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Cutting-Edge Biotechnologies and Applications of Natural Products in Drug R&D...
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Cutting-Edge Biotechnologies and Applications of Natural Products in Drug R&D and Disease Treatment

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

Deadline for manuscript submissions: 25 March 2026 | Viewed by 5471

Special Issue Editor

Prof. Dr. Sujay Paul

E-Mail Website1 Website2
Guest Editor
Tecnologico de Monterrey, School of Engineering and Sciences, Campus Queretaro, Queretaro 76130, Mexico
Interests: ncRNAs in human diseases; gene regulation; biomarker; therapy; anticancer phytochemicals; plant microRNA; nanotechnology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Recent advancements in biotechnology have revolutionized drug research and development (R&D), unlocking the therapeutic potential of natural products. This Special Issue will explore the intersection of cutting-edge biotechnologies and natural product-based drug discovery, focusing on innovative approaches to treating various diseases. Natural products derived from plants, microorganisms, and marine organisms have historically served as the foundation for many clinically approved drugs. With breakthroughs in synthetic biology, metabolic engineering, and AI-driven drug discovery, researchers can now optimize and modify these bioactive compounds more efficiently. This Special Issue will highlight the novel biotechnological strategies that are accelerating the development and formulation of potent natural therapeutic agents. Additionally, we will examine the role of natural products in addressing emerging health challenges, such as antimicrobial resistance, cancer, neurodegenerative disorders, and metabolic diseases. Contributions will also explore advances in drug formulation, delivery systems, and bioavailability enhancement, ensuring that natural-product-derived therapies reach their full potential in clinical applications. By bringing together experts in biotechnology, pharmacology, nanotechnology, and natural product chemistry, this Special Issue will provide a comprehensive overview of the latest research trends, challenges, and future directions in this rapidly evolving field. We invite the submission of original research articles, reviews, and perspectives that shed light on innovative methodologies and applications shaping the future of drug discovery and disease treatment.

Prof. Dr. Sujay Paul
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

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.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • natural products
  • bioactive compounds
  • natural product drug discovery and drug design
  • natural drug formulation
  • metabolic engineering for bioactive compounds
  • natural therapeutic agents
  • nanoformulations of natural compounds
  • synthetic biology for natural product biosynthesis
  • genome editing and creation of novel bioactive compounds

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Published Papers (4 papers)

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Research

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37 pages, 3637 KB  
Article
Lemon Juice-Assisted Green Extraction of Strawberry Enhances Neuroprotective Phytochemicals: Insights into Alzheimer’s-Related Pathways
by Youssef Mohamed Sharaf, Jilan A. Nazeam, Karema Abu-Elfotuh, Ayah M. H. Gowifel, Ahmed M. Atwa, Ehsan Khedre Mohamed, Ahmed M. E. Hamdan, Reema Almotairi, Amira M. Hamdan, Samir M. Osman and Hala M. El Hefnawy
Pharmaceuticals 2025, 18(12), 1892; https://doi.org/10.3390/ph18121892 - 15 Dec 2025
Viewed by 1284
Abstract
Background/Objective: Alzheimer’s disease (AD) is a neurodegenerative condition characterized by oxidative stress, neuroinflammation, amyloidogenesis, and tau-related pathology. This study investigated the macronutrient and phytochemical composition of strawberry (S), lemon (L), and lemon juice-assisted strawberry (S/L) extracts and evaluated their neuroprotective efficacy relative [...] Read more.
Background/Objective: Alzheimer’s disease (AD) is a neurodegenerative condition characterized by oxidative stress, neuroinflammation, amyloidogenesis, and tau-related pathology. This study investigated the macronutrient and phytochemical composition of strawberry (S), lemon (L), and lemon juice-assisted strawberry (S/L) extracts and evaluated their neuroprotective efficacy relative to selenium (Se) in an aluminum chloride (AlCl3)-induced rat model of AD. Methods: Macronutrients and phenolics were quantified in S, L, and S/L, and the extracts were profiled using high-performance liquid chromatography and electrospray ionization tandem mass-spectrometry. Male Sprague–Dawley rats received AlCl3 with or without S, L, S/L, or Se, and their cognitive performance was assessed using the Morris water maze, Y-maze, and conditioned avoidance tests. Markers of oxidative status, inflammation, cholinergic function, apoptotic signaling, and Wnt3/β-catenin pathway activity were quantified in the brain tissue, and cortico-hippocampal morphology was examined. Results: The S/L extract showed the highest carbohydrate, protein, and lipid content. The total phenolic content was highest in S/L (60.46 mg gallic acid equivalents/g), followed by L (55.08) and S (44.75), with S/L also being the richest in gallic, ellagic, and chlorogenic acids. S/L attenuated AlCl3-induced cognitive deficits, restored antioxidant status, suppressed neuroinflammation, improved cholinergic indices, modulated apoptotic signaling, and downregulated amyloidogenic and NLRP3 inflammasome markers, consistent with histological evidence of neuronal preservation. Conclusions: Lemon juice-assisted extraction enhanced the macronutrient and phenolic richness and multitarget neuroprotection of strawberries. S/L co-extracts represent promising functional food–derived adjuvants for AD management and support integrative compositional–mechanistic profiling to optimize natural product–based interventions. Full article
(This article belongs to the Special Issue Cutting-Edge Biotechnologies and Applications of Natural Products in Drug R&D and Disease Treatment)
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24 pages, 2632 KB  
Article
Therapeutic Potential of Glucose Oxidase-Loaded Biogenic Mesoporous Silica Nanoparticles in Ovarian Cancer
by Andrea G. Uriostegui-Pena, Padmavati Sahare, Gabriel Luna-Bárcenas and Sujay Paul
Pharmaceuticals 2025, 18(7), 1060; https://doi.org/10.3390/ph18071060 - 18 Jul 2025
Cited by 1 | Viewed by 1626
Abstract
Background/Objectives: Ovarian cancer (OC) remains one of the most lethal malignancies of the female reproductive system. Glucose oxidase (GOx) has emerged as a potential therapeutic agent in cancer treatment by inducing tumor starvation through glucose depletion. Nonetheless, its clinical application is constrained due [...] Read more.
Background/Objectives: Ovarian cancer (OC) remains one of the most lethal malignancies of the female reproductive system. Glucose oxidase (GOx) has emerged as a potential therapeutic agent in cancer treatment by inducing tumor starvation through glucose depletion. Nonetheless, its clinical application is constrained due to its systemic toxicity, immunogenicity, poor in vivo stability, and short half-life. These challenges can be addressed through nanotechnology; in particular, biogenic mesoporous silica nanoparticles (MSNs) offer promise as drug delivery systems (DDSs) that enhance therapeutic efficacy while minimizing side effects. Methods: Biogenic MSNs were extracted from the Equisetum myriochaetum plant via acid digestion, functionalized with 3-aminopropiltrietoxysilane (APTES) and glutaraldehyde (GTA), and loaded with GOx. The free and immobilized MSNs were characterized using FTIR, DLS, XRD, SEM/EDX, and BET techniques. A colorimetric approach was employed to quantify the enzymatic activity of both the free and immobilized GOx. The MTT assay was employed to assess the viability of SKOV3 cells. The obtained IC50 concentration of the nanoformulation was administered to SKOV3 cells to analyze the expression of cancer-related genes using RT-qPCR. Results: IC50 values of 60.77 ng/mL and 111.6 µg/mL were ascertained for the free and immobilized GOx, respectively. Moreover, a significant downregulation of the oncogene β-catenin (CTNNB1) was detected after 24 h with the nanoformulation. Conclusions: Our findings indicate that GOx-loaded biogenic MSNs may serve as a potential therapeutic agent for ovarian cancer. This is, to the best of our knowledge, the first report exploring the effect of GOx-loaded biogenic MSNs on SKOV3 cells. Full article
(This article belongs to the Special Issue Cutting-Edge Biotechnologies and Applications of Natural Products in Drug R&D and Disease Treatment)
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Review

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21 pages, 1974 KB  
Review
Mining Microbial Dark Matter: Advanced Cultivation Techniques for Bioactive Compound Discovery
by Minhui Ji, Bingda Ma, Jiayu Dong, Shan Liu, Ying Shi, Meiting Bu, Luoyi Wang and Ling Liu
Pharmaceuticals 2025, 18(10), 1583; https://doi.org/10.3390/ph18101583 - 20 Oct 2025
Viewed by 1729
Abstract
The vast majority of microorganisms in the environment remain uncultured using conventional laboratory techniques, representing an immense untapped reservoir of genetic and chemical diversity. Recent innovations in cultivation strategies, combined with advances in metagenomics, single-cell genomics, and synthetic biology, have opened new avenues [...] Read more.
The vast majority of microorganisms in the environment remain uncultured using conventional laboratory techniques, representing an immense untapped reservoir of genetic and chemical diversity. Recent innovations in cultivation strategies, combined with advances in metagenomics, single-cell genomics, and synthetic biology, have opened new avenues for accessing and harnessing bioactive natural products from these previously inaccessible microorganisms. This review highlights recent methodological and technological advancements in the cultivation and identification of novel microorganisms, and showcases the resulting discoveries of new natural products, demonstrating their potential for drug development. Full article
(This article belongs to the Special Issue Cutting-Edge Biotechnologies and Applications of Natural Products in Drug R&D and Disease Treatment)
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Other

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26 pages, 2283 KB  
Systematic Review
Emerging Breakthroughs in Nano-Ginseng Innovations and Their Therapeutic Implications in Type 2 Diabetes
by Pragya Tiwari, Kyeung-Il Park and Sayanti Mandal
Pharmaceuticals 2026, 19(1), 186; https://doi.org/10.3390/ph19010186 - 21 Jan 2026
Viewed by 350
Abstract
Background/Objectives: Diabetes is characterized by multiple metabolic disorders, defined by high blood sugar levels over a prolonged duration. Type 2 diabetes (T2D) comprises defective insulin secretion, its ineffective utilization, or both, resulting in hyperglycemia. The disease is one of the leading causes of [...] Read more.
Background/Objectives: Diabetes is characterized by multiple metabolic disorders, defined by high blood sugar levels over a prolonged duration. Type 2 diabetes (T2D) comprises defective insulin secretion, its ineffective utilization, or both, resulting in hyperglycemia. The disease is one of the leading causes of mortality, according to the WHO, and necessitates the development of advanced therapeutics. Methods: This systematic review was conducted in accordance with the PRISMA guidelines. The study and execution of the literature review followed a timeframe of 3–6 months, during which the conceptualization, execution, analysis, writing, and editing were conducted. Ginsenosides, triterpenoids from the Panax genus, are widely recognized for their promising antidiabetic effects, mediated through mechanisms that include glucose uptake, insulin secretion, antioxidant activity, and anti-inflammatory pathways. Ongoing clinical trials in patients with IGT or Type 2 diabetes have shown an improvement in insulin sensitivity and glucose control, and consolidate the therapeutic potential of ginseng pharmacotherapy. Results: This viewpoint summarizes the most recent discoveries on the hypoglycemic mechanisms of ginsenosides for Type 2 diabetes and its associated complications, with a major focus on ginseng-based drug development. An emphasis is placed on how ginsenosides control blood glucose levels and regulate signaling pathways, investigating their antidiabetic mechanisms and potential. Conclusions: Preclinical studies suggest that nano-innovations in ginseng have the potential to address therapeutic challenges, improve systemic circulation, lower the toxicity of biomolecules, and improve bioavailability, defining exciting outcomes. Furthermore, well-designed human clinical trials are necessary to understand the antidiabetic mechanisms and pharmacological potential of ginseng and/or ginsenosides in drug development. Full article
(This article belongs to the Special Issue Cutting-Edge Biotechnologies and Applications of Natural Products in Drug R&D and Disease Treatment)
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