Baicalin suppresses Propionibacterium acnes-induced skin inflammation by downregulating the NF-κB/MAPK signaling pathway and inhibiting activation of NLRP3 inflammasome

Fang, Fang; Xie, Zeping; Quan, Jingyu; Wei, Xiaohan; Wang, Linlin; Liu, Yang

doi:10.1590/1414-431x20209949

Cited by 23 publications

(22 citation statements)

References 33 publications

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“…9, 10) indicated involvements of MAPK, SYK, and PI3K as targets of baicalin. This result is in accordance with previously reported studies that baicalin inhibits p38 MAPK, and this mechanism may be responsible for its anti-inflammation effect [23,25,43,44]. MAPK is activated under the stress of cytokine; therefore, inhibiting MAPK is a promising approach for hyper-inflammatory disease, such as COVID-19 [45].…”

Section: Discussionsupporting

confidence: 92%

“…The produced cytokines can be released and cause further cycles of cytokine amplification that is harmful in acute inflammation condition, such as in COVID-19. According to previous reports, baicalin regulates the PI3K/AKT signal [24] and NF-κB [23,43], and these activities may be responsible for baicalin-induced anti-inflammatory effect [16,23,43]. Our analysis and the supportive data from the literature suggested that baicalin may protect the cell from pro-inflammatory factors, such as cytokine and chemokine, through disrupting several inflammation-associated signaling pathways inside the cell.…”

Section: Discussionsupporting

confidence: 77%

“…Recently, SB and several herbal formulas comprising SB were suggested as potential therapeutics to treat COVID-19 with supportive data provided from in silico approaches or system pharmacological studies [7,[19][20][21][22]. Baicalin is known to be responsible for the major biological effects of SB and exhibits anti-inflammatory and antiviral effects with low cytotoxicity [23][24][25]. Baicalin is the main composition of Flavocoxid, an approved medical food, which is classified as generally recognized as safe by regulatory requirement.…”

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confidence: 99%

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Study of Baicalin toward COVID-19 Treatment: In silico Target Analysis and in vitro Inhibitory Effects on SARS-CoV-2 Proteases

et al. 2021

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Negative impacts of COVID-19 on human health and economic and social activities urge scientists to develop effective treatments. Baicalin is a natural flavonoid, extracted from a traditional medicinal plant, previously reported with anti-inflammatory activity. In this study, we used pharmacophore fitting and molecular docking to screen and determine docking patterns and the binding affinity of baicalin on 3 major targets of SARS-CoV-2 (3-chymotrypsin-like cysteine protease [3CLpro], papain-like protease [PLpro], and RNA-dependent RNA polymerase). The obtained data revealed that baicalin has high pharmacophore fitting on 3CLpro and predicted good binding affinity on PLpro. Moreover, using the enzymatic assay, we examined the inhibitory effect of baicalin in vitro on the screened enzymes. Baicalin also exhibits inhibitory effect on these proteases in vitro. Additionally, we performed pharmacophore-based screening of baicalin on human targets and conducted pathway analysis to explore the potential cytoprotective effects of baicalin in the host cell that may be beneficial for COVID-19 treatment. The result suggested that baicalin has multiple targets in human cell that may induce multiple pharmacological effects. The result of pathway analysis implied that these targets may be associated with baicalin-induced bioactivities that are involved with signals of pro-inflammation factors, such as cytokine and chemokine. Taken together with supportive data from the literature, the bioactivities of bailalin may be beneficial for COVID-19 treatment by reducing cytokine-induced acute inflammation. In conclusion, baicalin is potentially a good candidate for developing new therapeutic to treat COVID-19.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 77%

mentioning

confidence: 99%

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Study of Baicalin toward COVID-19 Treatment: In silico Target Analysis and in vitro Inhibitory Effects on SARS-CoV-2 Proteases

et al. 2021

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“…5A). The expression of TNF-α protein in the model control group was signi cantly up-regulated, which was in agreement with a previous report [15]. Compared with the model control group, the expression of TNF-α protein was signi cantly down-regulated after BEO treatment (p < 0.0001, Fig.…”

Section: In Ammatory Mediator Production In the Rabbit Ear Acne Modelsupporting

confidence: 92%

The Acne-treatment Potential of Cinnamomum Camphora Chvar. Borneol Essential Oil in Vitro and in Vivo

Xiao

Xie

et al. 2021

Preprint

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Background: Acne is one of the most common chronic inflammatory skin diseases, abnormal proliferation of keratinocytes can block the hair follicle sebaceous glands result in the formation of acne. Most drugs to treat acne can cause a variety of side effects, therefore, it is important to seek natural and safe complementary and alternative therapies.Methods: The inhibitory effects of BEO were determined on the proliferation of human keratinocyte (HaCaT) cells induced by heat-inactivated Staphylococcus epidermidis and release of the inflammatory mediators. Further, a component-target-signal pathway for BEO’s effects on acne was constructed through network pharmacology and the mechanism of BEO action was studied in vivo through the rabbit ear acne model.Results: BEO inhibited both cell proliferation, induced by heat-inactivated Staphylococcus epidermidis (p < 0.0001), and release of the inflammatory mediators TNF-α (p < 0.0001) and IL-1β (p < 0.05) in a dose-dependent manner (r = -0.9952, -0.9492), in a HaCaT cell-model of acne. A network pharmacology analysis of the chemical components of BEO characterized these effects as multi-component, multi-target and multi-pathway. All targets were mainly associated with metabolic pathways, the toll-like receptor signaling pathway and the NF-κB signaling pathway. BEO also reduced the severity of acne lesions, induced by intracutaneous injection of S. epidermidis in a rabbit ear acne model. The expression of inflammatory mediators and key signaling pathway components, including TLR2, AKT, P13K, NF-κB, TNF-α, IL-1β in rabbit ear, and TNF-α and IL-1 β in serum, were down-regulated (p < 0.05), indicating that BEO acts by inhibiting the pro-inflammatory TLR2/PI3K-AKT/NF-κB signaling pathway.Conclusion: The current results showed that BEO has clear potential for development into a natural and safe anti-inflammatory skin preparation, which is an effective alternative to conventional treatments containing antibiotics and synthetic anti-inflammatory agents.

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“…Since P. acnes can induce the secretion of IL-1β, it may affect the ability of cells to fight infection and disease. According to some studies, P. acnes can stimulate inflammatory responses in monocytes by inducing IL-1β [ 34 , 35 ]. Furthermore, P. acnes can activate NLRP3 and cytokines in stimulated THP-1 cells (Fig.…”

Section: Discussionmentioning

confidence: 99%

Adipose-derived stem cells attenuate acne-related inflammation via suppression of NLRP3 inflammasome

Luo

Chen

et al. 2022

Stem Cell Res Ther

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Background Acne is a chronic facial disease caused by Propionibacterium acnes, which proliferates within sebum-blocked skin follicles and increases inflammatory cytokine production. Several therapeutic drugs and products have been proposed to treat acne, yet no single treatment that ensures long-term treatment efficacy for all patients is available. Here, we explored the use of facial autologous fat transplant of adipose-derived stem cells (ADSCs) to dramatically reduce acne lesions. Methods THP-1 cells were treated with active P. acnes for 24 h at different multiplicities of infection, and alterations in inflammatory factors were detected. To study the effect of THP-1 on inflammasome-related proteins, we first co-cultured ADSCs with THP-1 cells treated with P. acnes and evaluated the levels of these proteins in the supernatant. Further, an acne mouse model injected with ADSCs was used to assess inflammatory changes. Results Propionibacterium acnes-mediated stimulation of THP-1 cells had a direct correlation with the expression of active caspase-1 and interleukin (IL)-1β in an infection-dependent manner. ADSCs significantly reduced the production of IL-1β induced by P. acnes stimulation through the reactive oxygen species (ROS)/Nod-like receptor family pyrin domain-containing 3 (NLRP3)/caspase-1 pathway. The results showed that ADSCs inhibit the skin inflammation induced by P. acnes by blocking the NLRP3 inflammasome via reducing the secretion of IL-1β in vivo. Conclusions Our findings suggest that ADSCs can alter IL-1β secretion by restricting the production of mitochondria ROS, thereby inhibiting the NLRP3/caspase-1 pathway in P. acnes-induced inflammatory responses. This study indicates that anti‐acne therapy can potentially be developed by targeting the NLRP3 inflammasome.

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Baicalin suppresses Propionibacterium acnes-induced skin inflammation by downregulating the NF-κB/MAPK signaling pathway and inhibiting activation of NLRP3 inflammasome

Cited by 23 publications

References 33 publications

Study of Baicalin toward COVID-19 Treatment: In silico Target Analysis and in vitro Inhibitory Effects on SARS-CoV-2 Proteases

Study of Baicalin toward COVID-19 Treatment: In silico Target Analysis and in vitro Inhibitory Effects on SARS-CoV-2 Proteases

The Acne-treatment Potential of Cinnamomum Camphora Chvar. Borneol Essential Oil in Vitro and in Vivo

Adipose-derived stem cells attenuate acne-related inflammation via suppression of NLRP3 inflammasome

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