Antifungal properties of pristimerin and celastrol isolated from <i>Celastrus hypoleucus</i>

Luo, Du‐Qiang; Wang, Hong; Tian, Xuan; Shao, Hong-Jun; Liu, Ji‐Kai

doi:10.1002/ps.953

Cited by 56 publications

(25 citation statements)

References 19 publications

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“…In this study based on an experimental model of autoimmune arthritis (the AA model), we have described the mechanisms underlying the anti-arthritic activity of C. aculeatus Merrill (23) and celastrol, one of the bioactive components of Celastrus (23)(24)(25)(26). Most of the studies on celastrol are based on its antitumor activity (29).…”

Section: Discussionmentioning

confidence: 99%

“…In this study, we describe the anti-arthritic activity and the underlying mechanisms of the ethanol extract of Celastrus aculeatus Merrill (Celastrus) (23), a Chinese medicinal herb, and celastrol, a bioactive component of Celastrus (23)(24)(25)(26), using a well established model of RA, adjuvant-induced arthritis (AA) (27,28). Most of the literature on celastrol is devoted to its anticancer properties (29).…”

Section: Rheumatoid Arthritis (Ra)mentioning

confidence: 99%

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Celastrus-derived Celastrol Suppresses Autoimmune Arthritis by Modulating Antigen-induced Cellular and Humoral Effector Responses

Venkatesha¹,

Yu²,

Rajesh³

et al. 2011

Journal of Biological Chemistry

137

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Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation and articular damage. Proinflammatory cytokines, antibodies, and matrix-degrading enzymes orchestrate the pathogenic events in autoimmune arthritis. Accordingly, these mediators of inflammation are the targets of several anti-arthritic drugs. However, the prolonged use of such drugs is associated with severe adverse reactions. This limitation has necessitated the search for less toxic natural plant products that possess anti-arthritic activity. Furthermore, it is imperative that the mechanism of action of such products be explored before they can be recommended for further preclinical testing. Using the rat adjuvant-induced arthritis model of human RA, we demonstrate that celastrol derived from Celastrus has potent anti-arthritic activity. This suppression of arthritis is mediated via modulation of the key proinflammatory cytokines (IL-17, IL-6, and IFN-␥) in response to the diseaserelated antigens, of the IL-6/IL-17-related transcription factor STAT3, of antibodies directed against cyclic citrullinated peptides and Bhsp65, and of the activity of matrix metalloproteinase-9 and phospho-ERK. Most of the clinical and mechanistic attributes of celastrol are similar to those of Celastrus extract. Several studies have addressed the antitumor activity of celastrol. Our study highlights the anti-arthritic activity of Celastrusderived celastrol and the underlying mechanisms. These results provide a strong rationale for further testing and validation of the use of celastrol and the natural plant extract from Celastrus as an adjunct (with conventional drugs) or alternative modality for the treatment of RA. Rheumatoid arthritis (RA)2 is a chronic debilitating autoimmune disease affecting millions of people all over the world (1-3). Both cell-mediated and humoral immune reactions participate in the pathogenesis of RA (1, 4). Several proinflammatory cytokines secreted by immune cells, including TNF-␣, IL-1␤, IL-15, IL-18, and IFN-␥, have been shown to play a role in the initiation and progression of RA (4, 5). Over the past decade, a new subset of T helper cells producing IL-17 (Th17) has become the focus of RA pathogenesis (6, 7). Induction of a Th17 response involves IL-6 and TGF-␤, as well as the transcription factors STAT3 and retinoid related orphan receptor-␥t (ROR-␥t) (8, 9). In regard to the humoral response, serum levels of anti-cyclic citrullinated protein/peptide (aCCP) antibodies correlate well with the disease severity in RA patients and serve as the specific autoantibody marker for the diagnosis of RA (10, 11). In view of the above, modulation of the proinflammatory cytokines and aCCP antibody levels is a desired goal for the management of RA.A variety of drugs are available for the treatment of RA. These include corticosteroids, nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, and biologics (1, 12). However, besides their high cost, the use of these drugs is associated with severe adverse reacti...

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Section: Discussionmentioning

confidence: 99%

Section: Rheumatoid Arthritis (Ra)mentioning

confidence: 99%

Celastrus-derived Celastrol Suppresses Autoimmune Arthritis by Modulating Antigen-induced Cellular and Humoral Effector Responses

Venkatesha¹,

Yu²,

Rajesh³

et al. 2011

Journal of Biological Chemistry

137

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“…Quinonemethide triterpenoids isolated from T. regelii such as celastrol, iguestein, pristimerin, and tingenone are reported to possess several biological activities such as anticancer, anti-inflammatory, antimalarial, antioxidant, antiviral, and insecticidal activities (Luo et al 2005;Brinker et al 2007;Gao et al 2007;Su et al 2009;Ryu et al 2010) as well as antifungal activity (Dos Santos et al 2010). Furthermore, these triterpenoids induced an increase in intracellular reactive oxygen species (ROS) and mitochondrial dysfunction (Byun et al 2009), and the quinonemethide moiety with electrochemical potential is regarded as a key component of the triterpenoid (Ryu et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Downregulation of fungal cytochrome c peroxidase expression by antifungal quinonemethide triterpenoids

Seo

Lee

Park

et al. 2016

Journal of Applied Biological Chemistry

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To handle the development of antifungal drug resistance, the development of new structural modules and new modes of action for antifungals have been highlighted recently. Here, the antifungal activity of quinonemethidal triterpenoids such as celastrol, dihydrocelastrol, iguestein, pristimerin, and tingenone isolated from Tripterygium regelii were identified (MIC 0.269-19.02 µM). C. glabrata was the most susceptible to quinonemethide among the tested fungi. Furthermore, quinonemethide suppressed cyctochrome c peroxidase expression dramatically, decreasing fungal viability caused by the accumulation of hydrogen peroxide. Thus, cyctochrome c peroxidase downregulation of quinonemethide may be a key mode of action for antifungals.

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“…The triterpenoids pristimerin and celastrol isolated from the roots of Celastrus hypoleucus (Oliv) Warb f. Argurtior Loes (Celastraceae) exhibited inhibitory effects against diverse phytopathogenic fungi such as Rhizoctonia solani and Glomerelia cinguiata. 108 Examples of other triterpenes from medicinal plants also included a novel oleanane triterpenoid, triterpenetetrol (Figure 8), isolated from the chloroform extract of the aerial parts of Leontodon filii (Hochst. ex Seub.)…”

mentioning

confidence: 99%

Active antifungal substances from natural sources

Abad¹,

Ansuategui²,

Bermejo³

2006

Arkivoc

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The spread of multidrug-resistant strains of fungus and the reduced number of drugs available, makes it necessary to discover new classes of antifungals and compounds that inhibit these resistant mechanisms. This has led to a search for therapeutic alternatives, particularly among medicinal plants and compounds isolated from them used for their empirically antifungal properties. In these natural sources, a series of molecules with antifungal activity against different strains of fungus have been found, which are of great importance to humans and plants. In this article, we review the main sources of molecules with antimycotic activity obtained from the natural environment.

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Antifungal properties of pristimerin and celastrol isolated from Celastrus hypoleucus

Cited by 56 publications

References 19 publications

Celastrus-derived Celastrol Suppresses Autoimmune Arthritis by Modulating Antigen-induced Cellular and Humoral Effector Responses

Celastrus-derived Celastrol Suppresses Autoimmune Arthritis by Modulating Antigen-induced Cellular and Humoral Effector Responses

Downregulation of fungal cytochrome c peroxidase expression by antifungal quinonemethide triterpenoids

Active antifungal substances from natural sources

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