Piperlongumine activates Sirtuin1 and improves cognitive function in a murine model of Alzheimer’s disease

Go, Jun; Ha, Thi-Kim-Quy; Seo, Ji Yeon; Park, Tae-Shin; Ryu, Young‐Kyoung; Park, Hye-Yeon; Noh, Jung‐Ran; Kim, Yong‐Hoon; Hwang, Jung Hwan; Choi, Dong‐Hee; Hwang, Dae Youn; Kim, Sanghee; Lee, Chul‐Ho; Oh, Won Keun; Kim, Kyoung‐Shim

doi:10.1016/j.jff.2018.02.002

Cited by 21 publications

(20 citation statements)

References 52 publications

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“…2 ). However, previously, we have demonstrated that PL effectively decreases astrogliosis and microglia activation in the parietal cortex in animal models of AD ( 17 ). The results indicated that the inflammation and microglia activation that was triggered by pathological conditions were effectively suppressed by PL treatment.…”

Section: Discussionmentioning

confidence: 88%

“…PL was isolated from Piper longum . Preparation was performed as described in previous studies ( 17 - 19 ). Dried fruits (500 g) of Piper longum were extracted with ethyl acetate (EtOH; 1 liter x 3 times) at room temperature for 1 week.…”

Section: Methodsmentioning

confidence: 99%

“…The 3-month-old female mice were used as young controls (n=7). Multiple behaviour tests were performed on a single cohort of mice and the following order was obeyed: Open field test → novel object recognition test → nest-building behaviour test ( 17 , 20 ). All the animal experiments were approved by the Institutional Animal Use and Care Committee of the KRIBB (KRIBB-AEC-14074).…”

Section: Methodsmentioning

confidence: 99%

“…Cumulative evidence has indicated that PL has a number of pharmacological activities, including antidepressant, anxiolytic, anti-fungal, antidiabetic, antinociceptive and antitumour properties ( 11 - 16 ). Moreover, in our previous study, it was demonstrated that administration of PL improves cognitive function in a transgenic mouse model of AD ( 17 ). Thus, we hypothesized that PL would enhance cognitive function in aged mice.…”

Section: Introductionmentioning

confidence: 97%

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Piperlongumine decreases cognitive impairment and improves hippocampal function in aged mice

Park

Han

et al. 2018

Int J Mol Med

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Piperlongumine (PL), a biologically active compound from the Piper species, has been shown to exert various pharmacological effects in a number of conditions, including tumours, diabetes, pain, psychiatric disorders and neurodegenerative disease. In this study, we evaluated the therapeutic effects of PL on hippocampal function and cognition decline in aged mice. PL (50 mg/kg/day) was intragastrically administrated to 23-month-old female C57BL/6J mice for 8 weeks. Novel object recognition and nest building behaviour tests were used to assess cognitive and social functions. Additionally, immunohistochemistry and western blot analysis were performed to examine the effects of PL on the hippocampus. We found that the oral administration of PL significantly improved novel object recognition and nest building behaviour in aged mice. Although neither the percentage area occupied by astrocytes and microglia nor the level of 4-hydroxynonenal protein, a specific marker of lipid peroxidation, were altered by PL treatment, the phosphorylation levels of N-methyl-D-aspartate receptor subtype 2B (NR2B), calmodulin-dependent protein kinase II alpha (CaMKIIα) and extracellular signal-regulated kinase 1/2 (ERK1/2) were markedly increased in the hippocampus of aged mice following the administration of PL. We also found that PL treatment resulted in a CA3-specific increase in the phosphorylation level of cyclic AMP response element binding protein, which is recognized as a potent marker of neuronal plasticity, learning and memory. Moreover, the number of doublecortin-positive cells, a specific marker of neurogenesis, was significantly increased following PL treatment in the dentate gyrus of the hippocampus. On the whole, these data demonstrate that PL treatment may be a potential novel approach in the treatment of age-related cognitive impairment and hippocampal changes.

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Section: Discussionmentioning

confidence: 88%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

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Piperlongumine decreases cognitive impairment and improves hippocampal function in aged mice

Park

Han

et al. 2018

Int J Mol Med

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“…[13] Pipernonaline had the antiproliferation effect, antioxidant activity and antihyperlipidaemic activity, and it could improve cognitive function in a murine model of Alzheimer's disease. [14][15][16][17] However, the effects of extraction methods on biological activity and some active ingredients of P. longum were still unclear.…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory and antitumour activity of various extracts and compounds from the fruits of Piper longum L.

Guo

Xia

et al. 2019

Journal of Pharmacy and Pharmacology

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Objectives To explore effective extraction method and to find active constituents, we investigated the biological activity of three extracts and isolated active compounds from the fruits of Piper longum L. Methods Three extracts from the fruits were obtained by reflux, ultrasonic and supercritical fluid extraction, respectively. Active compounds were isolated by the bioassay-guided method. The anti-inflammatory activity, antiproliferation activity and cytotoxicity were evaluated. The apoptosis was detected by Hoechst 33258 staining assay. The relevant proteins were investigated by Western blot assay. Key findings The anti-inflammatory activity and cytotoxicity of supercritical fluid extract (SE) were stronger than those of the other two extracts. Among all isolated compounds, the anti-inflammatory activity of eight compounds was stronger than that of indomethacin, and compounds 8, 9, 11, 14 and 15 were found to possess anti-inflammatory effect for the first time. Compounds 1, 2, 3 and 14 exhibited significant cytotoxicity against cancer cells. SE and piperine were found to reduce colony formation, inhibit cell migration and promote apoptosis through increasing cleaved PARP and the ratio of Bax/Bcl-2. Conclusions The anti-inflammatory and antitumour effects of SE were better than those of the other two extracts. The compounds responsible for the activity were elucidated. SE and piperine inhibit cell growth through apoptosis.

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Piper longum L.: A comprehensive review on traditional uses, phytochemistry, pharmacology, and health‐promoting activities

Biswas

Ghorai

Mishra

et al. 2022

Phytotherapy Research

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Piper longum (family Piperaceae), commonly known as "long-pepper" or "Pippali" grows as a perennial shrub or as an herbaceous vine. It is native to the Indo-Malaya region and widely distributed in the tropical and subtropical world including the Indian subcontinent, Sri Lanka, Middle-East, and America. The fruits are mostly used as culinary spice and preservatives and are also a potent remedy in various traditional medicinal systems against bronchitis, cough, cold, snakebite, and scorpion-sting and are also used as a contraceptive. Various bioactive-phytochemicals including alkaloids, flavonoids, esters, and steroids were identified from the plant extracts and essential oils from the roots and fruits were reported as antimicrobial, antiparasitic, anthelminthic, mosquito-larvicidal, antiinflammatory, analgesic, antioxidant, anticancer, neuro-pharmacological, antihyperglycaemic, hepato-protective, antihyperlipidaemic, antiangiogenic, immunomodulatory, antiarthritic, antiulcer, antiasthmatic, cardioprotective, and anti-snake-venom agents. Many of its pharmacological properties were attributed to its antioxidative and antiinflammatory effects and its ability to modulate a number of signalling pathways and enzymes. This review comprehensively encompasses information on habit, distribution, ethnobotany, phytochemistry, and pharmacology of P. longum in relation to its medicinal importance and health benefits to validate the traditional claims supported by specific scientific experiments. In addition, it also discusses the safety and toxicity studies, application of green synthesis and nanotechnology as well as clinical trials performed with the plant also elucidating research gaps and future perspectives of its multifaceted uses.

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Piperlongumine activates Sirtuin1 and improves cognitive function in a murine model of Alzheimer’s disease

Cited by 21 publications

References 52 publications

Piperlongumine decreases cognitive impairment and improves hippocampal function in aged mice

Piperlongumine decreases cognitive impairment and improves hippocampal function in aged mice

Anti-inflammatory and antitumour activity of various extracts and compounds from the fruits of Piper longum L.

Piper longum L.: A comprehensive review on traditional uses, phytochemistry, pharmacology, and health‐promoting activities

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