The healing power of natural gifts: How the natural herbaceous plants targeting mitophagy can reverse diabetic complications.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetes is a chronic metabolic disorder characterized by a variety of etiological factors that progressively damage various tissues and organs due to prolonged metabolic dysregulation and elevated blood glucose levels. This condition poses significant risks to both physical and mental health. Natural botanical therapeutics are characterized by their "multi-component, multi-target, and multi-pathway" properties, and their safety profiles have been well established, particularly due to their relatively low hepatotoxic and nephrotoxic effects. Consequently, there is a growing preference among researchers for these agents.

AIM OF THE REVIEW: The current review aims to conduct a comprehensive analysis of the ethnopharmacological applications of natural herbaceous plants to mitophagy within the context of diabetic complications.

METHODS: An investigation into natural herbal remedies for diabetic complications was conducted, with a particular emphasis on the regulation of mitophagy. This study utilized traditional medical texts and ethnomedicinal literature as primary sources. Furthermore, relevant information related to ethnobotany, phytochemistry, and pharmacology is obtained from online databases, including PubMed and the China National Knowledge Infrastructure (CNKI), among others. "Diabetic complications", "mitophagy", "natural botanical drugs", "traditional Chinese medicine compounds", "single herbs extracts", and "active metabolites" were used as keywords when searching the databases. Consequently, pertinent articles published in recent years were collected and analyzed.

RESULT: The integration of herbal plants into managing diabetic complications offers several notable advantages, which can be examined from two primary perspectives. Firstly, the molecular mechanisms that regulate mitophagy are influenced by various signaling pathways, including, but not limited to PINK1/Parkin, PI3K/Akt/mTOR, and AMPK/ULK1. Consequently, pharmacological agents targeting a single pathway may encounter challenges in effectively engaging multiple biological processes. Furthermore, an expanding body of research suggests that numerous herbal plants and their bioactive constituents can modulate various biological targets. These compounds appear to interact with several critical targets associated with mitophagy during diabetic complications, such as PINK1, Parkin, LC3B, Beclin1, p62, ATG5, and Drp1. Secondly, herbal plants and their bioactive compounds have exhibited a favorable safety profile, particularly in terms of diminished hepatotoxicity and nephrotoxicity when compared to conventional Western pharmacotherapy. For example, various compound formulations, including Huangqi Danshen decoction, Ginseng Dingzhi decoction, Shexiang Baoxin pill, Tangzhiqing decoction, and Jianpi Xingqi Huoxue decoction, have been utilized in China for centuries, demonstrating promising clinical efficacy. Recently, an increasing number of researchers have sought to isolate active constituents from these clinically effective compound formulations using diverse chemical methodologies. This endeavor is driven by the necessity to address challenges related to complex ingredient compositions and intricate processing methods. The isolated active compounds have been utilized in cellular and animal studies to elucidate the molecular mechanisms that underlie the efficacy of these formulations.

CONCLUSIONS: Numerous traditional compound formulations from China have emerged as promising candidates for the development of pharmacological agents aimed at addressing diabetic complications. Notably, several of these formulations, which focus on the regulation of mitophagy, are currently the subject of extensive research by an increasing number of scholars.