Mechanistic insights and therapeutic potential of astilbin and apigenin in diabetic cardiomyopathy
Sachin Dhiman,
Sanchit Dhankhar,
Anjali Garg,
Manni Rohilla,
Monika Saini,
Thakur Gurjeet Singh,
Samrat Chauhan,
Samy Selim,
Soad K. Al Jaouni,
Sabina Yasmin,
Naseem Begum,
Aziza Alshahrani,
Mohammad Yousuf Ansari
Affiliations
Sachin Dhiman
Department of Pharmacology, Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, 140401, India
Sanchit Dhankhar
Department of Pharmacology, Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, 140401, India
Anjali Garg
Department of Pharmacology, Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, 140401, India; Swami Devi Dyal College of Pharmacy, GolpuraBarwala, Panchkula, Haryana, 134118, India
Manni Rohilla
Department of Pharmacology, Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, 140401, India; Swami Vivekanand College of Pharmacy, Ram Nagar, Banur, Punjab, 140601, India
Monika Saini
Swami Vivekanand College of Pharmacy, Ram Nagar, Banur, Punjab, 140601, India; M.M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, Haryana, 133206, India
Thakur Gurjeet Singh
Department of Pharmacology, Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, 140401, India
Samrat Chauhan
Department of Pharmacology, Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, 140401, India; Corresponding author.
Samy Selim
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, 72388, Saudi Arabia
Soad K. Al Jaouni
Department of Hematology/Oncology, Yousef Abdulatif Jameel Scientific Chair of Prophetic Medicine Application, Faculty of Medicine, King Abdulaziz University, Jeddah, 21589, Saudi Arabia
Sabina Yasmin
Department of Pharmaceutical Chemistry, College of Pharmacy, King Khalid University, Abha, 62529, Saudi Arabia
Naseem Begum
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, 62529, Saudi Arabia
Aziza Alshahrani
Department of Pharmacology, College of Pharmacy, King Khalid University, Abha, 62529, Saudi Arabia
Mohammad Yousuf Ansari
M.M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, Haryana, 133206, India; Corresponding author. MM College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, Haryana, 133207, India.
Diabetic cardiomyopathy (DCM) represents a critical complication of Diabetes mellitus (DM), characterized by structural and functional changes in the myocardium independent of coronary artery disease or hypertension. Emerging evidence highlights the significant roles of phytochemicals, particularly astilbin and apigenin, in modulating key molecular pathways implicated in DCM. This review synthesizes current mechanistic insights and therapeutic potential of these compounds, focusing on their interactions with AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptors (PPARs), O-linked N-acetylglucosamine (O-GlcNAc), sodium-glucose co-transporter 2 (SGLT2), protein kinase C (PKC), nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) pathways. Astilbin and apigenin have demonstrated the ability to improve cardiac function, mitigate oxidative stress, and reduce inflammatory responses in diabetic conditions. By activating AMPK and PPARs, these flavonoids enhance glucose uptake and fatty acid oxidation, contributing to improved metabolic homeostasis. Their inhibition of O-GlcNAcylation, SGLT2 activity, and PKC signaling further attenuates hyperglycemia-induced cellular damage. Additionally, suppression of NF-κB, MAPK, and JNK pathways by astilbin and apigenin results in reduced pro-inflammatory cytokine production and apoptotic cell death. Collectively, these interactions position astilbin and apigenin as promising therapeutic agents for ameliorating DCM, offering novel avenues for treatment strategies aimed at modulating multiple pathogenic pathways.
