γ-Mangostin isolated from Garcinia mangostana L. suppresses inflammation and alleviates symptoms of osteoarthritis via modulating miR-124-3p/IL-6/NF-κB signaling

Abstract

Osteoarthritis (OA) a disease associated with joints and become severe with age, due to softening, inflammation and degradation of cartilage in joints. The agents that can target OA is needed, specifically without any side effects. Garcinia mangostana L. (Mangosteen) a tropical fruit used to treat many skin and stomach associated ailments. γ-Mangostin (γ-MS) a key bioactive substance present in mangosteen. Here, we aimed to explore γ-MS potential in targeting the pro-inflammatory cytokine, factors and miRs in OA progression. Significantly, γ-MS suppresses the inflammatory cytokines (IL-6, TNF-α, and INF-γ) and factors (NF-κB, STAT3, and COX-2) which regulates/participate in the catabolic process of cartilage destruction. Result of Hematoxylin-eosin (H&E) staining of tissue sections of OA joints of γ-MS treated and non-treated mice confirm γ-MS improves the signs of injuries, and maintains the structural integrity of the articular cartilage (epiphyseal disk joints and bone marrow) and reduces inflammation. Mechanistically, γ-MS targets miR-98-5p and miR-124-3p which are found to suppress the expression IL-6 and NF-κB, respectively. But in OA these miRs are www.aging-us.com 6631 AGING inhibited, especially miR-124-3p which regulates not only NF-κB but also TNF-α, IL-6 and MMP7. With a further investigation underway, γ-MS represents an important source for treating and managing OA.

<p>Cytotoxic and Antiproliferative Effects of β-Mangostin on Rat C6 Glioma Cells Depend on Oxidative Stress Induction via PI3K/AKT/mTOR Pathway Inhibition</p>

“…7 Mangosteen fruit shells contain a variety of xanthone derivatives, mainly including α-mangostin, βmangostin and γ-mangostin. Previous reports have demonstrated that extracts of mangosteen have antitumoral, 8,9 antioxidant, [10][11][12] antiallergic, 13 anti-inflammatory, 14,15 antibacterial, 16 and antiviral activities. 17 β-Mangostin are xanthones, which have anticancer activity against several types of cancer cells, including hepatocellular carcinoma cells, 18 melanoma cells, 19 and cervical cancer cells.…”

Natural Xanthones and Skin Inflammatory Diseases: Multitargeting Mechanisms of Action and Potential Application

“…Similarly, inhibitory effects on the secretion of TNF-α and IL-6 were observed in LPS-stimulated mice with ED 50 of less than 100 mg/kg (Lee et al, 2013). Besides that, 3 was able to relieve inflammatory symptoms of osteoarthritis by inhibiting the expression of pro-inflammatory transcription factors STAT3 and NF-κB, as well as the expression of cytokines IL-6 and TNF-α (Chiu et al, 2020).…”

“…As an inflammatory disease, treatment of psoriasis commonly involves anti-TNF agents (Zhao et al, 2017). Inhibitory effects towards TNF-α are commonly observed as exhibiting anti-inflammatory effects of xanthones including 2 (Gutierrez-Orozco et al, 2013;Lee et al, 2013;Im et al, 2017;Herrera-Aco et al, 2019), 3 (Xu et al, 2018;Chiu et al, 2020), 5 (Lee et al, 2013) and 8 (Wang et al, 2018b) are considered potential compounds for psoriasis treatment. A complication commonly associated with psoriasis is inflammatory arthritis where pathogenesis involves similar immunological aberrations of inflammatory cytokines such as IL-17, IL-22, IL-23 and IFN-γ (Sankowski et al, 2013;Schön, 2019).…”

Mesenchymal stem cell-derived extracellular vesicles prevent the development of osteoarthritis via the circHIPK3/miR-124-3p/MYH9 axis

“…We found that several miRNAs were candidate binding targets of circHIPK3. With the highest binding score to circHIPK3 and a documented role in OA [ 56 ], miR-124-3p was selected for the follow-up research. Based on the predicted binding sites, we designed and built circHIPK3 wild-type plasmids and mutant-type plasmids (Fig.…”

“…Meanwhile, Chiu et al . observed that gamma-mangostin isolated from Garcinia mangostana L. suppresses inflammation and relieves OA symptoms by modulating miR-124-3p/IL-6/NF-kappaB signaling [ 56 ]. Wang et al found that down-regulation of lncRNA SNHG14 inhibits FSTL-1-mediated activation of NLRP3 and TLR4/NF-κB signalling pathway activation by targeting miR-124-3p, thus attenuating inflammatory reactions in OA [ 76 ].…”