Sign in to use this feature.

Years

Between: -

Subjects

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Journals

Article Types

Countries / Regions

Search Results (8)

Search Parameters:
Keywords = flavokawain B

Order results
Result details
Results per page
Select all
Export citation of selected articles as:
16 pages, 4126 KiB  
Article
Physicochemical Characterization, Skin Penetration, Anti-Melanogenesis and Safety Assessment of Flavokawain C Nanofibers
by Pamela Berilyn So, Ying-Chu Wang, Pao-Hsien Huang, Tzu-Hui Wu and Feng-Lin Yen
Int. J. Mol. Sci. 2025, 26(7), 2966; https://doi.org/10.3390/ijms26072966 - 25 Mar 2025
Viewed by 519
Abstract
Various whitening cosmetics are available in the market, usually containing active whitening ingredients. However, most of the reported active ingredients have low dermal penetration due to their lipophilic structure. Therefore, it is necessary to develop effective whitening agents and novel formulations to address [...] Read more.
Various whitening cosmetics are available in the market, usually containing active whitening ingredients. However, most of the reported active ingredients have low dermal penetration due to their lipophilic structure. Therefore, it is necessary to develop effective whitening agents and novel formulations to address this. In previous studies, natural compounds such as chalcones have shown inhibitory effects on tyrosinase. However, most chalcone compounds have the disadvantage of poor water solubility, which restricts their dermal absorption. Flavokawain C (FKC) is a natural chalcone obtained from the root of the kava tree (Piper methysticum) and can also be obtained through organic synthesis. Since FKC is a chalcone, it is also water-insoluble, showing poor dermal absorption. In this study, electrospinning technology was used to develop FKC nanofibers (FKCNFs) to improve FKC’s physicochemical properties. The results showed that FKCNFs significantly improved water solubility and percutaneous absorption. Based on the results of in vitro experiments with B16F10 melanoma cells, 10 µM FKCNFs repressed the expressions of melanogenesis-related proteins MITF and TRP2. Furthermore, cosmetic safety assessment revealed that FKCNFs displayed a good margin of safety. This study suggests that FKCNFs have great potential as an effective active ingredient for whitening cosmetics. Full article
(This article belongs to the Special Issue Pigment Cells: From Biology to Medicine)
Show Figures

Figure 1

16 pages, 4319 KiB  
Article
Anti-Apoptotic Effect of Flavokawain A on Ochratoxin-A-Induced Endothelial Cell Injury by Attenuation of Oxidative Stress via PI3K/AKT-Mediated Nrf2 Signaling Cascade
by Peramaiyan Rajendran, Abdullah M. Alzahrani, Vishnu Priya Veeraraghavan and Emad A. Ahmed
Toxins 2021, 13(11), 745; https://doi.org/10.3390/toxins13110745 - 21 Oct 2021
Cited by 16 | Viewed by 3200
Abstract
This study investigates the endothelial protective activity of flavokawain A (FKA) against oxidative stress induced by ochratoxin A (OTA), which acts as a mycotoxin, and its primary mechanisms in in vitro models. Reactive oxygen species, in general, regulate oxidative stress that significantly contributes [...] Read more.
This study investigates the endothelial protective activity of flavokawain A (FKA) against oxidative stress induced by ochratoxin A (OTA), which acts as a mycotoxin, and its primary mechanisms in in vitro models. Reactive oxygen species, in general, regulate oxidative stress that significantly contributes to the pathophysiology of endothelial dysfunctions. OTA exerts toxicity through inflammation and the accumulation of ROS. This research is aimed at exploring the defensive function of FKA against the endothelial injury triggered by OTA through the Nrf2 pathway regulated by PI3K/AKT. OTA exposure significantly increased the nuclear translocation of NFκB, whereas we found a reduction in inflammation via NFκB inhibition with FKA treatment. FKA increased the PI3K and AKT phosphorylation, which may lead to the stimulation of antioxidative and antiapoptotic signaling in HUVECs. It also upregulated the phosphorylation of Nrf2 and a concomitant expression of antioxidant genes, such as HO-1, NQO-1, and γGCLC, depending on the dose under the oxidative stress triggered by OTA. Knockdown of Nrf2 through small interfering RNA (siRNA) impedes the protective role of FKA against the endothelial toxicity induced by OTA. In addition, FKA enhanced Bcl2 activation while suppressing apoptosis marker proteins. Therefore, FKA is regarded as a potential agent against endothelial oxidative stress caused by the deterioration of the endothelium. The research findings showed that FKA plays a key role in activating the p-PI3K/p-AKT and Nrf2 signaling pathways, while suppressing caspase-dependent apoptosis. Full article
Show Figures

Graphical abstract

2 pages, 1000 KiB  
Correction
Correction: Hseu, Y.-C., et al. The In Vitro and In Vivo Anticancer Properties of Chalcone Flavokawain B through Induction of ROS-Mediated Apoptotic and Autophagic Cell Death in Human Melanoma Cells. Cancers 2020, 12, 2936
by You-Cheng Hseu, Yu-Chi Chiang, Yugandhar Vudhya Gowrisankar, Kai-Yuan Lin, Sheng-Teng Huang, Sirjana Shrestha, Geng-Ruei Chang and Hsin-Ling Yang
Cancers 2021, 13(2), 303; https://doi.org/10.3390/cancers13020303 - 15 Jan 2021
Cited by 2 | Viewed by 1850
Abstract
In the original article [...] Full article
24 pages, 5331 KiB  
Article
The In Vitro and In Vivo Anticancer Properties of Chalcone Flavokawain B through Induction of ROS-Mediated Apoptotic and Autophagic Cell Death in Human Melanoma Cells
by You-Cheng Hseu, Yu-Chi Chiang, Yugandhar Vudhya Gowrisankar, Kai-Yuan Lin, Sheng-Teng Huang, Sirjana Shrestha, Geng-Ruei Chang and Hsin-Ling Yang
Cancers 2020, 12(10), 2936; https://doi.org/10.3390/cancers12102936 - 12 Oct 2020
Cited by 39 | Viewed by 3527 | Correction
Abstract
Melanoma is the most prevalent type of skin cancer with high mortality rates. This study demonstrates the in vitro and in vivo anticancer properties of chalcone flavokawain B (FKB) induced ROS-mediated apoptosis and autophagy in human melanoma (human epithelial melanoma cell line A375 [...] Read more.
Melanoma is the most prevalent type of skin cancer with high mortality rates. This study demonstrates the in vitro and in vivo anticancer properties of chalcone flavokawain B (FKB) induced ROS-mediated apoptosis and autophagy in human melanoma (human epithelial melanoma cell line A375 and/or human skin lymph node derived melanoma cell line A2058) cells. Cell viability was calculated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the expression patterns of various apoptosis, autophagy-associated proteins were determined by Western blot methods. Annexin V was detected by flow cytometry, whereas acidic vesicular organelles (AVOs) and intracellular ROS levels were measured by fluorescence microscopy. The in vivo anticancer properties of FKB were evaluated by xenografting the A375 cells into nude mice. The results convey that FKB inhibited cell viability, B-Raf proto-oncogene, serine/threonine kinase (BRAF)/extracellular signal-regulated kinase (ERK) expression in human melanoma cells. Caspase-3 activation, poly (ADP-ribose) polymerase (PARP) cleavage pathway, and Bcl2 associated X (Bax)/B-cell lymphoma 2 (Bcl-2) dysregulation were involved in the execution of apoptosis. Moreover, FKB-induced autophagy was observed through increased microtubule-associated protein 1A/1B-light chain 3B (LC3-II) accumulation and AVOs formation, which was also associated with an increase in sequestosome 1 (SQSTM1/p62), decreased protein kinase B (AKT)/mammalian target of rapamycin (mTOR) expressions, and dysregulated Beclin-1/Bcl-2 levels. Autophagy inhibitors [3-methyladenine (3-MA)/chloroquine (CQ)] and LC3 silencing suppressed FKB-induced apoptosis by decreasing caspase-3 in melanoma cells. The antioxidant N-acetylcysteine (NAC) diminished FKB-induced apoptotic and autophagic cell death. However, the inhibition of apoptosis decreased FKB-induced autophagy (LC3-I/II). The in vivo study confirmed that FKB inhibited melanoma growth in A375-xenografted nude mice. This study concluded that FKB is critically associated with the execution and generation of ROS-modulated apoptotic and autophagic cell death of melanoma cells. FKB also repressed tumor growth in xenografted nude mice. Therefore, flavokawain B might be a potential anti-tumor agent in human melanoma treatment. Full article
Show Figures

Graphical abstract

26 pages, 9100 KiB  
Article
Flavokawain B and Doxorubicin Work Synergistically to Impede the Propagation of Gastric Cancer Cells via ROS-Mediated Apoptosis and Autophagy Pathways
by You-Cheng Hseu, Ruei-Wan Lin, Yi-Chun Shen, Kai-Yuan Lin, Jiunn-Wang Liao, Varadharajan Thiyagarajan and Hsin-Ling Yang
Cancers 2020, 12(9), 2475; https://doi.org/10.3390/cancers12092475 - 1 Sep 2020
Cited by 33 | Viewed by 4946
Abstract
Chalcone flavokawain B (FKB) possesses a chemopreventive and anti-cancer activity. Doxorubicin is a chemotherapeutic DNA intercalating agent widely used in malignancy treatment. The present study investigated whether synergistic effects exist between the combination of FKB (1.25–5 µg/mL) and doxorubicin (0.5 µg/mL) on the [...] Read more.
Chalcone flavokawain B (FKB) possesses a chemopreventive and anti-cancer activity. Doxorubicin is a chemotherapeutic DNA intercalating agent widely used in malignancy treatment. The present study investigated whether synergistic effects exist between the combination of FKB (1.25–5 µg/mL) and doxorubicin (0.5 µg/mL) on the apoptosis and autophagy in human gastric cancer (AGS) cells, and the possible in vitro and in vivo mechanisms. The MTT assay measured cell viability. Various apoptotic-, autophagy-associated protein expression was determined by the Western blot technique. FKB+doxorubicin synergy was estimated by the Chou-Talalay combination index (CI) method. In vivo studies were performed on BALB/c mice. Results showed that compared to FKB/doxorubicin treatments, low doses of FKB+doxorubicin suppressed AGS cell growth. FKB potentiated doxorubicin-induced DNA fragmentation, apoptotic cell death, and enhanced doxorubicin-mediated mitochondrial, death receptor pathways. FKB+doxorubicin activated increased LC3-II accumulation, p62/SQSTM1 expression, and AVO formation as compared to the FKB/doxorubicin alone treatments indicating autophagy in these cells. The death mechanism in FKB+doxorubicin-treated AGS cells is due to the activation of autophagy. FKB+doxorubicin-mediated dysregulated Bax/Bcl-2, Beclin-1/Bcl-2 ratios suggested apoptosis, autophagy induction in AGS cells. FKB+doxorubicin-induced LC3-II/AVOs downregulation was suppressed due to an apoptotic inhibitor Z-VAD-FMK. Whereas, 3-methyladenine/chloroquine weakened FKB+doxorubicin-induced apoptosis (decreased DNA fragmentation/caspase-3). Activation of ERK/JNK may be involved in FKB+doxorubicin-induced apoptosis and autophagy. FKB+doxorubicin-triggered ROS generation, but NAC attenuated FKB+doxorubicin-induced autophagic (LC3 accumulation) and apoptotic (caspase-3 activation and PARP cleavage) cell death. FKB+doxorubicin blocked gastric cancer cell xenografts in nude mice in vivo as compared to FKB/doxorubicin alone treatments. FKB and doxorubicin wielded synergistic anti-tumor effects in gastric cancer cells and is a promising therapeutic approach. Full article
Show Figures

Figure 1

18 pages, 4421 KiB  
Article
Melanogenic Inhibition and Toxicity Assessment of Flavokawain A and B on B16/F10 Melanoma Cells and Zebrafish (Danio rerio)
by Nurshafika Mohd Sakeh, Nurliyana Najwa Md Razip, Farah Idayu Mohd Ma’in, Mohammad Nazri Abdul Bahari, Naimah Latif, Muhammad Nadeem Akhtar, Zetty Norhana Balia Yusof and Syahida Ahmad
Molecules 2020, 25(15), 3403; https://doi.org/10.3390/molecules25153403 - 28 Jul 2020
Cited by 14 | Viewed by 4875
Abstract
Excessive production of melanin implicates hyperpigmentation disorders. Flavokawain A (FLA) and flavokawain B (FLB) have been reported with anti-melanogenic activity, but their melanogenic inhibition and toxicity effects on the vertebrate model of zebrafish are still unknown. In the present study, cytotoxic as well [...] Read more.
Excessive production of melanin implicates hyperpigmentation disorders. Flavokawain A (FLA) and flavokawain B (FLB) have been reported with anti-melanogenic activity, but their melanogenic inhibition and toxicity effects on the vertebrate model of zebrafish are still unknown. In the present study, cytotoxic as well as melanogenic effects of FLA and FLB on cellular melanin content and tyrosinase activity were evaluated in α-MSH-induced B16/F10 cells. Master regulator of microphthalmia-associated transcription factor (Mitf) and the other downstream melanogenic-related genes were verified via quantitative real time PCR (qPCR). Toxicity assessment and melanogenesis inhibition on zebrafish model was further observed. FLA and FLB significantly reduced the specific cellular melanin content by 4.3-fold and 9.6-fold decrement, respectively in α-MSH-induced B16/F10 cells. Concomitantly, FLA significantly reduced the specific cellular tyrosinase activity by 7-fold whilst FLB by 9-fold. The decrement of melanin production and tyrosinase activity were correlated with the mRNA suppression of Mitf which in turn down-regulate Tyr, Trp-1 and Trp-2. FLA and FLB exhibited non-toxic effects on the zebrafish model at 25 and 6.25 µM, respectively. Further experiments on the zebrafish model demonstrated successful phenotype-based depigmenting activity of FLA and FLB under induced melanogenesis. To sum up, our findings provide an important first key step for both of the chalcone derivatives to be further studied and developed as potent depigmenting agents. Full article
(This article belongs to the Special Issue Pharmaceutical Development)
Show Figures

Figure 1

14 pages, 1952 KiB  
Article
Design, Synthesis and Docking Studies of Flavokawain B Type Chalcones and Their Cytotoxic Effects on MCF-7 and MDA-MB-231 Cell Lines
by Addila Abu Bakar, Muhammad Nadeem Akhtar, Norlaily Mohd Ali, Swee Keong Yeap, Ching Kheng Quah, Wan-Sin Loh, Noorjahan Banu Alitheen, Seema Zareen, Zaheer Ul-Haq and Syed Adnan Ali Shah
Molecules 2018, 23(3), 616; https://doi.org/10.3390/molecules23030616 - 8 Mar 2018
Cited by 33 | Viewed by 6069
Abstract
Flavokawain B (1) is a natural chalcone extracted from the roots of Piper methysticum, and has been proven to be a potential cytotoxic compound. Using the partial structure of flavokawain B (FKB), about 23 analogs have been synthesized. Among them, compounds [...] Read more.
Flavokawain B (1) is a natural chalcone extracted from the roots of Piper methysticum, and has been proven to be a potential cytotoxic compound. Using the partial structure of flavokawain B (FKB), about 23 analogs have been synthesized. Among them, compounds 8, 13 and 23 were found in new FKB derivatives. All compounds were evaluated for their cytotoxic properties against two breast cancer cell lines, MCF-7 and MDA-MB-231, thus establishing the structure–activity relationship. The FKB derivatives 16 (IC50 = 6.50 ± 0.40 and 4.12 ± 0.20 μg/mL), 15 (IC50 = 5.50 ± 0.35 and 6.50 ± 1.40 μg/mL) and 13 (IC50 = 7.12 ± 0.80 and 4.04 ± 0.30 μg/mL) exhibited potential cytotoxic effects on the MCF-7 and MDA-MB-231 cell lines. However, the methoxy group substituted in position three and four in compound 2 (IC50 = 8.90 ± 0.60 and 6.80 ± 0.35 μg/mL) and 22 (IC50 = 8.80 ± 0.35 and 14.16 ± 1.10 μg/mL) exhibited good cytotoxicity. The lead compound FKB (1) showed potential cytotoxicity (IC50 = 7.70 ± 0.30 and 5.90 ± 0.30 μg/mL) against two proposed breast cancer cell lines. It is evident that the FKB skeleton is unique for anticancer agents, additionally, the presence of halogens (Cl and F) in position 2 and 3 also improved the cytotoxicity in FKB series. These findings could help to improve the future drug discovery process to treat breast cancer. A molecular dynamics study of active compounds revealed stable interactions within the active site of Janus kinase. The structures of all compounds were determined by 1H-NMR, EI-MS, IR and UV and X-ray crystallographic spectroscopy techniques. Full article
(This article belongs to the Section Organic Chemistry)
Show Figures

Graphical abstract

10 pages, 5043 KiB  
Article
In Silico Discovery of Potential Uridine-Cytidine Kinase 2 Inhibitors from the Rhizome of Alpinia mutica
by Ibrahim Malami, Ahmad Bustamam Abdul, Rasedee Abdullah, Nur Kartinee Bt Kassim, Peter Waziri and Imaobong Christopher Etti
Molecules 2016, 21(4), 417; https://doi.org/10.3390/molecules21040417 - 8 Apr 2016
Cited by 12 | Viewed by 6893
Abstract
Uridine-cytidine kinase 2 is implicated in uncontrolled proliferation of abnormal cells and it is a hallmark of cancer, therefore, there is need for effective inhibitors of this key enzyme. In this study, we employed the used of in silico studies to find effective [...] Read more.
Uridine-cytidine kinase 2 is implicated in uncontrolled proliferation of abnormal cells and it is a hallmark of cancer, therefore, there is need for effective inhibitors of this key enzyme. In this study, we employed the used of in silico studies to find effective UCK2 inhibitors of natural origin using bioinformatics tools. An in vitro kinase assay was established by measuring the amount of ADP production in the presence of ATP and 5-fluorouridine as a substrate. Molecular docking studies revealed an interesting ligand interaction with the UCK2 protein for both flavokawain B and alpinetin. Both compounds were found to reduce ADP production, possibly by inhibiting UCK2 activity in vitro. In conclusion, we have identified flavokawain B and alpinetin as potential natural UCK2 inhibitors as determined by their interactions with UCK2 protein using in silico molecular docking studies. This can provide information to identify lead candidates for further drug design and development. Full article
(This article belongs to the Section Natural Products Chemistry)
Show Figures

Graphical abstract

Back to TopTop