Kamishoyosan and Kamikihito protect against decreased KCC2 expression induced by the P. gingivalis lipopolysaccharide treatment in PC-12 cells and improve behavioral abnormalities in male mice
Kamishoyosan (KSS) and Kamikihito (KKT) have been traditionally prescribed for neuropsychiatric symptoms in Japan. However, the molecular mechanism of its effect is not elucidated enough. On the other hand, it has been reported that lipopolysaccharide derived from Porphyromonas gingivalis (P. g LPS)...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023099929 |
| _version_ | 1797383968074498048 |
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| author | Kazuo Tomita Yukiko Oohara Kento Igarashi Junichi Kitanaka Nobue Kitanaka Koh-ichi Tanaka Mehryar Habibi Roudkenar Amaneh Mohammadi Roushandeh Mitsutaka Sugimura Tomoaki Sato |
| author_facet | Kazuo Tomita Yukiko Oohara Kento Igarashi Junichi Kitanaka Nobue Kitanaka Koh-ichi Tanaka Mehryar Habibi Roudkenar Amaneh Mohammadi Roushandeh Mitsutaka Sugimura Tomoaki Sato |
| author_sort | Kazuo Tomita |
| collection | DOAJ |
| description | Kamishoyosan (KSS) and Kamikihito (KKT) have been traditionally prescribed for neuropsychiatric symptoms in Japan. However, the molecular mechanism of its effect is not elucidated enough. On the other hand, it has been reported that lipopolysaccharide derived from Porphyromonas gingivalis (P. g LPS) is involved not only in periodontal disease but also in the systemic diseases such as psychiatric disorders via neuroinflammation. Here, we investigated the molecular mechanism of KSS and KKT treatment by LPS-induced neuropathy using PC-12 cells. When P. g LPS was administrated during the NGF treatment, the KCC2 expression was decreased in PC-12 cells. P. g LPS treatment also decreased the WNK and phospho SPAK (pSPAK) expression and enhanced GSK-3β expression that negatively regulates WNK-SPAK signaling. Moreover, when KSS or KKT was administrated before P. g LPS treatment, the decrease of KCC2, WNK and pSPAK was rescued. KSS and KKT treatment also rescued the enhancement of GSK3β expression by P. g LPS treatment. Furthermore, KSS, KKT and/or oxytocin could rescue behavioral abnormalities caused by P. g LPS treatment by animal experiments. These effects were not shown in the Goreisan treatment, which has been reported to act on the central nervous system. These results indicate that KSS and KKT are candidates for therapeutic agents for neural dysfunction. |
| first_indexed | 2024-03-08T21:28:39Z |
| format | Article |
| id | doaj.art-e7dfc8c3678b4362ac037c0d50ff4df7 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-08T21:28:39Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-e7dfc8c3678b4362ac037c0d50ff4df72023-12-21T07:34:37ZengElsevierHeliyon2405-84402023-12-01912e22784Kamishoyosan and Kamikihito protect against decreased KCC2 expression induced by the P. gingivalis lipopolysaccharide treatment in PC-12 cells and improve behavioral abnormalities in male miceKazuo Tomita0Yukiko Oohara1Kento Igarashi2Junichi Kitanaka3Nobue Kitanaka4Koh-ichi Tanaka5Mehryar Habibi Roudkenar6Amaneh Mohammadi Roushandeh7Mitsutaka Sugimura8Tomoaki Sato9Department of Applied Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 890-8544, Japan; Division of Pharmacology, Department of Pharmacy, School of Pharmacy, Hyogo Medical University, Hyogo, 650-8530, Japan; Corresponding author. Department of Applied Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 890-8544, Japan.Department of Applied Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 890-8544, Japan; Department of Dental Anesthesiology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 890-8544, JapanDepartment of Applied Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 890-8544, Japan; Division of Pharmacology, Department of Pharmacy, School of Pharmacy, Hyogo Medical University, Hyogo, 650-8530, JapanLaboratory of Drug Addiction and Experimental Therapeutics, School of Pharmacy, Hyogo Medical University, Hyogo, 650-8530, JapanLaboratory of Drug Addiction and Experimental Therapeutics, School of Pharmacy, Hyogo Medical University, Hyogo, 650-8530, Japan; Department of Pharmacology, School of Medicine, Hyogo Medical University, Hyogo, 663-8501, JapanDepartment of Applied Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 890-8544, Japan; Division of Pharmacology, Department of Pharmacy, School of Pharmacy, Hyogo Medical University, Hyogo, 650-8530, JapanDepartment of Applied Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 890-8544, Japan; Burn and Regenerative Medicine Research Center, Velayat Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, 41937-13194, IranDepartment of Anatomy, School of Biomedical Sciences, Medicine & Health, UNSW Sydney, Sydney, NSW, 2052, AustraliaDepartment of Dental Anesthesiology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 890-8544, JapanDepartment of Applied Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 890-8544, JapanKamishoyosan (KSS) and Kamikihito (KKT) have been traditionally prescribed for neuropsychiatric symptoms in Japan. However, the molecular mechanism of its effect is not elucidated enough. On the other hand, it has been reported that lipopolysaccharide derived from Porphyromonas gingivalis (P. g LPS) is involved not only in periodontal disease but also in the systemic diseases such as psychiatric disorders via neuroinflammation. Here, we investigated the molecular mechanism of KSS and KKT treatment by LPS-induced neuropathy using PC-12 cells. When P. g LPS was administrated during the NGF treatment, the KCC2 expression was decreased in PC-12 cells. P. g LPS treatment also decreased the WNK and phospho SPAK (pSPAK) expression and enhanced GSK-3β expression that negatively regulates WNK-SPAK signaling. Moreover, when KSS or KKT was administrated before P. g LPS treatment, the decrease of KCC2, WNK and pSPAK was rescued. KSS and KKT treatment also rescued the enhancement of GSK3β expression by P. g LPS treatment. Furthermore, KSS, KKT and/or oxytocin could rescue behavioral abnormalities caused by P. g LPS treatment by animal experiments. These effects were not shown in the Goreisan treatment, which has been reported to act on the central nervous system. These results indicate that KSS and KKT are candidates for therapeutic agents for neural dysfunction.http://www.sciencedirect.com/science/article/pii/S2405844023099929KCC2LPSGABAOxytocinPC-12 cells |
| spellingShingle | Kazuo Tomita Yukiko Oohara Kento Igarashi Junichi Kitanaka Nobue Kitanaka Koh-ichi Tanaka Mehryar Habibi Roudkenar Amaneh Mohammadi Roushandeh Mitsutaka Sugimura Tomoaki Sato Kamishoyosan and Kamikihito protect against decreased KCC2 expression induced by the P. gingivalis lipopolysaccharide treatment in PC-12 cells and improve behavioral abnormalities in male mice Heliyon KCC2 LPS GABA Oxytocin PC-12 cells |
| title | Kamishoyosan and Kamikihito protect against decreased KCC2 expression induced by the P. gingivalis lipopolysaccharide treatment in PC-12 cells and improve behavioral abnormalities in male mice |
| title_full | Kamishoyosan and Kamikihito protect against decreased KCC2 expression induced by the P. gingivalis lipopolysaccharide treatment in PC-12 cells and improve behavioral abnormalities in male mice |
| title_fullStr | Kamishoyosan and Kamikihito protect against decreased KCC2 expression induced by the P. gingivalis lipopolysaccharide treatment in PC-12 cells and improve behavioral abnormalities in male mice |
| title_full_unstemmed | Kamishoyosan and Kamikihito protect against decreased KCC2 expression induced by the P. gingivalis lipopolysaccharide treatment in PC-12 cells and improve behavioral abnormalities in male mice |
| title_short | Kamishoyosan and Kamikihito protect against decreased KCC2 expression induced by the P. gingivalis lipopolysaccharide treatment in PC-12 cells and improve behavioral abnormalities in male mice |
| title_sort | kamishoyosan and kamikihito protect against decreased kcc2 expression induced by the p gingivalis lipopolysaccharide treatment in pc 12 cells and improve behavioral abnormalities in male mice |
| topic | KCC2 LPS GABA Oxytocin PC-12 cells |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023099929 |
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