【Abstract】 Objective To investigate the role of sGC-cGMP-PKG signalling Pathway in the amelioration of isoproterenol (ISO)-induced cardiac hypertrophy in mice by aqueous extract of Curcuma kwangsiensis root tubers (GYJS) and the related mechanism. Methods The study involved seventy-two KM male mice, which were randomly divided into six groups: a normal control group, a model group, a propranolol positive control group (40 mg/kg), and three GYJS groups with low (1 g/kg), medium (2 g/kg), and high (4 g/kg) doses. Apart from the control group, mice in each group were subcutaneously injected with ISO (10 mg/kg) on days 1-3 and ISO (5 mg/kg) on days 4-14 to create a mouse cardiac hypertrophy model. After daily subcutaneous injections for 4 hours, the mice in each group were orally administered the corresponding drugs for a dosing cycle of 14 days. The weight of the whole heart and left ventricle in mice was measured. The pathology of mouse myocardial tissues was observed using HE and Masson staining. The expression of GUCY1B3 and TGF-β1 in myocardial tissues was observed using IHC staining. The kit was used to measure serum levels of LDH, CK, and NO, as well as the activity of SOD and the content of MDA in myocardial tissues. Serum levels of cGMP were measured using ELISA, and qPCR was used to determine the content of cGMP. qPCR was also used to determine the content of ANP, BNP, GUCY1B3, PKGⅠ, and PDE5A mRNA expression levels. It is important to adhere strictly to metrics and units when reporting results. Compared to the model group, the propranolol group and each dose group of GYJS significantly reduced the whole heart weight index and left ventricular index of mice (P<0.001 or P<0.0001). They also reversed the hypertrophy of myocardial tissues and myocardial fibrosis of mice and elevated the expression of GUCY1B3 in the myocardial tissues of mice (P<0.05 or P<0.001). The study found that treatment with compound 01) resulted in a significant reduction of TGF-β1 expression (P<0.05 or P<0.01). Additionally, it led to a significant decrease in myocardial injury markers LDH and CK activity (P<0.05 or P<0.01), a significant increase in NO and cGMP content (P<0.05 or P<0.01), a significant decrease in myocardial oxidative stress indicator MDA content (P<0.05 or P<0.01), and a significant increase in SOD activity (P<0.05 or P<0.01).Results Compared with the model group, the propranolol group and each dose group of GYJS could significantly reduce the whole heart weight index and left ventricular index of mice (P<0.001 or P<0.0001), significantly reverse the hypertrophy of myocardial tissues and myocardial fibrosis in mice, significantly elevate the expression of GUCY1B3 in the myocardial tissues of mice (P<0.05 or P<0.01), significantly reduce the expression of TGF-β1 (P <0.05 or P<0.01), myocardial damage markers LDH and CK viability were significantly reduced (P<0.05 or P<0.01), NO and cGMP contents were significantly elevated (P<0.05 or P<0.01), myocardial oxidative stress indicator MDA content was significantly reduced (P<0.05 or P<0.01), SOD viability was significantly increased (P<0.05 or P< 0.01), myocardial hypertrophy markers ANP, BNP and PDEA mRNA expression levels were significantly reduced (P<0.05, P<0.01 or P<0.001), and the mRNA expression of GUCY1B3 and PKG Ⅰ was significantly increased (P<0.01 or P<0.001).Conclusion GYJS may improve cardiac hypertrophy by modulating the sGC-cGMP-PKG signaling pathway.