

FOLLOWUS
Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou (350122), China
College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou (350122), China
Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou (350122), China
Fujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou (350122), China
Department of Pediatrics, Case Western Reserve University School of Medicine, Rainbow Babies and Children's Hospital, Cleveland, OH (44106), USA
Correspondence to: Prof. PENG Jun, E-mail: pjunlab@hotmail.com
Accepted:09 February 2026,
Published:2026-11
Scan QR Code
WU Jin-kong, LI Ren-feng, WU Mei-zhu, et al. Qingda Granule and Its Individual Herbs Inhibit Hypertension-Induced Vascular Smooth Muscle Cells Proliferation via ERK and JNK Pathways[J]. Chinese Journal of Integrative Medicine, 2026, 32(11): 996-1004.
WU Jin-kong, LI Ren-feng, WU Mei-zhu, et al. Qingda Granule and Its Individual Herbs Inhibit Hypertension-Induced Vascular Smooth Muscle Cells Proliferation via ERK and JNK Pathways[J]. Chinese Journal of Integrative Medicine, 2026, 32(11): 996-1004. DOI: 10.1007/s11655-026-4041-z.
Objective: To investigate the specific role and underlying mechanisms of individual herbs in Qingda Granule (QDG) in attenuating hypertension and inhibiting proliferation of vascular smooth muscle cells (VSMCs). Methods: Spontaneously hypertensive rats (SHRs) and angiotensin Ⅱ (AngⅡ)-stimulated VSMCs were treated with QDG or its individual herbs. SHRs were divided into groups using a completely randomized design: SHRs
valsartan (Val)
QDG
Gastrodia elata Blume (Tianma
Gas)
Uncaria rhynchophylla Miz. ex Havil. (Gouteng
Unc)
Scutellaria baicalensis Georgi (Huangqin
Scu)
and Nelumbo nucifera Gaertn (Lianzixin
Nel)
6 in each group. All treatments were administered via intragastric gavage once daily for 10 weeks. Vascular function and pathological changes were evaluated by ultrasonography and HE staining. The proliferation of VSMCs was assayed by cell counting kit-8
immunohistochemistry (IHC)
and Western blot. RNA sequencing was performed to identify differentially expressed transcripts (DETs) in the abdominal aorta. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed to identify the key signaling pathways
and the expression of pathway-related proteins was subsequently verified by IHC and Western blot. Results: QDG and its individual herb treatments significantly attenuated the increase in pulse wave velocity and aortic wall thickness in SHRs. QDG inhibited the increased PCNA expression and cell viability in VSMCs. Unc
Scu
and Nel exhibited effects similar to QDG
while Gas did not show these effects. RNA sequencing analysis identified DETs in abdominal aortic tissues. KEGG analysis based on the DETs revealed that multiple common and unique signaling pathways were enriched. Among them
the MAPK pathway was enriched in the QDG
Unc
Scu
and Nel groups
but not in the Gas group
and the cAMP pathway was significantly enriched in all groups. IHC and Western blot analysis verified that compared with the SHR group
the QDG
Unc
Scu
and Nel groups inhibited MAPK pathway activation and promoted cAMP pathway activation in the abdominal aorta of SHR and Ang Ⅱ-stimulated A7R5s (P<0.05). However
Gas only inhibited the activation of the p38 MAPK pathway and promoted the activation of the cAMP pathway (P<0.05). Conclusions: The herbs in QDG exert significant antihypertensive effects by regulating common and unique pathways. Specifically
Unc
Scu
and Nel inhibit ERK and JNK pathway activation
which likely underlies QDG's suppression of VSMCs proliferation.
Benetos A, Petrovic M, Strandberg T. Hypertension management in older and frail older patients. Circ Res 2019;124:1045-1060.
An W, Luong LA, Bowden NP, Yang M, Wu W, Zhou X, et al. Cezanne is a critical regulator of pathological arterial remodelling by targeting β-catenin signalling. Cardiovasc Res 2021;118:638-653.
Xu Y, Zhang H, Chen Y, Pober JS, Zhou M, Zhou JH, et al. SRF SUMOylation modulates smooth muscle phenotypic switch and vascular remodeling. Nat Commun 2024;15:6919.
Chu X, Kheirollahi V, Lingampally A, Chelladurai P, Valasarajan C, Vazquez-Armendariz AI, et al. GLI1 + cells contribute to vascular remodeling in pulmonary hypertension. Circ Res 2024;134:e133-e149.
Lin JJ, Chen R, Yang LY, Gong M, Du MY, Mu SQ, et al. Hsa circ 0001402 alleviates vascular neointimal hyperplasia through a miR-183-5p-dependent regulation of vascular smooth muscle cell proliferation, migration, and autophagy. J Adv Res 2024;60:93-110.
Li R, Lou Q, Ji T, Li Y, Yang H, Ma Z, et al. Mechanism of astragalus mongholicus bunge ameliorating cerebral ischemiareperfusion injury: based on network pharmacology analysis and experimental verification. J Ethnopharmacol 2024;329:118157.
Wang Z, Mao Y, Zang Y, Zha Y, Sun J, Wei Z, et al. Transcriptomic analysis reveals the mechanism of isorhamnetin in the treatment of diabetes mellitus erectile dysfunction. Free Radical Biol Med 2024;224:366-381.
Yu N, Shen A, Chu J, Huang Y, Zhang L, Lin S, et al. Qingda Granule inhibits angiotensin Ⅱ induced VSMCs proliferation through MAPK and PI3K/AKT pathways. J Ethnopharmacol 2020;258:112767.
Hsu WH, Huang NK, Shiao YJ, Lu CK, Chao YM, Huang YJ, et al. Gastrodiae rhizoma attenuates brain aging via promoting neuritogenesis and neurodifferentiation. Phytomedicine 2021;87:153576.
Huang X, Wu P, Huang F, Xu M, Chen M, Huang K, et al. Baicalin attenuates chronic hypoxia-induced pulmonary hypertension via adenosine A2A receptor-induced SDF-1/ CXCR4/PI3K/AKT signaling. J Biomed Sci 2017;24:52.
Li Q, Wo D, Huang Y, Yu N, Zeng J, Chen H, et al. Alkaloids from Nelumbinis Plumula (AFNP) ameliorate aortic remodeling via RhoA/ROCK pathway. Biomed Pharmacother 2019;112:108651.
Li Y, Yang W, Zhu Q, Yang J, Wang Z. Protective effects on vascular endothelial cell in N'-nitro-L-arginine (L-NNA)- induced hypertensive rats from the combination of effective components of Uncaria rhynchophylla and Semen Raphani. BioSci Trends 2015;9:237-244.
Cheng Y, Shen A, Wu X, Shen Z, Chen X, Li J, et al. Qingda granule attenuates angiotensin Ⅱ-induced cardiac hypertrophy and apoptosis and modulates the PI3K/AKT pathway. Biomed Pharmacother 2021;133:111022.
Long LZ, Tan L, Xu FQ, Yang WW, Li HZ, Liu JG, et al. Qingda Granule attenuates hypertension-induced cardiac damage via regulating renin-angiotensin system pathway. Chin J Integr Med 2025;31:402-411.
Jia P, Chen D, Zhu Y, Wang M, Zeng J, Zhang L, et al. Liensinine improves AngⅡ-induced vascular remodeling via MAPK/TGF-β1/Smad2/3 signaling. J Ethnopharmacol 2023;317:116768.
Kim TJ, Lee JH, Lee JJ, Yu JY, Hwang BY, Ye SK, et al. Corynoxeine isolated from the hook of Uncaria rhynchophylla inhibits rat aortic vascular smooth muscle cell proliferation through the blocking of extracellular signal regulated kinase 1/2 phosphorylation. Biol Pharm Bull 2008;31:2073-2078.
Li J, Wang H, Shi X, Zhao L, Lv T, Yuan Q, et al. Antiproliferative and anti-migratory effects of Scutellaria strigillosa hemsley extracts against vascular smooth muscle cells. J Ethnopharmacol 2019;235:155-163.
Li X, Tong G, Zhang Y, Liu S, Jin Q, Chen H, et al. Neferine inhibits angiotensin Ⅱ-stimulated proliferation in vascular smooth muscle cells through heme oxygenase-1. Acta Pharmacol Sin 2010;31:679-686.
Peng CY, Pan SL, Huang YW, Guh JH, Chang YL, Teng CM. Baicalein attenuates intimal hyperplasia after rat carotid balloon injury through arresting cell-cycle progression and inhibiting ERK, akt, and NF-kappaB activity in vascular smooth-muscle cells. Naunyn-Schmiedeberg's Arch Pharmacol 2008;378:579-588.
Shah P, Hill R, Dion C, Clark SJ, Abakir A, Willems J, et al. Primordial germ cell DNA demethylation and development require DNA translesion synthesis. Nat Commun 2024;15:3734.
Wang Y, Lu M, Xiong L, Fan J, Zhou Y, Li H, et al. Drp1- mediated mitochondrial fission promotes renal fibroblast activation and fibrogenesis. Cell Death Dis 2020;11:29.
Ye C, Tong Y, Wu N, Wan GW, Zheng F, Chen JY, et al. Inhibition of miR-135a-5p attenuates vascular smooth muscle cell proliferation and vascular remodeling in hypertensive rats. Acta Pharmacol Sin 2021;42:1798-1807.
Ding L, Sun Y, Liang Y, Zhang J, Fu Z, Ren C, et al. Beta-cell Tipe1 orchestrates insulin secretion and cell proliferation by promoting Gαs/cAMP signaling via USP5. Adv Sci (Weinh Baden-Wurtt Ger) 2024;11:e2304940.
Jiang T, Xia Y, Lv J, Li B, Li Y, Wang S, et al. A novel protein encoded by circMAPK1 inhibits progression of gastric cancer by suppressing activation of MAPK signaling. Mol Cancer 2021;20:66.
Kuang Z, Bai J, Ni L, Hang K, Xu J, Ying L, et al. Withanolide B promotes osteogenic differentiation of human bone marrow mesenchymal stem cells via ERK1/2 and wnt/β-catenin signaling pathways. Int Immunopharmacol 2020;88:106960.
Wei L, Zhou Q, Tian H, Su Y, Fu GH, Sun T. Integrin β3 promotes cardiomyocyte proliferation and attenuates hypoxiainduced apoptosis via regulating the PTEN/akt/mTOR and ERK1/2 pathways. Int J Biol Sci 2020;16:644-654.
Chen YR, Wang SC, Huang SP, Su CC, Liu PL, Cheng WC, et al. Protodioscin inhibits bladder cancer cell migration and growth, and promotes apoptosis through activating JNK and p38 signaling pathways. Biomed Pharmacother 2022;156:113929.
Snieckute G, Genzor AV, Vind AC, Ryder L, Stoneley M, Chamois S, et al. Ribosome stalling is a signal for metabolic regulation by the ribotoxic stress response. Cell Metab 2022;34:2036-2046.e8.
Xiong Y, Cui X, Zhou Y, Chai G, Jiang X, Ge G, et al. Dehydrocostus lactone inhibits BLM-induced pulmonary fibrosis and inflammation in mice via the JNK and p38 MAPK-mediated NF-κB signaling pathways. Int Immunopharmacol 2021;98:107780.
Chuang SC, Chen CH, Chou YS, Ho ML, Chang JK. G protein-coupled estrogen receptor mediates cell proliferation through the cAMP/PKA/CREB pathway in murine bone marrow mesenchymal stem cells. Int J Mol Sci 2020;21:6490.
Yang Z, Yuan H, He H, Qi S, Zhu X, Hu X, et al. Unlocking the role of EIF5A: a potential diagnostic marker regulating the cell cycle and showing negative correlation with immune infiltration in lung adenocarcinoma. Int Immunopharmacol 2024;126:111227.
Yu W, Chen FC, Xu WN, Ding SL, Chen PB, Yang L, et al. Inhibition of Y1 receptor promotes osteogenesis in bone marrow stromal cells via cAMP/PKA/CREB pathway. Front Endocrinol 2020;11:583105.
0
Views
0
Downloads
0
CSCD
Publicity Resources
Related Articles
Related Author
Related Institution
京公网安备11010802024621