Regulation of Mitogen-Activated Protein Kinase Signaling Pathway and Proinflammatory Cytokines by Ursolic Acid in Murine Macrophages Infected with Mycobacterium avium

Pitaloka, Dian Ayu Eka; Cooper, Andrea; Artarini, Anita; Damayanti, Sophi; Sukandar, Elin Yulinah

doi:10.4081/idr.2020.8717

Cited by 8 publications

(10 citation statements)

References 25 publications

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“…The UA drug was extracted from many plants such as the whole grass of the Labiatae plant, Prunella vulgaris, and the leaves of the holly, holly, iron holly leaves. 33 The UA is a triterpenoid compound found in natural plants and has many biological effects such as sedative, 34 anti-inflammatory, 35 antibacterial, 36 and immune defense responses. 37 The Ursolic acid (UA), also promote osteoblast differentiation and new bone formation.…”

Section: Resultsmentioning

confidence: 99%

Ursolic Acid Loaded-Mesoporous Hydroxylapatite/ Chitosan Therapeutic Scaffolds Regulate Bone Regeneration Ability by Promoting the M2-Type Polarization of Macrophages

Yu¹,

Wang²,

Liu³

et al. 2021

IJN

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Purpose Mesoporous hydroxylapatite (MHAP) might be important for bone regeneration, and ursolic acid (UA) has anti-inflammatory effects. Accordingly, we developed, for the first time, ursolic acid-loaded MHAP-chitosan (MHAP-CS-UA) scaffolds to treat bone defects. Methods In vitro, we synthesize biomaterial scaffolds. By SEM, XRD, EDS and FTIR, we test the performance of the hybrid scaffolds. By drug release, flow cytometry, immunofluorescence, alizarin red staining, and Western blotting, we test the anti-inflammatory and osteo-inductive properties of scaffolds. In vivo, we verify osseointegration ability and bone regeneration. Results The MHAP is a rod-shaped structure with a length of 100~300nm and a diameter of 40~60nm. The critical structure gives the micro-scaffold a property of control release due to the pore sizes of 1.6~4.3 nm in hydroxyapatite and the hydrogen bonding between the scaffolds and UA drugs. The released UA drugs could notably inhibit the polarization of macrophages to pro-inflammatory macrophages (M1 type) and promote the expression of osteogenic-related genes (COL1, ALP and OPG) and osteogenic-related proteins (BMP-2, RUNX2 and COL1). Conclusion The MHAP-CS-UA scaffolds have good anti-inflammatory, osseointegration, osteo-inductivity and bone regeneration. And they will be the novel and promising candidates to cure the bone disease.

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Section: Resultsmentioning

confidence: 99%

Ursolic Acid Loaded-Mesoporous Hydroxylapatite/ Chitosan Therapeutic Scaffolds Regulate Bone Regeneration Ability by Promoting the M2-Type Polarization of Macrophages

Yu¹,

Wang²,

Liu³

et al. 2021

IJN

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“…It has been shown to promote phagocytosis, autophagy induction, and ROS production in macrophages ( Figure 3 ). Previous studies have revealed that UA promotes the intracellular killing effect of macrophages in mycobacterial infection ( 164 – 166 , 192 , 193 ). UA treatment significantly reduced the lung Mtb burden and pneumonic lung area ( 164 ) ( Table 2 ).…”

Section: Hdts Modulate Macrophage Functions For Mac Infectionmentioning

confidence: 99%

Modulating macrophage function to reinforce host innate resistance against Mycobacterium avium complex infection

et al. 2022

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Mycobacterium avium complex (MAC) is the main causative agent of infectious diseases in humans among nontuberculous mycobacteria (NTM) that are ubiquitous organisms found in environmental media such as soil as well as in domestic and natural waters. MAC is a primary causative agent of NTM-lung disease that threaten immunocompromised or structural lung disease patients. The incidence and the prevalence of M. tuberculosis infection have been reduced, while MAC infections and mortality rates have increased, making it a cause of global health concern. The emergence of drug resistance and the side effects of long-term drug use have led to a poor outcome of treatment regimens against MAC infections. Therefore, the development of host-directed therapy (HDT) has recently gained interest, aiming to accelerate mycobacterial clearance and reversing lung damage by employing the immune system using a novel adjuvant strategy to improve the clinical outcome of MAC infection. Therefore, in this review, we discuss the innate immune responses that contribute to MAC infection focusing on macrophages, chief innate immune cells, and host susceptibility factors in patients. We also discuss potential HDTs that can act on the signaling pathway of macrophages, thereby contributing to antimycobacterial activity as a part of the innate immune response during MAC infection. Furthermore, this review provides new insights into MAC infection control that modulates and enhances macrophage function, promoting host antimicrobial activity in response to potential HDTs and thus presenting a deeper understanding of the interactions between macrophages and MACs during infection.

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“…activated protein kinase (p38MAPK) [32]. Therefore, UA could avert SARS-CoV-2 infection from causing ALI through modulation of proinflammatory and inflammatory signaling pathways.…”

Section: Effective For Treatment Of Multiple Sclerosis By Inhibiting Th17mentioning

confidence: 99%

The possible role of ursolic acid in Covid-19: A real game changer

Al-Kuraishy

Al-Gareeb

Batiha

2022

Clinical Nutrition ESPEN

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Ursolic acid (UA) is a pentacyclic terpenoid is usually found in the fruit peels and stem bark as secondary metabolites. UA has antiviral, antibacterial, and antiparasitic properties. UA has a wide spectrum of pharmacological activities against different infections. Because of the greatest antiviral and anti-inflammatory properties of UA, so it could be a plausible therapeutic herbal medicine in Covid-19 treatment. Covid-19 is a recent worldwide virulent disease pandemic due to severe acute respiratory coronavirus disease 2 (SARS-CoV-2). The pathogenesis of SARS-CoV-2 infection is related to the direct cytopathic effect and exaggerated immune response by which acute lung injury (ALI) and/or acute respiratory distress syndrome might be developed in critical cases. UA may inhibit main protease of SARS-CoV-2, and inhibits the interface flanked by SARS-CoV-2 viral proteins and its entry point commonly recognized as angiotensin converting enzyme 2 (ACE2). In addition, UA attenuates SARS-CoV-2-induced inflammatory reactions and oxidative stress. Therefore, UA could avert SARS-CoV-2 infection from causing ALI. This opinion proposed that UA might be a potential candidate therapy against Covid-19 and can mitigate post-Covid-19 complications such as lung fibrosis. In this regards, forthcoming studies are reasonable to substantiate the therapeutic role of UA in Covid-19. However, taken into account that Covid-19 is yet to be investigating for further evaluations, therefore, clinical trials are recommended regarding use and dose of UA in Covid-19 treatment, as well as secondary effects.

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Regulation of Mitogen-Activated Protein Kinase Signaling Pathway and Proinflammatory Cytokines by Ursolic Acid in Murine Macrophages Infected with Mycobacterium avium

Cited by 8 publications

References 25 publications

Ursolic Acid Loaded-Mesoporous Hydroxylapatite/ Chitosan Therapeutic Scaffolds Regulate Bone Regeneration Ability by Promoting the M2-Type Polarization of Macrophages

Ursolic Acid Loaded-Mesoporous Hydroxylapatite/ Chitosan Therapeutic Scaffolds Regulate Bone Regeneration Ability by Promoting the M2-Type Polarization of Macrophages

Modulating macrophage function to reinforce host innate resistance against Mycobacterium avium complex infection

The possible role of ursolic acid in Covid-19: A real game changer

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