# Yixinshu attenuates myocardial infarction via SHP1/JAK2/STAT3-mediated regulation of mitochondrial function and apoptosis **Authors:** Xueting Wang, Xinrui Wang, Yang Liu, Yang Cui, Keyi Chen, Hongkun Wu, Mingshan Zhang, Ming Liao, Linyun Fu, Xiangchun Shen PMC · DOI: 10.1186/s13020-025-01299-4 · Chinese Medicine · 2026-03-04 ## TL;DR Yixinshu, a traditional Chinese medicine, protects the heart after a heart attack by improving mitochondrial function and reducing cell death through a specific molecular pathway. ## Contribution The study identifies the SHP1/JAK2/STAT3 pathway and dihydrotanshinone I as key mediators of Yixinshu's cardioprotective effects. ## Key findings - Yixinshu improved cardiac function and reduced infarct size in MI models. - Dihydrotanshinone I suppressed SHP1 and activated STAT3 to mitigate mitochondrial injury. - SHP1 overexpression reversed the protective effects of dihydrotanshinone I. ## Abstract Yixinshu (YXS), a traditional Chinese formula, is applied for coronary artery diseases in clinic, however, its cardioprotective mechanisms remain unclear. At present, the role and underlying mechanisms of YXS is to elucidate in enhancing post-myocardial infarction (MI) recovery. MI mouse models and hypoxia-injured cardiomyocytes were reproduced to evaluate YXS efficacy. The pharmacological targets and blood-absorbed compounds of YXS were determined by network pharmacology and LC–MS, respectively. Bioactive components were screened via molecular docking and surface plasmon resonance (SPR), and mechanisms were validated by molecular assays. YXS improved cardiac function and reduced infarct size. These effects were linked to preserved mitochondrial homeostasis and reduced apoptosis through the SHP1/JAK2/STAT3 pathway. Dihydrotanshinone Ⅰ (DHT), a key compound identified in plasma, suppressed SHP1, activated STAT3, and mitigated mitochondrial injury. SHP1 overexpression could abolish DHT’s protection effects. Taken together, YXS could exert cardioprotection in MI by modulating mitochondrial function and apoptosis via the SHP1/JAK2/STAT3 axis, and DHT is potential beneficial bioactive ingredient mediating these effects. The online version contains supplementary material available at 10.1186/s13020-025-01299-4. ## Linked entities - **Genes:** PTPN6 (protein tyrosine phosphatase non-receptor type 6) [NCBI Gene 5777], JAK2 (Janus kinase 2) [NCBI Gene 3717], STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] - **Chemicals:** DHT (PubChem CID 10635) - **Diseases:** myocardial infarction (MONDO:0005068) - **Species:** Mus musculus (taxon 10090) ## Full-text entities - **Genes:** Bbc3 (BCL2 binding component 3) [NCBI Gene 170770] {aka PUMA, PUMA/JFY1}, Tnfsf10 (tumor necrosis factor (ligand) superfamily, member 10) [NCBI Gene 22035] {aka A330042I21Rik, APO-2L, Ly81, TL2, Tnlg6a, Trail}, Ctf1 (cardiotrophin 1) [NCBI Gene 13019] {aka CT-1}, Bax (BCL2 associated X, apoptosis regulator) [NCBI Gene 24887], Bcl2 (BCL2, apoptosis regulator) [NCBI Gene 24224] {aka Bcl-2}, Jak2 (Janus kinase 2) [NCBI Gene 16452] {aka Fd17}, Casp3 (caspase 3) [NCBI Gene 25402] {aka CPP32-beta, Lice, Yama}, Ptpru (protein tyrosine phosphatase receptor type U) [NCBI Gene 19273] {aka Ftp-1, PCP-2, PTP, PTP-lambda, PTPlambda, Pcp2}, Anxa5 (annexin A5) [NCBI Gene 25673] {aka Anx5, CPB-I, LC5}, Bcl2l1 (BCL2-like 1) [NCBI Gene 12048] {aka Bcl(X)L, Bcl-XL, Bcl2l, BclX, bcl-x, bcl2-L-1}, Pmaip1 (phorbol-12-myristate-13-acetate-induced protein 1) [NCBI Gene 58801] {aka Noxa}, Jak1 (Janus kinase 1) [NCBI Gene 16451] {aka BAP004, C130039L05Rik}, Fadd (Fas associated via death domain) [NCBI Gene 14082] {aka Mort1/FADD}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Mcl1 (myeloid cell leukemia sequence 1) [NCBI Gene 17210] {aka Gm52627, Mcl-1}, Ptpn6 (protein tyrosine phosphatase, non-receptor type 6) [NCBI Gene 15170] {aka 70Z-SHP, Hcph, PTPTY-42, Ptp1C, SH-PTP1, SHP-1}, Actb (actin, beta) [NCBI Gene 11461] {aka Actx, E430023M04Rik, beta-actin}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, Stat3 (signal transducer and activator of transcription 3) [NCBI Gene 20848] {aka 1110034C02Rik, Aprf}, Cntf (ciliary neurotrophic factor) [NCBI Gene 12803], Jak3 (Janus kinase 3) [NCBI Gene 16453] {aka fae, wil}, Hsp90aa1 (heat shock protein 90, alpha (cytosolic), class A member 1) [NCBI Gene 15519] {aka 86kDa, 89kDa, Hsp86-1, Hsp89, Hsp90, Hspca}, Ndufs1 (NADH:ubiquinone oxidoreductase core subunit S1) [NCBI Gene 227197] {aka 5830412M15Rik, 9930026A05Rik}, Stat3 (signal transducer and activator of transcription 3) [NCBI Gene 25125], Lif (leukemia inhibitory factor) [NCBI Gene 16878], Tyk2 (tyrosine kinase 2) [NCBI Gene 54721] {aka JTK1}, Nr0b2 (nuclear receptor subfamily 0, group B, member 2) [NCBI Gene 23957] {aka SHP, SHP-1, Shp1}, Ldha (lactate dehydrogenase A) [NCBI Gene 16828] {aka Ldh1, Ldhm, l7R2}, Stat1 (signal transducer and activator of transcription 1) [NCBI Gene 20846] {aka 2010005J02Rik}, Bcl2l11 (BCL2 like 11) [NCBI Gene 12125] {aka 1500006F24Rik, Bim, Bod, bcl2-L-11}, Trp53 (transformation related protein 53) [NCBI Gene 22059] {aka Tp53, bbl, bfy, bhy, p44, p53}, Blnk (B cell linker) [NCBI Gene 17060] {aka BASH, Bca, Ly-57, Ly57, Lyw-57, SLP-65}, Bak1 (BCL2-antagonist/killer 1) [NCBI Gene 12018] {aka Bak, N-BAK1, N-Bak}, Ptpn6 (protein tyrosine phosphatase, non-receptor type 6) [NCBI Gene 116689] {aka Ptph6, Shp-1}, Bcl2 (B cell leukemia/lymphoma 2) [NCBI Gene 12043] {aka Bcl-2, C430015F12Rik, D630044D05Rik, D830018M01Rik}, Cat (catalase) [NCBI Gene 12359] {aka 2210418N07, Cas-1, Cas1, Cs-1}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Casp8 (caspase 8) [NCBI Gene 12370] {aka CASP-8, FLICE, MACH, Mch5}, Il11 (interleukin 11) [NCBI Gene 16156] {aka IL-11}, Dntt (deoxynucleotidyltransferase, terminal) [NCBI Gene 21673] {aka Tdt}, Stat6 (signal transducer and activator of transcription 6) [NCBI Gene 20852], Jak2 (Janus kinase 2) [NCBI Gene 24514], Casp3 (caspase 3) [NCBI Gene 12367] {aka A830040C14Rik, AC-3, CASP-3, CC3, CPP-32, CPP32}, Bax (BCL2-associated X protein) [NCBI Gene 12028] - **Diseases:** ischemia (MESH:D007511), necrosis (MESH:D009336), myocardial apoptosis (MESH:D065703), age-related disorders (MESH:D008569), OCR (MESH:D000860), MOMP (MESH:D015433), NRCMs (MESH:D007232), hypoxic (MESH:D002534), Heart Failure (MESH:D006333), infarct (MESH:D007238), cardiac remodeling (MESH:D020257), cardiac hypertrophy (MESH:D006332), myocardial injury (MESH:D009202), chest pain (MESH:D002637), coronary artery disease (MESH:D003324), CVDs (MESH:D002318), AMI (MESH:D009203), cancer (MESH:D009369), ischemic (MESH:D002545), IHD (MESH:D017202), angina pectoris (MESH:D000787), thrombotic occlusion of coronary arteries (MESH:D054059), inflammatory (MESH:D007249), cardiovascular and neurodegenerative diseases (MESH:D019636), reperfusion injury (MESH:D015427), cardiomyocyte loss (MESH:D016388), myocardial fibrosis (MESH:D005355), PCD (MESH:D003643), Coronary heart disease (MESH:D003327), ETC (MESH:D028361) - **Chemicals:** Tween-20 (MESH:D011136), PBS (MESH:D007854), eosin (MESH:D004801), glutaraldehyde (MESH:D005976), alkaloids (MESH:D000470), SDS (MESH:D012967), PVDF (MESH:C024865), DMSO (MESH:D004121), 4,6-diamidino-2-phenylindole (MESH:C007293), polyketides (MESH:D061065), glucose (MESH:D005947), ROS (MESH:D017382), EDC (MESH:C024565), FCCP (MESH:D002259), calcium (MESH:D002118), oligomycin (MESH:D009840), tyrosine (MESH:D014443), Ginsenoside Rd (MESH:C049863), ATP (MESH:D000255), water (MESH:D014867), Salvianolic acid B (MESH:C076944), tanshinone (MESH:C021751), Danshen Dripping Pill (MESH:C000604051), N-Hydroxysuccinimide (MESH:C001426), Co (MESH:D003035), CO2 (MESH:D002245), rotenone (MESH:D012402), arachidonic acid (MESH:D016718), paraformaldehyde (MESH:C003043), antimycin A (MESH:D000968), Agarose (MESH:D012685), terpenoids (MESH:D013729), Phenylmethyl sulfonyl fluoride (MESH:D010664), dUTP (MESH:C027078), shikimates (MESH:C000723335), 5-bromo-2'-deoxyuridine (MESH:D001973), salvianolic acids (MESH:C568740), N2 (MESH:D009584), tribromoethanol (MESH:C062527), amino acids (MESH:D000596), MTT (MESH:C070243), Carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (MESH:C108897), IP (MESH:C041508), Triton X-100 (MESH:D017830), uranyl acetate (MESH:C005460), acetonitrile (MESH:C032159), fatty acids (MESH:D005227), streptomycin (MESH:D013307), Paraffin (MESH:D010232), Ginsenoside (MESH:D036145), 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide (-), D- (MESH:D003903), H&E (MESH:D006371), methanol (MESH:D000432), p (MESH:D010758), PI (MESH:D010716), K (MESH:D011188), DHT (MESH:C000713095), formic acid (MESH:C030544), osmium tetroxide (MESH:D009993) - **Species:** Salvia miltiorrhiza (Chinese salvia, species) [taxon 226208], Schisandra chinensis (Chinese magnolia-vine, species) [taxon 50507], Ophiopogon japonicus (species) [taxon 100506], Panax ginseng (Asiatic ginseng, species) [taxon 4054], Rattus norvegicus (brown rat, species) [taxon 10116], Mus musculus (house mouse, species) [taxon 10090], Ligusticum chuanxiong [taxon 49555], Crataegus pinnatifida (Chinese hawthorn, species) [taxon 510735], Astragalus membranaceus (species) [taxon 649199] - **Cell lines:** H9C2 — Rattus norvegicus (Rat), Spontaneously immortalized cell line (CVCL_0286), fibroblasts — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0594), XF — Xenopus laevis (African clawed frog), Spontaneously immortalized cell line (CVCL_6E64) ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12958654/full.md ## Figures 7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12958654/full.md --- Source: https://tomesphere.com/paper/PMC12958654