New opportunities and challenges of natural products research: When target identification meets single-cell multiomics

Acta Pharmaceutica Sinica B, Journal Year: 2022, Volume and Issue: 12(11), P. 4011 - 4039

Published: Aug. 27, 2022

Language: Английский

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Advances in mechanism and regulation of PANoptosis: Prospects in disease treatment

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 9, 2023

PANoptosis, a new research hotspot at the moment, is cell death pattern in which pyroptosis, apoptosis, and necroptosis all occur same population. In essence, PANoptosis highly coordinated dynamically balanced programmed inflammatory pathway that combines main features of necroptosis. Many variables, such as infection, injury, or self-defect, may be involved occurrence with assembly activation PANoptosome being most critical. has been linked to development multiple systemic diseases human body, including infectious diseases, cancer, neurodegenerative diseases. Therefore, it necessary clarify process occurrence, regulatory mechanism its relation this paper, we summarized differences relations between three types death, emphatically expounded molecular patterns expectation facilitating application regulation disease treatment.

Language: Английский

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The role and mechanism of flavonoid herbal natural products in ulcerative colitis

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 158, P. 114086 - 114086

Published: Dec. 8, 2022

Ulcerative colitis (UC) is a chronic inflammatory disease of the intestine that presents clinically with abdominal pain, mucopurulent stools, and posterior urgency. The lesions UC are mainly concentrated in rectal colonic mucosa submucosa. For patients mild to moderate UC, best pharmacological treatment includes glucocorticoids, immunosuppressants, antibiotics, biologics, but long-term application can have serious toxic side effects. Currently, nearly 40% treated herbal natural products combination traditional medications reduce incidence Flavonoid most widely distributed polyphenols plants fruits, which certain antioxidant anti-inflammatory activities. achieved remarkable efficacy UC. mechanisms related anti-inflammation, promotion mucosal healing, maintenance intestinal immune homeostasis, regulation flora. In this paper, we summarize flavonoid components anti-ulcerative their reported past 10 years, provide basis for rational clinical use development new drugs.

Language: Английский

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Costunolide covalently targets NACHT domain of NLRP3 to inhibit inflammasome activation and alleviate NLRP3-driven inflammatory diseases

Acta Pharmaceutica Sinica B, Journal Year: 2022, Volume and Issue: 13(2), P. 678 - 693

Published: Sept. 25, 2022

The NLRP3 inflammasome's core and most specific protein, NLRP3, has a variety of functions in inflammation-driven diseases. Costunolide (COS) is the major active ingredient traditional Chinese medicinal herb Saussurea lappa anti-inflammatory activity, but principal mechanism molecular target COS remain unclear. Here, we show that covalently binds to cysteine 598 NACHT domain altering ATPase activity assembly inflammasome. We declare COS's great anti-inflammasome efficacy macrophages disease models gouty arthritis ulcerative colitis via inhibiting inflammasome activation. also reveal α-methylene-γ-butyrolactone motif sesquiterpene lactone certain group Taken together, identified as direct for its activity. COS, especially structure, might be used design produce novel inhibitors lead compound.

Language: Английский

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Natural compounds as safe therapeutic options for ulcerative colitis

Inflammopharmacology, Journal Year: 2022, Volume and Issue: 30(2), P. 397 - 434

Published: Feb. 25, 2022

Abstract Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology. Several conventional treatments for UC such as corticosteroids, immunosuppressive agents, tumor necrosis factor antagonist, integrin blockers, and interleukin salicylates are available but associated with the various limitations side-effects. None above helps to achieve ultimate goal therapy, i.e., maintenance remission in long-term. Natural remedies treatment show comparatively less side effects compared approaches, affordable. The current review presents details on role herbal drugs cure UC. Google, PubMed, Web Science, Scopus portals have been searched potentially relevant literature get latest developments updated information related use natural products used over centuries treat Some essential constituents exhibiting antiulcerogenic activity include gymnemic acid ( Gymnema sylvestre ), shagoal Zingiber officinale catechin Camellia sinensis curcumin Curcuma longa arctigenin Arctium lappa boswellic Boswellia serrata ). Although many plant-derived recommended UC, further research understand exact molecular mechanism still warranted establish their usefulness clinically.

Language: Английский

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Atractylenolide-1 targets SPHK1 and B4GALT2 to regulate intestinal metabolism and flora composition to improve inflammation in mice with colitis

Phytomedicine, Journal Year: 2022, Volume and Issue: 98, P. 153945 - 153945

Published: Jan. 15, 2022

Language: Английский

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Targeting macrophage TFEB-14-3-3 epsilon Interface by naringenin inhibits abdominal aortic aneurysm

Cell Discovery, Journal Year: 2022, Volume and Issue: 8(1)

Published: March 1, 2022

Abdominal aortic aneurysm (AAA) is a lethal cardiovascular disease, and there no proven drug treatment for this condition. In study, by using the Connectivity Map (CMap) approach, we explored naringenin, naturally occurring citrus flavonoid, as putative agent inhibiting AAA. We then validated prediction with two independent mouse models of AAA, calcium phosphate (CaPO4)-induced C57BL/6J mice angiotensin II-infused ApoE-/- mice. Naringenin effectively blocked formation AAAs progression established AAAs. Transcription factor EB (TFEB) master regulator lysosome biogenesis. Intriguingly, protective role naringenin on AAA was abolished macrophage-specific TFEB depletion in Unbiased interactomics, combined isothermal titration calorimetry (ITC) cellular thermal shift assays (CETSAs), further revealed that directly bound to 14-3-3 epsilon TFEB-14-3-3 interaction, therefore promoted nuclear translocation activation. On one hand, activated lysosome-dependent inhibition NLRP3 inflammasome repressed aneurysmal inflammation. other induced TFEB-dependent transcriptional activation GATA3, IRF4, STAT6 reparative M2 macrophage polarization. summary, derived or shows promising efficacy

Language: Английский

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Matrix stiffness regulates macrophage polarization in atherosclerosis

Pharmacological Research, Journal Year: 2022, Volume and Issue: 179, P. 106236 - 106236

Published: April 26, 2022

Language: Английский

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Gallic acid ameliorates dextran sulfate sodium-induced ulcerative colitis in mice via inhibiting NLRP3 inflammasome

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: Jan. 25, 2023

Background: Ulcerative colitis (UC) is a chronic recurrent inflammatory bowel disease (IBD). The conventional drugs for UC may induce severe side effects. Herbal medicine considered as complementary and alternative choice UC. Purpose: This study aims to estimate the effect of natural polyphenol gallic acid (GA) on NLRP3 inflammasome with dextran sulfate sodium (DSS)-induced in mice. Study design: body weights symptoms BALB/c mice were recorded. Histological evaluation, ELISA, q-PCR, immunohistochemistry, western blotting carried out observe morphology, cytokine contents, mRNA expressions, protein respectively. Lipopolysaccharide (LPS)-induced RAW264.7 macrophage was used probe GA's relative expression. Results: GA attenuated weight loss (p < 0.05), relieved symptoms, ameliorated colonic morphological injury 0.05) induced by DSS. also lowered contents TNF-α, IL-1β, IL-18, IL-33, IFN-γ serum colon mice, which elevated DSS, downregulated protein, expressions pathway tissue. Furthermore, iNOS 0.01), COX2 P-p65 suppressed NO release 0.001) LPS-induced cells. Conclusion: DSS-induced via inhibiting inflammasome. These findings furnish evidence anti-inflammatory herbal medicines containing

Language: Английский

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2D Cobalt Oxyhydroxide Nanozymes Inhibit Inflammation by Targeting the NLRP3 Inflammasome

Advanced Functional Materials, Journal Year: 2023, Volume and Issue: 33(27)

Published: April 19, 2023

Abstract Nucleotide‐binding domain and leucine rich repeat family pyrin containing 3 (NLRP3) inflammasomes are implicated in diverse inflammatory diseases, so their activation needs to be tightly controlled. Over generation of reactive oxygen species (ROS) is a key factor NLRP3 inflammasome activation. Consequently, nanozymes with ROS scavenging ability potential inhibitors promising therapeutic agents for related diseases. Herein, type 2D cobalt hydroxide oxide nanosheets (Co NSs), nanozyme excellent multienzyme‐like activity, possessing peroxidase (POD), catalase (CAT), superoxide dismutase (SOD) activities, exhibits superior properties protects cells from oxidative damage. Density functional theory (DFT) calculations further reveal these enzyme‐like catalytic reactions eliminating spontaneous CAT dominant under physiological conditions. Performing multienzyme properties, Co NSs present anti‐inflammation activity by blocking oligomerization ASC speck formation, thereby inhibiting assembly Importantly, treatment attenuates the severity LPS‐induced systemic inflammation DSS‐induced colitis. This study highlights successful strategy utilizing cobalt‐based scavenge provides valuable insights into underlying mechanism, demonstrating effects prevention NLRP3‐associatied

Language: Английский

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