Yokukansan Promotes Hippocampal Neurogenesis Associated with the Suppression of Activated Microglia in Gunn Rat

Overview

Journal J Neuroinflammation

Publisher Biomed Central

Date 2013 Dec 6

PMID 24305622

Citations 25

Authors

Motohide Furuya

Tsuyoshi Miyaoka

Toshiko Tsumori

Kristian Liaury

Sadayuki Hashioka

Rei Wake

Keiko Tsuchie

Michiyo Fukushima

Satoko Ezoe

Jun Horiguchi

Affiliations

Soon will be listed here.

Abstract

Background: The pathophysiology of schizophrenia (SCZ) remains unclear, and its treatment is far from ideal. We have previously reported that yokukansan (YKS), which is a traditional Japanese medicine, is effective as an adjunctive therapy for SCZ. However, the mechanisms underlying the action of YKS have not yet been completely elucidated. A recent meta-analysis study has shown that adjuvant anti-inflammatory drugs are effective for SCZ treatment, and it has been proposed that some of the cognitive deficits associated with inflammation may in part be related to inflammation-induced reductions in adult hippocampal neurogenesis. Although certain ingredients of YKS have potent anti-inflammatory activity, no study has determined if YKS has anti-inflammatory properties.

Methods: Using the Gunn rat, which has been reported as a possible animal model of SCZ, we investigated whether YKS affects cognitive dysfunction in an object-location test and the suppression of microglial activation and neurogenesis in the hippocampus.

Results: We found that YKS ameliorated spatial working memory in the Gunn rats. Furthermore, YKS inhibited microglial activation and promoted neurogenesis in the hippocampal dentate gyrus of these rats. These results suggest that the ameliorative effects of YKS on cognitive deficits may be mediated in part by the suppression of the inflammatory activation of microglia.

Conclusions: These findings shed light on the possible mechanism underlying the efficacy of YKS in treating SCZ.

Citing Articles

Successful treatment with traditional Japanese medicine (kampo medicine) Yokukansan as a migraine prophylactic drug: A case report.

Akiyama H, Hasegawa Y, Yamano Y Medicine (Baltimore). 2024; 103(30):e39072.

PMID: 39058870 PMC: 11272254. DOI: 10.1097/MD.0000000000039072.

The Serotonin-Mediated Anti-Allodynic Effect of Yokukansan on Paclitaxel-Induced Neuropathic Pain.

Yokomi H, Kato T, Narasaki S, Kamiya S, Taguchi S, Horikawa Y Medicina (Kaunas). 2024; 60(3).

PMID: 38541085 PMC: 10972347. DOI: 10.3390/medicina60030359.

A Prospective Randomized Study of the Herbal Medicine Yokukansan for Preventing Delirium After Gastrointestinal Cancer Surgery.

Tanio A, Yamamoto M, Uejima C, Tada Y, Yamanashi T, Matsuo R Yonago Acta Med. 2023; 66(4):432-439.

PMID: 38028268 PMC: 10674061. DOI: 10.33160/yam.2023.11.008.

Glycyrrhizae Radix suppresses lipopolysaccharide- and diazepam-induced nerve inflammation in the hippocampus, and contracts the duration of pentobarbital- induced loss of righting reflex in a mouse model.

Kawada K, Ishida T, Jobu K, Morisawa S, Nishida M, Tamura N J Nat Med. 2023; 77(3):561-571.

PMID: 37115471 DOI: 10.1007/s11418-023-01700-2.

Yokukansan Suppresses Gastric Hypersensitivity and Eosinophil-associated Microinflammation in Rats With Functional Dyspepsia.

Duan S, Imamura N, Kondo T, Kanda H, Kogure Y, Okugawa T J Neurogastroenterol Motil. 2022; 28(2):255-264.

PMID: 35362452 PMC: 8978130. DOI: 10.5056/jnm21204.

References

Hailer N, Grampp A, Nitsch R . Proliferation of microglia and astrocytes in the dentate gyrus following entorhinal cortex lesion: a quantitative bromodeoxyuridine-labelling study. Eur J Neurosci. 1999; 11(9):3359-64. DOI: 10.1046/j.1460-9568.1999.00808.x. View

Gordo A, Falcao A, Fernandes A, Brito M, Silva R, Brites D . Unconjugated bilirubin activates and damages microglia. J Neurosci Res. 2006; 84(1):194-201. DOI: 10.1002/jnr.20857. View

Duan X, Chang J, Ge S, Faulkner R, Kim J, Kitabatake Y . Disrupted-In-Schizophrenia 1 regulates integration of newly generated neurons in the adult brain. Cell. 2007; 130(6):1146-58. PMC: 2002573. DOI: 10.1016/j.cell.2007.07.010. View

Khaksa G, Zolfaghari M, Dehpour A, Samadian T . Anti-inflammatory and anti-nociceptive activity of disodium glycyrrhetinic acid hemiphthalate. Planta Med. 1996; 62(4):326-8. DOI: 10.1055/s-2006-957894. View

Vita A, De Peri L, Silenzi C, Dieci M . Brain morphology in first-episode schizophrenia: a meta-analysis of quantitative magnetic resonance imaging studies. Schizophr Res. 2005; 82(1):75-88. DOI: 10.1016/j.schres.2005.11.004. View

Imai Y, Ibata I, Ito D, Ohsawa K, Kohsaka S . A novel gene iba1 in the major histocompatibility complex class III region encoding an EF hand protein expressed in a monocytic lineage. Biochem Biophys Res Commun. 1996; 224(3):855-62. DOI: 10.1006/bbrc.1996.1112. View

Cheng C, Ho T, Lee E, Su S, Tang N, Hsieh C . Ferulic acid reduces cerebral infarct through its antioxidative and anti-inflammatory effects following transient focal cerebral ischemia in rats. Am J Chin Med. 2008; 36(6):1105-19. DOI: 10.1142/S0192415X08006570. View

Bussey T, DUCK J, Muir J, Aggleton J . Distinct patterns of behavioural impairments resulting from fornix transection or neurotoxic lesions of the perirhinal and postrhinal cortices in the rat. Behav Brain Res. 2000; 111(1-2):187-202. DOI: 10.1016/s0166-4328(00)00155-8. View

Dean O, Data-Franco J, Giorlando F, Berk M . Minocycline: therapeutic potential in psychiatry. CNS Drugs. 2012; 26(5):391-401. DOI: 10.2165/11632000-000000000-00000. View

10.

Kohman R, Bhattacharya T, Kilby C, Bucko P, Rhodes J . Effects of minocycline on spatial learning, hippocampal neurogenesis and microglia in aged and adult mice. Behav Brain Res. 2013; 242:17-24. PMC: 3725815. DOI: 10.1016/j.bbr.2012.12.032. View

11.

Ladeby R, Wirenfeldt M, Garcia-Ovejero D, Fenger C, Dissing-Olesen L, Dalmau I . Microglial cell population dynamics in the injured adult central nervous system. Brain Res Brain Res Rev. 2005; 48(2):196-206. DOI: 10.1016/j.brainresrev.2004.12.009. View

12.

Toulopoulou T, Grech A, Morris R, Schulze K, McDonald C, Chapple B . The relationship between volumetric brain changes and cognitive function: a family study on schizophrenia. Biol Psychiatry. 2004; 56(6):447-53. DOI: 10.1016/j.biopsych.2004.06.026. View

13.

Nukaya H, Yamashiro H, Fukazawa H, Ishida H, Tsuji K . Isolation of inhibitors of TPA-induced mouse ear edema from Hoelen, Poria cocos. Chem Pharm Bull (Tokyo). 1996; 44(4):847-9. DOI: 10.1248/cpb.44.847. View

14.

Kushida H, Fukutake M, Tabuchi M, Katsuhara T, Nishimura H, Ikarashi Y . Simultaneous quantitative analyses of indole and oxindole alkaloids of Uncaria Hook in rat plasma and brain after oral administration of the traditional Japanese medicine Yokukansan using high-performance liquid chromatography with tandem mass.... Biomed Chromatogr. 2013; 27(12):1647-56. DOI: 10.1002/bmc.2974. View

15.

Liaury K, Miyaoka T, Tsumori T, Furuya M, Wake R, Ieda M . Morphological features of microglial cells in the hippocampal dentate gyrus of Gunn rat: a possible schizophrenia animal model. J Neuroinflammation. 2012; 9:56. PMC: 3334707. DOI: 10.1186/1742-2094-9-56. View

16.

Song Y, Qu R, Zhu S, Zhang R, Ma S . Rhynchophylline attenuates LPS-induced pro-inflammatory responses through down-regulation of MAPK/NF-κB signaling pathways in primary microglia. Phytother Res. 2012; 26(10):1528-33. DOI: 10.1002/ptr.4614. View

17.

Sommer I, de Witte L, Begemann M, Kahn R . Nonsteroidal anti-inflammatory drugs in schizophrenia: ready for practice or a good start? A meta-analysis. J Clin Psychiatry. 2012; 73(4):414-9. DOI: 10.4088/JCP.10r06823. View

18.

Imamura S, Tabuchi M, Kushida H, Nishi A, Kanno H, Yamaguchi T . The blood-brain barrier permeability of geissoschizine methyl ether in Uncaria hook, a galenical constituent of the traditional Japanese medicine yokukansan. Cell Mol Neurobiol. 2011; 31(5):787-93. PMC: 11498390. DOI: 10.1007/s10571-011-9676-3. View

19.

Iwasaki K, Satoh-Nakagawa T, Maruyama M, Monma Y, Nemoto M, Tomita N . A randomized, observer-blind, controlled trial of the traditional Chinese medicine Yi-Gan San for improvement of behavioral and psychological symptoms and activities of daily living in dementia patients. J Clin Psychiatry. 2005; 66(2):248-52. DOI: 10.4088/jcp.v66n0214. View

20.

Fujiwara H, Takayama S, Iwasaki K, Tabuchi M, Yamaguchi T, Sekiguchi K . Yokukansan, a traditional Japanese medicine, ameliorates memory disturbance and abnormal social interaction with anti-aggregation effect of cerebral amyloid β proteins in amyloid precursor protein transgenic mice. Neuroscience. 2011; 180:305-13. DOI: 10.1016/j.neuroscience.2011.01.064. View