Anti-allergenic activity of polymethoxyflavones from Kaempferia parviflora

Kobayashi, Shoko; Kato, Taro; Azuma, Tsuneo; Kikuzaki, Hiroe; Abe, Keiko

doi:10.1016/j.jff.2014.12.029

Cited by 35 publications

(23 citation statements)

References 26 publications

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“…During the development of BACE1 inhibitors of natural products origin, many studies directed the attention toward naturally occurring polyphenolic compounds, like flavonoids, particularly polymethoxyflavones extracted from black ginger ( Kaempferia parviflora [KP]). KP plant was primarily known to have antioxidant, anticarcinogenic, and antifatigue properties . However, its extract consists mainly of three major components, namely polymethoxyflavones, 5,7‐dimethoxyflavone (DMF), 5,7,4′‐trimethoxyflavone (TMF), and 3,5,7,3′,4′‐pentamethoxyflavone (PMF), which showed considerable BACE1 inhibitory activity, with an insignificant effect on α‐secretase and other serine proteases.…”

Section: Bace1 As a Potential Target For The Treatment Of Alzheimer'smentioning

confidence: 99%

“…KP plant was primarily known to have antioxidant, anticarcinogenic, and antifatigue properties. 77 However, its extract consists mainly of three major components, namely polymethoxyflavones, 5,7-dimethoxyflavone (DMF), 5,7,4′-trimethoxyflavone (TMF), and 3,5,7,3′,4′-pentamethoxyflavone (PMF), which showed considerable BACE1 inhibitory activity, with an insignificant effect on α-secretase and other serine proteases. Youn et al carried out an in silico study utilizing a human BACE1 with nonpeptidyl polymethoxyflavones, to assess their mode of binding.…”

Section: Naturally-occurring Bace1 Inhibitorsmentioning

confidence: 99%

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BACE1 inhibitors: Current status and future directions in treating Alzheimer's disease

Moussa-Pacha

Abdin

Omar

et al. 2019

Medicinal Research Reviews

226

175

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Alzheimer's disease (AD) is an irreversible, progressive neurodegenerative brain disorder with no current cure. One of the important therapeutic approaches of AD is the inhibition of β‐site APP cleaving enzyme‐1 (BACE1), which is involved in the rate‐limiting step of the cleavage process of the amyloid precursor protein (APP) leading to the generation of the neurotoxic amyloid β (Aβ) protein after the γ‐secretase completes its function. The produced insoluble Aβ aggregates lead to plaques deposition and neurodegeneration. BACE1 is, therefore, one of the attractive targets for the treatment of AD. This approach led to the development of potent BACE1 inhibitors, many of which were advanced to late stages in clinical trials. Nonetheless, the high failure rate of lead drug candidates targeting BACE1 brought to the forefront the need for finding new targets to uncover the mystery behind AD. In this review, we aim to discuss the most promising classes of BACE1 inhibitors with a description and analysis of their pharmacodynamic and pharmacokinetic parameters, with more focus on the lead drug candidates that reached late stages of clinical trials, such as MK8931, AZD‐3293, JNJ‐54861911, E2609, and CNP520. In addition, the manuscript discusses the safety concerns and insignificant physiological effects, which were highlighted for the most successful BACE1 inhibitors. Furthermore, the review demonstrates with increasing evidence that despite tremendous efforts and promising results conceived with BACE1 inhibitors, the latest studies suggest that their clinical use for treating Alzheimer's disease should be reconsidered. Finally, the review sheds light on alternative therapeutic options for targeting AD.

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Section: Bace1 As a Potential Target For The Treatment Of Alzheimer'smentioning

confidence: 99%

Section: Naturally-occurring Bace1 Inhibitorsmentioning

confidence: 99%

BACE1 inhibitors: Current status and future directions in treating Alzheimer's disease

Moussa-Pacha

Abdin

Omar

et al. 2019

Medicinal Research Reviews

226

175

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“…Flavonoid glycosides such as naringin, hesperidin, neohesperidin, naringenin, and hesperetin and their respective aglycones, polymethoxylated flavones, and coumarins, like meranzin hydrate, are all components found in FA [ 6 – 9 ]. Various work published in the literature have established that these compounds possess astoundingly biomedical properties, such as prokinetic effect [ 2 ], antidepression activity [ 10 , 11 ], inflammation alleviating function [ 12 ], antioxidant and free-radical scavenging effect [ 13 ], anticarcinogenic activity [ 14 , 15 ], antihypersensitivity [ 16 ], and hypoglycemic and hypolipidemic effects [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Development of an Ultra-High Performance Liquid Chromatography Method for Simultaneous Determination of Six Active Compounds in Fructus aurantii and Rat Plasma and Its Application to a Comparative Pharmacokinetic Study in Rats Administered with Different Doses

Zhao

Huang

Yao

et al. 2018

Journal of Analytical Methods in Chemistry

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A rapid, accurate, and sensitive ultra-high performance liquid chromatography (UHPLC) method was established for simultaneously detecting naringin, hesperidin, neohesperidin, meranzin hydrate, naringenin, and hesperetin in Fructus aurantii (FA) decoction. Analysis was performed on Waters BEH (R) C18 (50 mm × 2.1 mm, 1.7 μm) at a flow rate of 0.2 mL/min by using (A) acetonitrile and (B) 0.5% acetic acid-water as the mobile phase. The method was well validated on linearity, precision, recoveries, and stability. Then, we used the same UHPLC conditions for quantitative analysis of meranzin hydrate, naringenin, and hesperetin in rat plasma. The method proved to be linear within the concentration ranges of 3.3–3300 ng/mL for meranzin hydrate, 6.95–3555 ng/mL for naringenin, and 1.8–236 ng/mL for hesperetin. The RSD of precision ranged from 1.22% to 9.08%, and the average extraction recovery ranged from 96.49 ± 1.42% to 102.01 ± 3.16%. Besides, we performed a comparative pharmacokinetic study after oral administration of FA decoction at a low dose of 15 g/kg and high dose of 30 g/kg body weight for seven days to rats. The AUC(0–t) and C max of meranzin hydrate, naringenin, and hesperetin were multiplied significantly with the increase of FA dosage, and the t 1/2 of meranzin hydrate was faster than naringenin and hesperetin in the two groups.

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“…Rat basophilic leukemia‐2H3 cells (RBL‐2H3) secrete various inflammatory mediators and have been used extensively for the study of allergic responses . Phorbol 12‐myristate 13‐acetate (PMA), an activator of PKC, and A23187, a calcium ionophore, increase intracellular calcium influx in RBL‐2H3 cells, thereby activating allergic inflammatory responses. Thus, in the present study, we used PMA and A23187 to examine the antiallergic effects of furan derivatives (Figure ) in RBL‐2H3 cells.…”

mentioning

confidence: 99%

“…The inhibitory effects of furan derivatives on degranulation were evaluated by the activity of β‐hexosaminidase . Treatment of RBL‐2H3 cells with 10 furan derivatives, followed by stimulation with PMA and A23187, revealed that compound F4 inhibited the release of β‐hexosaminidase (Figure ).…”

mentioning

confidence: 99%

Inhibitory Effects of 1‐(5‐Benzyl‐4‐(4‐chlorophenyl)‐2‐methylfuran‐3‐yl)ethan‐1‐one on Allergic Inflammatory Responses in Rat Basophilic Leukemia Cells

Yoo

Ahn

Joe

et al. 2015

Bulletin Korean Chem Soc

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Mast cells play a key role in allergic inflammatory process. Mast cell activation is controlled by immunoglobulin E (IgE). Aggregated FcεRI, IgE receptor on the surface of mast cells, triggers biological events such as degranulation and secretion of inflammatory mediators. 1 In addition, aggregation of FcεRI triggers the activation of intracellular signaling pathways, leading to increased intracellular calcium influx; cytoskeleton rearrangement; activation of Lyn, Syk, protein kinase C (PKC), and mitogen-activated protein kinases (MAPKs) 2 ; the and subsequent release of several inflammatory mediators, including histamine, proteases, de novo synthesized cytokines, and eicosanoids. 3 Rat basophilic leukemia-2H3 cells (RBL-2H3) secrete various inflammatory mediators and have been used extensively for the study of allergic responses. 3-9 Phorbol 12-myristate 13-acetate (PMA), an activator of PKC, and A23187, a calcium ionophore, increase intracellular calcium influx in RBL-2H3 cells, 3-10 thereby activating allergic inflammatory responses. Thus, in the present study, we used PMA and A23187 to examine the antiallergic effects of furan derivatives ( Figure 1) in RBL-2H3 cells.The inhibitory effects of furan derivatives on degranulation were evaluated by the activity of β-hexosaminidase. 3,6,8,10 Treatment of RBL-2H3 cells with 10 furan derivatives, followed by stimulation with PMA and A23187, revealed that compound F4 inhibited the release of β-hexosaminidase ( Figure 2). Moreover, this effect was dose dependent, at 100 μM concentration, blocking β-hexosaminidase release by 50% compared with the untreated control ( Figure 3). However, human T lymphoid cell line (Molt-4) and mouse leukemic monocyte/macrophage cell line (Raw264.7) were not affected in their immunological activities by this chemical (data not shown). MTT (3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assays 3 revealed that up to 100 μM concentration did not cause significant cytotoxicity in RBL-2H3 cells (Figure 4). Thus, these results indicated that compound F4 inhibited degranulation of RBL-2H3 cells but did not have cytotoxic effects in this cell line.It is also known that furan is listed as a possible carcinogen in humans, as well as in rat and mouse. 11 At a concentration of 50 μM, compound F4 did not show cytotoxicity or proliferation effect in human hepatocellular carcinoma cell line (HepG2) and human normal liver cell line (Chang). However, at 100 μM, cell proliferation of HepG2 cells was increased by 15 AE 8.2% and cell viability of Chang cells was decreased by 8 AE 3.8% compared with control. These findings need to be confirmed using further studies in future.Next, we investigated the inhibitory degranulation mechanism on MAPK signaling by immunoblotting. [3][4][5][6][7][8][9] MAPKs are key factors regulating the expression of inflammatory cytokine genes in immune cells 2,12,13 and phosphorylate a series of downstream factors in response to activation by several extracellular factors. 14,15 Thus, the development of MAPK inhi...

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Anti-allergenic activity of polymethoxyflavones from Kaempferia parviflora

Cited by 35 publications

References 26 publications

BACE1 inhibitors: Current status and future directions in treating Alzheimer's disease

BACE1 inhibitors: Current status and future directions in treating Alzheimer's disease

Development of an Ultra-High Performance Liquid Chromatography Method for Simultaneous Determination of Six Active Compounds in Fructus aurantii and Rat Plasma and Its Application to a Comparative Pharmacokinetic Study in Rats Administered with Different Doses

Inhibitory Effects of 1‐(5‐Benzyl‐4‐(4‐chlorophenyl)‐2‐methylfuran‐3‐yl)ethan‐1‐one on Allergic Inflammatory Responses in Rat Basophilic Leukemia Cells

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