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Plant-Derived Products in the Treatment of Internal Diseases: 2nd Edition

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A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Natural Products".

Deadline for manuscript submissions: 25 June 2026 | Viewed by 7503

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Special Issue Editors

Dr. Dorin Dragoş

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Guest Editor

First Department, Medical Semiology, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
Interests: phytotherapy; herbal medicine; integrative medicine; pshychosomatics; internal medicine; nephrology; cardiovascular; neurovascular; diabetes
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Adelina Vlad

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Guest Editor

Physiology Department, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
Interests: atherosclerosis; coronary artery disease; scavenger receptors; anesthetic preconditioning; endothelial progenitor cells; non coding RNA; nutraceuticals; phytocompounds
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In recent decades, tremendous progress has been made in the discovery of new drugs for the treatment of internal diseases, reflected in the considerable change in the prognostic and course of these diseases. However, importantly, severe or even life-threatening side effects mar the employment of these novel treatments. Despite the statements in the guidelines, patients are not actually encouraged to perform the much-needed lifestyle changes that would make at least some of these new drugs less necessary, if at all, especially for the management of cardiovascular diseases, diabetes, obesity, dyslipidemia, and chronic obstructive lung disease. There are many instances of inappropriate employment of conventional drugs in the treatment of symptoms/disorders for which those drugs are not indicated: antibiotics for viral diseases, coronary heart disease medication for unspecific (including psychosomatic) chest pain, blood pressure-lowering medication for emotion-related fluctuations in blood pressure, etc. Many honest practitioners acknowledge that they should use something else but lack the trust in or knowledge about alternative therapies. A large segment of the population prefers alternative treatments, one of the most popular being herbal treatment. Individuals relying on alternative therapies are more amenable to health-promoting lifestyle changes.

Unfortunately, among the researchers and practitioners of mainstream medicine, there is a high degree of skepticism about the effectiveness of natural products, given the paucity and low quality of evidence supporting them. Let us, those that understand the considerable and insufficiently tapped potential of natural products, provide high-quality studies and reviews promoting the use of these products!

Dr. Dorin Dragoş
Dr. Adelina Vlad
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

medicinal plants
phytotherapy
herbal treatment
natural products
herbalism
traditional medicine
cardiovascular disease
lung disease
liver disease
gastrointestinal disease
kidney disease
obesity
diabetes
rheumatological disease

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Related Special Issue

Therapeutic Potential of Natural Products in Internal Diseases in Pharmaceuticals (13 articles)

Published Papers (6 papers)

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Research

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20 pages, 3700 KB

Open AccessArticle

Fat Browning Effects of Catalpol and Rhoifolin from Rehmannia glutinosa (Gaertn.) and Lonicera japonica (Thunb.) in 3T3-L1 Adipocytes via the β3-AR Signaling Pathway

by Seung Min Choi, Sung Ho Lim, Ho Seon Lee, Gayoung Choi, Myeong Ji Kim, Hyunwoo Kim and Chang-Ik Choi

Pharmaceuticals 2026, 19(5), 787; https://doi.org/10.3390/ph19050787 (registering DOI) - 18 May 2026

Abstract

Background/Objectives: Promoting white adipose tissue (WAT) browning into thermogenic beige adipocytes is a promising anti-obesity strategy. Yanggyeoksanhwa-tang (YST) has been used traditionally to alleviate obesity-related conditions. Catalpol and rhoifolin are major bioactive components of Rehmannia glutinosa (Gaertn.) and Lonicera japonica (Thunb.) with known metabolic or anti-inflammatory effects. However, their direct roles in adipocyte browning and the mechanisms via β3-adrenergic receptor (β3-AR) signaling are not well defined, and this study addresses this gap. Methods: To evaluate browning potential, 3T3-L1 adipocytes were treated with catalpol and rhoifolin during differentiation. The expression of browning markers and lipid metabolism or catabolism transcription factors was analyzed using Western blotting and quantitative real-time polymerase chain reaction. The involvement of the β3-AR and adenosine monophosphate–activated protein kinase (AMPK) signaling pathways was further validated using specific agonists and antagonists. Results: Both compound treatments significantly upregulated beige-specific (Cd137, Cited, Tbx1, Cidea, Fgf21, Tmem26) and mitochondrial biogenesis markers (Cox4, Nrf1, Tfam), accompanied by a marked increase in thermogenic markers (UCP1, PGC-1α, Prdm16). Concurrently, lipolysis-related genes such as Atgl, Hsl, and Plin1 were elevated, while lipogenesis targets (Fasn, Lpl, Srebf1, Acaca) were downregulated through activation of the β3-AR signaling pathway. Conclusions: These findings suggest that catalpol and rhoifolin, key phytochemicals of YST, promote WAT browning and lipolysis. Our findings indicate that these compounds induce browning and modulate metabolism via the β3-AR pathway. These results serve as a cornerstone for natural anti-obesity therapy, pending further validation in vivo and clinical studies. Full article

(This article belongs to the Special Issue Plant-Derived Products in the Treatment of Internal Diseases: 2nd Edition)

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24 pages, 9854 KB

Open AccessArticle

DHDK, a Plant-Derived Natural Small Molecule, Protects Against Doxorubicin-Induced Cardiotoxicity via the PPARG-CPT1B-FAO Axis

by Jing Hong, Fangyu Zhang, Ruizhen Zhang, Hongyang Fu, Dongang Shen, Xinyue Wang, Yuting Yang, Jiamei Wu, Lin Meng, Hongyang Lü, Xiwei Jiang and Yunli Zhao

Pharmaceuticals 2025, 18(11), 1759; https://doi.org/10.3390/ph18111759 - 18 Nov 2025

Cited by 2 | Viewed by 1296

Abstract

Background: Doxorubicin (DOX) is a highly effective chemotherapy drug, but its use is limited by dose-dependent cardiotoxicity, driving the search for protective natural products. Although the herb Viscum coloratum (Kom.) Nakai is known for its cardiovascular benefits, the cardioprotective effects and mechanisms of its isolated compound, DHDK, remain unexplored. Methods: The protective effect of DHDK was first evaluated in DOX-injured H9c2 cardiomyocytes. Subsequently, an integrated network toxicology (incorporating DOX-induced toxicity targets and relevant chronic disease pathways such as aging and lipid metabolism) and pharmacology (DHDK) approach identified core targets, which were then refined through Protein–Protein Interaction (PPI) analysis and molecular docking. The underlying mechanism was investigated using lipidomics and validated through a series of in vitro assays, including CCK-8, q-PCR, biochemical tests, and flow cytometry, as well as in an in vivo rat model. Results: DHDK significantly alleviated DOX-induced cardiomyocyte toxicity. Integrated analysis identified 56 intersecting targets, with PPARG confirmed as the primary target via PPI and molecular docking. Lipidomics revealed that DHDK potently attenuated DOX-induced accumulation of pathogenic lipids (e.g., fatty acids, ceramides). Mechanistically, DHDK activated PPARG, which in turn upregulated CPT1B, a key regulator of fatty acid β-oxidation (FAO). This enhanced cell viability, ATP production, and mitochondrial membrane potential while reducing oxidative stress. These protective effects, which were abolished by the inhibition of PPARG or CPT1B, were further validated in vivo. Conclusion: This study demonstrates that DHDK exerts its cardioprotective effect by activating the PPARG-CPT1B-FAO axis, effectively correcting lipid metabolic disorders. Given that lipid dysregulation is a hallmark of various internal metabolic diseases, DHDK may also hold therapeutic potential for other heart conditions driven by metabolic disturbances, such as diabetic cardiomyopathy, highlighting its broad relevance to the field of internal diseases. Full article

(This article belongs to the Special Issue Plant-Derived Products in the Treatment of Internal Diseases: 2nd Edition)

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20 pages, 9688 KB

Open AccessArticle

Hypolipidemic Effects of Alpinia japonica Extracts: Modulation of PPAR Signaling, Gut Microbiota, and Intestinal Barrier Function in Hyperlipidemic Rats

by Liqing Zhou, Cong Fang, Hongwei Li, Yifan Lin, Huiqing Que, Hongxu Liu, Lihong Ma and Wenjin Lin

Pharmaceuticals 2025, 18(9), 1320; https://doi.org/10.3390/ph18091320 - 3 Sep 2025

Cited by 1 | Viewed by 1495

Abstract

Objectives: Alpinia japonica (A. japonica) is traditionally used for digestive disorders, but its hypolipidemic mechanisms remain unclear. This study investigated the lipid-lowering effects of its fruit (SJGS), rhizome (SJGJ), and leaf (SJY) extracts, exploring their bioactive constituents and organ-specific mechanisms. Methods: Sprague Dawley rats (n = 8/group) fed a high-fat diet received SJGS, SJGJ, or SJY (200 mg/kg/day) for 4 weeks. Serum lipids (TC, TG), liver enzymes (AST, ALT), and intestinal barrier markers (DAO) were measured. Gut microbiota (16S rDNA sequencing), hepatic histopathology, and ileal tight junction proteins were analyzed. Transcriptomics and qPCR assessed ileal gene expression. LC-MS identified chemical constituents, while network pharmacology predicted compound-target interactions. Results: All extracts significantly reduced serum TC (↓ 27–33%), TG (↓ 29–38%), AST/ALT (↓ 22–30%), and DAO (↓ 35–42%) versus controls (p < 0.05). They improved hepatic steatosis, enhanced intestinal barrier function, and modulated gut microbiota (↑ α-diversity, ↓ Firmicutes/Bacteroidetes ratio). Transcriptomics revealed PPAR signaling as the core pathway: SJGS/SJGJ downregulated fatty acid oxidation genes (ACSL1, ACOX1, ACADM), while SJY upregulated APOA1 (2.3-fold). LC-MS identified 33–48 compounds/part, with seven shared constituents. Network analysis prioritized three flavonoids (pinocembrin, luteolin, galangin) targeting TNF, AKT1, and PPAR pathways. Conclusions: The findings suggest A. japonica extracts ameliorate hyperlipidemia through distinct mechanisms—SJGS/SJGJ may inhibit fatty acid oxidation, while SJY potentially enhances APOA1-mediated clearance. Shared flavonoids likely contribute to these effects via PPAR signaling, supporting its traditional use. This study provides a scientific basis for the sustainable utilization of A. japonica resources. Full article

(This article belongs to the Special Issue Plant-Derived Products in the Treatment of Internal Diseases: 2nd Edition)

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19 pages, 2360 KB

Open AccessArticle

Lepisanthes alata Attenuates Carrageenan-Induced Inflammation and Pain in Rats: A Phytochemical-Based Approach

by Elvy Suhana Mohd Ramli, Nadia Mohamed Tarmizi, Nur Aqilah Kamaruddin and Mohd Amir Kamaruzzaman

Pharmaceuticals 2025, 18(8), 1142; https://doi.org/10.3390/ph18081142 - 31 Jul 2025

Cited by 3 | Viewed by 3206

Abstract

Background: Inflammation abrogates cellular organization and tissue homoeostasis, resulting in redness, swelling, heat, pain, and loss of function. A model of carrageenan-induced paw edema (CIE) is commonly utilized to test anti-inflammatory substances. Based on the ability of Lepisanthes alata (LA), a tropical plant that is rich in phytochemicals like polyphenols, this study assessed the optimal dose and the health benefits of LA in rats that had been induced with carrageenan to develop paw swelling. Methods: Twenty-four male Wistar rats were divided into four groups to which carrageenan was administered, after which, distilled water at oral dose (C + DW), sodium diclofenac 25 mg/kg (C + DS), LA extract in 250 mg/kg (C + LA250), and 500 mg/kg (C + LA500) was given, respectively. Paw edema was assessed in 24 h. Pain was assessed using the Rat Grimace Scale (RGS), cytokines, antioxidant activity, and tissue changes. Results: LA at 250 and 500 mg/kg significantly decreased paw edema and inflammatory markers in the results of both studies. Remarkably, LA 250 mg/kg significantly decreased RGS scores as well as IL-1β, TNF-α, and histological inflammation but had a positive effect on T-SOD levels. Conclusions: LA extract, especially at 250 mg/kg, shows potent anti-inflammatory, analgesic, and antioxidant properties in CIE rats. Full article

(This article belongs to the Special Issue Plant-Derived Products in the Treatment of Internal Diseases: 2nd Edition)

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37 pages, 1356 KB

Open AccessReview

Preclinical Pharmacological Actions of Alpinetin and Pinocembrin—A Comparative Review

by Xinxiang Chen, Siu Kan Law, Huajian Li, Mei Zhang, Wenying Yu, Yixiao Li, Ying Zhou, Albert Wing Nang Leung, Bo Wu, Chuanshan Xu and Mei Feng

Pharmaceuticals 2026, 19(5), 734; https://doi.org/10.3390/ph19050734 - 7 May 2026

Viewed by 427

Abstract

Background: Human diseases remain a major global health challenge, requiring effective therapeutic strategies. Traditional Chinese medicine (TCM) has been widely used in clinical settings. Many natural compounds, such as flavonoids from TCM, exhibit diverse pharmacological activities. Alpinetin and pinocembrin are structurally related flavonoids. Alpinetin is derived from Zingiberaceae plants, and pinocembrin is extracted from wild marjoram (origanum vulgare) or other natural sources. They possess a wide range of pharmacological activities or biological effects, including anti-inflammatory, anti-tumor, liver and kidney protection, cardiovascular protection, and antibacterial activities. Methods: The present comparative review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, using four major databases (PubMed, EMBASE, Web of Science, and Cochrane Library), as well as CNKI without language restrictions. Results: Pharmacokinetic studies reveal distinct absorption, metabolism, and excretion profiles. Alpinetin and pinocembrin undergo glucuronidation and interact with cytochrome P450 enzymes and transporters. However, alpinetin has demonstrated approximately 1.5-fold higher plasma exposure and slower clearance compared to pinocembrin. Mechanistically, alpinetin exerted therapeutic effects through modulation of the NF-κB/MAPK, PI3K/Akt, and PPAR-γ signaling pathways, resulting in a 2- to 3-fold reduction in pro-inflammatory cytokines. In contrast, pinocembrin exerted protective activity through the inhibition of HMGB1/TLR4 signaling, regulation of endoplasmic reticulum stress, and activation of Nrf2/HO-1, leading to a 1.8-fold increase in antioxidant enzyme activity. The minimum inhibitory concentrations were reduced by 2- to 4-fold against Gram-positive bacteria compared to alpinetin. Conclusions: These findings highlight the pharmacological potential of alpinetin and pinocembrin as promising candidates for the development of novel anti-tumor, anti-inflammatory, liver and kidney protection, cardiovascular protection, and antibacterial agents. However, research on the pharmacological actions of alpinetin and pinocembrin is still in the preclinical stage. Further research is required to validate their efficacy in clinical settings, especially for translation to clinical studies. This is critical to translating these natural flavonoids into effective therapeutic agents while addressing the regulatory challenges and pathways associated with botanical drugs in human diseases. Full article

(This article belongs to the Special Issue Plant-Derived Products in the Treatment of Internal Diseases: 2nd Edition)

Other

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28 pages, 6281 KB

Open AccessSystematic Review

Effectiveness and Safety of Liuwei Dihuang as an Adjunctive Therapy for Cognitive Impairment: A Systematic Review, Meta-Analysis, and Network Pharmacology Analysis

by Jihyun Hwang, Mi Hye Kim, Jeongrim Bak, Jong-Min Yun and Jungtae Leem

Pharmaceuticals 2026, 19(5), 776; https://doi.org/10.3390/ph19050776 (registering DOI) - 15 May 2026

Viewed by 167

Abstract

Background/Objectives: Liuwei Dihuang (LWDH) is a classical plant-derived herbal formula widely used for cognitive decline. This study aimed to evaluate its efficacy and safety in cognitive disorders and to explore its potential pharmacological mechanisms using network pharmacology. Methods: We searched 11 databases through November 2024 for randomized controlled trials comparing LWDH plus conventional therapy with conventional therapy alone in cognitive disorders. Meta-analysis was performed for clinical outcomes, and herb–compound–target and disease-target datasets were integrated to identify core molecular modules. Results: Twelve randomized controlled trials involving 1137 participants were included. Adjunctive LWDH was associated with improvements in Mini-Mental State Examination scores (MD = 2.34, 95% CI 0.88–3.79), activities of daily living, and quality of life. However, substantial heterogeneity and methodological limitations, including unclear randomization and blinding, were observed across studies, indicating a potential risk of bias. Fewer adverse events were reported in the LWDH plus conventional treatment group, although reporting quality was limited. The overall risk of bias was judged as “some concerns”. Network pharmacology analysis identified a broad set of overlapping genes between LWDH-associated targets and cognitive disorder-related genes, which were further refined through filtering procedures. Subsequent analyses suggested associations with pathways related to neurodegeneration, apoptosis, and central nervous system function; however, these findings are exploratory and based on in silico predictions. Conclusions: LWDH may be associated with potential adjunctive benefits in cognitive disorders. However, given the methodological limitations and clinical heterogeneity of the included studies, the findings should be interpreted with caution. The proposed pharmacological mechanisms are exploratory and require further validation. Well-designed randomized controlled trials are needed to establish more robust evidence. Full article

(This article belongs to the Special Issue Plant-Derived Products in the Treatment of Internal Diseases: 2nd Edition)

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