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Hyaluronic acid is a key metabolite of the ECM and plays an important role in moisturization, inflammation, cell migration and promotion of collagen synthesis ( Inflammation is known to upregulate hyaluronidase expression in various tissues, and plant bioactive metabolites can indirectly affect hyaluronidase activity by reducing pro-inflammatory cytokine production (Yi et al., 2019), ALE (83), Poria cocos bioactive metabolites (Subedi et al., 2017), Green mandarins (Wang et al., 2020) inhibit proinflammatory cytokines such as tumour necrosis factor alpha (TNF-), interleukin, and hyaluronidase

For example, addition of exogenous complex I substrates, such as glutamate plus malate, or -KG, significantly augmented NADH levels and mitochondrial membrane potential, which stimulated H 2 O 2 production by 10-fold in isolated rat brain mitochondria (95)

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While this can provide short-term relief, prostaglandins play essential roles far beyond pain (27)