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18 pages, 3618 KiB

Open AccessArticle

The Effect of Rubus idaeus Polyphenols Extract in Induced Endometriosis in Rats

by Elena-Mihaela Jianu, Raluca Maria Pop, Luciana Mădălina Gherman, Floricuța Ranga, Antonia-Mihaela Levai, Vasile Rus, Sorana D. Bolboacă, Roxana-Adelina Ștefan, Mădălin Mihai Onofrei, Ionel-Daniel Nati, Ioana Alexandra Stoia, Paul-Andrei Ștefan, Carina Mihu and Carmen Mihaela Mihu

Molecules 2024, 29(4), 778; https://doi.org/10.3390/molecules29040778 - 08 Feb 2024

Viewed by 887

Abstract

Endometriosis is a common gynecological condition with a complex physio-pathological background. This study aimed to assess the role of Rubus idaeus leaf extract (RiDE) as a potential therapeutic agent in reducing the size of the endometriotic lesions and modulate the plasma expression of [...] Read more.

Endometriosis is a common gynecological condition with a complex physio-pathological background. This study aimed to assess the role of Rubus idaeus leaf extract (RiDE) as a potential therapeutic agent in reducing the size of the endometriotic lesions and modulate the plasma expression of MMP-2, MMP-9, and TGF-β1. The endometriotic lesions were induced in a rat model by the autologous transplant of endometrium. Thirty-six female rats, Wistar breed, with induced endometriosis, were divided into four groups and underwent treatment for 28 days. The CTRL group received 0.5 mL/day of the vehicle; the DG group received 1 mg/kg b.w./day dienogest; the RiDG group received 0.25 mL/kg b.w./day RiDE and the D+RiDG group received 1 mg/kg b.w./day dienogest and 0.25 mL/kg b.w./day RiDE, respectively. Rats’ weight, endometriotic lesion diameter and grade, and plasma levels of MMP-2, MMP-9, and TGF-β1 were assessed before and after treatment. The administration of RiDE in association with dienogest vs. dienogest determined a lower weight gain and a reduction in diameter of the endometriotic lesions. RiDE administration restored MMP2 and MMP9 plasma levels to initial conditions. Rubus idaeus extract may help in reducing dienogest-associated weight gain, lower the size of endometriotic lesions, and have anti-inflammatory effects through MMP2 and MMP9 reduction. Full article

(This article belongs to the Special Issue Bioactive Molecules Targeting Inflammation Processes in Related Diseases)

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17 pages, 7923 KiB

Open AccessArticle

Therapeutic Potential of Curcumin, a Bioactive Compound of Turmeric, in Prevention of Streptozotocin-Induced Diabetes through the Modulation of Oxidative Stress and Inflammation

by Abdullah Khalid Alsulaim, Turki Hussain Almutaz, Abdulaziz Ahmed Albati and Arshad Husain Rahmani

Molecules 2024, 29(1), 128; https://doi.org/10.3390/molecules29010128 - 25 Dec 2023

Viewed by 1363

Abstract

This study evaluates the anti-diabetic potential and underlying mechanisms of curcumin in streptozotocin (STZ)-induced type 2 diabetes mellitus (T2DM) rats. The rats were randomly divided into four groups: normal control, negative control (diabetic group), diabetic group receiving glibenclamide (positive control group), and curcumin [...] Read more.

This study evaluates the anti-diabetic potential and underlying mechanisms of curcumin in streptozotocin (STZ)-induced type 2 diabetes mellitus (T2DM) rats. The rats were randomly divided into four groups: normal control, negative control (diabetic group), diabetic group receiving glibenclamide (positive control group), and curcumin plus STZ (treatment group). The anti-diabetic activities of curcumin were examined at a dose of 50 mg/kg body weight through physiological, biochemical, and histopathological analysis. Compared to the normal control group rats, elevated levels of glucose, creatinine, urea, triglycerides (TG), and total cholesterol (TC) and low levels of insulin were found in the negative control rats. Curcumin treatment showed a significant decrease in these parameters and an increase in insulin level as compared to negative control rats. In negative control rats, a reduced level of antioxidant enzymes and an increased level of lipid peroxidation and inflammatory marker levels were noticed. Oral administration of curcumin significantly ameliorated such changes. From histopathological findings, it was noted that diabetic rats showed changes in the kidney tissue architecture, including the infiltration of inflammatory cells, congestion, and fibrosis, while oral administration of curcumin significantly reduced these changes. Expression of IL-6 and TNF-α protein was high in diabetic rats as compared to the curcumin treatment groups. Hence, based on biochemical and histopathological findings, this study delivers a scientific suggestion that curcumin could be a suitable remedy in the management of diabetes mellitus. Full article

(This article belongs to the Special Issue Bioactive Molecules Targeting Inflammation Processes in Related Diseases)

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13 pages, 3368 KiB

Open AccessArticle

An In Vivo Assessment of the Effect of Hexane Extract from Endlicheria paniculata Branches and Its Main Compound, Methyldehydrodieugenol B, on Murine Sponge-Induced Inflammation

by Bruno Antonio Ferreira, Rafael Aparecido Carvalho Souza, Francyelle Borges Rosa de Moura, Tiara da Costa Silva, Tais da Silva Adriano, Eduardo de Faria Franca, Raquel Maria Ferreira de Sousa, Fernanda de Assis Araújo, João Henrique Ghilardi Lago and Alberto de Oliveira

Molecules 2023, 28(13), 5247; https://doi.org/10.3390/molecules28135247 - 06 Jul 2023

Viewed by 807

Abstract

The present study aims to explore the anti-inflammatory potential activity of the hexane extract from branches (HEB) of Endlicheria paniculata (Lauraceae) and its main compound, methyldehydrodieugenol B, in the inflammatory response induced by a murine implant sponge model. HPLC-ESI/MS analysis of HEB led [...] Read more.

The present study aims to explore the anti-inflammatory potential activity of the hexane extract from branches (HEB) of Endlicheria paniculata (Lauraceae) and its main compound, methyldehydrodieugenol B, in the inflammatory response induced by a murine implant sponge model. HPLC-ESI/MS analysis of HEB led to the identification of six chemically related neolignans, with methyldehydrodieugenol B as the main compound. An in silico analysis of the pharmacokinetic parameters of the identified compounds suggested moderate solubility but good absorption and biodistribution in vivo. Thus, the treatment of mice with HEB using in vivo assays indicated that HEB promoted pro-inflammatory, antiangiogenic, and antifibrogenic effects, whereas treatment with methyldehydrodieugenol B caused anti-inflammatory, antifibrogenic, and antiangiogenic effects. The obtained results shown the therapeutic potential of HEB and methyldehydrodieugenol B in the treatment of pathologies associated with inflammation and angiogenesis, including chronic wounds. Full article

(This article belongs to the Special Issue Bioactive Molecules Targeting Inflammation Processes in Related Diseases)

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12 pages, 1081 KiB

Open AccessFeature PaperArticle

Antibacterial and Analgesic Properties of Beta-Caryophyllene in a Murine Urinary Tract Infection Model

by Kayle Dickson, Cassidy Scott, Hannah White, Juan Zhou, Melanie Kelly and Christian Lehmann

Molecules 2023, 28(10), 4144; https://doi.org/10.3390/molecules28104144 - 17 May 2023

Cited by 3 | Viewed by 1909

Abstract

Beta-caryophyllene has demonstrated anti-inflammatory effects in a variety of conditions, including interstitial cystitis. These effects are mediated primarily via the activation of the cannabinoid type 2 receptor. Additional antibacterial properties have recently been suggested, leading to our investigation of the effects of beta-caryophyllene [...] Read more.

Beta-caryophyllene has demonstrated anti-inflammatory effects in a variety of conditions, including interstitial cystitis. These effects are mediated primarily via the activation of the cannabinoid type 2 receptor. Additional antibacterial properties have recently been suggested, leading to our investigation of the effects of beta-caryophyllene in a murine model of urinary tract infection (UTI). Female BALB/c mice were intravesically inoculated with uropathogenic Escherichia coli CFT073. The mice received either beta-caryophyllene, antibiotic treatment using fosfomycin, or combination therapy. After 6, 24, or 72 h, the mice were evaluated for bacterial burden in the bladder and changes in pain and behavioral responses using von Frey esthesiometry. In the 24 h model, the anti-inflammatory effects of beta-caryophyllene were also assessed using intravital microscopy. The mice established a robust UTI by 24 h. Altered behavioral responses persisted 72 h post infection. Treatment with beta-caryophyllene resulted in a significant reduction in the bacterial burden in urine and bladder tissues 24 h post UTI induction and significant improvements in behavioral responses and intravital microscopy parameters, representing reduced inflammation in the bladder. This study demonstrates the utility of beta-caryophyllene as a new adjunct therapy for the management of UTI. Full article

(This article belongs to the Special Issue Bioactive Molecules Targeting Inflammation Processes in Related Diseases)

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15 pages, 7159 KiB

Open AccessArticle

α-Tocopherol Protects Lipopolysaccharide-Activated BV2 Microglia

by Maria Ester La Torre, Antonia Cianciulli, Vincenzo Monda, Marcellino Monda, Francesca Martina Filannino, Laura Antonucci, Anna Valenzano, Giuseppe Cibelli, Chiara Porro, Giovanni Messina, Maria Antonietta Panaro, Antonietta Messina and Rita Polito

Molecules 2023, 28(8), 3340; https://doi.org/10.3390/molecules28083340 - 10 Apr 2023

Cited by 2 | Viewed by 1957

Abstract

Microglia, the resident macrophage-like population in the central nervous system, play a crucial role in the pathogenesis of many neurodegenerative disorders by triggering an inflammatory response that leads to neuronal death. Neuroprotective compounds to treat or prevent neurodegenerative diseases are a new field [...] Read more.

Microglia, the resident macrophage-like population in the central nervous system, play a crucial role in the pathogenesis of many neurodegenerative disorders by triggering an inflammatory response that leads to neuronal death. Neuroprotective compounds to treat or prevent neurodegenerative diseases are a new field of study in modern medicine. Microglia are activated in response to inflammatory stimuli. The pathogenesis of various neurodegenerative diseases is closely related to the constant activation of microglia due to their fundamental role as a mediator of inflammation in the brain environment. α-Tocopherol, also known as vitamin E, is reported to possess potent neuroprotective effects. The goal of this study was to investigate the biological effects of vitamin E on BV2 microglial cells, as a possible neuroprotective and anti-inflammatory agent, following stimulation with lipopolysaccharide (LPS). The results showed that the pre-incubation of microglia with α-tocopherol can guarantee neuroprotective effects during microglial activation induced by LPS. α-Tocopherol preserved the branched morphology typical of microglia in a physiological state. It also reduced the migratory capacity; the production of pro-inflammatory and anti-inflammatory cytokines such as TNF-α and IL-10; and the activation of receptors such as TRL4 and CD40, which modulate the PI3K-Akt signaling pathway. The results of this study require further insights and research, but they present new scenarios for the application of vitamin E as an antioxidant for the purpose of greater neuroprotection in vivo for the prevention of possible neurodegenerative diseases. Full article

(This article belongs to the Special Issue Bioactive Molecules Targeting Inflammation Processes in Related Diseases)

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14 pages, 1498 KiB

Open AccessCommunication

Cornus mas L. Extract Targets the Specific Molecules of the Th17/Treg Developmental Pathway in TNBS-Induced Experimental Colitis in Rats

by Marta Szandruk-Bender, Beata Nowak, Anna Merwid-Ląd, Alicja Z. Kucharska, Małgorzata Krzystek-Korpacka, Iwona Bednarz-Misa, Benita Wiatrak, Adam Szeląg, Narcyz Piórecki and Tomasz Sozański

Molecules 2023, 28(7), 3034; https://doi.org/10.3390/molecules28073034 - 29 Mar 2023

Cited by 2 | Viewed by 1138

Abstract

Given that one of the crucial events in the pathogenesis of inflammatory bowel disease is the loss of homeostasis between Th17 and Treg cells, targeting the specific molecules of the Th17/Treg axis developmental pathway is a promising strategy for inflammatory bowel disease prevention [...] Read more.

Given that one of the crucial events in the pathogenesis of inflammatory bowel disease is the loss of homeostasis between Th17 and Treg cells, targeting the specific molecules of the Th17/Treg axis developmental pathway is a promising strategy for inflammatory bowel disease prevention and treatment. The current study aimed to assess the impact of cornelian cherry (Cornus mas L.) extract, rich in iridoids and polyphenols known for their potential anti-inflammatory activity, at two doses (20 or 100 mg/kg) on the crucial factors for Th17/Treg cell differentiation in the course of experimental colitis and compare this action with that of sulfasalazine. This study was conducted on the biobank colon tissue samples collected during the previous original experiment, in which colitis in rats was induced by trinitrobenzenesulfonic acid (TNBS). The levels of IL-6, RORγt, total STAT3, p-STAT3, and Foxp3 were determined by ELISA. The expression of PIAS3 mRNA was quantified by qPCR. Cornelian cherry extract at a dose of 100 mg/kg counteracted the TNBS-induced elevation of IL-6, RORγt, and p-STAT3 levels and a decrease in Foxp3 level and PIAS3 mRNA expression, while given concomitantly with sulfasalazine was more effective than sulfasalazine alone in reversing the TNBS-induced changes in IL-6, RORγt, total STAT3, p-STAT3, Foxp3 levels, and PIAS3 mRNA expression. The beneficial effect of cornelian cherry extract on experimental colitis may be due to its immunomodulatory activity reflected by the influence on factors regulating the Th17/Treg axis. Full article

(This article belongs to the Special Issue Bioactive Molecules Targeting Inflammation Processes in Related Diseases)

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12 pages, 2774 KiB

Open AccessArticle

New Triterpenoids and Anti-Inflammatory Constituents from Glinus oppositifolius

by Jih-Jung Chen, Chang-Syun Yang, Yu-Hui Chen, Che-Yi Chao, Yu-Chang Chen and Yeuh-Hsiung Kuo

Molecules 2023, 28(7), 2903; https://doi.org/10.3390/molecules28072903 - 23 Mar 2023

Cited by 1 | Viewed by 1528

Abstract

Three new triterpenoids—spergulagenin B (1), spergulagenin C (2), and spergulagenin D (3)—were isolated from the aerial part of Glinus oppositifolius, along with 17 known compounds (4–20). The structures of these new compounds [...] Read more.

Three new triterpenoids—spergulagenin B (1), spergulagenin C (2), and spergulagenin D (3)—were isolated from the aerial part of Glinus oppositifolius, along with 17 known compounds (4–20). The structures of these new compounds were identified by spectroscopic and MS analyses. Compounds 3, 5, 19, and 20 were evaluated for inhibition of nitric oxide production in LPS-stimulated RAW 264.7 cells with IC₅₀ values of 17.03, 18.21, 16.30, and 12.64 μM, respectively. Compounds 3, 5, and 20 exhibited inhibitory effects on LPS-induced nitric oxide production in RAW 264.7 cells with IC₅₀ values of 18.35 ± 1.34, 17.56 ± 1.41, and 14.27 ± 1.29 μM, respectively. Full article

(This article belongs to the Special Issue Bioactive Molecules Targeting Inflammation Processes in Related Diseases)

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14 pages, 4320 KiB

Open AccessArticle

The Effect of Hydroxytyrosol in Type II Epithelial-Mesenchymal Transition in Human Skin Wound Healing

by Wafa Ali Batarfi, Mohd Heikal Mohd Yunus and Adila A. Hamid

Molecules 2023, 28(6), 2652; https://doi.org/10.3390/molecules28062652 - 15 Mar 2023

Cited by 3 | Viewed by 1280

Abstract

Skin wound healing is a multiphase physiological process that involves the activation of numerous types of cells and is characterized by four phases, namely haemostasis, inflammatory, proliferative, and remodeling. However, on some occasions this healing becomes pathological, resulting in fibrosis. Epithelial mesenchymal transition [...] Read more.

Skin wound healing is a multiphase physiological process that involves the activation of numerous types of cells and is characterized by four phases, namely haemostasis, inflammatory, proliferative, and remodeling. However, on some occasions this healing becomes pathological, resulting in fibrosis. Epithelial mesenchymal transition (EMT) is an important process in which epithelial cells acquire mesenchymal fibroblast-like characteristics. Hydroxytyrosol (HT) is a phenolic compound extracted from olive oil and has been proven to have several health benefits. The aim of this study was to determine the effect of HT in type II EMT in human skin wound healing via cell viability, proliferation, migration, and proteins expression. Human dermal fibroblasts (HDF) isolated from skin samples were cultured in different concentrations of HT and EMT model, induced by adding 5 ng/mL of transforming growth factor-beta (TGF-β) to the cells. HT concentrations were determined via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cells’ migrations were evaluated using scratch and transwell migration assay. Protein expressions were evaluated via immunocytochemistry. The result showed that HT at 0.2% and 0.4% significantly increased the proliferation rate of HDF (p < 0.05) compared to control. Scratch assay after 24 h showed increased cell migration in cells treated with 0.4% HT (p < 0.05) compared to the other groups. After 48 h, both concentrations of HT showed increased cell migration (p < 0.05) compared to the TGF-β group. Transwell migration revealed that HT enhanced the migration capacity of cells significantly (p < 0.05) as compared to TGF-β and the control group. In addition, HT supplemented cells upregulate the expression of epithelial marker E-cadherin while downregulating the expression of mesenchymal marker vimentin in comparison to TGF-β group and control group. This study showed that HT has the ability to inhibit EMT, which has potential in the inhibition of fibrosis and persistent inflammation related to skin wound healing. Full article

(This article belongs to the Special Issue Bioactive Molecules Targeting Inflammation Processes in Related Diseases)

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17 pages, 3090 KiB

Open AccessArticle

Development of a Novel Apigenin Dosage form as a Substitute for the Modern Triple Antithrombotic Regimen

by Antonios D. Tsiailanis, Constantinos C. Tellis, Paraskevi Papakyriakopoulou, Androniki D. Kostagianni, Vasileios Gkalpinos, Christos M. Chatzigiannis, Nikolaos Kostomitsopoulos, Georgia Valsami, Alexandros D. Tselepis and Andreas G. Tzakos

Molecules 2023, 28(5), 2311; https://doi.org/10.3390/molecules28052311 - 02 Mar 2023

Cited by 1 | Viewed by 1652

Abstract

The simultaneous administration of three antiplatelet agents has been proposed as an efficient strategy for the secondary prevention of atherothrombotic events and is included in the European guidelines. However, this strategy presented an increased risk of bleeding; therefore, the identification of new antiplatelet [...] Read more.

The simultaneous administration of three antiplatelet agents has been proposed as an efficient strategy for the secondary prevention of atherothrombotic events and is included in the European guidelines. However, this strategy presented an increased risk of bleeding; therefore, the identification of new antiplatelet agents, with improved efficacy and diminished side effects, is of great importance. In silico studies, UPLC/MS Q-TOF plasma stability, in vitro platelet aggregation experiments, and pharmacokinetic studies were exploited. In the present study, it has been predicted that the flavonoid apigenin could target different platelet activation pathways, including P2Y12, protease-activated receptor-1 (PAR-1), and cyclooxygenase 1 (COX-1). To enhance apigenin’s potency, hybridization with docosahexaenoic acid (DHA) was performed, as fatty acids have illustrated potent efficacy against cardiovascular diseases (CVDs). The new molecular hybrid, termed 4′-DHA-apigenin, demonstrated enhanced inhibitory activity against platelet aggregation induced by thrombin receptor activator peptide-6 (TRAP-6), adenosine diphosphate (ADP), and arachidonic acid (AA), with respect to the parent apigenin. The 4′-DHA-apigenin hybrid illustrated an almost 2-fold enhanced inhibitory activity, with respect to apigenin, and an almost 3-fold enhanced inhibitory activity, with respect to DHA, for the ADP-induced platelet aggregation. Additionally, the hybrid presented a more than 12-fold enhanced inhibitory activity with respect to DHA for the TRAP-6 induced platelet aggregation. Furthermore, a 2-fold enhanced inhibitory activity was recorded for the 4′-DHA-apigenin hybrid for the AA-induced platelet aggregation with respect to apigenin. To surmount the reduced LC-MS based plasma stability, a novel dosage form in olive oil has been developed. The 4′-DHA-apigenin olive oil-based formulation presented an enhanced antiplatelet inhibitory effect in three activation pathways. To further explore the pharmacokinetic profile of 4′-DHA-apigenin in olive oil formulations, a UPLC/MS Q-TOF protocol has been established to quantify the serum levels of apigenin after oral administration to C57BL/6J wild type mice. The olive oil-based formulation of 4′-DHA-apigenin demonstrated an increase in apigenin bioavailability of 262 %. This study may offer a new therapeutic strategy tailored to improve the treatment of CVDs. Full article

(This article belongs to the Special Issue Bioactive Molecules Targeting Inflammation Processes in Related Diseases)

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13 pages, 2384 KiB

Open AccessFeature PaperArticle

Acenocoumarol Exerts Anti-Inflammatory Activity via the Suppression of NF-κB and MAPK Pathways in RAW 264.7 Cells

by Hyun-Ju Han and Chang-Gu Hyun

Molecules 2023, 28(5), 2075; https://doi.org/10.3390/molecules28052075 - 22 Feb 2023

Cited by 10 | Viewed by 1872

Abstract

The repurposing of already-approved drugs has emerged as an alternative strategy to rapidly identify effective, safe, and conveniently available new therapeutic indications against human diseases. The current study aimed to assess the repurposing of the anticoagulant drug acenocoumarol for the treatment of chronic [...] Read more.

The repurposing of already-approved drugs has emerged as an alternative strategy to rapidly identify effective, safe, and conveniently available new therapeutic indications against human diseases. The current study aimed to assess the repurposing of the anticoagulant drug acenocoumarol for the treatment of chronic inflammatory diseases (e.g., atopic dermatitis and psoriasis) and investigate the potential underlying mechanisms. For this purpose, we used murine macrophage RAW 264.7 as a model in experiments aimed at investigating the anti-inflammatory effects of acenocoumarol in inhibiting the production of pro-inflammatory mediators and cytokines. We demonstrate that acenocoumarol significantly decreases nitric oxide (NO), prostaglandin (PG)E₂, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β levels in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Acenocoumarol also inhibits the expression of NO synthase (iNOS) and cyclooxygenase (COX)-2, potentially explaining the acenocoumarol-induced decrease in NO and PGE₂ production. In addition, acenocoumarol inhibits the phosphorylation of mitogen-activated protein kinases (MAPKs), c-Jun N terminal kinase (JNK), p38 MAPK, and extracellular signal-regulated kinase (ERK), in addition to decreasing the subsequent nuclear translocation of nuclear factor κB (NF-κB). This indicates that acenocoumarol attenuates the macrophage secretion of TNF-α, IL-6, IL-1β, and NO, inducing iNOS and COX-2 expression via the inhibition of the NF-κB and MAPK signaling pathways. In conclusion, our results demonstrate that acenocoumarol can effectively attenuate the activation of macrophages, suggesting that acenocoumarol is a potential candidate for drug repurposing as an anti-inflammatory agent. Full article

(This article belongs to the Special Issue Bioactive Molecules Targeting Inflammation Processes in Related Diseases)

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21 pages, 3291 KiB

Open AccessArticle

Synthesis and Biological Evaluation of Octahydroquinazolinones as Phospholipase A2, and Protease Inhibitors: Experimental and Theoretical Exploration

by Md. Afroz Bakht, Thangaiyan Pooventhiran, Renjith Thomas, Mehnaz Kamal, Israf Ud Din, Najeeb Ur Rehman, Imtiaz Ali, Noushin Ajmal and Mohamed Jawed Ahsan

Molecules 2023, 28(4), 1944; https://doi.org/10.3390/molecules28041944 - 17 Feb 2023

Cited by 2 | Viewed by 1640

Abstract

Phospholipase A2 (PLA2) promotes inflammation via lipid mediators and releases arachidonic acid (AA), and these enzymes have been found to be elevated in a variety of diseases, including rheumatoid arthritis, sepsis, and atherosclerosis. The mobilization of AA by PLA2 and subsequent synthesis of [...] Read more.

Phospholipase A2 (PLA2) promotes inflammation via lipid mediators and releases arachidonic acid (AA), and these enzymes have been found to be elevated in a variety of diseases, including rheumatoid arthritis, sepsis, and atherosclerosis. The mobilization of AA by PLA2 and subsequent synthesis of prostaglandins are regarded as critical events in inflammation. Inflammatory processes may be treated with drugs that inhibit PLA2, thereby blocking the COX and LOX pathways in the AA cascade. To address this issue, we report herein an efficient method for the synthesis of a series of octahydroquinazolinone compounds (4a–h) in the presence of the catalyst Pd-HPW/SiO₂ and their phospholipase A2, as well as protease inhibitory activities. Among eight compounds, two of them exhibited overwhelming results against PLA2 and protease. By using FT-IR, Raman, NMR, and mass spectroscopy, two novel compounds were thoroughly studied. After carefully examining the SAR of the investigated compounds against these enzymes, it was found that compounds (4a, 4b) containing both electron-donating and electron-withdrawing groups on the phenyl ring exhibited higher activity than compounds with only one of these groups. DFT studies were employed to study the electronic nature and reactivity properties of the molecules by optimizing at the BLYP/cc-pVDZ. Natural bond orbitals helped to study the various electron delocalizations in the molecules, and the frontier molecular orbitals helped with the reactivity and stability parameters. The nature and extent of the expressed biological activity of the molecule were studied using molecular docking with human non-pancreatic secretory phospholipase A2 (hnps-PLA2) (PDB ID: 1DB4) and protease K (PDB ID: 2PWB). The drug-ability of the molecule has been tested using ADMET, and pharmacodynamics data have been extracted. Both the compounds qualify for ADME properties and follow Lipinski’s rule of five. Full article

(This article belongs to the Special Issue Bioactive Molecules Targeting Inflammation Processes in Related Diseases)

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15 pages, 4796 KiB

Open AccessArticle

Neobaicalein Inhibits Th17 Cell Differentiation Resulting in Recovery of Th17/Treg Ratio through Blocking STAT3 Signaling Activation

by Jian-Yu Chen, Ying-Jie Yang, Xue-Qin Ma, Qi Cao, Shan-Shan Wei, Rong-Rong Pan, Li-Hong Nan, Yao-Jun Liu, Yan Cao, Xiao-Yun Tian, Shan Deng, Zai-Xing Cheng, Can-Jian Wang, Tao Chen, Yan-Fang Zheng and Ming-Qing Huang

Molecules 2023, 28(1), 18; https://doi.org/10.3390/molecules28010018 - 20 Dec 2022

Cited by 3 | Viewed by 1456

Abstract

Huangqin is the dried root of Scutellaria baicalensis Georgi, which has been widely utilized for heat-clearing (Qingre) and dewetting (Zaoshi), heat-killed (Xiehuo) and detoxifying (Jiedu) in the concept of Traditional Chinese Medicine and is used for treating inflammation and cancer in clinical formulas. [...] Read more.

Huangqin is the dried root of Scutellaria baicalensis Georgi, which has been widely utilized for heat-clearing (Qingre) and dewetting (Zaoshi), heat-killed (Xiehuo) and detoxifying (Jiedu) in the concept of Traditional Chinese Medicine and is used for treating inflammation and cancer in clinical formulas. Neobaicalein (NEO) is of flavonoid isolated from Huangqin and has been reported to possess prominent anti-inflammatory effects in published work. Th17/Treg balance shift to Th17 cells is an essential reason for autoimmune inflammatory diseases. However, the role NEO plays in Th17 and Treg and the underlying mechanism has not been elucidated yet. Network pharmacology-based study revealed that NEO predominantly regulated IL-17 signaling pathway. Moreover, our result shown that NEO (3–30 μmol/L) down-regulated Th17 differentiation and cellular supernatant and intracellular IL-17A level and tumor necrosis factor α production in a concentration-dependent manner. The further mechanism research revealed that NEO also specifically inhibited phosphorylation of STAT3(Tyr725) and STAT4 (Y693) without influence on activation of STAT5 and STAT6 in splenocytes. Immunofluorescence results illuminated that NEO effectively blocked STAT3 translocated into nucleus. Interestingly, NEO at appreciated dose could only inhibit Th17 cell differentiation and have no effect on Treg differentiation. The present study revealed that NEO effectively inhibited Th17 cell differentiation through specifically blocking the activation of STAT3 signaling without inactivation of STAT5 and STAT6. Additional inhibitory effect on activation of STAT4 by NEO also suggested the potential for antagonism against Th1 differentiation. All work suggested that NEO may be a potential candidate for immunoregulation and treating autoimmune inflammatory diseases through inhibiting immune cell viability and T cell differentiation. Full article

(This article belongs to the Special Issue Bioactive Molecules Targeting Inflammation Processes in Related Diseases)

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13 pages, 3868 KiB

Open AccessArticle

Potential Anti-Tumor Activity of Nardoguaianone L Isolated from Nardostachys jatamansi DC. in SW1990 Cells

by Chun-Yan Sang, Yi-Dan Zheng, Li-Mei Ma, Kai Wang, Cheng-Bo Wang, Tian Chai, Komila A. Eshbakova and Jun-Li Yang

Molecules 2022, 27(21), 7490; https://doi.org/10.3390/molecules27217490 - 03 Nov 2022

Cited by 1 | Viewed by 1487

Abstract

Natural products (NPs) were a rich source of diverse bioactive molecules. Most anti-tumor agents were built on natural scaffolds. Nardostachys jatamansi DC. was an important plant used to process the traditional Chinese herbal medicines “gansong”. Pancreatic cancer was the fourth most common cause [...] Read more.

Natural products (NPs) were a rich source of diverse bioactive molecules. Most anti-tumor agents were built on natural scaffolds. Nardostachys jatamansi DC. was an important plant used to process the traditional Chinese herbal medicines “gansong”. Pancreatic cancer was the fourth most common cause of cancer-related death in the world. Hence, there was an urgent need to develop novel agents for the treatment of pancreatic cancer. In this paper, nardoguaianone L (G-6) is isolated from N. jatamansi, which inhibited SW1990 cells colony formation and cell migration, and induced cell apoptosis. Furthermore, we analyzed the differential expression proteins after treatment with G-6 in SW1990 cells by using iTRAQ/TMT-based quantitative proteomics technology, and the results showed that G-6 regulated 143 proteins’ differential expression by GO annotation, including biological process, cellular component, and molecular function. Meanwhile, KEGG enrichment found that with Human T-cell leukemia virus, one infection was the most highly enhanced pathway. Furthermore, the MET/PTEN/TGF-β pathway was identified as a significant pathway that had important biological functions, including cell migration and motility by PPI network analysis in SW1990 cells. Taken together, our study found that G-6 is a potential anti-pancreatic cancer agent with regulation of MET/PTEN/TGF-β pathway. Full article

(This article belongs to the Special Issue Bioactive Molecules Targeting Inflammation Processes in Related Diseases)

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11 pages, 5399 KiB

Open AccessArticle

A Carabrane-Type Sesquiterpenolide Carabrone from Carpesium cernuum Inhibits SW1990 Pancreatic Cancer Cells by Inducing Ferroptosis

by Yi-Dan Zheng, Ying Zhang, Jun-Yi Ma, Chun-Yan Sang and Jun-Li Yang

Molecules 2022, 27(18), 5841; https://doi.org/10.3390/molecules27185841 - 09 Sep 2022

Cited by 3 | Viewed by 1793

Abstract

Pancreatic cancer has an extremely poor prognosis, and the clinical drugs for the treatment of pancreatic cancer are usually multi-drug combinations. Therefore, it is necessary to search for and find specific new bioactive agents against pancreatic cancer. Carabrone is a carabrane-type sesquiterpenolide extracted [...] Read more.

Pancreatic cancer has an extremely poor prognosis, and the clinical drugs for the treatment of pancreatic cancer are usually multi-drug combinations. Therefore, it is necessary to search for and find specific new bioactive agents against pancreatic cancer. Carabrone is a carabrane-type sesquiterpenolide extracted from Carpesium cernuum L., and this natural compound has been reported to be a potential anti-tumor agent. However, there are few reports on the function of carabrone related to anti-tumor activity in pancreatic cancer. Herein, cell experiments indicated that carabrone had anti-proliferation inhibition and anti-migration and anti-invasion activity against SW1990 cells. Furthermore, the tandem mass spectrometry and network pharmacology analysis showed that this activity may be related to the ferroptosis and Hippo signaling pathway. Taken together, our results demonstrated that carabrone exhibited prominent anti-pancreatic cancer activity and could be a promising agent against pancreatic cancer. Full article

(This article belongs to the Special Issue Bioactive Molecules Targeting Inflammation Processes in Related Diseases)

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18 pages, 1494 KiB

Open AccessArticle

Polyphenols from Dichrostachys cinerea Fruits Anti-Inflammatory, Analgesic, and Antioxidant Capacity in Freund’s Adjuvant-Induced Arthritic Rat Model

by Gisèle Atsang à Kiki, Raluca Maria Pop, Octavia Sabin, Ioana Corina Bocsan, Veronica Sanda Chedea, Sonia Ancuța Socaci, Alina Elena Pârvu, Egre Finsia, Takvou Francis, Zramah Mathieu and Anca Dana Buzoianu

Molecules 2022, 27(17), 5445; https://doi.org/10.3390/molecules27175445 - 25 Aug 2022

Cited by 2 | Viewed by 1811

Abstract

Dichrostachys cinerea (L.) Wigth & Arn. (DC) is widely used in traditional medicine against several inflammatory diseases, especially rheumatoid arthritis, because of its antioxidant and anti-inflammatory effects. This study aimed to characterize the polyphenol-rich DC fruit extracts and investigate the analgesic, anti-inflammatory, and [...] Read more.

Dichrostachys cinerea (L.) Wigth & Arn. (DC) is widely used in traditional medicine against several inflammatory diseases, especially rheumatoid arthritis, because of its antioxidant and anti-inflammatory effects. This study aimed to characterize the polyphenol-rich DC fruit extracts and investigate the analgesic, anti-inflammatory, and antioxidant effects in a rat inflammation model induced by complete Freund’s adjuvant (CFA). Water and ethanolic extracts were characterized using liquid chromatography coupled with mass spectrometry (LC-MS), Fourier-transform infrared (FTIR) spectroscopy, and gas chromatography coupled with mass spectrometry (GC-MS). The polyphenol-rich extracts were administered in three different concentrations for 30 days. Pain threshold, thermal hyperalgesia, edema, and serum biomarkers specific to inflammatory processes or oxidative stress were evaluated. Both extracts were rich in polyphenolic compounds, mainly flavan-3-ols, proanthocyanidins, and flavone glycosides, which had important in vitro antioxidant capacity. DC fruit extracts administration had the maximum antinociceptive and anti-inflammatory effects after one day since the CFA injection and showed promising results for long-term use as well. The measurement of pro-inflammatory cytokines, cortisol, and oxidative stress parameters showed that DC extracts significantly reduced these parameters, being dose and extract-type dependent. These results showed potential anti-inflammatory, analgesic, and antioxidative properties and revealed the necessity of using a standardized polyphenolic DC extract to avoid result variability. Full article

(This article belongs to the Special Issue Bioactive Molecules Targeting Inflammation Processes in Related Diseases)

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Review

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40 pages, 4309 KiB

Open AccessReview

Anti-Inflammatory and Cytotoxic Compounds Isolated from Plants of Euphorbia Genus

by Sarai Rojas-Jiménez, María Guadalupe Valladares-Cisneros, David Osvaldo Salinas-Sánchez, Julia Pérez-Ramos, Leonor Sánchez-Pérez, Salud Pérez-Gutiérrez and Nimsi Campos-Xolalpa

Molecules 2024, 29(5), 1083; https://doi.org/10.3390/molecules29051083 - 29 Feb 2024

Viewed by 672

Abstract

Euphorbia is a large genus of the Euphorbiaceae family. Around 250 species of the Euphorbia genus have been studied chemically and pharmacologically; different compounds have been isolated from these species, especially diterpenes and triterpenes. Several reports show that several species have anti-inflammatory activity, [...] Read more.

Euphorbia is a large genus of the Euphorbiaceae family. Around 250 species of the Euphorbia genus have been studied chemically and pharmacologically; different compounds have been isolated from these species, especially diterpenes and triterpenes. Several reports show that several species have anti-inflammatory activity, which can be attributed to the presence of diterpenes, such as abietanes, ingenanes, and lathyranes. In addition, it was found that some diterpenes isolated from different Euphorbia species have anti-cancer activity. In this review, we included compounds isolated from species of the Euphorbia genus with anti-inflammatory or cytotoxic effects published from 2018 to September 2023. The databases used for this review were Science Direct, Scopus, PubMed, Springer, and Google Scholar, using the keywords Euphorbia with anti-inflammatory or cytotoxic activity. In this review, 68 studies were collected and analyzed regarding the anti-inflammatory and anti-cancer activities of 264 compounds obtained from 36 species of the Euphorbia genus. The compounds included in this review are terpenes (95%), of which 68% are diterpenes, especially of the types ingenanes, abietanes, and triterpenes (approximately 15%). Full article

(This article belongs to the Special Issue Bioactive Molecules Targeting Inflammation Processes in Related Diseases)

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17 pages, 1091 KiB

Open AccessReview

Pharmacological Properties of Shionone: Potential Anti-Inflammatory Phytochemical against Different Diseases

by Varun Jaiswal and Hae-Jeung Lee

Molecules 2024, 29(1), 189; https://doi.org/10.3390/molecules29010189 - 28 Dec 2023

Cited by 1 | Viewed by 869

Abstract

Shionone is a triterpenoid that is the primary constituent of an important ancient Chinese medicine named Radix Asteris. It has emerged as an attractive candidate against different important diseases, including interstitial cystitis, colitis, cancer, Parkinson’s disease, and urinary tract infections, and was found [...] Read more.

Shionone is a triterpenoid that is the primary constituent of an important ancient Chinese medicine named Radix Asteris. It has emerged as an attractive candidate against different important diseases, including interstitial cystitis, colitis, cancer, Parkinson’s disease, and urinary tract infections, and was found to have a protective effect on multiple organs, including the colon, kidneys, lungs, brain, and bladder. The anti-inflammation activity of shionone may be considered an important property that imparts the positive health outcomes of shionone. Important molecular targets and markers such as TNF-α, STAT3, NLRP3, and NF-κB were also found to be targeted by shionone and were verified in different diseases. This suggests the possible potential of shionone against other diseases associated with these targets. Pharmacokinetic studies also support the therapeutic potential of shionone and provide the initial track that may be pursued for its development. Yet, the compilation of the pharmacological activities of shionone and its important genes and pathway targets are absent in the existing literature, which would direct its development as a therapeutic and/or supplement. Hence, the present review provides a compilation of information concerning pharmacological activities, highlights the existing holes, and proposes a specific direction for the expansion of shionone as a therapeutic against different diseases and conditions. Full article

(This article belongs to the Special Issue Bioactive Molecules Targeting Inflammation Processes in Related Diseases)

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29 pages, 1600 KiB

Open AccessReview

Potential Benefits of Antioxidant Phytochemicals in Type 2 Diabetes

by Arman Arabshomali, Shadi Bazzazzadehgan, Fakhri Mahdi and Zia Shariat-Madar

Molecules 2023, 28(20), 7209; https://doi.org/10.3390/molecules28207209 - 21 Oct 2023

Cited by 3 | Viewed by 1858

Abstract

The clinical relationship between diabetes and inflammation is well established. Evidence clearly indicates that disrupting oxidant-antioxidant equilibrium and elevated lipid peroxidation could be a potential mechanism for chronic kidney disease associated with type 2 diabetes mellitus (T2DM). Under diabetic conditions, hyperglycemia, especially inflammation, [...] Read more.

The clinical relationship between diabetes and inflammation is well established. Evidence clearly indicates that disrupting oxidant-antioxidant equilibrium and elevated lipid peroxidation could be a potential mechanism for chronic kidney disease associated with type 2 diabetes mellitus (T2DM). Under diabetic conditions, hyperglycemia, especially inflammation, and increased reactive oxygen species generation are bidirectionally associated. Inflammation, oxidative stress, and tissue damage are believed to play a role in the development of diabetes. Although the exact mechanism underlying oxidative stress and its impact on diabetes progression remains uncertain, the hyperglycemia-inflammation-oxidative stress interaction clearly plays a significant role in the onset and progression of vascular disease, kidney disease, hepatic injury, and pancreas damage and, therefore, holds promise as a therapeutic target. Evidence strongly indicates that the use of multiple antidiabetic medications fails to achieve the normal range for glycated hemoglobin targets, signifying treatment-resistant diabetes. Antioxidants with polyphenols are considered useful as adjuvant therapy for their potential anti-inflammatory effect and antioxidant activity. We aimed to analyze the current major points reported in preclinical, in vivo, and clinical studies of antioxidants in the prevention or treatment of inflammation in T2DM. Then, we will share our speculative vision for future diabetes clinical trials. Full article

(This article belongs to the Special Issue Bioactive Molecules Targeting Inflammation Processes in Related Diseases)

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