Molecules

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A Systematic Review on the Implication of Minerals in the Onset, Severity and Treatment of Periodontal Disease

by Alfonso Varela-López, Francesca Giampieri, Pedro Bullón, Maurizio Battino and José L. Quiles

Molecules 2016, 21(9), 1183; https://doi.org/10.3390/molecules21091183 - 7 Sep 2016

Cited by 25 | Viewed by 8448

Periodontal disease is an inflammatory disease with high prevalence in adults that leads to destruction of the teeth-supporting tissues. Periodontal therapy has been traditionally directed at reduction of the bacterial load to a level that encourages health-promoting bacteria and maintenance of oral-hygiene. The [...] Read more.

Periodontal disease is an inflammatory disease with high prevalence in adults that leads to destruction of the teeth-supporting tissues. Periodontal therapy has been traditionally directed at reduction of the bacterial load to a level that encourages health-promoting bacteria and maintenance of oral-hygiene. The role of nutrition in different chronic inflammatory diseases has been the subject of an increasing body of research in the last decades. In this sense, there has been an important increase in the volume of research on role of nutrition in periodontitis since the diet has known effects on the immune system and inflammatory cascades. Minerals play a key role in all these processes due to the multiple pathways where they participate. To clarify the role of the different minerals in the establishment, progression and/or treatment of this pathology, a systemically review of published literature cited in PubMed until May 2016 was conducted, which included research on the relationship of these elements with the onset and progression of periodontal disease. Among all the minerals, calcium dietary intake seems important to maintain alveolar bone. Likewise, dietary proportions of minerals that may influence its metabolism also can be relevant. Lastly, some observations suggest that all those minerals with roles in immune and/or antioxidant systems should be considered in future research. Full article

(This article belongs to the Special Issue 20th Anniversary of Molecules—Recent Advances in Natural Products)

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Open AccessReview

Antioxidative and Antidiabetic Effects of Natural Polyphenols and Isoflavones

by Aya Umeno, Masanori Horie, Kazutoshi Murotomi, Yoshihiro Nakajima and Yasukazu Yoshida

Molecules 2016, 21(6), 708; https://doi.org/10.3390/molecules21060708 - 30 May 2016

Cited by 191 | Viewed by 13655

Abstract

Many polyphenols that contain more than two phenolic hydroxyl groups are natural antioxidants and can provide health benefits to humans. These polyphenols include, for example, oleuropein, hydroxytyrosol, catechin, chlorogenic acids, hesperidin, nobiletin, and isoflavones. These have been studied widely because of their strong [...] Read more.

Many polyphenols that contain more than two phenolic hydroxyl groups are natural antioxidants and can provide health benefits to humans. These polyphenols include, for example, oleuropein, hydroxytyrosol, catechin, chlorogenic acids, hesperidin, nobiletin, and isoflavones. These have been studied widely because of their strong radical-scavenging and antioxidative effects. These effects may contribute to the prevention of diseases, such as diabetes. Insulin secretion, insulin resistance, and homeostasis are important factors in the onset of diabetes, a disease that is associated with dysfunction of pancreatic β-cells. Oxidative stress is thought to contribute to this dysfunction and the effects of antioxidants on the pathogenesis of diabetes have, therefore, been investigated. Here, we summarize the antioxidative effects of polyphenols from the perspective of their radical-scavenging activities as well as their effects on signal transduction pathways. We also describe the preventative effects of polyphenols on diabetes by referring to recent studies including those reported by us. Appropriate analytical approaches for evaluating antioxidants in studies on the prevention of diabetes are comprehensively reviewed. Full article

(This article belongs to the Special Issue 20th Anniversary of Molecules—Recent Advances in Natural Products)

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Open AccessReview

Recent Advances in the Analysis of Phenolic Compounds in Unifloral Honeys

by Marco Ciulu, Nadia Spano, Maria I. Pilo and Gavino Sanna

Molecules 2016, 21(4), 451; https://doi.org/10.3390/molecules21040451 - 8 Apr 2016

Cited by 96 | Viewed by 11511

Abstract

Honey is one of the most renowned natural foods. Its composition is extremely variable, depending on its botanical and geographical origins, and the abundant presence of functional compounds has contributed to the increased worldwide interest is this foodstuff. In particular, great attention has [...] Read more.

Honey is one of the most renowned natural foods. Its composition is extremely variable, depending on its botanical and geographical origins, and the abundant presence of functional compounds has contributed to the increased worldwide interest is this foodstuff. In particular, great attention has been paid by the scientific community towards classes of compounds like phenolic compounds, due to their capability to act as markers of unifloral honey origin. In this contribution the most recent progress in the assessment of new analytical procedures aimed at the definition of the qualitative and quantitative profile of phenolic compounds of honey have been highlighted. A special emphasis has been placed on the innovative aspects concerning the extraction procedures, along with the most recent strategies proposed for the analysis of phenolic compounds. Moreover, the centrality of validation procedures has been claimed and extensively discussed in order to ensure the fitness-for-purpose of the proposed analytical methods. In addition, the exploitation of the phenolic profile as a tool for the classification of the botanical and geographical origin has been described, pointing out the usefulness of chemometrics in the interpretation of data sets originating from the analysis of polyphenols. Finally, recent results in concerning the evaluation of the antioxidant properties of unifloral honeys and the development of new analytical approaches aimed at measuring this parameter have been reviewed. Full article

(This article belongs to the Special Issue 20th Anniversary of Molecules—Recent Advances in Natural Products)

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Open AccessReview

Coenzyme Q and Its Role in the Dietary Therapy against Aging

by Alfonso Varela-López, Francesca Giampieri, Maurizio Battino and José L. Quiles

Molecules 2016, 21(3), 373; https://doi.org/10.3390/molecules21030373 - 18 Mar 2016

Cited by 70 | Viewed by 12670

Abstract

Coenzyme Q (CoQ) is a naturally occurring molecule located in the hydrophobic domain of the phospholipid bilayer of all biological membranes. Shortly after being discovered, it was recognized as an essential electron transport chain component in mitochondria where it is particularly abundant. Since [...] Read more.

Coenzyme Q (CoQ) is a naturally occurring molecule located in the hydrophobic domain of the phospholipid bilayer of all biological membranes. Shortly after being discovered, it was recognized as an essential electron transport chain component in mitochondria where it is particularly abundant. Since then, more additional roles in cell physiology have been reported, including antioxidant, signaling, death prevention, and others. It is known that all cells are able to synthesize functionally sufficient amounts of CoQ under normal physiological conditions. However, CoQ is a molecule found in different dietary sources, which can be taken up and incorporated into biological membranes. It is known that mitochondria have a close relationship with the aging process. Additionally, delaying the aging process through diet has aroused the interest of scientists for many years. These observations have stimulated investigation of the anti-aging potential of CoQ and its possible use in dietary therapies to alleviate the effects of aging. In this context, the present review focus on the current knowledge and evidence the roles of CoQ cells, its relationship with aging, and possible implications of dietary CoQ in relation to aging, lifespan or age-related diseases. Full article

(This article belongs to the Special Issue 20th Anniversary of Molecules—Recent Advances in Natural Products)

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Open AccessReview

Targeting Reactive Carbonyl Species with Natural Sequestering Agents

by Sung Won Hwang, Yoon-Mi Lee, Giancarlo Aldini and Kyung-Jin Yeum

Molecules 2016, 21(3), 280; https://doi.org/10.3390/molecules21030280 - 27 Feb 2016

Cited by 27 | Viewed by 7019

Abstract

Reactive carbonyl species generated by the oxidation of polyunsaturated fatty acids and sugars are highly reactive due to their electrophilic nature, and are able to easily react with the nucleophilic sites of proteins as well as DNA causing cellular dysfunction. Levels of reactive [...] Read more.

Reactive carbonyl species generated by the oxidation of polyunsaturated fatty acids and sugars are highly reactive due to their electrophilic nature, and are able to easily react with the nucleophilic sites of proteins as well as DNA causing cellular dysfunction. Levels of reactive carbonyl species and their reaction products have been reported to be elevated in various chronic diseases, including metabolic disorders and neurodegenerative diseases. In an effort to identify sequestering agents for reactive carbonyl species, various analytical techniques such as spectrophotometry, high performance liquid chromatography, western blot, and mass spectrometry have been utilized. In particular, recent advances using a novel high resolution mass spectrometry approach allows screening of complex mixtures such as natural products for their sequestering ability of reactive carbonyl species. To overcome the limited bioavailability and bioefficacy of natural products, new techniques using nanoparticles and nanocarriers may offer a new attractive strategy for increased in vivo utilization and targeted delivery of bioactives. Full article

(This article belongs to the Special Issue 20th Anniversary of Molecules—Recent Advances in Natural Products)

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Open AccessReview

Curcumin and Health

by Mario Pulido-Moran, Jorge Moreno-Fernandez, Cesar Ramirez-Tortosa and MCarmen Ramirez-Tortosa

Molecules 2016, 21(3), 264; https://doi.org/10.3390/molecules21030264 - 25 Feb 2016

Cited by 434 | Viewed by 49856

Abstract

Nowadays, there are some molecules that have shown over the years a high capacity to act against relevant pathologies such as cardiovascular disease, neurodegenerative disorders or cancer. This article provides a brief review about the origin, bioavailability and new research on curcumin and [...] Read more.

Nowadays, there are some molecules that have shown over the years a high capacity to act against relevant pathologies such as cardiovascular disease, neurodegenerative disorders or cancer. This article provides a brief review about the origin, bioavailability and new research on curcumin and synthetized derivatives. It examines the beneficial effects on health, delving into aspects such as cancer, cardiovascular effects, metabolic syndrome, antioxidant capacity, anti-inflammatory properties, and neurological, liver and respiratory disorders. Thanks to all these activities, curcumin is positioned as an interesting nutraceutical. This is the reason why it has been subjected to several modifications in its structure and administration form that have permitted an increase in bioavailability and effectiveness against different diseases, decreasing the mortality and morbidity associated to these pathologies. Full article

(This article belongs to the Special Issue 20th Anniversary of Molecules—Recent Advances in Natural Products)

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Open AccessReview

Potential Use of Turkish Medicinal Plants in the Treatment of Various Diseases

by Gulay Ozkan, Senem Kamiloglu, Tugba Ozdal, Dilek Boyacioglu and Esra Capanoglu

Molecules 2016, 21(3), 257; https://doi.org/10.3390/molecules21030257 - 25 Feb 2016

Cited by 69 | Viewed by 14134

Abstract

Medicinal plants are sources of health-promoting substances, including phytochemicals and phytoalexins that comprise polyphenols, flavonoids, carotenoids, vitamins A, C, E and several other constituents. Many studies have indicated that medicinal plants have been used to treat human diseases for thousands of years owing [...] Read more.

Medicinal plants are sources of health-promoting substances, including phytochemicals and phytoalexins that comprise polyphenols, flavonoids, carotenoids, vitamins A, C, E and several other constituents. Many studies have indicated that medicinal plants have been used to treat human diseases for thousands of years owing to their antimicrobial and antioxidant activities. Medicinal plants reduce the oxidative stress in cells and prevent cancer, cardiovascular and inflammatory diseases, neurodegenerative and digestive system disorders. These potential beneficial effects have been attributed to the presence of bioactive compounds that show antioxidant properties by acting as free radical scavengers or metal chelators, reducing the reactions that produce reactive oxygen and nitrogen species (ROS/RNS). Considering the importance of medicinal plants in terms of their beneficial health effects, some of the medicinally important plants grown in Turkey are covered in this review with respect to their antioxidant potential and phytochemical profile. Full article

(This article belongs to the Special Issue 20th Anniversary of Molecules—Recent Advances in Natural Products)

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Open AccessReview

Molecular Mechanisms of Inhibition of Streptococcus Species by Phytochemicals

by Soheila Abachi, Song Lee and H. P. Vasantha Rupasinghe

Molecules 2016, 21(2), 215; https://doi.org/10.3390/molecules21020215 - 17 Feb 2016

Cited by 56 | Viewed by 13871

Abstract

This review paper summarizes the antibacterial effects of phytochemicals of various medicinal plants against pathogenic and cariogenic streptococcal species. The information suggests that these phytochemicals have potential as alternatives to the classical antibiotics currently used for the treatment of streptococcal infections. The phytochemicals [...] Read more.

This review paper summarizes the antibacterial effects of phytochemicals of various medicinal plants against pathogenic and cariogenic streptococcal species. The information suggests that these phytochemicals have potential as alternatives to the classical antibiotics currently used for the treatment of streptococcal infections. The phytochemicals demonstrate direct bactericidal or bacteriostatic effects, such as: (i) prevention of bacterial adherence to mucosal surfaces of the pharynx, skin, and teeth surface; (ii) inhibition of glycolytic enzymes and pH drop; (iii) reduction of biofilm and plaque formation; and (iv) cell surface hydrophobicity. Collectively, findings from numerous studies suggest that phytochemicals could be used as drugs for elimination of infections with minimal side effects. Full article

(This article belongs to the Special Issue 20th Anniversary of Molecules—Recent Advances in Natural Products)

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Open AccessReview

Organic Nanomaterials and Their Applications in the Treatment of Oral Diseases

by Maria Justina Roxana Virlan, Daniela Miricescu, Radu Radulescu, Cristina M. Sabliov, Alexandra Totan, Bogdan Calenic and Maria Greabu

Molecules 2016, 21(2), 207; https://doi.org/10.3390/molecules21020207 - 9 Feb 2016

Cited by 87 | Viewed by 11196

Abstract

There is a growing interest in the development of organic nanomaterials for biomedical applications. An increasing number of studies focus on the uses of nanomaterials with organic structure for regeneration of bone, cartilage, skin or dental tissues. Solid evidence has been found for [...] Read more.

There is a growing interest in the development of organic nanomaterials for biomedical applications. An increasing number of studies focus on the uses of nanomaterials with organic structure for regeneration of bone, cartilage, skin or dental tissues. Solid evidence has been found for several advantages of using natural or synthetic organic nanostructures in a wide variety of dental fields, from implantology, endodontics, and periodontics, to regenerative dentistry and wound healing. Most of the research is concentrated on nanoforms of chitosan, silk fibroin, synthetic polymers or their combinations, but new nanocomposites are constantly being developed. The present work reviews in detail current research on organic nanoparticles and their potential applications in the dental field. Full article

(This article belongs to the Special Issue 20th Anniversary of Molecules—Recent Advances in Natural Products)

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Open AccessReview

Chemopreventive and Therapeutic Effects of Edible Berries: A Focus on Colon Cancer Prevention and Treatment

by Sadia Afrin, Francesca Giampieri, Massimiliano Gasparrini, Tamara Y. Forbes-Hernandez, Alfonso Varela-López, José L. Quiles, Bruno Mezzetti and Maurizio Battino

Molecules 2016, 21(2), 169; https://doi.org/10.3390/molecules21020169 - 30 Jan 2016

Cited by 132 | Viewed by 20236

Abstract

Colon cancer is one of the most prevalent diseases across the world. Numerous epidemiological studies indicate that diets rich in fruit, such as berries, provide significant health benefits against several types of cancer, including colon cancer. The anticancer activities of berries are attributed [...] Read more.

Colon cancer is one of the most prevalent diseases across the world. Numerous epidemiological studies indicate that diets rich in fruit, such as berries, provide significant health benefits against several types of cancer, including colon cancer. The anticancer activities of berries are attributed to their high content of phytochemicals and to their relevant antioxidant properties. In vitro and in vivo studies have demonstrated that berries and their bioactive components exert therapeutic and preventive effects against colon cancer by the suppression of inflammation, oxidative stress, proliferation and angiogenesis, through the modulation of multiple signaling pathways such as NF-κB, Wnt/β-catenin, PI3K/AKT/PKB/mTOR, and ERK/MAPK. Based on the exciting outcomes of preclinical studies, a few berries have advanced to the clinical phase. A limited number of human studies have shown that consumption of berries can prevent colorectal cancer, especially in patients at high risk (familial adenopolyposis or aberrant crypt foci, and inflammatory bowel diseases). In this review, we aim to highlight the findings of berries and their bioactive compounds in colon cancer from in vitro and in vivo studies, both on animals and humans. Thus, this review could be a useful step towards the next phase of berry research in colon cancer. Full article

(This article belongs to the Special Issue 20th Anniversary of Molecules—Recent Advances in Natural Products)

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Olive Oil and the Hallmarks of Aging

by Lucía Fernández del Río, Elena Gutiérrez-Casado, Alfonso Varela-López and José M. Villalba

Molecules 2016, 21(2), 163; https://doi.org/10.3390/molecules21020163 - 29 Jan 2016

Cited by 72 | Viewed by 22393

Abstract

Aging is a multifactorial and tissue-specific process involving diverse alterations regarded as the “hallmarks of aging”, which include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion and altered intracellular communication. Virtually all [...] Read more.

Aging is a multifactorial and tissue-specific process involving diverse alterations regarded as the “hallmarks of aging”, which include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion and altered intracellular communication. Virtually all these hallmarks are targeted by dietary olive oil, particularly by virgin olive oil, since many of its beneficial effects can be accounted not only for the monounsaturated nature of its predominant fatty acid (oleic acid), but also for the bioactivity of its minor compounds, which can act on cells though both direct and indirect mechanisms due to their ability to modulate gene expression. Among the minor constituents of virgin olive oil, secoiridoids stand out for their capacity to modulate many pathways that are relevant for the aging process. Attenuation of aging-related alterations by olive oil or its minor compounds has been observed in cellular, animal and human models. How olive oil targets the hallmarks of aging could explain the improvement of health, reduced risk of aging-associated diseases, and increased longevity which have been associated with consumption of a typical Mediterranean diet containing this edible oil as the predominant fat source. Full article

(This article belongs to the Special Issue 20th Anniversary of Molecules—Recent Advances in Natural Products)

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Application of Bioactive Quercetin in Oncotherapy: From Nutrition to Nanomedicine

by Ju-Suk Nam, Ashish Ranjan Sharma, Lich Thi Nguyen, Chiranjib Chakraborty, Garima Sharma and Sang-Soo Lee

Molecules 2016, 21(1), 108; https://doi.org/10.3390/molecules21010108 - 19 Jan 2016

Cited by 149 | Viewed by 14577

Abstract

Phytochemicals as dietary constituents are being explored for their cancer preventive properties. Quercetin is a major constituent of various dietary products and recently its anti-cancer potential has been extensively explored, revealing its anti-proliferative effect on different cancer cell lines, both in vitro and [...] Read more.

Phytochemicals as dietary constituents are being explored for their cancer preventive properties. Quercetin is a major constituent of various dietary products and recently its anti-cancer potential has been extensively explored, revealing its anti-proliferative effect on different cancer cell lines, both in vitro and in vivo. Quercetin is known to have modulatory effects on cell apoptosis, migration and growth via various signaling pathways. Though, quercetin possesses great medicinal value, its applications as a therapeutic drug are limited. Problems like low oral bioavailability and poor aqueous solubility make quercetin an unreliable candidate for therapeutic purposes. Additionally, the rapid gastrointestinal digestion of quercetin is also a major barrier for its clinical translation. Hence, to overcome these disadvantages quercetin-based nanoformulations are being considered in recent times. Nanoformulations of quercetin have shown promising results in its uptake by the epithelial system as well as enhanced delivery to the target site. Herein we have tried to summarize various methods utilized for nanofabrication of quercetin formulations and for stable and sustained delivery of quercetin. We have also highlighted the various desirable measures for its use as a promising onco-therapeutic agent. Full article

(This article belongs to the Special Issue 20th Anniversary of Molecules—Recent Advances in Natural Products)

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Analgesic Potential of Essential Oils

by José Ferreira Sarmento-Neto, Lázaro Gomes Do Nascimento, Cícero Francisco Bezerra Felipe and Damião Pergentino De Sousa

Molecules 2016, 21(1), 20; https://doi.org/10.3390/molecules21010020 - 23 Dec 2015

Cited by 55 | Viewed by 21189

Abstract

Pain is an unpleasant sensation associated with a wide range of injuries and diseases, and affects approximately 20% of adults in the world. The discovery of new and more effective drugs that can relieve pain is an important research goal in both the [...] Read more.

Pain is an unpleasant sensation associated with a wide range of injuries and diseases, and affects approximately 20% of adults in the world. The discovery of new and more effective drugs that can relieve pain is an important research goal in both the pharmaceutical industry and academia. This review describes studies involving antinociceptive activity of essential oils from 31 plant species. Botanical aspects of aromatic plants, mechanisms of action in pain models and chemical composition profiles of the essential oils are discussed. The data obtained in these studies demonstrate the analgesic potential of this group of natural products for therapeutic purposes. Full article

(This article belongs to the Special Issue 20th Anniversary of Molecules—Recent Advances in Natural Products)

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Open AccessReview

Membrane Interactions of Phytochemicals as Their Molecular Mechanism Applicable to the Discovery of Drug Leads from Plants

by Hironori Tsuchiya

Molecules 2015, 20(10), 18923-18966; https://doi.org/10.3390/molecules201018923 - 16 Oct 2015

Cited by 159 | Viewed by 13800

Abstract

In addition to interacting with functional proteins such as receptors, ion channels, and enzymes, a variety of drugs mechanistically act on membrane lipids to change the physicochemical properties of biomembranes as reported for anesthetic, adrenergic, cholinergic, non-steroidal anti-inflammatory, analgesic, antitumor, antiplatelet, antimicrobial, and [...] Read more.

In addition to interacting with functional proteins such as receptors, ion channels, and enzymes, a variety of drugs mechanistically act on membrane lipids to change the physicochemical properties of biomembranes as reported for anesthetic, adrenergic, cholinergic, non-steroidal anti-inflammatory, analgesic, antitumor, antiplatelet, antimicrobial, and antioxidant drugs. As well as these membrane-acting drugs, bioactive plant components, phytochemicals, with amphiphilic or hydrophobic structures, are presumed to interact with biological membranes and biomimetic membranes prepared with phospholipids and cholesterol, resulting in the modification of membrane fluidity, microviscosity, order, elasticity, and permeability with the potencies being consistent with their pharmacological effects. A novel mechanistic point of view of phytochemicals would lead to a better understanding of their bioactivities, an insight into their medicinal benefits, and a strategic implication for discovering drug leads from plants. This article reviews the membrane interactions of different classes of phytochemicals by highlighting their induced changes in membrane property. The phytochemicals to be reviewed include membrane-interactive flavonoids, terpenoids, stilbenoids, capsaicinoids, phloroglucinols, naphthodianthrones, organosulfur compounds, alkaloids, anthraquinonoids, ginsenosides, pentacyclic triterpene acids, and curcuminoids. The membrane interaction’s applicability to the discovery of phytochemical drug leads is also discussed while referring to previous screening and isolating studies. Full article

(This article belongs to the Special Issue 20th Anniversary of Molecules—Recent Advances in Natural Products)

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Open AccessReview

Anti-Diabetic Potential of Noni: The Yin and the Yang

by Pratibha V. Nerurkar, Phoebe W. Hwang and Erik Saksa

Molecules 2015, 20(10), 17684-17719; https://doi.org/10.3390/molecules201017684 - 25 Sep 2015

Cited by 41 | Viewed by 18103

Abstract

Escalating trends of chronic diseases such as type-2 diabetes (T2D) have sparked a renewed interest in complementary and alternative medicine, including herbal products. Morinda citrifolia (noni) has been used for centuries by Pacific Islanders to treat various ailments. Commercial noni fruit juice has [...] Read more.

Escalating trends of chronic diseases such as type-2 diabetes (T2D) have sparked a renewed interest in complementary and alternative medicine, including herbal products. Morinda citrifolia (noni) has been used for centuries by Pacific Islanders to treat various ailments. Commercial noni fruit juice has been marketed as a dietary supplement since 1996. In 2003, the European Commission approved Tahitian noni juice as a novel food by the Health and Consumer Protection Directorate General. Among noni’s several health benefits, others and we have demonstrated the anti-diabetic effects of fermented noni fruit juice in animal models. Unfortunately, noni’s exciting journey from Polynesian medicine to the research bench does not reach its final destination of successful clinical outcomes when translated into commercial products. Noni products are perceived to be safe due to their “natural” origin. However, inadequate evidence regarding bioactive compounds, molecular targets, mechanism of action, pharmacokinetics, long-term safety, effective dosages, and/or unanticipated side effects are major roadblocks to successful translation “from bench side to bedside”. In this review we summarize the anti-diabetic potential of noni, differences between traditional and modern use of noni, along with beneficial clinical studies of noni products and challenges in clinical translation of noni’s health benefits. Full article

(This article belongs to the Special Issue 20th Anniversary of Molecules—Recent Advances in Natural Products)

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