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Neohesperidin: Biosynthesis, ADME, Biological and Pharmacological Activities

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  • First Online:
Handbook of Dietary Flavonoids

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Abstract

Neohesperidin (NHP) (3′,5,7-trihydroxy- 4′-methoxy flavanone) is a citrus flavonoid with inherent potent pharmacological properties. Neohesperidin dihydrochalcone (NHD) is a chalcone derivative of NHP used as an artificial sweetener which also showed to have various pharmacological properties especially antioxidant activity. This chapter encompasses biosynthetic pathways, physicochemical properties, Abrsoption, distribution, metabolism and excretion (ADME), basic molecular mechanism, and pharmacological activities in experimental animals and patents of NHP and NHD. In this regard, hydrolysis, glucuronidation, sulfation, glutamylation, N-butyryl glycylation, and lactylation are the major reactions involved in the metabolism of NHP. Extensive works have been done in assessing the anti-inflammatory, hepatoprotective, and neuroprotective activities of neohesperidin and neohesperidin dihydrochalcone in various in vitro models of diseases, but still various mechanisms contributing its pharmacological effects need further exploration. As previously stated in the in vitro studies, very few studies on the pharmacological activities of NHP and NHD were available, with certain activities such as cardioprotective, gastroprotective, and hepatoprotective being extensively researched. In mechanistic point of view, Akt/Nrf2/HO-1 and PPARγ, MAPK, and NF-κB are the predominant signalling pathways modulated by NHP and NHD for ameliorating various diseases both in in vitro and in vivo studies. Thus, further insights are needed for assessing the therapeutic efficacy of the NHP, which could modulate various therapeutic targets and signalling molecules for ameliorating various diseases. Among the citrus flavonoids, NHP could be a potential lead for treating diseases in the coming years, but more in vitro, in vivo, and clinical research is needed to assess its therapeutic efficacy.

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References

  • (FEEDAP), EP on A and P or S used in AF, Bampidis V, Azimonti G, de Bastos ML, Christensen H, Fašmon Durjava M et al (2021) Safety and efficacy of a feed additive consisting of a flavonoid-rich dried extract of citrus × aurantium L. fruit (bitter orange extract) for use in all animal species (FEFANA asbl). EFSA J (Wiley) 19(7):e06709. Available from: https://doi.org/10.2903/j.efsa.2021.6709

    Google Scholar 

  • Addi M, Elbouzidi A, Abid M, Tungmunnithum D, Elamrani A, Hano C (2022) An overview of bioactive flavonoids from citrus fruits. Appl Sci 12(1):29

    Article  CAS  Google Scholar 

  • Anthony P, Christian O, Nannan C, Donna M (2014) Method of inhibiting premature aging of human skin caused by exposure to infrared radiation (Patent US8765693B2). https://patents.google.com/patent/US8765693B2/en

  • Bellocco E, Barreca D, Laganà G, Leuzzi U, Tellone E, Ficarra S et al (2009) Influence of l-rhamnosyl-d-glucosyl derivatives on properties and biological interaction of flavonoids. Mol Cell Biochem 321(1):165–171. Available from: https://doi.org/10.1007/s11010-008-9930-2

    Article  CAS  PubMed  Google Scholar 

  • Bless Y, Jeong T, Bae B-H, Park Y, Choi M, Moon S et al (2001) Composition for preventing and treating atherosclerosis, hyperlipidemia, hepatic diseases and glycosemia, comprising neohesperidin dihydrochalcone (Patent KR100291142B1). https://patents.google.com/patent/KR100291145B1/en

  • Bozoğlan BK, Tunç S, Duman O (2014) Investigation of neohesperidin dihydrochalcone binding to human serum albumin by spectroscopic methods. J Lumin 155:198–204

    Article  Google Scholar 

  • Braune A, Engst W, Blaut M (2005) Degradation of neohesperidin dihydrochalcone by human intestinal bacteria. J Agric Food Chem 53(5):1782–1790

    Article  CAS  PubMed  Google Scholar 

  • Brett GM, Hollands W, Needs PW, Teucher BR, Dainty J, Davis BD et al (2008) Absorption, metabolism and excretion of flavanones from single portions of orange fruit and juice and effects of anthropometric variables and contraceptive pill use on flavanone excretion. Br J Nutr 101(5):664–675

    Article  Google Scholar 

  • Castillo J, Benavente O, del Rio JA (1992) Naringin and Neohesperidin levels during development of leaves, flower buds, and fruits of Citrus aurantium. Plant Physiol 99(1):67–73

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Castillo J, Benavente O, del Rio JA (1993) Hesperetin 7-O-glucoside and prunin in citrus species (C. aurantium and C. paradisi). A study of their quantitative distribution in immature fruits and as immediate precursors of neohesperidin and naringin in Citrus aurantium. J Agric Food Chem (ACS Publications) 41(11):1920–1924

    Article  CAS  Google Scholar 

  • Chakraborty S, Rakshit J, Bandyopadhyay J, Basu S (2018) Multi-functional neuroprotective activity of neohesperidin dihydrochalcone: a novel scaffold for Alzheimer’s disease therapeutics identified via drug repurposing screening. New J Chem (The Royal Society of Chemistry) 42(14):11755–11769

    CAS  Google Scholar 

  • Chakraborty S, Rakshit J, Bandyopadhyay J, Basu S (2021) Multi-target inhibition ability of neohesperidin dictates its neuroprotective activity: implication in Alzheimer’s disease therapeutics. Int J Biol Macromol 176:315–324. Available from: https://www.sciencedirect.com/science/article/pii/S0141813021003524

    Article  CAS  PubMed  Google Scholar 

  • Chang Y-w, Zhu W-j, Gu W, Sun J, Li Z-q, Wei X-e (2021) Neohesperidin promotes the osteogenic differentiation of bone mesenchymal stem cells by activating the Wnt/β-catenin signaling pathway. J Orthop Surg Res 16(1):334

    Article  PubMed  PubMed Central  Google Scholar 

  • Choi J-M, Yoon B-S, Lee S-K, Hwang J-K, Ryang R (2007) Antioxidant properties of Neohesperidin Dihydrochalcone: inhibition of Hypochlorous acid-induced DNA Strand breakage, protein degradation, and cell death. Biol Pharm Bull 30(2):324–330

    Article  CAS  PubMed  Google Scholar 

  • Choi S, Yu S, Lee J, Kim W (2021) Effects of Neohesperidin Dihydrochalcone (NHDC) on oxidative phosphorylation, cytokine production, and lipid deposition. Foods (Basel, Switzerland) MDPI 10(6):1408

    CAS  Google Scholar 

  • Cotelle N, Bernier J-L, Catteau J-P, Pommery J, Wallet J-C, Gaydou EM (1996) Antioxidant properties of hydroxy-flavones. Free Radic Biol Med 20(1):35–43

    Article  CAS  PubMed  Google Scholar 

  • Crespy V, Morand C, Besson C, Manach C, Demigne C, Remesy C (2002) Quercetin, but not its glycosides, is absorbed from the rat stomach. J Agric Food Chem 50(3):618–621

    Article  CAS  PubMed  Google Scholar 

  • Cui J, Wang G (2006) Isolation and structure identification of chemical constituents from buds of Lonicera ruprechtiana Regel. J Jilin Univ Med Ed 36:10–13

    Google Scholar 

  • Cyril L, Moreno AF, Patricia P (2011) Cosmetic kit, useful e.g. to treat oxidative stress, comprises first anhydrous composition having vitamin C, and second composition having neohesperidin dihydrochalcone, silicone elastomer and concave particles. France

    Google Scholar 

  • Dai Z, Fan H, Zhang C, Qi C, Wang P, Hao J et al (2021) Production system of blood sugar reducing functional biscuits containing neohesperidin dihydrochalcone (Patent US5300309A). China National Intellectual Property Administration

    Google Scholar 

  • Damiani LM (2019) Compositions for the treatment of hyperlipidemia. European Patent Office

    Google Scholar 

  • Deep ES (2022) [cited 2022 Aug 5]. Available from: https://www.ewg.org/skindeep/browse/ingredients/720910-NEOHESPERIDIN_DIHYDROCHALCONE/

  • Denaro M, Smeriglio A, Trombetta D (2021) Antioxidant and anti-inflammatory activity of citrus flavanones mix and its stability after in vitro simulated digestion. Antioxidants 10(2):140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ture MA, Dickson DW (2019) The neuropathological diagnosis of Alzheimer’s disease. Mol Neurodegener 14(1):32. Available from: https://doi.org/10.1186/s13024-019-0333-5

  • Di Donna L, De Luca G, Mazzotti F, Napoli A, Salerno R, Taverna D et al (2009) Statin-like principles of bergamot fruit (Citrus bergamia): isolation of 3-hydroxymethylglutaryl flavonoid glycosides. J Nat Prod 72(7):1352–1354

    Article  PubMed  Google Scholar 

  • Ebel J, Hahlbrock K (1982) Biosynthesis BT – the flavonoids: advances in research. In: Harborne JB, Mabry TJ (eds) The flavonoids. Springer US, Boston, pp 641–679. Available from: https://doi.org/10.1007/978-1-4899-2915-0_11

    Chapter  Google Scholar 

  • Feng F, Ye X, Li Q (2015) Medicine composition and application thereof in preparation of medicines for treating depression (Patent CN104622881A). https://patents.google.com/patent/CN104622881A/en

  • Frydman A, Weisshaus O, Huhman DV, Sumner LW, Bar-Peled M, Lewinsohn E et al (2005) Metabolic engineering of plant cells for biotransformation of hesperedin into neohesperidin, a substrate for production of the low-calorie sweetener and flavor enhancer NHDC. J Agric Food Chem (ACS Publications) 53(25):9708–9712

    Article  CAS  Google Scholar 

  • Gong Y, Dong R, Gao X, Li J, Jiang L, Zheng J et al (2019) Neohesperidin prevents colorectal tumorigenesis by altering the gut microbiota. Pharmacol Res 148:104460

    Article  CAS  PubMed  Google Scholar 

  • Guo C, Zhang H, Guan X, Zhou Z (2019) The anti-aging potential of neohesperidin and its synergistic effects with other citrus flavonoids in extending chronological lifespan of saccharomyces cerevisiae BY4742. Molecules 24(22):4093

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hahlbrock K, Grisebach H (1979) Enzymic controls in the biosynthesis of lignin and flavonoids. Annu Rev Plant Physiol 30(1):105–130

    Article  CAS  Google Scholar 

  • Hamdan D, El-Readi MZ, Tahrani A, Herrmann F, Kaufmann D, Farrag N et al (2011) Secondary metabolites of ponderosa lemon (Citrus pyriformis) and their antioxidant, anti-inflammatory, and cytotoxic activities. Zeitschrift für Naturforsch C 66(7–8):385–393

    CAS  Google Scholar 

  • Hamdan DI, Mahmoud MF, Wink M, El-Shazly AM (2014) Effect of hesperidin and neohesperidin from bittersweet orange (Citrus aurantium var. bigaradia) peel on indomethacin-induced peptic ulcers in rats. Environ Toxicol Pharmacol 37(3):907–915

    Article  CAS  PubMed  Google Scholar 

  • Hasegawa S, Maier VP (1972) Cinnamate hydroxylation and the enzymes leading from phenylpyruvate to p-coumarate synthesis in grapefruit tissues. Phytochemistry 11(4):1365–1370

    Article  CAS  Google Scholar 

  • Hasegawa S, Maier VP (1982) Some aspects of Citrus biochemistry and juice quality. In Proceedings of the international society of citriculture congress, November 9–12, 1981, Tokyo, Japan; K. Matsumoto, Ed. Shimizu, Japan: International Society of Citriculture, 1982–1983

    Google Scholar 

  • Herrera-Ruiz M, Román-Ramos R, Zamilpa A, Tortoriello J, Jiménez-Ferrer JE (2008) Flavonoids from Tilia americana with anxiolytic activity in plus-maze test. J Ethnopharmacol 118(2):312–317

    Article  CAS  PubMed  Google Scholar 

  • Hideaki M (2008) Medicine reinforcing anti-allergic effect without increasing adverse reaction of adrenocortical hormone and method for enhancing anti-allergic effect without increasing adverse reaction of adrenocortical hormone (Patent JP2008137985A). https://patents.google.com/patent/JP2008137985A/en

  • Hideaki M, Fellow D (2011) Whitening agent or pigmentation ameliorating agent based on the antioxidant action of neohesperidin

    Google Scholar 

  • Horowitz RM, Gentili B (1960) Flavonoids of the ponderosa lemon. Nature 185(4709):319

    Article  CAS  PubMed  Google Scholar 

  • Horowitz RM, Gentili B (1977) Flavonoid constituents of citrus. Citrus Sci Technol 1(1):397–426

    CAS  Google Scholar 

  • Howard T, Ian R (2014) Surface sterilisation by misting with a bioflavanoid solution comprising naringin and neohesperidin. EP2393356B1

    Google Scholar 

  • Hu L, Li L, Xu D, Xia X, Pi R, Xu D et al (2014) Protective effects of neohesperidin dihydrochalcone against carbon tetrachloride-induced oxidative damage in vivo and in vitro. Chem Biol Interact 213:51–59

    Article  CAS  PubMed  Google Scholar 

  • Huang X, Luo M (2013) Method for detection of effects of neohesperidin for resisting depression and promoting gastrointestinal motility

    Google Scholar 

  • Hwang S-L, Yen G-C (2008) Neuroprotective effects of the citrus flavanones against H2O2-induced cytotoxicity in PC12 cells. J Agric Food Chem (ACS Publications) 56(3):859–864

    Article  CAS  Google Scholar 

  • Jia S, Hu Y, Zhang W, Zhao X, Chen Y, Sun C et al (2015) Hypoglycemic and hypolipidemic effects of neohesperidin derived from Citrus aurantium L. in diabetic KK-Ay mice. Food Funct (The Royal Society of Chemistry) 6(3):878–886. Available from: https://doi.org/10.1039/C4FO00993B

  • Joshi R, Kulkarni YA, Wairkar S (2018) Pharmacokinetic, pharmacodynamic and formulations aspects of Naringenin: an update. Life Sci 215:43–56

    Article  CAS  PubMed  Google Scholar 

  • Jourdan PS, McIntosh CA, Mansell RL (1985) Naringin levels in citrus tissues: II. Quantitative distribution of Naringin in Citrus paradisi MacFad. Plant Physiol 77(4):903–908

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Karim N, Shishir MRI, Rashwan AK, Ke H, Chen W (2021) Suppression of palmitic acid-induced hepatic oxidative injury by neohesperidin-loaded pectin-chitosan decorated nanoliposomes. Int J Biol Macromol 183:908–917. Available from: https://www.sciencedirect.com/science/article/pii/S014181302100979X

    Article  CAS  PubMed  Google Scholar 

  • Kim H, Hye-sook L (2021) Skin external composition comprising neohesperidin dihydrochalcone. South Korea

    Google Scholar 

  • Kim Y-C, Koh K-S, Koh J-S (2002) Changes of some flavonoids in the peel of late maturing citrus during maturation. Prev Nutr Food Sci (The Korean Society of Food Science and Nutrition) 7(1):1–4

    CAS  Google Scholar 

  • Knekt P, Kumpulainen J, Järvinen R, Rissanen H, Heliövaara M, Reunanen A et al (2002) Flavonoid intake and risk of chronic diseases. Am J Clin Nutr 76(3):560–568

    Article  CAS  PubMed  Google Scholar 

  • Kwon M, Kim Y, Lee J, Manthey JA, Kim Y, Kim Y (2022) Neohesperidin Dihydrochalcone and Neohesperidin Dihydrochalcone-O-glycoside attenuate subcutaneous fat and lipid accumulation by regulating PI3K/AKT/mTOR pathway in vivo and in vitro. Nutrients 14(5):1087

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Landberg R, Manach C, Kerckhof F-M, Minihane A-M, Saleh RNM, De Roos B et al (2019) Future prospects for dissectinginter-individual variability in the absorption, distribution and elimination of plantbioactives of relevance for cardiometabolic endpoints. Eur J Nutr 58(2):21–36. Available from: https://doi.org/10.1007/s00394-019-02095-1

    Article  PubMed  PubMed Central  Google Scholar 

  • Lee J, Choi C (2022) Composition for preventing or protecting liver damage comprising neohesperidin dihydrochalcone against methylglyoxal. Korean Intellectual Property Office

    Google Scholar 

  • Lee J-H, Lee S-H, Kim YS, Jeong CS (2009) Protective effects of neohesperidin and poncirin isolated from the fruits of Poncirus trifoliata on potential gastric disease. Phyther Res (Wiley) 23(12):1748–1753

    Article  CAS  Google Scholar 

  • Lewinsohn E, Britsch L, Mazur Y, Gressel J (1989) Flavanone glycoside biosynthesis in citrus: Chalcone synthase, UDP-glucose:Flavanone-7-O-Glucosyl-transferase and -Rhamnosyl-transferase activities in cell-free extracts. Plant Physiol 91(4):1323–1328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Z, Jiang C, Wei Y, Cai Q, Zhong R, Chen S et al (2018) Application of the neohesperidin in prevention and treatment senile dementia is prepared (Patent CN107648245A). https://patents.google.com/patent/CN107648245A/en

  • Li A, Zhang X, Luo Q (2021) Neohesperidin alleviated pathological damage and immunological imbalance in rat myocardial ischemia-reperfusion injury via inactivation of JNK and NF-κB p65. Biosci Biotechnol Biochem 85(2):251–261. Available from: https://doi.org/10.1093/bbb/zbaa064

    Article  PubMed  Google Scholar 

  • Lina BAR, Dreef-van der Meulen HC, Leegwater DC (1990) Subchronic (13-week) oral toxicity of neohesperidin dihydrochalcone in rats. Food Chem Toxicol 28(7):507–513

    Article  CAS  PubMed  Google Scholar 

  • Liu H, Hongying L (2022) Use of neohesperidin (Patent US11260011B2). https://patents.google.com/patent/US11260011B2/en

  • Liu F, Han S, Ni Y (2017) Isolation and purification of four flavanones from peel of citrus changshanensis. J Food Process Preserv (Wiley) 41(6):e13278

    Article  Google Scholar 

  • Liu C, Hou W, Li S, Tsao R (2020) Extraction and isolation of acetylcholinesterase inhibitors from Citrus limon peel using an in vitro method. J Sep Sci (Wiley) 43(8):1531–1543

    Article  CAS  Google Scholar 

  • Lu W, Guo Q, Huang W (2011) Traditional Chinese medicine composition for treating dyspepsia and preparation method thereof (Patent CN101987124A). https://patents.google.com/patent/CN101987124A/en

  • Lu JF, Zhu MQ, Zhang H, Liu H, Xia B, Wang YL et al (2020) Neohesperidin attenuates obesity by altering the composition of the gut microbiota in high-fat diet-fed mice. FASEB J 34(9):12053–12071

    Article  CAS  PubMed  Google Scholar 

  • Mahmoud M, Hamdan D, Wink M, El-Shazly A (2013) Naringin and Rutin prevent D-Galactosamine-induced hepatic injury in rats via attenuation of the inflammatory cascade and oxidative stress. Eur Sci J 9(30 SE-Articles). https://doi.org/10.19044/esj.2013.v9n30p%25p. http://eujournal.org/index.php/esj/article/view/1951

  • Masao N, Shintaro K, Sachiko E, Fumiko I (1971) Flavonoids in citrus and related genera. Agric Biol Chem (Taylor & Francis) 35(11):1683–1706

    Article  Google Scholar 

  • Michitoku K, Hideaki M, Hideaki M (2005) Antiallergic agent. Japan

    Google Scholar 

  • Mink PJ, Scrafford CG, Barraj LM, Harnack L, Hong C-P, Nettleton JA et al (2007) Flavonoid intake and cardiovascular disease mortality: a prospective study in postmenopausal women. Am J Clin Nutr 85(3):895–909

    Article  CAS  PubMed  Google Scholar 

  • Miyake Y, Yamamoto K, Morimitsu Y, Osawa T (1998) Characteristics of Antioxidative flavonoid glycosides in lemon fruit. Food Sci Technol Int Tokyo 4(1):48–53

    Article  CAS  Google Scholar 

  • Murphy MP, LeVine H III (2010) Alzheimer’s disease and the amyloid-β peptide. J Alzheimers Dis (IOS Press) 19:311–323

    Article  Google Scholar 

  • Najmanová I, Vopršalová M, Saso L, Mladěnka P (2020) The pharmacokinetics of flavanones. Crit Rev Food Sci Nutr 60(18):3155–3171

    Article  PubMed  Google Scholar 

  • Nakabayashi T (1961) Studies on citrus flavonoids. 7. Flavonoid glycosides in species of sour orange. Nippon Nogei Kagaku Kaishi 35(10):945

    Article  CAS  Google Scholar 

  • Nishiura M, Esaki S, Kamiya S (1969) Flavonoids in citrus and related genera. Agric Biol Chem (Taylor & Francis) 33(8):1109–1118

    CAS  Google Scholar 

  • Osman AT, Sharkawi SMZ, Hassan MIA, Abo-youssef AM, Hemeida RAM (2021) Empagliflozin and neohesperidin protect against methotrexate-induced renal toxicity via suppression of oxidative stress and inflammation in male rats. Food Chem Toxicol 155:112406. Available from: https://www.sciencedirect.com/science/article/pii/S0278691521004397

    Article  CAS  PubMed  Google Scholar 

  • Ozen T, Telci I, Gul F, Demirtas I (2018) A comprehensive study on phytochemical contents, isolation and antioxidant capacities in wild mind, Mentha longifolia subsp. typhoides var. typhoides PH. Davis. Moroccan J Chem 6(4):601–614

    CAS  Google Scholar 

  • Peterson J, Dwyer J (1998) Flavonoids: dietary occurrence and biochemical activity. Nutr Res 18(12):1995–2018

    Article  CAS  Google Scholar 

  • Peterson JJ, Dwyer JT, Beecher GR, Bhagwat SA, Gebhardt SE, Haytowitz DB et al (2006) Flavanones in oranges, tangerines (mandarins), tangors, and tangelos: a compilation and review of the data from the analytical literature. J Food Compos Anal 19:S66–S73

    Article  CAS  Google Scholar 

  • Piao X-L, Wu Q, Han S, Kim H-Y, Lee S-H (2011) Simultaneous determination of flavanone glycosides in the fruit of Citrus paradisi and C. grandis by HPLC-PDA. Nat Prod Sci 17(4):337–341

    CAS  Google Scholar 

  • Rafael F, Antonio C, Francisco B (1994) Body and mouthfeel potentiated food and beverages containing neohesperidin dihydrochalcone. United states patent and trade mark office. https://patents.google.com/patent/US5300309A/en

  • Rafael F, Francisco B, Juan C, Helena M (2003) Sweetening compositions containing neohesperidin-dihydrochalcone and at least another high-intensity sweetener. European Patent Office

    Google Scholar 

  • Raymond WR, Maier VP (1977) Chalcone cyclase and flavonoid biosynthesis in grapefruit. Phytochemistry 16(10):1535–1539

    Article  CAS  Google Scholar 

  • Rouseff RL, Martin SF, Youtsey CO (1987) Quantitative survey of narirutin, naringin, hesperidin, and neohesperidin in citrus. J Agric Food Chem (ACS Publications) 35(6):1027–1030

    Article  CAS  Google Scholar 

  • Shi X, Yang Y (2018) The pharmaceutic usage of neohesperidin. China

    Google Scholar 

  • Shi L, Ji Z, Yu Q, Li Y (2014) Chemical constituents in methanol parts of Toddalia Asiatica (Linn) Lam. China Pharm 17:534–537

    CAS  Google Scholar 

  • Shi Q, Song X, Fu J, Su C, Xia X, Song E et al (2015) Artificial sweetener neohesperidin dihydrochalcone showed antioxidative, anti-inflammatory and anti-apoptosis effects against paraquat-induced liver injury in mice. Int Immunopharmacol 29(2):722–729. Available from: https://www.sciencedirect.com/science/article/pii/S1567576915301065

    Article  CAS  PubMed  Google Scholar 

  • Sinha D, Satapathy T, Jain P, Chandel JP, Sahu D, Sahu B et al (2019) In vitro antidiabetic effect of neohesperidin. J Drug Deliv Ther 9(6):102–109

    Article  Google Scholar 

  • Su C, Xia X, Shi Q, Song X, Fu J, Xiao C et al (2015) Neohesperidin Dihydrochalcone versus CCl 4 -induced hepatic injury through different mechanisms: the implication of free radical scavenging and Nrf2 activation. J Agric Food Chem 63:5468–5475

    Article  CAS  PubMed  Google Scholar 

  • Suárez J, Herrera MD, Marhuenda E (1996) Hesperidin and neohesperidin dihydrochalcone on different experimental models of induced gastric ulcer. Phyther Res (Wiley) 10(7):616–618

    Article  Google Scholar 

  • Suarez J, Herrera MD, Marhuenda E (1998) In vitro scavenger and antioxidant properties of hesperidin and neohesperidin dihydrochalcone. Phytomedicine 5(6):469–473

    Article  CAS  PubMed  Google Scholar 

  • Tae H, Lee N (2007) Flavonoid fractions comprising neohesperidin from citrus grandis, that having physiological activity (Patent KR100782023B1). https://patents.google.com/patent/KR100782023B1/en

  • Tan Z, Cheng J, Liu Q, Zhou L, Kenny J, Wang T et al (2017) Neohesperidin suppresses osteoclast differentiation, bone resorption and ovariectomised-induced osteoporosis in mice. Mol Cell Endocrinol 439:369–378. Available from: https://www.sciencedirect.com/science/article/pii/S0303720716303914

    Article  CAS  PubMed  Google Scholar 

  • Tomás-Navarro M, Vallejo F, Tomás-Barberán FA (2014) Bioavailability and metabolism of citrus fruit beverage flavanones in humans. In: Polyphenols in human health and disease. Elsevier, pp 537–551

    Chapter  Google Scholar 

  • Vedpal, Jayaram U, Wadhwani A, Dhanabal SP (2020) Isolation and characterization of flavonoids from the roots of medicinal plant Tadehagi triquetrum (L.) H.Ohashi. Nat Prod Res (Taylor & Francis) 34(13):1913–1918

    Article  CAS  Google Scholar 

  • Vescommi GC, Palazzini E, Zamponi V, Pantaleo MR (2013) Gastroresistant pharmaceutical formulations containing rifaximin (Patent CN101137350B). https://patents.google.com/patent/CN101137350B/en

  • Wang J-J, Cui P (2013) Neohesperidin attenuates cerebral ischemia–reperfusion injury via inhibiting the apoptotic pathway and activating the Akt/Nrf2/HO-1 pathway. J Asian Nat Prod Res 15(9):1023–1037

    Article  CAS  PubMed  Google Scholar 

  • Wang X, Pan Y, Jianshe M, Shi S, Zheng X, Xiang Z. Application of a liquid chromatography–tandem mass spectrometry method to the pharmacokinetics, bioavailability and tissue distribution of neohesperidin dihydrochalcone in rats. Xenobiotica (Taylor & Francis); 2014;44(6):555–561

    Google Scholar 

  • Wang J, Yuan Y, Zhang P, Zhang H, Liu X, Zhang Y (2018) Neohesperidin prevents Aβ25–35-induced apoptosis in primary cultured hippocampal neurons by blocking the S-Nitrosylation of protein-disulphide isomerase. Neurochem Res 43(9):1736–1744

    Article  CAS  PubMed  Google Scholar 

  • Wang S-W, Sheng H, Bai Y-F, Weng Y-Y, Fan X-Y, Lou L-J et al (2020) Neohesperidin enhances PGC-1α-mediated mitochondrial biogenesis and alleviates hepatic steatosis in high fat diet fed mice. Nutr Diabetes (Nature Publishing Group UK) 10(1):27

    CAS  Google Scholar 

  • Wang X-H, Dai C, Wang J, Liu R, Li L, Yin Z-S (2021) Therapeutic effect of neohesperidin on TNF-α-stimulated human rheumatoid arthritis fibroblast-like synoviocytes. Chin J Nat Med 19(10):741–749

    CAS  PubMed  Google Scholar 

  • Wei HH, Xiao Y, Gao Q, Liao S (2020) Whitening skin-care essence and preparation method thereof (Patent CN108186390B). https://patents.google.com/patent/CN108186390B/en

  • Wu H, Yang B, He Q, Chen K, Li X, Sun C (2013) Application of neohesperidin in hyperlipidemia prevention and treatment drug preparation (Patent CN103263427A). https://patents.google.com/patent/CN103263427A/en

  • Wu H, Yang B, He Q, Chen K, Li X, Sun C (2014) Application of neohesperidin in preparing of diabetes preventive treatment medicines. China, pp 1–14. https://patents.google.com/patent/CN102772424B/en

  • Wu H, Liu Y, Chen X, Zhu D, Ma J, Yan Y et al (2017) Neohesperidin exerts lipid-regulating effects in vitro and in vivo via fibroblast growth factor 21 and AMP-activated protein kinase/Sirtuin type 1/peroxisome proliferator-activated receptor gamma coactivator 1α Signaling Axis. Pharmacology 100(3–4):115–126

    Article  CAS  PubMed  Google Scholar 

  • Xia X, Fu J, Song X, Shi Q, Su C, Song E et al (2015) Neohesperidin dihydrochalcone down-regulates MyD88-dependent and -independent signaling by inhibiting endotoxin-induced trafficking of TLR4 to lipid rafts. Free Radic Biol Med 89:522–532

    Article  CAS  PubMed  Google Scholar 

  • Xia N, Wan W, Zhu S, Liu Q (2020) Synthesis of hydrophobic Propionyl Neohesperidin Ester using an Immobilied enzyme and description of its anti-proliferative and pro-apoptotic effects on MCF-7 human breast cancer cells. Front Bioeng Biotechnol 8:1025

    Article  PubMed  PubMed Central  Google Scholar 

  • Xiao Z, Xiao H, Zheng Q (2017) A kind of curcumin composition of Antialcoholic liver-protecting (Patent CN106266026A). https://patents.google.com/patent/CN106266026A/en

  • Xiaojun X, Jie W, Wang Y (2018) A kind of medicine for treating liver fibrosis (Patent CN107875164A). https://patents.google.com/patent/CN107875164A/en

  • Xu Y, Qu H, Cheng Y (1994) Isolation and purification of neohesperidin reference substance from Fructus Aurantii. Chinese Traditional and Herbal Drugs

    Google Scholar 

  • Xu H, Kulkarni KH, Singh R, Yang Z, Wang SWJ, Tam VH et al (2009) Disposition of naringenin via glucuronidation pathway is affected by compensating efflux transporters of hydrophilic glucuronides. Mol Pharm 6(6):1703–1715

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu F, Zang J, Chen D, Zhang T, Zhan H, Lu M et al (2012) Neohesperidin induces cellular apoptosis in human breast adenocarcinoma MDA-MB-231 cells via activating the Bcl-2/Bax-mediated Signaling pathway. Nat Prod Commun (SAGE Publications Inc) 7(11):1934578X1200701116

    Google Scholar 

  • Yang B, He Q, Cao J, Yingmeidan, Dong R, Zhu H (2017) Application of the neohesperidin in preventing and treating tumour medicine is prepared (Patent CN107028962A). https://patents.google.com/patent/CN107028962A/en

  • Yuan J, Wei F, Luo X, Zhang M, Qiao R, Zhong M et al (2020a) Multi-component comparative pharmacokinetics in rats after oral administration of Fructus aurantii extract, Naringin, Neohesperidin, and Naringin-Neohesperidin. Front Pharmacol 11:933

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yuan S, Zhang C, Zhu Y, Wang B (2020b) Neohesperidin ameliorates steroid-induced osteonecrosis of the femoral head by inhibiting the histone modification of lncrna hotair. Drug Des Devel Ther 14:5419–5430

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zamora-Ros R, Knaze V, Rothwell JA, Hémon B, Moskal A, Overvad K et al (2016) Dietary polyphenol intake in Europe: the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Eur J Nutr 55(4):1359–1375

    Article  CAS  PubMed  Google Scholar 

  • Zeng F (2020) Natural antiseptic composition for cosmetics and preparation process thereof (Patent CN111568841A). https://patents.google.com/patent/CN111568841A/en

  • Zhang J, Sun C, Yan Y, Chen Q, Luo F, Zhu X et al (2012a) Purification of naringin and neohesperidin from Huyou (Citrus changshanensis) fruit and their effects on glucose consumption in human HepG2 cells. Food Chem 135(3):1471–1478

    Article  CAS  PubMed  Google Scholar 

  • Zhang J, Zhu X, Luo F, Sun C, Huang J, Li X et al (2012b) Separation and purification of neohesperidin from the albedo of Citrus reticulata cv. Suavissima by combination of macroporous resin and high-speed counter-current chromatography. J Sep Sci (Wiley) 35(1):128–136

    Article  CAS  Google Scholar 

  • Zhang J, Fu X, Yang L, Wen H, Zhang L, Liu F et al (2020) Neohesperidin inhibits cardiac remodeling induced by Ang II in vivo and in vitro. Biomed Pharmacother 129:110364

    Article  CAS  PubMed  Google Scholar 

  • Zhang C, Yuan S, Chen Y, Wang B (2021a) Neohesperidin promotes the osteogenic differentiation of human bone marrow stromal cells by inhibiting the histone modifications of lncRNA SNHG1. Cell Cycle 20(19):1953–1966

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang F-X, Yuan Y-L-L, Cui S-S, Li M, Tan X, Qiu Z-C et al (2021b) Dissection of the potential pharmacological function of neohesperidin dihydrochalcone – a food additive – by in vivo substances profiling and network pharmacology. Food Funct 12(10):4325–4336

    Article  CAS  PubMed  Google Scholar 

  • Zhang F, Yuan Y, Wang J, Li Z, Cui S, Zhu F et al (2021c) Characterization of metabolism feature and potential pharmacological changes of morusin-a promising anti-tumor drug-by ultra-high-performance liquid chromatography coupled time-of-flight mass spectrometry and network pharmacology. Arab J Chem 14(2):102964. Available from: https://www.sciencedirect.com/science/article/pii/S1878535220305256

    Article  CAS  Google Scholar 

  • Zhang J, Hui Y, Liu F, Yang Q, Lu Y, Chang Y et al (2022) Neohesperidin protects angiotensin II-induced hypertension and vascular Remodeling. Front Pharmacol 13:890202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao T, Hu S, Ma P, Che D, Liu R, Zhang Y et al (2019) Neohesperidin suppresses IgE-mediated anaphylactic reactions and mast cell activation via Lyn-PLC-Ca2+ pathway. Phyther Res 33(8):2034–2043

    Article  CAS  Google Scholar 

  • Zou Z, Jia H, Zhang H, Gang D, Liu Y, Chang X et al (2013) Application of neohesperidin as antidepressant. China National Intellectual Property Administration

    Google Scholar 

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Authors and Affiliations

  1. Department of Pharmaceutical Technology, University College of Engineering, Anna University BIT Campus, Tiruchirappalli, Tamil Nadu, India

    P. Senthamil Selvan, E. Sanmuga Priya & P. Sivasakthi

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  1. P. Senthamil Selvan
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  2. E. Sanmuga Priya
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  3. P. Sivasakthi
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Correspondence to P. Senthamil Selvan .

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  1. Department of Analytical Chemistry and Food Science, Universidade de Vigo, Vigo, Spain

    Jianbo Xiao

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Selvan, P.S., Priya, E.S., Sivasakthi, P. (2023). Neohesperidin: Biosynthesis, ADME, Biological and Pharmacological Activities. In: Xiao, J. (eds) Handbook of Dietary Flavonoids. Springer, Cham. https://doi.org/10.1007/978-3-030-94753-8_33-1

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