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Pharmaceuticals
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Systems Biology and Network Pharmacology in Phytotherapy of Stress-Induced Disorders
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Systems Biology and Network Pharmacology in Phytotherapy of Stress-Induced Disorders

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

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 45322

Special Issue Editor

Prof. Dr. Alexander George Panossian

E-Mail Website
Guest Editor
Phytomed AB, 58344 Vastervick, Sweden
Interests: network pharmacology; neuroendocrine-immune system; stress; ageing; infalmmation; adaptogens
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Recent progress in phytotherapy research is currently associated with the rapid development of network pharmacology and systems biology concepts, which provide the tools for the understanding of both molecular mechanisms and the modes of action of plant extracts used in traditional medical systems, in purified active constituents, and for the discoveries of new effective and safe therapeutic agents.

Many components of the stress system, defined as the neuroendocrine-immune complex, mediate the effects of various herbal preparations that are used for the prevention and treatment of stress-induced symptoms and disorders, such as the following: fatigue, exhaustion, lack of energy, lack of endurance, difficulty concentrating, headache, sleeplessness, irritability, anxiety, depression, behavioral disorders, eating disorders, high blood pressure, impaired cognitive function, impaired mental performance (attention and memory), impaired physical performance (working capacity and precision), impaired recovery, sexual dysfunction, low-grade chronic systemic inflammation (inflammaging), cell degeneration, cellular senescence, etc.

However, rational and evidence-based use of selected herbal preparations is required for the effective and safe treatment of various stress-induced disorders and diseases.

This Special Issue is aimed at highlighting recent achievements, findings, and observations in the area of the phytotherapy of stress-induced disorders based on network pharmacology and systems biology approaches.

We encourage authors to submit the results of clinical and preclinical in vivo and in vitro studies of herbal preparations and purified compounds.

Prof. Dr. Alexander George Panossian
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 100 words) can be sent to the Editorial Office for announcement on this website.

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

  • systems biology
  • network pharmacology
  • phytotherapy
  • stress
  • medicinal plants
  • mental and behavioural disorders
  • fatigue

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Published Papers (6 papers)

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Research

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15 pages, 4366 KiB  
Article
Network Pharmacology of Ginseng (Part III): Antitumor Potential of a Fixed Combination of Red Ginseng and Red Sage as Determined by Transcriptomics
by Alexander Panossian, Sara Abdelfatah and Thomas Efferth
Pharmaceuticals 2022, 15(11), 1345; https://doi.org/10.3390/ph15111345 - 30 Oct 2022
Cited by 4 | Viewed by 2549
Abstract
Background: This study aimed to assess the effect of a fixed combination of Red Ginseng and Red Sage (RG–RS) on the gene expression of neuronal cells to evaluate the potential impacts on cellular functions and predict its relevance in the treatment of stress [...] Read more.
Background: This study aimed to assess the effect of a fixed combination of Red Ginseng and Red Sage (RG–RS) on the gene expression of neuronal cells to evaluate the potential impacts on cellular functions and predict its relevance in the treatment of stress and aging-related diseases and disorders. Methods: Gene expression profiling was conducted by transcriptome-wide mRNA microarray analyses of murine HT22 hippocampal cell culture after treatment with RG–RS preparation. Ingenuity pathway analysis (IPA) was performed with datasets of significantly upregulated or downregulated genes and the expected effects on the physiological and cellular function and the diseases were identified. Results: RG–RS deregulates 1028 genes associated with cancer and 139 with metastasis, suggesting a predicted decrease in tumorigenesis, the proliferation of tumor cells, tumor growth, metastasis, and an increase in apoptosis and autophagy by their effects on the various signaling and metabolic pathways, including the inhibition of Warburg’s aerobic glycolysis, estrogen-mediated S-phase entry signaling, osteoarthritis signaling, and the super-pathway of cholesterol biosynthesis. Conclusion: The results of this study provide evidence of the potential efficacy of the fixed combination of Red Ginseng (Panax ginseng C.A. Mey.) and Red Sage/Danshen (Salvia miltiorrhiza Bunge) in cancer. Further clinical and experimental studies are required to assess the efficacy and safety of RG–RS in preventing the progression of cancer, osteoarthritis, and other aging-related diseases. Full article
(This article belongs to the Special Issue Systems Biology and Network Pharmacology in Phytotherapy of Stress-Induced Disorders)
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19 pages, 3867 KiB  
Article
Berberine Overcomes Gemcitabine-Associated Chemoresistance through Regulation of Rap1/PI3K-Akt Signaling in Pancreatic Ductal Adenocarcinoma
by Keisuke Okuno, Caiming Xu, Silvia Pascual-Sabater, Masanori Tokunaga, Haiyong Han, Cristina Fillat, Yusuke Kinugasa and Ajay Goel
Pharmaceuticals 2022, 15(10), 1199; https://doi.org/10.3390/ph15101199 - 28 Sep 2022
Cited by 15 | Viewed by 5237
Abstract
Gemcitabine (Gem)-based chemotherapy is one of the first-line treatments for pancreatic ductal adenocarcinoma (PDAC). However, its clinical effect is limited due to development of chemoresistance. Various naturally occurring compounds, including Berberine (BBR), provide an anti-cancer efficacy with time-tested safety, individually and in combination [...] Read more.
Gemcitabine (Gem)-based chemotherapy is one of the first-line treatments for pancreatic ductal adenocarcinoma (PDAC). However, its clinical effect is limited due to development of chemoresistance. Various naturally occurring compounds, including Berberine (BBR), provide an anti-cancer efficacy with time-tested safety, individually and in combination with chemotherapeutic drugs. Accordingly, we hypothesized that BBR might enhance the chemosensitivity to Gem in PDAC. In this study, cell culture studies using MIA PaCa-2 and BxPC-3 cells, followed by analysis in patient-derived organoids were performed to evaluate the anti-cancer effects of BBR in PDAC. Considering that cancer is a significant manifestation of increased chronic inflammatory stress, systems biology approaches are prudent for the identification of molecular pathways and networks responsible for phytochemical-induced anti-cancer activity, we used these approaches for BBR-mediated chemosensitization to Gem. Firstly, Gem-resistant (Gem-R) PDAC cells were established, and the combination of BBR and Gem revealed superior anti-cancer efficacy in Gem-R cells. Furthermore, the combination treatment induced cell cycle arrest and apoptosis in Gem-R PDAC cells. Transcriptomic profiling investigated the Rap1 and PI3K-Akt signaling pathway as a key regulator of Gem-resistance and was a key mediator for BBR-mediated chemosensitization in PDAC cells. All cell culture-based findings were successfully validated in patient-derived organoids. In conclusion, we demonstrate that BBR-mediated reversal of chemoresistance to Gem manifests through Rap1/PI3K-Akt signaling in PDAC. Full article
(This article belongs to the Special Issue Systems Biology and Network Pharmacology in Phytotherapy of Stress-Induced Disorders)
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17 pages, 2879 KiB  
Article
A Combined Treatment with Berberine and Andrographis Exhibits Enhanced Anti-Cancer Activity through Suppression of DNA Replication in Colorectal Cancer
by Yinghui Zhao, Souvick Roy, Chuanxin Wang and Ajay Goel
Pharmaceuticals 2022, 15(3), 262; https://doi.org/10.3390/ph15030262 - 22 Feb 2022
Cited by 17 | Viewed by 3952
Abstract
The high morbidity and mortality associated with colorectal cancer (CRC) are largely due to the invariable development of chemoresistance to classic chemotherapies, as well as intolerance to their significant toxicity. Many pharmaceutical formulations screened from natural plant extracts offer safe, inexpensive, and multi-target [...] Read more.
The high morbidity and mortality associated with colorectal cancer (CRC) are largely due to the invariable development of chemoresistance to classic chemotherapies, as well as intolerance to their significant toxicity. Many pharmaceutical formulations screened from natural plant extracts offer safe, inexpensive, and multi-target therapeutic options. In this study, we demonstrated that Berberis vulgaris L. (Berberine) and Andrographis paniculata (Burm. f.) Nees (Andrographis) extracts exerted their synergistic amplified anti-cancer effects by jointly inhibiting cell viability, suppressing colony formation, and inducing cell cycle arrest. Consistent with our in-vitro findings, the amplified synergistic anti-cancer effects were also observed in subcutaneous xenograft preclinical animal models, as well as patient-derived primary tumor organoids. To explore the molecular mechanisms underlying the amplified synergistic anti-cancer effects, RNA sequencing was performed to identify candidate pathways and genes. A transcriptome analysis revealed that DNA-replication-related genes, including FEN1, MCM7, PRIM1, MCM5, POLA1, MCM4, and PCNA, may be responsible for the enhanced anticancer effects of these two natural extracts. Taken together, our data revealed the powerful enhanced synergistic anti-CRC effects of berberine and Andrographis and provide evidence for the combinational targeting of DNA-replication-related genes as a promising new strategy for the therapeutic option in the management of CRC patients. Full article
(This article belongs to the Special Issue Systems Biology and Network Pharmacology in Phytotherapy of Stress-Induced Disorders)
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Review

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22 pages, 3016 KiB  
Review
Network Pharmacology of Adaptogens in the Assessment of Their Pleiotropic Therapeutic Activity
by Alexander Panossian and Thomas Efferth
Pharmaceuticals 2022, 15(9), 1051; https://doi.org/10.3390/ph15091051 - 25 Aug 2022
Cited by 15 | Viewed by 3544
Abstract
The reductionist concept, based on the ligand–receptor interaction, is not a suitable model for adaptogens, and herbal preparations affect multiple physiological functions, revealing polyvalent pharmacological activities, and are traditionally used in many conditions. This review, for the first time, provides a rationale for [...] Read more.
The reductionist concept, based on the ligand–receptor interaction, is not a suitable model for adaptogens, and herbal preparations affect multiple physiological functions, revealing polyvalent pharmacological activities, and are traditionally used in many conditions. This review, for the first time, provides a rationale for the pleiotropic therapeutic efficacy of adaptogens based on evidence from recent gene expression studies in target cells and where the network pharmacology and systems biology approaches were applied. The specific molecular targets and adaptive stress response signaling mechanisms involved in nonspecific modes of action of adaptogens are identified. Full article
(This article belongs to the Special Issue Systems Biology and Network Pharmacology in Phytotherapy of Stress-Induced Disorders)
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33 pages, 2222 KiB  
Review
Network Pharmacology Approach for Medicinal Plants: Review and Assessment
by Fatima Noor, Muhammad Tahir ul Qamar, Usman Ali Ashfaq, Aqel Albutti, Ameen S. S. Alwashmi and Mohammad Abdullah Aljasir
Pharmaceuticals 2022, 15(5), 572; https://doi.org/10.3390/ph15050572 - 4 May 2022
Cited by 140 | Viewed by 23086
Abstract
Natural products have played a critical role in medicine due to their ability to bind and modulate cellular targets involved in disease. Medicinal plants hold a variety of bioactive scaffolds for the treatment of multiple disorders. The less adverse effects, affordability, and easy [...] Read more.
Natural products have played a critical role in medicine due to their ability to bind and modulate cellular targets involved in disease. Medicinal plants hold a variety of bioactive scaffolds for the treatment of multiple disorders. The less adverse effects, affordability, and easy accessibility highlight their potential in traditional remedies. Identifying pharmacological targets from active ingredients of medicinal plants has become a hot topic for biomedical research to generate innovative therapies. By developing an unprecedented opportunity for the systematic investigation of traditional medicines, network pharmacology is evolving as a systematic paradigm and becoming a frontier research field of drug discovery and development. The advancement of network pharmacology has opened up new avenues for understanding the complex bioactive components found in various medicinal plants. This study is attributed to a comprehensive summary of network pharmacology based on current research, highlighting various active ingredients, related techniques/tools/databases, and drug discovery and development applications. Moreover, this study would serve as a protocol for discovering novel compounds to explore the full range of biological potential of traditionally used plants. We have attempted to cover this vast topic in the review form. We hope it will serve as a significant pioneer for researchers working with medicinal plants by employing network pharmacology approaches. Full article
(This article belongs to the Special Issue Systems Biology and Network Pharmacology in Phytotherapy of Stress-Induced Disorders)
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Other

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13 pages, 566 KiB  
Hypothesis
An Open-Label, Pilot Trial of HRG80™ Red Ginseng in Chronic Fatigue Syndrome, Fibromyalgia, and Post-Viral Fatigue
by Jacob Teitelbaum and Sarah Goudie
Pharmaceuticals 2022, 15(1), 43; https://doi.org/10.3390/ph15010043 - 29 Dec 2021
Cited by 7 | Viewed by 5162
Abstract
Chronic fatigue syndrome and fibromyalgia (CFS/FMS) affect 2.1% of the world’s population and ~10–25% of people who have had COVID-19. Previous clinical data suggested that a unique Panax ginseng (C.A. Meyer, family Araliaceae) root extract (HRG80™ Red Ginseng) often resulted in marked improvement. [...] Read more.
Chronic fatigue syndrome and fibromyalgia (CFS/FMS) affect 2.1% of the world’s population and ~10–25% of people who have had COVID-19. Previous clinical data suggested that a unique Panax ginseng (C.A. Meyer, family Araliaceae) root extract (HRG80™ Red Ginseng) often resulted in marked improvement. We aimed to study this hydroponic form of red ginseng root, containing high levels of rare ginsenosides, for improving energy, cognition, and stamina. This open-label prospective study included participants with severe CFS/FMS who took a daily supplement of HRG80 capsules (200–400 mg) or tablets (100–200 mg) for one month. A total of 188 subject patients completed the one-month treatment trial. Of these, 60.1% rated themselves as improved, with 13.3% rating themselves as being much better. In this group, the mean composite score improved from 11.9 to 18.8 (p < 0.001), with a 67% average increase in energy, 44% average increase in overall well-being, 48% average improvement in mental clarity, 58% average composite improvement in the previous three measurements (primary outcome measure), 46% average improvement in sleep, 33% average decrease in pain, and 72% average increase in stamina. Our study showed that HRG80 red ginseng root powder resulted in a marked improvement in people with CFS and fibromyalgia. This included the subgroup with post-viral CFS/FMS. Full article
(This article belongs to the Special Issue Systems Biology and Network Pharmacology in Phytotherapy of Stress-Induced Disorders)
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