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For: Leu WJ, Chen JC, Guh JH. Extract From Plectranthus amboinicus Inhibit Maturation and Release of Interleukin 1β Through Inhibition of NF-κB Nuclear Translocation and NLRP3 Inflammasome Activation. Front Pharmacol 2019;10:573. [PMID: 31191313 PMCID: PMC6546882 DOI: 10.3389/fphar.2019.00573] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2019] [Accepted: 05/06/2019] [Indexed: 01/10/2023] Open

For:	Leu WJ, Chen JC, Guh JH. Extract From Plectranthus amboinicus Inhibit Maturation and Release of Interleukin 1β Through Inhibition of NF-κB Nuclear Translocation and NLRP3 Inflammasome Activation. Front Pharmacol 2019;10:573. [PMID: 31191313 PMCID: PMC6546882 DOI: 10.3389/fphar.2019.00573] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2019] [Accepted: 05/06/2019] [Indexed: 01/10/2023] Open

Number

Cited by Other Article(s)

Nazari M, Taremi S, Elahi R, Mostanadi P, Esmeilzadeh A. Therapeutic Properties of M2 Macrophages in Chronic Wounds: An Innovative Area of Biomaterial-Assisted M2 Macrophage Targeted Therapy. Stem Cell Rev Rep 2025;21:390-422. [PMID: 39556244 DOI: 10.1007/s12015-024-10806-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/16/2024] [Indexed: 11/19/2024]

Abstract

Wound healing is a dynamic, multi-stage process essential for restoring skin integrity. Dysregulated wound healing is often linked to impaired macrophage function, particularly in individuals with chronic underlying conditions. Macrophages, as key regulators of wound healing, exhibit significant phenotypic diversity, ranging from the pro-healing M2 phenotype to the pro-inflammatory M1 phenotype. Imbalances in the M1/M2 ratio or hyperactivation of the M1 phenotype can delay the normal healing. Consequently, strategies aimed at suppressing the M1 phenotype or promoting the shift of local skin macrophages toward the M2 phenotype can potentially treat chronic non-healing wounds. This manuscript provides an overview of macrophages' role in normal and pathological wound-healing processes. It examines various therapeutic approaches targeting M2 macrophages, such as ex vivo-activated macrophage therapy, immunopharmacological strategies, and biomaterial-directed macrophage polarization. However, it also highlights that M2 macrophage therapies and immunopharmacological interventions may have drawbacks, including rapid phenotypic changes, adverse effects on other skin cells, biotoxicity, and concerns related to biocompatibility, stability, and drug degradation. Therefore, there is a need for more targeted macrophage-based therapies that ensure optimal biosafety, allowing for effective reprogramming of dysregulated macrophages and improved therapeutic outcomes. Recent advances in nano-biomaterials have demonstrated promising regenerative potential compared to traditional treatments. This review discusses the progress of biomaterial-assisted macrophage targeting in chronic wound repair and addresses the challenges faced in its clinical application. Additionally, it explores novel design concepts for combinational therapies, such as incorporating regenerative particles like exosomes into dressing materials or encapsulating them in microneedling systems to enhance wound healing rates.

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Yu C, Hsieh P, Chao S, Liao Y, Yu C, Chueh PJ, Peng C, Lee S. Carvacrol inhibits the progression of oral submucous fibrosis via downregulation of PVT1/miR-20a-5p-mediated pyroptosis. J Cell Mol Med 2024;28:e70112. [PMID: 39320020 PMCID: PMC11423347 DOI: 10.1111/jcmm.70112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Revised: 09/01/2024] [Accepted: 09/16/2024] [Indexed: 09/26/2024] Open

Xu F, Yang F, Qiu Y, Wang C, Zou Q, Wang L, Li X, Jin M, Liu K, Zhang S, Zhang Y, Li B. The alleviative effect of C-phycocyanin peptides against TNBS-induced inflammatory bowel disease in zebrafish via the MAPK/Nrf2 signaling pathways. FISH & SHELLFISH IMMUNOLOGY 2024;145:109351. [PMID: 38171429 DOI: 10.1016/j.fsi.2023.109351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Revised: 12/23/2023] [Accepted: 12/29/2023] [Indexed: 01/05/2024]

Abstract

INTRODUCTION

Ulcerative colitis (UC) is an incurable and highly complex chronic inflammatory bowel disease (IBD) affecting millions of people worldwide. C-phycocyanin (C-PC) has been reported to possess outstanding anti-inflammatory activities and can effectively inhibit various inflammation-related diseases. Whether C-PC-derived bioactive peptides can inhibit intestinal inflammation is worth research and consideration.

METHODS

The inhibition activities of three anti-neuroinflammatory peptides were evaluated using 2-4-6-trinitrobenzen sulfonic acid (TNBS)-induced zebrafish colitis model. Subsequently, the abilities of peptides to promote gastrointestinal motility were also examined. The changes in the intestinal pathological symptoms and ultrastructure of intestinal, reactive oxygen species (ROS) levels, and antioxidant enzymes were then determined after co-treatment with peptides and TNBS. Transcriptome analysis was used to investigate the underlying ameliorating TNBS-induced colitis effects molecular mechanisms of better activity peptide. Furthermore, quantitative reverse-transcription polymerase chain reaction and molecular docking techniques verified the mRNA sequencing results.

RESULTS

Three peptides, MHLWAAK, MAQAAEYYR and MDYYFEER, which significantly inhibit macrophage migration, were synthesized. The results showed that these peptides could effectively alleviate the inflammatory responses in the TNBS-induced zebrafish model of colitis. In addition, co-treatment with TNBS and C-PC peptides could decrease ROS production and increase antioxidant enzyme activities in zebrafish larvae. Moreover, MHLWAAK had the most significantly therapeutic effects on colitis in zebrafish. The transcriptome analysis suggests that the effect of MHLWAAK on TNBS-induced colitis may be associated with the modulation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and mitogen-activated protein kinase (MAPK) signaling pathway associated genes. In addition, molecular docking was conducted to study the prospective interaction between peptides and the key proteins that streamline the Nrf2 and MAPK signaling pathways. IL-6, JNK3, TNF-α, KEAP1-NRF2 complex and MAPK may be the core targets of MHLWAAK in treating colitis.

CONCLUSION

The results suggested that the three C-PC-derived peptides could ameliorate TNBS-induced colitis in zebrafish, and these peptides might be a promising therapeutic candidate for UC treatment.

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Affiliation(s)

Fenghua Xu Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250103, China; Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Jinan, 250103, China; Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, 266000, China
Fei Yang Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250103, China; Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Jinan, 250103, China
Yuezi Qiu Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250103, China; Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Jinan, 250103, China
Chuansen Wang Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250103, China; Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Jinan, 250103, China
Qinglin Zou Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250103, China; Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Jinan, 250103, China
Lizhen Wang Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250103, China; Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Jinan, 250103, China
Xiaobin Li Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250103, China; Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Jinan, 250103, China
Meng Jin Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250103, China; Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Jinan, 250103, China
Kechun Liu Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250103, China; Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Jinan, 250103, China
Shanshan Zhang Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250103, China; Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Jinan, 250103, China.
Yun Zhang Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250103, China; Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Jinan, 250103, China.
Bing Li Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, 266000, China.

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Cavalcante-Silva J, Koh TJ. Targeting the NOD-Like Receptor Pyrin Domain Containing 3 Inflammasome to Improve Healing of Diabetic Wounds. Adv Wound Care (New Rochelle) 2023;12:644-656. [PMID: 34841901 PMCID: PMC10701516 DOI: 10.1089/wound.2021.0148] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Accepted: 11/08/2021] [Indexed: 12/21/2022] Open

Abstract

Significance: Chronic skin wounds are a significant health problem around the world, often leading to amputation and even death. Although persistent inflammation is a hallmark of these poorly healing wounds, few available therapies have been designed to target inflammation. In this review, we summarize available evidence of the role of the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome in impaired wound healing and describe strategies to inhibit the inflammasome to improve wound healing. Recent Advances: The NLRP3 inflammasome plays an important physiological role in skin wound healing, during which transient inflammasome activity contributes to both epidermal and dermal healing. In contrast, sustained activity of the NLRP3 inflammasome leads to impaired epidermal and dermal healing associated with diabetes. Of importance, preclinical studies have demonstrated that inhibiting the NLRP3 inflammasome-induced resolution of inflammation, increased granulation tissue formation and collagen deposition, and accelerated reepithelialization and wound closure. Critical Issues: NLRP3 inflammasome inhibitors have appealing potential for translation into therapies for chronic wounds. Although preclinical studies have shown promising results, there is a need for human/clinical studies to evaluate dosing formulations, potential therapeutic effects, dose-response relationships, and possible side effects. Future Directions: Among strategies to inhibit the NLRP3 inflammasome, glyburide, metformin, peroxisome proliferator-activated receptor agonists, and the dipeptidyl peptidase 4 inhibitor saxagliptin appear to be closest to clinical translation, as these drugs are already Food and Drug Administration approved for other indications. Future clinical studies are needed to develop topical formulations of these drugs, and to assess the safety and efficacy of these inhibitors, to improve healing of chronic wounds.

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Barbosa MDO, Wilairatana P, Leite GMDL, Delmondes GDA, da Silva LYS, Júnior SCA, Dantas LBR, Bezerra DS, de Beltrão ICSL, Dias DDQ, Ribeiro-Filho J, Felipe CFB, Coutinho HDM, de Menezes IRA, Kerntopf Mendonça MR. Plectranthus Species with Anti-Inflammatory and Analgesic Potential: A Systematic Review on Ethnobotanical and Pharmacological Findings. Molecules 2023;28:5653. [PMID: 37570622 PMCID: PMC10419981 DOI: 10.3390/molecules28155653] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Revised: 07/09/2023] [Accepted: 07/20/2023] [Indexed: 08/13/2023] Open

Abstract

The use of medicinal plants to treat inflammatory conditions and painful processes has attracted the attention of scientists and health professionals due to the evidence that natural products can promote significant therapeutic benefits associated with fewer adverse effects compared to conventional anti-inflammatory drugs. The genus Plectranthus is composed of various plants with pharmacological potential, which are used to treat various diseases in traditional communities worldwide. The present study systematically reviewed Plectranthus species with anti-inflammatory and analgesic potential. To this end, a systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. The search was conducted on the following databases: PubMed, ScienceDirect, SciVerse Scopus, and Web of Science. Different combinations of search terms were used to ensure more excellent article coverage. After the selection, a total of 45 articles were included in this review. This study identified twelve Plectranthus species indicated for the treatment of different inflammatory conditions, such as wounds, fever, bronchitis, abscess, asthma, hepatitis, labyrinthitis, tonsillitis, and uterine inflammation. The indications for pain conditions included headache, sore throat, heartburn, menstrual cramp, colic, toothache, stomachache, migraine, chest pain, abdominal pain, local pain, labor pain, and recurring pain. Among the listed species, ten plants were found to be used according to traditional knowledge, although only four of them have been experimentally studied. When assessing the methodological quality of preclinical in vivo assays, most items presented a risk of bias. The SR results revealed the existence of different Plectranthus species used to treat inflammation and pain. The results of this systematic review indicate that Plectranthus species have the potential to be used in the treatment of diseases with an inflammatory component, as well as in the management of pain. However, given the risk of biases, the experimental analysis of these species through preclinical testing is crucial for their safe and effective use.

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Affiliation(s)

Maysa de Oliveira Barbosa Department of Biological Chemistry, Regional University of Cariri-URCA, Crato 63105-000, CE, Brazil; (M.d.O.B.); (G.M.d.L.L.); (L.Y.S.d.S.); (L.B.R.D.); (D.S.B.); (I.C.S.L.d.B.); (D.d.Q.D.); (H.D.M.C.); (M.R.K.M.)
Polrat Wilairatana Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
Giovana Mendes de Lacerda Leite Department of Biological Chemistry, Regional University of Cariri-URCA, Crato 63105-000, CE, Brazil; (M.d.O.B.); (G.M.d.L.L.); (L.Y.S.d.S.); (L.B.R.D.); (D.S.B.); (I.C.S.L.d.B.); (D.d.Q.D.); (H.D.M.C.); (M.R.K.M.)
Gyllyandeson de Araújo Delmondes Collegiate of Nursing, Federal University of Vale do São Francisco (UNIVASF), Petrolina 56304-917, PE, Brazil;
Lucas Yure Santos da Silva Department of Biological Chemistry, Regional University of Cariri-URCA, Crato 63105-000, CE, Brazil; (M.d.O.B.); (G.M.d.L.L.); (L.Y.S.d.S.); (L.B.R.D.); (D.S.B.); (I.C.S.L.d.B.); (D.d.Q.D.); (H.D.M.C.); (M.R.K.M.)
Silvio Caetano Alves Júnior Oswaldo Cruz Foundation (FIOCRUZ), Fiocruz Ceará, Eusébio 61773-270, CE, Brazil; (S.C.A.J.); (J.R.-F.)
Lindaiane Bezerra Rodrigues Dantas Department of Biological Chemistry, Regional University of Cariri-URCA, Crato 63105-000, CE, Brazil; (M.d.O.B.); (G.M.d.L.L.); (L.Y.S.d.S.); (L.B.R.D.); (D.S.B.); (I.C.S.L.d.B.); (D.d.Q.D.); (H.D.M.C.); (M.R.K.M.)
Daniel Souza Bezerra Department of Biological Chemistry, Regional University of Cariri-URCA, Crato 63105-000, CE, Brazil; (M.d.O.B.); (G.M.d.L.L.); (L.Y.S.d.S.); (L.B.R.D.); (D.S.B.); (I.C.S.L.d.B.); (D.d.Q.D.); (H.D.M.C.); (M.R.K.M.)
Izabel Cristina Santiago Lemos de Beltrão Department of Biological Chemistry, Regional University of Cariri-URCA, Crato 63105-000, CE, Brazil; (M.d.O.B.); (G.M.d.L.L.); (L.Y.S.d.S.); (L.B.R.D.); (D.S.B.); (I.C.S.L.d.B.); (D.d.Q.D.); (H.D.M.C.); (M.R.K.M.)
Diógenes de Queiroz Dias Department of Biological Chemistry, Regional University of Cariri-URCA, Crato 63105-000, CE, Brazil; (M.d.O.B.); (G.M.d.L.L.); (L.Y.S.d.S.); (L.B.R.D.); (D.S.B.); (I.C.S.L.d.B.); (D.d.Q.D.); (H.D.M.C.); (M.R.K.M.)
Jaime Ribeiro-Filho Oswaldo Cruz Foundation (FIOCRUZ), Fiocruz Ceará, Eusébio 61773-270, CE, Brazil; (S.C.A.J.); (J.R.-F.)
Cícero Francisco Bezerra Felipe Department of Molecular Biology, Federal University of Paraiba, João Pessoa 58051-900, PB, Brazil;
Henrique Douglas Melo Coutinho Department of Biological Chemistry, Regional University of Cariri-URCA, Crato 63105-000, CE, Brazil; (M.d.O.B.); (G.M.d.L.L.); (L.Y.S.d.S.); (L.B.R.D.); (D.S.B.); (I.C.S.L.d.B.); (D.d.Q.D.); (H.D.M.C.); (M.R.K.M.)
Irwin Rose Alencar de Menezes Department of Biological Chemistry, Regional University of Cariri-URCA, Crato 63105-000, CE, Brazil; (M.d.O.B.); (G.M.d.L.L.); (L.Y.S.d.S.); (L.B.R.D.); (D.S.B.); (I.C.S.L.d.B.); (D.d.Q.D.); (H.D.M.C.); (M.R.K.M.)
Marta Regina Kerntopf Mendonça Department of Biological Chemistry, Regional University of Cariri-URCA, Crato 63105-000, CE, Brazil; (M.d.O.B.); (G.M.d.L.L.); (L.Y.S.d.S.); (L.B.R.D.); (D.S.B.); (I.C.S.L.d.B.); (D.d.Q.D.); (H.D.M.C.); (M.R.K.M.)

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Chen R, Li F, Zhou K, Xing M, Zhang X, Zhao X, Wu C, Han Z, Zhou Y, Yan L, Xia D. Component identification of modified sanmiao pills by UPLC-Xevo G2-XS QTOF and its anti-gouty arthritis mechanism based on network pharmacology and experimental verification. JOURNAL OF ETHNOPHARMACOLOGY 2023;311:116394. [PMID: 36940736 DOI: 10.1016/j.jep.2023.116394] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 03/01/2023] [Accepted: 03/13/2023] [Indexed: 06/18/2023]

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Modified sanmiao pills (MSMP), a traditional Chinese medicine (TCM) formula, is consisted of rhizome of Smilax glabra Roxb., Cortexes of Phellodendron chinensis Schneid., rhizome of Atractylodes chinensis (DC.) Koidz., and roots of Cyathula officinalis Kuan. in a ratio of 3:3:2:1. This formula has been broadly applied to treat gouty arthritis (GA) in China.

AIMS OF THE STUDY

To elaborate the pharmacodynamic material basis and pharmacological mechanism of MSMP against GA.

MATERIALS AND METHODS

UPLC-Xevo G2-XS QTOF combined with UNIFI platform was applied to qualitatively assess the chemical compounds of MSMP. Network pharmacology and molecular docking were used to identify the active compounds, core targets and key pathways of MSMP against GA. The GA mice model was established by MSU suspension injecting into ankle joint. The swelling index of ankle joint, expressions of inflammatory cytokines, and histopathological changes in mice ankle joints were determined to validate the therapeutic effect of MSMP against GA. The protein expressions of TLRs/MyD88/NF-κB signaling pathway and NLRP3 inflammasome in vivo was detected by Western blotting.

RESULTS

In total, 34 chemical compounds and 302 potential targets of MSMP were ascertained, of which 28 were overlapping targets pertaining to GA. 143 KEGG enrichment pathway were obtained, of which the NOD-like receptor signaling pathway, Toll-like receptor signaling pathway, and NF-κB signaling pathway were strongly associated with GA. In silico study indicated that the active compounds had excellent binding affinity to core targets. In vivo study confirmed that MSMP observably decreased swelling index and alleviated pathological damage to ankle joints in acute GA mice. Besides, MSMP significantly inhibited the secretion of inflammatory cytokines (IL-1β, IL-6, and TNF-α) induced by MSU, as well as the expression levels of key proteins involved in TLRs/MyD88/NF-κB signaling pathway and NLRP3 inflammasome.

CONCLUSION

MSMP possessed a pronounced therapeutic effect on acute GA. Results from network pharmacology and molecular docking showed that obaculactone, oxyberberine, and neoisoastilbin might treat gouty arthritis by down-regulating TLRs/MyD88/NF-κB signaling pathway and NLRP3 inflammasome.

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Bimolata W, Bhattacharya R, Goswami A, Dey PK, Mitra A. Spectral Light Treatment Influenced Morpho-Physiological Properties and Carvacrol Accumulation in Indian Borage. JOURNAL OF PLANT GROWTH REGULATION 2023:1-15. [PMID: 37359317 PMCID: PMC10201491 DOI: 10.1007/s00344-023-11028-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Accepted: 05/05/2023] [Indexed: 06/28/2023]

Zhang Y, Zhang X, Zhang N, Yu S, Zhong Y, Zhao K. Leukadherin-1 inhibits NLRP3 inflammasome by blocking inflammasome assembly. Int Immunopharmacol 2023;118:110024. [PMID: 36958209 DOI: 10.1016/j.intimp.2023.110024] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 03/02/2023] [Accepted: 03/08/2023] [Indexed: 03/25/2023]

Development of electrospun Plectranthus amboinicus loaded PCL polymeric nanofibrous scaffold for skin wound healing application: in-vitro and in-silico analysis. JOURNAL OF POLYMER RESEARCH 2023. [DOI: 10.1007/s10965-023-03474-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/17/2023]

Sumpio BJ, Mezghani I, Wang E, Li Z, Valsami EA, Theocharidis G, Veves A. Experimental treatments in clinical trials for diabetic foot ulcers: wound healers in the pipeline. Expert Opin Investig Drugs 2023;32:95-99. [PMID: 36749693 DOI: 10.1080/13543784.2023.2178418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]

Natural Monoterpenes as Potential Therapeutic Agents against Atherosclerosis. Int J Mol Sci 2023;24:ijms24032429. [PMID: 36768748 PMCID: PMC9917110 DOI: 10.3390/ijms24032429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Revised: 01/12/2023] [Accepted: 01/16/2023] [Indexed: 01/28/2023] Open

Rayate AS, Nagoba BS, Mumbre SS, Mavani HB, Gavkare AM, Deshpande AS. Current scenario of traditional medicines in management of diabetic foot ulcers: A review. World J Diabetes 2023;14:1-16. [PMID: 36684382 PMCID: PMC9850800 DOI: 10.4239/wjd.v14.i1.1] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 11/04/2022] [Accepted: 12/06/2022] [Indexed: 01/10/2023] Open

Abstract

Diabetic foot infections and diabetic foot ulcers (DFU) cause significant suffering and are often recurring. DFU have three important pathogenic factors, namely, microangiopathy causing local tissue anoxia, neuropathy making the foot prone to injuries from trivial trauma, and local tissue hyperglycaemia favouring infection and delaying the wound healing. DFU have been the leading cause for non-traumatic amputations of part or whole of the limb. Western medicines focus mainly on euglycaemia, antimicrobials, debridement and wound cover with grafts, and off-loading techniques. Advances in euglycaemic control, foot care and footwear, systemic antimicrobial therapy, and overall health care access and delivery, have resulted in an overall decrease in amputations. However, the process of wound care after adequate debridement remains a major cost burden globally, especially in developing nations. This process revolves around two basic concerns regarding control/eradication of local infection and promotion of faster healing in a chronic DFU without recurrence. Wound modulation with various dressings and techniques are often a costly affair. Some aspects of the topical therapy with modern/Western medicines are frequently not addressed. Cost of and compliance to these therapies are important as both the wounds and their treatment are “chronic.” Naturally occurring agents/medications from traditional medicine systems have been used frequently in different cultures and nations, though without adequate clinical base/relevance. Traditional Chinese medicine involves restoring yin-yang balance, regulating the ‘chi’, and promoting local blood circulation. Traditional medicines from India have been emphasizing on ‘naturally’ available products to control wound infection and promote all the aspects of wound healing. There is one more group of chemicals which are not pharmaceutical agents but can create acidic milieu in the wound to satisfy the above-mentioned basic concerns. Various natural and plant derived products (e.g., honey, aloe vera, oils, and calendula) and maggots are also used for wound healing purposes. We believe that patients with a chronic wound are so tired physically, emotionally, and financially that they usually accept native traditional medicine which has the same cultural base, belief, and faith. Many of these products have never been tested in accordance to “evidence-based medicine.” There are usually case reports and experience-based reports about these products. Recently, there have been some trials (in vitro and in vivo) to verify the claims of usage of traditional medicines in management of DFU. Such studies show that these natural products enhance the healing process by controlling infection, stimulating granulation tissue, antimicrobial action, promoting fibroblastic activity and collagen deposition, etc. In this review, we attempt to study and analyse the available literature on results of topical traditional medicines, which are usually advocated in the management of DFU. An integrated and ‘holistic’ approach of both modern and traditional medicine may be more acceptable to the patient, cost effective, and easy to administer and monitor. This may also nevertheless lead to further improvement in quality of life and decrease in the rates of amputations for DFU.

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Nicolas M, Lasalo M, Chow S, Antheaume C, Huet K, Hnawia E, Guillemin GJ, Nour M, Matsui M. Anti-inflammatory activities of Coleus forsteri (formerly Plectranthus forsteri) extracts on human macrophages and chemical characterization. Front Pharmacol 2023;13:1081310. [PMID: 36699063 PMCID: PMC9868419 DOI: 10.3389/fphar.2022.1081310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Accepted: 12/22/2022] [Indexed: 01/11/2023] Open

Fontana G, Bruno M, Sottile F, Badalamenti N. The Chemistry and the Anti-Inflammatory Activity of Polymethoxyflavonoids from Citrus Genus. Antioxidants (Basel) 2022;12:antiox12010023. [PMID: 36670885 PMCID: PMC9855034 DOI: 10.3390/antiox12010023] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 12/15/2022] [Accepted: 12/21/2022] [Indexed: 12/24/2022] Open

Srivastava P, Sondak T, Sivashanmugam K, Kim KS. A Review of Immunomodulatory Reprogramming by Probiotics in Combating Chronic and Acute Diabetic Foot Ulcers (DFUs). Pharmaceutics 2022;14:2436. [PMID: 36365254 PMCID: PMC9699442 DOI: 10.3390/pharmaceutics14112436] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 11/02/2022] [Accepted: 11/08/2022] [Indexed: 08/29/2023] Open

Sim SL, Kumari S, Kaur S, Khosrotehrani K. Macrophages in Skin Wounds: Functions and Therapeutic Potential. Biomolecules 2022;12:1659. [PMID: 36359009 PMCID: PMC9687369 DOI: 10.3390/biom12111659] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 11/04/2022] [Accepted: 11/05/2022] [Indexed: 08/29/2023] Open

Lin CW, Hung CM, Chen WJ, Chen JC, Huang WY, Lu CS, Kuo ML, Chen SG. New Horizons of Macrophage Immunomodulation in the Healing of Diabetic Foot Ulcers. Pharmaceutics 2022;14:pharmaceutics14102065. [PMID: 36297499 PMCID: PMC9606988 DOI: 10.3390/pharmaceutics14102065] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 09/22/2022] [Accepted: 09/23/2022] [Indexed: 11/16/2022] Open

Wang X, Zhang S, Shang H, Wang C, Zhou F, Liu Y, Jiang Y, Gao P, Li N, Liu D, Shen M, Zhu R, Shi Y, Wei K. Evaluation of the antiviral effect of four plant polysaccharides against duck circovirus. Res Vet Sci 2022;152:446-457. [PMID: 36148714 DOI: 10.1016/j.rvsc.2022.09.009] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Revised: 09/06/2022] [Accepted: 09/09/2022] [Indexed: 11/19/2022]

Affiliation(s)

Xiangkun Wang Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, China; Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, Taian, China
Shuyu Zhang Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, China; Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, Taian, China
Hongqi Shang Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, China; Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, Taian, China
Cheng Wang Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, China; Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, Taian, China
Fan Zhou Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, China; Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, Taian, China
Yong Liu Shandong Feicheng Animal Husbandry and Veterinary Health Center, Taian, China
Yunxuan Jiang Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, China; Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, Taian, China
Panpan Gao Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, China; Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, Taian, China
Ning Li Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, China; Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, Taian, China
Defeng Liu Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, China; Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, Taian, China
Mingyue Shen Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, China; Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, Taian, China
Ruiliang Zhu Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, China; Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, Taian, China
Youfei Shi Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, China; Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, Taian, China.
Kai Wei Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, China; Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, Taian, China.

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Dahchour A. Anxiolytic and antidepressive potentials of rosmarinic acid: A review with a focus on antioxidant and anti-inflammatory effects. Pharmacol Res 2022;184:106421. [PMID: 36096427 DOI: 10.1016/j.phrs.2022.106421] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 08/29/2022] [Accepted: 08/30/2022] [Indexed: 10/14/2022]

Lin CW, Chen CC, Huang WY, Chen YY, Chen ST, Chou HW, Hung CM, Chen WJ, Lu CS, Nian SX, Chen SG, Chang HW, Chang VH, Liu LY, Kuo ML, Chang SC. Restoring Pro-healing/remodeling- associated M2a/c Macrophages using ON101 Accelerates Diabetic Wound Healing. JID INNOVATIONS 2022;2:100138. [PMID: 36017415 PMCID: PMC9396230 DOI: 10.1016/j.xjidi.2022.100138] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Revised: 04/26/2022] [Accepted: 04/27/2022] [Indexed: 01/05/2023] Open

Affiliation(s)

Ching-Wen Lin Oneness Biotech Co., Ltd., Taipei, Taiwan
Chih-Chiang Chen Department of Dermatology, Taipei Veterans General Hospital, Taipei, Taiwan Department of Dermatology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
Wen-Yen Huang Microbio Co., Ltd, Taipei, Taiwan
Yen-Yu Chen Oneness Biotech Co., Ltd., Taipei, Taiwan
Shiou-Ting Chen Microbio Co., Ltd, Taipei, Taiwan
Hung-Wen Chou Oneness Biotech Co., Ltd., Taipei, Taiwan
Chien-Ming Hung Microbio Co., Ltd, Taipei, Taiwan
Wan-Jiun Chen Oneness Biotech Co., Ltd., Taipei, Taiwan
Chia-Sing Lu NTU YongLin Institute of Health, National Taiwan University, Taipei, Taiwan
Shi-Xin Nian Department of Dermatology, Taipei Veterans General Hospital, Taipei, Taiwan
Shyi-Gen Chen Oneness Biotech Co., Ltd., Taipei, Taiwan Division of Plastic and Reconstructive Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
Hsuen-Wen Chang TMU Laboratory Animal Center, Office of Research and Development, Taipei Medical University, Taipei, Taiwan
Vincent H.S. Chang TMU Laboratory Animal Center, Office of Research and Development, Taipei Medical University, Taipei, Taiwan Department of Physiology, School of Medicine, Taipei Medical University, Taipei, Taiwan The PhD Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
Li-Ying Liu Department of Dermatology, Taipei Veterans General Hospital, Taipei, Taiwan
Ming-Liang Kuo Microbio Shanghai Co., Ltd., Shanghai, China
Shun-Cheng Chang Division of Plastic Surgery, Integrated Burn & Wound Care Center, Department of Surgery, Shuang-Ho Hospital; Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan Correspondence: Shun-Cheng Chang, Division of Plastic Surgery, Integrated Burn & Wound Care Center, Department of Surgery, Shuang-Ho Hospital; Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Number 291, Zhongzheng Road, Zhonghe District, New Taipei City 235, Taiwan.

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Kang X, Jin D, Jiang L, Zhang Y, Zhang Y, An X, Duan L, Yang C, Zhou R, Duan Y, Sun Y, Lian F. Efficacy and mechanisms of traditional Chinese medicine for COVID-19: a systematic review. Chin Med 2022;17:30. [PMID: 35227280 PMCID: PMC8883015 DOI: 10.1186/s13020-022-00587-7] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Accepted: 02/22/2022] [Indexed: 01/12/2023] Open

Huang YY, Lin CW, Cheng NC, Cazzell SM, Chen HH, Huang KF, Tung KY, Huang HL, Lin PY, Perng CK, Shi B, Liu C, Ma Y, Cao Y, Li Y, Xue Y, Yan L, Li Q, Ning G, Chang SC. Effect of a Novel Macrophage-Regulating Drug on Wound Healing in Patients With Diabetic Foot Ulcers: A Randomized Clinical Trial. JAMA Netw Open 2021;4:e2122607. [PMID: 34477854 PMCID: PMC8417758 DOI: 10.1001/jamanetworkopen.2021.22607] [Citation(s) in RCA: 62] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open

Abstract

IMPORTANCE

Delayed healing of diabetic foot ulcers (DFUs) is known to be caused by dysregulated M1/M2-type macrophages, and restoring the balance between these macrophage types plays a critical role in healing. However, drugs used to regulate M1/M2 macrophages have not yet been studied in large randomized clinical trials.

OBJECTIVE

To compare the topical application of ON101 cream with use of an absorbent dressing (Hydrofiber; ConvaTec Ltd) when treating DFUs.

DESIGN, SETTING, AND PARTICIPANTS

This multicenter, evaluator-blinded, phase 3 randomized clinical trial was performed in 21 clinical and medical centers across the US, China, and Taiwan from November 23, 2012, to May 11, 2020. Eligible patients with debrided DFUs of 1 to 25 cm2 present for at least 4 weeks and with Wagner grade 1 or 2 were randomized 1:1 to receive ON101 or control absorbent dressings.

INTERVENTIONS

Twice-daily applications of ON101 or a absorbent dressing changed once daily or 2 to 3 times a week for 16 weeks, with a 12-week follow-up.

MAIN OUTCOMES AND MEASURES

The primary outcome was the incidence of complete healing, defined as complete re-epithelialization at 2 consecutive visits during the treatment period assessed on the full-analysis set (FAS) of all participants with postrandomization data collected. Safety outcomes included assessment of the incidences of adverse events, clinical laboratory values, and vital signs.

RESULTS

In the FAS, 236 eligible patients (175 men [74.2%]; mean [SD] age, 57.0 [10.9] years; mean [SD] glycated hemoglobin level, 8.1% [1.6%]) with DFUs classified as Wagner grade 1 or 2 (mean [SD] ulcer area, 4.8 [4.4] cm2) were randomized to receive either the ON101 cream (n = 122) or the absorbent dressing (n = 114) for as long as 16 weeks. The incidence of complete healing in the FAS included 74 patients (60.7%) in the ON101 group and 40 (35.1%) in the comparator group during the 16-week treatment period (difference, 25.6 percentage points; odds ratio, 2.84; 95% CI, 1.66-4.84; P < .001). A total of 7 (5.7%) treatment-emergent adverse events occurred in the ON101 group vs 5 (4.4%) in the comparator group. No treatment-related serious adverse events occurred in the ON101 group vs 1 (0.9%) in the comparator group.

CONCLUSIONS AND RELEVANCE

In this multicenter randomized clinical trial, ON101 exhibited better healing efficacy than absorbent dressing alone in the treatment of DFUs and showed consistent efficacy among all patients, including those with DFU-related risk factors (glycated hemoglobin level, ≥9%; ulcer area, >5 cm2; and DFU duration, ≥6 months).

TRIAL REGISTRATION

ClinicalTrials.gov Identifier: NCT01898923.

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Affiliation(s)

Yu-Yao Huang Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan City, Taiwan Department of Medical Nutritional Therapy, Chang Gung Memorial Hospital, Taoyuan City, Taiwan
Ching-Wen Lin Oneness Biotech Company Limited, Taipei, Taiwan
Nai-Chen Cheng Division of Plastic Surgery, Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
Shawn M. Cazzell Limb Preservation Platform Inc, Fresno, California
Hsin-Han Chen Plastic and Reconstruction Surgery, China Medical University Hospital, Taichung, Taiwan
Kuo-Feng Huang Plastic Surgery Center, Chi-Mei Medical Center, Tainan, Taiwan
Kwang-Yi Tung Department of Surgery, Mackay Memorial Hospital, Taipei, Taiwan
Hsuan-Li Huang Division of Cardiology, Buddhist Tzu Chi General Hospital, Taipei, Taiwan
Pao-Yuan Lin Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Kaohsiung, Taiwan
Cherng-Kang Perng Division of Plastic and Reconstructive Surgery, Taipei Veterans General Hospital, Taipei, Taiwan Department of Surgery, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan
Bimin Shi Department of Endocrinology, The First Affiliated Hospital of Soochow University, Jiangsu, China
Chang Liu Department of Burn and Plastic Surgery, Affiliated Hospital of Jiangsu University, Jiangsu, China
Yujin Ma Department of Endocrinology, The First Affiliated Hospital of Henan Science and Technology University, Henan, China
Yemin Cao Department of Vascular Anomalies, Shanghai TCM (Traditional Chinese Medicine)–Integrated Hospital, Shanghai, China
Yanbing Li Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangdong, China
Yaoming Xue Department of Endocrinology, Nanfang Hospital of Southern Medical University, Guangdong, China
Li Yan Department of Endocrinology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangdong, China
Qiu Li Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, China
Guang Ning Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases, Shanghai, China Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the People’s Republic of China, Shanghai, China Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai, China Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shun-Cheng Chang Division of Plastic Surgery, Department of Surgery, Integrated Burn and Wound Care Center, Taipei Medical University-Shuang Ho Hospital, Ministry of Health and Welfare, New Taipei City, Taiwan Division of Plastic Surgery, Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

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Chen PY, Wang C, Zhang Y, Yuan C, Yu B, Ke XG, Wu HZ, Yang YF, Xiao XC. Predicting the Molecular Mechanism of “Angong Niuhuang Pills” in the Treatment of COVID-19 Based on Network Pharmacology. Nat Prod Commun 2021. [DOI: 10.1177/1934578x211024032] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open

Koycheva IK, Vasileva LV, Amirova KM, Marchev AS, Balcheva-Sivenova ZP, Georgiev MI. Biotechnologically Produced Lavandula angustifolia Mill. Extract Rich in Rosmarinic Acid Resolves Psoriasis-Related Inflammation Through Janus Kinase/Signal Transducer and Activator of Transcription Signaling. Front Pharmacol 2021;12:680168. [PMID: 33986690 PMCID: PMC8111009 DOI: 10.3389/fphar.2021.680168] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Accepted: 04/12/2021] [Indexed: 12/11/2022] Open

Lee J, Hong SM, Park N, Lee J, Jang SG, Cho ML, Kwok SK, Ju JH, Park SH. Red ginseng extracts as an adjunctive therapeutic for gout: preclinical and clinical evidence. FOOD AGR IMMUNOL 2020. [DOI: 10.1080/09540105.2020.1854189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022] Open

Affiliation(s)

Jennifer Lee Division of Rheumatology, Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
Seung-Min Hong The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, Republic of Korea
NaRae Park CiSTEM Laboratory, Convergent Research Consortium for Immunologic Disease, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Republic of Korea
Jaeseon Lee The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, Republic of Korea
Se Gwang Jang The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, Republic of Korea
Mi-La Cho The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, Republic of Korea
Seung-Ki Kwok Division of Rheumatology, Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, Republic of Korea
Ji Hyeon Ju Division of Rheumatology, Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea CiSTEM Laboratory, Convergent Research Consortium for Immunologic Disease, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Republic of Korea
Sung-Hwan Park Division of Rheumatology, Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, Republic of Korea

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Chalcones Display Anti-NLRP3 Inflammasome Activity in Macrophages through Inhibition of Both Priming and Activation Steps-Structure-Activity-Relationship and Mechanism Studies. Molecules 2020;25:molecules25245960. [PMID: 33339319 PMCID: PMC7767297 DOI: 10.3390/molecules25245960] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Revised: 12/11/2020] [Accepted: 12/13/2020] [Indexed: 12/13/2022] Open

Abstract

Chalcones are responsible for biological activity throughout fruits, vegetables, and medicinal plants in preventing and treating a variety of inflammation-related diseases. However, their structure-activity relationship (SAR) in inhibiting inflammasome activation has not been explored. We synthesized numerous chalcones and determined their SAR on lipopolysaccharide (LPS)-primed ATP-induced NLRP3 inflammasome activation. 11Cha1 displayed good inhibitory activity on release reaction of caspase-1, IL-1β, and IL-18. It significantly inhibited LPS-induced phosphorylation and proteolytic degradation of IĸB-α and nuclear translocation of NF-ĸB, but had little effect on mitogen-activated protein kinases (MAPKs) activities. Furthermore, 11Cha1 blocked LPS-induced up-regulation of NLRP3, pro-caspase-1, ASC, IL-18, and IL-1β, indicating the suppression on priming step of inflammasome activation. ASC dimerization and oligomerization are considered to be direct evidence for inflammasome activation. 11Cha1 profoundly inhibited ATP-induced formation of ASC dimers, trimers, and oligomers, and the assembly of ASC, pro-caspase-1, and NLRP3 in inflammasome formation. Decrease of intracellular K⁺ levels is the common cellular activity elicited by all NLRP3 inflammasome activators. 11Cha1 substantially diminished ATP-mediated K⁺ efflux, confirming the anti-NLRP3 inflammasome activity of 11Cha1. In summary, the SAR of chalcone derivatives in anti-inflammasome activities was examined. Besides, 11Cha1 inhibited both priming and activation steps of NLRP3 inflammasome activation. It inhibited NF-ĸB activation and subsequently suppressed the up-regulation of NLRP3 inflammasome components including NLRP3, ASC, pro-caspase-1, pro-IL-18, and pro-IL-1β. Next, 11Cha1 blocked ATP-mediated K⁺ efflux and suppressed the assembly and activation of NLRP3 inflammasome, leading to the inhibition of caspase-1 activation and proteolytic cleavage, maturation, and secretion of IL-1β and IL-18.

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Bian HT, Wang GH, Huang JJ, Liang L, Xiao L, Wang HL. Scutellarin protects against lipopolysaccharide-induced behavioral deficits by inhibiting neuroinflammation and microglia activation in rats. Int Immunopharmacol 2020;88:106943. [PMID: 33182053 DOI: 10.1016/j.intimp.2020.106943] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 07/28/2020] [Accepted: 08/25/2020] [Indexed: 12/15/2022]

Liu L, Xu X, Zhang N, Zhang Y, Zhao K. Acetylase inhibitor SI-2 is a potent anti-inflammatory agent by inhibiting NLRP3 inflammasome activation. Int Immunopharmacol 2020;87:106829. [PMID: 32736194 DOI: 10.1016/j.intimp.2020.106829] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 07/20/2020] [Accepted: 07/20/2020] [Indexed: 12/31/2022]

Huoxuezhitong capsule ameliorates MIA-induced osteoarthritis of rats through suppressing PI3K/ Akt/ NF-κB pathway. Biomed Pharmacother 2020;129:110471. [PMID: 32768958 DOI: 10.1016/j.biopha.2020.110471] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 06/16/2020] [Accepted: 06/24/2020] [Indexed: 12/19/2022] Open

Bian H, Wang G, Huang J, Liang L, Zheng Y, Wei Y, Wang H, Xiao L, Wang H. Dihydrolipoic acid protects against lipopolysaccharide-induced behavioral deficits and neuroinflammation via regulation of Nrf2/HO-1/NLRP3 signaling in rat. J Neuroinflammation 2020;17:166. [PMID: 32450903 PMCID: PMC7249417 DOI: 10.1186/s12974-020-01836-y] [Citation(s) in RCA: 67] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Accepted: 05/03/2020] [Indexed: 02/07/2023] Open

Abstract

Background

Recently, depression has been identified as a prevalent and severe mental disorder. However, the mechanisms underlying the depression risk remain elusive. The neuroinflammation and NLRP3 inflammasome activation are known to be involved in the pathology of depression. Dihydrolipoic acid (DHLA) has been reported as a strong antioxidant and exhibits anti-inflammatory properties in various diseases, albeit the direct relevance between DHLA and depression is yet unknown. The present study aimed to investigate the preventive effect and potential mechanism of DHLA in the lipopolysaccharide (LPS)-induced sickness behavior in rats.

Methods

Adult male Sprague–Dawley rats were utilized. LPS and DHLA were injected intraperitoneally every 2 days and daily, respectively. Fluoxetine (Flu) was injected intraperitoneally daily. PD98059, an inhibitor of ERK, was injected intraperitoneally 1 h before DHLA injection daily. Small interfering ribonucleic acid (siRNA) for nuclear factor erythroid 2-like (Nrf2) was injected into the bilateral hippocampus 14 days before the DHLA injection. Depression-like behavior tests were performed. Western blot and immunofluorescence staining detected the ERK/Nrf2/HO-1/ROS/NLRP3 pathway-related proteins.

Results

The DHLA and fluoxetine treatment exerted preventive effects in LPS-induced sickness behavior rats. The DHLA treatment increased the expression of ERK, Nrf2, and HO-1 but decreased the ROS generation levels and reduced the expression of NLRP3, caspase-1, and IL-1β in LPS-induced sickness behavior rats. PD98059 abolished the effects of DHLA on preventive effect as well as the levels of Nrf2 and HO-1 proteins. Similarly, Nrf2 siRNA reversed the preventive effect of DHLA administration via the decreased expression of HO-1.

Conclusions

These findings suggested that DHLA exerted a preventive effect via ERK/Nrf2/HO-1/ROS/NLRP3 pathway in LPS-induced sickness behavior rats. Thus, DHLA may serve as a potential therapeutic strategy for depression.

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Qi R, Zhang W, Zheng L, Xu M, Rong R, Zhu T, Yang C. Cyclic helix B peptide ameliorates renal tubulointerstitial fibrosis induced by unilateral ureter obstruction via inhibiting NLRP3 pathway. ANNALS OF TRANSLATIONAL MEDICINE 2020;8:167. [PMID: 32309314 PMCID: PMC7154394 DOI: 10.21037/atm.2020.02.12] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]

Hongyan L, Mengjiao Z, Chunyan W, Yaruo H. Rhynchophyllin attenuates neuroinflammation in Tourette syndrome rats via JAK2/STAT3 and NF-κB pathways. ENVIRONMENTAL TOXICOLOGY 2019;34:1114-1120. [PMID: 31231976 DOI: 10.1002/tox.22813] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Revised: 06/03/2019] [Accepted: 06/06/2019] [Indexed: 06/09/2023]