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12 pages, 2880 KiB

Open AccessArticle

Astragalus Complanatus Ethanol Attenuates Septic Shock by Exerting Anti-Inflammatory Effects on Macrophages

by Yo Sep Hwang, Jeewon Lim, Hyang Ran Yoon, Seong-Hoon Park, Aeyung Kim, Jun-Pil Jang, Hee Jun Cho and Hee Gu Lee

Int. J. Mol. Sci. 2024, 25(1), 384; https://doi.org/10.3390/ijms25010384 - 27 Dec 2023

Cited by 3 | Viewed by 1531

Abstract

Sepsis is a systemic inflammatory syndrome that results in multiple-organ failure caused by a dysregulated host immune response to microbial infection. Astragali complanati semen extract (ACSE) exhibits pharmacological activities, including antioxidant, anticancer, antiaging, and anti-diabetes effects. It is widely used in traditional medicine [...] Read more.

Sepsis is a systemic inflammatory syndrome that results in multiple-organ failure caused by a dysregulated host immune response to microbial infection. Astragali complanati semen extract (ACSE) exhibits pharmacological activities, including antioxidant, anticancer, antiaging, and anti-diabetes effects. It is widely used in traditional medicine to treat liver and kidney diseases; however, the protective effect of ACSE on sepsis and its mechanisms are unknown. In the present study, we investigated the anti-inflammatory effects and potential mechanisms of the action of ACSE on sepsis. We show that ACSE improved survival rates in mouse models of acute sepsis induced by CLP (cecal ligation and puncture) and LPS stimulation. ACSE administration decreased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in sepsis-induced mice. Furthermore, ACSE reduced the levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in the serum of septic mice. ACSE treatment inhibited the expression of these proinflammatory genes in LPS-stimulated J774 macrophages. Moreover, ACSE inhibited the phosphorylation of the IκB kinase (IKK) and the nuclear translocation of p65 NF-κB by LPS stimulation in macrophages. These results reveal the mechanism underlying the protective effect of ACSE against sepsis by inhibiting NF-κB activation and suggest that ACSE could be a potential therapeutic candidate to treat acute inflammatory diseases. Full article

(This article belongs to the Special Issue Natural Products as Source of Molecules for Drugs and Therapy)

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25 pages, 10861 KiB

Open AccessArticle

Unlocking Prognostic Genes and Multi-Targeted Therapeutic Bioactives from Herbal Medicines to Combat Cancer-Associated Cachexia: A Transcriptomics and Network Pharmacology Approach

by Subramanian Muthamil, Pandiyan Muthuramalingam, Hyun-Yong Kim, Hyun-Jun Jang, Ji-Hyo Lyu, Ung Cheol Shin, Younghoon Go, Seong-Hoon Park, Hee Gu Lee, Hyunsuk Shin and Jun Hong Park

Int. J. Mol. Sci. 2024, 25(1), 156; https://doi.org/10.3390/ijms25010156 - 21 Dec 2023

Cited by 1 | Viewed by 1907

Abstract

Cachexia is a devastating fat tissue and muscle wasting syndrome associated with every major chronic illness, including cancer, chronic obstructive pulmonary disease, kidney disease, AIDS, and heart failure. Despite two decades of intense research, cachexia remains under-recognized by oncologists. While numerous drug candidates [...] Read more.

Cachexia is a devastating fat tissue and muscle wasting syndrome associated with every major chronic illness, including cancer, chronic obstructive pulmonary disease, kidney disease, AIDS, and heart failure. Despite two decades of intense research, cachexia remains under-recognized by oncologists. While numerous drug candidates have been proposed for cachexia treatment, none have achieved clinical success. Only a few drugs are approved by the FDA for cachexia therapy, but a very low success rate is observed among patients. Currently, the identification of drugs from herbal medicines is a frontier research area for many diseases. In this milieu, network pharmacology, transcriptomics, cheminformatics, and molecular docking approaches were used to identify potential bioactive compounds from herbal medicines for the treatment of cancer-related cachexia. The network pharmacology approach is used to select the 32 unique genes from 238 genes involved in cachexia-related pathways, which are targeted by 34 phytocompounds identified from 12 different herbal medicines used for the treatment of muscle wasting in many countries. Gene expression profiling and functional enrichment analysis are applied to decipher the role of unique genes in cancer-associated cachexia pathways. In addition, the pharmacological properties and molecular interactions of the phytocompounds were analyzed to find the target compounds for cachexia therapy. Altogether, combined omics and network pharmacology approaches were used in the current study to untangle the complex prognostic genes involved in cachexia and phytocompounds with anti-cachectic efficacy. However, further functional and experimental validations are required to confirm the efficacy of these phytocompounds as commercial drug candidates for cancer-associated cachexia. Full article

(This article belongs to the Special Issue Natural Products as Source of Molecules for Drugs and Therapy)

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15 pages, 3327 KiB

Open AccessArticle

Oat (Avena sativa L.) Sprouts Restore Skin Barrier Function by Modulating the Expression of the Epidermal Differentiation Complex in Models of Skin Irritation

by Hyo-Sung Kim, Hyun-Jeong Hwang, Woo-Duck Seo and Sun-Hee Do

Int. J. Mol. Sci. 2023, 24(24), 17274; https://doi.org/10.3390/ijms242417274 - 8 Dec 2023

Cited by 1 | Viewed by 1897

Abstract

Oats (Avena sativa L.) are used as therapeutic plants, particularly in dermatology. Despite numerous studies on their skin moisturization, anti-inflammation, and antioxidation effects, the precise molecular mechanisms of these effects are only partially understood. In this study, the efficacy of oat sprouts [...] Read more.

Oats (Avena sativa L.) are used as therapeutic plants, particularly in dermatology. Despite numerous studies on their skin moisturization, anti-inflammation, and antioxidation effects, the precise molecular mechanisms of these effects are only partially understood. In this study, the efficacy of oat sprouts in the treatment of allergic contact dermatitis (ACD) was investigated, and their specific phytoconstituents and exact mechanisms of action were identified. In the in vivo ACD model, by stimulating the mitogen-activated protein kinase signaling pathway, oat sprouts increased the expression levels of proteins associated with skin barrier formation, which are produced during the differentiation of keratinocytes. In addition, in a lipopolysaccharide-induced skin irritation model using HaCaT, steroidal saponins (avenacoside B and 26-deglucoavenacoside B) and a flavonoid (isovitexin-2-o-arabinoside) of oat sprouts regulated the genetic expression of the same proteins located on the adjacent locus of human chromosomes known as the epidermal differentiation complex (EDC). Furthermore, oat sprouts showed immunomodulatory functions. These findings suggest the potential for expanding the use of oat sprouts as a treatment option for various diseases characterized by skin barrier disruption. Full article

(This article belongs to the Special Issue Natural Products as Source of Molecules for Drugs and Therapy)

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14 pages, 7976 KiB

Open AccessArticle

Ginsenoside Rg3 Protects against Diabetic Cardiomyopathy and Promotes Adiponectin Signaling via Activation of PPAR-γ

by Chenyang Zhang, Huifang Yu, Jingxue Ye, Hongna Tong, Min Wang and Guibo Sun

Int. J. Mol. Sci. 2023, 24(23), 16736; https://doi.org/10.3390/ijms242316736 - 24 Nov 2023

Cited by 8 | Viewed by 1567

Abstract

Ginsenoside Rg3 extracted from Panax notoginseng has therapeutic effects on diabetes and heart diseases. However, the underlying mechanism of ginsenoside Rg3 on diabetic cardiomyopathy (DCM) remains unclear. 24-week-old diabetic db/db mice were treated with ginsenoside Rg3 for 12 weeks, then body weight, serum [...] Read more.

Ginsenoside Rg3 extracted from Panax notoginseng has therapeutic effects on diabetes and heart diseases. However, the underlying mechanism of ginsenoside Rg3 on diabetic cardiomyopathy (DCM) remains unclear. 24-week-old diabetic db/db mice were treated with ginsenoside Rg3 for 12 weeks, then body weight, serum lipids, adiponectin levels, as well as cardiac function and pathological morphology, were measured. The targets of ginsenoside Rg3 and its regulation of the adiponectin pathway were also evaluated on 3T3-L1 or H9c2 cells. Ginsenoside Rg3 directly bound to PPAR-γ, improving adiponectin secretion and promoting adiponectin signaling. Significantly attenuated overweight, hyperglycemia, and hyperlipidemia, as well as alleviated lipid accumulation and dysfunction in adipose, liver, and heart tissues, were observed in the ginsenoside Rg3-treated group. Ginsenoside Rg3 could be a promising drug targeting PPAR-γ to treat diabetic cardiomyopathy. Full article

(This article belongs to the Special Issue Natural Products as Source of Molecules for Drugs and Therapy)

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18 pages, 5849 KiB

Open AccessArticle

Metformin Suppresses Stemness of Non-Small-Cell Lung Cancer Induced by Paclitaxel through FOXO3a

by Zhimin Tang, Yilan Zhang, Zhengyi Yu and Zhijun Luo

Int. J. Mol. Sci. 2023, 24(23), 16611; https://doi.org/10.3390/ijms242316611 - 22 Nov 2023

Cited by 3 | Viewed by 1900

Abstract

Cancer stem cells (CSCs) play a pivotal role in drug resistance and metastasis. Among the key players, Forkhead box O3a (FOXO3a) acts as a tumor suppressor. This study aimed to unravel the role of FOXO3a in mediating the inhibitory effect of metformin on [...] Read more.

Cancer stem cells (CSCs) play a pivotal role in drug resistance and metastasis. Among the key players, Forkhead box O3a (FOXO3a) acts as a tumor suppressor. This study aimed to unravel the role of FOXO3a in mediating the inhibitory effect of metformin on cancer stemness derived from paclitaxel (PTX)-resistant non-small-cell lung cancer (NSCLC) cells. We showed that CSC-like features were acquired by the chronic induction of resistance to PTX, concurrently with inactivation of FOXO3a. In line with this, knockdown of FOXO3a in PTX-sensitive cells led to changes toward stemness, while overexpression of FOXO3a in PTX-resistant cells mitigated stemness in vitro and remarkably curbed the tumorigenesis of NSCLC/PTX cells in vivo. Furthermore, metformin suppressed the self-renewal ability of PTX-resistant cells, reduced the expression of stemness-related markers (c-MYC, Oct4, Nanog and Notch), and upregulated FOXO3a, events concomitant with the activation of AMP-activated protein kinase (AMPK). All these changes were recapitulated by silencing FOXO3a in PTX-sensitive cells. Intriguingly, the introduction of the AMPK dominant negative mutant offset the inhibitory effect of metformin on the stemness of PTX-resistant cells. In addition, FOXO3a levels were elevated by the treatment of PTX-resistant cells with MK2206 (an Akt inhibitor) and U0126 (a MEK inhibitor). Collectively, our findings indicate that metformin exerts its effect on FOXO3a through the activation of AMPK and the inhibition of protein kinase B (Akt) and MAPK/extracellular signal-regulated kinase (MEK), culminating in the suppression of stemness in paclitaxel-resistant NSCLC cells. Full article

(This article belongs to the Special Issue Natural Products as Source of Molecules for Drugs and Therapy)

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15 pages, 2886 KiB

Open AccessArticle

Alismol Purified from the Tuber of Alisma orientale Relieves Acute Lung Injury in Mice via Nrf2 Activation

by Kyun Ha Kim, Soyeon Kim, Min Jung Kwun, Ji Yeon Lee, Sei-Ryang Oh, Jun-Yong Choi and Myungsoo Joo

Int. J. Mol. Sci. 2023, 24(21), 15573; https://doi.org/10.3390/ijms242115573 - 25 Oct 2023

Cited by 2 | Viewed by 1328

Abstract

Since the ethanol extract of Alisma orientale Juzepzuk (EEAO) suppresses lung inflammation by suppressing Nuclear Factor-kappa B (NF-κB) and activating Nuclear Factor Erythroid 2-related Factor 2 (Nrf2), we set out to identify chemicals constituting EEAO that suppress lung inflammation. Here, we provide evidence [...] Read more.

Since the ethanol extract of Alisma orientale Juzepzuk (EEAO) suppresses lung inflammation by suppressing Nuclear Factor-kappa B (NF-κB) and activating Nuclear Factor Erythroid 2-related Factor 2 (Nrf2), we set out to identify chemicals constituting EEAO that suppress lung inflammation. Here, we provide evidence that among the five most abundant chemical constituents identified by Ultra Performance Liquid Chromatography (UPLC) and Nuclear Magnetic Resonance (NMR), alismol is one of the candidate constituents that suppresses lung inflammation in a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model and protects mice from ALI-like symptoms. Alismol did not induce cytotoxicity or reactive oxygen species (ROS). When administered to the lung of LPS-induced ALI mice (n = 5/group), alismol decreased the level of neutrophils and of the pro-inflammatory molecules, including Tumor Necrosis Factor-alpha (TNF-α), Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Monocyte Chemoattractant Protein-1 (MCP-1), Interferon-gamma (IFN-γ), and Cyclooxygenase-2 (COX-2), suggesting an anti-inflammatory activity of alismol. Consistent with these findings, alismol ameliorated the key features of the inflamed lung of ALI, such as high cellularity due to infiltrated inflammatory cells, the development of hyaline membrane structure, and capillary destruction. Unlike EEAO, alismol did not suppress NF-κB activity but rather activated Nrf2. Consequently, alismol induced the expression of prototypic genes regulated by Nrf2, including Heme Oxygenase-1 (HO-1), NAD(P)H: quinine oxidoreductase-1 (NQO-1), and glutamyl cysteine ligase catalytic units (GCLC). Alismol activating Nrf2 appears to be associated with a decrease in the ubiquitination of Nrf2, a key suppressive mechanism for Nrf2 activity. Together, our results suggest that alismol is a chemical constituent of EEAO that contributes at least in part to suppressing some of the key features of ALI by activating Nrf2. Full article

(This article belongs to the Special Issue Natural Products as Source of Molecules for Drugs and Therapy)

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16 pages, 4598 KiB

Open AccessArticle

Castanopsis sieboldii Extract Alleviates Acute Liver Injury by Antagonizing Inflammasome-Mediated Pyroptosis

by Jae Min Kim, Sam Seok Cho, Sohi Kang, Changjong Moon, Ji Hye Yang and Sung Hwan Ki

Int. J. Mol. Sci. 2023, 24(15), 11982; https://doi.org/10.3390/ijms241511982 - 26 Jul 2023

Cited by 3 | Viewed by 1551

Abstract

Castanopsis sieboldii (CS), a subtropical species, was reported to have antioxidant and antibacterial effects. However, the anti-inflammatory effects of CS have not been studied. This study aimed to investigate whether the 70% ethanol extract of the CS leaf (CSL3) inhibited lipopolysaccharide (LPS)-induced inflammatory [...] Read more.

Castanopsis sieboldii (CS), a subtropical species, was reported to have antioxidant and antibacterial effects. However, the anti-inflammatory effects of CS have not been studied. This study aimed to investigate whether the 70% ethanol extract of the CS leaf (CSL3) inhibited lipopolysaccharide (LPS)-induced inflammatory responses and LPS and ATP-induced pyroptosis in macrophages. CSL3 treatment inhibited NO release and iNOS expression in LPS-stimulated cells. CSL3 antagonized NF-κB and AP-1 activation, which was due to MAPK (p38, ERK, and JNK) inhibition. CSL3 successfully decreased NLRP3 inflammasome activation and increased IL-1β expression. CSL3 treatment diminished LPS and ATP-induced pore formation in GSDMD. The in vivo effect of CSL3 on acute liver injury was evaluated in a CCl₄-treated mouse model. CCl₄ treatment increased the activity of serum alanine aminotransferase and aspartate aminotransferase, which decreased by CSL3. In addition, CCl₄-induced an increase in TNF-α, and IL-6 levels decreased by CSL3 treatment. Furthermore, we verified that the CCl₄-induced inflammasome and pyroptosis-related gene expression in liver tissue and release of IL-1β into serum were suppressed by CSL3 treatment. Our results suggest that CSL3 protects against acute liver injury by inhibiting inflammasome formation and pyroptosis. Full article

(This article belongs to the Special Issue Natural Products as Source of Molecules for Drugs and Therapy)

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16 pages, 7371 KiB

Open AccessArticle

by Sura Kim, Ji-Hyo Lyu, Beodeul Yang, Soyeon Kim, Jung-Hoon Kim, Hyungwoo Kim and Suin Cho

Int. J. Mol. Sci. 2023, 24(7), 6091; https://doi.org/10.3390/ijms24076091 - 23 Mar 2023

Cited by 1 | Viewed by 1817

Abstract

Fraxinus rhynchophylla Hance bark has been used to treat patients with inflammatory or purulent skin diseases in China, Japan, and Korea. This study was undertaken to determine the mechanism responsible for the effects of F. rhynchophylla and whether it has a therapeutic effect [...] Read more.

Fraxinus rhynchophylla Hance bark has been used to treat patients with inflammatory or purulent skin diseases in China, Japan, and Korea. This study was undertaken to determine the mechanism responsible for the effects of F. rhynchophylla and whether it has a therapeutic effect in mice with contact dermatitis (CD). In this study, the active compounds in F. rhynchophylla, their targets, and target gene information for inflammatory dermatosis were investigated using network-based pharmacological analysis. Docking analysis was conducted using AutoDock Vina. In addition, the therapeutic effect of an ethanolic extract of F. rhynchophylla (EEFR) on skin lesions and its inhibitory effects on histopathological abnormalities, inflammatory cytokines, and chemokines were evaluated. Finally, its inhibitory effects on the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signalling pathways were observed in RAW 264.7 cells. In our results, seven active compounds were identified in F. rhynchophylla, and six were associated with seven genes associated with inflammatory dermatosis and exhibited a strong binding affinity (<−6 kcal/mol) to prostaglandin G/H synthase 2 (PTGS2). In a murine 1-fluoro-2,4-dinitrobenzene (DNFB) model, topical EEFR ameliorated the surface symptoms of CD and histopathological abnormalities. EEFR also reduced the levels of tumour necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-6, and monocyte chemotactic protein (MCP)-1 in inflamed tissues and inhibited PTGS2, the nuclear translocation of NF-κB (p65), and the activation of c-Jun N-terminal kinases (JNK) in RAW 264.7 cells. In conclusion, the bark of F. rhynchophylla has potential use as a therapeutic or cosmetic agent, and the mechanism responsible for its effects involves the suppression of inflammatory mediators, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (IκB)-α degradation, the nuclear translocation of NF-κB, and JNK phosphorylation. Full article

(This article belongs to the Special Issue Natural Products as Source of Molecules for Drugs and Therapy)

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Review

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26 pages, 2126 KiB

Open AccessReview

Essential-Oils-Loaded Biopolymeric Nanoparticles as Strategies for Microbial and Biofilm Control: A Current Status

by Alejandra Romero-Montero, Luis Javier Melgoza-Ramírez, Jesús Augusto Ruíz-Aguirre, Alejandra Chávez-Santoscoy, Jonathan Javier Magaña, Hernán Cortés, Gerardo Leyva-Gómez and María Luisa Del Prado-Audelo

Int. J. Mol. Sci. 2024, 25(1), 82; https://doi.org/10.3390/ijms25010082 - 20 Dec 2023

Cited by 2 | Viewed by 1784

Abstract

The emergence of bacterial strains displaying resistance to the currently available antibiotics is a critical global concern. These resilient bacteria can form biofilms that play a pivotal role in the failure of bacterial infection treatments as antibiotics struggle to penetrate all biofilm regions. [...] Read more.

The emergence of bacterial strains displaying resistance to the currently available antibiotics is a critical global concern. These resilient bacteria can form biofilms that play a pivotal role in the failure of bacterial infection treatments as antibiotics struggle to penetrate all biofilm regions. Consequently, eradicating bacteria residing within biofilms becomes considerably more challenging than their planktonic counterparts, leading to persistent and chronic infections. Among various approaches explored, essential oils loaded in nanoparticles based on biopolymers have emerged, promising strategies that enhance bioavailability and biological activities, minimize side effects, and control release through regulated pharmacokinetics. Different available reviews analyze nanosystems and essential oils; however, usually, their main goal is the analysis of their antimicrobial properties, and progress in biofilm combat is rarely discussed, or it is not the primary objective. This review aims to provide a global vision of biofilm conformation and describes mechanisms of action attributed to each EO. Furthermore, we present a comprehensive overview of the latest developments in biopolymeric nanoparticles research, especially in chitosan- and zein-based nanosystems, targeting multidrug-resistant bacteria in both their sessile and biofilm forms, which will help to design precise strategies for combating biofilms. Full article

(This article belongs to the Special Issue Natural Products as Source of Molecules for Drugs and Therapy)

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32 pages, 3271 KiB

Open AccessReview

Effects of Essential Oils and Fragrant Compounds on Appetite: A Systematic Review

by Nhi Phuc Khanh Nguyen, Khoa Nguyen Tran, Ly Thi Huong Nguyen, Heung-Mook Shin and In-Jun Yang

Int. J. Mol. Sci. 2023, 24(9), 7962; https://doi.org/10.3390/ijms24097962 - 27 Apr 2023

Cited by 7 | Viewed by 7637

Abstract

Appetite dysregulation is one of the factors contributing to anorexia, bulimia nervosa, obesity, and diabetes. Essential oils or fragrant compounds have been proven to regulate food intake and energy expenditure; hence, this study aimed to summarize their effects on appetite and the underlying [...] Read more.

Appetite dysregulation is one of the factors contributing to anorexia, bulimia nervosa, obesity, and diabetes. Essential oils or fragrant compounds have been proven to regulate food intake and energy expenditure; hence, this study aimed to summarize their effects on appetite and the underlying mechanisms. The PubMed and Web of Science databases were searched until July 2022. Only two of the 41 studies were performed clinically, and the remaining 39 used animal models. Oral administration was the most common route, and a dosage range of 100–2000 mg/kg for mice or 2–32 mg/kg for rats was applied, with a duration of 12 days to 4 weeks, followed by inhalation (10⁻⁶–10⁻³ mg/cage or 10⁻⁹–10⁻² mg/cm³ within 1 h). Approximately 11 essential oil samples and 22 fragrant compounds were found to increase appetite, while 12 essential oils and seven compounds decreased appetite. These fragrant components can exert appetite-regulating effects via leptin resistance, the activity of sympathetic/parasympathetic nerves, or the mRNA expression of neuropeptide Y (NPY)/agouti-related protein (AgRP), cocaine- and amphetamine-regulated transcript (CART)/proopiomelanocortin (POMC) in the hypothalamus. Fragrance memory and cognitive processes may also play roles in appetite regulation. The findings of this study accentuate the potential of essential oils and fragrant compounds to regulate appetite and eating disorders. Full article

(This article belongs to the Special Issue Natural Products as Source of Molecules for Drugs and Therapy)

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