Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Mini-Review Article

Kaempferol: A Dietary Flavonol in Alleviating Obesity

Author(s): Hamid Reza Nejabati*, Sadeneh Nikzad and Leila Roshangar

Volume 29, Issue 20, 2023

Published on: 20 July, 2023

Page: [1547 - 1556] Pages: 10

DOI: 10.2174/1381612829666230719121548

Price: $65

Abstract

Obesity is considered as a chronic and high-prevalence disease on a global scale which affects all genders and ages. Although various drugs have been confirmed for the treatment of obesity, these medications have been shown to have a number of adverse effects on health. It is highlighted that natural products have an alleviative role in a broad spectrum of diseases, in particular obesity, and diabetes. Kaempferol (KMP), a plant- derived flavonol, is considerably engaged in the suppression of oxidative stress, radical scavenging, opposing cellular toxicity, and induction of the production and release of growth factors. This flavonol combats obesity by suppressing adipogenesis, regulating lipid and glucose metabolism, changing gut microbiota, and activating autophagy. Also, studies have shown that KMP exerts its anti-obesity actions by decreasing the accumulation of lipids and triglycerides (TGs), increasing fatty acid oxidation, and regulating multiple metabolic genes in the adipocytes. Considering that KMP may be a potential candidate for combating obesity, this paper summarizes the possible therapeutic roles of KMP in the treatment and prevention of this disease.

Next »
[1]
Wang L, Zhou B, Zhao Z, et al. Body-mass index and obesity in urban and rural China: Findings from consecutive nationally representative surveys during 2004-18. Lancet 2021; 398(10294): 53-63.
[http://dx.doi.org/10.1016/S0140-6736(21)00798-4] [PMID: 34217401]
[2]
Wyatt SB, Winters KP, Dubbert PM. Overweight and obesity: Prevalence, consequences, and causes of a growing public health problem. Am J Med Sci 2006; 331(4): 166-74.
[http://dx.doi.org/10.1097/00000441-200604000-00002] [PMID: 16617231]
[3]
WHOK. Obesity and overweight. 2021. https://www.who.int/ en/news-room/fact-sheets/detail/obesity-and-overweight (accessed June 20, 2021).
[4]
Chang YC, Liu PH, Lee WJ, et al. Common variation in the fat mass and obesity-associated (FTO) gene confers risk of obesity and modulates BMI in the Chinese population. Diabetes 2008; 57(8): 2245-52.
[http://dx.doi.org/10.2337/db08-0377] [PMID: 18487448]
[5]
Lettieri-Barbato D, Giovannetti E, Aquilano K. Effects of dietary restriction on adipose mass and biomarkers of healthy aging in human. Aging (Albany NY) 2016; 8(12): 3341-55.
[http://dx.doi.org/10.18632/aging.101122] [PMID: 27899768]
[6]
Salas-Salvadó J, Díaz-López A, Ruiz-Canela M, et al. Effect of a lifestyle intervention program with energy-restricted mediterranean diet and exercise on weight loss and cardiovascular risk factors: One-year results of the PREDIMED-Plus trial. Diabetes Care 2019; 42(5): 777-88.
[http://dx.doi.org/10.2337/dc18-0836] [PMID: 30389673]
[7]
Ladabaum U, Mannalithara A, Myer PA, Singh G. Obesity, abdominal obesity, physical activity, and caloric intake in US adults: 1988 to 2010. Am J Med 2014; 127(8): 717-727.e12.
[http://dx.doi.org/10.1016/j.amjmed.2014.02.026] [PMID: 24631411]
[8]
Liberini CG, Ghidewon M, Ling T, et al. Early life overnutrition impairs plasticity of non-neuronal brainstem cells and drives obesity in offspring across development in rats. Int J Obes 2020; 44(12): 2405-18.
[http://dx.doi.org/10.1038/s41366-020-00658-5] [PMID: 32999409]
[9]
Blüher M. Obesity: Global epidemiology and pathogenesis. Nat Rev Endocrinol 2019; 15(5): 288-98.
[http://dx.doi.org/10.1038/s41574-019-0176-8] [PMID: 30814686]
[10]
Pilitsi E, Farr OM, Polyzos SA, et al. Pharmacotherapy of obesity: Available medications and drugs under investigation. Metabolism 2019; 92: 170-92.
[http://dx.doi.org/10.1016/j.metabol.2018.10.010] [PMID: 30391259]
[11]
Kim KK, Cho HJ, Kang HC, Youn BB, Lee KR. Effects on weight reduction and safety of short-term phentermine administration in Korean obese people. Yonsei Med J 2006; 47(5): 614-25.
[http://dx.doi.org/10.3349/ymj.2006.47.5.614] [PMID: 17066505]
[12]
Torgerson JS, Hauptman J, Boldrin MN, Sjöström L. XENical in the prevention of diabetes in obese subjects (XENDOS) study: A randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care 2004; 27(1): 155-61.
[http://dx.doi.org/10.2337/diacare.27.1.155] [PMID: 14693982]
[13]
Cui S, Zhao N, Lu W, et al. Effect of different Lactobacillus species on volatile and nonvolatile flavor compounds in juices fermentation. Food Sci Nutr 2019; 7(7): 2214-23.
[http://dx.doi.org/10.1002/fsn3.1010] [PMID: 31367350]
[14]
Reddy PH, Manczak M, Yin X, et al. Protective effects of indian spice curcumin against amyloid-β in Arlzheimer’s disease. J Alzheimers Dis 2018; 61(3): 843-66.
[http://dx.doi.org/10.3233/JAD-170512] [PMID: 29332042]
[15]
Senturk Parreidt T, Lindner M, Rothkopf I, Schmid M, Müller K. The development of a uniform alginate-based coating for cantaloupe and strawberries and the characterization of water barrier properties. Foods 2019; 8(6): 203.
[http://dx.doi.org/10.3390/foods8060203] [PMID: 31212593]
[16]
Shang A, Cao SY, Xu XY, et al. Bioactive compounds and biological functions of garlic (Allium sativum L.). Foods 2019; 8(7): 246.
[http://dx.doi.org/10.3390/foods8070246] [PMID: 31284512]
[17]
Shang A, Gan RY, Xu XY, Mao QQ, Zhang PZ, Li HB. Effects and mechanisms of edible and medicinal plants on obesity: An updated review. Crit Rev Food Sci Nutr 2021; 61(12): 2061-77.
[http://dx.doi.org/10.1080/10408398.2020.1769548] [PMID: 32462901]
[18]
Tang GY, Meng X, Li Y, Zhao CN, Liu Q, Li HB. Effects of vegetables on cardiovascular diseases and related mechanisms. Nutrients 2017; 9(8): 857.
[http://dx.doi.org/10.3390/nu9080857] [PMID: 28796173]
[19]
Tao J, Li S, Gan RY, Zhao CN, Meng X, Li HB. Targeting gut microbiota with dietary components on cancer: Effects and potential mechanisms of action. Crit Rev Food Sci Nutr 2020; 60(6): 1025-37.
[http://dx.doi.org/10.1080/10408398.2018.1555789] [PMID: 30632784]
[20]
Xu XY, Zhao CN, Cao SY, Tang GY, Gan RY, Li HB. Effects and mechanisms of tea for the prevention and management of cancers: An updated review. Crit Rev Food Sci Nutr 2020; 60(10): 1693-705.
[http://dx.doi.org/10.1080/10408398.2019.1588223] [PMID: 30869995]
[21]
Zhou DD, Luo M, Shang A, et al. Antioxidant food components for the prevention and treatment of cardiovascular diseases: Effects, mechanisms, and clinical studies. Oxid Med Cell Longev 2021; 2021: 1-17.
[http://dx.doi.org/10.1155/2021/6627355] [PMID: 33574978]
[22]
Xu XY, Zhao CN, Li BY, et al. Effects and mechanisms of tea on obesity. Crit Rev Food Sci Nutr 2023; 63(19): 3716-33.
[http://dx.doi.org/10.1080/10408398.2021.1992748] [PMID: 34704503]
[23]
Li JJ, Huang CJ, Xie D. Anti-obesity effects of conjugated linoleic acid, docosahexaenoic acid, and eicosapentaenoic acid. Mol Nutr Food Res 2008; 52(6): 631-45.
[http://dx.doi.org/10.1002/mnfr.200700399] [PMID: 18306430]
[24]
Trigueros L, Peña S, Ugidos AV, Sayas-Barberá E, Pérez-Álvarez JA, Sendra E. Food ingredients as anti-obesity agents: A review. Crit Rev Food Sci Nutr 2013; 53(9): 929-42.
[http://dx.doi.org/10.1080/10408398.2011.574215] [PMID: 23768185]
[25]
Xu Y, Wang N, Tan HY, et al. Panax notoginseng saponins modulate the gut microbiota to promote thermogenesis and beige adipocyte reconstruction via leptin-mediated AMPKα/STAT3 signaling in diet-induced obesity. Theranostics 2020; 10(24): 11302-23.
[http://dx.doi.org/10.7150/thno.47746] [PMID: 33042284]
[26]
Dai J, Mumper RJ. Plant phenolics: Extraction, analysis and their antioxidant and anticancer properties. Molecules 2010; 15(10): 7313-52.
[http://dx.doi.org/10.3390/molecules15107313] [PMID: 20966876]
[27]
D’Archivio M, Filesi C, Di Benedetto R, Gargiulo R, Giovannini C, Masella R. Polyphenols, dietary sources and bioavailability. Ann Ist Super Sanita 2007; 43(4): 348-61.
[PMID: 18209268]
[28]
Bangar SP, Chaudhary V, Sharma N, Bansal V, Ozogul F, Lorenzo JM. Kaempferol: A flavonoid with wider biological activities and its applications. Crit Rev Food Sci Nutr 2022; 1-25.
[http://dx.doi.org/10.1080/10408398.2022.2067121] [PMID: 35468008]
[29]
Meena D, Vimala K, Kannan S. Combined delivery of DOX and kaempferol using PEGylated gold nanoparticles to target colon cancer. J Cluster Sci 2022; 33(1): 173-87.
[http://dx.doi.org/10.1007/s10876-020-01961-x]
[30]
Shrestha R, Mohankumar K, Martin G, et al. Flavonoids kaempferol and quercetin are nuclear receptor 4A1 (NR4A1, Nur77) ligands and inhibit rhabdomyosarcoma cell and tumor growth. J Exp Clin Cancer Res 2021; 40(1): 392.
[http://dx.doi.org/10.1186/s13046-021-02199-9] [PMID: 34906197]
[31]
Vimalraj S, Saravanan S, Hariprabu G, et al. Kaempferol-zinc(II) complex synthesis and evaluation of bone formation using zebrafish model. Life Sci 2020; 256: 117993.
[http://dx.doi.org/10.1016/j.lfs.2020.117993] [PMID: 32574664]
[32]
Xiao HB, Sui GG, Lu XY, Sun ZL. Kaempferol modulates Angiopoietin-like protein 2 expression to lessen the mastitis in mice. Pharmacol Rep 2018; 70(3): 439-45.
[http://dx.doi.org/10.1016/j.pharep.2017.11.006] [PMID: 29627690]
[33]
Nejabati HR, Roshangar L. Kaempferol: A potential agent in the prevention of colorectal cancer. Physiol Rep 2022; 10(20): e15488.
[http://dx.doi.org/10.14814/phy2.15488] [PMID: 36259115]
[34]
Nejabati HR, Roshangar L. Kaempferol as a potential neuroprotector in Alzheimer’s disease. J Food Biochem 2022; 46(12): e14375.
[http://dx.doi.org/10.1111/jfbc.14375] [PMID: 35929364]
[35]
Ren J, Lu Y, Qian Y, Chen B, Wu T, Ji G. Recent progress regarding kaempferol for the treatment of various diseases (Review). Exp Ther Med 2019; 18(4): 2759-76.
[http://dx.doi.org/10.3892/etm.2019.7886] [PMID: 31572524]
[36]
Imran M, Rauf A, Shah ZA, et al. Chemo-preventive and therapeutic effect of the dietary flavonoid kaempferol: A comprehensive review. Phytother Res 2019; 33(2): 263-75.
[http://dx.doi.org/10.1002/ptr.6227] [PMID: 30402931]
[37]
Imran M, Salehi B, Sharifi-Rad J, et al. Kaempferol: A key emphasis to its anticancer potential. Molecules 2019; 24(12): 2277.
[http://dx.doi.org/10.3390/molecules24122277] [PMID: 31248102]
[38]
Jiang H, Engelhardt UH, Thräne C, Maiwald B, Stark J. Determination of flavonol glycosides in green tea, oolong tea and black tea by UHPLC compared to HPLC. Food Chem 2015; 183: 30-5.
[http://dx.doi.org/10.1016/j.foodchem.2015.03.024] [PMID: 25863606]
[39]
Xiao J, Muzashvili TS, Georgiev MI. Advances in the biotechnological glycosylation of valuable flavonoids. Biotechnol Adv 2014; 32(6): 1145-56.
[http://dx.doi.org/10.1016/j.biotechadv.2014.04.006] [PMID: 24780153]
[40]
Crespy V, Morand C, Besson C, et al. The splanchnic metabolism of flavonoids highly differed according to the nature of the compound. Am J Physiol Gastrointest Liver Physiol 2003; 284(6): G980-8.
[http://dx.doi.org/10.1152/ajpgi.00223.2002] [PMID: 12736148]
[41]
Lehtonen HM, Lehtinen O, Suomela JP, Viitanen M, Kallio H. Flavonol glycosides of sea buckthorn (Hippophaë rhamnoides ssp. sinensis) and lingonberry (Vaccinium vitis-idaea) are bioavailable in humans and monoglucuronidated for excretion. J Agric Food Chem 2010; 58(1): 620-7.
[http://dx.doi.org/10.1021/jf9029942] [PMID: 20050706]
[42]
Williamson G, Kay CD, Crozier A. The bioavailability, transport, and bioactivity of dietary flavonoids: A review from a historical perspective. Compr Rev Food Sci Food Saf 2018; 17(5): 1054-112.
[http://dx.doi.org/10.1111/1541-4337.12351] [PMID: 33350159]
[43]
Day AJ, DuPont MS, Ridley S, et al. Deglycosylation of flavonoid and isoflavonoid glycosides by human small intestine and liver β-glucosidase activity. FEBS Lett 1998; 436(1): 71-5.
[http://dx.doi.org/10.1016/S0014-5793(98)01101-6] [PMID: 9771896]
[44]
Németh K, Plumb GW, Berrin JG, et al. Deglycosylation by small intestinal epithelial cell beta-glucosidases is a critical step in the absorption and metabolism of dietary flavonoid glycosides in humans. Eur J Nutr 2003; 42(1): 29-42.
[http://dx.doi.org/10.1007/s00394-003-0397-3] [PMID: 12594539]
[45]
Walgren RA, Lin JT, Kinne RK, Walle T. Cellular uptake of dietary flavonoid quercetin 4′-beta-glucoside by sodium-dependent glucose transporter SGLT1. J Pharmacol Exp Ther 2000; 294(3): 837-43.
[PMID: 10945831]
[46]
Chuang SY, Lin YK, Lin CF, Wang PW, Chen EL, Fang JY. Elucidating the skin delivery of aglycone and glycoside flavonoids: How the structures affect cutaneous absorption. Nutrients 2017; 9(12): 1304.
[http://dx.doi.org/10.3390/nu9121304] [PMID: 29189718]
[47]
Fukuhara K, Nakanishi I, Kansui H, et al. Enhanced radical-scavenging activity of a planar catechin analogue. J Am Chem Soc 2002; 124(21): 5952-3.
[http://dx.doi.org/10.1021/ja0178259] [PMID: 12022823]
[48]
Dang Y, Lin G, Xie Y, et al. Quantitative determination of myricetin in rat plasma by ultra performance liquid chromatography tandem mass spectrometry and its absolute bioavailability. Drug Res (Stuttg) 2014; 64(10): 516-22.
[PMID: 24357136]
[49]
Yao Y, Lin G, Xie Y, et al. Preformulation studies of myricetin: A natural antioxidant flavonoid. Pharmazie 2014; 69(1): 19-26.
[PMID: 24601218]
[50]
Fang Y, Cao W, Xia M, Pan S, Xu X. Study of structure and permeability relationship of flavonoids in Caco-2 cells. Nutrients 2017; 9(12): 1301.
[http://dx.doi.org/10.3390/nu9121301] [PMID: 29186068]
[51]
Otake Y, Hsieh F, Walle T. Glucuronidation versus oxidation of the flavonoid galangin by human liver microsomes and hepatocytes. Drug Metab Dispos 2002; 30(5): 576-81.
[http://dx.doi.org/10.1124/dmd.30.5.576] [PMID: 11950790]
[52]
Tian XJ, Yang XW, Yang X, Wang K. Studies of intestinal permeability of 36 flavonoids using Caco-2 cell monolayer model. Int J Pharm 2009; 367(1-2): 58-64.
[http://dx.doi.org/10.1016/j.ijpharm.2008.09.023] [PMID: 18848870]
[53]
Ezzat HM, Elnaggar YSR, Abdallah OY. Improved oral bioavailability of the anticancer drug catechin using chitosomes: Design, in-vitro appraisal and in-vivo studies. Int J Pharm 2019; 565: 488-98.
[http://dx.doi.org/10.1016/j.ijpharm.2019.05.034] [PMID: 31100382]
[54]
Qiao L, Sun Y, Chen R, et al. Sonochemical effects on 14 flavonoids common in citrus: Relation to stability. PLoS One 2014; 9(2): e87766.
[http://dx.doi.org/10.1371/journal.pone.0087766] [PMID: 24516562]
[55]
Xiang D, Wang C, Wang W, et al. Gastrointestinal stability of dihydromyricetin, myricetin, and myricitrin: An in vitro investigation. Int J Food Sci Nutr 2017; 68(6): 704-11.
[http://dx.doi.org/10.1080/09637486.2016.1276518] [PMID: 28114854]
[56]
Kawabata Y, Wada K, Nakatani M, Yamada S, Onoue S. Formulation design for poorly water-soluble drugs based on biopharmaceutics classification system: Basic approaches and practical applications. Int J Pharm 2011; 420(1): 1-10.
[http://dx.doi.org/10.1016/j.ijpharm.2011.08.032] [PMID: 21884771]
[57]
Stella VJ, Nti-Addae KW. Prodrug strategies to overcome poor water solubility. Adv Drug Deliv Rev 2007; 59(7): 677-94.
[http://dx.doi.org/10.1016/j.addr.2007.05.013] [PMID: 17628203]
[58]
Leuner C, Dressman J. Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm 2000; 50(1): 47-60.
[http://dx.doi.org/10.1016/S0939-6411(00)00076-X] [PMID: 10840192]
[59]
Wang Y, Yan Y, Cui J, et al. Encapsulation of water-insoluble drugs in polymer capsules prepared using mesoporous silica templates for intracellular drug delivery. Adv Mater 2010; 22(38): 4293-7.
[http://dx.doi.org/10.1002/adma.201001497] [PMID: 20564713]
[60]
Zhao J, Yang J, Xie Y. Improvement strategies for the oral bioavailability of poorly water-soluble flavonoids: An overview. Int J Pharm 2019; 570: 118642.
[http://dx.doi.org/10.1016/j.ijpharm.2019.118642] [PMID: 31446024]
[61]
Cao J, Zhang Y, Chen W, Zhao X. The relationship between fasting plasma concentrations of selected flavonoids and their ordinary dietary intake. Br J Nutr 2010; 103(2): 249-55.
[http://dx.doi.org/10.1017/S000711450999170X] [PMID: 19747418]
[62]
DuPont MS, Day AJ, Bennett RN, Mellon FA, Kroon PA. Absorption of kaempferol from endive, a source of kaempferol-3-glucuronide, in humans. Eur J Clin Nutr 2004; 58(6): 947-54.
[http://dx.doi.org/10.1038/sj.ejcn.1601916] [PMID: 15164116]
[63]
Nielsen SE, Kall M, Justesen U, Schou A, Dragsted LO. Human absorption and excretion of flavonoids after broccoli consumption. Cancer Lett 1997; 114(1-2): 173-4.
[http://dx.doi.org/10.1016/S0304-3835(97)04654-5] [PMID: 9103283]
[64]
Bonetti A, Marotti I, Dinelli G. Urinary excretion of kaempferol from common beans (Phaseolus vulgaris L.) in humans. Int J Food Sci Nutr 2007; 58(4): 261-9.
[http://dx.doi.org/10.1080/09637480601154228] [PMID: 17566888]
[65]
Lee B, Kwon M, Choi JS, Jeong HO, Chung HY, Kim HR. Kaempferol isolated from Nelumbo nucifera inhibits lipid accumulation and increases fatty acid oxidation signaling in adipocytes. J Med Food 2015; 18(12): 1363-70.
[http://dx.doi.org/10.1089/jmf.2015.3457] [PMID: 26280739]
[66]
Chang C, Tzeng TF, Liou SS, Chang YS, Liu IM. Kaempferol regulates the lipid-profile in high-fat diet-fed rats through an increase in hepatic PPARα levels. Planta Med 2011; 77(17): 1876-82.
[http://dx.doi.org/10.1055/s-0031-1279992] [PMID: 21728151]
[67]
Yu SF, Shun CT, Chen TM, Chen YH. 3-O-beta-D-glucosyl-(1->6)-beta-D-glucosyl-kaempferol isolated from Sauropus androgenus reduces body weight gain in Wistar rats. Biol Pharm Bull 2006; 29(12): 2510-3.
[http://dx.doi.org/10.1248/bpb.29.2510] [PMID: 17142992]
[68]
da-Silva WS, Harney JW, Kim BW, et al. The small polyphenolic molecule kaempferol increases cellular energy expenditure and thyroid hormone activation. Diabetes 2007; 56(3): 767-76.
[http://dx.doi.org/10.2337/db06-1488] [PMID: 17327447]
[69]
Gregoire FM, Smas CM, Sul HS. Understanding adipocyte differentiation. Physiol Rev 1998; 78(3): 783-809.
[http://dx.doi.org/10.1152/physrev.1998.78.3.783] [PMID: 9674695]
[70]
Ali AT, Hochfeld WE, Myburgh R, Pepper MS. Adipocyte and adipogenesis. Eur J Cell Biol 2013; 92(6-7): 229-36.
[http://dx.doi.org/10.1016/j.ejcb.2013.06.001] [PMID: 23876739]
[71]
Schadinger SE, Bucher NLR, Schreiber BM, Farmer SR. PPARγ2 regulates lipogenesis and lipid accumulation in steatotic hepatocytes. Am J Physiol Endocrinol Metab 2005; 288(6): E1195-205.
[http://dx.doi.org/10.1152/ajpendo.00513.2004] [PMID: 15644454]
[72]
Macdougald OA, Lane MD. Adipocyte differentiation: When precursors are also regulators. Curr Biol 1995; 5(6): 618-21.
[http://dx.doi.org/10.1016/S0960-9822(95)00125-4] [PMID: 7552171]
[73]
Rufino AT, Costa VM, Carvalho F, Fernandes E. Flavonoids as antiobesity agents: A review. Med Res Rev 2021; 41(1): 556-85.
[http://dx.doi.org/10.1002/med.21740] [PMID: 33084093]
[74]
Byun MR, Jeong H, Bae SJ, Kim AR, Hwang ES, Hong JH. TAZ is required for the osteogenic and anti-adipogenic activities of kaempferol. Bone 2012; 50(1): 364-72.
[http://dx.doi.org/10.1016/j.bone.2011.10.035] [PMID: 22108137]
[75]
Park UH, Jeong JC, Jang JS, et al. Negative regulation of adipogenesis by kaempferol, a component of Rhizoma polygonati falcatum in 3T3-L1 cells. Biol Pharm Bull 2012; 35(9): 1525-33.
[http://dx.doi.org/10.1248/bpb.b12-00254] [PMID: 22975504]
[76]
Park UH, Hwang JT, Youn H, Kim EJ, Um SJ. Kaempferol antagonizes adipogenesis by repressing histone H3K4 methylation at PPARγ target genes. Biochem Biophys Res Commun 2022; 617(Pt 1): 48-54.
[http://dx.doi.org/10.1016/j.bbrc.2022.05.098] [PMID: 35679710]
[77]
Lee YJ, Choi HS, Seo MJ, Jeon HJ, Kim KJ, Lee BY. Kaempferol suppresses lipid accumulation by inhibiting early adipogenesis in 3T3-L1 cells and zebrafish. Food Funct 2015; 6(8): 2824-33.
[http://dx.doi.org/10.1039/C5FO00481K] [PMID: 26174858]
[78]
Torres-Villarreal D, Camacho A, Castro H, Ortiz-Lopez R, de la Garza AL. Anti-obesity effects of kaempferol by inhibiting adipogenesis and increasing lipolysis in 3T3-L1 cells. J Physiol Biochem 2019; 75(1): 83-8.
[http://dx.doi.org/10.1007/s13105-018-0659-4] [PMID: 30539499]
[79]
Muni Swamy G, Ramesh G, Devi Prasad R, Meriga B. Astragalin, (3-O-glucoside of kaempferol), isolated from Moringa oleifera leaves modulates leptin, adiponectin secretion and inhibits adipogenesis in 3T3-L1 adipocytes. Arch Physiol Biochem 2020; 128(4): 938-44.
[PMID: 32216601]
[80]
Lee LS, Choi JH, Sung MJ, et al. Green tea changes serum and liver metabolomic profiles in mice with high-fat diet-induced obesity. Mol Nutr Food Res 2015; 59(4): 784-94.
[http://dx.doi.org/10.1002/mnfr.201400470] [PMID: 25631872]
[81]
Tong L, Wang L, Yao S, et al. PPARδ attenuates hepatic steatosis through autophagy-mediated fatty acid oxidation. Cell Death Dis 2019; 10(3): 197.
[http://dx.doi.org/10.1038/s41419-019-1458-8] [PMID: 30814493]
[82]
Varga T, Czimmerer Z, Nagy L. PPARs are a unique set of fatty acid regulated transcription factors controlling both lipid metabolism and inflammation. Biochim Biophys Acta Mol Basis Dis 2011; 1812(8): 1007-22.
[http://dx.doi.org/10.1016/j.bbadis.2011.02.014] [PMID: 21382489]
[83]
Escher P, Braissant O, Basu-Modak S, Michalik L, Wahli W, Desvergne B. Rat PPARs: quantitative analysis in adult rat tissues and regulation in fasting and refeeding. Endocrinology 2001; 142(10): 4195-202.
[http://dx.doi.org/10.1210/endo.142.10.8458] [PMID: 11564675]
[84]
Poulsen LC, Siersbæk M, Mandrup S. PPARs: Fatty acid sensors controlling metabolism. Semin Cell Dev Biol 2012; 23(6): 631-9.
[http://dx.doi.org/10.1016/j.semcdb.2012.01.003] [PMID: 22273692]
[85]
Rupasinghe HPV, Sekhon-Loodu S, Mantso T, Panayiotidis MI. Phytochemicals in regulating fatty acid β-oxidation: Potential underlying mechanisms and their involvement in obesity and weight loss. Pharmacol Ther 2016; 165: 153-63.
[http://dx.doi.org/10.1016/j.pharmthera.2016.06.005] [PMID: 27288729]
[86]
López M. Hypothalamic AMPK and energy balance. Eur J Clin Invest 2018; 48(9): e12996.
[http://dx.doi.org/10.1111/eci.12996] [PMID: 29999521]
[87]
Montero M, de la Fuente S, Fonteriz RI, Moreno A, Alvarez J. Effects of long-term feeding of the polyphenols resveratrol and kaempferol in obese mice. PLoS One 2014; 9(11): e112825.
[http://dx.doi.org/10.1371/journal.pone.0112825] [PMID: 25386805]
[88]
Zang Y, Zhang L, Igarashi K, Yu C. The anti-obesity and anti-diabetic effects of kaempferol glycosides from unripe soybean leaves in high-fat-diet mice. Food Funct 2015; 6(3): 834-41.
[http://dx.doi.org/10.1039/C4FO00844H] [PMID: 25599885]
[89]
Li H, Kang JH, Han JM, et al. Anti-obesity effects of soy leaf via regulation of adipogenic transcription factors and fat oxidation in diet-induced obese mice and 3T3-L1 adipocytes. J Med Food 2015; 18(8): 899-908.
[http://dx.doi.org/10.1089/jmf.2014.3388] [PMID: 25826408]
[90]
Chen Y, Zhang C, Jin MN, et al. Flavonoid derivative exerts an antidiabetic effect via AMPK activation in diet-induced obesity mice. Nat Prod Res 2016; 30(17): 1988-92.
[http://dx.doi.org/10.1080/14786419.2015.1101105] [PMID: 26511291]
[91]
Qin N, Chen Y, Jin MN, et al. Anti-obesity and anti-diabetic effects of flavonoid derivative (Fla-CN) via microRNA in high fat diet induced obesity mice. Eur J Pharm Sci 2016; 82: 52-63.
[http://dx.doi.org/10.1016/j.ejps.2015.11.013] [PMID: 26598088]
[92]
Gan CC, Ni TW, Yu Y, et al. Flavonoid derivative (Fla-CN) inhibited adipocyte differentiation via activating AMPK and up-regulating microRNA-27 in 3T3-L1 cells. Eur J Pharmacol 2017; 797: 45-52.
[http://dx.doi.org/10.1016/j.ejphar.2017.01.009] [PMID: 28088385]
[93]
Alkhalidy H, Moore W, Wang A, et al. Kaempferol ameliorates hyperglycemia through suppressing hepatic gluconeogenesis and enhancing hepatic insulin sensitivity in diet-induced obese mice. J Nutr Biochem 2018; 58: 90-101.
[http://dx.doi.org/10.1016/j.jnutbio.2018.04.014] [PMID: 29886193]
[94]
Nie JP, Qu ZN, Chen Y, et al. Discovery and anti-diabetic effects of novel isoxazole based flavonoid derivatives. Fitoterapia 2020; 142: 104499.
[http://dx.doi.org/10.1016/j.fitote.2020.104499] [PMID: 32058049]
[95]
Tang H, Zeng Q, Tang T, Wei Y, Pu P. Kaempferide improves glycolipid metabolism disorder by activating PPARγ in high-fat-diet-fed mice. Life Sci 2021; 270: 119133.
[http://dx.doi.org/10.1016/j.lfs.2021.119133] [PMID: 33508298]
[96]
Romero-Juárez PA, Visco DB, Manhães-de-Castro R, et al. Dietary flavonoid kaempferol reduces obesity-associated hypothalamic microglia activation and promotes body weight loss in mice with obesity. Nutr Neurosci 2023; 26(1): 25-39.
[PMID: 34905445]
[97]
Eckburg PB, Bik EM, Bernstein CN, et al. Diversity of the human intestinal microbial flora. Science 2005; 308(5728): 1635-8.
[http://dx.doi.org/10.1126/science.1110591] [PMID: 15831718]
[98]
Abenavoli L, Scarpellini E, Colica C, et al. Gut microbiota and obesity: A role for probiotics. Nutrients 2019; 11(11): 2690.
[http://dx.doi.org/10.3390/nu11112690] [PMID: 31703257]
[99]
Torres-Fuentes C, Schellekens H, Dinan TG, Cryan JF. The microbiota–gut–brain axis in obesity. Lancet Gastroenterol Hepatol 2017; 2(10): 747-56.
[http://dx.doi.org/10.1016/S2468-1253(17)30147-4] [PMID: 28844808]
[100]
Xu Y, Wang N, Tan HY, Li S, Zhang C, Feng Y. Gut-liver axis modulation of Panax notoginseng saponins in nonalcoholic fatty liver disease. Hepatol Int 2021; 15(2): 350-65.
[http://dx.doi.org/10.1007/s12072-021-10138-1] [PMID: 33656663]
[101]
Cao SY, Zhao CN, Xu XY, et al. Dietary plants, gut microbiota, and obesity: Effects and mechanisms. Trends Food Sci Technol 2019; 92: 194-204.
[http://dx.doi.org/10.1016/j.tifs.2019.08.004]
[102]
Lee P, Yacyshyn BR, Yacyshyn MB. Gut microbiota and obesity: An opportunity to alter obesity through faecal microbiota transplant (FMT). Diabetes Obes Metab 2019; 21(3): 479-90.
[http://dx.doi.org/10.1111/dom.13561] [PMID: 30328245]
[103]
Zhang YJ, Li S, Gan RY, Zhou T, Xu DP, Li HB. Impacts of gut bacteria on human health and diseases. Int J Mol Sci 2015; 16(12): 7493-519.
[http://dx.doi.org/10.3390/ijms16047493] [PMID: 25849657]
[104]
Wang T, Wu Q, Zhao T. Preventive effects of kaempferol on high- fat diet-induced obesity complications in C57BL/6 mice. BioMed Res Int 2020; 2020: 1-9.
[http://dx.doi.org/10.1155/2020/4532482] [PMID: 32337249]
[105]
Chaves WF, Pinheiro IL, da Silva LO, et al. Neonatal administration of kaempferol does not alter satiety but increases somatic growth and reduces adiposity in offspring of high-fat diet dams. Life Sci 2020; 259: 118224.
[http://dx.doi.org/10.1016/j.lfs.2020.118224] [PMID: 32768574]
[106]
Bian Y, Lei J, Zhong J, et al. Kaempferol reduces obesity, prevents intestinal inflammation, and modulates gut microbiota in high-fat diet mice. J Nutr Biochem 2022; 99: 108840.
[http://dx.doi.org/10.1016/j.jnutbio.2021.108840] [PMID: 34419569]
[107]
Zhang F, Yang M, Xu J, et al. Coreopsis tinctoria and its flavonoids ameliorate hyperglycemia in obese mice induced by high-fat diet. Nutrients 2022; 14(6): 1160.
[http://dx.doi.org/10.3390/nu14061160] [PMID: 35334817]
[108]
Choi AMK, Ryter SW, Levine B. Autophagy in human health and disease. N Engl J Med 2013; 368(7): 651-62.
[http://dx.doi.org/10.1056/NEJMra1205406] [PMID: 23406030]
[109]
Watanabe T, Kuma A, Mizushima N. Physiological role of autophagy in metabolism and its regulation mechanism. Jpn J Clin Med 2011; 69 (Suppl. 1): 775-81.
[PMID: 21766696]
[110]
Zhang Y, Sowers JR, Ren J. Targeting autophagy in obesity: From pathophysiology to management. Nat Rev Endocrinol 2018; 14(6): 356-76.
[http://dx.doi.org/10.1038/s41574-018-0009-1] [PMID: 29686432]
[111]
Singh R. Autophagy in the control of food intake. Adipocyte 2012; 1(2): 75-9.
[http://dx.doi.org/10.4161/adip.18966] [PMID: 23700515]
[112]
Varshney R, Gupta S, Roy P. Cytoprotective effect of kaempferol against palmitic acid-induced pancreatic β-cell death through modulation of autophagy via AMPK/mTOR signaling pathway. Mol Cell Endocrinol 2017; 448: 1-20.
[http://dx.doi.org/10.1016/j.mce.2017.02.033] [PMID: 28237721]
[113]
Varshney R, Varshney R, Mishra R, Gupta S, Sircar D, Roy P. Kaempferol alleviates palmitic acid-induced lipid stores, endoplasmic reticulum stress and pancreatic β-cell dysfunction through AMPK/mTOR-mediated lipophagy. J Nutr Biochem 2018; 57: 212-27.
[http://dx.doi.org/10.1016/j.jnutbio.2018.02.017] [PMID: 29758481]
[114]
Abdullah A, Ravanan P. Kaempferol mitigates endoplasmic reticulum stress induced cell death by targeting caspase 3/7. Sci Rep 2018; 8(1): 2189.
[http://dx.doi.org/10.1038/s41598-018-20499-7] [PMID: 29391535]
[115]
Rahul, Siddique Y.H. Neurodegenerative diseases and flavonoids: Special reference to kaempferol. CNS Neurol Disord Drug Targets 2021; 20(4): 327-42.
[http://dx.doi.org/10.2174/1871527320666210129122033] [PMID: 33511932]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy