Polymethoxyflavonoids from &lt;i&gt;Kaempferia parviflora&lt;/i&gt; Induce Adipogenesis on 3T3-L1 Preadipocytes by Regulating Transcription Factors at an Early Stage of Differentiation

Horikawa, Takumi; Shimada, Tsutomu; Okabe, Yui; Kinoshita, Kaoru; Koyama, Kiyotaka; Miyamoto, Ken‐ichi; Ichinose, Koji; Takahashi, Kunio; Aburada, Masaki

doi:10.1248/bpb.35.686

Cited by 41 publications

(21 citation statements)

References 32 publications

(26 reference statements)

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“…4) Therefore, it is important to investigate alternative sources of more efficacious and safer therapeutics. Recently, a number of natural products were discovered that affect adipocyte differentiation [5][6][7][8][9][10][11] and are therefore attracting increased attention.The fruit of Terminalia bellirica (GAERTN.) ROXB.…”

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confidence: 99%

Gallic Acid, the Active Ingredient of <i>Terminalia bellirica</i>, Enhances Adipocyte Differentiation and Adiponectin Secretion

Makihara

Koike

Ohta

et al. 2016

Biological & Pharmaceutical Bulletin

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Visceral obesity induces the onset of metabolic disorders such as insulin resistance and diabetes mellitus. Adipose tissue is considered as a potential pharmacological target for treating metabolic disorders. The fruit of Terminalia bellirica is extensively used in Ayurvedic medicine to treat patients with diseases such as diabetes mellitus. We previously investigated the effects of a hot water extract of T. bellirica fruit (TB) on obesity and insulin resistance in spontaneously obese type 2 diabetic mice. To determine the active ingredients of TB and their molecular mechanisms, we focused on adipocyte differentiation using mouse 3T3-L1 cells, which are widely used to study adipocyte physiology. We show here that TB enhanced the differentiation of 3T3-L1 cells to mature adipocytes and that one of the active main components was identified as gallic acid. Gallic acid (10-30 µM) enhanced the expression and secretion of adiponectin via adipocyte differentiation and also that of fatty acid binding protein-4, which is the target of peroxisome proliferator-activated receptor gamma (PPARγ), although it does not alter the expression of the upstream genes PPARγ and CCAAT enhancer binding protein alpha. In the PPARγ ligand assay, the binding of gallic acid to PPARγ was undetectable. These findings indicate that gallic acid mediates the therapeutic effects of TB on metabolic disorders by regulating adipocyte differentiation. Therefore, TB shows promise as a candidate for preventing and treating patients with metabolic syndrome.Key words Terminalia bellirica; gallic acid; adipocyte differentiation; adiponectin; metabolic-disorder therapy Visceral obesity induces the onset of metabolic syndrome symptoms such as insulin resistance, diabetes mellitus, abnormal lipid metabolism, and hypertension. Adipose tissue is an endocrine organ that secretes various adipocytokines associated with the accumulation of visceral fat and insulin sensitivity.1) The adipocytes of obese individuals become hypertrophic with a diminished ability to secrete adiponectin, which enhances insulin sensitivity. Adipose tissue plays a major role in mediating the actions of insulin, and is therefore considered a potential pharmacological target for treating the symptoms of metabolic syndrome.Thiazolidinediones are antidiabetic agents that stimulate adipocyte differentiation and enhance insulin sensitivity, 2,3) however they cause adverse effects such as unexpected weight gain, edema, and hepatotoxicity. 4) Therefore, it is important to investigate alternative sources of more efficacious and safer therapeutics. Recently, a number of natural products were discovered that affect adipocyte differentiation [5][6][7][8][9][10][11] and are therefore attracting increased attention.The fruit of Terminalia bellirica (GAERTN.) ROXB. is extensively used in Ayurvedic medicine in India and neighboring countries. Although the fruit of T. bellirica is used to treat various ailments, including diabetes mellitus, [12][13][14] the mechanism is unknown. T. bellirica extract has ...

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Gallic Acid, the Active Ingredient of <i>Terminalia bellirica</i>, Enhances Adipocyte Differentiation and Adiponectin Secretion

Makihara

Koike

Ohta

et al. 2016

Biological & Pharmaceutical Bulletin

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“…6 3,5,7,4'-Tetramethoxyflavone (8) and 3,5,7,3',4'-pentamethoxyflavone (10) have an effect similar to that of nobiletin, which strongly promotes the differentiation of 3T3-L1 preadipocytes into mature adipocytes via transcriptional activation of peroxisome proliferatoractivated receptor γ (PPARγ), yet lacks ligand-binding activity. 22 The active constituents of the anti-allergic activity of K. parviflora have been identified as 5-hydroxy-7-methoxyflavone (1), 5-hydroxy-7,4'-dimethoxyflavone (7), and 5-hydroxy-3,7,3',4'-tetramethoxyflavone (11). 13 In addition, 3,5,7,3',4'-pentamethoxyflavone (10) inhibits Pglycoprotein function.…”

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confidence: 99%

Anti-osteoporotic and Antioxidant Activities by Rhizomes ofKaempferia parvifloraWall. ex Baker

et al. 2016

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− In this report, we investigated the antioxidant (peroxyl radical-scavenging and reducing capacities) and anti-osteoporotic activities of extracts and isolated constituents (1 -16) from the rhizomes of Kaempferia parviflora Wall. ex Baker on pre-osteoclastic RAW 264.7 cells. Compound 5 exhibited significant peroxyl radicalscavenging capacity, with TE value of 8.47 ± 0.52 µM, while compound 13 showed significant reducing capacity, with CUPRAC value of 5.66 ± 0.26 µM, at 10.0 µM. In addition, flavonoid compounds 2, 4, 6, 8, 10, 12, and terpene compound 15 showed significant inhibition of tartrate-resistant acid phosphatase (TRAP) in NF-κB ligand-induced osteoclastic RAW 264.7 cells, with values ranging from 16.97 ± 1.02 to 64.67 ± 2.76%. These results indicated that K. parviflora could be excellent sources for the antioxidant and anti-osteoporotic traditional medicinal plants.

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“…Moreover, polymethoxyflavonoids and sakuranetin isolated from Kaempferia parviflora and Smallanthus fruticosus, respectively, enhanced adipocyte differentiation via GATA-2 mRNA expression [26,27]. Platycodin D from Platycodon grandiflorus and baicalin from Scutellaria baicalensis have been reported to inhibit adipogenesis via upregulating KLF2 and via upregulating KLF2 and downregulating KLF15 mRNA levels, respectively; mRNA levels were measured at 2-7 days after induction [28,29].…”

Section: Discussionmentioning

confidence: 99%

Cineromycin B isolated from Streptomyces cinerochromogenes inhibits adipocyte differentiation of 3T3-L1 cells via Krüppel-like factors 2 and 3

et al. 2015

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Polymethoxyflavonoids from <i>Kaempferia parviflora</i> Induce Adipogenesis on 3T3-L1 Preadipocytes by Regulating Transcription Factors at an Early Stage of Differentiation

Cited by 41 publications

References 32 publications

Gallic Acid, the Active Ingredient of <i>Terminalia bellirica</i>, Enhances Adipocyte Differentiation and Adiponectin Secretion

Gallic Acid, the Active Ingredient of <i>Terminalia bellirica</i>, Enhances Adipocyte Differentiation and Adiponectin Secretion

Anti-osteoporotic and Antioxidant Activities by Rhizomes ofKaempferia parvifloraWall. ex Baker

Cineromycin B isolated from Streptomyces cinerochromogenes inhibits adipocyte differentiation of 3T3-L1 cells via Krüppel-like factors 2 and 3

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