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Bioactive Compounds from Natural Products for the Prevention and Treatment of Chronic Diseases 2.0

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: 30 April 2024 | Viewed by 11216

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Dr. Dong-Sung Lee

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College of Pharmacy, Chosun University, Gwangju, 61452, Korea
Interests: natural products; bioactive natural compunds; inflammation; neuroinflammation; neuroprotection; oxidative stress; skin diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Natural products may be the oldest form of medicine in human history. In particular, the types of medicine and functional foods using natural compounds are increasing. The aging of society due to the extension of life expectancy is one of the reasons treatments using natural compounds are receiving attention. As the elderly population increases, the number of patients with chronic and degenerative diseases does as well. These diseases have a high risk of side effects due to the nature of taking medicine for extended periods. Therefore, the relatively high safety and low side effects of natural products are very advantageous in the treatment of chronic diseases in this aging society. For these reasons, this Special Issue aims to identify bioactive compounds from natural products for the prevention and treatment of chronic diseases through signaling pathways in vitro or in vivo. We invite you to contribute your current work to this Special Issue as original research articles, review articles, and short communications.

Dr. Dong-Sung Lee
Guest Editor

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Keywords

natural products
natural products isolation
bioactive natural compounds
inflammation
neurodegenerative diseases
skin diseases
cancer
metabolic syndrome
chronic diseases

Published Papers (9 papers)

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Research

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12 pages, 1453 KiB

Open AccessArticle

Labdane-Type Diterpenoids from Streptomyces griseorubens and Their Antimicrobial and Cytotoxic Activities

by Chang-Su Heo, Jong Soon Kang, Jeong-Wook Yang, Min Ah Lee, Hwa-Sun Lee and Hee Jae Shin

Int. J. Mol. Sci. 2024, 25(6), 3311; https://doi.org/10.3390/ijms25063311 - 14 Mar 2024

Viewed by 578

Abstract

Chemical investigation of the ethyl acetate (EtOAc) extract from a marine-derived actinomycete, Streptomyces griseorubens, resulted in the discovery of five new labdane-type diterpenoids: chlorolabdans A-C (1–3), epoxylabdans A and B (4 and 5), along with one known analog (6). The structures of the new compounds were determined by spectroscopic analysis (HR-ESIMS, 1D, and 2D NMR) and by comparing their experimental data with those in the literature. The new compounds were evaluated for their antimicrobial activity, and 2 displayed significant activity against Gram-positive bacteria, with minimum inhibitory concentration (MIC) values ranging from 4 to 8 µg/mL. Additionally, 1, 2, and 4 were tested for their cytotoxicity against seven blood cancer cell lines by CellTiter-Glo (CTG) assay and six solid cancer cell lines by sulforhodamine B (SRB) assay; 1, 2, and 4 exhibited cytotoxic activities against some blood cancer cell lines, with concentration causing 50% cell growth inhibition (IC₅₀) values ranging from 1.2 to 22.5 µM. Full article

(This article belongs to the Special Issue Bioactive Compounds from Natural Products for the Prevention and Treatment of Chronic Diseases 2.0)

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12 pages, 3084 KiB

Open AccessArticle

Dihydropashanone Isolated from Lindera erythrocarpa, a Potential Natural Product for the Treatment of Neurodegenerative Diseases

by Zhiming Liu, Chi-Su Yoon, Hwan Lee, Hyeong-Kyu Lee and Dong-Sung Lee

Int. J. Mol. Sci. 2024, 25(5), 2545; https://doi.org/10.3390/ijms25052545 - 22 Feb 2024

Viewed by 510

Abstract

Lindera erythrocarpa, a flowering plant native to eastern Asia, has been reported to have neuroprotective activity. However, reports on the specific bioactive compounds in L. erythrocarpa are finite. The aim of this study was to investigate the anti-neuroinflammatory and neuroprotective effects of the compounds isolated from L. erythrocarpa. Dihydropashanone, a compound isolated from L. erythrocarpa extract, was found to have protected mouse hippocampus HT22 cells from glutamate-induced cell death. The antioxidant and anti-inflammatory properties of dihydropashanone in mouse microglial BV2 and HT22 cells were explored in this study. The results reveal that dihydropashanone inhibits lipopolysaccharide-induced inflammatory response and suppresses the activation of nuclear factor (NF)-κB in BV2 cells. In addition, dihydropashanone reduced the buildup of reactive oxygen species in HT22 cells and induced activation of the nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase (HO)-1 signaling pathway in BV2 and HT22 cells. Our results suggest that dihydropashanone reduces neuroinflammation by decreasing NF-κB activation in microglia cells and protects neurons from oxidative stress via the activation of the Nrf2/HO-1 pathway. Thus, our data suggest that dihydropashanone offers a broad range of applications in the treatment of neurodegenerative illnesses. Full article

(This article belongs to the Special Issue Bioactive Compounds from Natural Products for the Prevention and Treatment of Chronic Diseases 2.0)

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15 pages, 5141 KiB

Open AccessArticle

1,5,6-Trimethoxy-2,7-dihydroxyphenanthrene from Dendrobium officinale Exhibited Antitumor Activities for HeLa Cells

by Chong Liang, Chonglun Zhang, Yinlin Zhuo, Baocheng Gong, Weizhuo Xu and Guogang Zhang

Int. J. Mol. Sci. 2023, 24(20), 15375; https://doi.org/10.3390/ijms242015375 - 19 Oct 2023

Cited by 1 | Viewed by 888

Abstract

Natural products are irreplaceable reservoirs for cancer treatments. In this study, 12 phenanthrene compounds were extracted and isolated from Dendrobium officinale. Each chemical structure was identified using comprehensive NMR analysis. All compounds were evaluated for their cytotoxic activities against five tumor cell lines, i.e., HeLa, MCF-7, SK-N-AS, Capan-2 and Hep G2. Compound 5, 1,5,6-trimethoxy-2,7-dihydroxyphenanthrene, displayed the most significant cytotoxic effect against HeLa and Hep G2 cells, with an IC₅₀ of 0.42 and 0.20 μM. For Hela cells, further experiments demonstrated that compound 5 could obviously inhibit cell migration, block cell cycle in the G0/G1 phase and induce apoptosis. Expression measurements for p53 indicated that knock down of p53 by siRNA could mitigate the apoptosis induced by compound 5. Therefore, the compound 5 is a potential candidate drug for HeLa cells in cervical cancer. Full article

(This article belongs to the Special Issue Bioactive Compounds from Natural Products for the Prevention and Treatment of Chronic Diseases 2.0)

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15 pages, 5961 KiB

Open AccessArticle

Biosynthesis of Vanillin by Rational Design of Enoyl-CoA Hydratase/Lyase

by Qi Ye, Weizhuo Xu, Yanan He, Hao Li, Fan Zhao, Jinghai Zhang and Yongbo Song

Int. J. Mol. Sci. 2023, 24(17), 13631; https://doi.org/10.3390/ijms241713631 - 04 Sep 2023

Cited by 1 | Viewed by 963

Abstract

Vanillin holds significant importance as a flavoring agent in various industries, including food, pharmaceuticals, and cosmetics. The CoA-dependent pathway for the biosynthesis of vanillin from ferulic acid involved feruloyl-CoA synthase (Fcs) and enoyl-CoA hydratase/lyase (Ech). In this research, the Fcs and Ech were derived from Streptomyces sp. strain V-1. The sequence conservation and structural features of Ech were analyzed by computational techniques including sequence alignment and molecular dynamics simulation. After detailed study for the major binding modes and key amino acid residues between Ech and substrates, a series of mutations (F74W, A130G, A130G/T132S, R147Q, Q255R, ΔT90, ΔTGPEIL, ΔN1-11, ΔC260-287) were obtained by rational design. Finally, the yield of vanillin produced by these mutants was verified by whole-cell catalysis. The results indicated that three mutants, F74W, Q147R, and ΔN1-11, showed higher yields than wild-type Ech. Molecular dynamics simulations and residue energy decomposition identified the basic residues K37, R38, K561, and R564 as the key residues affecting the free energy of binding between Ech and feruloyl-coenzyme A (FCA). The large changes in electrostatic interacting and polar solvating energies caused by the mutations may lead to decreased enzyme activity. This study provides important theoretical guidance as well as experimental data for the biosynthetic pathway of vanillin. Full article

(This article belongs to the Special Issue Bioactive Compounds from Natural Products for the Prevention and Treatment of Chronic Diseases 2.0)

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19 pages, 3447 KiB

Open AccessArticle

Cytotoxic and Apoptotic Effects of Pinostilbene and Bortezomib Combination Treatment on Human Multiple Myeloma Cells

by Anna Staskiewicz, Erica Wong, Michael Tucker, Riya Farhin, Jonathan Park, Rana Saade, Tina Alkhazali, Tu Dang and Xinyu Wang

Int. J. Mol. Sci. 2023, 24(16), 12590; https://doi.org/10.3390/ijms241612590 - 09 Aug 2023

Cited by 2 | Viewed by 1231

Abstract

Multiple myeloma (MM) is a cancer of plasma cells in the bone marrow characterized by bone lesions, hypercalcemia, anemia, and renal failure. Bortezomib (BTZ), a common treatment for MM, is a proteasome inhibitor that induces apoptosis in MM cells. However, high doses of BTZ can be very toxic, signifying a need for a synergistic drug combination to improve treatment efficacy. Resveratrol (RES), a phenolic compound found in grapes, has been shown to inhibit MM cell growth. We sought to identify a synergistic combination of BTZ with a RES derivative and analyze the effects on reducing viability and inducing apoptosis in human MM cells. BTZ as well as RES and its derivatives pinostilbene (PIN) and piceatannol (PIC) decreased MM cell viability in a dose- and time-dependent manner and increased expression of cleaved proapoptotic proteins poly(ADP-ribose) polymerase 1 (PARP1) and caspase-3 in a dose-dependent manner. The combination of 5 nM BTZ and 5 μM PIN was identified to have synergistic cytotoxic effects in MM RPMI 8226 cells. MM RPMI 8226 cells treated with this combination for 24 h showed increased cleaved PARP1 and caspase-3 expression and higher percentages of apoptotic cells versus cells treated with the individual compounds alone. The treatment also showed increased apoptosis induction in MM RPMI 8226 cells co-cultured with human bone marrow stromal HS-5 cells in a Transwell model used to mimic the bone marrow microenvironment. Expression of oxidative stress defense proteins (catalase, thioredoxin, and superoxide dismutase) in RPMI 8226 cells were reduced after 24 h treatment, and cytotoxic effects of the treatment were ameliorated by antioxidant N-acetylcysteine (NAC), suggesting the treatment impacts antioxidant levels in RPMI 8226 cells. Our results suggest that this combination of BTZ and PIN decreases MM cell viability synergistically by inducing apoptosis and oxidative stress in MM cells. Full article

(This article belongs to the Special Issue Bioactive Compounds from Natural Products for the Prevention and Treatment of Chronic Diseases 2.0)

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19 pages, 7389 KiB

Open AccessArticle

EPs^® 7630 Stimulates Tissue Repair Mechanisms and Modifies Tight Junction Protein Expression in Human Airway Epithelial Cells

by Lei Fang, Liang Zhou, Žarko Kulić, Martin D. Lehner, Michael Tamm and Michael Roth

Int. J. Mol. Sci. 2023, 24(13), 11230; https://doi.org/10.3390/ijms241311230 - 07 Jul 2023

Cited by 2 | Viewed by 1684

Abstract

Airway epithelium repair after infection consists of wound repair, re-synthesis of the extracellular matrix (ECM), and tight junction proteins. In humans, EPs^® 7630 obtained from Pelargonium sidoides roots reduces the severity and duration of acute respiratory tract infections. The effect of EPs^® 7630 on tissue repair of rhinovirus-16 (RV-16) infected and control human airway epithelial cells was assessed for: (i) epithelial cell proliferation by manual cell counts, (ii) epithelial wound repair by “scratch assay”, (iii) ECM composition by Western-blotting and cell-based ELISA, and (iv) epithelial tight junction proteins by Western-blotting. EPs^® 7630 stimulated cell proliferation through cAMP, CREB, and p38 MAPK. EPs^® 7630 significantly improved wound repair. Pro-inflammatory collagen type-I expression was reduced by EPs^® 7630, while fibronectin was increased. Virus-binding tight junction proteins desmoglein2, desmocollin2, ZO-1, claudin1, and claudin4 were downregulated by EPs^® 7630. The RV16-induced shift of the ECM towards the pro-inflammatory type was prevented by EPs^® 7630. Most of the effects of EPs^® 7630 on tissue repair and regeneration were sensitive to inhibition of cAMP-induced signaling. The data suggest that EPs^® 7630-dependent modification of epithelial cell metabolism and function might underlie the faster recovery time from viral infections, as reported by others in clinical studies. Full article

(This article belongs to the Special Issue Bioactive Compounds from Natural Products for the Prevention and Treatment of Chronic Diseases 2.0)

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11 pages, 2309 KiB

Open AccessArticle

Anti-Skin Inflammatory and Anti-Oxidative Effects of the Neoflavonoid Latifolin Isolated from Dalbergia odorifera in HaCaT and BJ-5ta Cells

by Linsha Dong, Hwan Lee, Zhiming Liu and Dong-Sung Lee

Int. J. Mol. Sci. 2023, 24(8), 7371; https://doi.org/10.3390/ijms24087371 - 17 Apr 2023

Cited by 1 | Viewed by 1256

Abstract

Skin is the first line of defense in the body against external stimulation and injury. Inflammation and oxidative stress in skin cells are the initiators and promoters of several skin diseases. Latifolin is a natural flavonoid isolated from Dalbergia odorifera T. Chen. This study aimed to evaluate the anti-inflammatory and antioxidant properties of latifolin. The anti-inflammatory effects were evaluated using tumor necrosis factor-α/interferon-γ (TNF-α/IFN-γ)-treated HaCaT cells, revealing that latifolin inhibited the secretion of Interleukin 6 (IL-6); Interleukin 8 (IL-8); Regulated upon Activation, Normal T Cell Expressed and Presumably Secreted (RANTES); and Macrophage-derived chemokine (MDC) while decreasing the expression of Intercellular Adhesion Molecule 1 (ICAM-1). The results of western blots and immunofluorescence demonstrated that the activation of Janus kinase 2 (JAK2), Signal transducer and activator of transcription 1 (STAT1), Signal transducer and activator of transcription 3 (STAT3), and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) cells signaling pathways were significantly inhibited by latifolin. The antioxidant properties were evaluated using t-BHP-induced BJ-5ta cells. Latifolin increased the viability of t-BHP-induced BJ-5ta cells. Additionally, fluorescent staining of reactive oxygen species (ROS) showed that the production of ROS was inhibited by latifolin. Additionally, latifolin reduced the phosphorylation of p38 and JNK. The results indicate that latifolin has potential anti-inflammatory and antioxidant properties, and may be a candidate natural compound for the treatment of skin diseases. Full article

(This article belongs to the Special Issue Bioactive Compounds from Natural Products for the Prevention and Treatment of Chronic Diseases 2.0)

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27 pages, 4825 KiB

Open AccessArticle

Aspalathin and Other Rooibos Flavonoids Trapped α-Dicarbonyls and Inhibited Formation of Advanced Glycation End Products In Vitro

by Katarzyna Bednarska and Izabela Fecka

Int. J. Mol. Sci. 2022, 23(23), 14738; https://doi.org/10.3390/ijms232314738 - 25 Nov 2022

Cited by 5 | Viewed by 2074

Abstract

The excessive dietary intake of simple sugars and abnormal metabolism in certain diseases contribute to the increased production of α-dicarbonyls (α-DCs), such as methylglyoxal (MGO) and glyoxal (GO), the main precursors of the formation of advanced glycation end products (AGEs). AGEs play a vital role, for example, in the development of cardiovascular diseases and diabetes. Aspalathus linearis (Burman f.) R. Dahlgren (known as rooibos tea) exhibits a wide range of activities beneficial for cardio-metabolic health. Thus, the present study aims to investigate unfermented and fermented rooibos extracts and their constituents for the ability to trap MGO and GO. The individual compounds identified in extracts were tested for the capability to inhibit AGEs (with MGO or GO as a glycation agent). Ultra-high-performance liquid chromatography coupled with an electrospray ionization mass spectrometer (UHPLC–ESI–MS) was used to investigate α-DCs’ trapping capacities. To evaluate the antiglycation activity, fluorescence measurement was used. The extract from the unfermented rooibos showed a higher ability to capture MGO/GO and inhibit AGE formation than did the extract from fermented rooibos, and this effect was attributed to a higher content of dihydrochalcones. The compounds detected in the extracts, such as aspalathin, nothofagin, vitexin, isovitexin, and eriodictyol, as well as structurally related phloretin and phloroglucinol (formed by the biotransformation of certain flavonoids), trapped MGO, and some also trapped GO. AGE formation was inhibited the most by isovitexin. However, it was the high content of aspalathin and its higher efficiency than that of metformin that determined the antiglycation and trapping properties of green rooibos. Therefore, A. linearis, in addition to other health benefits, could potentially be used as an α-DC trapping agent and AGE inhibitor. Full article

(This article belongs to the Special Issue Bioactive Compounds from Natural Products for the Prevention and Treatment of Chronic Diseases 2.0)

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Review

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33 pages, 4373 KiB

Open AccessReview

Phytochemistry and Biological Studies of Endemic Hawaiian Plants

by Pornphimon Meesakul, Tyler Shea, Roland Fenstemacher, Shi Xuan Wong, Yutaka Kuroki, Aya Wada and Shugeng Cao

Int. J. Mol. Sci. 2023, 24(22), 16323; https://doi.org/10.3390/ijms242216323 - 14 Nov 2023

Viewed by 858

Abstract

The Hawaiian Islands are renowned for their exceptional biodiversity and are host to a plethora of endemic plant species, which have been utilized in traditional Hawaiian medicine. This scientific review provides an in-depth analysis of the phytochemistry and biological studies of selected endemic Hawaiian plants, highlighting their medicinal properties and therapeutic potential. A literature search was conducted, utilizing major academic databases such as SciFinder, Scopus, Web of Science, PubMed, Google Scholar, Science Direct, and the Scientific Information Database. The primary objective of this search was to identify relevant scholarly articles pertaining to the topic of the review, which focused on the phytochemistry and biological studies of endemic Hawaiian plants. Utilizing these databases, a comprehensive range of literature was obtained, facilitating a comprehensive examination of the subject matter. This review emphasizes the rich phytochemical diversity and biological activities found in Endemic Hawaiian plants, showcasing their potential as sources of novel therapeutic agents. Given the unique biodiversity of Hawaii and the cultural significance of these plants, continued scientific exploration, conservation, and sustainable utilization of these valuable resources is necessary to unlock the full potential of these plant species in drug discovery and natural product-based therapeutics. Full article

(This article belongs to the Special Issue Bioactive Compounds from Natural Products for the Prevention and Treatment of Chronic Diseases 2.0)

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