on their bioavailability, intestinal absorption, metabolism, and interaction with target tissues. The identification of phenolic compounds metabolites (PCM), in biological samples, after food ingestion rich in PC is a first step to understand the overall effect on human health. However, their wide range of physicochemical properties, levels of abundance, and lack of reference standards, renders its identification and quantification a challenging task for existing analytical platforms. The most frequent approaches to metabolomics analysis combine mass spectrometry and NMR, parallel technologies that provide an overview of the metabolome and high-power compound elucidation. In this scenario, the aim of this review is to summarize the pre-analytical separation processes for plasma and urine samples and the technologies applied in quantitative and qualitative analysis of PCM. Additionally, a comparison of targeted and non-targeted approaches is presented, not available in previous reviews, which may be useful for future metabolomics studies of PCM.

Antimicrobials from Medicinal Plants: An Emergent Strategy to Control Oral Biofilms

Oral microbial biofilms, directly related to oral diseases, particularly caries and periodontitis, exhibit virulence factors that include acidification of the oral microenvironment and the formation of biofilm enriched with exopolysaccharides, characteristics and common mechanisms that, ultimately, justify the increase in antibiotics resistance. In this line, the search for natural products, mainly obtained through plants, and derived compounds with bioactive potential, endorse unique biological properties in the prevention of colonization, adhesion, and growth of oral bacteria. The present review aims to provide a critical and comprehensive view of the in vitro antibiofilm activity of various medicinal plants, revealing numerous species with antimicrobial properties, among which, twenty-four with biofilm inhibition/reduction percentages greater than 95%. In particular, the essential oils of Cymbopogon citratus (DC.) Stapf and Lippia alba (Mill.) seem to be the most promising in fighting microbial biofilm in Streptococcus mutans, given their high capacity to reduce biofilm at low concentrations.

Antimicrobial properties of marine fungi from sponges and brown algae of Mauritius

ABSTRACT Purpose of the study: Marine fungi of Mauritius have been poorly studied. There are numerous reports on the bioactive secondary metabolites that are produced by fungi around the world. Yet, research on the molecular characterisation and the pharmaceutical potential of marine fungi in Mauritius is rather scanty. Method: The samples, which consisted of three sponges Haliclona sp., Iotrochota sp. and Biemna sp. and two brown algae Turbinaria conoides and Sargassum portierianum, were collected in the North of Mauritius during winter. No sporulating structures were observed from the fungal cultures making morphological analysis impossible. The molecular characterisation of the selected isolates was carried out by the amplification of the ITS regions and phylogenetic analysis. The antimicrobial properties were then determined using the disc diffusion and the minimum inhibitory concentration (MIC) assay. Results: Genus level identification was made from molecular data and for some isolates, species-level identification was even possible. Twelve fungi that showed the best antimicrobial properties were identified as Peniophora sp., Aspergillus cristatus, Acremonium sp., Cordyceps memorabilis, Aspergillus ochraceus, Biscogniauxia sp., Aspergillus keratitidis, Exserohilum rostratum, Chromocleista sp., Nigrospora oryzae, Aspergillus flavipes and Mycosphaerella. The lowest MIC result of 0.0098 mg/mL was obtained with Chromocleista sp. mycelium extract against Staphylococcus aureus. The MIC of the mycelium extracts was lower than the broth extracts for most isolates indicating that the antimicrobial compounds are not secreted. Conclusion: Marine fungi from the Mauritian waters have immense potential in the search for natural products against antibiotic-resistant bacteria.

Potential Application of Plant-Based Functional Foods in the Development of Immune Boosters.

Immune dysfunction, which is responsible for the development of human diseases including cancer, is caused by a variety of factors. Therefore, regulation of the factors influencing the immune response is a potentially effective strategy to counter diseases. Presently, several immune adjuvants are used in clinical practice to enhance the immune response and host defense ability; however, synthetic drugs can exert negative side effects. Thus, the search for natural products of plant origin as new leads for the development of potent and safe immune boosters is gaining considerable research interest. Plant-based functional foods have been shown to exert several immunomodulatory effects in humans; therefore, the application of new agents to enhance immunological and specific host defenses is a promising approach. In this comprehensive review, we have provided an up-to-date report on the use as well as the known and potential mechanisms of bioactive compounds obtained from plant-based functional foods as natural immune boosters. Plant-based bioactive compounds promote immunity through multiple mechanisms, including influencing the immune organs, cellular immunity, humoral immunity, nonspecific immunity, and immune-related signal transduction pathways. Enhancement of the immune response in a natural manner represents an excellent prospect for disease prevention and treatment and is worthy of further research and development using approaches of modern science and technology.

Receptor-Based Pharmacophore Modeling in the Search for Natural Products for COVID-19 Mpro.

Considering the urgency of the COVID-19 pandemic, we developed a receptor-based pharmacophore model for identifying FDA-approved drugs and hits from natural products. The COVID-19 main protease (Mpro) was selected for the development of the pharmacophore model. The model consisted of a hydrogen bond acceptor, donor, and hydrophobic features. These features demonstrated good corroboration with a previously reported model that was used to validate the present model, showing an RMSD value of 0.32. The virtual screening was carried out using the ZINC database. A set of 208,000 hits was extracted and filtered using the ligand pharmacophore mapping, applying the lead-like properties. Lipinski’s filter and the fit value filter were used to minimize hits to the top 2000. Simultaneous docking was carried out for 200 hits for natural drugs belonging to the FDA-approved drug database. The top 28 hits from these experiments, with promising predicted pharmacodynamic and pharmacokinetic properties, are reported here. To optimize these hits as Mpro inhibitors and potential treatment options for COVID-19, bench work investigations are needed.

N-Benzyl-linoleamide, a Constituent of Lepidium meyenii (Maca), Is an Orally Bioavailable Soluble Epoxide Hydrolase Inhibitor That Alleviates Inflammatory Pain.

Lepidium meyenii (maca), a plant indigenous to the Peruvian Andes, recently has been utilized globally for claimed health or recreational benefits. The search for natural products that inhibit soluble epoxide hydrolase (sEH), with therapeutically relevant potencies and concentrations, led to the present study on bioactive amide secondary metabolites found in L. meyenii, the macamides. Based on known and suspected macamides, 19 possible macamides were synthesized and characterized. The majority of these amides displayed excellent inhibitory potency (IC50 ≈ 20-300 nM) toward the recombinant mouse, rat, and human sEH. Quantitative analysis of commercial maca products revealed that certain products contain known macamides (1-5, 8-12) at therapeutically relevant total concentrations (≥3.29 mg/g of root), while the inhibitory potency of L. meyenii extracts directly correlates with the sum of concentration/IC50 ratios of macamides present. Considering both its in vitro efficacy and high abundance in commercial products, N-benzyl-linoleamide (4) was identified as a particularly relevant macamide that can be utilized for in vivo studies. Following oral administration in the rat, compound 4 not only displayed acceptable pharmacokinetic characteristics but effectively reduced lipopolysaccharide-induced inflammatory pain. Inhibition of sEH by macamides provides a plausible biological mechanism of action to account for several beneficial effects previously observed with L. meyenii treatments.