Juglanin ameliorates UVB‑induced skin carcinogenesis via anti‑inflammatory and proapoptotic effects in vivo and in vitro.[Pubmed: 29620254]

Ultraviolet (UV) radiation induces skin injury, and is associated with the development and formation of melanoma, which is a highly lethal form of skin cancer. Juglanin is a natural product, which is predominantly extracted from Polygonum aviculare, and is considered a functional component among its various compounds. Juglanin has been reported to exert marked protective effects in various diseases via the inhibition of inflammation and tumor cell growth. The present study aimed to explore the effects of juglanin on human skin cancer induced by UV and to reveal the underlying molecular mechanism. In the present study, immunohistochemical analysis, western blot analysis, RT-qPCR analysis and flow cytometry assays were mainly used in vivo and/or in vitro. The results indicated that in mice, UVB exposure increased susceptibility to carcinogens, and accelerated disease pathogenesis. Conversely, juglanin was able to ameliorate this condition via inhibition of inflammation, suppression of cell proliferation and induction of apoptosis via p38/c‑Jun N‑terminal kinase (JNK) blockage, nuclear factor (NF)‑κB inactivation and caspase stimulation in vivo. In addition, in vitro, the present study demonstrated that treatment of UVB‑stimulated B16F10 melanoma cells with juglanin resulted in a dose‑dependent decrease in cell viability, as well as increased apoptosis via the upregulation of caspase expression and poly (ADP‑ribose) polymerase cleavage. In addition, juglanin markedly attenuated p38/JNK signaling, inactivated the phosphoinositide 3‑kinase/protein kinase B pathway and suppressed UVB‑induced NF‑κB activation. Taken together, these results indicated the possibility of applying juglanin in combination with UVB as a potential therapeutic strategy for preventing skin cancer.

Polygonum aviculare L. extract and quercetin attenuate contraction in airway smooth muscle.[Pubmed: 29449621]

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Juglanin ameliorates LPS-induced neuroinflammation in animal models of Parkinson's disease and cell culture via inactivating TLR4/NF-κB pathway.[Pubmed: 29136779]

Parkinson's disease (PD) is a common neuro-degenerative disorder, and novel therapeutic targets are required for the treatment of PD. Juglanin is a natural compound extracted from the crude Polygonum aviculare, exhibiting anti-inflammatory, anti-oxidant and anti-cancer activities. In our study, PD in mice was induced by systemic LPS treatment as evidenced by enhanced α-synuclein and reduced tyrosine hydroxylase (TH), which were reversed by juglanin treatment. Moreover, juglanin administration attenuated LPS-caused behavioral and memory impairments and reduced LPS-induced enhancement of neuro-degenerative markers, including amyloid β (Aβ) and p-Tau. Additionally, juglanin ameliorated synaptic functionality through promoting the expression of synaptic markers, such as SYP, PSD-95 and SNAP-25. Toll-like receptor 4 (TLR4) signaling in brain regulates neuroinflammation, contributing to neurodegenerative diseases. Furthermore, LPS induced neuroinflammation through the acceleration of various pro-inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-18 (IL-18) and Cyclooxygenase-2 (COX-2), via activating TLR4/nuclear factor (NF)-κB pathway in hippocampus of mice and microglia cells. Juglanin significantly reduced LPS-induced production of pro-inflammatory cytokines and blocked TLR4/NF-κB pathway. We also found that LPS-induced astrocytes (AST) activity was prevented by juglanin through down-regulating glial fibrillary acidic protein (GFAP) and Iba1 in vivo and in vitro. Together, our results indicated that juglanin ameliorated neuroinflammation-related memory impairment, and neurodegeneration through impeding TLR4/NF-κB, indicating its potential for PD prevention.

The protective effect of juglanin on fructose-induced hepatitis by inhibiting inflammation and apoptosis through TLR4 and JAK2/STAT3 signaling pathways in fructose-fed rats.[Pubmed: 27261609]

High fructose-feeding is an essential causative factor leading to the development and progression of hepatitis associated with high levels of endotoxin (LPS). Juglanin, as a natural compound extracted from the crude Polygonum aviculare, displayed inhibitory activity against inflammation response and cancer growth. However, researches about its role on anti-inflammation and apoptosis are far from available. Here, it is the first time that juglanin was administrated to investigate whether it inhibits fructose-feeding-induced hepatitis in rats and to elucidate the possible mechanism by which juglanin might recover it. Fructose-feeding rats were orally administrated with juglanin of 5, 10 and 20mg/kg for 6 weeks, respectively. Juglanin exerted prevention of fructose-feeding-stimulated increased LPS levels, accelerated alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) and up-regulated inflammatory cytokines expression in serum, mainly including tumor necrosis factor-alpha (TNF-a), Interleukin 1beta (IL-1β), Interleukin 6 (IL-6) and Interleukin 18 (IL-18). Meanwhile, toll-like receptor 4 (TLR4)-modulated mitogen-activated protein kinase (MAPK)/nuclear factor kappa B (NF-κB) and apoptosis-related Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway are involved in the progression of hepatic injury and inflammation. And juglanin was found to suppress fructose-feeding-induced activation of these signaling pathways compared with the model group administrated only with fructose. These results indicate that juglanin represses inflammatory response and apoptosis via TLR4-regulated MAPK/NF-κB and JAK2/STAT3 signaling pathway respectively in rats with hepatitis induced by LPS for fructose-feeding. Treatment of juglanin might be an effective therapeutic strategy for preventing hepatitis.