Effect of caffeine on ovariectomy-induced osteoporosis in rats

Xu, Huanhuan; Liu, Titi; Hu, Lihong; Jin, Li; Gan, Chunxia; Xu, Jing; Chen, Fei; Xiang, Zemin; Sheng, Jun

doi:10.1016/j.biopha.2019.108650

Cited by 48 publications

(68 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Considerable accumulated evidence has demonstrated that G6PDH exhibits higher enzyme activities in RCC patients, which could be used as a biomarker for clinical diagnosis ( Spencer and Stanton, 2017 ; Zhang et al, 2017b ). Caffeine (1,3,7-trimethylxanthine), a naturally occurring plant xanthine alkaloid found in tea, coffee, cocoa, and many other food products, has been shown to possess numerous biological functions ( Xu et al, 2019 ). A previous case–control study concluded that caffeine consumption can reduce the risk of developing RCC ( Antwi et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Caffeine Targets G6PDH to Disrupt Redox Homeostasis and Inhibit Renal Cell Carcinoma Proliferation

Liu

et al. 2020

Front. Cell Dev. Biol.

Self Cite

View full text Add to dashboard Cite

Glucose-6-phosphate dehydrogenase (G6PDH) is the rate-limiting enzyme in the pentose phosphate pathway (PPP) and plays a crucial role in the maintenance of redox homeostasis by producing nicotinamide adenine dinucleotide phosphate (NADPH), the major intracellular reductant. G6PDH has been shown to be a biomarker and potential therapeutic target for renal cell carcinoma (RCC). Here, we report a previously unknown biochemical mechanism through which caffeine, a well-known natural small molecule, regulates G6PDH activity to disrupt cellular redox homeostasis and suppress RCC development and progression. We found that caffeine can inhibit G6PDH enzymatic activity. Mechanistically, caffeine directly binds to G6PDH with high affinity ( K D = 0.1923 μM) and competes with the coenzyme NADP + for G6PDH binding, as demonstrated by the decreased binding affinities of G6PDH for its coenzyme and substrate. Molecular docking studies revealed that caffeine binds to G6PDH at the structural NADP + binding site, and chemical cross-linking analysis demonstrated that caffeine inhibits the formation of dimeric G6PDH. G6PDH inhibition abrogated the inhibitory effects of caffeine on RCC cell growth. Moreover, inhibition of G6PDH activity by caffeine led to a reduction in the intracellular levels of NADPH and reactive oxygen species (ROS), and altered the expression of redox-related proteins in RCC cells. Accordingly, caffeine could inhibit tumor growth through inhibition of G6PDH activity in vivo . Taken together, these results demonstrated that caffeine can target G6PDH to disrupt redox homeostasis and inhibit RCC tumor growth, and has potential as a therapeutic agent for the treatment of RCC.

show abstract

Section: Introductionmentioning

confidence: 99%

Caffeine Targets G6PDH to Disrupt Redox Homeostasis and Inhibit Renal Cell Carcinoma Proliferation

Liu

et al. 2020

Front. Cell Dev. Biol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…The results showed that the ALP and OCN levels in the MC group were significantly increased, further proving that the OP model induced by retinoic acid was successful. ALP activity is an important indicator related to bone turnover [3]. In our study, RPP treatment appeared to ameliorate ALP and OCN levels, especially OCN levels, which were not significantly different from NC and PC groups.…”

Section: Discussionmentioning

confidence: 38%

“…OP has become one of the most challenging orthopedic diseases of the 21st century [1,3]. The treatment methods for OP aim to prevent bone absorption and promote new bone formation.…”

Section: Discussionmentioning

confidence: 99%

“…According to the World Health Organization report, with the global population aging, approximately 72% of women and 62% of men over 50 years old are estimated to suffer from OP or osteopenia by 2022 [2]. OP has a high incidence of fractures and mortality rates and has become a global epidemic [3]. The bone maintains structural and functional stability through continuous bone remodeling [4].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of Rambutan Peel (Nepheliumlappaceum) PhenolicExtract on RANKL-Induced Differentiation of RAW264.7 Cells into Osteoclasts and Retinoic Acid-Induced Osteoporosis in Rats

Zhuang

Sun²,

Liu³

et al. 2020

Nutrients

View full text Add to dashboard Cite

Previous studies have shown that rambutan peel phenolic (RPP) extract has excellent biological activities due to its abundant phenolic content and profile. In this study, the potential anti-osteoporosis (OP) effects of RPP were evaluated by suppressing receptor activator nuclear factor-kappa B ligand (RANKL)-induced differentiation of RAW264.7 cells into osteoclasts and amelioratingretinoic acid-induced OP in rats. Our results showed that RPP efficiently decreased the formation of tartrate-resistant acid phosphatase (TRAP)-positive cells and reduced total TRAP activity in RAW264.7 cells under RANKL stimulation. RPP treatment significantlyameliorated retinoid acid-induced calcium loss in rats (p < 0.05). The serum phosphorus level of osteoporotic rats was increased by RPP treatment, and the serum levels of total alkaline phosphatase and osteocalcin in osteoporotic rats were further reduced. RPP treatment improved the qualities of the femur and tibia, such asbone mineral density, bone length, bone maximum load, cortical bone area ratio, and trabecularelative bone density in osteoporotic rats to some extent. Furthermore, histological analysis showed that RPP effectively improved the bone microstructure of osteoporotic rats by regulating the cortical bone thickness and trabecular bone separation. These results indicate that RPP could have potential applications as a newnutraceutical and functional food in the prevention of OP.

show abstract

“…However, there was no relationship between calcium and vitamin D intakes (as obtained from Caffeine is a naturally occurring plant xanthine alkaloid that is widely consumed worldwide and found in many beverages, including tea, coffee, and cocoa. Although moderate caffeine intake is generally thought to have positive effects on human health, its effect on bone metabolism is controversial (24). In rats with osteoporosis due to ovariectomy, medium or high doses of caffeine have been shown to have no detrimental effect on the skeletal system (24).…”

Section: Nhanes 2005-2008 (The National Health and Nutrition Examinationmentioning

confidence: 99%

Post-menopausal osteoporosis: do body composition, nutritional habits, and physical activity affect bone mineral density?

Akkuş¹,

Atalay²

2020

Nutr Hosp

View full text Add to dashboard Cite

show abstract

Effect of caffeine on ovariectomy-induced osteoporosis in rats

Cited by 48 publications

References 45 publications

Caffeine Targets G6PDH to Disrupt Redox Homeostasis and Inhibit Renal Cell Carcinoma Proliferation

Caffeine Targets G6PDH to Disrupt Redox Homeostasis and Inhibit Renal Cell Carcinoma Proliferation

Effects of Rambutan Peel (Nepheliumlappaceum) PhenolicExtract on RANKL-Induced Differentiation of RAW264.7 Cells into Osteoclasts and Retinoic Acid-Induced Osteoporosis in Rats

Post-menopausal osteoporosis: do body composition, nutritional habits, and physical activity affect bone mineral density?

Contact Info

Product

Resources

About