Lycorine Attenuates Autophagy in Osteoclasts via an Axis of mROS/TRPML1/TFEB to Reduce LPS-Induced Bone Loss

Park, Hyun-Jung; Gholam-Zadeh, Malihatosadat; Suh, Jae-Hee; Choi, Hye‐Seon

doi:10.1155/2019/8982147

Cited by 25 publications

(40 citation statements)

References 31 publications

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“…Protein extraction, separation by SDS-PAGE, transfer to nitrocellulose membranes, blocking, incubation with secondary antibodies, and development were performed as previously described [10]. Primary antibodies against phospho-IKKα/β (S176/180) (#2697, Cell Signaling, Danvers, MA, USA), lamin B (#13435, Cell Signaling), p65 (sc-372, Santa Cruz Biotechnology, Santa Cruz, CA, USA), PP2A (sc-13600, Santa Cruz Biotechnology), and β-actin (A5441, Sigma-Aldrich) were incubated with the membranes overnight at 4 • C.…”

Section: Western Blot Analysismentioning

confidence: 99%

“…The fluorescent probe 2',7'-dichlorofluorescein diacetate (H 2 DCFDA) (Thermo Fisher Scientific, Waltham, MA, USA) and the Mito-SOX red mitochondrial superoxide indicator (Invitrogen, Carlsbad, CA, USA) were used to evaluate intracellular ROS and mitochondrial ROS, respectively, as described [10].…”

Section: Determination Of Intracellular and Mitochondrial Reactive Oxmentioning

confidence: 99%

“…When a ROS scavenger, N-acetyl cysteine NAC, or an inhibitor of NADPH oxidase, diphenyleneiodonium chloride (DPI), was co-applied with DAC to LPS-induced OCs, the inhibitory effects of DAC on the number of OCs and the OC area were completely abolished ( Figure 3C). We also previously demonstrated that LPS induces OC differentiation by stimulating cROS [12] and mitochondrial ROS (mROS) production [10]. That prompted us to wonder whether DAC may decrease ROS to reduce LPS-induced OC formation.…”

Section: Dac Decreases Both Nf-kb Activation and The Up-regulation Ofmentioning

confidence: 99%

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Dauricine Protects from LPS-Induced Bone Loss via the ROS/PP2A/NF-κB Axis in Osteoclasts

et al. 2020

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Dauricine (DAC), an isoquinoline alkaloid, exhibits anti-inflammatory activity. We hypothesized that DAC may prevent the inflammatory bone loss induced by lipopolysaccharide (LPS). LPS-induced bone loss was decreased by DAC in female C57BL/6J mice as evaluated by micro-computerized tomography (μCT) analysis. In vivo tartrate-resistant acid phosphatase (TRAP) staining showed that the increased number of osteoclasts (OCs) in LPS-treated mice was attenuated by DAC, indicating that DAC exhibited bone sparing effects through acting on OCs. DAC also decreased the differentiation and activity of OCs after LPS stimulation in vitro. LPS-induced cytosolic reactive oxygen species (cROS) oxidized PP2A, a serine/threonine phosphatase, leading to the activation of IKKα/β, followed by the nuclear localization of p65. DAC decreased LPS-induced ROS, resulting in the recovery of the activity of PP2A by reducing its oxidized form. Consequently, DAC reduced the phosphorylation of IKKα/β to block the nuclear localization of p65, which decreased NF-κB activation. Taken together, DAC reduced the differentiation and activity of OCs by decreasing ROS via the ROS/PP2A/NF-κB axis, resulting in protection from LPS-induced bone loss. We have demonstrated that LPS-induced bone loss was inhibited by DAC via its action on OCs, implying the therapeutic potential of DAC against inflammatory bone loss.

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Section: Western Blot Analysismentioning

confidence: 99%

Section: Determination Of Intracellular and Mitochondrial Reactive Oxmentioning

confidence: 99%

Section: Dac Decreases Both Nf-kb Activation and The Up-regulation Ofmentioning

confidence: 99%

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Dauricine Protects from LPS-Induced Bone Loss via the ROS/PP2A/NF-κB Axis in Osteoclasts

et al. 2020

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“…It has been reported that drugs that inhibit inflammation and oxidation effectively attenuated lung damage, including astaxanthin, cordycepin, and linarin (Bi et al 2017 ; Han et al 2018 ; Lei et al 2018 ). Lycorine has been reported to be an effective inhibitor of tumor development and also had many other benefits, including reducing LPS-induced bone loss in mice and inhibiting intervertebral disc degeneration (Park et al 2019 ; Wang et al 2018 ). Here, we found that lycorine alleviated lung injury and inhibited pulmonary edema, inflammatory response, and oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Lycorine attenuates lipopolysaccharide-induced acute lung injury through the HMGB1/TLRs/NF-κB pathway

Meng

Fei

et al. 2020

3 Biotech

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Lung injury associated with systemic inflammatory response is a common problem affecting human health. Previous studies have shown that lycorine exerts a anti-inflammatory effect. However, whether lycorine alleviates lung injury remains unclear. To explore this issue, BALB/c mice and MLE-12 cells were treated with lipopolysaccharide (LPS) to establish lung injury mouse model and cell model, respectively. Glycyrrhizic acid, known as an inhibitor of ALI, was also used to study the effects of lycorine in vitro. Our results showed that after LPS treatment, the lung injury score, lung wet-to-dry weight ratio, and malondialdehyde (MDA) production in the lung tissues and the expression levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 in bronchoalveolar lavage fluid were significantly increased, whereas their levels were decreased by lycorine. Additionally, LPS injection activated the high-mobility group box 1 (HMGB1)/Toll-like receptors (TLRs)/NF-κB pathway. However, lycorine treatment attenuated the activity of the HMGB1/TLRs/NF-κB pathway in the lung tissues. In vitro studies showed that lycorine administration significantly decreased the levels of inflammatory cytokines and MDA and attenuated the activity of the HMGB1/TLRs/NF-κB pathway in LPS-treated cells. Moreover, the inhibitory effects of lycorine on the inflammatory response and oxidative stress in LPS-treated lung cells were similar with that of glycyrrhizic acid, and this inhibition was intensified by both lycorine and glycyrrhizic acid treatment. We suggest that lycorine could alleviate LPS-induced lung injury of inflammation and oxidative stress by blocking the HMGB1/TLRs/NF-κB pathway, which gives a new perspective for ALI therapy to treat lycorine as a potential treatment clinically.

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“…e inhibitory effect is stronger than that of dexamethasone. In addition, lycorine can also inhibit the production of PGE2 and IL-6 in macrophages to play an antipyretic and analgesic role [37].…”

Section: Lycorinementioning

confidence: 99%

Research Progress on Anti‐Inflammatory Effects and Mechanisms of Alkaloids from Chinese Medical Herbs

Liu

Chen

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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As the spectrum of diseases keeps changing and life pace keeps going faster, the probability and frequency of diseases caused by human inflammatory reactions also keep increasing. How to develop effective anti-inflammatory drugs has become the hotspot of researches. It has been found that alkaloids from Chinese medical herbs have anti-inflammatory, analgesic, antitumor, anticonvulsant, diuretic, and antiarrhythmic effects, among which the anti-inflammatory effect is very prominent and commonly used in the treatment of rheumatoid arthritis, ankylosing spondylitis, and other rheumatic immune diseases, but its mechanism of action has not been well explained. Based on this, this paper will classify alkaloids according to structural types and review the plant sources, applicable diseases, and anti-inflammatory mechanisms of 16 kinds of alkaloids commonly used in clinical treatment, such as berberine, tetrandrine, and stephanine, with the aim of providing a reference for drug researches and clinical applications. Isoquinoline AlkaloidsIsoquinoline alkaloids are widely distributed in 27 sections of plants, such as Menispermaceae, Berberidaceae, Papaveraceae, and Ranunculaceae [4]. Isoquinoline alkaloids, taking isoquinoline or tetrahydroisoquinoline as the basic parent nucleus, can be divided into 20 categories, including simple isoquinoline, benzylisoquinoline, phenethyl isoquinoline, naphthyl isoquinoline, aporphine, morphine,

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Lycorine Attenuates Autophagy in Osteoclasts via an Axis of mROS/TRPML1/TFEB to Reduce LPS-Induced Bone Loss

Cited by 25 publications

References 31 publications

Dauricine Protects from LPS-Induced Bone Loss via the ROS/PP2A/NF-κB Axis in Osteoclasts

Dauricine Protects from LPS-Induced Bone Loss via the ROS/PP2A/NF-κB Axis in Osteoclasts

Lycorine attenuates lipopolysaccharide-induced acute lung injury through the HMGB1/TLRs/NF-κB pathway

Research Progress on Anti‐Inflammatory Effects and Mechanisms of Alkaloids from Chinese Medical Herbs

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