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Natural Compounds for Disease and Health II

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: closed (28 February 2025) | Viewed by 15764

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Dr. George P.H. Leung

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Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
Interests: natural products; cardiovascular pharmacology; regulation of vascular tone; angiogenesis; ischemic injury; nucleoside transporters
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Dr. Jingjing Li

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Guest Editor

Department of Rehabilitation Sciences, Hong Kong Polytechnic University, Hong Kong, China
Interests: phytomedicine; angiogenesis; tumor- associated macrophages; tumor microenvironment
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Dear Colleagues,

Even as medicine continues to advance, we still see more disease than ever before. Acute and chronic diseases impose a heavy burden on the healthcare system since patients are usually required to take medications for a certain period or time, or even for life, in order to treat or limit the deterioration of their diseases. In addition to drug treatment and lifestyle modification, many people also choose to consume natural products that are presented as or as being beneficial effects for health. Therefore, there has been an exponential increase in the number of preclinical and clinical studies related to the pharmacology of natural products. Some interesting active ingredients have been found that may serve as the lead compounds for the development of novel therapeutic agents.

For this Special Issue of Molecules, entitled “Natural Compounds for Disease and Health II”, we invite researchers to present novel data on the pharmacological actions of natural products and their active ingredients, accounting for their potential implications for the treatment of various diseases and the promotion of health. Original papers or reviews are welcome.

Dr. George P.H. Leung
Dr. Jingjing Li
Guest Editors

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Keywords

natural products
phytochemistry
structure–activity relationship
mechanism of action
anti-aging
cancer
cardiovascular diseases
digestive diseases
endocrine disorders
immune diseases
infections
inflammation
liver diseases
metabolic diseases
musculoskeletal diseases
neurodegenerative diseases
pain
psychiatric diseases
renal diseases
respiratory diseases

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Natural Compounds for Disease and Health in Molecules (16 articles)

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16 pages, 2264 KiB

Open AccessArticle

Therapeutic Potential of Myricitrin in a db/db Mouse Model of Type 2 Diabetes

by Sang Ryong Kim, Young-Je Kim, HwiCheol Kim, Sojeong Park and Un Ju Jung

Molecules 2025, 30(7), 1460; https://doi.org/10.3390/molecules30071460 - 25 Mar 2025

Viewed by 340

Abstract

Type 2 diabetes is characterized by insulin resistance, which contributes to dysregulated glucose and lipid metabolism and is associated with chronic inflammation. While previous studies have examined the effects of myricitrin in streptozotocin-induced diabetic models, its impact on the db/db mouse, a model that better reflects insulin resistance-associated metabolic disturbances, remains unclear. In this study, mice were divided into three groups (db/+, db/db, and db/db + 0.02% myricitrin) and were fed their respective diets for five weeks. Myricitrin supplementation reduced fat mass, adipocyte size, and plasma leptin levels, which were elevated in db/db mice. Although myricitrin did not affect fasting blood glucose levels, it lowered plasma insulin, hemoglobin A1c, postprandial glucose levels, and the homeostasis model assessment of insulin resistance, suggesting improvements in insulin sensitivity and glucose homeostasis. Enhanced pancreatic insulin expression, along with reduced hepatic gluconeogenic enzyme activities and mRNA expression, contributed to the improved glucose homeostasis observed in myricitrin-supplemented mice. Additionally, myricitrin reduced hepatic triglyceride levels and lipid droplet accumulation by inhibiting hepatic fatty acid synthase activity. It also decreased plasma inflammatory marker levels and their mRNA expression in adipose tissue. These findings suggest that myricitrin may be a promising therapeutic candidate for type 2 diabetes. Full article

(This article belongs to the Special Issue Natural Compounds for Disease and Health II)

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24 pages, 2805 KiB

Open AccessFeature PaperArticle

Chemical Analysis and Antioxidant Activities of Resin Fractions from Pistacia lentiscus L. var. Chia in Neuroblastoma SH-SY5Y Cells

by Achilleas Georgantopoulos, Foteini D. Kalousi, Federica Pollastro, Ioannis Tsialtas, Natasa P. Kalogiouri and Anna-Maria G. Psarra

Molecules 2025, 30(5), 997; https://doi.org/10.3390/molecules30050997 - 21 Feb 2025

Viewed by 645

Abstract

Chios mastiha is the natural aromatic resin of Pistacia lentiscus L. var. Chia, Anacardiaceae, which is exclusively cultivated in the southern part of the Greek island of Chios. Chios mastiha (P. lenticonus/Chios mastiha) is well-known for its distinctive taste and aroma and has been known since ancient times due to its healing properties in gastrointestinal and inflammatory disorders and because of its anti-bacterial and anti-fungal activities. In this study, the chemical composition, applying LC-QTOF-MS/MS analysis, and the antioxidant activities of three different polarity P. lenticonus/Chios mastiha fractions, apolar, medium polar, and polar, were characterized in human neuroblastoma SH-SY5Y cells. Chemical analysis of the fractions unveiled new components of P. lenticonus/Chios mastiha, mainly fatty acids compounds, known for their antioxidant activity and regulatory effects on lipid metabolism. By applying the MTT assay and confocal microscopy analysis, we showed that P. lenticonus/Chios mastiha fractions, especially the apolar and medium polar fractions, enriched in triterpenes and fatty acids, caused suppression of the H₂O₂-induced reduction in cell viability, ROS production, and depolarization of the mitochondrial membrane potential, in SH-SY5Y cells. Moreover, Western blot analysis revealed that apolar fraction, enriched in fatty acids, induced expression of the PPARα, which is well-known for its antioxidant activities and its crucial role in lipid metabolism. Induction of PPARα, a GR target gene, was also accompanied by an increase in GR protein levels. Enhanced antioxidant activities of the apolar fraction may be correlated with its chemical composition, enriched in fatty acids and triterpenoids. Thus, our results indicate the neuroprotective actions of P. lenticonus/Chios mastiha fractions, highlighting their potential application as neuroprotective agents in neurodegenerative diseases. Full article

(This article belongs to the Special Issue Natural Compounds for Disease and Health II)

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17 pages, 2192 KiB

Open AccessArticle

Zephycandidine A and Synthetic Analogues—Synthesis and Evaluation of Biological Activity

by Thomas Klaßmüller, Florian Lengauer, Julia Blenninger, Franz Geisslinger, Karin Bartel and Franz Bracher

Molecules 2025, 30(3), 752; https://doi.org/10.3390/molecules30030752 - 6 Feb 2025

Viewed by 611

Abstract

A convenient total synthesis of the imidazo[1,2-f]phenanthridine-type Amaryllidaceae alkaloid zephycandidine A (3) was developed, which further allowed us to perform modifications of substituents on benzenoid ring A and imidazole ring D. The biological activities of all synthesized compounds were evaluated, and it was reported that activities against cancer cells of the parent alkaloid were poorly reproducible, while the closely related analogue THK-121 (11) showed a strong inhibitory effect on proliferation. Additionally, our novel analogue significantly induced cell death via the intrinsic apoptosis pathway, evident by the loss of mitochondrial membrane potential, increased mitochondrial oxidative stress, and disrupted mitochondrial structure in the same cells. At the same time, healthy cells were less affected by the treatment with THK-121 (11), indicating a potential therapeutic margin. Full article

(This article belongs to the Special Issue Natural Compounds for Disease and Health II)

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9 pages, 2103 KiB

Open AccessArticle

Isolation of Anti-Prion Compounds from Curcuma phaeocaulis Valeton Extract

by Jaehyeon Kim, Hakmin Lee, Hye Mi Kim, Ji Hoon Kim, Sanghoon Byun, Sungeun Lee, Chul Young Kim and Chongsuk Ryou

Molecules 2024, 29(17), 4034; https://doi.org/10.3390/molecules29174034 - 26 Aug 2024

Viewed by 1128

Abstract

Prion diseases, known as a group of fatal neurodegenerative disorders caused by prions, remain incurable despite extensive research efforts. In a recent study, crude extract from Curcuma phaeocaulis Valeton (Cp) showed promising anti-prion efficacy in in vitro and in vivo models, prompting further investigation into their active compounds. We endeavored to identify the chemical constituents of the Cp extract and discover potential anti-prion agents. With the use of centrifugal partition chromatography (CPC), major constituents were isolated from the n-hexane (HX) fraction of the extract in a single step. Spectroscopic analysis confirmed the presence of curcumenone, curcumenol, and furanodienone. Subsequent efficacy testing in a cell culture model of prion disease identified curcumenol and furanodienone as active compounds. This study underscores the potential of natural products in the search for effective treatments against prion diseases. Full article

(This article belongs to the Special Issue Natural Compounds for Disease and Health II)

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13 pages, 2257 KiB

Open AccessArticle

Cytotoxic Activity of Lepidium virginicum L. Methanolic Extract on Human Colorectal Cancer Cells, Caco-2, through p53-Mediated Apoptosis

by Renata Gallegos-Saucedo, Tonatiuh Barrios-García, Eduardo E. Valdez-Morales, Emmanuel Cabañas-García, Alma Barajas-Espinosa, Yenny Adriana Gómez-Aguirre and Raquel Guerrero-Alba

Molecules 2024, 29(16), 3920; https://doi.org/10.3390/molecules29163920 - 20 Aug 2024

Viewed by 1936

Abstract

Colorectal cancer (CRC) is the third most common type of cancer worldwide. Its treatment options have had a limited impact on cancer remission prognosis. Therefore, there is an ongoing need to discover novel anti-cancer agents. Medicinal plants have gained recognition as a source of anti-cancer bioactive compounds. Recently, ethanolic extract of L. virginicum stems ameliorated dinitrobenzene sulfonic acid (DNBS)-induced colitis by modulating the intestinal immune response. However, no scientific study has demonstrated this potential cytotoxic impact on colon cancer cells. The objective of this study was to evaluate the cytotoxic effect of the methanolic extract of L. virginicum (ELv) on a human colorectal adenocarcinoma cell line (Caco-2) and to identify and quantify the phenolic compounds present in ELv extracts by liquid chromatography-mass spectrometry analysis. The cytotoxic activity was assessed using cell viability assays by reduction in the compound 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH). MTT and LDH assays revealed that the ELv decreases cell viability in the Caco-2 cell line in a concentration-dependent manner. Cell death was a result of DNA fragmentation and p53-mediated apoptosis. Eight phenolic acids and five flavonoids were identified and quantified in the stems. In conclusion, our findings demonstrate that the extract of L. virginicum possesses cytotoxic properties on Caco-2 cell line, suggesting that it could be a potential source of new drugs against CRC. Full article

(This article belongs to the Special Issue Natural Compounds for Disease and Health II)

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14 pages, 7189 KiB

Open AccessArticle

Artemisinin Confers Cytoprotection toward Hydrogen Peroxide-Induced Cell Apoptosis in Retinal Pigment Epithelial Cells in Correlation with the Increased Acetylation of Histone H4 at Lysine 8

by Chao Yang, Lijun Ge, Xiyong Yu, Philip Lazarovici and Wenhua Zheng

Molecules 2024, 29(8), 1789; https://doi.org/10.3390/molecules29081789 - 15 Apr 2024

Cited by 2 | Viewed by 1728

Abstract

Increased oxidative stress is one of the critical pathologies inducing age-related macular degeneration (AMD), characterized by retinal pigment epithelial (RPE) cell damage and death. The unbalanced acetylation and deacetylation of histones have been implicated in AMD pathogenesis or hydrogen peroxide (H₂O₂)-induced cell damage. Therefore, strategies aimed at controlling the balance between acetylation and deacetylation may effectively protect RPE cells from oxidative damage. Artemisinin is an antimalarial lactone drug derived from Artemisia annua, with antioxidant activity known to modulate histone acetylation in the brain, but its effect on the retina is unknown. In this study, we aimed to investigate whether Artemisinin exerts a cytoprotective effect on oxidative stress-induced apoptosis in RPE cells by regulating histone acetylation. We hypothesized that Artemisinin confers cytoprotection toward H₂O₂-induced apoptosis in RPE cells through this mechanism. In the present study, we found that Artemisinin at a sub-clinic dosage of 20 μM inhibited the H₂O₂-induced cell viability decrease and B-cell lymphoma 2 (Bcl-2) protein level decrease and attenuated the H₂O₂-induced decrease in the histone H4 lysine (Lys) 8 acetylation [Acetyl-H4 (Lys 8)] level in the retinal RPE cell line D407. As expected, histone deacetylase inhibitor Trichostatin A at the concentration of 250 nM increased the Acetyl-H4 (Lys 8) level in D407 cells and attenuated the H₂O₂-induced cell viability decrease and apoptosis. Similar findings were obtained using adult RPE (ARPE)19 cells, another human RPE cell line, and primary human RPE cell cultures. In conclusion, these results confirmed our hypothesis and indicated that Artemisinin attenuated H₂O₂-induced apoptosis in apparent correlation with the increase in the Acetyl-H4 (Lys 8) level, which is associated with gene transcription and cell survival. By modulating histone acetylation, Artemisinin may restore the balance between acetylation and deacetylation and enhance the resistance and survival of RPE cells under oxidative stress. Our study provides novel mechanistic insights into the effect of Artemisinin on histone acetylation and apoptosis in RPE cells and supports the potential application of Artemisinin in the prevention and/or treatment of AMD. Full article

(This article belongs to the Special Issue Natural Compounds for Disease and Health II)

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15 pages, 3340 KiB

Open AccessArticle

Neuroprotective Effects of Polysaccharides and Gallic Acid from Amauroderma rugosum against 6-OHDA-Induced Toxicity in SH-SY5Y Cells

by Panthakarn Rangsinth, Nattaporn Pattarachotanant, Wen Wang, Polly Ho-Ting Shiu, Chengwen Zheng, Renkai Li, Tewin Tencomnao, Siriporn Chuchawankul, Anchalee Prasansuklab, Timothy Man-Yau Cheung, Jingjing Li and George Pak-Heng Leung

Molecules 2024, 29(5), 953; https://doi.org/10.3390/molecules29050953 - 22 Feb 2024

Cited by 2 | Viewed by 2471

Abstract

The pharmacological activity and medicinal significance of Amauroderma rugosum (AR) have rarely been documented. We examined the antioxidant and neuroprotective effects of AR on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in an SH-SY5Y human neuroblastoma cell model of Parkinson’s disease (PD) and explored the active ingredients responsible for these effects. The results showed that the AR aqueous extract could scavenge reactive oxygen species and reduce SH-SY5Y cell death induced by 6-OHDA. In addition, the AR aqueous extract increased the survival of Caenorhabditis elegans upon juglone-induced toxicity. Among the constituents of AR, only polysaccharides and gallic acid exhibited antioxidant and neuroprotective effects. The AR aqueous extract reduced apoptosis and increased the expression of phospho-Akt, phospho-mTOR, phospho-MEK, phospho-ERK, and superoxide dismutase-1 in 6-OHDA-treated SH-SY5Y cells. The polysaccharide-rich AR extract was slightly more potent than the aqueous AR extract; however, it did not affect the expression of phospho-Akt or phospho-mTOR. In conclusion, the AR aqueous extract possessed antioxidant and neuroprotective properties against 6-OHDA-induced toxicity in SH-SY5Y cells. The mechanism of action involves the upregulation of the Akt/mTOR and MEK/ERK-dependent pathways. These findings indicate the potential utility of AR and its active ingredients in preventing or treating neurodegenerative disorders associated with oxidative stress such as PD. Full article

(This article belongs to the Special Issue Natural Compounds for Disease and Health II)

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19 pages, 4469 KiB

Open AccessArticle

Microfluidic Diffusion Sizing Applied to the Study of Natural Products and Extracts That Modulate the SARS-CoV-2 Spike RBD/ACE2 Interaction

by Jason Fauquet, Julie Carette, Pierre Duez, Jiuliang Zhang and Amandine Nachtergael

Molecules 2023, 28(24), 8072; https://doi.org/10.3390/molecules28248072 - 13 Dec 2023

Viewed by 3303

Abstract

The interaction between SARS-CoV-2 spike RBD and ACE2 proteins is a crucial step for host cell infection by the virus. Without it, the entire virion entrance mechanism is compromised. The aim of this study was to evaluate the capacity of various natural product classes, including flavonoids, anthraquinones, saponins, ivermectin, chloroquine, and erythromycin, to modulate this interaction. To accomplish this, we applied a recently developed a microfluidic diffusional sizing (MDS) technique that allows us to probe protein-protein interactions via measurements of the hydrodynamic radius (R_h) and dissociation constant (K_D); the evolution of R_h is monitored in the presence of increasing concentrations of the partner protein (ACE2); and the K_D is determined through a binding curve experimental design. In a second time, with the protein partners present in equimolar amounts, the R_h of the protein complex was measured in the presence of different natural products. Five of the nine natural products/extracts tested were found to modulate the formation of the protein complex. A methanol extract of Chenopodium quinoa Willd bitter seed husks (50 µg/mL; bisdesmoside saponins) and the flavonoid naringenin (1 µM) were particularly effective. This rapid selection of effective modulators will allow us to better understand agents that may prevent SARS-CoV-2 infection. Full article

(This article belongs to the Special Issue Natural Compounds for Disease and Health II)

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19 pages, 4258 KiB

Open AccessFeature PaperReview

Rosmarinus officinalis L. as Fascinating Source of Potential Anticancer Agents Targeting Aromatase and COX-2: An Overview

by Adriana Gargano, Ilario Greco, Carmine Lupia, Stefano Alcaro and Francesca Alessandra Ambrosio

Molecules 2025, 30(8), 1733; https://doi.org/10.3390/molecules30081733 - 12 Apr 2025

Viewed by 372

Abstract

Cancer is the second leading cause of death in the world, with scientific evidence indicating that the enzymes aromatase and cyclooxygenase 2 are upregulated in several types of cancer. Over the past 30 years, natural compounds have played a crucial role in cancer chemotherapy, and to date, many phytocompounds have been reported to interact with these enzymes, inhibiting their activity. Notably, several phytocompounds found in Rosmarinus officinalis L., a medicinal plant native to the Mediterranean region and cultivated around the world, have shown the ability to interact with these enzymes. This review examines the role of the main compounds contained in Rosmarinus officinalis L. as potential anticancer agents acting on aromatase and cyclooxygenase-2. Full article

(This article belongs to the Special Issue Natural Compounds for Disease and Health II)

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24 pages, 2797 KiB

Open AccessReview

Clerodendrum trichotomum Thunberg—An Ornamental Shrub with Medical Properties

by Jan Gomulski and Izabela Grzegorczyk-Karolak

Molecules 2024, 29(14), 3272; https://doi.org/10.3390/molecules29143272 - 10 Jul 2024

Cited by 3 | Viewed by 1816

Abstract

Harlequin glory bower (Clerodendrum trichotomum) is a shrub or small tree belonging to the Lamiaceae family, native to Japan, Korea, and eastern China. It has esthetic value and in Europe, it is cultivated as an ornamental plant. Its sweet-smelling flowers have a white or pink crown. The calyx turns from green to pink–purple over time, providing an especially decorative touch around surrounding the ripe deep-blue fruits that persist until winter. In the areas of its natural occurrence, the leaves and young shoots of C. trichotomum, and sometimes the roots, flowers and fruits, are used in folk medicine due to its anti-inflammatory, analgesic, anticancer, sedative, and hypotensive effects. Products based on Harlequin glory are also used in the treatment of rheumatoid arthritis, joint pain, skin inflammation, or asthma. Preliminary research on the composition of raw material suggests that its health-promoting effect is associated with the presence of numerous secondary metabolites, including phenylpropanoids, flavonoids, lignans, terpenoids, steroids, alkaloids, and anthraquinones. This work reviews the current state of knowledge about the phytochemistry and in vitro and in vivo pharmacological properties of the extracts and main active components isolated from C. trichotomum. It also indicates that before it can be used in modern medicine, further research is necessary regarding the safety and efficacy of the raw material, its mechanisms of action, and dosage. Full article

(This article belongs to the Special Issue Natural Compounds for Disease and Health II)

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