Current research on how active metabolites of TCM modulate mitochondrial dysfunction in the prevention and treatment of IBD is summarized, providing new insights into the pathogenesis of the disease and opening up new avenues and strategies for the prevention, treatment, and research on IBD treatment with TCM.
Abstract
Inflammatory Bowel Disease (IBD) is a chronic relapsing inflammatory condition of the intestine, characterized by symptoms such as chronic diarrhea, abdominal pain, and weight loss. The pathogenesis of IBD is complex, with mitochondrial dysfunction being considered a key factor in its onset, progression, and persistence. Mitochondria, as the primary energy suppliers within cells, not only produce adenosine triphosphate (ATP) but also play crucial roles in regulating cellular metabolism, maintaining redox balance, and controlling cell death processes. Targeting mitochondria to regulate mitochondrial functions, including energy metabolism, oxidative stress, mitophagy, dynamics, and biogenesis, as well as maintaining the dynamic balance of the “gut microbiota-mitochondria axis,” has emerged as a promising strategy for the prevention and treatment of IBD. Traditional Chinese Medicine (TCM) has shown potential multi-target regulatory properties in preclinical studies; however, robust clinical validation and target-specific pharmacological evidence remain limited. This review explores the mechanisms and underlying connections between mitochondrial dysfunction and IBD, summarizing the current research on how active metabolites of TCM modulate mitochondrial dysfunction in the prevention and treatment of IBD. It provides new insights into the pathogenesis of the disease and opens up new avenues and strategies for the prevention, treatment, and research on IBD treatment with TCM.
Diabetic cardiomyopathy (DCM) is a common diabetes-related complication that can progress to heart failure. Early-stage DCM is asymptomatic, requiring advanced imaging for diagnosis, and currently lacks approved targeted therapies, highlighting the urgent need for DCM-specific drugs. Emerging evidence suggests that iron homeostasis imbalance and mitochondrial dysfunction are closely interconnected and synergistically drive DCM onset and progression. This review provides a comprehensive overview of the molecular interplay between ferroptosis and mitochondrial damage in DCM and evaluates the therapeutic potential of three intervention categories: (1) Standard glucose-lowering agents; (2) Novel mechanism-targeted therapies (iron chelators, mitochondrial protectants); and (3) Multi-targeting traditional Chinese medicine (TCM) and their bioactive compounds. While Sodium-glucose co-transporter-2 inhibitors and other antidiabetic drugs provide modest protection against DCM progression, they exhibit limited efficacy, do not fully restore mitochondrial function, and are associated with adverse effects. Emerging targeted therapies such as iron chelators and mitochondrial protectants face safety concerns and lack extensive clinical validation, with their potential drug-drug interactions remaining uncertain. In contrast, selected TCM-derived bioactive compounds have shown cardioprotective potential through multi-target regulation of ferroptosis and mitochondrial homeostasis in preclinical DCM models. Additional TCM with demonstrated efficacy in ferroptosis and mitochondrial function are also reviewed. Given the multifactorial nature of DCM, combination therapies targeting ferroptosis and mitochondrial dysfunction may offer superior outcomes. Future drug development should prioritize agents - whether synthetic or natural - that precisely regulate these interrelated pathways, enabling personalized treatment strategies for DCM.
Yiting Tang, Qian Wu, Yu-Peng Chen et al.· World Journal of Diabetes· 0 citations
Mitochondrial dysfunction has emerged as a convergent pathogenic mechanism across inflammatory and degenerative disorders, functioning not as a passive consequence but as an active amplifier of tissue injury, immune dysregulation, and impaired repair. Consistently observed mitochondrial abnormalities include excessive reactive oxygen species production, impaired oxidative phosphorylation, defective mitophagy, altered fission-fusion dynamics, and release of mitochondrial danger-associated molecular patterns, particularly cell-free mitochondrial DNA (cf-mtDNA), which serves both as a proinflammatory mediator and a potential circulating biomarker of disease activity. These alterations create self-reinforcing networks in which mitochondrial stress promotes innate immune activation, sustains inflammatory signaling, and accelerates structural or functional decline in vulnerable tissues. Mitochondria-targeted pharmacology has expanded rapidly, encompassing organelle-directed antioxidants, modulators of mitochondrial quality control, biogenesis or metabolic enhancers, nano-enabled delivery platforms, and emerging mitochondrial replacement strategies. Despite strong mechanistic appeal and encouraging preclinical data, clinical translation remains limited by the absence of validated pharmacodynamic biomarkers, an incomplete understanding of disease endotypes, inconsistent tissue target engagement, delivery barriers to mitochondria-rich compartments, and poor predictive value of animal models for human disease biology. The cf-mtDNA and related mitochondrial signatures are increasingly attracting attention for patient stratification, phenotyping, and therapeutic monitoring, although assay standardization remains unresolved. This review focuses on the core mechanisms that link mitochondrial dysfunction to disease progression. It also examines biomarker development and the major barriers to translation. Emerging approaches such as nanotechnology and mitochondrial replacement are discussed as supplementary strategies, not as the main focus of the review.
L. Elabbasy· Current opinion in pharmacol...· 0 citations
Type 2 diabetes mellitus (T2DM) is fundamentally linked to gut microbiota dysbiosis, a condition that triggers a cascade of pathophysiological changes including aberrant host-microbe co-metabolism, compromised intestinal barrier integrity, and chronic low-grade inflammation, which collectively drive insulin resistance. While conventional therapies have limitations, traditional Chinese medicine (TCM) presents a promising therapeutic strategy. This review comprehensively elucidates the pathophysiological link between gut dysbiosis and T2DM. It then systematically summarizes the multi-target mechanisms by which TCM exerts its therapeutic effects, including: remodeling the gut microbial ecosystem; reprogramming host-microbe co-metabolism of short-chain fatty acids (SCFAs), bile acids (BAs), and branched-chain amino acids (BCAAs); reinforcing the intestinal barrier to mitigate metabolic endotoxemia; and modulating key signaling pathways involved in inflammation and immunity, etc. Key clinical evidence is also summarized. Furthermore, the review critically evaluates the preclinical and clinical evidence supporting these mechanisms, highlighting both therapeutic potential and current challenges, such as the need for standardization. Finally, current limitations and future prospects are considered, proposing a path forward for integrating microbiota-targeted TCM therapies into the modern, evidence-based management of T2DM.
Zhiping Ding, Qunfang Li, Z. Li et al.· Chinese Journal of Natural M...· 0 citations
Mitochondria are indispensable organelles that serve as the powerhouses of cells, playing a crucial role in maintaining cellular energy homeostasis. Consequently, mitochondrial dysfunction is recognized as a key pathogenic factor in a wide range of common diseases, including cardiovascular diseases, neurodegenerative disorders, metabolic syndromes and cancers. Due to their multitarget properties and favorable safety profiles, natural products have shown significant potential for regulating key mitochondrial biological processes, including mitobiogenesis, mitophagy, mitochondrial dynamics (fusion and fission), oxidative phosphorylation, and mitochondria-mediated apoptosis. Therefore, they have become an important resource for mitochondria-targeted therapy. Despite significant progress in mechanistic studies in vitro, translating these findings into clinical applications remains a major challenge. This translational gap is primarily due to unfavorable pharmaceutical properties, such as low bioavailability, poor targeted delivery, and rapid metabolic clearance. Additionally, the precise mechanisms governing mitochondria remain to be fully elucidated. In this review, we systematically summarize the specific mitochondrial pathological phenotypes in various diseases and provide a comprehensive overview of natural products that correspond to these phenotypes, along with their mechanisms of action. We also analyze common challenges associated with the absorption, distribution, metabolism, and excretion of these products. By bridging the gap between basic research and clinical application, this review aims to accelerate the development of novel therapeutic strategies for mitochondria-related diseases.
Xinyue Liu, Hu Li, Xuekai Wang et al.· Chinese Journal of Natural M...· 0 citations
Cancer cachexia is a multifactorial systemic syndrome characterized by progressive muscle loss, with or without adipose tissue depletion, that cannot be reversed by conventional nutritional support. It affects cancer patients and is associated with reduced treatment tolerance, impaired physical function, poor quality of life, and increased mortality. The understanding of cachexia has evolved recently, from the perception of a simple nutritional disorder to a complex immune–metabolic syndrome, based on tumor–host interactions, systemic inflammation, metabolic dysregulation, and multi-organ dysfunction. This review summarizes the progression of cachexia research, highlighting key findings involving inflammatory cytokines, proteolytic pathways, mitochondrial dysfunction, and immune dysregulation. The development of therapeutic strategies is examined, from early nutritional and appetite-stimulating interventions to contemporary targeted therapies, including ghrelin receptor agonists, cytokine inhibitors, and anabolic agents. Despite advances in mechanistic understanding, numerous trials targeting single pathways have failed to produce meaningful functional or survival benefits, underscoring the limitations of reductionist approaches. Emerging evidence supports a paradigm shift toward multimodal, biomarker-guided, and patient-centered interventions that address the interconnected biological mechanisms underlying cachexia. Particular emphasis is given to novel immunomodulatory strategies, including agents such as R-ketorolac, which may restore immune homeostasis and target the root causes of cachexia. It is hypothesized that future therapeutic success will likely depend on integrated approaches combining immunological, metabolic, nutritional, and rehabilitative interventions.
Lingbing Zhang, Jeffrey A. Norton· Cancers· 0 citations
Acute kidney injury (AKI) is a clinically significant syndrome characterized by rapid deterioration of renal function. Despite its complex and multifactorial pathogenesis, effective targeted therapies remain scarce. Mitochondrial dysfunction is increasingly recognized as a central driver of AKI progression. Mitochondrial transcription factor A (TFAM), a nucleus-encoded protein that governs mitochondrial DNA (mtDNA) maintenance, transcription and replication, plays an essential role in preserving mitochondrial integrity and biogenesis. This review systematically synthesizes current knowledge on TFAM biology, with a focus on its structural features, regulatory networks, and dynamic changes in the context of AKI. We integrate evidence showing that TFAM upregulation, whether through pharmacological interventions or genetic manipulation, consistently protects against tubular cell injury, preserves mitochondrial function, and attenuates inflammation across diverse AKI models. By providing a conceptual framework that links TFAM's molecular functions to its pathophysiological roles in the kidney, this review highlights TFAM as a promising therapeutic node. We also identify key knowledge gaps and propose future research directions to facilitate the translation of TFAM-targeted strategies into clinical practice.