Objective: The proinflammatory cytokine interleukin‐1β (IL‐1β) induces the production of high levels of nitric oxide (NO) in human chondrocytes. Green tea (Camellia sinensis) polyphenols are potent antiinflammatory agents and have been shown to inhibit NO production in tumor cell lines. In the present study, we examined the effect of epigallocatechin‐3‐gallate (EGCG), a green tea polyphenol, on IL‐1β–induced production of NO in primary human osteoarthritis (OA) chondrocytes.Methods: Human chondrocytes were derived from OA cartilage and were treated with EGCG (100 μM) and IL‐1β (2 ng/ml) for different periods, and inducible nitric oxide synthase (iNOS) messenger RNA and protein expression was determined by real‐time quantitative reverse transcriptase–polymerase chain reaction and Western blotting, respectively. Production of NO was determined as nitrite in culture supernatant. Activation and translocation of nuclear factor κB (NF‐κB), levels of inhibitor of nuclear factor κB (IκB), and NF‐κB DNA binding activity were determined by Western blotting and a highly sensitive and specific enzyme‐linked immunosorbent assay. Activity of IκB kinase was determined using in vitro kinase assay.Results: Human chondrocytes cotreated with EGCG produced significantly less NO compared with chondrocytes stimulated with IL‐1β alone (P < 0.005). The inhibition of NO production correlated with the suppression of induction and expression of NF‐κB–dependent gene iNOS. EGCG inhibited the activation and translocation of NF‐κB to the nucleus by suppressing the degradation of its inhibitory protein IκBα in the cytoplasm.Conclusion: Our results indicate that EGCG inhibits the IL‐1β–induced production of NO in human chondrocytes by interfering with the activation of NF‐κB through a novel mechanism. Our data further suggest that EGCG may be a therapeutically effective inhibitor of IL‐1β–induced inflammatory effects that are dependent on NF‐κB activation in human OA chondrocytes.

Osteoarthritis (OA) is a debilitating, progressive disease of diarthrodial joints associated with aging. At the molecular level, OA is characterized by an imbalance between anabolic (i.e. extracellular matrix biosynthesis) and catabolic (i.e. extracellular matrix degradation) pathways in which articular cartilage is the principal site of tissue injury responses. The pathophysiology of OA also involves the synovium in that ‘nonclassical’ inflammatory synovial processes contribute to OA progression. Chondrocytes are critical to the OA process in that the progression of OA can be judged by the vitality of chondrocytes and their ability to resist apoptosis. Growth factors exemplified by insulin-like growth factor-1, its binding proteins and transforming growth factor-β contribute to anabolic pathways including compensatory biosynthesis of extracellular matrix proteins. Catabolic pathways are altered by cytokine genes such as interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) which are upregulated in OA. In addition, IL-1 and TNF-α downregulate extracellular matrix protein biosynthesis while concomitantly upregulating matrix metalloproteinase (MMP) gene expression. When MMPs are activated, cartilage extracellular matrix degradation ensues apparently because levels of endogenous cartilage MMP inhibitors cannot regulate MMP activity. Therapeutic strategies designed to modulate the imbalance between anabolic and catabolic pathways in OA may include neutralizing cytokine activity or MMP gene expression or inhibiting signaling pathways which result in apoptosis dependent on mature caspase activity or mitogen-activated protein kinase (MAPK) activity. MAPK activity appears critical for regulating chondrocyte and synoviocyte apoptosis and MMP genes.

Neurodegenerative disorders encompass a wide range of pathological conditions caused by progressive damage to the neuronal cells and nervous-system connections, which primarily target neuronal dysfunction and result in problems with mobility, cognition, coordination, sensation, and strength. Molecular insights have revealed that stress-related biochemical alterations such as abnormal protein aggregation, extensive generation of reactive oxygen and nitrogen species, mitochondrial dysfunction, and neuroinflammation may lead to damage to neuronal cells. Currently, no neurodegenerative disease is curable, and the available standard therapies can only provide symptomatic treatment and delay the progression of the disease. Interestingly, plant-derived bioactive compounds have drawn considerable attention due to their well-established medicinal properties, including anti-apoptotic, antioxidant, anti-inflammatory, anticancer, and antimicrobial properties, as well as neuroprotective, hepatoprotective, cardioprotective, and other health benefits. Plant-derived bioactive compounds have received far more attention in recent decades than synthetic bioactive compounds in the treatment of many diseases, including neurodegeneration. By selecting suitable plant-derived bioactive compounds and/or plant formulations, we can fine tune the standard therapies because the therapeutic efficacy of the drugs is greatly enhanced by combinations. A plethora of in vitro and in vivo studies have demonstrated plant-derived bioactive compounds’ immense potential, as proven by their capacity to influence the expression and activity of numerous proteins implicated in oxidative stress, neuroinflammation, apoptosis, and aggregation. Thus, this review mostly focuses on the antioxidant, anti-inflammatory, anti-aggregation, anti-cholinesterase, and anti-apoptotic properties of several plant formulations and plant-derived bioactive compounds and their molecular mechanisms against neurodegenerative disorders.