Chrysin’s Antioxidant Effects on the Nervous System Show Its Potential Therapeutic Significance

Chrysin’s Antioxidant Effects on the Nervous System Show Its Potential Therapeutic Significance Anyi Li

Abstract: Chrysin is a compound that is mostly found in various plants, honey and propolis. Chrysin is widely used as a nonprescription drug for bodybuilding, dealing with anxiety, or reducing inflammation. Recent research shows chrysin’s significance in controlling depression-like behavior of women.

Chrysin (also called 5,7dihydroxyflavone, chemical formula: C15H10O4, structure is shown by figure 1) is a common member of the flavone family, which is a class of flavonoids that are common in plants. 1

Figure 1: Structure of Chrysin.

Flavonoids are important component in the pigeon of plants, especially purple flowers, which indicates that it is a common chemical frequently ingested by humans. Additionally, Flavones do not have physiological effects in the human body and lack antioxidant food value. 2 Chrysin, on the other hand, is not only found in plants like the passion flowers, but also found in products that are related to bees, for instance, honey and propolis.3 Chrysin is known for its function as an antioxidant. According to a group of researchers from Neyshabur University and Mashhad University in Iran, chrysin is one of the flavones that shows antioxidant properties, which is mainly supported by the double bond between carbons 2 and 3, and the carbonyl group on carbon 4 (see figure 1). Since ring B and ring C contain no oxygenation, chrysin is also related to other biological abilities like antitoxic and antiinflammatory effects.4 There has been abundant research about the physical benefit of honey. In 2014, two researchers from Chulalongkorn University, Thailand, Pongsathon Premratanachai and Chanpen Chanchao, wrote a review journal about propolis’s anticancer properties, among which chrysin plays an effective role. According to Premratanachai and Chanchao, chrysin has a broad influence on the apoptotic process. 5 Despite flavonoids seems to be ineffective in human body, several recent researches show the potential therapeutic significant in cognition and nervous system of chrysin. Back in 1992, researchers from the Instituto de Biologfa Celular conducted an experiment on mice that indicates chrysin’s properties of anxiety decline. They used mice as experimental subjects, putting them into an elevated plus-maze (shown by figure 2) and observing the time they spent on the open and closed arms of the maze: greater trial times indicate anxiety in the mice, while low trial times reveal sedative activity.

Figure 2: Setting of an elevated plus-maze.

According to their experiment, chrysin has the potential ability of reducing anxiety among mice (see figure 3 below). However, this research group only tested chrysin contained medicine in living creatures, without explaining much about the biochemical process cause by the injection of chrysin in the living body.6

Figure 3: The mean percentage of open arm entries in the researchof InstitutodeBiologfa Celular.Asshown bythe figure, chrysin (CHRY) has lower open arm entries percentage thanthecomparisongroup,DZ, whichisanothermedicine.

Moreover, a study in 2012 by the researchers from Research Center for Pharmacology and Toxicology shows that long-term treatment of chrysin significantly alleviates the neuronal damages which are increased accompanied by a large proliferation in glial fibrillary acidic protein. Similar to the prior experiment in 1992, they had chosen rats as their experimental subject. According to these researchers, the experiment on rats and the comparison on their escape latency in the Morris water maze shows that chrysin improves cognitive deficits. By the biochemical testing, researchers also found that chrysin reduced superoxide dismutase, indicating that it may have therapeutic potential for the treatment of neurodegeneration and dementia, which are caused by decreased cerebral blood flow.7 A recent research in October 2019 by Jonathan Cueto-Escobedo from Universidad Veracruzana et al. provides a deeper understanding about the antidepressant-likeeffectsofchrysin(see figure 4 for the graphing abstract).

Figure4:A graphingabstractoftheresearchofCueto-Escobedo et al.

They explained the context that the neurobiology of depression is related to sexual hormone functions, resulting in females being at increased risk of depression than males due to the presence of ovarian hormones, which is a type of hormone that only exists in the female body. In the human brain, there exists steroid hormones like progesterone and allopregnanolone, which produce time-dependent effects on neurotransmitter pathways. One of the indirect actions to support this process can modulate the γ-amino-butyric acid (GABA)ergic system, a neurotransmission that might decrease when the concentrations of steroid hormones are low in the human brain, causing people to present anxiety and depression-like behavior. GABAergic compounds include neurosteroids and plantderived flavonoids, which include chrysin as well. Same as the experiments in 2012, this group of researchers did their testing on rats by using the elevated plus-maze. However, this research on rats is focusing on finding out the effectiveness of GABAergic on ovarian hormones and female anxiety and depression-like behaviors, so they used female rats. The experiment they use is FST, which is a model that rats are forced to swim in without any possibility of escape, creating a valid chance to observe the anxiety of the subjects.8 According to their results, chrysin and fluoxetine “blocked the reduction of

grooming that was triggered by unpredictable chronic stress” (CuetoEscobedo, et al. 2020), presenting chrysin’s significance in reducing stress, anxiety, and depression-like behavior (see figure 5 forthe table of the test). 9

Figure 5: The table that show the effect of treatment on crossing, rearing and grooming in the LAT. Data of rearing group and grooming group reflects the effectiveness of chrysin-

1 “Flavonoids.” Linus Pauling Institute, Micronutrient Information Center, Oregon State University, 2 Apr. 2020, lpi.oregonstate.edu/mic/dietaryfactors/phytochemicals/flavonoids. 2 ibid. 3 ibid. 4 Samarghandian, Saeed, et al. “Protective Effects of Chrysin Against Drugs and Toxic Agents.” DoseResponse : a Publication of International Hormesis Society, SAGE Publications, 23 June 2017, www.ncbi.nlm.nih.gov/pmc/articles/PMC54844 30/ . 5 Premratanachai, Pongsathon, and Chanpen Chanchao. “Review of the Anticancer Activities of Bee Products.” Asian Pacific Journal of Tropical Biomedicine, Asian Pacific Tropical Medicine Press, May 2014, www.ncbi.nlm.nih.gov/pmc/articles/PMC398504 6/ . 6Wolfman,Claudia,etal.“PossibleAnxiolyticEffects of Chrysin, a Central Benzodiazepine Receptor Ligand Isolated from Passiflora Coerulea.” Pharmacology Biochemistry and Behavior, Elsevier, 26 Nov. 2002, contained medicine in reducing anxiety and depression-like behavior.

This study also introduces GABAA receptor, which plays an effective role in the treatment of anxiolytic-like actions: “The binding of GABA with its receptor opens chloride ion channels to hyperpolarize the neuron and decrease neural activity. These neurophysiological actions are related to the anxiolytic effects of benzodiazepines, barbiturates, psychoactive drugs, and some neurosteroids” (Cueto-Escobedo, et al. 2020). Chrysin is able to interact with GABAA as well. 10 Chrysin, as a component that is common in honey, plants, and many types of dietary supplies, shows its strong potential practice in anti-anxiety or antidepressant medications. Although there are still many properties of chrysin that remain unknown, such as whether its effect on male rats without ovarian hormones would be the same as on female rats, chrysin shows its therapeutic significance on physical and mental fields.

www.sciencedirect.com/science/article/pii/009130 5 794901031.

7 He, Xiao-Li, et al. “Chrysin Improves Cognitive Deficits and Brain Damage Induced by Chronic Cerebral Hypoperfusion in Rats.” European Journal of Pharmacology, U.S. National Library of Medicine, 5 Apr. 2012, www.ncbi.nlm.nih.gov/pubmed/22314218. 8 Can, Adem, et al. “The Mouse Forced Swim Test.” Journal of Visualized Experiments : JoVE, MyJove Corporation, 29 Jan. 2012, www.ncbi.nlm.nih.gov/pmc/articles/PMC3353513/ . 9 Cueto-Escobedo, Jonathan, et al. “Involvement of GABAergicSystemintheAntidepressant-likeEffects ofChrysin(5,7-Dihydroxyflavone)inOvariectomized Rats in the Forced Swim Test: Comparison with Neurosteroids.”BehaviouralBrainResearch,Elsevier,14 Mar. 2020, www.sciencedirect.com/science/article/pii/S01664 3 2820302898. 10 ibid.