Jingui Shenqi pill (金匮肾气丸 ) treats cardiorenal syndrome by inhibiting mitogen-activated protein kinase signaling pathway and reducing inflammatory response

doi:10.19852/j.cnki.jtcm.2025.05.012

Abstract

Abstract:

OBJECTIVE: To confirm the therapeutic effect and mechanism of Jingui Shenqi pill (金匮肾气丸, JGSQP) on cardiorenal syndrome.

METHODS: Doxorubicin was used to build heart-kidney coinjury rat model. After the modeling was completed, JGSQP gavage intervention was performed. The cardiac function of rats in each group was evaluated by ultrasound detection. Serum of rats was collected and examined for markers of heart and kidney damage. Enzyme linked immunosorbent assay detected serum inflammatory factors interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) expression. Quantitative real-time polymerase chain reaction (PCR) and Western blot detected the changes of related genes and proteins.

RESULTS: JGSQP significantly increased left ventricular ejection fraction (EF) and left ventricular shortening fraction (FS) values, decreased the heart and kidney damage markers and fibrosis levels (P < 0.05). Furthermore, it can reduce IL-1β, IL-6, and TNF-α inflammatory expression (P < 0.05). Mechanistically, JGSQP significantly inhibited the expression of key genes and proteins of mitogen-activated protein kinase (MAPK) signaling pathway (P < 0.05).

CONCLUSIONS: Jingui Shenqi pill can exert therapeutic effects on cardiorenal syndrome by inhibiting the activation of the MAPK signaling pathway and inflammatory responses.

Key words: cardiorenal syndrome, mitogen-activated protein kinase, inflammatory cytokines, signal transduction, Jingui Shenqi pill

HUANG Shuyan, DING Xinyue, ZHANG Hui, LIU Zongjun, LUAN Yuling, XING Lina. Jingui Shenqi pill (金匮肾气丸 ) treats cardiorenal syndrome by inhibiting mitogen-activated protein kinase signaling pathway and reducing inflammatory response[J]. Journal of Traditional Chinese Medicine, 2025, 45(5): 1059-1066.

Figures/Tables 4

Figure 1 Effect of JGSQP on rats injury and fibrosis A: cardiac ultrasound results of rats treated with JGSQP; B: rats EF statistical column; C: rats FS statistical column; D: results of heart masson staining after intervention with JGSQP (× 20); E: results of kidney masson staining after intervention with JGSQP (× 40). A1, D1, E1: control group; A2, D2, E2: DOX group; A3, D3, E3: JGSQP-L group; A4, D4, E4: JGSQP-M group; A5, D5, E5: JGSQP-H group. DOX: doxorubicin group (3 mg/kg doxorubicin was injected intraperitoneally once/week for 6 weeks); JGSQP-L: JGSQP low-dose group (0.5 g/kg JGSQP were administered by gavage for 8 weeks); JGSQP-M: JGSQP medium-dose group (1.0 g/kg JGSQP were administered by gavage for 8 weeks); JGSQP-H: JGSQP high-dose group (2.0 g/kg JGSQP were administered by gavage for 8 weeks). JGSQP: Jingui Shenqi pill; EF: ejection fraction; DOX: doxorubicin. Differences were evaluated by one-way analysis of variance. Data are presented as mean ± standard deviation (n = 8). aP < 0.05, compared with the control group, bP < 0.05, compared with the DOX group.

Figure 2 Effect of JGSQP on improving cardiorena function in rats A: ELISA of BNP, nt-pro BNP, MYO, cTNI expression in rats serum; A1: BNP; A2: nt-pro BNP; A3: MYO; A4: cTNI; B: rats serum SCr, BUN, Cys-C, UA expression; B1: SCr; B2: BUN; B3: Cys-C; B4: UA; C: rats 24 h urine protein. DOX: doxorubicin group (3 mg/kg doxorubicin was injected intraperitoneally once/week for 6 weeks); JGSQP-L: JGSQP low-dose group (0.5 g/kg JGSQP were administered by gavage for 8 weeks); JGSQP-M: JGSQP medium-dose group (1.0 g/kg JGSQP were administered by gavage for 8 weeks); JGSQP-H: JGSQP high-dose group (2.0 g/kg JGSQP were administered by gavage for 8 weeks). JGSQP: Jingui Shenqi pill; ELISA: enzyme linked immunosorbent assay; BNP: brain natriuretic peptide; nt-pro BNP: N-terminal pro-brain natriuretic peptide; MYO: myoglobin; Ctn-I:cardiac troponin Ⅰ; Scr: serum creatinine; BUN: blood urea nitrogen; Cys-C: cystatin C; UA: uric acid; DOX: doxorubicin. Differences were evaluated by one-way analysis of variance. Data are presented as mean ± standard deviation (n = 8). aP < 0.05, compared with the control group, bP < 0.05, compared with the DOX group.

Figure 3 JGSQP for the treatment of inflammation in rats A: expression of AST and LDH in serum of rats treated with JGSQP; B: ELISA of IL-1β, IL-6 and TNF-α expression in rats serum. A1: AST; A2: LDH; B1: IL-1β; B2: IL-6; B3: TNF-α. DOX: doxorubicin group (3 mg/kg doxorubicin was injected intraperitoneally once/week for 6 weeks); JGSQP-L: JGSQP low-dose group (0.5 g/kg JGSQP were administered by gavage for 8 weeks); JGSQP-M: JGSQP medium-dose group (1.0 g/kg JGSQP were administered by gavage for 8 weeks); JGSQP-H: JGSQP high-dose group (2.0 g/kg JGSQP were administered by gavage for 8 weeks). JGSQP: Jingui Shenqi pill; ELISA: enzyme linked immunosorbent assay; AST: aspartate transaminase; LDH: lactate dehydrogenase assay; IL-1β: interleukin-1β; IL-6: interleukin-6; TNF-α: tumor necrosis factor-α; DOX: doxorubicin. Differences were evaluated by one-way analysis of variance. Data are presented as mean ± standard deviation (n = 8). aP < 0.05, compared with the control group; bP < 0.05, compared with the DOX group.

Figure 4 JGSQP can inhibit the activation of MAPK pathway A: PCR results of Mapk8ip2, Mapk8ip3, Mapk1, Mapk3 in rat heart; A1: Mapk8ip2; A2: Mapk8ip3; A3: Mapk1; A4: Mapk3; B: PCR results of Mapk8ip2, Mapk8ip3, Mapk1, Mapk3 in rat kidney; B1: Mapk8ip2; B2: Mapk8ip3; B3: Mapk1; B4: Mapk3; C: Western blot measured rats heart P-MAPK-2, SAPK/JNK, Erk protein expression. The column shows protein expression. C1: Western blot image of rats heart P-MAPK-2, SAPK/JNK, Erk protein expression; C2: P-MAPK-2 protein expression; C3: SAPK/JNK protein expression; C4: Erk protein expression; D: Western blotting measured rats kidney P-MAPK-2, SAPK/JNK, P-P38 MAPK protein expression; D1: Western blotting image of rats kidney P-MAPK-2, SAPK/JNK, P-P38 MAPK protein expression; D2: P-MAPK-2 protein expression; D3: SAPK/JNK protein expression; D4: P-P38 MAPK protein expression; 1: control group; 2: DOX group; 3: JGSQP-L group; 4: JGSQP-M group; 5: JGSQP-H group. DOX: doxorubicin group (3 mg/kg doxorubicin was injected intraperitoneally once/week for 6 weeks); JGSQP-L: JGSQP low-dose group (0.5 g/kg JGSQP were administered by gavage for 8 weeks); JGSQP-M: JGSQP medium-dose group (1.0 g/kg JGSQP were administered by gavage for 8 weeks); JGSQP-H: JGSQP high-dose group (2.0 g/kg JGSQP were administered by gavage for 8 weeks). JGSQP: Jingui Shenqi pill; PCR: quantitative real?time polymerase chain reaction ; Mapk8ip2: mitogen-activated protein kinase 8 interacting protein 2; Mapk8ip3: mitogen-activated protein kinase 8 interacting protein 3; Mapk1: mitogen-activated protein kinase 1; Mapk3: mitogen-activated protein kinase 3; P-MAPKAPK-2: phospho-mitogen-activated protein kinase-activated protein kinase 2; SAPK/JNK: stress-activated protein kinase/c-jun N-terminal kinase; Erk: extracellular signal-regulated kinase; P-P38 MAPK: phospho-p38 mitogen-activated protein kinase; COX4: cytochrome c oxidase subunit 4; DOX: doxorubicin. Differences were evaluated by one-way analysis of variance. Data are presented as mean ± standard deviation (n = 8). aP < 0.05, compared with the control group; bP < 0.05, compared with the DOX group.

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