Mangiferin: Possible uses in the prevention and treatment of mixed osteoarthritic pain

Abstract

Osteoarthritis (OA) pain has been proposed to be a mixed pain state, because in some patients, central nervous system factors are superimposed upon the more traditional peripheral factors. In addition, a considerable amount of preclinical and clinical evidence has shown that, accompanying the central neuroplasticity changes and partially driven by a peripheral nociceptive input, a real neuropathic component occurs that are particularly linked to disease severity and progression. Hence, innovative strategies targeting neuroprotection and particularly neuroinflammation to prevent and treat OA pain could be introduced. Mangiferin (MG) is a glucosylxanthone that is broadly distributed in higher plants, such as Mangifera indica L. Previous studies have documented its analgesic, anti‐inflammatory, antioxidant, neuroprotective, and immunomodulatory properties. In this paper, we propose its potential utility as a multitargeted compound for mixed OA pain, even in the context of multimodal pharmacotherapy. This hypothesis is supported by three main aspects: the cumulus of preclinical evidence around this xanthone, some preliminary clinical results using formulations containing MG in clinical musculoskeletal or neuropathic pain, and by speculations regarding its possible mechanism of action according to recent advances in OA pain knowledge.

Mangiferin Relieves Lipopolysaccharide-Induced Injury by Up-Regulating miR-181a via Targeting PTEN in ATDC5 Cells

“…It was reported that LPS could contribute to low-grade cell inflammation (Huang and Kraus, 2016), while OA is exactly the low-grade inflammatory state mentioned above. Besides, previous investigations have demonstrated that MF was a xanthonoid with anti-inflammatory capacity, and it was reported to be a promising therapeutic drug for OA (Luczkiewicz et al, 2014;Saha et al, 2016;Qu et al, 2017b;Garrido-Suarez and Garrido, 2019). Previous investigations elucidated that MF markedly suppressed the productions of IL-6, IL-1b, and TNF-a in LPS-triggered primary hepatocytes, BALB/c mice mammary gland, and peritoneal macrophages (Jeong et al, 2014;Pan et al, 2016;Qu et al, 2017a).…”

“…Studies have already been conducted to investigate the influences of MF on bone-related diseases. For example, MF was reported to be effective in the treatment and prevention of mixed osteoarthritic pain (Garrido-Suarez and Garrido, 2019). Besides, an earlier literature clarified that MF exhibited anti-osteoclastogenic effects in the prevention and treatment of bone diseases, such as osteoporosis, erosive arthritis, and so on (Ang et al, 2011).…”

The Traditional Uses, Phytochemistry, Pharmacology, Toxicology, and Clinical Uses of Metagentiana Rhodantha (Franch.) T.N.Ho and S.W.Liu, an Ethnomedicine in Southwest China

“…Secoiridiods are characteristic substances of MR, while their contents are very low. Studies have indicated that secoiridiod glycosides possess wide biological activities such as anti-inflammatory and immunoregulatory (Saravanan et al, 2014a;Saravanan et al, 2014b;Wang et al, 2019a), analgesic (Liu et al, 2016;Garrido-Suárez et al, 2020), anti-tumor (Shao et al, 2017;Wu et al, 2017), hypoglycemic (Vaidya et al, 2013aDhanavathy, 2015;Vaidya et al, 2012;Vaidya et al, 2009), neuroprotective (Wang et al, 2019b;Wu et al, 2019) effects. Currently, about 20 iridoids secoiridoids (1～20) have been isolated from MR (Ma et al, 1996;Xu et al, 2008;Yao, 2013;Pan et al, 2015).…”

“…Recently, Garrido-Suárez et al (2020) proposed therapeutic potential of MAF as a multi-targeted compound in mixed OA pain based on three main aspects including the preclinical evidence of this xanthone, applications of formulas containing MAF in some preliminary clinical studies on musculoskeletal or neuropathic pain, and speculations regarding its possible mechanism of action in accordance with research advances in OA pain.…”

Allelopathy and allelopathic substances of mango (Mangifera indicaL.)

“…Mangiferin (2‐β‐D‐glucopyranosyl‐1,3,6,7‐tetrahydroxy‐[9H]‐xanthen‐9‐one) was first isolated from mango leaves, and it has been documented its analgesic, anti‐inflammatory, antioxidant, neuroprotective, and immunomodulatory properties (Garrido‐Suárez, Garrido, Piñeros, & Delgado‐Hernández, 2020; Imran et al, 2017). A number of secondary substances in many classes such as phenolic acids, flavonoids, terpenoids, and carotenoids have also been isolated from the extracts from various parts of mango plants such as leaves, roots, bark, flowers, fruits, and seeds (Table 3).…”