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Therapeutic Effects of Natural Products on Human Diseases: 2nd Edition

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A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Pharmaceutical Science".

Deadline for manuscript submissions: 27 October 2025 | Viewed by 12566

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Special Issue Editor

Prof. Dr. Seung Ho Lee

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Guest Editor

Department of Nano-Bioengineering, Incheon National University, Incheon, Republic of Korea
Interests: natural products; natural extracts; cancer; neurodegenerative diseases; immunological disorders; metabolic diseases; oriental medicine; micro-organisms; algae; functional foods
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Special Issue Information

Dear Colleagues,

Natural products are compounds or substances produced by living organisms that are found in nature. Since natural sources are considered potential resources for developing lead compounds in drug discovery, a significant number of studies have focused on finding new therapeutic effects of natural products on human diseases, such as cancer, neurodegenerative diseases, immunological disorders, and metabolic diseases.

This Special Issue, entitled “Therapeutic Effects of Natural Products on Human Diseases”, welcomes submissions of either research manuscripts or scientific reviews covering the therapeutic effects of various natural products (plants, microorganisms, algae, foods, animals, etc.) on human diseases. Importantly, mechanistic studies evaluated by in vitro and/or in vivo experiments to identify major molecules and/or cellular pathways of targeted therapeutic action of natural compounds should be involved.

Prof. Dr. Seung Ho Lee
Guest Editor

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Keywords

natural products
natural extracts
cancer
neurodegenerative diseases
immunological disorders
metabolic diseases
oriental medicine
microorganisms
algae
functional foods

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Published Papers (8 papers)

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Research

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24 pages, 4652 KiB

Open AccessArticle

Anti-Inflammatory Effects of Hyeonggaeyeongyo-tang: Evidence from In Vitro and In Vivo Studies

by Keun Hee Lee, Min Hee Kim and Hae Jeong Nam

Life 2025, 15(4), 587; https://doi.org/10.3390/life15040587 - 2 Apr 2025

Viewed by 283

Abstract

Hyeonggaeyeongyo-tang (HGYGT), a traditional herbal formula, is used to treat inflammatory otorhinolaryngological diseases such as otitis media and sinusitis. In this study, we investigated the anti-inflammatory effects of HGYGT in LPS-stimulated RAW 264.7 cells (in vitro) and a carrageenan (CA)-induced rat paw edema model (in vivo). In LPS-stimulated RAW 264.7 cells, treatment with HGYGT (100 and 300 μg/mL) significantly reduced nitric oxide (NO) production by 24.5% and 51.3%, respectively (p < 0.05, p < 0.01). It also significantly suppressed the production of PGE2 (49.8%), IL-1β (42.7%), IL-6 (45.6%), and TNF-α (47.2%) at 300 μg/mL (p < 0.01). A Western blot analysis confirmed that HGYGT (300 μg/mL) significantly downregulated iNOS and COX-2 expression by 58.4% and 53.1%, respectively, while COX-1 remained unaffected. And HGYGT treatment at 300 μg/mL markedly inhibited NF-κB activation by 44.9% (p < 0.01). Furthermore, HGYGT selectively inhibited JNK phosphorylation by 46.7% (p < 0.01), without significantly affecting ERK1/2 or p38 MAPKs. In the CA-induced rat paw edema model, oral administration of HGYGT (1.0 g/kg) reduced paw swelling by 31.5% at 4 h post-injection (p < 0.01) and significantly decreased iNOS expression in inflamed paw tissues by 43.2% (p < 0.01). A histological analysis revealed that HGYGT (1.0 g/kg) reduced inflammatory cell infiltration by 39.6% in the affected tissue (p < 0.05), demonstrating its anti-inflammatory potential. Our findings demonstrate that HGYGT exerts anti-inflammatory effects by suppressing the JNK and NF-κB signaling pathways in LPS-stimulated RAW 264.7 cells, reducing the production of inflammatory mediators. Notably, HGYGT selectively inhibits COX-2 without affecting COX-1 and preferentially suppresses the JNK pathway. Moreover, its in vivo anti-inflammatory effects were confirmed through iNOS inhibition and histopathological analysis. These findings provide robust scientific evidence supporting the traditional use of HGYGT and its anti-inflammatory properties. Full article

(This article belongs to the Special Issue Therapeutic Effects of Natural Products on Human Diseases: 2nd Edition)

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16 pages, 1709 KiB

Open AccessArticle

Anti-Inflammatory Effects and Human Skin Safety of the Eastern Traditional Herb Mosla japonica

by Hyun-Ju Han and Chang-Gu Hyun

Life 2025, 15(3), 418; https://doi.org/10.3390/life15030418 - 7 Mar 2025

Viewed by 569

Abstract

Traditional knowledge has long provided natural solutions for disease prevention and treatment, complementing modern medicine. Mosla japonica (Korean mint) has been traditionally valued for its pesticidal, dehumidifying, anti-swelling, and detoxifying properties. This study explores its anti-inflammatory potential using M. japonica extract (MJE) in LPS-stimulated RAW 264.7 macrophages and evaluates its safety for human skin applications. MJE significantly reduced inflammatory mediators such as nitric oxide (NO), prostaglandin E₂ (PGE₂), and key cytokines (IL-1β, IL-6, TNF-α) in a dose-dependent manner. It also suppressed the expression of iNOS and COX-2, enzymes crucial for inflammation. Mechanistically, MJE inhibited NF-κB activation by stabilizing IκBα, thereby reducing inflammation-related gene expression. Additionally, it downregulated ERK, JNK, and p38 in the MAPK signaling pathway, further contributing to its anti-inflammatory effects. A primary skin irritation test confirmed MJE’s safety, showing no significant skin reactions at 100 μg/mL. These findings highlight MJE’s strong anti-inflammatory properties and potential for dermatological applications. This study underscores the pharmacological value of M. japonica and its integration into modern scientific research, aligning with global biodiversity frameworks such as the Nagoya Protocol. Future research may further expand its applications in medicine and skincare. Full article

(This article belongs to the Special Issue Therapeutic Effects of Natural Products on Human Diseases: 2nd Edition)

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25 pages, 4138 KiB

Open AccessArticle

Resveratrol-Enhanced Human Neural Stem Cell-Derived Exosomes Mitigate MPP+-Induced Neurotoxicity Through Activation of AMPK and Nrf2 Pathways and Inhibition of the NLRP3 Inflammasome in SH-SY5Y Cells

by Ming-Chang Chiang, Yu-Ping Yang, Christopher J. B. Nicol, Tairui Chiang and Chiahui Yen

Life 2025, 15(2), 294; https://doi.org/10.3390/life15020294 - 13 Feb 2025

Cited by 2 | Viewed by 1072

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder primarily characterized by the loss of dopaminergic neurons in the substantia nigra. Mitochondrial dysfunction, oxidative stress, and neuroinflammation are recognized as critical pathological mechanisms driving neurodegeneration in PD. Exosome (Exo)-based therapies, particularly those derived from human neural stem cells (hNSCs), offer promising neuroprotective effects due to their ability to transfer bioactive molecules that modulate cellular processes. Resveratrol (RES), a polyphenolic compound with potent antioxidant and anti-inflammatory properties, has been shown to enhance the therapeutic potential of stem cell (SC)-derived Exos. This study investigated the neuroprotective effects of RES-treated hNSCs-derived Exos (RES-hNSCs-Exos) on SH-SY5Y cells exposed to 1-methyl-4-phenylpyridinium (MPP⁺), a neurotoxin commonly used to model Parkinsonian neurotoxicity. Treating SH-SY5Y cells with MPP⁺ led to significant reductions in cell viability, mitochondrial dysfunction, increased oxidative stress, and the activation of inflammatory pathways. Treatment with RES-hNSCs-Exos rescued SH-SY5Y cells from MPP⁺-induced toxicity by improving cell viability, enhancing ATP production, increasing mitochondrial biogenesis, and reducing reactive oxygen species (ROS) generation. The findings also demonstrated the increased expression of essential genes involved in mitochondrial biogenesis, such as PGC1α, NRF1, and Tfam, indicating improved mitochondrial function in the presence of RES-hNSCs-Exos. Further analysis revealed that these protective effects were mediated by activating the AMP-activated protein kinase (AMPK) and Nrf2 signaling pathways, which promoted mitochondrial health and reduced oxidative stress. Moreover, RES-hNSCs-Exos treatment suppressed neuroinflammation by downregulating NLRP3 inflammasome activation and reducing the secretion of pro-inflammatory cytokines IL-1β and IL-18. In conclusion, the results suggest that RES-hNSCs-Exos exhibit potent neuroprotective effects against MPP⁺-induced neurotoxicity by enhancing mitochondrial function, reducing oxidative stress, and inhibiting neuroinflammation. These findings highlight the potential of hNSCs-Exos as a novel therapeutic strategy for neurodegenerative diseases like PD, with RES as a valuable enhancer of Exos efficacy. Full article

(This article belongs to the Special Issue Therapeutic Effects of Natural Products on Human Diseases: 2nd Edition)

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19 pages, 3898 KiB

Open AccessArticle

Nephroprotective Effect of Aged Black Garlic Extract as a Functional Flock Medicinal on Sodium Benzoate-Induced Chronic Kidney Disease in Albino Rats

by Marwa A. Sheir, Ameerah M. Almaski, Manal A. Almughamisi, Suha H. Abduljawad, Essam M. Elsebaie and Rania A. Ahmed

Life 2025, 15(2), 217; https://doi.org/10.3390/life15020217 - 31 Jan 2025

Viewed by 1212

Abstract

Sodium benzoate, a common food preservative, has been linked to oxidative stress, inflammation, and potential damage to various organs, including the kidneys. Aged black garlic (ABG) offers significant potential in supporting body health through its powerful antioxidant and anti-inflammatory properties, which can help reduce cellular damage and inflammation and, thus, improve organ functions. The purpose of this investigation is to investigate the ameliorative effect of aged black garlic extract (ABG extract) on the nephrotoxicity and oxidative stress induced by sodium benzoate. A total of thirty-two adult male albino rats were divided randomly into four groups: Group 1: control; Group 2: orally given ABG extract (200 mg/kg bw) daily for 4 weeks; Group 3: administrated orally by sodium benzoate daily for 4 weeks; Group 4: cotreated with both ABG extract and sodium benzoate for 30 days. This included histological examinations, a histochemical demonstration of DNA contents, and an immunohistochemical demonstration of pro-apoptotic protein caspase-3, as well as a biochemical evaluation of renal MDA, CAT, SOD, GPx, and IL-1β levels. Moreover, serum and urinary urea, uric acid, creatinine, sodium, and potassium levels were also determined, as well as serum C-reactive protein. FI (30 days), FER, and BWG% were calculated as well as urinary volume and protein being measured. The findings revealed that ABG extract significantly improved all histopathological and physiological changes (p < 0.05) induced by SB as renal tissue was significantly improved, DNA contents were restored, and capase-3 immunoreactivity was diminished. Additionally, oxidative and inflammatory markers, and renal function parameters, were significantly improved. These results showed that ABG extract possesses significant ameliorative effects against the nephrotoxicity induced by sodium benzoate; this may be mediated by its antioxidant activity. Full article

(This article belongs to the Special Issue Therapeutic Effects of Natural Products on Human Diseases: 2nd Edition)

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13 pages, 1399 KiB

Open AccessArticle

Verbascum ponticum (Stef.) Extract Induces Lung Cancer Apoptosis via Mitochondrial-Dependent Apoptosis Pathway

by Pawan S. Faris

Life 2024, 14(11), 1520; https://doi.org/10.3390/life14111520 - 20 Nov 2024

Viewed by 1192

Abstract

Non-small-cell lung carcinoma remains a significant health concern due to its high incidence and mortality rates. Traditional medicines play a central role in cancer therapy, with plant-derived bioactive compounds being studied for their potential to offer fewer side effects than conventional treatments. In traditional Kurdish medicine, different Verbascum species are used to treat burns, inflammation, and other conditions. While some species extracts have shown cytotoxic effects against several cancer cell lines like A549, the efficacy and mechanisms of action of the other species like Verbascum ponticum (V. ponticum) remain to be elucidated. Therefore, this study aimed to explore the effect of V. ponticum (Stef.) extract, collected from the Kurdistan region of the Iraq mountains, on A549 cells. A comprehensive approach was employed, utilizing immunocytochemical and functional analyses to assess apoptotic morphology, DNA fragmentation, alongside assays for cellular and mitochondrial function, proliferation, and viability. Additionally, the study investigated AIF mitochondrial translocation and evaluated mitochondrial membrane potential using the Rhodamine 123 assay. The results showed that the V. ponticum flower extract induced mitochondrial-mediated apoptosis in A549 cells via disruption of mitochondrial membrane potential, release of AIF, and translocation to the nucleus, independently of the caspase-3-activation pathway. These findings emphasize the potential of V. ponticum in lung cancer strategic treatments, meriting further phytochemical studies to identify the bioactive compounds it contains. Full article

(This article belongs to the Special Issue Therapeutic Effects of Natural Products on Human Diseases: 2nd Edition)

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Review

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14 pages, 1131 KiB

Open AccessReview

Anti-Cancer Strategies Using Anaerobic Spore-Forming Bacteria Clostridium: Advances and Synergistic Approaches

by Saloni Singh, Geun-Hyung Kim, Kwang-Rim Baek and Seung-Oh Seo

Life 2025, 15(3), 465; https://doi.org/10.3390/life15030465 - 14 Mar 2025

Viewed by 667

Abstract

Despite ongoing advancements, cancer remains a significant global health concern, with a persistent challenge in identifying a definitive cure. While various cancer therapies have been developed and approved, offering treatments for smaller neoplasms, their efficacy diminishes in solid tumors and hypoxic environments, particularly for chemotherapy and radiation therapy. A novel approach, Clostridium-based therapy, has emerged as a promising candidate for current solid tumor treatments due to its unique affinity for the hypoxic tumor microenvironment. This review examines the potential of Clostridium in cancer treatment, encompassing direct tumor lysis, immune modulation, and synergistic effects with existing cancer therapies. Advancements in synthetic biology have further enhanced its potential through genetic modifications, such as the removal of alpha toxin gene from Clostridium novyi-NT, the implementation of targeted approaches, and reduction in systemic toxicity. Although preclinical and clinical studies have demonstrated that Clostridium-based treatments combined with other therapies hold promise for complete cancer eradication, challenges persist. Through this review, we also propose that the integration of various methods and technologies together with Clostridium-based therapy may lead to the complete eradication of cancer in the future. Full article

(This article belongs to the Special Issue Therapeutic Effects of Natural Products on Human Diseases: 2nd Edition)

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16 pages, 1771 KiB

Open AccessReview

The Influence of a Plant-Based Diet on Skin Health: Inflammatory Skin Diseases, Skin Healing, and Plant-Based Sources of Micro- and Macro-Nutrients

by Mildred Min, Anurag Tarmaster, Apple Bodemer and Raja K. Sivamani

Life 2024, 14(11), 1439; https://doi.org/10.3390/life14111439 - 7 Nov 2024

Cited by 3 | Viewed by 5120

Abstract

Dietary patterns have been shown to worsen or alleviate several dermatological diseases. A well-balanced, plant-based diet is known to have anti-inflammatory, probiotic, and antioxidant properties, along with weight loss-promoting effects. Moreover, a plant-based diet has a low glycemic load, improving metabolic disease. Due to these qualities, plant-based diets may have beneficial effects on inflammatory skin conditions. In this review, we aim to discuss the possible mechanisms by which a plant-based diet reduces disease severity in psoriasis, acne, hidradenitis suppurativa, and atopic dermatitis. We also aim to clarify how a plant-based diet may influence skin healing and identify sources of vitamins, nutrients, fatty acids, and protein in a well-balanced, plant-based diet. We performed a literature search on PubMed/MEDLINE databases with the following keywords: “plant-based” OR “vegan” OR “vegetarian” OR “meat” OR “diet” AND “psoriasis” OR “hidradenitis suppurativa” OR “acne” OR “atopic dermatitis” OR “skin healing” OR “dermatology”. Our findings demonstrate that plant-based foods may improve inflammatory skin diseases by supporting the gut microbiome, exerting anti-inflammatory effects, providing barrier support, and improving glycemic control. With the proper education, there is an abundance of plant-based food sources or supplements that contain riboflavin, vitamin B12, vitamin A, omega-3 fatty acids, and protein, thereby ameliorating the risk of nutritional deficiencies. Thus, a plant-based diet may have therapeutic potential in dermatology. In spite of the evidence available, there is a paucity of clinical studies focusing specifically on plant-based diets and dermatologic conditions and further investigation is warranted. Full article

(This article belongs to the Special Issue Therapeutic Effects of Natural Products on Human Diseases: 2nd Edition)

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Other

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9 pages, 3324 KiB

Open AccessCase Report

Resolution of Symptoms of Suspected Nonatypical Endometrial Hyperplasia Using Herbal Medicine Modified Sihogyeji-Tang Monotherapy: A Case Report with Ultrasound Monitoring

by Eunbyul Cho, Pyung-Wha Kim, Cheol-Hyun Kim, Changsop Yang and Stella Roh

Life 2025, 15(2), 256; https://doi.org/10.3390/life15020256 - 7 Feb 2025

Viewed by 1462

Abstract

This case report presents the therapeutic effects of herbal medicine modified Sihogyeji-tang monotherapy for suspected nonatypical endometrial hyperplasia (EH), documented through transabdominal ultrasonography monitoring and clinical symptom assessment. A 38-year-old woman presented with hypomenorrhea and ovulation-related pain, headache, body aches, and nausea since April 2023. The patient was clinically assessed as having nonatypical EH based on the ultrasound findings and clinical symptoms. She was treated with modified Sihogyeji-tang twice daily from 3 June 2023 to 29 December 2023. Treatment outcomes were evaluated using regular transabdominal ultrasonography measurements of endometrial thickness and changes in menstrual patterns, including cycle length and blood volume. Menstrual symptoms showed notable improvements: severe ovulation pain decreased from NRS 7–8 to 0, menstrual volume increased from 2 to 3 medium pads to 4 to 5 large pads per day during peak flow, and menstrual duration normalized from 4 to 6 days. Symptoms associated with ovulation and menstruation, headache, chills, and nausea resolved. At the 3-month follow-up visit after 7 months of herbal medicine treatment, endometrial thickness measured during the secretory phase had normalized to 1.40 cm (normal range: 0.7–1.4 cm). The coexisting uterine myoma remained stable throughout the treatment and follow-up. No adverse events were reported during the entire course of treatment. This case demonstrated that modified Sihogyeji-tang alone may effectively improve suspected nonatypical EH and its associated symptoms. Improvement was objectively assessed using ultrasound measurements and was sustained over a 9-month follow-up. Full article

(This article belongs to the Special Issue Therapeutic Effects of Natural Products on Human Diseases: 2nd Edition)

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