Natural Product Research Research Articles

In silico prediction and biological assessment of novel angiogenesis modulators from traditional Chinese medicine.

Uncontrolled angiogenesis is a common denominator underlying many deadly and debilitating diseases such as myocardial infarction, chronic wounds, cancer, and age-related macular degeneration. As the current range of FDA-approved angiogenesis-based medicines are far from meeting clinical demands, the vast reserve of natural products from traditional Chinese medicine (TCM) offers an alternative source for developing pro-angiogenic or anti-angiogenic modulators. Here, we investigated 100 traditional Chinese medicine-derived individual metabolites which had reported gene expression in MCF7 cell lines in the Gene Expression Omnibus (GSE85871). We extracted literature angiogenic activities for 51 individual metabolites, and subsequently analysed their predicted targets and differentially expressed genes to understand their mechanisms of action. The angiogenesis phenotype was used to generate decision trees for rationalising the poly-pharmacology of known angiogenesis modulators such as ferulic acid and curculigoside and validated by an in vitro endothelial tube formation assay and a zebrafish model of angiogenesis. Moreover, using an in silico model we prospectively examined the angiogenesis-modulating activities of the remaining 49 individual metabolites. In vitro, tetrahydropalmatine and 1 beta-hydroxyalantolactone stimulated, while cinobufotalin and isoalantolactone inhibited endothelial tube formation. In vivo, ginsenosides Rb3 and Rc, 1 beta-hydroxyalantolactone and surprisingly cinobufotalin, restored angiogenesis against PTK787-induced impairment in zebrafish. In the absence of PTK787, deoxycholic acid and ursodeoxycholic acid did not affect angiogenesis. Despite some limitations, these results suggest further refinements of in silico prediction combined with biological assessment will be a valuable platform for accelerating the research and development of natural products from traditional Chinese medicine and understanding their mechanisms of action, and also for other traditional medicines for the prevention and treatment of angiogenic diseases.

From structural determination of natural products in complex mixtures to single cell resolution: Perspectives on advances and challenges for mass spectrometry

The search for new Natural Products is one of the oldest interests for research in chemistry. The history of this discipline is very prolific, from its initial uses as medicine to advanced omics strategies to understand the mechanics of biological controls in living cells. The discoveries of morphine, penicillin, taxol and many other natural products revolutionized human health. During the last 40 years, excellent reviews published by Dr. David Newman and Dr. Gordon Crag have revealed that the pharmaceutical industry’s research into natural products has lost some of its steam. Nevertheless, new natural products for antimicrobials, antifungals, and anticancer drugs remained the main alternative. Furthermore, research institutes have seen great vigor, and several startup companies have emerged worldwide, seeking therapeutic alternatives based in natural products. Innovations on spectrometric hardware, allowing broader coverage of chemical classes and spatial mapping, and in software, enabling the interpretation of large volumes of data, afforded a renewed interest in natural products and are considered the most important enabling technology for the new companies. In this perspective article we give some historical context to exciting developments, on software and spatial resolution, that promise to pave the way for a bright future of Natural Products research.

Enhancing chemical and biological diversity by co-cultivation.

In natural product research, microbial metabolites have tremendous potential to provide new therapeutic agents since extremely diverse chemical structures can be found in the nearly infinite microbial population. Conventionally, these specialized metabolites are screened by single-strain cultures. However, owing to the lack of biotic and abiotic interactions in monocultures, the growth conditions are significantly different from those encountered in a natural environment and result in less diversity and the frequent re-isolation of known compounds. In the last decade, several methods have been developed to eventually understand the physiological conditions under which cryptic microbial genes are activated in an attempt to stimulate their biosynthesis and elicit the production of hitherto unexpressed chemical diversity. Among those, co-cultivation is one of the most efficient ways to induce silenced pathways, mimicking the competitive microbial environment for the production and holistic regulation of metabolites, and has become a golden methodology for metabolome expansion. It does not require previous knowledge of the signaling mechanism and genome nor any special equipment for cultivation and data interpretation. Several reviews have shown the potential of co-cultivation to produce new biologically active leads. However, only a few studies have detailed experimental, analytical, and microbiological strategies for efficiently inducing bioactive molecules by co-culture. Therefore, we reviewed studies applying co-culture to induce secondary metabolite pathways to provide insights into experimental variables compatible with high-throughput analytical procedures. Mixed-fermentation publications from 1978 to 2022 were assessed regarding types of co-culture set-ups, metabolic induction, and interaction effects.

Chitinase is a Potent Insecticidal Molecular Target of Camptothecin and Its Derivatives

Camptothecin (CPT) is a prominent molecule in natural product research because of its application prospects in medicine and agriculture. In this study, CPT and its derivatives were discovered to be competitive inhibitors of group II and group h insect chitinases, both of which are key components of insect chitinolytic systems. CPT and 7-ethyl-10-hydroxycamptothecin (SN-38) inhibited group II chitinase from Ostrinia furnacalis (OfChtII) with Ki values of 5.1 and 2.0 μM, respectively. Results from tryptophan fluorescence spectroscopy, molecular docking analysis, and molecular dynamics simulations revealed that both CPT and SN-38 inhibit OfChtII-C1 by interacting with solvent-exposed tryptophan residues in a substrate-binding cleft. CPT exhibited high insecticidal activity toward the orthopteran pest Locusta migratoria, possibly because of the midgut metabolism of CPT, with only moderate activities toward lepidopteran pests. Even though SN-38 exhibited much lower insecticidal activities than CPT, it still showed higher inhibitory activity toward chitinase. This study reports a new molecular target of CPT and provides insights into molecular design of CPT-based insecticides against different kinds of pests.

Ligand-observed in-tube NMR in natural products research: A review on enzymatic biotransformations, protein–ligand interactions, and in-cell NMR spectroscopy

Natural product-observed NMR methods have considerably expanded the potentialities for in-tube NMR monitoring of complex enzymatic biotransformations and investigation of protein-natural product interactions even in living cells. We review, herein, the significant advantages of ligand-observed in-situ NMR monitoring of enzymatic biotransformations without restoring to laborious and time-consuming chromatographic methods. Emphasis will be given to the potentialities of the use of the NMR bioreactor: (i) to investigate through saturation transfer difference (STD), the capacity of natural products to serve as enzyme substrates, (ii) to monitor multiple biotransformation products of natural products with the use of immobilized enzymes and (iii) to investigate interactions of biotransformed products with protein targets. The use of STD and its variants, transfer effect Noes for PHArmacophore Mapping (INPHARMA) NMR, in conjunction with computational methods, can provide excellent tools in investigating competitive binding modes even in proteins with multiple binding sites. The method has been successfully applied in the study of unsaturated free fatty acids (UFFAs)-serum albumin complexes in which the location and conformational states of UFFAs could not be determined accurately, despite numerous X-ray structural studies, due to conformational averaging. This combined method, thus, may find promising applications in the field of protein-natural product recognition research. The emerging concept of in-cell NMR and recent applications will be discussed since they can provide atomic level insights into natural product-protein interactions in living cells without the need of isotope labelled techniques.

Targeting critical pathways in ferroptosis and enhancing antitumor therapy of Platinum drugs for colorectal cancer.

Colorectal cancer (CRC) can be resistant to platinum drugs, possibly through ferroptosis suppression, albeit the need for further work to completely understand this mechanism. This work aimed to sum up current findings pertaining to oxaliplatin resistance (OR) or resistance to ascertain the potential of ferroptosis to regulate oxaliplatin effects. In this review, tumor development relating to iron homeostasis, which includes levels of iron that ascertain cells' sensitivity to ferroptosis, oxidative stress, or lipid peroxidation in colorectal tumor cells that are connected with ferroptosis initiation, especially the role of c-Myc/NRF2 signaling in regulating iron homeostasis, coupled with NRF2/GPX4-mediated ferroptosis are discussed. Importantly, ferroptosis plays a key role in OR and ferroptotic induction may substantially reverse OR in CRC cells, which in turn could inhibit the imbalance of intracellular redox induced by oxaliplatin and ferroptosis, as well as cause chemotherapeutic resistance in CRC. Furthermore, fundamental research of small molecules, ferroptosis inducers, GPX4 inhibitors, or natural products for OR coupled with their clinical applications in CRC have also been summarized. Also, potential molecular targets and mechanisms of small molecules or drugs are discussed as well. Suggestively, OR of CRC cells could significantly be reversed by ferroptosis induction, wherein this result is discussed in the current review. Prospectively, the existing literature discussed in this review will provide a solid foundation for scientists to research the potential use of combined anticancer drugs which can overcome OR via targeting various mechanisms of ferroptosis. Especially, promising therapeutic strategies, challenges ,and opportunities for CRC therapy will be discussed.

C-H modification of natural products: a minimalist enabling tactic for drug discovery, API processing and bioconjugation.

Intrusion into the C-H chemical space of natural products through the strategic deployment of C-H functionalization reactions could lead to incredibly new molecular diversities with an unforeseen impact on biological functions. Based on this hypothesis, semisynthetic C-H modification of natural products is emerging as a minimalist tactic in natural product based drug discovery. Several examples of C-H modification of natural products, resulting in functional gains in key pharmacological attributes viz. potency, aqueous solubility and DMPK profile, along with opportunities in allied areas such as API processing, bioconjugation, and target deconvolution, continue to surface in the recent literature. The strategy has already recorded commercial success in the development of antineoplastic drugs topotecan and irinotecan and in industrial production of pravastatin, calcitriol and artemisinin. This Feature Article highlights the broad contours of this evolving paradigm at the interface of natural product and synthetic chemistry research to accelerate and widen the scope of natural product-based drug discovery.

Production of high molecular-ordered stilbene oligomers for the study of their biological activity: total synthesis, bio-catalyzed synthesis and production by plant systems.

Though the iconic stilbene resveratrol and its related dimers constitute a top storyline in the field of natural product research, resveratrol oligomers (condensation >2) have been left aside despite their higher biological activity compared to that of the monomers. This situation largely results from the difficulty of getting them in sufficient quantities to enable evaluation of their biological properties in vivo. We present here a synthetic and critical analysis of the methods used for the production of high molecular-ordered stilbene oligomers of potential biomedical interest, gathering the most salient data regarding the approaches employed to prepare them by total synthesis, use of biomimetic approaches or through plant systems.

Formulation of Herbal Tea from Nepalese Medicinal Plants: Phenolic Assay, Proximate Composition and In-vivo Toxicity Profiling of Medicinal Plants with Nutritive Benefits

Herbal tea, also known as tisane, is a beverage made from the infusion or decoction of plant material in hot water. True tea comes from the Camellia sinensis plant, while tisane (herbal tea) comes from a water-based infusion of herbs, spices, flowers, leaves etc. This study aimed to formulate and determine the nutraceutical value (proximate analysis), phytochemical value (total phenolic content) and in-vivo toxicity of the different medicinal plants used to prepare three different types of herbal tea formulations. Natural Product Research Laboratory (NPRL)-1 [Asparagus officinalis L., Phyllanthus emblica L., Mentha piperita L., Elettaria cardamomum (L.) Maton and Camellia sinensis (L.) Kuntze], NPRL-2 [Ocimum tenuiflorum L., Bergenia ciliate (Haw.) Sternb., Elettaria cardamom (L.) maton and Camellia sinensis (L.) Kuntze] and NPRL-3 [Salvia rosmarinus Spenn., Cymbopogon citratus (DC.) Stapf, Senegalia catechu (L.f.) P.J.H.Hurter & Mabb. Elettaria cardamomum (L.) Maton and Withania somnifera (L.) Dunal] herbal tea formulations were prepared from these selected medicinal plants. They were respectively tested for their properties. All the plants included were highly nutritional and none were found toxic. The results suggested that herbal tea made up of these potent plants’ parts can be a good choice for health-promoting benefits. These formulations could further be studied for their other beneficial activities.

Phytochemical Investigation of Marker Compounds from Indigenous Korean Salix Species and Their Antimicrobial Effects.

Salix species, including willow trees, are distributed in the temperate regions of Asian countries, including South Korea. Willow trees are used to treat pain and inflammatory diseases. Due to the medicinal properties of willow trees, pharmacological studies of other Salix spp. have gained attention; however, only a few studies have investigated the phytochemicals of these species. As part of our ongoing natural product research to identify bioactive phytochemicals and elucidate their chemical structures from natural resources, we investigated the marker compounds from indigenous Korean Salix species, namely, Salix triandra, S. chaenomeloides, S. gracilistyla, S. koriyanagi, S. koreensis, S. pseudolasiogyne, S. caprea, and S. rorida. The ethanolic extract of each Salix sp. was investigated using high-performance liquid chromatography combined with thin-layer chromatography and liquid chromatography−mass spectrometry-based analysis, and marker compounds of each Salix sp. were isolated. The chemical structures of the marker compounds (1−8), 3-(4-hydroxyphenyl)propyl β-D-glucopyranoside (1), 2-O-acetylsalicin (2), 1-O-p-coumaroyl glucoside (3), picein (4), isograndidentatin B (5), 2′-O-acetylsalicortin (6), dihydromyricetin (7), and salicin (8) were elucidated via nuclear magnetic resonance spectroscopy and high-resolution liquid chromatography−mass spectrometry using ultrahigh-performance liquid chromatography coupled with a G6545B Q-TOF MS system with a dual electrospray ionization source. The identified marker compounds 1−8 were examined for their antimicrobial effects against plant pathogenic fungi and bacteria. Dihydromyricetin (7) exhibited antibacterial activity against Staphylococcus aureus, inducing 32.4% inhibition at a final concentration of 125 μg/mL with an MIC50 value of 250 μg/mL. Overall, this study isolated the marker compounds of S. triandra, S. chaenomeloides, S. gracilistyla, S. koriyanagi, S. koreensis, S. pseudolasiogyne, S. caprea, and S. rorida and identified the anti-Staphylococcus aureus bacterial compound dihydromyricetin.

Ethnomedicinal plants used by Kani tribals to treat Rheumatism in Kalakad Mundanthurai Tiger Reserve, Tamil Nadu, India

Background: The search for safe and alternative remedy for rheumatic disorders from herbal resources is increasing nowadays hence the medicinal plants constitute a promising role in modern medication system due to the presence of several bioactive compounds. The people inhabiting in the forest areas are often affected with several skeleton-muscular disorders especially with rhematic problems, hence the present study was undertaken to document the plants used to treat such diseases. Methods: The present study was carried out to document the traditional knowledge of medicinal plants used in treating rheumatism by Kani tribes who live in the KMTR region in the Southern Western Ghats of Tamil Nadu, India. Extensive field studies were conducted in five hamlets of Kani tribes focusing on the plants used in treating rheumatism. The data was collected using questionnaires, interviews and discussions among the traditional practitioners and other people of the hamlet. Results: The present ethnobotanical survey has led to the documentation of 59 species of medicinal plants belonging to 33 families. Of these, 26 species are the major utilized plants while 33 plant species are used in least quantity. Leaves are widely utilized against rheumatic problems. The medicinal formulations are prepared in the form of decoction, paste and powder which are administered topically or orally based on the disease condition. Conclusion: The medicinal plants were documented with the focus on conserving the ethnic knowledge of Kani tribes as documentary evidence for plant-based natural product research. Among the documented plants, Cardiospermum halicacabum, Elettaria cardamomum, Elephantopus scaber, Cymbopogon citratus, Allium cepa, Sida acuta, Pergularia daemia, and Lawsonia inermis were frequently cited and requires further pharmacological studies to develop an effective drug against chronic illnesses. Keywords: Ethnic community, Folk medicine, Rheumatism, Western Ghats

Supercritical CO2 extraction of spices: A systematic study with focus on terpenes and piperamides from black pepper (Piper nigrum L.)

Black pepper (P. nigrum L.) is considered one of the most valuable spices and a promising candidate in natural product research. In this study, the influence of different combinations of pressures (100–300 bar) and temperatures (40–60 °C) on the supercritical CO2 (SC-CO2) recovery of several key compounds from black pepper was evaluated systematically. The extraction curves showed that terpenes were recovered in a short time under all studied conditions. In contrast, higher pressure values were required to extract piperamides efficiently. Furthermore, the differences in the extraction kinetics of piperine, piperettine, pellitorine, guineensine, and N-isobutyl-2,4,14-eicosatrienamide were linked with several structural features, such as the nature of the amine group or the terminal part of the fatty acid. The data from the isocratic experiments represented the starting point for designing a two-step pressure gradient SC-CO2 process in which one terpene-rich and one piperamide-rich product were successively obtained.

New opportunities and challenges of natural products research: When target identification meets single-cell multiomics.

Natural products, and especially the active ingredients found in traditional Chinese medicine (TCM), have a thousand-year-long history of clinical use and a strong theoretical basis in TCM. As such, traditional remedies provide shortcuts for the development of original new drugs in China, and increasing numbers of natural products are showing great therapeutic potential in various diseases. This paper reviews the molecular mechanisms of action of natural products from different sources used in the treatment of inflammatory diseases and cancer, introduces the methods and newly emerging technologies used to identify and validate the targets of natural active ingredients, enumerates the expansive list of TCM used to treat inflammatory diseases and cancer, and summarizes the patterns of action of emerging technologies such as single-cell multiomics, network pharmacology, and artificial intelligence in the pharmacological studies of natural products to provide insights for the development of innovative natural product-based drugs. Our hope is that we can make use of advances in target identification and single-cell multiomics to obtain a deeper understanding of actions of mechanisms of natural products that will allow innovation and revitalization of TCM and its swift industrialization and internationalization.

Preparation and Application of Molecularly Imprinted Polymers for Flavonoids: Review and Perspective.

The separation and detection of flavonoids from various natural products have attracted increasing attention in the field of natural product research and development. Depending on the high specificity of molecularly imprinted polymers (MIPs), MIPs are proposed as efficient adsorbents for the selective extraction and separation of flavonoids from complex samples. At present, a comprehensive review article to summarize the separation and purification of flavonoids using molecular imprinting, and the employment of MIP-based sensors for the detection of flavonoids is still lacking. Here, we reviewed the general preparation methods of MIPs towards flavonoids, including bulk polymerization, precipitation polymerization, surface imprinting and emulsion polymerization. Additionally, a variety of applications of MIPs towards flavonoids are summarized, such as the different forms of MIP-based solid phase extraction (SPE) for the separation of flavonoids, and the MIP-based sensors for the detection of flavonoids. Finally, we discussed the advantages and disadvantages of the current synthetic methods for preparing MIPs of flavonoids and prospected the approaches for detecting flavonoids in the future. The purpose of this review is to provide helpful suggestions for the novel preparation methods of MIPs for the extraction of flavonoids and emerging applications of MIPs for the detection of flavonoids from natural products and biological samples.

Editorial of International Journal of Pharmacy and Integrated Health Sciences

It is a great pleasure to introduce this issue on emerging ideas in health services research, biological, pharmaceutical, integrated health sciences in the International Journal of Pharmacy & Integrated Health Sciences (IJPIHS). We editor encourage studies with rigorous methodology and contributions because this is essential to ensure that the conclusions drawn from the journal's publications are true and reliable. All articles provide interesting, novel and useful results covering different areas pharmaceutical chemistry, pharmaceutics, pharmacogenomics, pharmacology, natural product research, nanotechnology, bioinformatics, biotechnology, environmental sciences and genetic engineering. The newest studies dealing with biomedical applications are summarized in this issue of IJPIHS, with "new frontiers" playing a crucial role in this regard. Review articles and original research covering all facets of pharmaceutical and integrated health sciences, as well as cutting-edge protocols and techniques to assess healthcare professionals' knowledge, attitudes, and practices regarding various clinical issues, are among the contributions for this issue.

Enhanced Identification of Ginsenosides Simultaneously from Seven Panax Herbal Extracts by Data-Dependent Acquisition Including a Preferred Precursor Ions List Derived from an In-House Programmed Virtual Library.

Data-dependent acquisition (DDA) is widely utilized for metabolite identification in natural product research and food science, which, however, can suffer from low coverage. A potential solution to improve DDA coverage is to include the precursor ions list (PIL). Here, we aimed to construct a PIL-containing DDA strategy based on an in-house library of ginsenosides (VLG) and identify ginsenosides simultaneously from seven Panax herbal extracts. VLG, combined with mass defect filtering, could efficiently screen the ginsenoside precursors and elaborate the separate PIL involved in DDA for each ginseng extract. Consequently, we could characterize 500 ginsenosides, including 176 ones with unknown masses. Using the Panax ginseng extract, the superiority of this strategy was embodied in targeting more known ginsenoside masses and newly acquiring the MS2 spectra of 13 components. Conclusively, knowledge-based large-scale molecular prediction and PIL-DDA can represent a powerful targeted/untargeted strategy beneficial to novel natural compound discovery.

AI-Driven Synthetic Biology for Non-Small Cell Lung Cancer Drug Effectiveness-Cost Analysis in Intelligent Assisted Medical Systems.

According to statistics, in the 185 countries' 36 types of cancer, the morbidity and mortality of lung cancer take the first place, and non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer (International Agency for Research on Cancer, 2018), (Bray et al., 2018). Significantly in many developing countries, limited medical resources and excess population seriously affect the diagnosis and treatment of alung cancer patients. The 21st century is an era of life medicine, big data, and information technology. Synthetic biology is known as the driving force of natural product innovation and research in this era. Based on the research of NSCLC targeted drugs, through the cross-fusion of synthetic biology and artificial intelligence, using the idea of bioengineering, we construct an artificial intelligence assisted medical system and propose a drug selection framework for the personalized selection of NSCLC patients. Under the premise of ensuring the efficacy, considering the economic cost of targeted drugs as an auxiliary decision-making factor, the system predicts the drug effectiveness-cost then. The experiment shows that our method can rely on the provided clinical data to screen drug treatment programs suitable for the patient's conditions and assist doctors in making an efficient diagnosis.

Identification of Photocatalytic Alkaloids from Coptidis Rhizome by an Offline HPLC/CC/SCD Approach.

Natural products continue to be a valuable source of active metabolites; however, researchers of natural products are mostly focused on the biological effects, and their chemical utility has been less explored. Furthermore, low throughput is a bottleneck for classical natural product research. In this work, a new offline HPLC/CC/SCD (high performance liquid chromatography followed by co-crystallization and single crystal diffraction) workflow was developed that greatly expedites the discovery of active compounds from crude natural product extracts. The photoactive total alkaloids of the herbal medicine Coptidis rhizome were firstly separated by HPLC, and the individual peaks were collected. A suitable coformer was screened by adding it to the individual peak solution and observing the precipitation, which was then redissolved and used for co-crystallization. Seven new co-crystals were obtained, and all the single crystals were subjected to X-ray diffraction analysis. The molecular structures of seven alkaloids from milligrams of crude extract were resolved within three days. NDS greatly decreases the required crystallization amounts of alkaloids to the nanoscale and enables rapid stoichiometric inclusion of all the major alkaloids with full occupancy, typically without disorder, affording well-refined structures. It is noteworthy that anomalous scattering by the coformer sulfur atoms enables reliable assignment of absolute configuration of stereogenic centers. Moreover, the identified alkaloids were firstly found to be photocatalysts for the green synthesis of benzimidazoles. This study demonstrates a new and green phytochemical workflow that can greatly accelerate natural product discovery from complex samples.

IN VITRO ASSESSMENT OF ANTIMICROBIAL AND ANTIOXIDANT ACTIVITIES OF EXTRACTS OF YEMENI FAGONIA SCHWEINFURTHII HADIDI

Background: Antioxidant and antimicrobial properties of plant extracts are attributed to bioactive components derived from medicinal plants. This study inspected into the antimicrobial and antioxidant effects of extracts from Fagonia schweinfurthii Hadidi aerial portions. Method: Several solvents, including n-hexane, ethyl acetate, and methanol, were utilized sequentially to extract secondary metabolites from F. schweinfurthii aerial parts. Antimicrobial activity was evaluated using the well diffusion method and broth serial dilution, whilst antioxidant activity was evaluated using the 2, 2-diphenyl-1-picrylhydrazyl radical scavenging method. Results: The findings exposed that the studied fungal strains (Candida albicans and Trichophyton rubrum) were resistant to all plant extracts. F. schweinfurthii methanol and ethyl acetate extracts demonstrated inhibitory effects on Gram-positive and Gram-negative tested bacteria with minimum inhibitory concentration between 2.5 and 20 mg/ml. In addition, the most sensitive bacterium was Proteus vulgaris, with an inhibitory concentration (2.5 and 5 mm). While the most resistant bacterium was Staphylococcus epidermidis. Due to the physical and chemical properties of the solvents, different extracts of F. schweinfurthii aerial parts exhibited diverse antioxidant capabilities in the antioxidant activity experiment. Methanol and ethyl acetate extracts exhibited IC50 values of 236 ± 0.2µg/ml and 359.4± 0.6µg/ml, respectively. Conclusion: According to the findings of this study, the aerial portions of F. schweinfurthii could be considered a possible source of natural antioxidants as well as a valuable source of antibacterial agents against bacteria that cause ear infections. Peer Review History: Received: 5 July 2022; Revised: 20 August; Accepted: 9 September, Available online: 15 September 2022 Academic Editor: Dr. DANIYAN Oluwatoyin Michael, Obafemi Awolowo University, ILE-IFE, Nigeria, toyinpharm@gmail.com UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file: Reviewer's Comments: Average Peer review marks at initial stage: 5.0/10 Average Peer review marks at publication stage: 7.0/10 Reviewers: Ali Jaber, Laboratory for Research and Development of Medicines and Natural Products, RDMPN, Faculty of Pharmacy, Lebanese University, Beirut, Lebanon. Dr. Sangeetha Arullappan, Universiti Tunku Abdul Rahman, Malaysia, sangeetha@utar.edu.my Similar Articles: INVESTIGATION OF LIPOIDIAL CONTENTS AND THEIR ANTIMICROBIAL ACTIVITY OF FORSSKAOLEA VIRIDIS AND TRICHODESMA EHRENBERGII WILDLY DISTRIBUTED IN EGYPT ANTI-INFLAMMATORY AND ANTI-OXIDANT ACTIVITIES OF METHANOL EXTRACT OF BAPHIA NITIDA

Secondary Metabolites of Nicotiana tabacum and Their Biological Activities: A Review

Nicotiana tabacum (tobacco) is one of the most commercially farming products in the world. Indonesia is one of the top ten tobacco producing countries in the world since 1990’s. Based on literature studies, tobacco has the main secondary metabolites such as cembranoids and flavonoids. They have fine biological activities as antiviral, antimicrobial, antioxidant, antiHIV, anti-proliferative, anti-inflammatory, anti-parasitic, anti-termite, and cytotoxicity effects. Therefore, N. tabacum is potential for further investigation on natural products research. This review aims to provide scientific evidences related to structure activity relationship between secondary metabolites and biological activities of N. tabacum.