Dataset Information

Patchouli Alcohol Modulates the Pregnancy X Receptor/Toll-like Receptor 4/Nuclear Factor Kappa B Axis to Suppress Osteoclastogenesis.

ABSTRACT: The incidence of osteoporosis, which is primarily characterized by plethoric osteoclast (OC) formation and severe bone loss, has increased in recent years. Millions of people worldwide, especially postmenopausal women, suffer from osteoporosis. The drugs commonly used to treat osteoporosis still exist many disadvantages, but natural extracts provide options for the treatment of osteoporosis. Therefore, the identification of cost-effective natural compounds is important. Patchouli alcohol (PA), a natural compound extracted from Pogostemon cablin that exerts anti-inflammatory effects, is used as a treatment for gastroenteritis. However, no research on the use of Patchouli alcohol in osteoporosis has been reported. We found that PA dose-dependently inhibited the receptor activator of nuclear factor kappa-B ligand (RANKL)-induced formation and function of OCs without cytotoxicity. Furthermore, these inhibitory effects were reflected in the significant effect of PA on the NF-κB signaling pathway, as PA suppressed the transcription factors NFATc1 and c-Fos. We also determined that PA activated expression of the nuclear receptor pregnane X receptor (PXR) and promoted the PXR/Toll-like receptor 4 (TLR4) axis to inhibit the nuclear import of NF-κB (p50 and p65). Additionally, PA exerted therapeutic effects against osteoporosis in ovariectomized (OVX) mice, supporting the use of PA as a treatment for osteoporosis in the future.

SUBMITTER: Lu Q

PROVIDER: S-EPMC8227438 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Patchouli Alcohol Modulates the Pregnancy X Receptor/Toll-like Receptor 4/Nuclear Factor Kappa B Axis to Suppress Osteoclastogenesis.

Lu Qian Q Jiang Chao C Hou Jialong J Qian Hao H Chu Feifan F Zhang Weiqi W Ye Mengke M Chen Ziyi Z Liu Jian J Yao Hanbing H Zhang Jianfeng J Xu Jiake J Wang Te T Fan Shunwu S Wang Qingqing Q

Frontiers in pharmacology 20210608

The incidence of osteoporosis, which is primarily characterized by plethoric osteoclast (OC) formation and severe bone loss, has increased in recent years. Millions of people worldwide, especially postmenopausal women, suffer from osteoporosis. The drugs commonly used to treat osteoporosis still exist many disadvantages, but natural extracts provide options for the treatment of osteoporosis. Therefore, the identification of cost-effective natural compounds is important. Patchouli alcohol (PA), a ...[more]

PMID: 34177594

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Project description:Clinical evidence shows that postmenpausal women are almost twice as likely to develop Alzheimer's disease (AD) as men of the same age, and estrogen is closely related to the occurrence of AD. Estrogen receptor (ER) α is mainly expressed in the mammary gland and other reproductive organs like uterus while ERβ is largely distributed in the hippocampus and cardiovascular system, suggesting that ERβ selective agonist is a valuable drug against neurodegenerative diseases with low tendency in inducing cancers of breast and other reproductive organs. In this study we identified a natural product patchouli alcohol (PTA) as a selective ERβ agonist which improved the cognitive defects in female APP/PS1 mice, and explore the underlying mechanisms. Six-month-old female APP/PS1 mice were administered PTA (20, 40 mg · kg-1 · d-1, i.g.) for 90 days. We first demonstrated that PTA bound to ERβ with a dissociation constant (KD) of 288.9 ± 35.14 nM in microscale thermophoresis. Then we showed that PTA administration dose-dependently ameliorated cognitive defects evaluated in Morris water maze and Y-maze testes. Furthermore, PTA administration reduced amyloid plaque deposition in the hippocampus by promoting microglial phagocytosis; PTA administration improved synaptic integrity through enhancing BDNF/TrkB/CREB signaling, ameliorated oxidative stress by Catalase level, and regulated Bcl-2 family proteins in the hippocampus. The therapeutic effects of PTA were also observed in vitro: PTA (5, 10, 20 μM) dose-dependently increased phagocytosis of o-FAM-Aβ42 in primary microglia and BV2 cells through enhancing ERβ/TLR4 signaling; PTA treatment ameliorated o-Aβ25-35-induced reduction of synapse-related proteins VAMP2 and PSD95 in primary neurons through enhancing ERβ/BDNF/TrkB/CREB pathways; PTA treatment alleviated o-Aβ25-35-induced oxidative stress in primary neurons through targeting ERβ and increasing Catalase expression. Together, this study has addressed the efficacy of selective ERβ agonist in the amelioration of AD and highlighted the potential of PTA as a drug lead compound against the disease.

Dataset Information

Patchouli Alcohol Modulates the Pregnancy X Receptor/Toll-like Receptor 4/Nuclear Factor Kappa B Axis to Suppress Osteoclastogenesis.

Publications

Patchouli Alcohol Modulates the Pregnancy X Receptor/Toll-like Receptor 4/Nuclear Factor Kappa B Axis to Suppress Osteoclastogenesis.

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