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Therapeutic Effects of Natural Bioactive Compounds in the Management of Human Diseases

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A special issue of Current Issues in Molecular Biology (ISSN 1467-3045). This special issue belongs to the section "Biochemistry, Molecular and Cellular Biology".

Deadline for manuscript submissions: closed (30 April 2025) | Viewed by 10173

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Special Issue Editors

Dr. Sara Spinelli

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Guest Editor

Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy
Interests: human physiology; cell physiology; membrane transport systems; bioactive compound; oxidative stress; human health

Dr. Alessia Remigante

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Guest Editor

Prof. Dr. Rossana Morabito

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Special Issue Information

Dear Colleagues,

The Special Issue, entitled “Therapeutic Effects of Natural Bioactive Compounds in the Management of Human Diseases”, welcomes high-quality research articles, as well as review articles, focusing on targets and molecular mechanisms underlying several common pathological conditions related to increased oxidative stress and inflammatory processes and their possible modulation through natural bioactive compounds. Recently, these molecules have attracted considerable attention due to their potential employment as low-toxicity therapies that can prevent, reduce, or restore chronic disease-induced damage.

The extraordinary activity of functional bioactives is displayed via their antioxidant, anti-inflammatory, and anti-glycant properties, which collectively provide a potential new strategy in the management of several pathological conditions (e.g., diabetes, obesity, and rheumatic and neurodegenerative diseases, among others). Understanding the molecular and functional mechanisms and/or pathways through which these substances may support human health remains an open question worth exploring. In this perspective, studies using animal, as well as cell-based models, are welcome.

Dr. Sara Spinelli
Dr. Alessia Remigante
Prof. Dr. Rossana Morabito
Guest Editors

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Keywords

natural bioactive compound
human health
chronic diseases
molecular target
oxidative stress
inflammation
cancer
diabetes

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Published Papers (10 papers)

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Research

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21 pages, 1873 KiB

Open AccessArticle

Pharmacological Evaluation of Angelica keiskei Extract: Molecular Interaction Analysis in Hepatocellular Carcinoma

by Alka Ashok Singh, Minseok Song and Gun-Do Kim

Curr. Issues Mol. Biol. 2025, 47(6), 401; https://doi.org/10.3390/cimb47060401 - 29 May 2025

Viewed by 311

Abstract

Hepatocellular carcinoma (HCC), the most prevalent primary liver cancer, is the most significant cause of cancer-related death globally, with limited treatment options, including surgical resection, liver transplantation, ablation, chemoembolization, immunotherapy, and radiation. Angelica keiskei, a plant that is rich in chalcones and flavonoids, has demonstrated interesting anticancer properties. This study assesses the pharmacological effects of Angelica keiskei extract on HepG2 cells in order to investigate its efficacy as a therapeutic intervention for HCC. Using in vitro cell culture models, HepG2 cells were treated with different doses of the extract, and its cytotoxic and apoptotic effects were studied. GC-MS analysis revealed the presence of several bioactive compounds, including DDMP, which are likely involved in the observed effects. The MTT assay revealed a considerable, dose-dependent reduction in cell viability, with higher dosages causing notable morphological alterations. An antibody apoptotic array indicated significant changes in apoptotic proteins, specifically IGFBP1, BAD, and Bid. Cluster heatmaps, volcano plots, STRING analysis, Voom-mean variance trends, Glimma plots, and PCA were used to obtain an understanding of the molecular interactions involved. These results suggest that Angelica keiskei extract can cause apoptosis in HepG2 cells, with DDMP appearing as a potentially significant contributor. However, more experimental validation is required to determine the precise molecular mechanisms driving these favorable effects and their clinical implications in HCC. Full article

(This article belongs to the Special Issue Therapeutic Effects of Natural Bioactive Compounds in the Management of Human Diseases)

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12 pages, 1581 KiB

Open AccessArticle

Anti-Inflammatory Effects of Caulerpa okamurae Extracts on Porphyromonas gingivalis-Stimulated RAW 264.7 Macrophages

by Chae-yun Lee, Min-jeong Kim and Hyun-jin Kim

Curr. Issues Mol. Biol. 2025, 47(6), 388; https://doi.org/10.3390/cimb47060388 - 23 May 2025

Viewed by 296

Abstract

Caulebra okamurae (C. okamurae), a green seaweed, has been reported to exhibit pharmacological properties, including anti-obesity and anti-diabetic effects. This study investigated the anti-inflammatory effects of C. okamurae extracts on periodontal health. The cell viability of RAW 264.7 macrophages was dose-dependently assessed using an MTS assay. The anti-inflammatory activity of C. okamurae on Porphyromonas gingivalis (P. gingivalis)-stimulated RAW 264.7 macrophages was evaluated by measuring nitric oxide (NO) production. mRNA expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β were quantified via quantitative real-time PCR (qRT-PCR). The protein expression of iNOS, p-IKKα/β, p-IκBα, and NF-κB p65 was examined using Western blot and immunofluorescence. The results demonstrated that C. okamurae extracts exhibited no cytotoxicity in RAW 264.7 macrophages at concentrations of 0.2, 2, 20, and 200 μg/mL. The extracts dose-dependently reduced NO production, downregulated mRNA levels of proinflammatory cytokines, and inhibited iNOS expression in P. gingivalis-stimulated RAW 264.7 macrophages, a model commonly used to study periodontal inflammation. Furthermore, the extracts suppressed the phosphorylation of IKKα/β and IκBα and prevented the NF-κB p65 nuclear translocation. These findings suggest that C. okamurae extracts inhibit NF-κB signaling activation triggered by the periodontal pathogen, highlighting their potential anti-inflammatory effects, relevant to periodontal disease. Full article

(This article belongs to the Special Issue Therapeutic Effects of Natural Bioactive Compounds in the Management of Human Diseases)

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14 pages, 8775 KiB

Open AccessArticle

Enhanced Bioactivity of Fermented Aralia cordata Extract for Glucose and Immune Modulation

by Heejong Shin, Hwapyung Kim, Gwangpyung Kim, Yikyoung Kim and Boyong Kim

Curr. Issues Mol. Biol. 2025, 47(4), 294; https://doi.org/10.3390/cimb47040294 - 21 Apr 2025

Viewed by 326

Abstract

Excessive glucose absorption is a major contributing factor of metabolic disorders that necessitates effective therapeutic strategies. This study investigates the potential of fermented Aralia cordata extract (FACE) in regulating glucose transport and immune responses under high-glucose stress conditions. Caco-2 intestinal cells and L cells were treated with FACE to determine effects on key glucose-regulating proteins and cytokines. FACE treatment inhibited the expression of glucose transporters SGLT1 and GLUT2 while promoting GLP-1 secretion. This effect was associated with HDAC and somatostatin suppression, along with AMPK-γ upregulation. Notably, FACE inhibited DPP-4 expression, further enhancing GLP-1 stability and function. Immunomodulatory effects also occurred, specifically FACE promotion of T lymphocyte differentiation, with a stronger influence on Th2 cell development. Additionally, FACE increased the secretion of essential molecules for immune balance and inflammation control, including antimicrobial peptides LL-37 and defensin, along with cytokines IL-4 and IL-13. These findings suggest that FACE exerts dual effects of improving glucose regulation and modulating immune responses, highlighting its potential as a novel bioactive material for managing metabolic disorders and enhancing intestinal immunity. Further research is warranted to explore its clinical applicability in therapeutic formulations. Full article

(This article belongs to the Special Issue Therapeutic Effects of Natural Bioactive Compounds in the Management of Human Diseases)

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13 pages, 2936 KiB

Open AccessArticle

Anti-Inflammatory Effects of Apostichopus japonicus Extract in Porphyromonas gingivalis-Stimulated RAW 264.7 Cells

by Min-jeong Kim and Hyun-jin Kim

Curr. Issues Mol. Biol. 2024, 46(12), 13405-13417; https://doi.org/10.3390/cimb46120799 - 24 Nov 2024

Viewed by 1085

Abstract

Apostichopus japonicus has been used both as a food and in traditional medicine. However, its anti-inflammatory effects in periodontal diseases have not been studied. We examined the anti-inflammatory properties of Apostichopus japonicus extract in RAW 264.7 cells stimulated by Porphyromonas gingivalis. The cytotoxicity of Apostichopus japonicus extract was evaluated using the MTS assay. Its effect on NO production was then measured using the NO assay. The mRNA expression of inducible nitric oxide synthase (iNOS) and the pro-inflammatory cytokines IL-1β and IL-6 were assessed using quantitative real-time PCR (qRT-PCR). Western blotting was performed to investigate the expression of regulatory proteins involved in the NF-κB and MAPK signaling pathways. Apostichopus japonicus extract significantly inhibited NO production without cytotoxicity in RAW 264.7 cells. Following Porphyromonas gingivalis stimulation, treatment with the extract decreased iNOS mRNA expression and protein levels, which are responsible for NO production. The extract also suppressed the mRNA expression of pro-inflammatory cytokines. Additionally, Apostichopus japonicus extract inhibited NF-κB activation by regulating signaling molecules such as IKK and IκBα, while also preventing the phosphorylation of MAPK, including ERK, p38, and JNK, showing anti-inflammatory potential. Therefore, it may be a promising natural candidate for the development of new preventive and therapeutic strategies for periodontitis. Full article

(This article belongs to the Special Issue Therapeutic Effects of Natural Bioactive Compounds in the Management of Human Diseases)

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Review

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25 pages, 1205 KiB

Open AccessReview

Antioxidant Naturally Occurring Pleiotropically Acting Bioactive Compounds, as Polymeric Nanotherapeutics Against Autoimmune Diseases Progression

by Panagiotis Theodosis-Nobelos, Fani-Niki Varra, Michail Varras, Georgios Papagiouvannis and Eleni A. Rekka

Curr. Issues Mol. Biol. 2025, 47(6), 411; https://doi.org/10.3390/cimb47060411 - 1 Jun 2025

Viewed by 311

Abstract

Autoimmune diseases are driven by chronic inflammation and oxidative stress, thus requiring innovative therapeutic approaches. Polymeric nanotherapeutics incorporating antioxidant bioactive compounds offer a promising strategy for immune modulation and enhanced drug delivery. This review explores the application of polymer-based nanocarriers for improving the solubility, bioavailability, and targeted delivery of antioxidant compounds in autoimmune disease treatment. A comprehensive analysis of recent advancements in polymeric nanoformulations, including poly(lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG), chitosan, and hyaluronic acid, was conducted. The therapeutic efficacy of various antioxidant-loaded nanoparticles has been assessed in both preclinical and clinical studies. Phenolic antioxidants, such as resveratrol, curcumin, quercetin, and epigallocatechin-3-gallate, exhibit potent anti-inflammatory effects; however, their poor solubility limits their clinical application. Nanocarriers such as dendrosomes, tannic acid-based reactive oxygen species (ROS)-scavenging nanoparticles, and folic acid-functionalized systems enhance drug stability, controlled drug release, and macrophage targeting. Carotenoid and bilirubin nanoparticles further demonstrate immunomodulatory effects in multiple sclerosis, psoriasis, rheumatoid arthritis, and inflammatory bowel disease. Polymeric antioxidant nanotherapeutics provide targeted and sustained drug delivery, offering improved efficacy and reduced toxicity. Future research should focus on optimizing these nanocarriers for clinical translation and patient-centered therapeutic strategies. Full article

(This article belongs to the Special Issue Therapeutic Effects of Natural Bioactive Compounds in the Management of Human Diseases)

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39 pages, 1821 KiB

Open AccessReview

Alpha-Lipoic Acid in Diabetic Peripheral Neuropathy: Addressing the Challenges and Complexities Surrounding a 70-Year-Old Compound

by Iliya Mangarov, Yulian Voynikov, Valentina Petkova, Simeon Iliev, Ivanka Kostadinova, Lyubomir Marinov and Irina Nikolova

Curr. Issues Mol. Biol. 2025, 47(6), 402; https://doi.org/10.3390/cimb47060402 - 29 May 2025

Viewed by 790

Abstract

Alpha-lipoic acid (ALA, also known as thioctic acid) was discovered nearly 90 years ago and began to be used in clinical practice in the late 1950s. Numerous nonclinical and clinical studies have investigated ALA for treating diabetic peripheral neuropathy (DPN) and various other diseases. The rising global prevalence of DPN necessitates timely treatment; however, there is currently no effective cure. Current guideline-recommended therapies for DPN provide symptom relief rather than modifying the disease. Among the pathogenesis-oriented therapies, ALA holds a unique position as a universal antioxidant, essential for every cell in the body. This review highlights the ongoing issues and challenges in using ALA to treat DPN. While confronting a complex disease with poorly understood pathophysiology, we also have an endogenous substance with pleiotropic effects on all cells in the human body. It becomes clear that this is a highly multifactorial process that will likely never be precisely defined. This does not diminish the significance of ALA in treating DPN but underscores the need for a deeper understanding of when to start therapy, dosage, duration, and monitoring. In this comprehensive review, we evaluate the achievements of the past 70 years and highlight gaps in ALA’s role in treating DPN. Full article

(This article belongs to the Special Issue Therapeutic Effects of Natural Bioactive Compounds in the Management of Human Diseases)

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20 pages, 1561 KiB

Open AccessReview

Hepatoprotective and Fat-Accumulation-Reductive Effects of Curcumin on Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

by Jasmine Harumi Sabini and Kris Herawan Timotius

Curr. Issues Mol. Biol. 2025, 47(3), 159; https://doi.org/10.3390/cimb47030159 - 27 Feb 2025

Cited by 1 | Viewed by 1019

Abstract

Fat accumulation is the hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD). Given the intimidating nature of its treatment, curcumin (CUR) emerges as a potential therapeutic agent due to its proven effectiveness in managing MASLD. This review aimed to evaluate previous reports on the hepatoprotective and fat-accumulation-reductive effects of CUR administration in preventing or treating MASLD. CUR administration can modulate serum liver enzymes and lipid profiles. The fat accumulation of MASLD is the primary cause of oxidative stress and inflammation. By reducing fat accumulation, CUR may attenuate the inflammation and oxidative stress in MASLD. In addition, CUR has been proven to restore the dysfunctional cellular energy metabolism capacity and attenuate fibrogenesis (antifibrotic agent). Their hepatoprotective effects are associated with fat accumulation in MASLD. Lipid metabolism (lipogenesis, lipolysis, and lipophagy) is correlated with their hepatoprotective effects. CUR has prophylactic and therapeutic effects, particularly in early-stage MASLD, primarily when it is used as a fat reducer. It can be considered an excellent natural therapeutic drug for MASLD because it protects the liver and attenuates fat accumulation, especially in the early stage of MASLD development. Full article

(This article belongs to the Special Issue Therapeutic Effects of Natural Bioactive Compounds in the Management of Human Diseases)

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29 pages, 3076 KiB

Open AccessReview

A Comprehensive Review on Bioactive Molecules and Advanced Microorganism Management Technologies

by Adil Farooq Wali, Sirajunisa Talath, Sathvik B. Sridhar, Javedh Shareef, Manjunatha Goud, Imran Rashid Rangraze, Nowar Nizar Alaani and Omnia Ibrahim Mohamed

Curr. Issues Mol. Biol. 2024, 46(11), 13223-13251; https://doi.org/10.3390/cimb46110789 - 20 Nov 2024

Viewed by 1885

Abstract

The advent of new strains of resistant microbes and the concomitant growth in multidrug resistance have made antimicrobial resistance an urgent public health concern. New antimicrobials are desperately needed to boost the success rates of treating infectious diseases and save lives. There are many intriguing biomolecules with antibacterial action, which are mostly unexplored in microorganisms. This review article describes the importance of natural compounds against microorganisms using advanced techniques to protect individuals from diseases. We have conducted an extensive literature review using databases such as SCOPUS, SCI, PUBMED, ScienceDirect, and Medline to gather relevant information. Our review covers various microorganism sources for antimicrobials, antifungal drugs, micro-culturing techniques, and microbial-based microsystems’ applications. Every kind of higher trophic life depends on microorganisms for sustenance. The unseen majority is essential to understanding how humans and other living forms can survive anthropogenic climate change. The article discusses antimicrobial substances and the latest techniques and strategies for developing effective treatments. Novel model systems and cutting-edge biomolecular and computational methodologies could help researchers enhance antimicrobial resistance by completely capitalizing on lead antimicrobials. Full article

(This article belongs to the Special Issue Therapeutic Effects of Natural Bioactive Compounds in the Management of Human Diseases)

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15 pages, 1802 KiB

Open AccessReview

The Role of Licorice Chalcones as Molecular Genes and Signaling Pathways Modulator—A Review of Experimental Implications for Nicotine-Induced Non-Small Cell Lung Cancer Treatment

by Naser A. Alsharairi

Curr. Issues Mol. Biol. 2024, 46(6), 5894-5908; https://doi.org/10.3390/cimb46060352 - 13 Jun 2024

Viewed by 2189

Abstract

Lung cancer (LC) represents the leading cause of global cancer deaths, with cigarette smoking being considered a major risk factor. Nicotine is a major hazardous compound in cigarette smoke (CS), which stimulates LC progression and non-small cell lung cancer (NSCLC) specifically through activation of the nicotinic acetylcholine receptor (α7nAChR)-mediated cell-signaling pathways and molecular genes involved in proliferation, angiogenesis, and metastasis. Chalcones (CHs) and their derivatives are intermediate plant metabolites involved in flavonol biosynthesis. Isoliquiritigenin (ILTG), licochalcone A–E (LicoA–E), and echinatin (ECH) are the most common natural CHs isolated from the root of Glycyrrhiza (also known as licorice). In vitro and/or vivo experiments have shown that licorice CHs treatment exhibits a range of pharmacological effects, including antioxidant, anti-inflammatory, and anticancer effects. Despite advances in NSCLC treatment, the mechanisms of licorice CHs in nicotine-induced NSCLC treatment remain unknown. Therefore, the aim of this paper is to review experimental studies through the PubMed/Medline database that reveal the effects of licorice CHs and their potential mechanisms in nicotine-induced NSCLC treatment. Full article

(This article belongs to the Special Issue Therapeutic Effects of Natural Bioactive Compounds in the Management of Human Diseases)

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Other

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11 pages, 3256 KiB

Open AccessBrief Report

Periplosides Extract from Cortex periplocae Improve Collagen Antibody-Induced Arthritis by Regulating Macrophage Polarization

by Que Wang, Xiaoyu Xiong, Li Chen, Fenghua Zhu, Xiaoqian Yang, Weimin Zhao, Shijun He, Jianping Zuo and Zemin Lin

Curr. Issues Mol. Biol. 2024, 46(12), 14095-14105; https://doi.org/10.3390/cimb46120843 - 13 Dec 2024

Viewed by 960

Abstract

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized primarily by the synovial infiltration of inflammatory cells. Macrophage infiltration in the joint synovium is one of the early hallmarks of RA disease activity. Cortex periplocae, which has been widely employed in traditional Chinese medicine (TCM) to alleviate RA, harbors a bioactive compound known as Periploca sepium periplosides (PePs). In this study, collagen antibody-induced arthritis (CAIA) was established in mice through the administration of collagen antibodies and lipopolysaccharide (LPS), followed by treatment with PePs. The therapeutic effects of PePs were evaluated by measuring paw thickness, clinical arthritis scores, and histological changes in joint tissues. Flow cytometry and qRT-PCR were used to assess macrophage polarization in vivo and in vitro. The findings indicate that PePs effectively attenuated CAIA by suppressing the polarization of RAW264.7 cells towards the M1 phenotype while promoting their polarization towards the M2 phenotype. These results provide valuable insights into the scientific significance of PePs as a potential therapeutic agent for RA. Full article

(This article belongs to the Special Issue Therapeutic Effects of Natural Bioactive Compounds in the Management of Human Diseases)

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