molecules-logo

Journal Browser

Journal Browser

Phytochemical and Pharmacological Evaluation of Natural Products

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 44414

Special Issue Editors

1. Faculty of Sciences, Arab American University, Jenin P.O. Box 240, Palestine
2. Al-Qasemi Research Center- Al-Qasemi Academic College, Baqa-El-Gharbia P.O. Box 124, Israel
Interests: drug resistance; novel compounds and drug discovery; secondary metabolites; structure–function relationship; advanced extraction and fractionation strategies; phytochemical screening and composition; computer-aided drug design; non-communicable diseases; communicable diseases
Special Issues, Collections and Topics in MDPI journals
Computational Biochemistry, Research Centre Jülich & University Düsseldorf, Germany
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Nigeria

Special Issue Information

Dear Colleagues,

Natural products are metabolites originating from living organisms and in particular from plants, microorganisms, and animals. These provide a myriad of active compounds, serving as a continuous source for drug discovery. Remarkably, half of the drugs approved during the last 15 years are natural-product-based.

Phytochemical evaluation is a major tool in understanding natural product content and composition. Such evaluation contributes important information regarding the wide variety of phytochemicals present in the organism, in addition to compound structure. In turn, this information enables a better understanding of pharmacological activities and sheds light on the structure–activity relationship. Evaluation ranges from a basic phytochemical screening, involving simple tools (e.g., spectroptometric methods) to gain an image of phytochemical groups, to detailed isolation and identification of novel compounds using high-end chemical analysis, including GC–MS and NMR for accurate structure determination. Isolation steps of compounds of interest as well as structural elucidation form the basis of drug discovery and provide a template for the deployment of computer-aided drug design tools for rational modifications of the isolated natural product.

Pharmacological evaluation is mandatory in profiling the activities of natural products and can exploit computational lead design strategies for either unravelling mechanistic aspects or toward evolving more active congeners. Using different docking algorithms, natural products can be screened against pharmacological receptors to compute ligand–receptor interaction energies or to generate pharmacophore models. With molecular dynamics simulation, the effect of receptor flexibility and water molecules can be captured and assessed in a time-dependent manner. Filtering based on physicochemical descriptors and ADMET profiling using computational modeling is also possible for the selection and prioritization of natural-product-based compounds for further testing. Thus, the combined data from both experimental and simulation perspectives are significant and valuable to our understanding of potential applications.

We invite researchers to contribute with original and review articles presenting their work in natural product evaluation, in respect of phytochemistry and pharmacology. We welcome papers presenting and discussing the various steps of phytochemical evaluation of known and less known origins, with an emphasis on works which include phytochemical and pharmacological evaluations as well as computational studies into the structures and pharmacological mechanisms of natural products. These evaluations should preferably integrate the presented information and perspectives into a deeper understanding of structure–activity relations.

Prof. Dr. Hilal Zaid
Dr. Zipora Tietel
Prof. Dr. Birgit Strodel
Dr. Olujide Olubiyi
Guest Editors

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. Molecules is an international peer-reviewed open access semimonthly 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 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

  • Drug resistance
  • Novel compounds and drug discovery
  • Secondary metabolites
  • Structure–function relationship
  • Advanced extraction and fractionation strategies
  • Phytochemical screening and composition
  • Computer aided drug design
  • Non-communicable diseases
  • Communicable diseases

Published Papers (16 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

14 pages, 2325 KiB  
Article
Tinosporaside from Tinospora cordifolia Encourages Skeletal Muscle Glucose Transport through Both PI-3-Kinase- and AMPK-Dependent Mechanisms
by Akansha Mishra, Khushbu Sharma, Jyotsana Pandey, Kapil Dev, Sleman Kadan, Mahendra Sahai, Ishbal Ahmad, Arvind K. Srivastava, Akhilesh K. Tamrakar, Hilal Zaid and Rakesh Maurya
Molecules 2023, 28(2), 483; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules28020483 - 04 Jan 2023
Cited by 1 | Viewed by 1848
Abstract
The stem of Tinospora cordifolia has been traditionally used in traditional Indian systems of medicine for blood sugar control, without the knowledge of the underlying mechanism and chemical constitution responsible for the observed anti-diabetic effect. In the present study, Tinosporaside, a diterpenoid isolated [...] Read more.
The stem of Tinospora cordifolia has been traditionally used in traditional Indian systems of medicine for blood sugar control, without the knowledge of the underlying mechanism and chemical constitution responsible for the observed anti-diabetic effect. In the present study, Tinosporaside, a diterpenoid isolated from the stem of T. cordifolia, was investigated for its effects on glucose utilization in skeletal muscle cells, which was followed by determining the anti-hyperglycemic efficacy in our diabetic db/db mice model. We found that tinosporaside augmented glucose uptake by increasing the translocation of GLUT4 to the plasma membrane in L6 myotubes, upon prolonged exposure for 16 h. Moreover, tinosporaside treatment significantly increased the phosphorylation of protein kinase B/AKT (Ser-473) and 5′ AMP-activated protein kinase (AMPK, Thr-172). These effects were abolished in the presence of the wortmannin and compound C. Administration of tinosporaside to db/db mice improved glucose tolerance and peripheral insulin sensitivity associated with increased gene expression and phosphorylation of the markers of phosphoinositide 3-kinases (PI3Ks) and AMPK signaling in skeletal muscle tissue. The findings revealed that tinosporaside exerted its antidiabetic efficacy by enhancing the rate of glucose utilization in skeletal muscle, mediated by PI3K- and AMPK-dependent signaling mechanisms. Full article
(This article belongs to the Special Issue Phytochemical and Pharmacological Evaluation of Natural Products)
Show Figures

Graphical abstract

11 pages, 1135 KiB  
Article
Anti-Inflammatory and Antinociceptive Activities of the Essential Oil of Tagetes parryi A. Gray (Asteraceae) and Verbenone
by Hansel E. González-Velasco, María S. Pérez-Gutiérrez, Ángel J. Alonso-Castro, Juan R. Zapata-Morales, Perla del C. Niño-Moreno, Nimsi Campos-Xolalpa and Marco M. González-Chávez
Molecules 2022, 27(9), 2612; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27092612 - 19 Apr 2022
Cited by 5 | Viewed by 1684
Abstract
Tagetes parryi is a plant empirically used to treat gastrointestinal and inflammatory diseases, its essential oil (EOTP) was obtained from the aerial parts, and the composition was elucidated by GC-MS. The in vivo and in vitro anti-inflammatory activities and the antinociceptive activity of [...] Read more.
Tagetes parryi is a plant empirically used to treat gastrointestinal and inflammatory diseases, its essential oil (EOTP) was obtained from the aerial parts, and the composition was elucidated by GC-MS. The in vivo and in vitro anti-inflammatory activities and the antinociceptive activity of EOTP and (1S)-(-)-verbenone (VERB) were assessed. The major compounds identified for EOTP were verbenone (33.39%), dihydrotagetone (26.88%), and tagetone (20.8%). EOTP and VERB diminished the ear oedema induced with TPA by 93.77 % and 81.13 %, respectively. EOTP and VERB decreased inflammation in a 12-O-tetradecanoylphorbol-13-acetate (TPA) chronic model with ED50 = 54.95 mg/kg and 45.24 mg/kg, respectively. EOTP (15 µg/mL) inhibited the in vitro production of the pro-inflammatory mediators NO (67.02%), TNF-α (69.21%), and IL-6 (58.44%) in LPS-stimulated macrophages. In the acetic induced writhing test, EOTP and VERB showed antinociceptive effects with ED50 = 84.93 mg/kg and ED50 = 45.24 mg/kg, respectively. In phase 1 of the formalin test, EOTP and VERB showed no antinociceptive effects, whereas in phase 2, EOTP (ED50 = 35.45 mg/kg) and VERB (ED50 = 24.84 mg/kg) showed antinociceptive effects. The antinociceptive actions of ETOP and VERB were blocked with the co-administration of L-NAME. This study suggests that EOTP and VERB might be used in the treatment of pain and inflammatory problems. Full article
(This article belongs to the Special Issue Phytochemical and Pharmacological Evaluation of Natural Products)
Show Figures

Figure 1

16 pages, 1402 KiB  
Article
LC/ESI/TOF-MS Characterization, Anxiolytic and Antidepressant-like Effects of Mitragyna speciosa Korth Extract in Diabetic Rats
by Lin Chen, Shizao Fei and Opeyemi Joshua Olatunji
Molecules 2022, 27(7), 2208; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27072208 - 28 Mar 2022
Cited by 7 | Viewed by 2509
Abstract
In this study, the attenuative effects of the hydro-alcoholic extract from Mitragyna speciosa (MSE) against diabetes-induced anxiety and depression-like behaviors were examined. In addition, UPLC/ESI/TOF-MS analysis was performed to identify the phytochemical nature of MSE. DM was induced using a combination of high [...] Read more.
In this study, the attenuative effects of the hydro-alcoholic extract from Mitragyna speciosa (MSE) against diabetes-induced anxiety and depression-like behaviors were examined. In addition, UPLC/ESI/TOF-MS analysis was performed to identify the phytochemical nature of MSE. DM was induced using a combination of high fructose/streptozotocin, and the diabetic rats were treated with MSE (50 and 200 mg/kg) for 5 weeks. After treatment, the animals were subjected to a forced swim test, open field test and elevated plus-maze tests. Additionally, proinflammatory cytokines and oxidative stress parameters were evaluated in the brain tissues of the rats. UPLC/ESI/TOF-MS analysis revealed that MSE is abundantly rich in polyphenolic constituents, notably flavonoid and phenolic glycosides. Behavioral tests and biochemical analyses indicated that diabetic rats showed significantly increased anxiety and depressive-like behavioral deficits, brain oxidative stress and pro-inflammatory cytokines levels (IL-1β, IL-6 and TNF-α). Treatment with MSE (50 and 200 mg/kg) significantly attenuated increased blood glucose level, depressive and anxiety-like behaviors in diabetic rats. Additionally, the antioxidant enzymes activities were markedly increased in MSE-treated animals, while TNF-α, IL-1β and IL-6 cytokines were notably suppressed. Taken together, these results suggested that MSE has potentials as antidepressant and anxiolytic-like effects and improves the brain oxido-inflammatory status in diabetic rats. Full article
(This article belongs to the Special Issue Phytochemical and Pharmacological Evaluation of Natural Products)
Show Figures

Figure 1

16 pages, 1205 KiB  
Article
LC-ESI-MS/MS Characterization of Concentrated Polyphenolic Fractions from Rhododendron luteum and Their Anti-Inflammatory and Antioxidant Activities
by Lena Łyko, Marta Olech and Renata Nowak
Molecules 2022, 27(3), 827; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27030827 - 26 Jan 2022
Cited by 12 | Viewed by 3096
Abstract
The high biological potential of polyphenols encourages the search for new natural sources of and biomedical applications for these compounds. Rhododendron luteum Sweet was previously reported to contain pharmaceutically active polyphenols. The present research investigates the polyphenolic fractions in R. luteum leaves, including [...] Read more.
The high biological potential of polyphenols encourages the search for new natural sources of and biomedical applications for these compounds. Rhododendron luteum Sweet was previously reported to contain pharmaceutically active polyphenols. The present research investigates the polyphenolic fractions in R. luteum leaves, including a determination of the free and bound phenolic acid and flavonoid contents and their anti-inflammatory and antioxidant activities. LC-ESI-MS/MS (liquid chromatography/electrospray ionization triple quadrupole mass spectrometry) analysis revealed a great abundance of free (e.g., 5-O-caffeoylquinic acid, ferulic acid, protocatechuic acid, catechin, and dihydromyricetin) and bound (e.g., caffeic acid, p-coumaric, protocatechuic acid, myricetin, quercetin) phenolics. The R. luteum samples exhibited high anti-inflammatory potential in lipoxygenase (IC50: 0.33 ± 0.01–2.96 ± 0.06 mg dry extract (DE)/mL) and hyaluronidase (IC50: 78.76 ± 2.09 – 429.07 ± 31.08 µg DE/mL) inhibition capacity assays. Some samples also had the ability to inhibit cyclooxygenase 1 (IC50: 311.8 ± 10.95 µg DE/mL) and cyclooxygenase 2 (IC50: 53.40 ± 5.07; 608.09 ± 14.78 µg DE/mL). All fractions showed excellent antioxidant activity in the Oxygen Radical Absorbance Capacity (ORAC) assay (5.76–221.81 g Trolox/g DE), ABTS•+ radical scavenging ability (0.62 ± 0.03 – 5.09 ± 0.23 g Trolox/g DE), and moderate ion (Fe2+) chelating power. This paper expands our knowledge of the phytochemistry and pharmacological activity of R. luteum polyphenols. It reveals, for the first time, the presence of dihydromyricetin, afzelin, and laricitrin in the plant material. It indicates biologically active polyphenolic fractions that should be further investigated or which could be efficiently used in pharmaceutical, cosmetic, or nutraceutical applications. Full article
(This article belongs to the Special Issue Phytochemical and Pharmacological Evaluation of Natural Products)
Show Figures

Graphical abstract

18 pages, 3167 KiB  
Article
Fucoidan and Alginate from the Brown Algae Colpomenia sinuosa and Their Combination with Vitamin C Trigger Apoptosis in Colon Cancer
by Reem Al Monla, Zeina Dassouki, Nouha Sari-Chmayssem, Hiba Mawlawi and Hala Gali-Muhtasib
Molecules 2022, 27(2), 358; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27020358 - 06 Jan 2022
Cited by 22 | Viewed by 3197
Abstract
Brown seaweeds are producers of bioactive molecules which are known to inhibit oncogenic growth. Here, we investigated the antioxidant, cytotoxic, and apoptotic effects of two polysaccharides from the brown algae Colpomenia sinuosa, namely fucoidan and alginate, in a panel of cancer cell [...] Read more.
Brown seaweeds are producers of bioactive molecules which are known to inhibit oncogenic growth. Here, we investigated the antioxidant, cytotoxic, and apoptotic effects of two polysaccharides from the brown algae Colpomenia sinuosa, namely fucoidan and alginate, in a panel of cancer cell lines and evaluated their effects when combined with vitamin C. Fucoidan and alginate were isolated from brown algae and characterized by HPLC, FTIR, and NMR spectroscopy. The results indicated that highly sulfated fucoidans had higher antioxidant and cytotoxic effects than alginate. Human colon cancer cells were the most sensitive to the algal treatments, with fucoidan having an IC50 value (618.9 µg/mL1) lower than that of alginate (690 µg/mL1). The production of reactive oxygen species was increased upon treatment of HCT-116 cells with fucoidan and alginate, which suggest that these compounds may trigger cell death via oxidative damage. The combination of fucoidan with vitamin C showed enhanced effects compared to treatment with fucoidan alone, as evidenced by the significant inhibitory effects on HCT-116 colon cancer cell viability. The combination of the algal polysaccharides with vitamin C caused enhanced degeneration in the nuclei of cells, as evidenced by DAPI staining and increased the subG1 population, suggesting the induction of cell death. Together, these results suggest that fucoidan and alginate from the brown algae C. sinuosa are promising anticancer compounds, particularly when used in combination with vitamin C. Full article
(This article belongs to the Special Issue Phytochemical and Pharmacological Evaluation of Natural Products)
Show Figures

Figure 1

18 pages, 4852 KiB  
Article
Anti-Inflammatory Activities of the Ethanol Extract of Prasiola japonica, an Edible Freshwater Green Algae, and Its Various Solvent Fractions in LPS-Induced Macrophages and Carrageenan-Induced Paw Edema via the AP-1 Pathway
by Laily Rahmawati, Sang Hee Park, Dong Seon Kim, Hwa Pyoung Lee, Nur Aziz, Chae Young Lee, Seung A Kim, Seok Gu Jang, Dong Sam Kim and Jae Youl Cho
Molecules 2022, 27(1), 194; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27010194 - 29 Dec 2021
Cited by 9 | Viewed by 2801
Abstract
Prasiola japonica possesses several biological activities. However, reports on the anti-inflammatory activities and molecular mechanisms of its different solvent fractions remain limited. In this study, we investigated the potential anti-inflammatory activities of P. japonica ethanol extract (Pj-EE) and four solvent fractions of Pj-EE [...] Read more.
Prasiola japonica possesses several biological activities. However, reports on the anti-inflammatory activities and molecular mechanisms of its different solvent fractions remain limited. In this study, we investigated the potential anti-inflammatory activities of P. japonica ethanol extract (Pj-EE) and four solvent fractions of Pj-EE made with hexane (Pj-EE-HF), chloroform (Pj-EE-CF), butanol (Pj-EE-BF), or water (Pj-EE-WF) in both in vitro (LPS-induced macrophage-like RAW264.7 cells) and in vivo (carrageenan-induced acute paw edema mouse models) experiments. The most active solvent fraction was selected for further analysis. Various in vitro and in vivo assessments, including nitric oxide (NO), cytokines, luciferase assays, real-time polymerase chain reactions, and immunoblotting analyses were performed to evaluate the underlying mechanisms. In addition, the phytochemical constituents were characterized by Liquid chromatography-tandem mass spectrometry. In in vitro studies, the highest inhibition of NO production was observed in Pj-EE-CF. Further examination revealed that Pj-EE-CF decreased the expression of inflammation-related cytokines in LPS-induced RAW264.7 cells and suppressed subsequent AP-1-luciferase activity by inhibition of phosphorylation events in the AP-1 signaling pathway. Pj-EE-CF treatment also demonstrated the strongest reduction in thickness and volume of carrageenan-induced paw edema, while Pj-EE-BF showed the lowest activity. Furthermore, Pj-EE-CF also reduced gene expression and cytokines production in tissue lysates of carrageenan-induced paw edema. These findings support and validate the evidence that Pj-EE, and especially Pj-EE-CF, could be a good natural source for an anti-inflammatory agent that targets the AP1 pathway. Full article
(This article belongs to the Special Issue Phytochemical and Pharmacological Evaluation of Natural Products)
Show Figures

Figure 1

17 pages, 4214 KiB  
Article
Anti-Gastritis and Anti-Lung Injury Effects of Pine Tree Ethanol Extract Targeting Both NF-κB and AP-1 Pathways
by Seung A Kim, Jieun Oh, Se Rin Choi, Choong Hwan Lee, Byoung-Hee Lee, Mi-Nam Lee, Mohammad Amjad Hossain, Jong-Hoon Kim, Sarah Lee and Jae Youl Cho
Molecules 2021, 26(20), 6275; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26206275 - 16 Oct 2021
Cited by 8 | Viewed by 2436
Abstract
An ethanol extract (Pd-EE) of Pinus densiflora Siebold and Zucc was derived from the branches of pine trees. According to the Donguibogam, pine resin has the effects of lowering the fever, reducing pain, and killing worms. The purpose of this study is to [...] Read more.
An ethanol extract (Pd-EE) of Pinus densiflora Siebold and Zucc was derived from the branches of pine trees. According to the Donguibogam, pine resin has the effects of lowering the fever, reducing pain, and killing worms. The purpose of this study is to investigate whether Pd-EE has anti-inflammatory effects. During in vitro trials, NO production, as well as changes in the mRNA levels of inflammation-related genes and the phosphorylation levels of related proteins, were confirmed in RAW264.7 cells activated with lipopolysaccharide depending on the presence or absence of Pd-EE treatment. The activities of transcription factors were checked in HEK293T cells transfected with adapter molecules in the inflammatory pathway. The anti-inflammatory efficacy of Pd-EE was also estimated in vivo with acute gastritis and acute lung injury models. LC-MS analysis was conducted to identify the components of Pd-EE. This extract reduced the production of NO and the mRNA expression levels of iNOS, COX-2, and IL-6 in RAW264.7 cells. In addition, protein expression levels of p50 and p65 and phosphorylation levels of FRA1 were decreased. In the luciferase assay, the activities of NF-κB and AP-1 were lowered. In acute gastritis and acute lung injury models, Pd-EE suppressed inflammation, resulting in alleviated damage. Full article
(This article belongs to the Special Issue Phytochemical and Pharmacological Evaluation of Natural Products)
Show Figures

Figure 1

16 pages, 1677 KiB  
Article
Junipers of Various Origins as Potential Sources of the Anticancer Drug Precursor Podophyllotoxin
by Diana I. Ivanova, Paraskev T. Nedialkov, Alexander N. Tashev, Marta Olech, Renata Nowak, Yana E. Ilieva, Zlatina K. Kokanova-Nedialkova, Teodora N. Atanasova, George Angelov and Hristo M. Najdenski
Molecules 2021, 26(17), 5179; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26175179 - 26 Aug 2021
Cited by 13 | Viewed by 2899
Abstract
Juniper representatives are natural sources of plenty of bioactive metabolites and have been used since ancient times as folk remedies against tapeworms, warts, cancer, etc. The antiproliferative activities of junipers are attributed to podophyllotoxin (PPT), which is a precursor for the synthesis of [...] Read more.
Juniper representatives are natural sources of plenty of bioactive metabolites and have been used since ancient times as folk remedies against tapeworms, warts, cancer, etc. The antiproliferative activities of junipers are attributed to podophyllotoxin (PPT), which is a precursor for the synthesis of efficient anticancer drugs. However, the natural sources of PPT, Sinopodophyllum hexandrum (Royle) T. S. Ying and Podophyllum peltatum L., are already endangered species because of their intensive industrial exploitation. Therefore, identification of other sources of PPT is necessary. This study is a broad comparative investigation of junipers, for which original sources have been accessed from different continents of the world. The present research is aimed at the identification of species, producing PPT and other lignans at concentrations that are sufficient for the high antiproliferative activity of the corresponding extracts. Cytotoxic juniper leaf extracts demonstrated a broad spectrum of activity on a panel of cancer cell lines. The antiproliferative properties of junipers were attributed to the combined activity of great diversity of lignans (podophyllotoxin, deoxypodophyllotoxin, β-peltatin, yatein, matairesinol, anhydropodorhizol, etc.), detected by UHPLC-HRMS and LC-ESI-MS/MS in the corresponding extracts. Several species of the genus Juniperus L. were outlined as perspective sources of drug precursors with potential pharmaceutical applications. Full article
(This article belongs to the Special Issue Phytochemical and Pharmacological Evaluation of Natural Products)
Show Figures

Figure 1

27 pages, 2484 KiB  
Article
Gundelia tournefortii: Fractionation, Chemical Composition and GLUT4 Translocation Enhancement in Muscle Cell Line
by Sleman Kadan, Sarit Melamed, Shoshana Benvalid, Zipora Tietel, Yoel Sasson and Hilal Zaid
Molecules 2021, 26(13), 3785; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26133785 - 22 Jun 2021
Cited by 3 | Viewed by 2105
Abstract
Type 2 diabetes (T2D) is a chronic metabolic disease, which could affect the daily life of patients and increase their risk of developing other diseases. Synthetic anti-diabetic drugs usually show severe side effects. In the last few decades, plant-derived drugs have been intensively [...] Read more.
Type 2 diabetes (T2D) is a chronic metabolic disease, which could affect the daily life of patients and increase their risk of developing other diseases. Synthetic anti-diabetic drugs usually show severe side effects. In the last few decades, plant-derived drugs have been intensively studied, particularly because of a rapid development of the instruments used in analytical chemistry. We tested the efficacy of Gundelia tournefortii L. (GT) in increasing the translocation of glucose transporter-4 (GLUT4) to the myocyte plasma membrane (PM), as a main strategy to manage T2D. In this study, GT methanol extract was sub-fractionated into 10 samples using flash chromatography. The toxicity of the fractions on L6 muscle cells, stably expressing GLUTmyc, was evaluated using the MTT assay. The efficacy with which GLUT4 was attached to the L6 PM was evaluated at non-toxic concentrations. Fraction 6 was the most effective, as it stimulated GLUT4 translocation in the absence and presence of insulin, 3.5 and 5.2 times (at 250 μg/mL), respectively. Fraction 1 and 3 showed no significant effects on GLUT4 translocation, while other fractions increased GLUT4 translocation up to 2.0 times. Gas chromatography–mass spectrometry of silylated fractions revealed 98 distinct compounds. Among those compounds, 25 were considered anti-diabetic and glucose disposal agents. These findings suggest that GT methanol sub-fractions exert an anti-diabetic effect by modulating GLUT4 translocation in L6 muscle cells, and indicate the potential of GT extracts as novel therapeutic agents for T2D. Full article
(This article belongs to the Special Issue Phytochemical and Pharmacological Evaluation of Natural Products)
Show Figures

Figure 1

16 pages, 1955 KiB  
Article
β-Sitosterol-D-Glucopyranoside Mimics Estrogenic Properties and Stimulates Glucose Utilization in Skeletal Muscle Cells
by Jyotsana Pandey, Kapil Dev, Sourav Chattopadhyay, Sleman Kadan, Tanuj Sharma, Rakesh Maurya, Sabyasachi Sanyal, Mohammad Imran Siddiqi, Hilal Zaid and Akhilesh Kumar Tamrakar
Molecules 2021, 26(11), 3129; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26113129 - 24 May 2021
Cited by 6 | Viewed by 2568
Abstract
Estrogenic molecules have been reported to regulate glucose homeostasis and may be beneficial for diabetes management. Here, we investigated the estrogenic effect of β-sitosterol-3-O-D-glucopyranoside (BSD), isolated from the fruits of Cupressus sempervirens and monitored its ability to regulate glucose utilization in skeletal [...] Read more.
Estrogenic molecules have been reported to regulate glucose homeostasis and may be beneficial for diabetes management. Here, we investigated the estrogenic effect of β-sitosterol-3-O-D-glucopyranoside (BSD), isolated from the fruits of Cupressus sempervirens and monitored its ability to regulate glucose utilization in skeletal muscle cells. BSD stimulated ERE-mediated luciferase activity in both ERα and ERβ-ERE luc expression system with greater response through ERβ in HEK-293T cells, and induced the expression of estrogen-regulated genes in estrogen responsive MCF-7 cells. In silico docking and molecular interaction studies revealed the affinity and interaction of BSD with ERβ through hydrophobic interaction and hydrogen bond pairing. Furthermore, prolonged exposure of L6-GLUT4myc myotubes to BSD raised the glucose uptake under basal conditions without affecting the insulin-stimulated glucose uptake, the effect associated with enhanced translocation of GLUT4 to the cell periphery. The BSD-mediated biological response to increase GLUT4 translocation was obliterated by PI-3-K inhibitor wortmannin, and BSD significantly increased the phosphorylation of AKT (Ser-473). Moreover, BSD-induced GLUT4 translocation was prevented in the presence of fulvestrant. Our findings reveal the estrogenic activity of BSD to stimulate glucose utilization in skeletal muscle cells via PI-3K/AKT-dependent mechanism. Full article
(This article belongs to the Special Issue Phytochemical and Pharmacological Evaluation of Natural Products)
Show Figures

Figure 1

14 pages, 632 KiB  
Article
Antioxidant, Anti-Inflammatory, and Inhibition of Acetylcholinesterase Potentials of Cassia timoriensis DC. Flowers
by Maram B. Alhawarri, Roza Dianita, Khairul Niza Abd Razak, Suriani Mohamad, Toshihiko Nogawa and Habibah A. Wahab
Molecules 2021, 26(9), 2594; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26092594 - 29 Apr 2021
Cited by 7 | Viewed by 3064
Abstract
Despite being widely used traditionally as a general tonic, especially in South East Asia, scientific research on Cassia timoriensis, remains scarce. In this study, the aim was to evaluate the in vitro activities for acetylcholinesterase (AChE) inhibitory potential, radical scavenging ability, and [...] Read more.
Despite being widely used traditionally as a general tonic, especially in South East Asia, scientific research on Cassia timoriensis, remains scarce. In this study, the aim was to evaluate the in vitro activities for acetylcholinesterase (AChE) inhibitory potential, radical scavenging ability, and the anti-inflammatory properties of different extracts of C. timoriensis flowers using Ellman’s assay, a DPPH assay, and an albumin denaturation assay, respectively. With the exception of the acetylcholinesterase activity, to the best of our knowledge, these activities were reported for the first time for C. timoriensis flowers. The phytochemical analysis confirmed the existence of tannins, flavonoids, saponins, terpenoids, and steroids in the C. timoriensis flower extracts. The ethyl acetate extract possessed the highest phenolic and flavonoid contents (527.43 ± 5.83 mg GAE/g DW and 851.83 ± 10.08 mg QE/g DW, respectively) as compared to the other extracts. In addition, the ethyl acetate and methanol extracts exhibited the highest antioxidant (IC50 20.12 ± 0.12 and 34.48 ± 0.07 µg/mL, respectively), anti-inflammatory (92.50 ± 1.38 and 92.22 ± 1.09, respectively), and anti-AChE (IC50 6.91 ± 0.38 and 6.40 ± 0.27 µg/mL, respectively) activities. These results suggest that ethyl acetate and methanol extracts may contain bioactive compounds that can control neurodegenerative disorders, including Alzheimer’s disease, through high antioxidant, anti-inflammatory, and anti-AChE activities. Full article
(This article belongs to the Special Issue Phytochemical and Pharmacological Evaluation of Natural Products)
Show Figures

Graphical abstract

14 pages, 2140 KiB  
Article
Comparison of Multiple Bioactive Constituents in the Corolla and Other Parts of Abelmoschus manihot
by Shengxin Yin, Yuqi Mei, Lifang Wei, Lisi Zou, Zhichen Cai, Nan Wu, Jiahuan Yuan, Xunhong Liu, Haitao Ge, Dianguang Wang and Dandan Wang
Molecules 2021, 26(7), 1864; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26071864 - 25 Mar 2021
Cited by 5 | Viewed by 1773
Abstract
Abelmoschus manihot (L.) Medic (AM), called Huangshukui in Chinese, is a widely used medicinal plant. Each part of AM has medicinal value, including Abelmoschi Radix (AR), Abelmoschi Herba (AH), Abelmoschi Folium (AF), Abelmoschi Corolla (AC), and Abelmoschi Semen (AS). However, only AC is [...] Read more.
Abelmoschus manihot (L.) Medic (AM), called Huangshukui in Chinese, is a widely used medicinal plant. Each part of AM has medicinal value, including Abelmoschi Radix (AR), Abelmoschi Herba (AH), Abelmoschi Folium (AF), Abelmoschi Corolla (AC), and Abelmoschi Semen (AS). However, only AC is documented in the Chinese Pharmacopoeia. In order to investigate whether there is any difference between AC and the other parts of AM, an analytical method based on ultra-fast performance liquid chromatography coupled with triple quadrupole-linear ion trap mass spectrometry (UFLC-QTRAP-MS/MS) was established for the simultaneous determination of 35 constituents in different parts of AM. Moreover, principal components analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were applied to classify and evaluate the different parts of AM based on the content of the 35 constituents. The total contents of the 35 constituents in AC were significantly higher than in the other parts of AM and the results revealed significant differences between AC and the other parts of AM. Eight constituents were remarkably related to the sample classifications. This research does not just provide the basic information for revealing the distribution patterns in different parts of AM from the same origin, but also complements some of the scientific data for the comprehensive quality evaluation of AC. Full article
(This article belongs to the Special Issue Phytochemical and Pharmacological Evaluation of Natural Products)
Show Figures

Figure 1

Review

Jump to: Research

21 pages, 1884 KiB  
Review
Anti-Diabetic Potential of Plant-Based Pentacyclic Triterpene Derivatives: Progress Made to Improve Efficacy and Bioavailability
by Michael Oboh, Laurencia Govender, Muthulisi Siwela and Blessing Nkazimulo Mkhwanazi
Molecules 2021, 26(23), 7243; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26237243 - 29 Nov 2021
Cited by 20 | Viewed by 3289
Abstract
Diabetes mellitus (DM) results from the inability of the pancreas to produce sufficient insulin or weakened cellular response to the insulin produced, which leads to hyperglycemia. Current treatments of DM focus on the use of oral hypoglycemic drugs such as acarbose, alpha-glucose inhibitors, [...] Read more.
Diabetes mellitus (DM) results from the inability of the pancreas to produce sufficient insulin or weakened cellular response to the insulin produced, which leads to hyperglycemia. Current treatments of DM focus on the use of oral hypoglycemic drugs such as acarbose, alpha-glucose inhibitors, sulphonylureas, thiazolidinediones, and biguanides to control blood glucose levels. However, these medications are known to have various side effects in addition to their bioavailability, efficacy, and safety concerns. These drawbacks have increased interest in the anti-diabetic potential of plant-derived bioactive compounds such as oleanolic and maslinic acids. Although their efficacy in ameliorating blood glucose levels has been reported in several studies, their bioavailability and efficacy remain of concern. The current review examines the anti-diabetic effects of oleanolic, maslinic, asiatic, ursolic, and corosolic acids and their derivatives, as well as the progress made thus far to enhance their bioavailability and efficacy. The literature for the current review was gathered from leading academic databases—including Google Scholar and PubMed—the key words listed below were used. The literature was searched as widely and comprehensively as possible without a defined range of dates. Full article
(This article belongs to the Special Issue Phytochemical and Pharmacological Evaluation of Natural Products)
Show Figures

Figure 1

18 pages, 3374 KiB  
Review
Cheminformatic Characterization of Natural Antimicrobial Products for the Development of New Lead Compounds
by Samson Olaitan Oselusi, Alan Christoffels and Samuel Ayodele Egieyeh
Molecules 2021, 26(13), 3970; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26133970 - 29 Jun 2021
Cited by 10 | Viewed by 3290
Abstract
The growing antimicrobial resistance (AMR) of pathogenic organisms to currently prescribed drugs has resulted in the failure to treat various infections caused by these superbugs. Therefore, to keep pace with the increasing drug resistance, there is a pressing need for novel antimicrobial agents, [...] Read more.
The growing antimicrobial resistance (AMR) of pathogenic organisms to currently prescribed drugs has resulted in the failure to treat various infections caused by these superbugs. Therefore, to keep pace with the increasing drug resistance, there is a pressing need for novel antimicrobial agents, especially from non-conventional sources. Several natural products (NPs) have been shown to display promising in vitro activities against multidrug-resistant pathogens. Still, only a few of these compounds have been studied as prospective drug candidates. This may be due to the expensive and time-consuming process of conducting important studies on these compounds. The present review focuses on applying cheminformatics strategies to characterize, prioritize, and optimize NPs to develop new lead compounds against antimicrobial resistance pathogens. Moreover, case studies where these strategies have been used to identify potential drug candidates, including a few selected open-access tools commonly used for these studies, are briefly outlined. Full article
(This article belongs to the Special Issue Phytochemical and Pharmacological Evaluation of Natural Products)
Show Figures

Figure 1

21 pages, 1021 KiB  
Review
The Occurrence and Biological Activity of Tormentic Acid—A Review
by Marta Olech, Wojciech Ziemichód and Natalia Nowacka-Jechalke
Molecules 2021, 26(13), 3797; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26133797 - 22 Jun 2021
Cited by 17 | Viewed by 2568
Abstract
This review focuses on the natural sources and pharmacological activity of tormentic acid (TA; 2α,3β,19α-trihydroxyurs-2-en-28-oic acid). The current knowledge of its occurrence in various plant species and families is summarized. Biological activity (e.g., anti-inflammatory, antidiabetic, antihyperlipidemic, hepatoprotective, cardioprotective, neuroprotective, anti-cancer, anti-osteoarthritic, antinociceptive, antioxidative, [...] Read more.
This review focuses on the natural sources and pharmacological activity of tormentic acid (TA; 2α,3β,19α-trihydroxyurs-2-en-28-oic acid). The current knowledge of its occurrence in various plant species and families is summarized. Biological activity (e.g., anti-inflammatory, antidiabetic, antihyperlipidemic, hepatoprotective, cardioprotective, neuroprotective, anti-cancer, anti-osteoarthritic, antinociceptive, antioxidative, anti-melanogenic, cytotoxic, antimicrobial, and antiparasitic) confirmed in in vitro and in vivo studies is compiled and described. Biochemical mechanisms affected by TA are indicated. Moreover, issues related to the biotechnological methods of production, effective eluents, and TA derivatives are presented. Full article
(This article belongs to the Special Issue Phytochemical and Pharmacological Evaluation of Natural Products)
Show Figures

Graphical abstract

24 pages, 1415 KiB  
Review
Contributions from Mexican Flora for the Treatment of Diabetes Mellitus: Molecules of Psacalium decompositum (A. Gray) H. Rob & Brettell
by Manuel Jiménez-Estrada, Maira Huerta-Reyes, Rosario Tavera-Hernández, J. Javier Alvarado-Sansininea and Ana Berenice Alvarez
Molecules 2021, 26(10), 2892; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26102892 - 13 May 2021
Cited by 7 | Viewed by 3127
Abstract
Diabetes mellitus (DM) is cited as a serious worldwide health problem that occupies second place in causes of annual mortality in Mexico. Among Mexican flora, nearly 300 plant species have been employed as hypoglycemic in popular use. Thus, their study entertains great relevance [...] Read more.
Diabetes mellitus (DM) is cited as a serious worldwide health problem that occupies second place in causes of annual mortality in Mexico. Among Mexican flora, nearly 300 plant species have been employed as hypoglycemic in popular use. Thus, their study entertains great relevance In this context, this work contributes a clear and timely review of the plant species utilized in Traditional Mexican Medicine and experimental biological models in which not only have the hypoglycemic properties of the extracts and the isolated compounds been considered, but also the anti-inflammatory and antioxidant properties, taking into account an integral focus based on the complex mechanisms involved in the pathogenesis and physiopathology of DM. Among the species reviewed, we highlight Psacalium decompositum (Asteraceae), due to the potent hypoglycemic, anti-inflammatory, and antioxidant activity of the sesquiterpenes identified as majority compounds isolated from the root, such as cacalol and cacalone that also possess the capacity of increasing insulin levels. In this manner, the present manuscript attempts to contribute necessary information for the future study of bioactive molecules that are useful in the treatment of DM, as well as also being a contribution to the knowledge and diffusion of Mexican Traditional Medicine. Full article
(This article belongs to the Special Issue Phytochemical and Pharmacological Evaluation of Natural Products)
Show Figures

Figure 1

Back to TopTop