Hederagenin Suppresses Inflammation and Cartilage Degradation to Ameliorate the Progression of Osteoarthritis: An In vivo and In vitro Study

Shen, Yue; Teng, Li; Qu, Yuhan; Huang, Yuehui; Peng, Yi; Tang, Min; Fu, Qiang

doi:10.1007/s10753-022-01763-5

Cited by 15 publications

(8 citation statements)

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“…Among the bioactive compounds investigated, the mechanism of action of hederagenin has been extensively studied in several studies. In fact, hederagenin has been reported to have anti-tumour and anti-inflammatory effects by regulating the NFκB, PI3K/AKT and JAK2/STAT3/MAPK signalling pathways, and by reducing the expression of pro-inflammatory cytokines or enzyme production, including Tumor Necrosis Factor- α (TNF-α), interleukin 6 (IL-6), NO, prostaglandin E2 (PGE 2 ), inducible nitric oxide synthase (iNOS) and COX-2 ( Zhang et al, 2012 ; Lee et al, 2015 ; Kim et al, 2017 ; Yu et al, 2020 ; Shen et al, 2023 ). Our results indicate the accordance between the molecular docking and the previous studies thereby confirming the efficacy of hederagenin as a prominent lead compound for the management of inflammation and cancer development.…”

Section: Resultsmentioning

confidence: 99%

In vitro antiproliferative, anti-inflammatory effects and molecular docking studies of natural compounds isolated from Sarcocephalus pobeguinii (Hua ex Pobég)

et al. 2023

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Background:Sarcocephalus pobeguinii (Hua ex Pobég) is used in folk medicine to treat oxidative-stress related diseases, thereby warranting the investigation of its anticancer and anti-inflammatory properties. In our previous study, the leaf extract of S. pobeguinii induced significant cytotoxic effect against several cancerous cells with high selectivity indexes towards non-cancerous cells.Aim: The current study aims to isolate natural compounds from S. pobeguinii, and to evaluate their cytotoxicity, selectivity and anti-inflammatory effects as well as searching for potential target proteins of bioactive compounds.Methods: Natural compounds were isolated from leaf, fruit and bark extracts of S. pobeguinii and their chemical structures were elucidated using appropriate spectroscopic methods. The antiproliferative effect of isolated compounds was determined on four human cancerous cells (MCF-7, HepG2, Caco-2 and A549 cells) and non-cancerous Vero cells. Additionally, the anti-inflammatory activity of these compounds was determined by evaluating the nitric oxide (NO) production inhibitory potential and the 15-lipoxygenase (15-LOX) inhibitory activity. Furthermore, molecular docking studies were carried out on six putative target proteins found in common signaling pathways of inflammation and cancer.Results: Hederagenin (2), quinovic acid 3-O-[α-D-quinovopyranoside] (6) and quinovic acid 3-O-[β-D-quinovopyranoside] (9) exhibited significant cytotoxic effect against all cancerous cells, and they induced apoptosis in MCF-7 cells by increasing caspase-3/-7 activity. (6) showed the highest efficacy against all cancerous cells with poor selectivity (except for A549 cells) towards non-cancerous Vero cells; while (2) showed the highest selectivity warranting its potential safety as a chemotherapeutic agent. Moreover, (6) and (9) significantly inhibited NO production in LPS-stimulated RAW 264.7 cells which could mainly be attributed to their high cytotoxic effect. Besides, the mixture nauclealatifoline G and naucleofficine D (1), hederagenin (2) and chletric acid (3) were active against 15-LOX as compared to quercetin. Docking results showed that JAK2 and COX-2, with the highest binding scores, are the potential molecular targets involved in the antiproliferative and anti-inflammatory effects of bioactive compounds.Conclusion: Overall, hederagenin (2), which selectively killed cancer cells with additional anti-inflammatory effect, is the most prominent lead compound which may be further investigated as a drug candidate to tackle cancer progression.

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Section: Resultsmentioning

confidence: 99%

In vitro antiproliferative, anti-inflammatory effects and molecular docking studies of natural compounds isolated from Sarcocephalus pobeguinii (Hua ex Pobég)

et al. 2023

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“…In an in vitro study, hederagenin exerted chondroprotective and anti-inflammatory effects by suppressing the JAK2/STAT3/MAPK pathway, inhibited extracellular matrix degradation, elevated Aggrecan and Collagen II levels, and reduced levels of MMPs and ADAMTS5. In addition, this pentacyclic triterpenoid saponin inhibited cartilage destruction in rats induced by monosodium iodoacetate [137]. Hederagenin 3-O-(2-O-acetyl)-α-L-arabinopyranoside and the dichloromethane fraction of Dipsaci radix also improved osteoblastic differentiation of human alveolar bone marrow-derived mesenchymal stem cells.…”

Section: Biological Activities Of Dipsacus and Scabiosa Species 61 St...mentioning

confidence: 87%

Dipsacus and Scabiosa Species—The Source of Specialized Metabolites with High Biological Relevance: A Review

Skała

Szopa

2023

Molecules

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The genera Dipsacus L. and Scabiosa L. of the Caprifoliaceae family are widely distributed in Europe, Asia, and Africa. This work reviews the available literature on the phytochemical profiles, ethnomedicinal uses, and biological activities of the most popular species. These plants are rich sources of many valuable specialized metabolites with beneficial medicinal properties, such as triterpenoid derivatives, iridoids, phenolic acids, and flavonoids. They are also sources of essential oils. The genus Dipsacus has been used for centuries in Chinese and Korean folk medicines to treat bone (osteoporosis) and joint problems (rheumatic arthritis). The Korean Herbal Pharmacopoeia and Chinese Pharmacopoeia include Dipsaci radix, the dried roots of D. asperoides C.Y.Cheng & T.M.Ai. In addition, S. comosa Fisch. ex Roem & Schult. and S. tschiliiensis Grunning are used in traditional Mongolian medicine to treat liver diseases. The current scientific literature data indicate that these plants and their constituents have various biological properties, including inter alia antiarthritic, anti-neurodegenerative, anti-inflammatory, antioxidant, anticancer, and antimicrobial activities; they have also been found to strengthen tendon and bone tissue and protect the liver, heart, and kidney. The essential oils possess antibacterial, antifungal, and insecticidal properties. This paper reviews the key biological values of Dipsacus and Scabiosa species, as identified by in vitro and in vivo studies, and presents their potential pharmacological applications.

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“…It was found that (6aR,11aR)‐9,10‐dimethoxy‐6a,11a‐dihydro‐6H‐benzofurano[3,2‐c]chromen‐3‐ol can act on tyrosine tRNA synthetase and tryptophanyl tRNA synthetase TrpRS to modulate the biosynthesis of aminoacyl‐tRNA, regulate DNA damage and apoptosis (Chen et al., 2018). Hederagenin has a variety of pharmacological effects such as reversing hyperlipidemia, anti‐depression, anti‐lipid peroxidation, liver protection, and anti‐inflammation (Choi et al., 2001; Gülçin et al., 2006; Lin et al., 2021; Shen et al., 2023; Yamahara et al., 1979; Yang et al., 2022). Notably, hederagenin can play a protective role in blood vessel wall by modulating lipid metabolism disorder and lipid deposition (Lu et al., 2015).…”

Section: Discussionmentioning

confidence: 99%

Mechanism analysis of Buyang Huanwu decoction in treating atherosclerosis based on network pharmacology and in vitro experiments

Wang,

Li,

2024

Chem Biol Drug Des

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Atherosclerosis (AS) is one of the main risk factors of ischemic cardiovascular and cerebrovascular diseases. Buyang Huanwu decoction (BYHWT) is a classic Chinese medicine prescription that is used for treating AS. However, the underlying pharmacological mechanism remains unclear. This study aims to clarify the molecular mechanism of BYHWT in treatment of AS through network pharmacology and in vitro experiments. Molecular structure information and targets of core components of BYHWT were obtained from PubChem and UniProtKB databases. Genes involved in AS were obtained from DisGeNet, GeneCards and OMIM databases. The core targets of BYHWT in AS treatment were identified by protein–protein interaction (PPI) network analysis with STRING platform, and analyzed by gene ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomics (KEGG) pathway enrichment analysis. Molecular docking was used to verify the binding affinity between the core targets and the bioactive ingredients. HUVEC viability, inflammatory response and mRNA expression levels of core target genes were evaluated by cell counting kit 8 assay, enzyme‐linked immunosorbent assay (ELISA) and qRT‐PCR. A total of 60 candidate compounds and 325 predicted target genes were screened. PPI network analysis suggested that TP53, SRC, STAT3, and AKT1 may be the core targets. BYHWT in AS treatment was associated with 46 signaling pathways. GA120, baicalein, and 3,9‐di‐o‐methylnissolin had good binding affinity with core target proteins. Baicalein treatment could significantly promoted the viability and repress the inflammatory response of HUVEC cells stimulated by ox‐LDL. In addition, Baicalein can regulate the expression of core targets including AKT1, MAPK1, PIK3CA, JUN, TP53, SRC, EGFR, and ESR1. In conclusion, BYHWT and its main bioactive component baicalein, inhibit inflammatory response and modulate multiple downstream genes of endothelial cells, and show good potential to block the progression of AS and cardiovascular/cerebrovascular diseases.

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Hederagenin Suppresses Inflammation and Cartilage Degradation to Ameliorate the Progression of Osteoarthritis: An In vivo and In vitro Study

Cited by 15 publications

References 68 publications

In vitro antiproliferative, anti-inflammatory effects and molecular docking studies of natural compounds isolated from Sarcocephalus pobeguinii (Hua ex Pobég)

In vitro antiproliferative, anti-inflammatory effects and molecular docking studies of natural compounds isolated from Sarcocephalus pobeguinii (Hua ex Pobég)

Dipsacus and Scabiosa Species—The Source of Specialized Metabolites with High Biological Relevance: A Review

Mechanism analysis of Buyang Huanwu decoction in treating atherosclerosis based on network pharmacology and in vitro experiments

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