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Anticancer, Antioxidant, and Anti-inflammatory Activities of Natural Products

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

Deadline for manuscript submissions: closed (30 June 2024) | Viewed by 18119

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Prof. Dr. Anna Bogucka-Kocka

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Chair and Department of Biology with Genetics, Medical University of Lublin, Chodźki Str. 4a, 20-093 Lublin, Poland
Interests: chemoprevention; herbal medicine; biological activities; natural product drug discovery; pharmacology; molecular biology; genetics
Special Issues, Collections and Topics in MDPI journals

Dr. Katarzyna Dos Santos Szewczyk

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Department of Pharmaceutical Botany, Medical University of Lublin, 20-093 Lublin, Poland
Interests: phytochemicals; natural product chemistry; bioactivity; phytochemical analysis; extraction; biological activities; phenolic compounds; natural product isolation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is devoted to presenting research concerning the antioxidant, anticancer, and anti-inflammatory activities of natural products.

Medicinal plants have been traditionally used in the treatment of several human diseases, and their therapeutic properties can be assigned to the different chemical compounds isolated within them. Of considerable importance, compounds with antioxidant, anticancer, or anti-inflammatory properties may be found in plants and are responsible for their preventive effects in various diseases caused by oxidative stress, among others. Oxidative stress plays a pivotal role in morbidity among people with multifarious diseases. There is a lot of research involving the influence of oxidative stress on the impairment of cells, tissues, and even the whole body. Moreover, many reports suggest that free radicals are involved in the triggering of various disorders, such as arteriosclerosis, Alzheimer’s, and Parkinson’s diseases, as well as many types of cancer.

Recently, scientists have focused on the discovery of plant substances that work effectively against various diseases without causing significant side effects. Therefore, in most respects, natural products are becoming more popular than synthetic ones, as they seem to possess lower toxicity levels and a higher efficacy. Thus, it is of crucial importance to provide new sources of natural compounds with significant therapeutic profiles.

Prof. Dr. Anna Bogucka-Kocka
Dr. Katarzyna Dos Santos Szewczyk
Guest Editors

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Keywords

natural products
anticancer
antioxidant
anti-inflammatory
plant extracts
derived compounds
oxidative stress

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Published Papers (8 papers)

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Research

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18 pages, 2049 KiB

Open AccessArticle

Ethyl Acetate Fraction from Eleutherococcus divaricatus Root Extract as a Promising Source of Compounds with Anti-Hyaluronidase, Anti-Tyrosinase, and Antioxidant Activity but Not Anti-Melanoma Activity

by Jakub Gębalski, Milena Małkowska, Sylwia Wnorowska, Dorota Gawenda-Kempczyńska, Maciej Strzemski, Magdalena Wójciak, Artur Słomka, Jan Styczyński and Daniel Załuski

Molecules 2024, 29(15), 3640; https://doi.org/10.3390/molecules29153640 - 1 Aug 2024

Viewed by 1241

Abstract

Eleutherococcus divaricatus (Siebold and Zucc.) S. Y. Hu. has been used in Traditional Chinese Medicine (TCM) due to its anticancer, immunostimulant, and anti-inflammatory activities. However, its mechanism of action and chemical composition are still insufficiently understood and require more advanced research, especially for cases in which anti-inflammatory properties are beneficial. The aim of this study was to evaluate the impact of E. divaricatus root extracts and fractions on proinflammatory serum hyaluronidase and tyrosinase in children diagnosed with acute lymphoblastic leukemia. Antioxidant and anti-melanoma activities were also examined and correlated with metabolomic data. For the first time, we discovered that the ethyl acetate fraction significantly inhibits hyaluronidase activity, with mean group values of 55.82% and 63.8% for aescin used as a control. However, interestingly, the fraction showed no activity against human tyrosinase, and in A375 melanoma cells treated with a doxorubicin fraction, doxorubicin activity decreased. This fraction exhibited the most potent antioxidant activity, which can be attributed to high contents of polyphenols, especially caffeic acid (24 mg/g). The findings suggest an important role of the ethyl acetate fraction in hyaluronidase inhibition, which may additionally indicate its anti-inflammatory property. The results suggest that this fraction can be used in inflammatory-related diseases, although with precautions in cases of patients undergoing chemotherapy. Full article

(This article belongs to the Special Issue Anticancer, Antioxidant, and Anti-inflammatory Activities of Natural Products)

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28 pages, 4440 KiB

Open AccessArticle

Immunomodulatory, Antioxidant, and Potential Anticancer Activity of the Polysaccharides of the Fungus Fomitiporia chilensis

by Roberto T. Abdala-Díaz, Virginia Casas-Arrojo, Pablo Castro-Varela, Cristian Riquelme, Paloma Carrillo, Miguel Ángel Medina, Casimiro Cárdenas, José Becerra and Claudia Pérez Manríquez

Molecules 2024, 29(15), 3628; https://doi.org/10.3390/molecules29153628 - 31 Jul 2024

Viewed by 1287

Abstract

Fomitiporia species have aroused the interest of numerous investigations that reveal their biological activity and medicinal potential. The present investigation shows the antioxidant, anticancer, and immunomodulatory activity of acidic polysaccharides obtained from the fungus Fomitiporia chilensis. The acidic polysaccharides were obtained for acidic precipitation with 2% O-N-cetylpyridinium bromide. Chemical analysis was performed using FT-IR and GC-MS methods. The antioxidant capacity of acidic polysaccharides from F. chilensis was evaluated by scavenging free radicals with an ABTS assay. Macrophage proliferation and cytokine production assays were used to determine the immunomodulatory capacity of the polysaccharides. Anti-tumor and cytotoxicity activity was evaluated with an MTT assay in the U-937, HTC-116, and HGF-1 cell lines. The effect of polysaccharides on the cell cycle of the HCT-116 cell line was determined for flow cytometry. Fourier Transform-infrared characterization revealed characteristic absorption peaks for polysaccharides, whereas the GC-MS analysis detected three peaks corresponding to D-galactose, galacturonic acid, and D-glucose. The secreted TNF-α concentration was increased when the cell was treated with 2 mg mL⁻¹ polysaccharides, whereas the IL-6 concentration was increased with all of the evaluated polysaccharide concentrations. A cell cycle analysis of HTC-116 treated with polysaccharides evidenced that the acidic polysaccharides from F. chilensis induce an increase in the G0/G1 cell cycle phase, increasing the apoptotic cell percentage. Results from a proteomic analysis suggest that some of the molecular mechanisms involved in their antioxidant and cellular detoxifying effects and justify their traditional use in heart diseases. Proteomic data are available through ProteomeXchange under identifier PXD048361. The study on acidic polysaccharides from F. chilensis has unveiled their diverse biological activities, including antioxidant, anticancer, and immunomodulatory effects. These findings underscore the promising therapeutic applications of acidic polysaccharides from F. chilensis, warranting further pharmaceutical and medicinal research exploration. Full article

(This article belongs to the Special Issue Anticancer, Antioxidant, and Anti-inflammatory Activities of Natural Products)

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15 pages, 997 KiB

Open AccessArticle

Potential Anti-Inflammatory Constituents from Aesculus wilsonii Seeds

by Ping Zhang, Lequan Yu, Huina Cao, Jingya Ruan, Fei Li, Lijie Wu, Yi Zhang and Tao Wang

Molecules 2024, 29(5), 1136; https://doi.org/10.3390/molecules29051136 - 3 Mar 2024

Viewed by 1306

Abstract

A chemical study of Aesculus wilsonii Rehd. (also called Suo Luo Zi) and the in vitro anti-inflammatory effects of the obtained compounds was conducted. Retrieving results through SciFinder showed that there were four unreported compounds, aeswilosides I–IV (1–4), along with fourteen known isolates (5–18). Their structures were elucidated by extensive spectroscopic methods such as UV, IR, NMR, [α]_D, and MS spectra, as well as acid hydrolysis. Among the known ones, compounds 5, 6, 8–10, and 12–16 were obtained from the Aesculus genus for the first time; compounds 7, 11, 17, and 18 were first identified from this plant. The NMR data of 5 and 18 were reported first. The effects of 1–18 on the release of nitric oxide (NO) from lipopolysaccharide (LPS)-induced RAW264.7 cells were determined. The results showed that at concentrations of 10, 25, and 50 μM, the novel compounds, aeswilosides I (1) and IV (4), along with the known ones, 1-(2-methylbutyryl)phloroglucinyl-glucopyranoside (10) and pisuminic acid (15), displayed significant inhibitory effects on NO production in a concentration-dependent manner. It is worth mentioning that compound 10 showed the best NO inhibitory effect with a relative NO production of 88.1%, which was close to that of the positive drug dexamethasone. The Elisa experiment suggested that compounds 1, 4, 10, and 15 suppressed the release of TNF-α and IL-1β as well. In conclusion, this study enriches the spectra of compounds with potential anti-inflammatory effects in A. wilsonii and provides new references for the discovery of anti-inflammatory lead compounds, but further mechanistic research is still needed. Full article

(This article belongs to the Special Issue Anticancer, Antioxidant, and Anti-inflammatory Activities of Natural Products)

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17 pages, 10719 KiB

Open AccessArticle

6-Shogaol Ameliorates Liver Inflammation and Fibrosis in Mice on a Methionine- and Choline-Deficient Diet by Inhibiting Oxidative Stress, Cell Death, and Endoplasmic Reticulum Stress

by Ah Young Yang, Kiryeong Kim, Hyun Hee Kwon, Jaechan Leem and Jeong Eun Song

Molecules 2024, 29(2), 419; https://doi.org/10.3390/molecules29020419 - 15 Jan 2024

Cited by 1 | Viewed by 2101

Abstract

Non-alcoholic steatohepatitis (NASH) is becoming an increasingly serious global health threat, distinguished by hepatic lipid accumulation, inflammation, and fibrosis. There is a lack of approved pharmaceutical interventions for this disease, highlighting the urgent need for effective treatment. This study explores the hepatoprotective potential of 6-shogaol, a natural compound derived from ginger, in a methionine- and choline-deficient (MCD) dietary mouse model of NASH. Male C57BL/6J mice were subjected to the MCD diet for 4 weeks to induce NASH, with concurrent intraperitoneal administration of 6-shogaol (20 mg/kg) three times a week. While 6-shogaol did not impact body weight, liver weight, or hepatic lipid accumulation, it effectively mitigated liver injury, inflammation, and fibrosis in MCD diet-fed mice. Mechanistically, 6-shogaol inhibited lipid and DNA oxidation, restored hepatic glutathione levels, and regulated the expression of pro-oxidant and antioxidant enzymes. Furthermore, 6-shogaol inhibited apoptosis and necroptosis, as indicated by a decrease in TUNEL-stained cells and downregulation of apoptosis- and necroptosis-associated proteins. Additionally, 6-shogaol alleviated endoplasmic reticulum (ER) stress, as demonstrated by decreased expression of molecules associated with unfolded protein response pathways. These findings underscore the potential of 6-shogaol as a therapeutic intervention for NASH by targeting pathways related to oxidative stress, cell death, and ER stress. Full article

(This article belongs to the Special Issue Anticancer, Antioxidant, and Anti-inflammatory Activities of Natural Products)

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15 pages, 3385 KiB

Open AccessArticle

Triterpenoid and Coumarin Isolated from Astilbe grandis with Anti-Inflammatory Effects through Inhibiting the NF-κB Pathway in LPS-Induced RAW264.7 Cells

by Jin-Fang Luo, Lan Yue, Tian-Tai Wu, Chen-Liang Zhao, Jiang-Hai Ye, Kang He and Juan Zou

Molecules 2023, 28(15), 5731; https://doi.org/10.3390/molecules28155731 - 28 Jul 2023

Cited by 2 | Viewed by 1635

Abstract

The roots of Astilbe grandis, known as “Ma sang gou bang”, are used as a Miao traditional medicine with anti-inflammatory and analgesic properties. However, the active components and mechanism of action of this plant remain mostly uncharacterized. The aim of this study was to identify its active components and verify their pharmacological activity. The extract of A. grandis root was separated using various chromatographic methods. As a result, we obtained one novel triterpenoid, named astigranlactone (1), which has an unusual lactone moiety formed between C-7 and C-27. Additionally, a known coumarin compound, 11-O-galloyl bergenin (2) was isolated from this plant. The structures of these two compounds were elucidated by extensive NMR experiments in conjunction with HR-ESI-MS data. To the best of our knowledge, both compounds were isolated from this species for the first time. Moreover, we tested the anti-inflammation effect of the two compounds by establishing a cellular inflammation model induced by LPS in RAW264.7 cells. The effect of different concentrations of these compounds on the activity of RAW264.7 cells was assessed using a CCK8 assay. The levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in the supernatant of each group were evaluated using the Griess method and an enzyme-linked immunosorbent assay (ELISA). Western blot and quantitative real-time PCR (qRT-RCR) were used to measure the levels of cyclooxygenase 2 (COX-2) and nitric oxide synthase (iNOS) gene expression. Our findings revealed that these two compounds inhibited the high levels of NO, TNF-α, IL-6, IL-1β, COX-2, and iNOS (induced by LPS). Mechanistic studies demonstrated that these two compounds reduced the activation of the nuclear transcription factor-B (NF-κB) signaling pathway by inhibiting the phosphorylation of p65. Therefore, our study indicates that compounds 1 and 2 can exert a definite anti-inflammatory effect by inhibiting the NF-κB signaling pathway. Full article

(This article belongs to the Special Issue Anticancer, Antioxidant, and Anti-inflammatory Activities of Natural Products)

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15 pages, 1439 KiB

Open AccessArticle

Phytochemical Profiling, Antioxidant and Tyrosinase Regulatory Activities of Extracts from Herb, Leaf and In Vitro Culture of Achillea millefolium (Yarrow)

by Karolina Czech, Katarzyna Gaweł-Bęben, Agnieszka Szopa, Wirginia Kukula-Koch, Thomas Jakschitz, Günther Bonn, Shah Hussain, Paweł Kubica, Halina Ekiert and Kazimierz Głowniak

Molecules 2023, 28(12), 4791; https://doi.org/10.3390/molecules28124791 - 15 Jun 2023

Viewed by 2857

Abstract

Achillea millefolium L. is one of the most known medicinal plants with a broad spectrum of applications in the treatment of inflammation, pain, microbial infections and gastrointestinal disorders. In recent years, the extracts from A. millefolium have also been applied in cosmetics with cleansing, moisturizing, shooting, conditioning and skin-lightening properties. The growing demand for naturally derived active substances, worsening environmental pollution and excessive use of natural resources are causing increased interest in the development of alternative methods for the production of plant-based ingredients. In vitro plant cultures are an eco-friendly tool for continuous production of desired plant metabolites, with increasing applicability in cosmetics and dietary supplements. The purpose of the study was to compare phytochemical composition and antioxidant and tyrosinase inhibitory properties of aqueous and hydroethanolic extracts from A. millefolium obtained from field conditions (AmL and AmH extracts) and in vitro cultures (AmIV extracts). In vitro microshoot cultures of A. millefolium were obtained directly from seeds and harvested following 3 weeks of culture. Extracts prepared in water, 50% ethanol and 96% ethanol were compared for the total polyphenolic content, phytochemical content using the ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UHPLC-hr-qTOF/MS), antioxidant activity by DPPH scavenging assay and the influence on the activity of mushroom and murine tyrosinases. The phytochemical content of AmIV extracts was significantly different from AmL and AmH extracts. Most of the polyphenolic compounds identified in AmL and AmH extracts were present in AmIV extracts only in trace amounts and the major constituents presented in AmIV extracts were fatty acids. The total content of polyphenols in AmIV exceeded 0.25 mg GAE/g of dried extract, whereas AmL and AmH extracts contained from 0.46 ± 0.01 to 2.63 ± 0.11 mg GAE/g of dried extract, depending on the solvent used. The low content of polyphenols was most likely responsible for the low antioxidant activity of AmIV extracts (IC₅₀ values in DPPH scavenging assay >400 µg/mL) and the lack of tyrosinase inhibitory properties. AmIV extracts increased the activity of mushroom tyrosinase and tyrosinase present in B16F10 murine melanoma cells, whereas AmL and AmH extracts showed significant inhibitory potential. The presented data indicated that microshoot cultures of A. millefolium require further experimental research before they can be implemented as a valuable raw material for the cosmetics industry. Full article

(This article belongs to the Special Issue Anticancer, Antioxidant, and Anti-inflammatory Activities of Natural Products)

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Review

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27 pages, 1391 KiB

Open AccessReview

Anti-Neuroinflammatory Effects of Adaptogens: A Mini-Review

by Dagmara Wróbel-Biedrawa and Irma Podolak

Molecules 2024, 29(4), 866; https://doi.org/10.3390/molecules29040866 - 15 Feb 2024

Cited by 4 | Viewed by 4907

Abstract

Introduction: Adaptogens are a group of plants that exhibit complex, nonspecific effects on the human body, increasing its ability to adapt, develop resilience, and survive in stress conditions. They are found in many traditional medicinal systems and play a key role in restoring the body’s strength and stamina. Research in recent years has attempted to elucidate the mechanisms behind their pharmacological effects, but it appears that these effects are difficult to define precisely and involve multiple molecular pathways. Neuroinflammation: In recent years, chronic inflammation has been recognized as one of the common features of many central nervous system disorders (dementia and other neurodegenerative diseases, depression, anxiety, ischemic stroke, and infections). Because of the specific nature of the brain, this process is called neuroinflammation, and its suppression can result in an improvement of patients’ condition and may promote their recovery. Adaptogens as anti-inflammatory agents: As has been discovered, adaptogens display anti-inflammatory effects, which suggests that their application may be broader than previously thought. They regulate gene expression of anti- and proinflammatory cytokines (prostaglandins, leukotriens) and can modulate signaling pathways (e.g., NF-κB). Aim: This mini-review aims to present the anti-neuroinflammatory potential of the most important plants classified as adaptogens: Schisandra chinensis, Eleutherococcus senticosus, Rhodiola rosea and Withania somnifera. Full article

(This article belongs to the Special Issue Anticancer, Antioxidant, and Anti-inflammatory Activities of Natural Products)

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42 pages, 19891 KiB

Open AccessReview

Progress in Antimelanoma Research of Natural Triterpenoids and Their Derivatives: Mechanisms of Action, Bioavailability Enhancement and Structure Modifications

by Marta Grudzińska, Bogna Stachnik, Agnieszka Galanty, Agnieszka Sołtys and Irma Podolak

Molecules 2023, 28(23), 7763; https://doi.org/10.3390/molecules28237763 - 24 Nov 2023

Cited by 5 | Viewed by 1778

Abstract

Melanoma is one of the most dangerous forms of skin cancer, characterized by early metastasis and rapid development. In search for effective treatment options, much attention is given to triterpenoids of plant origin, which are considered promising drug candidates due to their well described anticancer properties and relatively low toxicity. This paper comprehensively summarizes the antimelanoma potential of natural triterpenoids, that are also used as scaffolds for the development of more effective derivatives. These include betulin, betulinic acid, ursolic acid, maslinic acid, oleanolic acid, celastrol and lupeol. Some lesser-known triterpenoids that deserve attention in this context are 22β-hydroxytingenone, cucurbitacins, geoditin A and ganoderic acids. Recently described mechanisms of action are presented, together with the results of preclinical in vitro and in vivo studies, as well as the use of drug delivery systems and pharmaceutical technologies to improve the bioavailability of triterpenoids. This paper also reviews the most promising structural modifications, based on structure–activity observations. In conclusion, triterpenoids of plant origin and some of their semi-synthetic derivatives exert significant cytotoxic, antiproliferative and chemopreventive effects that can be beneficial for melanoma treatment. Recent data indicate that their poor solubility in water, and thus low bioavailability, can be overcome by complexing with cyclodextrins, or the use of nanoparticles and ethosomes, thus making these compounds promising antimelanoma drug candidates for further development. Full article

(This article belongs to the Special Issue Anticancer, Antioxidant, and Anti-inflammatory Activities of Natural Products)

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