Bergapten exerts inhibitory effects on diabetes-related osteoporosis via the regulation of the PI3K/AKT, JNK/MAPK and NF-κB signaling pathways in osteoprotegerin knockout mice

Xue-ju, LI; Zhu, Zhe; Han, Si-Lin; Zhang, Zilong

doi:10.3892/ijmm.2016.2794

Cited by 45 publications

(34 citation statements)

References 37 publications

(35 reference statements)

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“…Akt1 silencing in mice leads to bone formation disorders in which the differentiation and survival of osteoblasts is inhibited (Kawamura et al, ; Peng et al, ). In contrast, Li et al showed that PI3K/Akt activates the mammalian target of rapamycin (mTOR) to promote osteoporosis (Li, Zhu, Han, & Zhang, ). In this study, the levels of active Akt in the BMSCs of OVX rats were significantly lower than those of healthy rats after 2 weeks of osteogenesis induction.…”

Section: Discussionmentioning

confidence: 99%

Arctigenin promotes bone formation involving PI3K/Akt/PPARγ signaling pathway

Chen

Lan

et al. 2020

Chem Biol Drug Des

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This study investigated the mechanisms through which arctigenin promotes osteogenesis. Bone marrow mesenchymal stem cells (BMSCs) from ovariectomized (OVX) rats were differentiated into osteoblasts, and osteogenesis was evaluated via Alizarin Red S (ARS) staining and alkaline phosphatase (ALP) measurements in cultured BMSCs. The levels of phosphorylated AKT serine/threonine kinase 1 (p‐Akt), and peroxisome proliferator‐activated receptor gamma (PPARγ) expression were quantified by Western blot analysis. The levels of urine calcium (U‐Ca), urine phosphorus (U‐P), serum ALP, and bone mineral density (BMD) of OVX rats were assessed in vivo. The results showed that treatment with arctigenin in rat BMSCs enhanced mineralization, increased ALP activity, increased the expression of Akt and p‐Akt, and decreased PPARγ expression, consistent with its ability to promote osteoblast differentiation. Furthermore, arctigenin prevented OVX‐induced osteoporosis in rats by increasing BMD and ALP activity and inhibiting the loss of Ca and P. In contrast, treatment with LY294002, a selective inhibitor of the phosphatidylinositol 3‐kinase (PI3K), produced the opposite phenotype. These data suggest that the protective effects of arctigenin on BMSCs and OVX rat models result from the induction of osteogenesis involving the PI3K/Akt/PPARγ axis.

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Section: Discussionmentioning

confidence: 99%

Arctigenin promotes bone formation involving PI3K/Akt/PPARγ signaling pathway

Chen

Lan

et al. 2020

Chem Biol Drug Des

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“…It decreases the content of malondialdehyde (p < 0.05) in the skin of mice volume/trabecular volume ratio (BV/TV), trabecular thickness, and trabecular number. These data must be verified in human studies (Li et al, 2016).…”

Section: In Ratsmentioning

confidence: 92%

“…These data must be verified in human studies (Li et al, 2016). It decreases the content of malondialdehyde (p < 0.05) in the skin of mice volume/trabecular volume ratio (BV/TV), trabecular thickness, and trabecular number.…”

Section: Animal (Level 6) Bergamot and Boxthorn Extractmentioning

confidence: 92%

“…The oral administration of Bergapten (BEO) at 10 or 20 mg/kg daily for 20 weeks was able to significantly increase bone volume/trabecular volume ratio (BV/TV), trabecular thickness, and trabecular number (p < 0.01 for 10 mg/kg and p < 0.001 for 20 mg/kg) (Li et al, 2016).…”

Section: Effects In Animalsmentioning

confidence: 99%

“…Although native to South-East Asia, 80% of bergamot is produced in Calabria, southern Italy, where it grows extensively. The main preparations used are bergamot extracts (BE), with high content of flavonoids, such as neoeriocitrin, neohesperidin, naringin (Toth et al, 2015), bergamot polyphenolic fraction (BPF) (Bruno, Pandolfo, Crucitti, Maisano, Zoccali, et al, 2017), bergamot essential oil (BEO) (Watanabe et al, 2015), and aromasticks with bergamot/sandalwood or frankincense/mandarin/lavender (Dyer, Cleary, McNeill, Ragsdale-Lowe, & Osland, 2016) bergamot/vetivert/geranium (Wiebe, 1998), bergamot/lavender/cedarwood (Graham, Browne, Cox, & Graham, 2003) and bergamot juice (BJ) (Impellizzeri et al, 2015), bergamot/boxthorn extract (Shao, 2003) or bergamot essential oil plus other citrus essential oils plus grapefruit juice (Li, Zhu, Han, & Zhang, 2016) or bergamot flavonoids and other phytoextracts (Babish et al, 2016;Saiyudthong & Marsden, 2011). Bergamot essential oil (BEO) and bergamot juice (BJ) contain up to 93-96% of volatile compounds, such as monoterpenes (25-53% of limonene), as well as discrete quantities of linalool (2-20%) and linalyl acetate (15-40%).…”

Section: Introductionmentioning

confidence: 99%

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Efficacy of bergamot: From anti‐inflammatory and anti‐oxidative mechanisms to clinical applications as preventive agent for cardiovascular morbidity, skin diseases, and mood alterations

Perna

Spadaccini

Botteri

et al. 2019

Food Science & Nutrition

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We summarize the effects of bergamot (extract, juice, essential oil, and polyphenolic fraction) on cardiovascular, bone, inflammatory, skin diseases, mood alteration, anxiety, pain, and stress. This review included a total of 31 studies (20 studies on humans with 1709 subjects and 11 in animals (rats and mice)). In humans, bergamot‐derived extract (BE) exerts positive effects on hyperlipidemia with an oral dose from 150 mg to 1000 mg/day of flavonoids administered from 30 to 180 days, demonstrating an effect on body weight and in modulating total cholesterol, triglycerides, LDL, and HDL. Studies in animals confirm promising data on glucose control (500/1000 mg/day of BE with a treatment lasting 30 days) are available in rats. In animals models, bergamot essential oil (BEO, 10 mg/kg or 20 mg/kg daily for 20 weeks) increases bone volume, decreases psoriatic plaques, increases skin collagen content, and promotes hair growth. Bergamot juice (20 mg/kg) is promising in terms of pro‐inflammatory cytokine reduction. In humans, aromatherapy (from 15 to 30 min) does not appear to be useful in order to reduce stress, anxiety, and nausea, compared to placebo. Compared to baseline, BE topical application and BEO aromatherapy reduce blood diastolic and systolic pressure and could have a significant effect on improving mental conditions.

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Bergapten: A review of its pharmacology, pharmacokinetics, and toxicity

Liang

Xie

et al. 2021

Phytotherapy Research

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Bergapten is a natural furocoumarin, also known as 5-methoxypsoralen, and its medicinal value has been paid more and more attention. By sorting out the pharmacological literature of bergapten, we found that bergapten has a wide range of pharmacological effects, including neuroprotection, organ protection, anticancer, antiinflammatory, antimicrobial, and antidiabetes effects. However，bergapten has complex impacts on the hepatic metabolic enzyme. Moreover, pharmacokinetic studies showed that bergapten has higher absolute bioavailability and can cross the blood-brain barrier and has a great potential for treating brain disease, but the mechanism needs further clarification to make greater use of its ability to treat brain diseases. Furthermore, the phototoxicity of bergapten combined with ultraviolet light has always been mentioned. In view of its wide range of pharmacological activities, bergapten is expected to be a potential drug candidate for the treatment of diabetes and diabetes-induced osteoporosis, epilepsy, Alzheimer's disease, depression, and cancer. However, further studies are needed to elucidate its molecular mechanisms and targets. The phototoxicity of bergapten as a side effect should be further avoided. On the other hand, the photoactivation of bergapten in the anticancer aspect can be better utilized.

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Bergapten exerts inhibitory effects on diabetes-related osteoporosis via the regulation of the PI3K/AKT, JNK/MAPK and NF-κB signaling pathways in osteoprotegerin knockout mice

Cited by 45 publications

References 37 publications

Arctigenin promotes bone formation involving PI3K/Akt/PPARγ signaling pathway

Arctigenin promotes bone formation involving PI3K/Akt/PPARγ signaling pathway

Efficacy of bergamot: From anti‐inflammatory and anti‐oxidative mechanisms to clinical applications as preventive agent for cardiovascular morbidity, skin diseases, and mood alterations

Bergapten: A review of its pharmacology, pharmacokinetics, and toxicity

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