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13 pages, 2319 KiB

Open AccessArticle

Centipeda minima Extract Inhibits Inflammation and Cell Proliferation by Regulating JAK/STAT Signaling in Macrophages and Keratinocytes

by Yuanqiang Ma, Byoung Ha Kim, Sang Kyu Yun and Yoon-Seok Roh

Molecules 2023, 28(4), 1723; https://doi.org/10.3390/molecules28041723 - 11 Feb 2023

Cited by 3 | Viewed by 2691

Abstract

Psoriasis, a chronic inflammation-mediated skin disease, affects 2–3% of the global population. It is characterized by keratinocyte hyperproliferation and immune cell infiltration. The JAK/STAT3 and JAK/STAT1 signaling pathways play an important role in the development of psoriasis when triggered by IL-6 and IFN-γ, [...] Read more.

Psoriasis, a chronic inflammation-mediated skin disease, affects 2–3% of the global population. It is characterized by keratinocyte hyperproliferation and immune cell infiltration. The JAK/STAT3 and JAK/STAT1 signaling pathways play an important role in the development of psoriasis when triggered by IL-6 and IFN-γ, which are produced by dendritic cells and T-lymphocytes. Thus, blocking JAK/STAT signaling may be a potential strategy for treating psoriasis. Therefore, we examined the effects of CMX, an extract of Centipeda minima enriched in Brevilin A, Arnicolide D, Arnicolide C, and Microhelenin C, on macrophages and keratinocytes. We established an in vitro model of psoriasis, based on an inflammation-associated keratinocyte proliferation model, and used macrophages and keratinocytes treated with LPS, IL-6, or IFN-γ to evaluate the effect of CMX. We found that CMX reduced pro-inflammatory cytokine production, by inhibiting lipopolysaccharide (LPS)-induced JAK1/2 and STAT1/3 phosphorylation in macrophages. Moreover, CMX-downregulated chemokine expression and cell proliferation compared with components in HaCaT cells, induced by rh-IL-6 and rh-IFN-γ, respectively. Consistently, we demonstrated that the reduction in chemokine expression and hyperproliferation was mediated by the regulation of IFN-γ-activated JAK/STAT1 and IL-6-activated JAK/STAT3 signaling. In conclusion, CMX inhibited JAK/STAT-mediated inflammatory responses and cell proliferation in macrophages and keratinocytes. Consequently, CMX may have potential uses as a therapeutic agent for treating psoriasis. Full article

(This article belongs to the Special Issue Bioactive Molecules: Isolation, Synthesis, Analysis, and Application in Medicinal Chemistry)

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14 pages, 1605 KiB

Open AccessArticle

Isolation, Structural Analysis and Biological Activity Assays of Biselisabethoxanes A and B: Two Dissymmetric Bis-Diterpenes from the Southwestern Caribbean Sea Gorgonian Coral Pseudopterogorgia elisabethae

by Ileana I. Rodríguez, Abimael D. Rodríguez and Charles L. Barnes

Molecules 2022, 27(22), 7879; https://doi.org/10.3390/molecules27227879 - 15 Nov 2022

Cited by 2 | Viewed by 1623

Abstract

Two novel dissymmetric diterpenoids, biselisabethoxanes A and B (1 and 2), were isolated from the hexane extracts of the gorgonian coral Pseudopterogorgia elisabethae. Biselisabethoxane A (1) represents the first example of a marine-derived C₄₀ dimer made of [...] Read more.

Two novel dissymmetric diterpenoids, biselisabethoxanes A and B (1 and 2), were isolated from the hexane extracts of the gorgonian coral Pseudopterogorgia elisabethae. Biselisabethoxane A (1) represents the first example of a marine-derived C₄₀ dimer made of two distinct diterpene fragments, whereas biselisabethoxane B (2) is a fused heterodimer stemming from coupling of two amphilectane-based fragments. The structures of 1 and 2 were elucidated based on 1D and 2D NMR spectral data analysis. The molecular structure of 1 was subsequently confirmed by X-ray crystallographic analysis. When evaluated for their inhibitory effects in a series of well-established biological activity assays the isolated compounds were shown to moderately inhibit the growth of Mycobacterium tuberculosis. Full article

(This article belongs to the Special Issue Bioactive Molecules: Isolation, Synthesis, Analysis, and Application in Medicinal Chemistry)

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11 pages, 1948 KiB

Open AccessArticle

Supramolecular Protein-Polyelectrolyte Assembly at Near Physiological Conditions—Water Proton NMR, ITC, and DLS Study

by Alexander Marin, Marc B. Taraban, Vanshika Patel, Y. Bruce Yu and Alexander K. Andrianov

Molecules 2022, 27(21), 7424; https://doi.org/10.3390/molecules27217424 - 1 Nov 2022

Cited by 6 | Viewed by 1881

Abstract

The in vivo potency of polyphosphazene immunoadjuvants is inherently linked to the ability of these ionic macromolecules to assemble with antigenic proteins in aqueous solutions and form physiologically stable supramolecular complexes. Therefore, in-depth knowledge of interactions in this biologically relevant system is a [...] Read more.

The in vivo potency of polyphosphazene immunoadjuvants is inherently linked to the ability of these ionic macromolecules to assemble with antigenic proteins in aqueous solutions and form physiologically stable supramolecular complexes. Therefore, in-depth knowledge of interactions in this biologically relevant system is a prerequisite for a better understanding of mechanism of immunoadjuvant activity. Present study explores a self-assembly of polyphosphazene immunoadjuvant—PCPP and a model antigen—lysozyme in a physiologically relevant environment—saline solution and neutral pH. Three analytical techniques were employed to characterize reaction thermodynamics, water-solute structural organization, and supramolecular dimensions: isothermal titration calorimetry (ITC), water proton nuclear magnetic resonance (wNMR), and dynamic light scattering (DLS). The formation of lysozyme–PCPP complexes at near physiological conditions was detected by all methods and the avidity was modulated by a physical state and dimensions of the assemblies. Thermodynamic analysis revealed the dissociation constant in micromolar range and the dominance of enthalpy factor in interactions, which is in line with previously suggested model of protein charge anisotropy and small persistence length of the polymer favoring the formation of high affinity complexes. The paper reports advantageous use of wNMR method for studying protein-polymer interactions, especially for low protein-load complexes. Full article

(This article belongs to the Special Issue Bioactive Molecules: Isolation, Synthesis, Analysis, and Application in Medicinal Chemistry)

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16 pages, 2739 KiB

Open AccessArticle

(−)-Adaline from the Adalia Genus of Ladybirds Is a Potent Antagonist of Insect and Specific Mammalian Nicotinic Acetylcholine Receptors

by David P. Richards, Rohit N. Patel, Ian R. Duce, Bhupinder P. S. Khambay, Michael A. Birkett, John A. Pickett and Ian R. Mellor

Molecules 2022, 27(20), 7074; https://doi.org/10.3390/molecules27207074 - 20 Oct 2022

Cited by 2 | Viewed by 2359

Abstract

Ladybird beetles (Coleoptera: Coccinellidae) possess strong chemical defences that are secreted in response to stress and are also found on the coating of eggs, which are rich in alkaloids that are responsible for their toxicity to other species. Recent studies have shown that [...] Read more.

Ladybird beetles (Coleoptera: Coccinellidae) possess strong chemical defences that are secreted in response to stress and are also found on the coating of eggs, which are rich in alkaloids that are responsible for their toxicity to other species. Recent studies have shown that alkaloids from several species of ladybird beetle can target nicotinic acetylcholine receptors (nAChRs) acting as receptor antagonists. Here, we have explored the actions of (−)-adaline, found in the 2-spot (Adalia bipunctata) and 10-spot (Adalia decempunctata) ladybirds, on both mammalian (α1β1γδ, α7, α4β2, α3β4) and insect nAChRs using patch-clamp of TE671 cells and locust brain neurons natively expressing nAChRs, as well as two-electrode voltage clamp of Xenopus laevis oocytes recombinantly expressing nAChRs. All nAChR subtypes were antagonised by (−)-adaline in a time-dependent, voltage-dependent and non-competitive manner with the lowest IC₅₀s at rat α3β4 (0.10 μM) and locust neuron (1.28 μM) nAChRs, at a holding potential of −75 mV. The data imply that (−)-adaline acts as an open channel blocker of nAChRs. Full article

(This article belongs to the Special Issue Bioactive Molecules: Isolation, Synthesis, Analysis, and Application in Medicinal Chemistry)

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12 pages, 2668 KiB

Open AccessArticle

Cholesterol Alters the Phase Separation in Model Membranes Containing hBest1

by Pavel Videv, Kirilka Mladenova, Tonya D. Andreeva, Jong Hun Park, Veselina Moskova-Doumanova, Svetla D. Petrova and Jordan A. Doumanov

Molecules 2022, 27(13), 4267; https://doi.org/10.3390/molecules27134267 - 2 Jul 2022

Cited by 1 | Viewed by 1737

Abstract

Human retinal pigment epithelial (RPE) cells express the transmembrane Ca²⁺-dependent Cl⁻ channel bestrophin-1 (hBest1) of the plasma membrane. Mutations in the hBest1 protein are associated with the development of distinct pathological conditions known as bestrophinopathies. The interactions between hBest1 and [...] Read more.

Human retinal pigment epithelial (RPE) cells express the transmembrane Ca²⁺-dependent Cl⁻ channel bestrophin-1 (hBest1) of the plasma membrane. Mutations in the hBest1 protein are associated with the development of distinct pathological conditions known as bestrophinopathies. The interactions between hBest1 and plasma membrane lipids (cholesterol (Chol), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and sphingomyelin (SM)) determine its lateral organization and surface dynamics, i.e., their miscibility or phase separation. Using the surface pressure/mean molecular area (π/A) isotherms, hysteresis and compressibility moduli (C_s⁻¹) of hBest1/POPC/Chol and hBest1/SM/Chol composite Langmuir monolayers, we established that the films are in an LE (liquid-expanded) or LE-LC (liquid-condensed) state, the components are well-mixed and the Ca²⁺ ions have a condensing effect on the surface molecular organization. Cholesterol causes a decrease in the elasticity of both films and a decrease in the ΔG_mix^π values (reduction of phase separation) of hBest1/POPC/Chol films. For the hBest1/SM/Chol monolayers, the negative values of ΔG_mix^π are retained and equalized with the values of ΔG_mix^π in the hBest1/POPC/Chol films. Shifts in phase separation/miscibility by cholesterol can lead to changes in the structure and localization of hBest1 in the lipid rafts and its channel functions. Full article

(This article belongs to the Special Issue Bioactive Molecules: Isolation, Synthesis, Analysis, and Application in Medicinal Chemistry)

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14 pages, 1448 KiB

Open AccessArticle

Benzamides Substituted with Quinoline-Linked 1,2,4-Oxadiazole: Synthesis, Biological Activity and Toxicity to Zebrafish Embryo

by Bin-Long Sun, Ying-Ying Wang, Sen Yang, Min-Ting Tu, Ying-Ying Shao, Yi Hua, Yi Zhou and Cheng-Xia Tan

Molecules 2022, 27(12), 3946; https://doi.org/10.3390/molecules27123946 - 20 Jun 2022

Cited by 7 | Viewed by 1859

Abstract

To develop new compounds with high activity, broad spectrum and low-toxicity, 17 benzamides substituted with quinoline-linked 1,2,4-oxadiazole were designed using the splicing principle of active substructures and were synthesized. The biological activities were evaluated against 10 fungi, indicating that some of the synthetic [...] Read more.

To develop new compounds with high activity, broad spectrum and low-toxicity, 17 benzamides substituted with quinoline-linked 1,2,4-oxadiazole were designed using the splicing principle of active substructures and were synthesized. The biological activities were evaluated against 10 fungi, indicating that some of the synthetic compounds showed excellent fungicidal activities. For example, at 50 mg/L, the inhibitory activity of 13p (3-Cl-4-Cl substituted, 86.1%) against Sclerotinia sclerotiorum was superior to that of quinoxyfen (77.8%), and the inhibitory activity of 13f (3-CF₃ substituted, 77.8%) was comparable to that of quinoxyfen. The fungicidal activities of 13f and 13p to Sclerotinia sclerotiorum were better than that of quinoxyfen (14.19 mg/L), with EC₅₀ of 6.67 mg/L and 5.17 mg/L, respectively. Furthermore, the acute toxicity of 13p was 19.42 mg/L, classifying it as a low-toxic compound. Full article

(This article belongs to the Special Issue Bioactive Molecules: Isolation, Synthesis, Analysis, and Application in Medicinal Chemistry)

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11 pages, 1384 KiB

Open AccessArticle

Biological Activities of Lichen-Derived Monoaromatic Compounds

by Thanh-Hung Do, Thuc-Huy Duong, Huy Truong Nguyen, Thi-Hien Nguyen, Jirapast Sichaem, Chuong Hoang Nguyen, Huu-Hung Nguyen and Nguyen Phuoc Long

Molecules 2022, 27(9), 2871; https://doi.org/10.3390/molecules27092871 - 30 Apr 2022

Cited by 15 | Viewed by 2766

Abstract

Lichen-derived monoaromatic compounds are bioactive compounds, associated with various pharmacological properties: antioxidant, antifungal, antiviral, cytotoxicity, and enzyme inhibition. However, little is known about data regarding alpha-glucosidase inhibition and antimicrobial activity. Very few compounds were reported to have these activities. In this paper, a [...] Read more.

Lichen-derived monoaromatic compounds are bioactive compounds, associated with various pharmacological properties: antioxidant, antifungal, antiviral, cytotoxicity, and enzyme inhibition. However, little is known about data regarding alpha-glucosidase inhibition and antimicrobial activity. Very few compounds were reported to have these activities. In this paper, a series of monoaromatic compounds from a lichen source were isolated and structurally elucidated. They are 3,5-dihydroxybenzoic acid (1), 3,5-dihydroxybenzoate methyl (2), 3,5-dihydroxy-4-methylbenzoic acid (3), 3,5-dihydroxy-4-methoxylbenzoic acid (4), 3-hydroxyorcinol (5), atranol (6), and methyl hematommate (7). To obtain more derivatives, available compounds from the previous reports such as methyl β-orsellinate (8), methyl orsellinate (9), and D-montagnetol (10) were selected for bromination. Electrophilic bromination was applied to 8–10 using NaBr/H₂O₂ reagents to yield products methyl 5-bromo-β-orsellinate (8a), methyl 3,5-dibromo-orsellinate (9a), 3-bromo-D-montagnetol (10a), and 3,5-dibromo-D-montagnetol (10b). Compounds were evaluated for alpha-glucosidase inhibition and antimicrobial activity against antibiotic-resistant, pathogenic bacteria Enterococcus faecium, Staphylococcus aureus, and Acinetobacter baumannii. Compound 4 showed stronger alpha-glucosidase inhibition than others with an IC₅₀ value of 24.0 µg/mL. Synthetic compound 9a exhibited remarkable activity against Staphylococcus aureus with a MIC value of 4 µg/mL. Molecular docking studies were performed to confirm the consistency between in vitro and in silico studies. Full article

(This article belongs to the Special Issue Bioactive Molecules: Isolation, Synthesis, Analysis, and Application in Medicinal Chemistry)

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27 pages, 10067 KiB

Open AccessArticle

α-Glucosidase Inhibitory and Antimicrobial Benzoylphloroglucinols from Garcinia schomburgakiana Fruits: In Vitro and In Silico Studies

by Huy Truong Nguyen, Thanh-Trung Nguyen, Thuc-Huy Duong, Nguyen-Minh-An Tran, Chuong Hoang Nguyen, Thi-Hong-Anh Nguyen and Jirapast Sichaem

Molecules 2022, 27(8), 2574; https://doi.org/10.3390/molecules27082574 - 15 Apr 2022

Cited by 12 | Viewed by 2581

Abstract

α-Glucosidase plays a role in hydrolyzing complex carbohydrates into glucose, which is easily absorbed, causing postprandial hyperglycemia. Inhibition of α-glucosidase is therefore an ideal approach to preventing this condition. A novel polyprenylated benzoylphloroglucinol, which we named schomburgkianone I (1), was isolated [...] Read more.

α-Glucosidase plays a role in hydrolyzing complex carbohydrates into glucose, which is easily absorbed, causing postprandial hyperglycemia. Inhibition of α-glucosidase is therefore an ideal approach to preventing this condition. A novel polyprenylated benzoylphloroglucinol, which we named schomburgkianone I (1), was isolated from the fruit of Garcinia schomburgkiana, along with an already-reported compound, guttiferone K (2). The structures of the two compounds were determined using NMR and HRESIMS analysis, and comparisons were made with previous studies. Compounds 1 and 2 exhibited potent α-glucosidase inhibition (IC_50s of 21.2 and 34.8 µM, respectively), outperforming the acarbose positive control. Compound 1 produced wide zones of inhibition against Staphylococcus aureus and Enterococcus faecium (of 21 and 20 mm, respectively), compared with the 19 and 20 mm zones of compound 2, at a concentration of 50 µg/mL. The MIC value of compound 1 against S. aureus was 13.32 µM. An in silico molecular docking model suggested that both compounds are potent inhibitors of enzyme α-glucosidase and are therefore leading candidates as therapies for diabetes mellitus. Full article

(This article belongs to the Special Issue Bioactive Molecules: Isolation, Synthesis, Analysis, and Application in Medicinal Chemistry)

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16 pages, 2122 KiB

Open AccessArticle

Anti-Neuroinflammatory Components from Clausena lenis Drake

by Si-Si Zhu, Yi-Fan Zhang, Meng Ding, Ke-Wu Zeng, Peng-Fei Tu and Yong Jiang

Molecules 2022, 27(6), 1971; https://doi.org/10.3390/molecules27061971 - 18 Mar 2022

Cited by 3 | Viewed by 2540

Abstract

Clausena lenis Drake (C. lenis) is a folk medicinal herb to treat influenza, colds, bronchitis, and malaria. The 95% and 50% ethanol extract of C. lenis showed significant nitric oxide (NO) inhibition activity in BV-2 microglial cells stimulated by lipopolysaccharide (LPS). [...] Read more.

Clausena lenis Drake (C. lenis) is a folk medicinal herb to treat influenza, colds, bronchitis, and malaria. The 95% and 50% ethanol extract of C. lenis showed significant nitric oxide (NO) inhibition activity in BV-2 microglial cells stimulated by lipopolysaccharide (LPS). Bio-guided isolation of the active extract afforded five new compounds, including a chlorine-containing furoquinoline racemate, (±)-claulenine A (1), an amide alkaloid, claulenine B (2), a prenylated coumarin, claulenin A (3), a furocoumarin glucoside, clauleside A (4), and a multi-prenylated p-hydroxybenzaldehyde, claulenin B (5), along with 33 known ones. Their structures were determined via spectroscopic methods, and the absolute configurations of new compounds were assigned via the electronic circular dichroism (ECD) calculations and single-crystal X-ray diffraction analysis. Compounds 2, 23, 27, 28, 33, and 34 showed potent anti-neuroinflammatory effects on LPS-induced NO production in BV-2 microglial cells, with IC₅₀ values in the range of 17.6–40.9 μM. The possible mechanism was deduced to interact with iNOS through molecular docking. Full article

(This article belongs to the Special Issue Bioactive Molecules: Isolation, Synthesis, Analysis, and Application in Medicinal Chemistry)

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16 pages, 6974 KiB

Open AccessArticle

Design, Synthesis and Cytotoxicity of Thiazole-Based Stilbene Analogs as Novel DNA Topoisomerase IB Inhibitors

by Jin-Chuan Liu, Bo Chen, Jia-Lin Yang, Jian-Quan Weng, Qian Yu and De-Xuan Hu

Molecules 2022, 27(3), 1009; https://doi.org/10.3390/molecules27031009 - 2 Feb 2022

Cited by 8 | Viewed by 2238

Abstract

A series of new thiazole-based stilbene analogs were designed, synthesized and evaluated for DNA topoisomerase IB (Top1) inhibitory activity. Top1-mediated relaxation assays showed that the synthesized compounds possessed variable Top1 inhibitory activity. Among them, (E)-2-(3-methylstyryl)-4-(4-fluorophenyl)thiazole (8) acted as a [...] Read more.

A series of new thiazole-based stilbene analogs were designed, synthesized and evaluated for DNA topoisomerase IB (Top1) inhibitory activity. Top1-mediated relaxation assays showed that the synthesized compounds possessed variable Top1 inhibitory activity. Among them, (E)-2-(3-methylstyryl)-4-(4-fluorophenyl)thiazole (8) acted as a potent Top1 inhibitor with high Top1 inhibition of ++++ which is comparable to that of CPT. A possible binding mode of compound 8 with Top1–DNA complex was further provided by molecular docking. An MTT assay against human breast cancer (MCF-7) and human colon cancer (HCT116) cell lines revealed that the majority of these compounds showed high cytotoxicity, with IC₅₀ values at micromolar concentrations. Compounds 8 and (E)-2-(4-tert-butylstyryl)-4-(4-fluorophenyl)thiazole (11) exhibited the most potent cytotoxicity with IC₅₀ values of 0.78 and 0.62 μM against MCF-7 and HCT116, respectively. Moreover, the preliminary structure–activity relationships of thiazole-based stilbene analogs was also discussed. Full article

(This article belongs to the Special Issue Bioactive Molecules: Isolation, Synthesis, Analysis, and Application in Medicinal Chemistry)

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Review

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29 pages, 2737 KiB

Open AccessReview

Ascorbate Is a Primary Antioxidant in Mammals

by Junichi Fujii, Tsukasa Osaki and Tomoki Bo

Molecules 2022, 27(19), 6187; https://doi.org/10.3390/molecules27196187 - 21 Sep 2022

Cited by 14 | Viewed by 4585

Abstract

Ascorbate (vitamin C in primates) functions as a cofactor for a number of enzymatic reactions represented by prolyl hydroxylases and as an antioxidant due to its ability to donate electrons, which is mostly accomplished through non-enzymatic reaction in mammals. Ascorbate directly reacts with [...] Read more.

Ascorbate (vitamin C in primates) functions as a cofactor for a number of enzymatic reactions represented by prolyl hydroxylases and as an antioxidant due to its ability to donate electrons, which is mostly accomplished through non-enzymatic reaction in mammals. Ascorbate directly reacts with radical species and is converted to ascorbyl radical followed by dehydroascorbate. Ambiguities in physiological relevance of ascorbate observed during in vivo situations could be attributed in part to presence of other redox systems and the pro-oxidant properties of ascorbate. Most mammals are able to synthesize ascorbate from glucose, which is also considered to be an obstacle to verify its action. In addition to animals with natural deficiency in the ascorbate synthesis, such as guinea pigs and ODS rats, three strains of mice with genetic removal of the responsive genes (GULO, RGN, or AKR1A) for the ascorbate synthesis have been established and are being used to investigate the physiological roles of ascorbate. Studies using these mice, along with ascorbate transporter (SVCT)-deficient mice, largely support its ability in protection against oxidative insults. While combined actions of ascorbate in regulating epigenetics and antioxidation appear to effectively prevent cancer development, pharmacological doses of ascorbate and dehydroascorbate may exert tumoricidal activity through redox-dependent mechanisms. Full article

(This article belongs to the Special Issue Bioactive Molecules: Isolation, Synthesis, Analysis, and Application in Medicinal Chemistry)

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37 pages, 2788 KiB

Open AccessReview

Anthocyanins as Key Phytochemicals Acting for the Prevention of Metabolic Diseases: An Overview

by Madalina Nistor, Roxana Pop, Adela Daescu, Adela Pintea, Carmen Socaciu and Dumitrita Rugina

Molecules 2022, 27(13), 4254; https://doi.org/10.3390/molecules27134254 - 1 Jul 2022

Cited by 21 | Viewed by 4363

Abstract

Anthocyanins are water-soluble pigments present in fruits and vegetables, which render them an extensive range of colors. They have a wide distribution in the human diet, are innocuous, and, based on numerous studies, have supposed preventive and therapeutical benefits against chronic affections such [...] Read more.

Anthocyanins are water-soluble pigments present in fruits and vegetables, which render them an extensive range of colors. They have a wide distribution in the human diet, are innocuous, and, based on numerous studies, have supposed preventive and therapeutical benefits against chronic affections such as inflammatory, neurological, cardiovascular, digestive disorders, diabetes, and cancer, mostly due to their antioxidant action. Despite their great potential as pharmaceutical applications, they have a rather limited use because of their rather low stability to environmental variations. Their absorption was noticed to occur best in the stomach and small intestine, but the pH fluctuation of the digestive system impacts their rapid degradation. Urine excretion and tissue distribution also occur at low rates. The aim of this review is to highlight the chemical characteristics of anthocyanins and emphasize their weaknesses regarding bioavailability. It also targets to deliver an update on the recent advances in the involvement of anthocyanins in different pathologies with a focus on in vivo, in vitro, animal, and human clinical trials. Full article

(This article belongs to the Special Issue Bioactive Molecules: Isolation, Synthesis, Analysis, and Application in Medicinal Chemistry)

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46 pages, 43333 KiB

Open AccessReview

Plants Secondary Metabolites as Blood Glucose-Lowering Molecules

by Mayadah Bashir Shehadeh, Ghadeer A. R. Y. Suaifan and Ala’ Mustafa Abu-Odeh

Molecules 2021, 26(14), 4333; https://doi.org/10.3390/molecules26144333 - 17 Jul 2021

Cited by 50 | Viewed by 9562

Abstract

Recently, significant advances in modern medicine and therapeutic agents have been achieved. However, the search for effective antidiabetic drugs is continuous and challenging. Over the past decades, there has been an increasing body of literature related to the effects of secondary metabolites from [...] Read more.

Recently, significant advances in modern medicine and therapeutic agents have been achieved. However, the search for effective antidiabetic drugs is continuous and challenging. Over the past decades, there has been an increasing body of literature related to the effects of secondary metabolites from botanical sources on diabetes. Plants-derived metabolites including alkaloids, phenols, anthocyanins, flavonoids, stilbenoids, saponins, tannins, polysaccharides, coumarins, and terpenes can target cellular and molecular mechanisms involved in carbohydrate metabolism. In addition, they can grant protection to pancreatic beta cells from damage, repairing abnormal insulin signaling, minimizing oxidative stress and inflammation, activating AMP-activated protein kinase (AMPK), and inhibiting carbohydrate digestion and absorption. Studies have highlighted many bioactive naturally occurring plants’ secondary metabolites as candidates against diabetes. This review summarizes the current knowledge compiled from the latest studies published during the past decade on the mechanism-based action of plants-derived secondary metabolites that can target various metabolic pathways in humans against diabetes. It is worth mentioning that the compiled data in this review will provide a guide for researchers in the field, to develop candidates into environment-friendly effective, yet safe antidiabetics. Full article

(This article belongs to the Special Issue Bioactive Molecules: Isolation, Synthesis, Analysis, and Application in Medicinal Chemistry)

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