Methanol extraction fraction from Citrus Sudachi peel exerts lipid reducing effects in cultured cells

Xu, Wenting; Miyamoto, Licht; Aihara, Haruna; Yamaoka, Tomomi; Tanaka, Naonobu; Tsuchihashi, Yuki; Ikeda, Yasumasa; Takahashi, Toshiaki; Kashiwada, Yoshiki; Tsuchiya, Koichiro

doi:10.2152/jmi.65.225

Cited by 8 publications

(6 citation statements)

References 9 publications

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“…Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay basically as previous reports. ,− One hundred microliters of suspension of exponentially growing cells (2 × 10 4 /mL) was seeded into a 96-well plate and precultured for 24 h at 37 °C. Then, 100 μL of medium containing various concentrations of each reagent was added to the wells, which is followed by exposure for 48 h at 37 °C.…”

Section: Methodsmentioning

confidence: 99%

Novel Hydrophilic Camptothecin Derivatives Conjugated to Branched Glycerol Trimer Suppress Tumor Growth without Causing Diarrhea in Murine Xenograft Models of Human Lung Cancer

et al. 2020

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Camptothecin possesses broad antitumor spectra on various cancers. In spite of its marked tumor-suppressing potency, camptothecin is too hydrophobic to be solved in water and therefore not currently in clinical use. CPT-11 (irinotecan) is one of the hydrophilic analogues of camptothecin and widely prescribed. However, its water solubility is still low and furthermore evokes severe diarrhea. Therefore, we designed and synthesized novel highly hydrophilic camptothecin derivatives by conjugating SN38 with branched glycerol trimer (SN38-BGL), which we have been developing as a unique strategy to endow hydrophobic molecule with much hydrophilicity, to maximize the benefit of CPT-11 and minimize the adverse effects. The SN38-BGLs exhibited equivalent or slightly stronger tumor-suppressing effects in murine xenograft human lung cancer models compared to CPT-11. However, neither early- nor late-onset diarrhea was observed when SN38-BGL was administered. Heights of villi in jejunum and ileum were bigger than those from CPT-11-treated mice, indicating that SN38-BGL is less harmful than CPT-11. Ex vivo digestion by liver microsome did not yield SN38 but a couple of other molecules against our expectations, which suggests the involvement of other active metabolites than SN38 and may explain the differences. Hence, SN38-BGLs can be a novel hydrophilic camptothecin derivative without causing severe diarrhea.

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Section: Methodsmentioning

confidence: 99%

Novel Hydrophilic Camptothecin Derivatives Conjugated to Branched Glycerol Trimer Suppress Tumor Growth without Causing Diarrhea in Murine Xenograft Models of Human Lung Cancer

et al. 2020

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“…Sudachitin is a rare polymethoxylated flavone found in the peels of C. sudachi [33,87]. Studies have shown that in cellular and animal models, the extracts from C. sudachi peel which is enriched in sudachitin, could ameliorate hyperlipidemia and obesity, possibly due to an augmented AMPK activity and PPARα transcription [87].…”

Section: Sudachitinmentioning

confidence: 99%

Therapeutic Potential of Bioactive Flavonoids from Citrus Fruit Peels toward Obesity and Diabetes Mellitus

Yip

2023

Future Pharmacology

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Obesity is associated with a significantly increased risk of cardiovascular and metabolic diseases such as diabetes mellitus. Recently, a growing body of evidence shows that phytochemicals, especially many flavonoids, place an inhibitory regulatory effect on adipogenesis, obesity and diabetes. With computer-aided drug discovery, the action modes of more and more bioactive flavonoids are being identified and confirmed at the molecular level. Citrus fruit peels are particularly rich in bioactive flavonoids which have demonstrated strong therapeutic potentials in regulating lipid metabolisms. However, they are usually thrown away after consuming the flesh, sometimes even causing environmental problems. Thus, extraction of useful flavonoids from citrus fruit waste for pharmaceutical industry could be a profitable and environmentally friendly solution in the future, advocating the concepts of circular economy and sustainable society. The aim of this review is to summarize current evidence on the antiobesity and antidiabetic potentials of identified bioactive flavonoids extracted from the peels of citrus fruits. Our results suggest that various citrus fruit peels could be potential sources for novel drugs and nutraceuticals. Combining experimental data and artificial intelligence methods to study citrus flavonoids would facilitate the discovery of novel drugs against obesity and obesity-related metabolic diseases.

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“…Consumption of sudachi peel extraction prevents excessive fat deposition. Treatment with sudachi peel extraction decreased intracellular lipid levels, mediated by AMP-activated protein kinase activation in murine C2C12 myotubes [19]. Consumption of sudachi peel extraction suppressed body weight gain and WAT inflammation in mice that were fed a high-fat diet (HFD) [20].…”

Section: Introductionmentioning

confidence: 99%

Sudachitin and Nobiletin Stimulate Lipolysis via Activation of the cAMP/PKA/HSL Pathway in 3T3-L1 Adipocytes

Abe

Sato

Murotomi

2023

Foods

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Polymethoxyflavones are flavonoids that are abundant in citrus fruit peels and have beneficial effects on human health. Previous studies have demonstrated that the polymethoxyflavones, namely sudachitin and nobiletin, ameliorate obesity and diabetes in humans and rodents. Although nobiletin induces lipolysis in adipocytes, lipolytic pathway activation by sudachitin has not been clarified in adipocytes. In this study, the effect of sudachitin on lipolysis was elucidated in murine 3T3-L1 adipocytes. Glycerol release into the medium and activation of the cyclic AMP (cAMP)/protein kinase A (PKA)/hormone-sensitive lipase (HSL) pathway was evaluated in 3T3-L1-differentiated adipocytes. Treatment with sudachitin and nobiletin for 24 and 48 h did not induce cytotoxicity at concentrations of up to 50 μM. Sudachitin and nobiletin at concentrations of 30 and 50 μM increased intracellular cAMP and medium glycerol levels in 3T3-L1 adipocytes. Western blotting revealed that sudachitin and nobiletin dose-dependently increased protein levels of phosphorylated PKA substrates and phosphorylated HSL. Sudachitin- and nobiletin-induced glycerol release, phosphorylation of PKA substrates, and HSL phosphorylation were suppressed by pharmacological inhibition of adenylate cyclase and PKA. These findings indicated that sudachitin, similar to nobiletin, exerts anti-obesogenic effects, at least in part through the induction of lipolysis in adipocytes.

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Methanol extraction fraction from Citrus Sudachi peel exerts lipid reducing effects in cultured cells

Cited by 8 publications

References 9 publications

Novel Hydrophilic Camptothecin Derivatives Conjugated to Branched Glycerol Trimer Suppress Tumor Growth without Causing Diarrhea in Murine Xenograft Models of Human Lung Cancer

Novel Hydrophilic Camptothecin Derivatives Conjugated to Branched Glycerol Trimer Suppress Tumor Growth without Causing Diarrhea in Murine Xenograft Models of Human Lung Cancer

Therapeutic Potential of Bioactive Flavonoids from Citrus Fruit Peels toward Obesity and Diabetes Mellitus

Sudachitin and Nobiletin Stimulate Lipolysis via Activation of the cAMP/PKA/HSL Pathway in 3T3-L1 Adipocytes

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