Changrui enema inhibits inflammation-induced angiogenesis in acute radiation proctitis by regulating NF-κB and VEGF

Gao, Jinsheng; Li, Yousong; Yang, Xi; Hu, Min; Xu, Jie; Cheng, Lin; Cao, Kaiqi; Liu, Likun; Wang, Xixing

doi:10.1590/s0102-865020200050000002

Jinsheng Gao

MD, Associate Professor, Department of Oncology, Shanxi Province Research Institute of Traditional Chinese Medicine, Taiyuan, China. Conception and design of the study, analysis and interpretation of data, manuscript writing, final approval.

* The authors contributed equally to this work.

http://orcid.org/0000-0001-6184-802X

Yousong Li

MD, Associate Professor, Department of Traditional Chinese Medicine, Shanxi Bethune Hospital, Taiyuan, China. Analysis and interpretation of data.

* The authors contributed equally to this work.

http://orcid.org/0000-0002-3584-9798

Xi Yang

MD, Postdoctor, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China. Analysis and interpretation of data.

* The authors contributed equally to this work.

http://orcid.org/0000-0001-5177-8208

Min Hu

PhD, Department of Oncology, Shanxi Province Research Institute of Traditional Chinese Medicine, Taiyuan, China. Technical procedures, analysis and interpretation of data.

http://orcid.org/0000-0002-8372-9387

Jie Xu

PhD, Department of Oncology, Shanxi Province Research Institute of Traditional Chinese Medicine, Taiyuan, China. Technical procedures, analysis and interpretation of data.

http://orcid.org/0000-0003-0802-8174

Lin Cheng

PhD, Department of Oncology, Shanxi Province Research Institute of Traditional Chinese Medicine, Taiyuan, China. Technical procedures, analysis and interpretation of data.

http://orcid.org/0000-0001-9317-3805

Kaiqi Cao

PhD, Department of Oncology, Shanxi Province Research Institute of Traditional Chinese Medicine, Taiyuan, China. Manuscript writing.

http://orcid.org/0000-0001-6074-7120

Likun Liu

Full Professor, Department of Oncology, Shanxi Province Research Institute of Traditional Chinese Medicine, Taiyuan, China. Conception and design of the study.

http://orcid.org/0000-0002-3861-3115

Xixing Wang

Full Professor, Department of Oncology, Shanxi Province Research Institute of Traditional Chinese Medicine, Taiyuan, China. Conception and design of the study, provision of reagents, materials and analysis tools.

http://orcid.org/0000-0002-9413-0601

Correspondence: Jinsheng Gao Department of Oncology Shanxi Province Research Institute of Traditional Chinese Medicine No. 46 Bingzhou West Street, Yingze District Taiyuan 030012 Shanxi, P.R. China Phone: 86-351-4668039 gjs1121@126.com

*
The authors contributed equally to this work.

Conflict of interest: none

MD, Associate Professor, Department of Oncology, Shanxi Province Research Institute of Traditional Chinese Medicine, Taiyuan, China. Conception and design of the study, analysis and interpretation of data, manuscript writing, final approval.

MD, Associate Professor, Department of Traditional Chinese Medicine, Shanxi Bethune Hospital, Taiyuan, China. Analysis and interpretation of data.

MD, Postdoctor, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China. Analysis and interpretation of data.

PhD, Department of Oncology, Shanxi Province Research Institute of Traditional Chinese Medicine, Taiyuan, China. Technical procedures, analysis and interpretation of data.

PhD, Department of Oncology, Shanxi Province Research Institute of Traditional Chinese Medicine, Taiyuan, China. Manuscript writing.

Full Professor, Department of Oncology, Shanxi Province Research Institute of Traditional Chinese Medicine, Taiyuan, China. Conception and design of the study.

Full Professor, Department of Oncology, Shanxi Province Research Institute of Traditional Chinese Medicine, Taiyuan, China. Conception and design of the study, provision of reagents, materials and analysis tools.

Figures (5)
Tables (2)

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Figure 1
Changrui enema treatment ameliorated general signs of mice after irradiation. A. The difference in the general signs score of normal mice and ARP mice at 1 week was significant (*** P ﹤0.001). The general signs score was decreased in western medicine enema group and Changrui enema group compared with that of ARP mice at 1 week (* P ﹤0.05, ** P ﹤0.01). The high-dose Changrui enema treatment was more effective than western medicine enema treatment (* P ﹤0.05). B. The difference in the general signs score of normal mice and ARP mice at 2 weeks was significant (*** P ﹤0.001). The general signs score was decreased in western medicine enema group and Changrui enema group compared with that of ARP mice at 2 weeks (* P ﹤0.05). The high-dose Changrui enema treatment was more effective than western medicine enema treatment (* P ﹤0.05). C. The body weight change of ARP mice was decreased compared with that of normal mice at 8 to 14 days (* P ﹤0.05, ** P ﹤0.01, *** P ﹤0.001). Western medicine enema treatment increased body weight of mice compared with that of ARP mice at 2 to 6 days and 10 days (# P ﹤0.05, ## P ﹤0.01, ### P ﹤0.001). Changrui enema treatment also significantly restored body weight of ARP mice (Δ P ﹤0.05, ΔΔ P ﹤0.01, ΔΔΔ P ﹤0.001).

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Figure 2
Changrui enema treatment did not affect spleen index and liver index. A. There was no significant difference in liver index at 1 week or 2 weeks between normal mice and ARP mice. Compared with ARP mice, liver index was not changed by Changrui enema treatment. B. The difference in liver index at 2 week between normal mice and ARP mice was also not significant. C. There was no significant difference in spleen index at 1 week between normal mice and ARP mice. Compared with ARP mice, spleen index was not changed by Changrui enema treatment. However, spleen index of mice was decreased by western medicine (* P < 0.05). D. The difference in spleen index at 2 week between normal mice and ARP mice was also not significant. Compared with ARP mice, spleen index was not changed by Changrui enema treatment. However, spleen index of mice was decreased by western medicine (*** P < 0.001), suggesting that the use of dexamethasone combined with gentamicin might reduce the weight of spleen and affect immunity responsiveness.

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Figure 3
The expression of IL-1β, NF-κB, VEGF, AQP1, AQP3, p-ERK1/2 and p-JNK in different groups was tested by western blot. Western blot was performed to test the expression of IL-1β, NF-κB, VEGF, AQP1, AQP3, p-ERK1/2 and p-JNK in different groups (n=10 for each group). Compared to normal mice, the expression of IL-1β, NF-κB, VEGF, AQP1 and p-ERK1/2 was increased in ARP mice group and the expression of AQP3 and p-JNK was decreased in ARP mice group. Changrui enema and western medicine not only inhibited the expression of IL-1β, NF-κB, VEGF, AQP1 and p-ERK1/2, but also up-regulated the expression of AQP3 and p-JNK (* P <0.05, ** P <0.01, *** P <0.001).

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Figure 4
The immunohistochemistry imagines and AOD values of NF-κB, VEGF, AQP1 and AQP3 in different groups. A. HE stain and the immunohistochemistry of NF-κB, VEGF, AQP1 and AQP3 of the rectal tissues in different groups (n=10 for each group) were observed under light microscopy (Scale: ×400). The expression of NF-κB (B), VEGF (C) and AQP1 (D) was increased in ARP mice group and was inhibited by Changrui enema and western medicine. E. The expression of AQP3 was decreased in ARP mice group and was up-regulated by Changrui enema and western medicine (* P <0.05, ** P <0.01, *** P <0.001). F. The result showed that there was a positive correlation between VEGF and AQP1.

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Figure 5
Absolute number of lymphocyte and the expression of Bax and Bcl-2 in spleen in different groups were observed and tested. A. Western blot was performed to test the expression of Bax and Bcl-2 in spleen in different groups (n=10 for each group). B. Absolute number of lymphocyte was reduced in spleen of mice treated with dexamethasone and gentamicin combination enema for 2 weeks (*** P <0.001). C. Compared to normal mice, the expression of Bax was increased in spleen tissue of mice treated by dexamethasone combined with gentamicin (*** P <0.001). D. The expression of Bcl-2 was decreased in spleen tissue of mice treated by dexamethasone combined with gentamicin (*** P <0.001).

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Table 1
Herb medicines of Changrui enema.

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Table 2
Comparison of pathological grades of rectal tissue under light microscopy of mice in different groups.

Traditional Chinese medicine	Used part	Chinese Name	Proportion	Traditional effects
Sanguisorba officinalis L.	Root	Diyu	30g	Hemostasis and relieving pain
Agrimonia pilosa Ledeb.	Stem and leaf	Xianhecao	15g	Hemostasis and detoxification
Panax pseudoginseng	Root	Sanqi	6g	Hemostasis and relieving pain
Bletilla striata	Tuber	Baiji	30g	Hemostasis and astringent
Colla corii asini	Donkey-hide gelatin	Ejiao	12g	Hemostasis and hematopoiesis
Rheum officinale Baill.	Root and stem	Daihuang	10g	Clearing heat and detoxification
Acacia catechu	Peeled branch and trunk	Ercha	6g	Hemostasis and clearing heat

Pathological grade	Normal mice	ARP mice	Western medicine	Low-dose Changrui	Middle-dose Changrui	High-dose Changrui
Grade 0	10	0	0	0	0	1
Grade 1	0	0	2	1	3	4
Grade 2	0	1	4	5	5	5
Grade 3	0	4	3	4	2	0
Grade 4 Ridit value	0 0.0917	5 0.8433^***	1 0.5925^#	0 0.6017^#	0 0.4967^##	0 0.3742^###

[1] Correspondence: Jinsheng Gao Department of Oncology Shanxi Province Research Institute of Traditional Chinese Medicine No. 46 Bingzhou West Street, Yingze District Taiyuan 030012 Shanxi, P.R. China Phone: 86-351-4668039 gjs1121@126.com

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Changrui enema inhibits inflammation-induced angiogenesis in acute radiation proctitis by regulating NF-κB and VEGF ¹ 1 Research performed at Department of Central Laboratory, Dongshan Science and Education Park, Shanxi Province Research Institute of Traditional Chinese Medicine, Taiyuan, China.

Abstract

Purpose

Methods

Results

Conclusions

Brasil

Brasil

Changrui enema inhibits inflammation-induced angiogenesis in acute radiation proctitis by regulating NF-κB and VEGF 1 1 Research performed at Department of Central Laboratory, Dongshan Science and Education Park, Shanxi Province Research Institute of Traditional Chinese Medicine, Taiyuan, China.

Abstract

Purpose

Methods

Results

Conclusions

Changrui enema inhibits inflammation-induced angiogenesis in acute radiation proctitis by regulating NF-κB and VEGF ¹ 1 Research performed at Department of Central Laboratory, Dongshan Science and Education Park, Shanxi Province Research Institute of Traditional Chinese Medicine, Taiyuan, China.