Asghar Aqsa, Qasim Muhammad, Noor Fatima, Ashfaq Usman Ali, Tahir Ul Qamar Muhammad, Masoud Muhammad Shareef, Bhatti Rashid, Almatroudi Ahmad, Alrumaihi Faris, Allemailem Khaled S
Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan.
National Centre of Excellence in Molecular Biology, The University of Punjab, Lahore, Pakistan.
Nat Prod Res. 2023 Nov-Dec;37(22):3733-3740. doi: 10.1080/14786419.2023.2252565. Epub 2023 Sep 4.
Congestive cardiac failure (CCF) is a pathophysiologic state when the heart is not able to maintain its cardiac output to meet the demand of metabolising tissues. CCF is responsible for approximately 2.9 million deaths worldwide. The heterogeneous nature of CCF draws the attention of researchers to find more enthralling and promising diagnostic and treatment options. (Arjuna) is an evergreen, deciduous tree exhibited various astringent, anti-bacterial, and anti-microbial properties. is being used in various regions for anginal pain, hypertension, congestive heart failure, and dyslipidemia. Although previous studies have demonstrated the therapeutic potential of , the exact molecular mechanism underlying its protective effect on the heart remains unclear. In this study, a network pharmacology technique was used to explore the active ingredients, potential targets in for the treatment of CCF. In the framework of this study, we explored the active ingredient-target-pathway network and figured out that oleanolic acid, arjunolic acid, luteolin, kaempferol, cholesterol, ellagic acid 4-O-xylopyranoside 3,3'-dimethyl ether, and cyclohexyl (2,4-dimethyl phenyl) methanone contributed significantly to the development of CCF by affecting AKT1, MAPK14, TNF, IL6, ESR1, and HSP90AA1 genes. Molecular docking analysis further validated the activities of these compounds against potential targets. To sum up, integrated network pharmacology and docking analysis revealed that exerts its cardioprotective effect by acting on various signalling pathways, including the thyroid hormone, VEGF signalling pathway, AGE-RAGE signalling pathway in diabetic complications, HIF signalling pathway, sphingolipid signalling pathway, and oestrogen signalling pathways. Overall, this study provides valuable insights into the molecular mechanism of in CCF and highlights its potential as a promising preventive treatment for this condition.
充血性心力衰竭（CCF）是一种病理生理状态，即心脏无法维持其心输出量以满足代谢组织的需求。CCF在全球范围内导致约290万人死亡。CCF的异质性促使研究人员关注寻找更具吸引力和前景的诊断与治疗方案。（Arjuna）是一种常绿落叶乔木，具有多种收敛、抗菌和抗微生物特性。它在各个地区被用于治疗心绞痛、高血压、充血性心力衰竭和血脂异常。尽管先前的研究已经证明了（Arjuna）的治疗潜力，但其对心脏保护作用的确切分子机制仍不清楚。在本研究中，采用网络药理学技术探索（Arjuna）治疗CCF的活性成分、潜在靶点。在本研究框架内，我们探索了活性成分-靶点-通路网络，发现齐墩果酸、阿朱那酸、木犀草素、山奈酚、胆固醇、鞣花酸4-O-木糖吡喃糖苷3,3'-二甲醚和环己基（2,4-二甲基苯基）甲酮通过影响AKT1、MAPK14、TNF、IL6、ESR1和HSP90AA1基因对CCF的发展有显著影响。分子对接分析进一步验证了这些化合物对潜在靶点的活性。综上所述，综合网络药理学和对接分析表明，（Arjuna）通过作用于多种信号通路发挥其心脏保护作用，包括甲状腺激素、VEGF信号通路、糖尿病并发症中的AGE-RAGE信号通路、HIF信号通路、鞘脂信号通路和雌激素信号通路。总体而言，本研究为（Arjuna）在CCF中的分子机制提供了有价值的见解，并突出了其作为这种疾病有前景的预防性治疗方法的潜力。
