Medicinal Natural Products Research Articles

Antioxidant, Antibacterial, and Phytochemical Screening of Ethanolic Crude Extracts of Libyan Peganum harmala Seeds

Peganum harmala is one of the most famous medicinal plants and natural products commonly used in traditional medicine and extensively spread in Middle and East Asia and North Africa. This study aimed to evaluate the radical scavenging activity of ethanolic crude extracts of P. harmala seeds from Libya using DPPH assay; to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentrations (MBC) of the P. harmala seeds crude extracts against Gram-negative Salmonella typhi ATCC14028 and Escherichia coli ATCC 25922 and also Gram-positive Bacillus subtilis ATCC 6633 and Staphylococcus aureus ATCC 33591; and to screen the phytochemicals in the ethanolic crude extracts of the Libyan P. harmala seeds using gas chromatography-mass spectrometry (GC-MS). The IC50 value of P. harmala seeds extract was 179.62±7.32 μg/mL. The MIC ranged from 1.95 to 31.25 mg/mL while the MBC ranged from 7.80 to 62.50 mg/mL. The eight compounds identified were harmine, harmaline, leptalorine, hexahydro fluorene, 3-methoxy-6-methyl, 1H-pyrido [3,4-b]indole,2,34,9- tetrahydro-6methoxy-1-methyl, 9,12-octadienoic acid ethyl ester, linoleic acid ethyl ester, 9,12-octadienoic acid (z,z). This study has, therefore, revealed the antixodant and antibacterial efficacy of P. harmala ethanolic extract. Thus, it could be further developed as a substitute for chemical antioxidants and as antibacterials agent.

Modeling Pharmacokinetic Natural Product-Drug Interactions for Decision-Making: A NaPDI Center Recommended Approach.

The popularity of botanical and other purported medicinal natural products (NPs) continues to grow, especially among patients with chronic illnesses and patients managed on complex prescription drug regimens. With few exceptions, the risk of a given NP to precipitate a clinically significant pharmacokinetic NP-drug interaction (NPDI) remains understudied or unknown. Application of static or dynamic mathematical models to predict and/or simulate NPDIs can provide critical information about the potential clinical significance of these complex interactions. However, methods used to conduct such predictions or simulations are highly variable. Additionally, published reports using mathematical models to interrogate NPDIs are not always sufficiently detailed to ensure reproducibility. Consequently, guidelines are needed to inform the conduct and reporting of these modeling efforts. This recommended approach from the Center of Excellence for Natural Product Drug Interaction Research describes a systematic method for using mathematical models to interpret the interaction risk of NPs as precipitants of potential clinically significant pharmacokinetic NPDIs. A framework for developing and applying pharmacokinetic NPDI models is presented with the aim of promoting accuracy, reproducibility, and generalizability in the literature. SIGNIFICANCE STATEMENT: Many natural products (NPs) contain phytoconstituents that can increase or decrease systemic or tissue exposure to, and potentially the efficacy of, a pharmaceutical drug; however, no regulatory agency guidelines exist to assist in predicting the risk of these complex interactions. This recommended approach from a multi-institutional consortium designated by National Institutes of Health as the Center of Excellence for Natural Product Drug Interaction Research provides a framework for modeling pharmacokinetic NP-drug interactions.

Iron-Catalyzed Radical Activation Mechanism for Denitrogenative Rearrangement Over C(sp3 )-H Amination.

An iron-catalyzed denitrogenative rearrangement of 1,2,3,4-tetrazole is developed over the competitive C(sp3 )-H amination. This catalytic rearrangement reaction follows an unprecedented metalloradical activation mechanism. Employing the developed method, a wide number of complex-N-heterocyclic product classes have been accessed. The synthetic utility of this radical activation method is showcased with the short synthesis of a bioactive molecule. Collectively, this discovery underlines the progress of radical activation strategy that should find wide application in the perspective of medicinal chemistry, drug discovery and natural product synthesis research.

Iron‐Catalyzed Radical Activation Mechanism for Denitrogenative Rearrangement Over C(sp3)–H Amination

AbstractAn iron‐catalyzed denitrogenative rearrangement of 1,2,3,4‐tetrazole is developed over the competitive C(sp3)–H amination. This catalytic rearrangement reaction follows an unprecedented metalloradical activation mechanism. Employing the developed method, a wide number of complex‐N‐heterocyclic product classes have been accessed. The synthetic utility of this radical activation method is showcased with the short synthesis of a bioactive molecule. Collectively, this discovery underlines the progress of radical activation strategy that should find wide application in the perspective of medicinal chemistry, drug discovery and natural product synthesis research.

Propagation and ex-situ conservation of Lomelosia minoana subsp. minoana and Scutellaria hirta - two ornamental and medicinal Cretan endemics (Greece)

Human needs and concomitant commercial trade to date trigger the demand of new ornamental plants and new natural medicinal products. The current study includes preliminary seed germination trials and presents the development of effective vegetative propagation protocols for Lomelosia minoana subsp. minoana (Dipsacaceae) and Scutellaria hirta (Lamiaceae), both globally rare, local endemics of Crete (Greece) with potential ornamental and medicinal value. Based on material collected directly from the wild, seed germination was succeeded (38%, T50: 10.74) only for L. minoana subsp. minoana. The optimal indole-3-butyric acid concentrations for effective rooting of cuttings were 2000 mg L-1 for L. minoana subsp. minoana (85%) and 4000 mg L-1 for S. hirta (50%). Seasonal differences were observed in respective rooting rates of the studied taxa. The detected rooting rates for L. minoana subsp. minoana cuttings are above standards to allow possible commercial application in the ornamental industry. Although the detected rooting rate (50%) for S. hirta was adequate for its ex situ conservation, it seems almost marginal for future commercial application and further investigation is needed. The sustainable utilization of these Cretan endemics studied herein provides new input for the ornamental-horticultural and cosmetic-pharmaceutical industries. This study shows how rare and endemic wild plant species can be progressively domesticated and introduced into sustainable cultivation systems in order to avoid the depletion of unique phytogenetic resources.

Progress in heterologous biosynthesis of forskolin.

Forskolin, a class of labdane-type diterpenoid, has significant medicinal value in anticancer, antiasthmatic, antihypertensive, and heart-strengthening treatments. The main source of natural forskolin is its extraction from the cork tissue of the root of Coleus forskohlii. However, conventional modes of extraction pose several challenges. In recent years, the construction of microbial cell factories to produce medicinal natural products via synthetic biological methods has effectively solved the current problems and is a research hotspot in this field. This review summarizes the recent progress in the heterologous synthesis of forskolin via synthetic biological technology, analyzes the current challenges, and proposes corresponding strategies.

Plants as a promising source for the treatment of parkinson disease: A systemic review

Parkinson’s disease is a progressive neurodegenerative disorder characterized by the loss of the nigrostriatal system’s pigmented dopaminergic neurons with a subsequent drop in dopamine. PD refers to such motor disorders such as resting tremor, muscle stiffness, and slow motion. Recent studies have shown that there has been an increasing interest in natural products particularly plants, for the treatment of Parkinson’s disease. The anti-PD effects of these natural products are considered to be due to their regulation ability; development of reactive oxygen species, neuroinflammation, production of dopamine, excitotoxicity, metal homeostasis, mitochondrial function, and cellular signaling pathways, all of which are disordered in the PD brain.This review explores neuronal degeneration observed in Parkinson’s disease has been slowed down or reversed by medicinal plants and natural products and their constituents. Keywords: Parkinson’s disease, Medicinal plants constituents, Dopamine, Neurodegeneration.

Antioxidant activities, tyrosinase inhibition activity and bioactive compounds content of broken rice fermented with Amylomyces rouxii

Solid state fermentation (SSF) utilizing filamentous fungus Amylomyces rouxii was investigated as a bio-processing strategy to enhance the bioactive properties of broken rice. Fermentation was carried out for 18 days and samples were withdrawn at 2-days interval. Established methods were deployed to assess the changes in bioactive properties and compounds content in fermented broken rice. The bioactive properties studied were total phenolic content (TPC), total flavonoid content (TFC), DPPH-radical scavenging activity and ferric-reducing antioxidant power (FRAP). Additionally, tyrosinase inhibition activity, which represents anti-pigmentation/browning property, was evaluated. Free phenolic acids and organic acids content were determined through high performance liquid chromatography (HPLC). The results showed that fermentation significantly increased the total phenolic content of broken rice from 0.03 mg GAE/g sample to 3.94 mg GAE/g sample and total flavonoid content from 0.04 to 1.71 mg QE/g sample. By the end of the fermentation, DPPH-radical scavenging of fermented broken rice was enhanced to 94.22%, compared to 9.03% in the unfermented sample. It was also observed that FRAP and tyrosinase inhibition activity of fermented broken rice were improved up to 39- fold and 50-fold, respectively. Kojic acid, a potent antioxidant and tyrosinase inhibitor, was detected in fermented broken rice, along with oxalic and ascorbic acid. Gallic, protocatechuic and 4-hydroxybenzoic acids were enhanced upon fermentation. This study manifested the positive effect of broken rice after fermentation with A. rouxii and thus revealed the potential of fermented broken rice as a promising natural bio-ingredients in food, cosmetics and medicinal products.

Genus Rosas : A Review of Ethnobotany, Phytochemistry and Traditional Aspects According to Islamic Traditional Medicine (ITM).

Rosa spp. is an important genus in the Rosaceae family which is a source of medicinal natural products, particularly polyphenolic and terpenoid compounds and is used in several traditional medicines such as Islamic Traditional Medicine (ITM) to cure various diseases. Plants in this genus are known to possess anti-inflammatory, antidiabetic, anti-constipation, cardioprotective and neuroprotective activities. Furthermore, phytochemical investigationshave reported Rosa species to contain a wide range of chemical compounds including quercetin, kaempferol, catechin, citronellol, limonene, lycopene, carvacrol, thymol, ascorbic acid (vitamin C), rosmarinic acid, etc. The current review is an attempt to cover the available findings on the ethnobotany and photochemistry of this genus as well as its medicinal aspects in ITM.

Evaluating the potency of Sulawesi propolis compounds as ACE-2 inhibitors through molecular docking for COVID-19 drug discovery preliminary study

Coronavirus disease (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Up to date, there has been no specific cure to treat the disease. Indonesia is one of the countries that is still fighting to control virus transmission. Yet, at the same time, Indonesia has a rich biodiversity of natural medicinal products that potentially become an alternative cure. Thus, this study examined the potency of a natural medicinal product, Sulawesi propolis compounds produced by Tetragonula sapiens, inhibiting angiotensin-converting activity enzyme-2 (ACE-2), a receptor of SARS-CoV-2 in the human body. In this study, molecular docking was done to analyze the docking scores as the representation of binding affinity and the interaction profiles of propolis compounds toward ACE-2. The results illustrated that by considering the docking score and the presence of interaction with targeted sites, five compounds, namely glyasperin A, broussoflavonol F, sulabiroins A, (2S)-5,7-dihydroxy-4′-methoxy-8-prenylflavanone and isorhamnetin are potential to inhibit the binding of ACE-2 and SARS-CoV-2, with the docking score of −10.8, −9.9, −9.5, −9.3 and −9.2 kcal/mol respectively. The docking scores are considered to be more favorable compared to MLN-4760 as a potent inhibitor.

Screening and identification of bioactive compounds from citrus against non-structural protein 3 protease of hepatitis C virus genotype 3a by fluorescence resonance energy transfer assay and mass spectrometry.

BACKGROUNDHepatitis C virus genotype 3a (HCV G3a) is highly prevalent in Pakistan. Due to the elevated cost of available Food and Drug Administration-approved drugs against HCV, medicinal natural products of potent antiviral activity should be screened for the cost-effective treatment of the disease. Furthermore, from natural products, active compounds against vital HCV proteins like non-structural protein 3 (NS3) protease could be identified to prevent viral proliferation in the host.AIMTo develop cost-effective HCV genotype 3a NS3 protease inhibitors from citrus fruit extracts.METHODSFull-length NS3 without co-factor non-structural protein 4A (NS4A) and codon optimized NS3 protease in fusion with NS4A were expressed in Escherichia coli. The expressed protein was purified by metal ion affinity chromatography and gel filtration. Citrus fruit extracts were screened using fluorescence resonance energy transfer (FRET) assay against the protease and polyphenols were identified as potential inhibitors using electrospray ionization-mass spectrometry (MS)/MS technique. Among different polyphenols, highly potent compounds were screened using molecular modeling approaches and consequently the most active compound was further evaluated against HCV NS4A-NS3 protease domain using FRET assay.RESULTSNS4A fused with NS3 protease domain gene was overexpressed and the purified protein yield was high in comparison to the lower yield of the full-length NS3 protein. Furthermore, in enzyme kinetic studies, NS4A fused with NS3 protease proved to be functionally active compared to full-length NS3. So it was concluded that co-factor NS4A fusion is essential for the purification of functionally active protease. FRET assay was developed and validated by the half maximal inhibitory concentration (IC50) values of commercially available inhibitors. Screening of citrus fruit extracts against the native purified fused NS4A-NS3 protease domain showed that the grapefruit mesocarp extract exhibits the highest percentage inhibition 91% of protease activity. Among the compounds identified by LCMS analysis, hesperidin showed strong binding affinity with the protease catalytic triad having S-score value of -10.98.CONCLUSIONFused NS4A-NS3 protease is functionally more active, which is effectively inhibited by hesperidin from the grapefruit mesocarp extract with an IC50 value of 23.32 µmol/L.

An Overview of Methods of Extraction, Isolation and Characterization of Natural Medicinal Plant Products in Improved Traditional Medicine Research

Herbal plants are very important in traditional community use and enrich our plant biodiversity and conservation. Natural products are vital substances of traditional knowledge systems in complementary and alternative medicine, nutraceutical, food supplements, and pharmaceutical bioactive metabolites of new chemical entities. Bioactive secondary metabolites from herbal plants of different forms are main sources and provide major opportunities for drug active pharmaceuticals due to the diverse flora and fauna biodiversity that produces the necessary available chemical diversity. There has been an increasing popularity in phytochemical research within the high through put (HTS) screening programs in search of lead. Phytochemicals of herbal extracts for traditional uses contain various types of bioactive metabolites of pharmaceutical and pharmacotherapeutic nature, and many phytomedicines for different therapeutic areas have been derived from herbal products. This paper is aimed at giving an insight into the extraction, isolation, and characterization of the rich medicinal plant biodiversity of potential pharmaceutical importance and the major drawbacks and challenges in the extraction, isolation, and characterization of phytochemicals in plant extracts. Phytochemicals in medicinal plants have been studied with more emphasis on the extraction process which is a vital stage in the analysis of bioactive compounds in medicinal plant research. The advantages and disadvantages of the different extraction methods is important to discuss following the regulatory guidelines and different pharmacopoeia. The analysis of bioactive molecules in herbal products involves the applications of various phytochemical screening methods, and the use of chromatographic techniques such as TLC and HPLC, including in some cases the non-chromatographic methods like Fourier Transform Infra-Red (FTIR), immunoassay. This paper has been motivated by the challenges faced by most pharmacy students in data mining of information on phytochemical screening and testing of biological activities in projects related to herbal plants research. This write up is also geared towards providing students with information on the preclinical drug discovery process towards the formulation of an improved traditional medicine/ phytomedicine.

Discovery of Bioactive Compounds from Traditionally used Medicinal Plants: A Profile of Nilufar Z. Mamadalieva

Discovery of Bioactive Compounds from Traditionally used Medicinal Plants: A Profile of Nilufar Z. Mamadalieva

The Importance of Using Medicinal Plants and Natural Products in Order to Treat Depression, Regarding Iranian Traditional and Islamic Medicine and Laboratory Studies

Introduction: Depression is a chronic and common disease and is currently used to treat antidepressants such as tricyclics, which sometimes lead to the activity of certain brain chemicals called neurotransmitters. The use of chemical and industrial drugs by their patients can be due to the lack of treatment for depression. Therefore, in order to promote health, the use of natural products and herbs, and clinical trials and studies with traditional medicine approaches to the treatment of depression is important. In the past, natural products have also been used. The Qurchr('39')an and Islam, while analyzing the causes and phenomena of depression, have addressed the ways of its treatment. In particular, this study has been conducted in line with the on the revival of traditional Iranian and Islamic medicine, and it seems necessary.
 Material and Methods: In this paper, materials based on electronic library resources, including scientific articles and relevant books from foreign and domestic authoritative journals and websites, have been conducted with proper keyword searches. The medicinal herbs used in depression in traditional medicine and modern medicine, the teachings of the Islamic religion, the reports presented in this regard in English and Persian, and the experiences of the several years of research on various indigenous herbs seeking research You know, it was a benchmark for study and was studied after collection.
 Results: In traditional medicine, for the treatment of many diseases, such as depression and anxiety, some herbs such as Citrus aurantium L. and Ocimum basilicum have been known and used for many years. Studies on Echium amoenum L. and Feijoa sellowiana have also been carried out today. It is also used to treat acupuncture. In traditional medicine, and of course, Islam and the Quran, depression has been discussed and appropriate solutions have been presented. So that natural products derived from medicinal plants are known and recommended. Meanwhile, in Islam and the Qurchr('39')an, healthy, halal and herbal remedies have also been addressed. In ancient Traditional Iranian medicine, it has been given great importance to the theme of sport, heroism and its moral outcomes. Also, Islamic scholars believed in the benefits of spiritual education and its role in physical strengthening. Relaxing exercises also significantly reduced depression.
 Conclusion: Given that patients with depression may be susceptible to suicide due to frustration. The use of medicinal herbs and traditional medicine and Iranian medicine, in view of their desirable, natural and safe effects, is necessary. According to Islamic texts, practical commitment to Islamic beliefs can be a deterrent to many psychological disorders. Reading the Qurchr('39')an, believing in God, practicing the teachings of the Qurchr('39')an and prayer, and other divine duties are also effective in creating calm and promoting the health and treatment of diseases such as depression.

P.108 Effect of a natural medicinal product on neural response to psychosocial stress is associated with personality traits

Neural activity within the ventromedial prefrontal cortex (vmPFC) is a critical determinant of stressor-induced anxiety. Pharmacological activation of the vmPFC during stress protects against stress-induced social anxiety suggesting that altering the excitatory/inhibitory (E/I) tone in the vmPFC may promote stress resilience. E/I balance is maintained, in part, by endogenous cannabinoid (eCB) signaling with the calcium dependent retrograde release of 2-arachidonoylglycerol (2-AG) suppressing presynaptic neurotransmitter release. We hypothesized that raising 2-AG levels, via inhibition of its degradation enzyme monoacylglycerol lipase (MAGL) with KML29, would shift vmPFC E/I balance and promote resilience. In acute slice experiments, bath application of KML29 (100 nM) augmented evoked excitatory neurotransmission as evidenced by a left-shift in fEPSP I/O curve, and decreased sIPSC amplitude. In whole-cell recordings, KML29 increased resting membrane potential but reduced the after depolarization, bursting rate, membrane time constant and slow after hyperpolarization. Intra-vmPFC administration of KML29 (200ng/0.5μL/hemisphere) prior to inescapable stress (IS) exposure (25, 5s tail shocks) prevented stress induced anxiety as measured by juvenile social exploration 24 h after stressor exposure. Conversely, systemic administration of KML29 (40 mg/kg, i.p.) 2 h before IS exacerbated stress induced anxiety. MAGL inhibition in the vmPFC may promote resilience by augmenting the output of neurons that project to brainstem and limbic structures that mediate stress responses.

Aqueous enzyme-ultrasonic pretreatment for efficient isolation of essential oil from Artemisia argyi and investigation on its chemical composition and biological activity

The in-depth study of plant essential oil (EO) to provide valuable resources for the development of natural medicinal products is one of the current research hotspots. The present work realized the efficient isolation of EO from Artemisia argyi leaves using aqueous enzyme-ultrasonic pretreatment followed by microwave-assisted hydrodistillation (EUP-MHD). Because of the synergistic reaction mechanism, the combination of enzyme and ultrasound doubly improved the separation of EO. After the optimization process (single factor experiments, Plackett–Burman design, and Box–Behnken design), mixed enzyme (cellulose + pectinase + papain), concentration of 10 U/mg, ultrasonic frequency of 45 kHz, ultrasonic power of 200 W, ultrasonic time of 20 min, reaction temperature of 50 °C, pH of 5, microwave power of 650 W, microwave time of 10 min, and liquid-solid ratio of 10 mL/g performed best, with the yield of EO of 5.32 ± 0.20 mg/g. A distinct advantage of this technique was found as compared with other techniques, which highlighted the positive influence of the pretreatment process. Additionally, the oxygenated components of EO from EUP-MHD accounted for a higher proportion than other methods, including eucalyptol, borneol, camphor, neointermedeol, and terpinen-4-ol. Finally, the evaluation of the biological activity of A. argyi EO pointed out that the EO had excellent antioxidant activity and higher inhibitory activity against Phytophthora capsica but presented weaker cytotoxic activity. In general, the technique used in this study is promising in the field of separating EO from crop materials.

Deploying Microbial Synthesis for Halogenating and Diversifying Medicinal Alkaloid Scaffolds.

Plants produce some of the most potent therapeutics and have been used for thousands of years to treat human diseases. Today, many medicinal natural products are still extracted from source plants at scale as their complexity precludes total synthesis from bulk chemicals. However, extraction from plants can be an unreliable and low-yielding source for human therapeutics, making the supply chain for some of these life-saving medicines expensive and unstable. There has therefore been significant interest in refactoring these plant pathways in genetically tractable microbes, which grow more reliably and where the plant pathways can be more easily engineered to improve the titer, rate and yield of medicinal natural products. In addition, refactoring plant biosynthetic pathways in microbes also offers the possibility to explore new-to-nature chemistry more systematically, and thereby help expand the chemical space that can be probed for drugs as well as enable the study of pharmacological properties of such new-to-nature chemistry. This perspective will review the recent progress toward heterologous production of plant medicinal alkaloids in microbial systems. In particular, we focus on the refactoring of halogenated alkaloids in yeast, which has created an unprecedented opportunity for biosynthesis of previously inaccessible new-to-nature variants of the natural alkaloid scaffolds.

New Advances in the Synthetic Application of Enantiomeric 1-Phenylethylamine (α-PEA): Privileged Chiral Inducer and Auxiliary.

New developments in the synthesis, resolution, and synthetic applications of chiral 1-phenylethylamine (α-PEA) reported in the last decade have been reviewed. In particular, improvements in the synthesis of α-PEA and its derivatives and chiral resolution, as well as their applications in the resolution of other compounds, were discussed. α-PEA was used as a chiral auxiliary in the diastereoselective synthesis of medicinal substances and natural products. Chiral ligands with α-PEA moieties were applied in asymmetric reactions, and effective modular chiral organocatalysts were constructed with α-PEA fragments and used in important synthetic reactions.

Cross-dehydrogenative Coupling Reactions Between Formamidic C(sp2)-H and X-H (X = C, O, N) Bonds.

In the last decade, the scientific community has witnessed explosive growth in research on the direct carbamoylation of C-H and X-H (X = N, O) bonds with formamides via cross-dehydrogenative coupling reactions. This novel approach is an effective means of preparing a variety of carboxamide, carbamate as well as urea derivatives, which are prevalent in medicinal chemistry and natural product synthesis. This review elaborates the most important advances and developments in the field, with an emphasis on the reaction patterns and mechanisms.

Marine Cyanobacteria and Microalgae Metabolites-A Rich Source of Potential Anticancer Drugs.

Cancer is at present one of the utmost deadly diseases worldwide. Past efforts in cancer research have focused on natural medicinal products. Over the past decades, a great deal of initiatives was invested towards isolating and identifying new marine metabolites via pharmaceutical companies, and research institutions in general. Secondary marine metabolites are looked at as a favorable source of potentially new pharmaceutically active compounds, having a vast structural diversity and diverse biological activities; therefore, this is an astonishing source of potentially new anticancer therapy. This review contains an extensive critical discussion on the potential of marine microbial compounds and marine microalgae metabolites as anticancer drugs, highlighting their chemical structure and exploring the underlying mechanisms of action. Current limitation, challenges, and future research pathways were also presented.