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Biomolecules
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Phytochemical Omics in Medicinal Plants
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Phytochemical Omics in Medicinal Plants

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Natural and Bio-inspired Molecules".

Deadline for manuscript submissions: closed (31 March 2020) | Viewed by 164472

Special Issue Editor

Prof. Dr. Jen-Tsung Chen

E-Mail Website
Guest Editor
Department of Life Sciences, National University of Kaohsiung, Kaohsiung 811, Taiwan
Interests: bioactive compounds; chromatography techniques; medicinal plants; phytochemicals; plant biotechnology; plant growth regulators; plant secondary metabolites
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Since prehistoric times, medicinal plants (herbs) and tonics have been used in traditional medical practices for curing diseases and to provide health benefits. A huge array of phytochemicals have been identified in medicinal plants, such as carotenoids, phenolic acids, flavonoids, and lignans, which have a wide range of biological activities, including antioxidant, antibacterial effect, anticancer, anti-inflammatory, neuroprotection, and so on. Generally, naturally occurring compounds possess complicate bioactive effects and their efficacy is difficult to be clarified. Therefore, comprehensive approaches on the synthesis and biological function of phytochemicals are needed.

In the past decade, multi-omics technology is an emerging field as a powerful tool to gain deep-insights into biological systems. This Special Issue aims to integrate recent innovative approaches using high-throughput technologies (omics), such as genomics, transcriptomics, proteomics, and metabolomics, as well as bioinformatics and other related topics, including biotechnology attempts, to make significant progress in understanding the relationship between phytochemicals and human health.

Dr. Jen-Tsung Chen
Guest Editor

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 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

  • bioactive compounds
  • bioinformatics
  • biotechnology
  • herbs
  • genomics
  • medicinal plant
  • metabolomics
  • omics
  • phytochemicals
  • proteomics
  • transcriptomics

Published Papers (28 papers)

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Editorial

Jump to: Research, Review

7 pages, 201 KiB  
Editorial
Phytochemical Omics in Medicinal Plants
by Jen-Tsung Chen
Biomolecules 2020, 10(6), 936; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10060936 - 21 Jun 2020
Cited by 8 | Viewed by 3085
Abstract
Medicinal plants are used to treat diseases and provide health benefits, and their applications are increasing around the world [...] Full article
(This article belongs to the Special Issue Phytochemical Omics in Medicinal Plants)

Research

Jump to: Editorial, Review

14 pages, 2490 KiB  
Article
In Vitro Anti-Inflammatory, Anti-Oxidant, and Cytotoxic Activities of Four Curcuma Species and the Isolation of Compounds from Curcuma aromatica Rhizome
by Aknarin Pintatum, Wisanu Maneerat, Emilie Logie, Emmy Tuenter, Maria E. Sakavitsi, Luc Pieters, Wim Vanden Berghe, Tawanun Sripisut, Suwanna Deachathai and Surat Laphookhieo
Biomolecules 2020, 10(5), 799; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10050799 - 21 May 2020
Cited by 40 | Viewed by 4598
Abstract
The genus Curcuma is part of the Zingiberaceae family, and many Curcuma species have been used as traditional medicine and cosmetics in Thailand. To find new cosmeceutical ingredients, the in vitro anti-inflammatory, anti-oxidant, and cytotoxic activities of four Curcuma species as well as [...] Read more.
The genus Curcuma is part of the Zingiberaceae family, and many Curcuma species have been used as traditional medicine and cosmetics in Thailand. To find new cosmeceutical ingredients, the in vitro anti-inflammatory, anti-oxidant, and cytotoxic activities of four Curcuma species as well as the isolation of compounds from the most active crude extract (C. aromatica) were investigated. The crude extract of C. aromatica showed 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity with an IC50 value of 102.3 μg/mL. The cytotoxicity effect of C. aeruginosa, C. comosa, C. aromatica, and C. longa extracts assessed with the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay at 200 μg/mL were 12.1 ± 2.9, 14.4 ± 4.1, 28.6 ± 4.1, and 46.9 ± 8.6, respectively. C. aeruginosa and C. comosa presented apoptosis cells (57.7 ± 3.1% and 32.6 ± 2.2%, respectively) using the CytoTox-ONE™ assay. Different crude extracts or phytochemicals purified from C. aromatica were evaluated for their anti-inflammatory properties. The crude extract of C. aromatica showed the highest potential to inhibit NF-κB activity, followed by C. aeruginosa, C. comosa, and C. longa, respectively. Among the various purified phytochemicals curcumin, germacrone, curdione, zederone, and curcumenol significantly inhibited NF-κB activation in tumor necrosis factor (TNF) stimulated HaCaT keratinocytes. Of all compounds, curcumin was the most potent anti-inflammatory. Full article
(This article belongs to the Special Issue Phytochemical Omics in Medicinal Plants)
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12 pages, 4689 KiB  
Article
Low Concentration of Withaferin a Inhibits Oxidative Stress-Mediated Migration and Invasion in Oral Cancer Cells
by Tzu-Jung Yu, Jen-Yang Tang, Fu Ou-Yang, Yen-Yun Wang, Shyng-Shiou F. Yuan, Kevin Tseng, Li-Ching Lin and Hsueh-Wei Chang
Biomolecules 2020, 10(5), 777; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10050777 - 17 May 2020
Cited by 32 | Viewed by 3029
Abstract
Withaferin A (WFA) has been reported to inhibit cancer cell proliferation based on high cytotoxic concentrations. However, the low cytotoxic effect of WFA in regulating cancer cell migration is rarely investigated. The purpose of this study is to investigate the changes in migration [...] Read more.
Withaferin A (WFA) has been reported to inhibit cancer cell proliferation based on high cytotoxic concentrations. However, the low cytotoxic effect of WFA in regulating cancer cell migration is rarely investigated. The purpose of this study is to investigate the changes in migration and mechanisms of oral cancer Ca9-22 cells after low concentrations of WFA treatment. WFA under 0.5 μM at 24 h treatment shows no cytotoxicity to oral cancer Ca9-22 cells (~95% viability). Under this condition, WFA triggers reactive oxygen species (ROS) production and inhibits 2D (wound healing) and 3D cell migration (transwell) and Matrigel invasion. Mechanically, WFA inhibits matrix metalloproteinase (MMP)-2 and MMP-9 activities but induces mRNA expression for a group of antioxidant genes, such as nuclear factor, erythroid 2-like 2 (NFE2L2), heme oxygenase 1 (HMOX1), glutathione-disulfide reductase (GSR), and NAD(P)H quinone dehydrogenase 1 (NQO1)) in Ca9-22 cells. Moreover, WFA induces mild phosphorylation of the mitogen-activated protein kinase (MAPK) family, including extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 expression. All WFA-induced changes were suppressed by the presence of ROS scavenger N-acetylcysteine (NAC). Therefore, these results suggest that low concentration of WFA retains potent ROS-mediated anti-migration and -invasion abilities for oral cancer cells. Full article
(This article belongs to the Special Issue Phytochemical Omics in Medicinal Plants)
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21 pages, 4152 KiB  
Article
A Biochemometric Approach for the Identification of In Vitro Anti-Inflammatory Constituents in Masterwort
by Julia Zwirchmayr, Ulrike Grienke, Scarlet Hummelbrunner, Jacqueline Seigner, Rainer de Martin, Verena M. Dirsch and Judith M. Rollinger
Biomolecules 2020, 10(5), 679; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10050679 - 28 Apr 2020
Cited by 15 | Viewed by 3255
Abstract
Peucedanum ostruthium (L.) Koch, commonly known as masterwort, has a longstanding history as herbal remedy in the Alpine region of Austria, where the roots and rhizomes are traditionally used to treat disorders of the gastrointestinal and respiratory tract. Based on a significant NF-κB [...] Read more.
Peucedanum ostruthium (L.) Koch, commonly known as masterwort, has a longstanding history as herbal remedy in the Alpine region of Austria, where the roots and rhizomes are traditionally used to treat disorders of the gastrointestinal and respiratory tract. Based on a significant NF-κB inhibitory activity of a P. ostruthium extract (PO-E), this study aimed to decipher those constituents contributing to the observed activity using a recently developed biochemometric approach named ELINA (Eliciting Nature’s Activities). This -omics tool relies on a deconvolution of the multicomponent mixture, which was employed by generating microfractions with quantitative variances of constituents over several consecutive fractions. Using an optimized and single high-performance counter-current chromatographic (HPCCC) fractionation step 31 microfractions of PO-E were obtained. 1H NMR data and bioactivity data from three in vitro cell-based assays, i.e., an NF-ĸB reporter-gene assay and two NF-κB target-gene assays (addressing the endothelial adhesion molecules E-selectin and VCAM-1) were collected for all microfractions. Applying heterocovariance analyses (HetCA) and statistical total correlation spectroscopy (STOCSY), quantitative variances of 1H NMR signals of neighboring fractions and their bioactivities were correlated. This revealed distinct chemical features crucial for the observed activities. Complemented by LC-MS-CAD data this biochemometric approach differentiated between active and inactive constituents of the complex mixture, which was confirmed by NF-κB reporter-gene testing of the isolates. In this way, four furanocoumarins (imperatorin, ostruthol, saxalin, and 2’-O-acetyloxypeucedanin), one coumarin (ostruthin), and one chromone (peucenin) were identified as NF-κB inhibiting constituents of PO-E contributing to the observed NF-ĸB inhibitory activity. Additionally, this approach also enabled the disclose of synergistic effects of the PO-E metabolites imperatorin and peucenin. In sum, prior to any isolation an early identification of even minor active constituents, e.g. peucenin and saxalin, ELINA enables the targeted isolation of bioactive constituents and, thus, to effectively accelerate the NP-based drug discovery process. Full article
(This article belongs to the Special Issue Phytochemical Omics in Medicinal Plants)
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10 pages, 2626 KiB  
Article
Green Tea Catechin (-)-Epigallocatechin-3-Gallate (EGCG) Facilitates Fracture Healing
by Sung-Yen Lin, Jung Yu Kan, Cheng-Chang Lu, Han Hsiang Huang, Tsung-Lin Cheng, Hsuan-Ti Huang, Cheng-Jung Ho, Tien-Ching Lee, Shu-Chun Chuang, Yi-Shan Lin, Lin Kang and Chung-Hwan Chen
Biomolecules 2020, 10(4), 620; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10040620 - 16 Apr 2020
Cited by 25 | Viewed by 4662
Abstract
Green tea drinking can ameliorate postmenopausal osteoporosis by increasing the bone mineral density. (-)-Epigallocatechin-3-gallate (EGCG), the abundant and active compound of tea catechin, was proven to be able to reduce bone loss and ameliorate microarchitecture in female ovariectomized rats. EGCG can also enhance [...] Read more.
Green tea drinking can ameliorate postmenopausal osteoporosis by increasing the bone mineral density. (-)-Epigallocatechin-3-gallate (EGCG), the abundant and active compound of tea catechin, was proven to be able to reduce bone loss and ameliorate microarchitecture in female ovariectomized rats. EGCG can also enhance the osteogenic differentiation of murine bone marrow mesenchymal stem cells and inhibit the osteoclastogenesis in RAW264.7 cells by modulation of the receptor activator of nuclear factor-kB (RANK)/RANK ligand (RANKL)/osteoprotegrin (OPG) (RANK/RANKL/OPG) pathway. Our previous study also found that EGCG can promote bone defect healing in the distal femur partially via bone morphogenetic protein-2 (BMP-2). Considering the osteoinduction property of BMP-2, we hypothesized that EGCG could accelerate the bone healing process with an increased expression of BMP-2. In this manuscript, we studied whether the local use of EGCG can facilitate tibial fracture healing. Fifty-six 4-month-old rats were randomly assigned to two groups after being weight-matched: a control group with vehicle treatment (Ctrl) and a study group with 10 µmol/L, 40 µL, EGCG treatment (EGCG). Two days after the operation, the rats were treated daily with EGCG or vehicle by percutaneous local injection for 2 weeks. The application of EGCG enhanced callus formation by increasing the bone volume and subsequently improved the mechanical properties of the tibial bone, including the maximal load, break load, stiffness, and Young’s modulus. The results of the histology and BMP-2 immunohistochemistry staining showed that EGCG treatment accelerated the bone matrix formation and produced a stronger expression of BMP-2. Taken together, this study for the first time demonstrated that local treatment of EGCG can accelerate the fracture healing process at least partly via BMP-2. Full article
(This article belongs to the Special Issue Phytochemical Omics in Medicinal Plants)
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19 pages, 4565 KiB  
Article
Bacopa monnieri and Their Bioactive Compounds Inferred Multi-Target Treatment Strategy for Neurological Diseases: A Cheminformatics and System Pharmacology Approach
by Rajendran Jeyasri, Pandiyan Muthuramalingam, Vellaichami Suba, Manikandan Ramesh and Jen-Tsung Chen
Biomolecules 2020, 10(4), 536; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10040536 - 02 Apr 2020
Cited by 53 | Viewed by 7820
Abstract
Neurological diseases (NDs), especially Alzheimer’s and Spinocerebellar ataxia (SCA), can severely cause biochemical abnormalities in the brain, spinal cord and other nerves of human beings. Their ever-increasing prevalence has led to a demand for new drug development. Indian traditional and Ayurvedic medicine used [...] Read more.
Neurological diseases (NDs), especially Alzheimer’s and Spinocerebellar ataxia (SCA), can severely cause biochemical abnormalities in the brain, spinal cord and other nerves of human beings. Their ever-increasing prevalence has led to a demand for new drug development. Indian traditional and Ayurvedic medicine used to combat the complex diseases from a holistic and integrative point of view has shown efficiency and effectiveness in the treatment of NDs. Bacopa monnieri is a potent Indian medicinal herb used for multiple ailments, but is significantly known as a nootropic or brain tonic and memory enhancer. This annual herb has various active compounds and acts as an alternative and complementary medicine in various countries. However, system-level insights of the molecular mechanism of a multiscale treatment strategy for NDs is still a bottleneck. Considering its prominence, we used cheminformatics and system pharmacological approaches, with the aim to unravel the various molecular mechanisms represented by Bacopa-derived compounds in identifying the active human targets when treating NDs. First, using cheminformatics analysis combined with the drug target mining process, 52 active compounds and their corresponding 780 direct receptors were retrieved and computationally validated. Based on the molecular properties, bioactive scores and comparative analysis with commercially available drugs, novel and active compounds such as asiatic acid (ASTA) and loliolide (LLD) to treat the Alzheimer’s and SCA were identified. According to the interactions among the active compounds, the targets and diseases were further analyzed to decipher the deeper pharmacological actions of the drug. NDs consist of complex regulatory modules that are integrated to dissect the therapeutic effects of compounds derived from Bacopa in various pathological features and their encoding biological processes. All these revealed that Bacopa compounds have several curative activities in regulating the various biological processes of NDs and also pave the way for the treatment of various diseases in modern medicine. Full article
(This article belongs to the Special Issue Phytochemical Omics in Medicinal Plants)
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21 pages, 3133 KiB  
Article
UV-B Radiation Largely Promoted the Transformation of Primary Metabolites to Phenols in Astragalus mongholicus Seedlings
by Yang Liu, Jia Liu, Ann Abozeid, Ke-Xin Wu, Xiao-Rui Guo, Li-Qiang Mu and Zhong-Hua Tang
Biomolecules 2020, 10(4), 504; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10040504 - 26 Mar 2020
Cited by 26 | Viewed by 3305
Abstract
Ultraviolet-B (UV-B) radiation (280–320 nm) may induce photobiological stress in plants, activate the plant defense system, and induce changes of metabolites. In our previous work, we found that between the two Astragalus varieties prescribed by the Chinese Pharmacopoeia, Astragalus mongholicus has better tolerance [...] Read more.
Ultraviolet-B (UV-B) radiation (280–320 nm) may induce photobiological stress in plants, activate the plant defense system, and induce changes of metabolites. In our previous work, we found that between the two Astragalus varieties prescribed by the Chinese Pharmacopoeia, Astragalus mongholicus has better tolerance to UV-B. Thus, it is necessary to study the metabolic strategy of Astragalus under UV-B radiation further. In the present study, we used untargeted gas chromatography-mass spectrometry (GC-MS) and targeted liquid chromatography-mass spectrometry (LC-MS techniques) to investigate the profiles of primary and secondary metabolic. The profiles revealed the metabolic response of Astragalus to UV-B radiation. We then used real-time polymerase chain reaction (RT-PCR) to obtain the transcription level of relevant genes under UV-B radiation (UV-B supplemented in the field, λmax = 313 nm, 30 W, lamp-leaf distance = 60 cm, 40 min·day−1), which annotated the responsive mechanism of phenolic metabolism in roots. Our results indicated that supplemental UV-B radiation induced a stronger shift from carbon assimilation to carbon accumulation. The flux through the phenylpropanoids pathway increased due to the mobilization of carbon reserves. The response of metabolism was observed to be significantly tissue-specific upon the UV-B radiation treatment. Among phenolic compounds, C6C1 carbon compounds (phenolic acids in leaves) and C6C3C6 carbon compounds (flavones in leaves and isoflavones in roots) increased at the expense of C6C3 carbon compounds. Verification experiments show that the response of phenolics in roots to UV-B is activated by upregulation of relevant genes rather than phenylalanine. Overall, this study reveals the tissues-specific alteration and mechanism of primary and secondary metabolic strategy in response to UV-B radiation. Full article
(This article belongs to the Special Issue Phytochemical Omics in Medicinal Plants)
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16 pages, 7340 KiB  
Article
Luteolin-7-O-Glucoside Inhibits Oral Cancer Cell Migration and Invasion by Regulating Matrix Metalloproteinase-2 Expression and Extracellular Signal-Regulated Kinase Pathway
by Bharath Kumar Velmurugan, Jen-Tsun Lin, B. Mahalakshmi, Yi-Ching Chuang, Chia-Chieh Lin, Yu-Sheng Lo, Ming-Ju Hsieh and Mu-Kuan Chen
Biomolecules 2020, 10(4), 502; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10040502 - 26 Mar 2020
Cited by 27 | Viewed by 3133
Abstract
Oral squamous cell carcinoma is the sixth most common type of cancer globally, which is associated with high rates of cancer-related deaths. Metastasis to distant organs is the main reason behind worst prognostic outcome of oral cancer. In the present study, we aimed [...] Read more.
Oral squamous cell carcinoma is the sixth most common type of cancer globally, which is associated with high rates of cancer-related deaths. Metastasis to distant organs is the main reason behind worst prognostic outcome of oral cancer. In the present study, we aimed at evaluating the effects of a natural plant flavonoid, luteolin-7-O-glucoside, on oral cancer cell migration and invasion. The study findings showed that in addition to preventing cell proliferation, luteolin-7-O-glucoside caused a significant reduction in oral cancer cell migration and invasion. Mechanistically, luteolin-7-O-glucoside caused a reduction in cancer metastasis by reducing p38 phosphorylation and downregulating matrix metalloproteinase (MMP)-2 expression. Using a p38 inhibitor, SB203580, we proved that luteolin-7-O-glucoside exerts anti-migratory effects by suppressing p38-mediated increased expression of MMP-2. This is the first study to demonstrate the luteolin-7-O-glucoside inhibits cell migration and invasion by regulating MMP-2 expression and extracellular signal-regulated kinase pathway in human oral cancer cell. The study identifies luteolin-7-O-glucoside as a potential anti-cancer candidate that can be utilized clinically for improving oral cancer prognosis. Full article
(This article belongs to the Special Issue Phytochemical Omics in Medicinal Plants)
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16 pages, 7024 KiB  
Article
Network Pharmacology-Based Approaches of Rheum undulatum Linne and Glycyrriza uralensis Fischer Imply Their Regulation of Liver Failure with Hepatic Encephalopathy in Mice
by Su Youn Baek, Eun Hye Lee, Tae Woo Oh, Hyun Ju Do, Kwang-Youn Kim, Kwang-Il Park and Young Woo Kim
Biomolecules 2020, 10(3), 437; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10030437 - 12 Mar 2020
Cited by 8 | Viewed by 3195
Abstract
Rheum undulatum and Glycyrrhiza uralensis have been used as supplementary ingredients in various herbal medicines. They have been reported to have anti-inflammatory and antioxidant effects and, therefore, have potential in the treatment and prevention of various liver diseases. Considering that hepatic encephalopathy (HE) [...] Read more.
Rheum undulatum and Glycyrrhiza uralensis have been used as supplementary ingredients in various herbal medicines. They have been reported to have anti-inflammatory and antioxidant effects and, therefore, have potential in the treatment and prevention of various liver diseases. Considering that hepatic encephalopathy (HE) is often associated with chronic liver failure, we investigated whether an R. undulatum and G. uralensis extract mixture (RG) could reduce HE. We applied systems-based pharmacological tools to identify the active ingredients in RG and the pharmacological targets of RG by examining mechanism-of-action profiles. A CCl4-induced HE mouse model was used to investigate the therapeutic mechanisms of RG on HE. We successfully identified seven bioactive ingredients in RG with 40 potential targets. Based on an integrated target–disease network, RG was predicted to be effective in treating neurological diseases. In animal models, RG consistently relieved HE symptoms by protecting blood–brain barrier permeability via downregulation of matrix metalloproteinase-9 (MMP-9) and upregulation of claudin-5. In addition, RG inhibited mRNA expression levels of both interleukin (IL)-1β and transforming growth factor (TGF)-β1. Based on our results, RG is expected to function various biochemical processes involving neuroinflammation, suggesting that RG may be considered a therapeutic agent for treating not only chronic liver disease but also HE. Full article
(This article belongs to the Special Issue Phytochemical Omics in Medicinal Plants)
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9 pages, 1946 KiB  
Article
Targeted Isolation of Lignans from Trachelospermum asiaticum Using Molecular Networking and Hierarchical Clustering Analysis
by Jiho Lee, Hong Seok Yang, Hyogeun Jeong, Jung-Hwan Kim and Heejung Yang
Biomolecules 2020, 10(3), 378; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10030378 - 01 Mar 2020
Cited by 6 | Viewed by 2799
Abstract
High-resolution-mass-spectrometry (HR-MS) methods rapidly provide extensive structural information for the isolation of metabolites in natural products. However, they may occasionally provide more information than required and interfere with the targeted analysis of natural products. In this study, we aimed to selectively isolate lignans [...] Read more.
High-resolution-mass-spectrometry (HR-MS) methods rapidly provide extensive structural information for the isolation of metabolites in natural products. However, they may occasionally provide more information than required and interfere with the targeted analysis of natural products. In this study, we aimed to selectively isolate lignans from Trachelospermum asiaticum by applying the Global Natural Product Social Molecular Networking (GNPS) platform and hierarchical clustering analysis (HCA). T. asiaticum, which contains lignans, triterpenoids and flavonoids that possess various biological activities, was analyzed in a data-dependent acquisition (DDA) analysis mode using HR-MS. The preprocessed MS spectra were applied not only to GNPS for molecular networking but also to HCA based on similarity patterns between two nodes. The combination of these two methods reliably helped in the targeted isolation of lignan-type metabolites, which are expected to possess potent anti-cancer or anti-inflammatory activities. Full article
(This article belongs to the Special Issue Phytochemical Omics in Medicinal Plants)
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22 pages, 4926 KiB  
Article
Acorus gramineusand and Euodia ruticarpa Steam Distilled Essential Oils Exert Anti-Inflammatory Effects Through Decreasing Th1/Th2 and Pro-/Anti-Inflammatory Cytokine Secretion Ratios In Vitro
by Tzu-He Yeh and Jin-Yuarn Lin
Biomolecules 2020, 10(2), 338; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10020338 - 19 Feb 2020
Cited by 22 | Viewed by 3326
Abstract
To clarify the effects of steam distilled essential oils (SDEO) from herbs used in traditional Chinese medicine on immune functions, two potential herbs, Acorus gramineusand (AG) and Euodia ruticarpa (ER) cultivated in Taiwan, were selected to assess their immunomodulatory effects using mouse primary [...] Read more.
To clarify the effects of steam distilled essential oils (SDEO) from herbs used in traditional Chinese medicine on immune functions, two potential herbs, Acorus gramineusand (AG) and Euodia ruticarpa (ER) cultivated in Taiwan, were selected to assess their immunomodulatory effects using mouse primary splenocytes and peritoneal macrophages. T helper type 1 lymphocytes (Th1) (IL-2), Th2 (IL-5), pro-inflammatory (TNF-α) and anti-inflammatory (IL-10) cytokines secreted by correspondent immune cells treated with SDEO samples were determined using enzyme-linked immunosorbent assay. The total amounts of potential phytochemicals, including total flavonoids, polyphenols and saponins, in these two selected SDEOs were measured and correlated with cytokine levels secreted by immune cells. Our results evidenced that ER SDEO is rich in total flavonoids, polyphenols and saponins. Treatments with AG and ER SDEO significantly (p < 0.05) increased IL-5/IL-2 (Th2/Th1) cytokine secretion ratios by splenocytes, suggesting that both AG and ER SDEO have the Th2-polarization property and anti-inflammatory potential. In addition, AG and ER SDEO, particularly ER SDEO, markedly decreased TNF-α/IL-10 secretion ratios by macrophages in the absence or presence of lipopolysaccharide (LPS), exhibiting substantial effects on spontaneous and LPS-induced inflammation. Significant correlations were found between the total polyphenols, flavonoids or saponins content in the two selected SDEOs and Th1/Th2 immune balance or anti-inflammatory ability in linear, non-linear or biphasic manners, respectively. In conclusion, our results suggest that AG and ER, particularly ER, SDEO have immunomodulatory potential in shifting the Th1/Th2 balance toward Th2 polarization in splenocytes and inhibiting inflammation in macrophages in the absence or presence of LPS. Full article
(This article belongs to the Special Issue Phytochemical Omics in Medicinal Plants)
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17 pages, 3300 KiB  
Article
Licochalcone D Induces ROS-Dependent Apoptosis in Gefitinib-Sensitive or Resistant Lung Cancer Cells by Targeting EGFR and MET
by Ha-Na Oh, Mee-Hyun Lee, Eunae Kim, Ah-Won Kwak, Goo Yoon, Seung-Sik Cho, Kangdong Liu, Jung-Il Chae and Jung-Hyun Shim
Biomolecules 2020, 10(2), 297; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10020297 - 13 Feb 2020
Cited by 30 | Viewed by 3343
Abstract
Licochalcone D (LCD), a flavonoid isolated from a Chinese medicinal plant Glycyrrhiza inflata, has a variety of pharmacological activities. However, the anti-cancer effects of LCD on non-small cell lung cancer (NSCLC) have not been investigated yet. The amplification of MET (hepatocyte growth [...] Read more.
Licochalcone D (LCD), a flavonoid isolated from a Chinese medicinal plant Glycyrrhiza inflata, has a variety of pharmacological activities. However, the anti-cancer effects of LCD on non-small cell lung cancer (NSCLC) have not been investigated yet. The amplification of MET (hepatocyte growth factor receptor) compensates for the inhibition of epidermal growth factor receptor (EGFR) activity due to tyrosine kinase inhibitor (TKI), leading to TKI resistance. Therefore, EGFR and MET can be attractive targets for lung cancer. We investigated the anti-proliferative and apoptotic effects of LCD in lung cancer cells HCC827 (gefitinib-sensitive) and HCC827GR (gefitinib-resistant) through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, pull-down/kinase assay, cell cycle analysis, Annexin-V/7-ADD staining, reactive oxygen species (ROS) assay, mitochondrial membrane potential (MMP) assay, multi-caspase assay, and Western blot analysis. The results showed that LCD inhibited phosphorylation and the kinase activity of EGFR and MET. In addition, the predicted pose of LCD was competitively located at the ATP binding site. LCD suppressed lung cancer cells growth by blocking cell cycle progression at the G2/M transition and inducing apoptosis. LCD also induced caspases activation and poly (ADP-ribose) polymerase (PARP) cleavage, thus displaying features of apoptotic signals. These results provide evidence that LCD has anti-tumor effects by inhibiting EGFR and MET activities and inducing ROS-dependent apoptosis in NSCLC, suggesting that LCD has the potential to treat lung cancer. Full article
(This article belongs to the Special Issue Phytochemical Omics in Medicinal Plants)
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16 pages, 4077 KiB  
Article
Accumulation of Anthocyanins through Overexpression of AtPAP1 in Solanum nigrum Lin. (Black Nightshade)
by Saophea Chhon, Jin Jeon, Joonyup Kim and Sang Un Park
Biomolecules 2020, 10(2), 277; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10020277 - 11 Feb 2020
Cited by 26 | Viewed by 4390
Abstract
Black nightshade (Solanum nigrum) belongs to the Solanaceae family and is used as a medicinal herb with health benefits. It has been reported that the black nightshade plant contains various phytochemicals that are associated with antitumor activities. Here we employed a [...] Read more.
Black nightshade (Solanum nigrum) belongs to the Solanaceae family and is used as a medicinal herb with health benefits. It has been reported that the black nightshade plant contains various phytochemicals that are associated with antitumor activities. Here we employed a genetic approach to study the effects of overexpression of Arabidopsis thaliana production of anthocyanin pigment 1 (AtPAP1) in black nightshade. Ectopic expression of AtPAP1 resulted in enhanced accumulation of anthocyanin pigments in vegetative and reproductive tissues of the transgenic plants. Analysis of anthocyanin revealed that delphinidin 3-O-rutinoside-5-O-glucoside, delphinidin 3,5-O-diglucoside, delphinidin 3-O-rutinoside, petunidin 3-O-rutinoside (cis-p-coumaroyl)-5-O-glucoside, petunidin 3-(feruloyl)-rutinoside-5-glucoside, and malvidin 3-(feruloyl)-rutinoside-5-glucoside are highly induced in the leaves of AtPAP1 overexpression lines. Furthermore, ectopic expression of AtPAP1 evoked expression of early and late biosynthetic genes of the general phenylpropanoid and flavonoid pathways that include phenylalanine ammonia-lyase (PAL), cinnamate-4-hydroxylase (C4H), 4-coumarate CoA ligase (4CL), chalcone isomerase (CHI), and quinate hydroxycinnamoyl transferase (HCT), which suggests these genes might be transcriptional targets of AtPAP1 in black nightshade. Concomitantly, the total content of anthocyanin in the transgenic black nightshade plants was higher compared to the control plants, which supports phenotypic changes in color. Our data demonstrate that a major anthocyanin biosynthetic regulator, AtPAP1, can induce accumulation of anthocyanins in the heterologous system of black nightshade through the conserved flavonoid biosynthesis pathway in plants. Full article
(This article belongs to the Special Issue Phytochemical Omics in Medicinal Plants)
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13 pages, 5716 KiB  
Article
Asiatic Acid, Extracted from Centella asiatica and Induces Apoptosis Pathway through the Phosphorylation p38 Mitogen-Activated Protein Kinase in Cisplatin-Resistant Nasopharyngeal Carcinoma Cells
by Yen-Tze Liu, Yi-Ching Chuang, Yu-Sheng Lo, Chia-Chieh Lin, Yi-Ting Hsi, Ming-Ju Hsieh and Mu-Kuan Chen
Biomolecules 2020, 10(2), 184; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10020184 - 25 Jan 2020
Cited by 38 | Viewed by 4390
Abstract
Nasopharyngeal carcinoma (NPC) is an important issue in Asia because of its unique geographical and ethnic distribution. Cisplatin-based regimens are commonly the first-line used chemotherapy, but resistance and toxicities remain a problem. Therefore, the use of anticancer agents derived from natural products may [...] Read more.
Nasopharyngeal carcinoma (NPC) is an important issue in Asia because of its unique geographical and ethnic distribution. Cisplatin-based regimens are commonly the first-line used chemotherapy, but resistance and toxicities remain a problem. Therefore, the use of anticancer agents derived from natural products may be a solution. Asiatic acid (AA), extracted from Centella asiatica, was found to have anticancer activity in various cancers. The aim of this study is to examine the cytotoxic effect and mediated mechanism of AA in cisplatin-resistant NPC cells. The results shows that AA significantly reduce the cell viability of cisplatin-resistant NPC cell lines (cis NPC-039 and cis NPC-BM) in dose and time dependent manners caused by apoptosis through the both intrinsic and extrinsic apoptotic pathways, including altered mitochondrial membrane potential, activated death receptors, increased Bax expression, and upregulated caspase 3, 8, and 9. The Western blot analysis of AA-treated cell lines reveals that the phosphorylation of MAPK pathway proteins is involved. Further, the results of adding inhibitors of these proteins indicates that the phosphorylation of p38 are the key mediators in AA-induced apoptosis in cisplatin-resistant human NPC cells. This is the first study to demonstrate the AA-induced apoptotic pathway through the phosphorylation p38 in human cisplatin-resistant nasopharyngeal carcinoma. AA is expected to be another therapeutic option for cisplatin-resistant NPC because of the promising anti-cancer effect and fewer toxic properties. Full article
(This article belongs to the Special Issue Phytochemical Omics in Medicinal Plants)
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19 pages, 3666 KiB  
Article
Bioactivities of Geranium wallichianum Leaf Extracts Conjugated with Zinc Oxide Nanoparticles
by Banzeer Ahsan Abbasi, Javed Iqbal, Riaz Ahmad, Layiq Zia, Sobia Kanwal, Tariq Mahmood, Canran Wang and Jen-Tsung Chen
Biomolecules 2020, 10(1), 38; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10010038 - 26 Dec 2019
Cited by 84 | Viewed by 6395
Abstract
This study attempts to obtain and test the bioactivities of leaf extracts from a medicinal plant, Geranium wallichianum (GW), when conjugated with zinc oxide nanoparticles (ZnONPs). The integrity of leaf extract-conjugated ZnONPs (GW-ZnONPs) was confirmed using various techniques, including Ultraviolet–visible spectroscopy, X-Ray Diffraction, [...] Read more.
This study attempts to obtain and test the bioactivities of leaf extracts from a medicinal plant, Geranium wallichianum (GW), when conjugated with zinc oxide nanoparticles (ZnONPs). The integrity of leaf extract-conjugated ZnONPs (GW-ZnONPs) was confirmed using various techniques, including Ultraviolet–visible spectroscopy, X-Ray Diffraction, Fourier Transform Infrared Spectroscopy, energy-dispersive spectra (EDS), scanning electron microscopy, transmission electron microscopy, and Raman spectroscopy. The size of ZnONPs was approximately 18 nm, which was determined by TEM analysis. Additionally, the energy-dispersive spectra (EDS) revealed that NPs have zinc in its pure form. Bioactivities of GW-ZnONPs including antimicrobial potentials, cytotoxicity, antioxidative capacities, inhibition potentials against α-amylase, and protein kinases, as well as biocompatibility were intensively tested and confirmed. Altogether, the results revealed that GW-ZnONPs are non-toxic, biocompatible, and have considerable potential in biological applications. Full article
(This article belongs to the Special Issue Phytochemical Omics in Medicinal Plants)
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13 pages, 2004 KiB  
Article
Combined Use of Deep Eutectic Solvents, Macroporous Resins, and Preparative Liquid Chromatography for the Isolation and Purification of Flavonoids and 20-Hydroxyecdysone from Chenopodium quinoa Willd
by Jia Zeng, Xianchao Shang, Peng Zhang, Hongwei Wang, Yanlong Gu and Jia-Neng Tan
Biomolecules 2019, 9(12), 776; https://0-doi-org.brum.beds.ac.uk/10.3390/biom9120776 - 25 Nov 2019
Cited by 13 | Viewed by 3594
Abstract
Deep eutectic solvents (DESs) were used in combination with macroporous resins to isolate and purify flavonoids and 20-hydroxyecdysone from Chenopodium quinoa Willd by preparative high-performance liquid chromatography (HPLC). The extraction performances of six DESs and the adsorption/desorption performances of five resins (AB-8, D101, [...] Read more.
Deep eutectic solvents (DESs) were used in combination with macroporous resins to isolate and purify flavonoids and 20-hydroxyecdysone from Chenopodium quinoa Willd by preparative high-performance liquid chromatography (HPLC). The extraction performances of six DESs and the adsorption/desorption performances of five resins (AB-8, D101, HPD 400, HPD 600, and NKA-9) were investigated using the total flavonoid and 20-hydroxyecdysone extraction yields as the evaluation criteria, and the best-performing DES (choline chloride/urea, DES-6) and macroporous resin (D101) were further employed for phytochemical extraction and DES removal, respectively. The purified extract was subjected to preparative HPLC, and the five collected fractions were purified in a successive round of preparative HPLC to isolate three flavonoids and 20-hydroxyecdysone, which were identified by spectroscopic techniques. The use of a DES in this study significantly facilitated the preparative-scale isolation and purification of polar phytochemicals from complex plant systems. Full article
(This article belongs to the Special Issue Phytochemical Omics in Medicinal Plants)
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14 pages, 4626 KiB  
Article
Clerodane Diterpene Ameliorates Inflammatory Bowel Disease and Potentiates Cell Apoptosis of Colorectal Cancer
by Jia-Huei Zheng, Shian-Ren Lin, Feng-Jen Tseng, May-Jywan Tsai, Sheng-I Lue, Yi-Chen Chia, Mindar Woon, Yaw-Syan Fu and Ching-Feng Weng
Biomolecules 2019, 9(12), 762; https://0-doi-org.brum.beds.ac.uk/10.3390/biom9120762 - 21 Nov 2019
Cited by 6 | Viewed by 2936
Abstract
Inflammatory bowel disease (IBD) is general term for ulcerative colitis and Crohn’s disease, which is chronic intestinal and colorectal inflammation caused by microbial infiltration or immunocyte attack. IBD is not curable, and is highly susceptible to develop into colorectal cancer. Finding agents to [...] Read more.
Inflammatory bowel disease (IBD) is general term for ulcerative colitis and Crohn’s disease, which is chronic intestinal and colorectal inflammation caused by microbial infiltration or immunocyte attack. IBD is not curable, and is highly susceptible to develop into colorectal cancer. Finding agents to alleviate these symptoms, as well as any progression of IBD, is a critical effort. This study evaluates the anti-inflammation and anti-tumor activity of 16-hydroxycleroda-3,13-dien-15,16-olide (HCD) in in vivo and in vitro assays. The result of an IBD mouse model induced using intraperitoneal chemical azoxymethane (AOM)/dextran sodium sulfate (DSS) injection showed that intraperitoneal HCD adminstration could ameliorate the inflammatory symptoms of IBD mice. In the in vitro assay, cytotoxic characteristics and retained signaling pathways of HCD treatment were analyzed by MTT assay, cell cycle analysis, and Western blotting. From cell viability determination, the IC50 of HCD in Caco-2 was significantly lower in 2.30 μM at 48 h when compared to 5-fluorouracil (5-FU) (66.79 μM). By cell cycle and Western blotting analysis, the cell death characteristics of HCD treatment in Caco-2 exhibited the involvement of extrinsic and intrinsic pathways in cell death, for which intrinsic apoptosis was predominantly activated via the reduction in growth factor signaling. These potential treatments against colon cancer demonstrate that HCD could provide a promising adjuvant as an alternative medicine in combating colorectal cancer and IBD. Full article
(This article belongs to the Special Issue Phytochemical Omics in Medicinal Plants)
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13 pages, 1214 KiB  
Article
Variation in Chemical Composition and Biological Activities of Flos Chrysanthemi indici Essential Oil under Different Extraction Methods
by Chang-Liang Jing, Rui-Huan Huang, Yan Su, Yi-Qiang Li and Cheng-Sheng Zhang
Biomolecules 2019, 9(10), 518; https://0-doi-org.brum.beds.ac.uk/10.3390/biom9100518 - 21 Sep 2019
Cited by 22 | Viewed by 3629
Abstract
Flos Chrysanthemi indici, an important medicinal and aromatic plant in China, is considered to have many different preservative and pharmacological properties. Considering the capability of essential oils (EOs), the present study is conducted to compare different extraction methods in order to improve [...] Read more.
Flos Chrysanthemi indici, an important medicinal and aromatic plant in China, is considered to have many different preservative and pharmacological properties. Considering the capability of essential oils (EOs), the present study is conducted to compare different extraction methods in order to improve yield and biological activities. Hydro-distillation (HD), steam-distillation (SD), solvent-free microwave extraction (SFME), and supercritical fluid extraction (SFE) are employed to prepare EOs from Flos Chrysanthemi indici. A total of 71 compounds are assigned by gas chromatography/mass spectrometry (GC–MS) in comparison with retention indices. These include 32 (HD), 16 (SD), 31 (SFME) and 38 (SFE) compounds. Major constituents of EOs differ according to the extraction methods were heptenol, tricosane, camphor, borneol, and eucalyptol. EOs extracted by SFME exhibit higher antioxidant activity. All EOs show varying degrees of antimicrobial activity, with minimum inhibitory concentration (MIC) ranging from 0.0625 to 0.125 mg/mL and SFME and SFE prove to be efficient extraction methods. EOs alter the hyphal morphology of Alternaria alternata, with visible bumps forming on the mycelium. Overall, these results indicate that the extraction method can significantly influence the composition and biological activity of EOs and SFME and SFE are outstanding methods to extract EOs with high yield and antimicrobial activity. Full article
(This article belongs to the Special Issue Phytochemical Omics in Medicinal Plants)
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17 pages, 4250 KiB  
Article
Polysaccharide Fraction Extracted from Endophytic Fungus Trichoderma atroviride D16 Has an Influence on the Proteomics Profile of the Salvia miltiorrhiza Hairy Roots
by Wei Peng, Qian-liang Ming, Xin Zhai, Qing Zhang, Khalid Rahman, Si-jia Wu, Lu-ping Qin and Ting Han
Biomolecules 2019, 9(9), 415; https://0-doi-org.brum.beds.ac.uk/10.3390/biom9090415 - 26 Aug 2019
Cited by 9 | Viewed by 3002
Abstract
Trichoderma atroviride develops a symbiont relationship with Salvia miltiorrhiza and this association involves a number of signaling pathways and proteomic responses between both partners. In our previous study, we have reported that polysaccharide fraction (PSF) of T. atroviride could promote tanshinones accumulation in [...] Read more.
Trichoderma atroviride develops a symbiont relationship with Salvia miltiorrhiza and this association involves a number of signaling pathways and proteomic responses between both partners. In our previous study, we have reported that polysaccharide fraction (PSF) of T. atroviride could promote tanshinones accumulation in S. miltiorrhiza hairy roots. Consequently, the present data elucidates the broad proteomics changes under treatment of PSF. Furthermore, we reported several previously undescribed and unexpected responses, containing gene expression patterns consistent with biochemical stresses and metabolic patterns inside the host. In summary, the PSF-induced tanshinones accumulation in S. miltiorrhiza hairy roots may be closely related to Ca2+ triggering, peroxide reaction, protein phosphorylation, and jasmonic acid (JA) signal transduction, leading to an increase in leucine-rich repeat (LRR) protein synthesis. This results in the changes in basic metabolic flux of sugars, amino acids, and protein synthesis, along with signal defense reactions. The results reported here increase our understanding of the interaction between T. atroviride and S. miltiorrhiza and specifically confirm the proteomic responses underlying the activities of PSF. Full article
(This article belongs to the Special Issue Phytochemical Omics in Medicinal Plants)
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15 pages, 3867 KiB  
Article
The Methodological Trends of Traditional Herbal Medicine Employing Network Pharmacology
by Won-Yung Lee, Choong-Yeol Lee, Youn-Sub Kim and Chang-Eop Kim
Biomolecules 2019, 9(8), 362; https://0-doi-org.brum.beds.ac.uk/10.3390/biom9080362 - 13 Aug 2019
Cited by 101 | Viewed by 11821
Abstract
Natural products, including traditional herbal medicine (THM), are known to exert their therapeutic effects by acting on multiple targets, so researchers have employed network pharmacology methods to decipher the potential mechanisms of THM. To conduct THM-network pharmacology (THM-NP) studies, researchers have employed different [...] Read more.
Natural products, including traditional herbal medicine (THM), are known to exert their therapeutic effects by acting on multiple targets, so researchers have employed network pharmacology methods to decipher the potential mechanisms of THM. To conduct THM-network pharmacology (THM-NP) studies, researchers have employed different tools and databases for constructing and analyzing herb–compound–target networks. In this study, we attempted to capture the methodological trends in THM-NP research. We identified the tools and databases employed to conduct THM-NP studies and visualized their combinatorial patterns. We also constructed co-author and affiliation networks to further understand how the methodologies are employed among researchers. The results showed that the number of THM-NP studies and employed databases/tools have been dramatically increased in the last decade, and there are characteristic patterns in combining methods of each analysis step in THM-NP studies. Overall, the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was the most frequently employed network pharmacology database in THM-NP studies. Among the processes involved in THM-NP research, the methodology for constructing a compound–target network has shown the greatest change over time. In summary, our analysis describes comprehensive methodological trends and current ideas in research design for network pharmacology researchers. Full article
(This article belongs to the Special Issue Phytochemical Omics in Medicinal Plants)
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Review

Jump to: Editorial, Research

41 pages, 3186 KiB  
Review
Phenolic Compounds Exerting Lipid-Regulatory, Anti-Inflammatory and Epigenetic Effects as Complementary Treatments in Cardiovascular Diseases
by Laura Toma, Gabriela Maria Sanda, Loredan Stefan Niculescu, Mariana Deleanu, Anca Volumnia Sima and Camelia Sorina Stancu
Biomolecules 2020, 10(4), 641; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10040641 - 21 Apr 2020
Cited by 40 | Viewed by 6632
Abstract
Atherosclerosis is the main process behind cardiovascular diseases (CVD), maladies which continue to be responsible for up to 70% of death worldwide. Despite the ongoing development of new and potent drugs, their incomplete efficacy, partial intolerance and numerous side effects make the search [...] Read more.
Atherosclerosis is the main process behind cardiovascular diseases (CVD), maladies which continue to be responsible for up to 70% of death worldwide. Despite the ongoing development of new and potent drugs, their incomplete efficacy, partial intolerance and numerous side effects make the search for new alternatives worthwhile. The focus of the scientific world turned to the potential of natural active compounds to prevent and treat CVD. Essential for effective prevention or treatment based on phytochemicals is to know their mechanisms of action according to their bioavailability and dosage. The present review is focused on the latest data about phenolic compounds and aims to collect and correlate the reliable existing knowledge concerning their molecular mechanisms of action to counteract important risk factors that contribute to the initiation and development of atherosclerosis: dyslipidemia, and oxidative and inflammatory-stress. The selection of phenolic compounds was made to prove their multiple benefic effects and endorse them as CVD remedies, complementary to allopathic drugs. The review also highlights some aspects that still need clear scientific explanations and draws up some new molecular approaches to validate phenolic compounds for CVD complementary therapy in the near future. Full article
(This article belongs to the Special Issue Phytochemical Omics in Medicinal Plants)
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22 pages, 358 KiB  
Review
Can Medicinal Plants and Bioactive Compounds Combat Lipid Peroxidation Product 4-HNE-Induced Deleterious Effects?
by Fei-Xuan Wang, Hong-Yan Li, Yun-Qian Li and Ling-Dong Kong
Biomolecules 2020, 10(1), 146; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10010146 - 16 Jan 2020
Cited by 6 | Viewed by 4486
Abstract
The toxic reactive aldehyde 4-hydroxynonenal (4-HNE) belongs to the advanced lipid peroxidation end products. Accumulation of 4-HNE and formation of 4-HNE adducts induced by redox imbalance participate in several cytotoxic processes, which contribute to the pathogenesis and progression of oxidative stress-related human disorders. [...] Read more.
The toxic reactive aldehyde 4-hydroxynonenal (4-HNE) belongs to the advanced lipid peroxidation end products. Accumulation of 4-HNE and formation of 4-HNE adducts induced by redox imbalance participate in several cytotoxic processes, which contribute to the pathogenesis and progression of oxidative stress-related human disorders. Medicinal plants and bioactive natural compounds are suggested to be attractive sources of potential agents to mitigate oxidative stress, but little is known about the therapeutic potentials especially on combating 4-HNE-induced deleterious effects. Of note, some investigations clarify the attenuation of medicinal plants and bioactive compounds on 4-HNE-induced disturbances, but strong evidence is needed that these plants and compounds serve as potent agents in the prevention and treatment of disorders driven by 4-HNE. Therefore, this review highlights the pharmacological basis of these medicinal plants and bioactive compounds to combat 4-HNE-induced deleterious effects in oxidative stress-related disorders, such as neurotoxicity and neurological disorder, eye damage, cardiovascular injury, liver injury, and energy metabolism disorder. In addition, this review briefly discusses with special attention to the strategies for developing potential therapies by future applications of these medicinal plants and bioactive compounds, which will help biological and pharmacological scientists to explore the new vistas of medicinal plants in combating 4-HNE-induced deleterious effects. Full article
(This article belongs to the Special Issue Phytochemical Omics in Medicinal Plants)
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17 pages, 1618 KiB  
Review
Mechanistic Pathways and Molecular Targets of Plant-Derived Anticancer ent-Kaurane Diterpenes
by Md. Shahid Sarwar, Yi-Xuan Xia, Zheng-Ming Liang, Siu Wai Tsang and Hong-Jie Zhang
Biomolecules 2020, 10(1), 144; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10010144 - 16 Jan 2020
Cited by 37 | Viewed by 4753
Abstract
Since the first discovery in 1961, more than 1300 ent-kaurane diterpenoids have been isolated and identified from different plant sources, mainly the genus Isodon. Chemically, they consist of a perhydrophenanthrene subunit and a cyclopentane ring. A large number of reports describe [...] Read more.
Since the first discovery in 1961, more than 1300 ent-kaurane diterpenoids have been isolated and identified from different plant sources, mainly the genus Isodon. Chemically, they consist of a perhydrophenanthrene subunit and a cyclopentane ring. A large number of reports describe the anticancer potential and mechanism of action of ent-kaurane compounds in a series of cancer cell lines. Oridonin is one of the prime anticancer ent-kaurane diterpenoids that is currently in a phase-I clinical trial in China. In this review, we have extensively summarized the anticancer activities of ent-kaurane diterpenoids according to their plant sources, mechanistic pathways, and biological targets. Literature analysis found that anticancer effect of ent-kauranes are mainly mediated through regulation of apoptosis, cell cycle arrest, autophagy, and metastasis. Induction of apoptosis is associated with modulation of BCL-2, BAX, PARP, cytochrome c, and cleaved caspase-3, -8, and -9, while cell cycle arrest is controlled by cyclin D1, c-Myc, p21, p53, and CDK-2 and -4. The most common metastatic target proteins of ent-kauranes are MMP-2, MMP-9, VEGF, and VEGFR whereas LC-II and mTOR are key regulators to induce autophagy. Full article
(This article belongs to the Special Issue Phytochemical Omics in Medicinal Plants)
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20 pages, 1933 KiB  
Review
Neuroprotective Effects of Quercetin in Alzheimer’s Disease
by Haroon Khan, Hammad Ullah, Michael Aschner, Wai San Cheang and Esra Küpeli Akkol
Biomolecules 2020, 10(1), 59; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10010059 - 30 Dec 2019
Cited by 267 | Viewed by 16218
Abstract
Quercetin is a flavonoid with notable pharmacological effects and promising therapeutic potential. It is widely distributed among plants and found commonly in daily diets predominantly in fruits and vegetables. Neuroprotection by quercetin has been reported in several in vitro studies. It has been [...] Read more.
Quercetin is a flavonoid with notable pharmacological effects and promising therapeutic potential. It is widely distributed among plants and found commonly in daily diets predominantly in fruits and vegetables. Neuroprotection by quercetin has been reported in several in vitro studies. It has been shown to protect neurons from oxidative damage while reducing lipid peroxidation. In addition to its antioxidant properties, it inhibits the fibril formation of amyloid-β proteins, counteracting cell lyses and inflammatory cascade pathways. In this review, we provide a synopsis of the recent literature exploring the relationship between quercetin and cognitive performance in Alzheimer’s disease and its potential as a lead compound in clinical applications. Full article
(This article belongs to the Special Issue Phytochemical Omics in Medicinal Plants)
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30 pages, 2227 KiB  
Review
Anticancer Plants: A Review of the Active Phytochemicals, Applications in Animal Models, and Regulatory Aspects
by Tariq Khan, Muhammad Ali, Ajmal Khan, Parveen Nisar, Sohail Ahmad Jan, Shakeeb Afridi and Zabta Khan Shinwari
Biomolecules 2020, 10(1), 47; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10010047 - 27 Dec 2019
Cited by 187 | Viewed by 28003
Abstract
The rising burden of cancer worldwide calls for an alternative treatment solution. Herbal medicine provides a very feasible alternative to western medicine against cancer. This article reviews the selected plant species with active phytochemicals, the animal models used for these studies, and their [...] Read more.
The rising burden of cancer worldwide calls for an alternative treatment solution. Herbal medicine provides a very feasible alternative to western medicine against cancer. This article reviews the selected plant species with active phytochemicals, the animal models used for these studies, and their regulatory aspects. This study is based on a meticulous literature review conducted through the search of relevant keywords in databases, Web of Science, Scopus, PubMed, and Google Scholar. Twenty plants were selected based on defined selection criteria for their potent anticancer compounds. The detailed analysis of the research studies revealed that plants play an indispensable role in fighting different cancers such as breast, stomach, oral, colon, lung, hepatic, cervical, and blood cancer cell lines. The in vitro studies showed cancer cell inhibition through DNA damage and activation of apoptosis-inducing enzymes by the secondary metabolites in the plant extracts. Studies that reported in vivo activities of these plants showed remarkable results in the inhibition of cancer in animal models. Further studies should be performed on exploring more plants, their active compounds, and the mechanism of anticancer actions for use as standard herbal medicine. Full article
(This article belongs to the Special Issue Phytochemical Omics in Medicinal Plants)
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38 pages, 592 KiB  
Review
Recent Trends in the Application of Chromatographic Techniques in the Analysis of Luteolin and Its Derivatives
by Aleksandra Maria Juszczak, Marijana Zovko-Končić and Michał Tomczyk
Biomolecules 2019, 9(11), 731; https://0-doi-org.brum.beds.ac.uk/10.3390/biom9110731 - 12 Nov 2019
Cited by 50 | Viewed by 5887
Abstract
Luteolin is a flavonoid often found in various medicinal plants that exhibits multiple biological effects such as antioxidant, anti-inflammatory and immunomodulatory activity. Commercially available medicinal plants and their preparations containing luteolin are often used in the treatment of hypertension, inflammatory diseases, and even [...] Read more.
Luteolin is a flavonoid often found in various medicinal plants that exhibits multiple biological effects such as antioxidant, anti-inflammatory and immunomodulatory activity. Commercially available medicinal plants and their preparations containing luteolin are often used in the treatment of hypertension, inflammatory diseases, and even cancer. However, to establish the quality of such preparations, appropriate analytical methods should be used. Therefore, the present paper provides the first comprehensive review of the current analytical methods that were developed and validated for the quantitative determination of luteolin and its C- and O-derivatives including orientin, isoorientin, luteolin 7-O-glucoside and others. It provides a systematic overview of chromatographic analytical techniques including thin layer chromatography (TLC), high performance thin layer chromatography (HPTLC), liquid chromatography (LC), high performance liquid chromatography (HPLC), gas chromatography (GC) and counter-current chromatography (CCC), as well as the conditions used in the determination of luteolin and its derivatives in plant material. Full article
(This article belongs to the Special Issue Phytochemical Omics in Medicinal Plants)
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27 pages, 1360 KiB  
Review
On the Neuroprotective Effects of Naringenin: Pharmacological Targets, Signaling Pathways, Molecular Mechanisms, and Clinical Perspective
by Zeinab Nouri, Sajad Fakhri, Fardous F. El-Senduny, Nima Sanadgol, Ghada E. Abd-ElGhani, Mohammad Hosein Farzaei and Jen-Tsung Chen
Biomolecules 2019, 9(11), 690; https://0-doi-org.brum.beds.ac.uk/10.3390/biom9110690 - 03 Nov 2019
Cited by 74 | Viewed by 6149
Abstract
As a group of progressive, chronic, and disabling disorders, neurodegenerative diseases (NDs) affect millions of people worldwide, and are on the rise. NDs are known as the gradual loss of neurons; however, their pathophysiological mechanisms have not been precisely revealed. Due to the [...] Read more.
As a group of progressive, chronic, and disabling disorders, neurodegenerative diseases (NDs) affect millions of people worldwide, and are on the rise. NDs are known as the gradual loss of neurons; however, their pathophysiological mechanisms have not been precisely revealed. Due to the complex pathophysiological mechanisms behind the neurodegeneration, investigating effective and multi-target treatments has remained a clinical challenge. Besides, appropriate neuroprotective agents are still lacking, which raises the need for new therapeutic agents. In recent years, several reports have introduced naturally-derived compounds as promising alternative treatments for NDs. Among natural entities, flavonoids are multi-target alternatives affecting different pathogenesis mechanisms in neurodegeneration. Naringenin is a natural flavonoid possessing neuroprotective activities. Increasing evidence has attained special attention on the variety of therapeutic targets along with complex signaling pathways for naringenin, which suggest its possible therapeutic applications in several NDs. Here, in this review, the neuroprotective effects of naringenin, as well as its related pharmacological targets, signaling pathways, molecular mechanisms, and clinical perspective, are described. Moreover, the need to develop novel naringenin delivery systems is also discussed to solve its widespread pharmacokinetic limitation. Full article
(This article belongs to the Special Issue Phytochemical Omics in Medicinal Plants)
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14 pages, 7273 KiB  
Review
The Exploration of Natural Compounds for Anti-Diabetes from Distinctive Species Garcinia linii with Comprehensive Review of the Garcinia Family
by Ting-Hsu Chen, May-Jywan Tsai, Yaw-Syan Fu and Ching-Feng Weng
Biomolecules 2019, 9(11), 641; https://0-doi-org.brum.beds.ac.uk/10.3390/biom9110641 - 23 Oct 2019
Cited by 19 | Viewed by 4350
Abstract
Approximately 400 Garcinia species are distributed around the world. Previous studies have reported the extracts from bark, seed, fruits, peels, leaves, and stems of Garcinia mangostana, G. xanthochymus, and G. cambogia that were used to treat adipogenesis, inflammation, obesity, cancer, cardiovascular diseases, [...] Read more.
Approximately 400 Garcinia species are distributed around the world. Previous studies have reported the extracts from bark, seed, fruits, peels, leaves, and stems of Garcinia mangostana, G. xanthochymus, and G. cambogia that were used to treat adipogenesis, inflammation, obesity, cancer, cardiovascular diseases, and diabetes. Moreover, the hypoglycemic effects and underlined actions of different species such as G. kola, G. pedunculata, and G. prainiana have been elucidated. However, the anti-hyperglycemia of G. linii remains to be verified in this aspect. In this article, the published literature was collected and reviewed based on the medicinal characteristics of the species Garcinia, particularly in diabetic care to deliberate the known constituents from Garcinia and further focus on and isolate new compounds of G. linii (Taiwan distinctive species) on various hypoglycemic targets including α-amylase, α-glucosidase, 5′-adenosine monophosphate-activated protein kinase (AMPK), insulin receptor kinase, peroxisome proliferator-activated receptor gamma (PPARγ), and dipeptidyl peptidase-4 (DPP-4) via the molecular docking approach with Gold program to explore the potential candidates for anti-diabetic treatments. Accordingly, benzopyrans and triterpenes are postulated to be the active components in G. linii for mediating blood glucose. To further validate the potency of those active components, in vitro enzymatic and cellular function assays with in vivo animal efficacy experiments need to be performed in the near future. Full article
(This article belongs to the Special Issue Phytochemical Omics in Medicinal Plants)
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