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Natural Products in Lifestyle-Related Diseases: Molecular Mechanisms, Prevention and Treatments
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Natural Products in Lifestyle-Related Diseases: Molecular Mechanisms, Prevention and Treatments

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 25 September 2025 | Viewed by 3522

Special Issue Editor

Dr. Takanobu Takata

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Guest Editor
Department of Life Science, Medical Research Institute, Kanazawa Medical University, Uchinada 920-0293, Japan
Interests: traditional medicine; lifestyle-related diseases; advanced glycation end-products

Special Issue Information

Dear Colleagues,

Lifestyle-related diseases (LSRDs), including diabetes mellitus (DM), cardiovascular disease (CVD), non-alcoholic hepatosteatosis (NASH), cancer, sarcopenia, and Alzheimer's disease (AD), are major issues worldwide. Many researchers have analyzed the mechanisms of LSRDs based on molecular research and their prevention/treatment methods have been explored.

Recently, natural products have gained focus due to their ability to prevent and cure LSRDs. Although natural products’ mechanisms of prevention/treatment are yet to be thoroughly analyzed in order to provide evidence at the molecular level or a basis in molecular science, known effects are involved for some LSRDs (e.g., DM, CVD, and NASH) that Western medicine (modern medicine) is unable to effectively employ. Extracts from plants, animals, and minerals are used to compile natural products. In medicinal history, various components (e.g., low-molecular-weight compounds, polysaccharides, and proteins) were isolated from natural products and proven to treat certain LSRDs. However, evidence regarding the mechanisms through which they are able to do so is difficult to come by, because crude drugs contain various compounds that should be delivered via oral administration, where their various compounds are digested, absorbed, and metabolized, leading to the occurrence of various phenomena for the body’s organs. Therefore, these factors should be explored experimentally both in vitro and in vivo regarding natural products’ mechanisms of action towards LSRDs, the analyses of which should be grounded in molecular-level research in order to pioneer 21st century medicine.

Dr. Takanobu Takata
Guest Editor

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Keywords

  • natural products
  • crude drugs
  • lifestyle-related diseases
  • diabetes mellitus
  • cardiovascular disease
  • non-alcoholic hepatosteatosis
  • cancer
  • sarcopenia
  • Alzheimer’s disease

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Published Papers (2 papers)

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Research

20 pages, 7902 KiB  
Article
Analysis of the Setomimycin Biosynthetic Gene Cluster from Streptomyces nojiriensis JCM3382 and Evaluation of Its α-Glucosidase Inhibitory Activity Using Molecular Docking and Molecular Dynamics Simulations
by Kyung-A Hyun, Xuhui Liang, Yang Xu, Seung-Young Kim, Kyung-Hwan Boo, Jin-Soo Park, Won-Jae Chi and Chang-Gu Hyun
Int. J. Mol. Sci. 2024, 25(19), 10758; https://doi.org/10.3390/ijms251910758 - 6 Oct 2024
Cited by 2 | Viewed by 1612
Abstract
The formation of atroposelective biaryl compounds in plants and fungi is well understood; however, polyketide aglycone synthesis and dimerization in bacteria remain unclear. Thus, the biosynthetic gene cluster (BGC) responsible for antibacterial setomimycin production from Streptomyces nojiriensis JCM3382 was examined in comparison with [...] Read more.
The formation of atroposelective biaryl compounds in plants and fungi is well understood; however, polyketide aglycone synthesis and dimerization in bacteria remain unclear. Thus, the biosynthetic gene cluster (BGC) responsible for antibacterial setomimycin production from Streptomyces nojiriensis JCM3382 was examined in comparison with the BGCs of spectomycin, julichromes, lincolnenins, and huanglongmycin. The setomimycin BGC includes post-polyketide synthase (PKS) assembly/cycling enzymes StmD (C-9 ketoreductase), StmE (aromatase), and StmF (thioesterase) as key components. The heterodimeric TcmI-like cyclases StmH and StmK are proposed to aid in forming the setomimycin monomer. In addition, StmI (P-450) is predicted to catalyze the biaryl coupling of two monomeric setomimycin units, with StmM (ferredoxin) specific to the setomimycin BGC. The roles of StmL and StmN, part of the nuclear transport factor 2 (NTF-2)-like protein family and unique to setomimycin BGCs, could particularly interest biochemists and combinatorial biologists. α-Glucosidase, a key enzyme in type 2 diabetes, hydrolyzes carbohydrates into glucose, thereby elevating blood glucose levels. This study aimed to assess the α-glucosidase inhibitory activity of EtOAc extracts of JCM 3382 and setomimycin. The JCM 3382 EtOAc extract and setomimycin exhibited greater potency than the standard inhibitor, acarbose, with IC50 values of 285.14 ± 2.04 μg/mL and 231.26 ± 0.41 μM, respectively. Molecular docking demonstrated two hydrogen bonds with maltase-glucoamylase chain A residues Thr205 and Lys480 (binding energy = −6.8 kcal·mol−1), two π–π interactions with Trp406 and Phe450, and one π–cation interaction with Asp542. Residue-energy analysis highlighted Trp406 and Phe450 as key in setomimycin’s binding to maltase-glucoamylase. These findings suggest that setomimycin is a promising candidate for further enzymological research and potential antidiabetic therapy. Full article
(This article belongs to the Special Issue Natural Products in Lifestyle-Related Diseases: Molecular Mechanisms, Prevention and Treatments)
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14 pages, 2624 KiB  
Article
Biological Properties of Oleanolic Acid Derivatives Bearing Functionalized Side Chains at C-3
by Gianfranco Fontana, Natale Badalamenti, Maurizio Bruno, Filippo Maggi, Federica Dell’Annunziata, Nicoletta Capuano, Mario Varcamonti and Anna Zanfardino
Int. J. Mol. Sci. 2024, 25(15), 8480; https://doi.org/10.3390/ijms25158480 - 3 Aug 2024
Viewed by 1282
Abstract
Triterpene acids are a class of pentacyclic natural carboxylic compounds endowed with a variety of biological activities including antitumor, antimicrobial, and hepatoprotective effects. In this work, several oleanolic acid derivatives were synthesized by structurally modifying them on the C-3 position. All synthesized derivatives [...] Read more.
Triterpene acids are a class of pentacyclic natural carboxylic compounds endowed with a variety of biological activities including antitumor, antimicrobial, and hepatoprotective effects. In this work, several oleanolic acid derivatives were synthesized by structurally modifying them on the C-3 position. All synthesized derivatives were evaluated for possible antibacterial and antiviral activity, and among all the epimers, 6 and 7 demonstrated the best biological activities. Zone-of-inhibition analyses were conducted against two strains, E. coli as a Gram-negative and S. aureus as a Gram-positive model. Subsequently, experiments were performed using the microdilution method to determine the minimum inhibitory concentration (MIC). The results showed that only the derivative with reduced hydrogen bonding ability on ring A possesses remarkable activity toward E. coli. The conversion from acid to methyl ester implies a loss of activity, probably due to a reduced affinity with the bacterial membrane. Before the antiviral activity, the cytotoxicity of triterpenes was evaluated through a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Samples 6 and 7 showed less than 50% cytotoxicity at 0.625 and 1 mg/mL, respectively. The antiviral activity against SARS-CoV-2 and PV-1 did not indicate that triterpene acids had any inhibitory capacity in the sub-toxic concentration range. Full article
(This article belongs to the Special Issue Natural Products in Lifestyle-Related Diseases: Molecular Mechanisms, Prevention and Treatments)
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