Chi Teng Vong

Spinal cord injury is a neurological disorder resulting from trauma, typically affecting sensory and motor function at the injury site, even leading to paralysis and internal dysfunction. The treatment of spinal cord injury mainly relies on pharmacological and surgical interventions; however, significant challenges remain in the protection and repair of neural tissues. Autophagy, an intracellular process responsible for the degradation and recycling of macromolecular components, plays a vital role in spinal cord injury, alleviating the severity of injury by inhibiting cell apoptosis and inflammatory responses. In this review, we provide an overview of the physiological mechanisms underlying autophagy and spinal cord injury and detail the crosstalk between autophagy and other modes of cell death in spinal cord injury. In addition, we discuss the potential of targeting autophagy as a therapeutic strategy for spinal cord injury through approaches that focus on promoting or inhibiting this process, targeting specific autophagic substrates or pathways, and combining autophagy modulation with other neuroprotective or restorative interventions. In summary, this review proposes that strict regulation of autophagy may represent a viable strategy for the treatment of spinal cord injury.

Diabetes mellitus is a chronic metabolic disorder, which is characterized by high blood glucose levels, and this can lead to serious diabetic complications. According to the World Health Organization, approximately 830 million adults worldwide are living with diabetes in 2024, with its prevalence continuing to rise steadily over the years. To treat this disease, researchers have developed a variety of first-line drugs, such as sulfonylureas and thiazolidinediones. Despite their long clinical use, there are still many drawbacks and limitations. One of the main drawbacks is low bioavailability, this causes the diabetic patients to take the drugs frequently to lower the blood glucose levels continuously. Some patients may have to take multiple drugs to increase the effectiveness of lowering blood glucose levels. To address these limitations, nano-based drug delivery systems have emerged to overcome these problems. It has emerged as a promising approach for diabetes management, which offers controlled and localized release of anti-diabetic drugs, thus enhancing therapeutic efficacy. This review discusses recent advances in the field of nano-based drug delivery systems for diabetes management, safety and toxicity profiles of anti-diabetic drugs, and future perspectives for the development of nanomedicine in diabetic treatment. Literature search was conducted using electronic databases, and only English literatures were used and published between 2014 and 2024. Recent advancements in nanotechnology have facilitated the development of various nanocarriers, such as polymeric carrier nanoparticles, nanoliposomes, nanocrystals, nanosuspension and inorganic nanoparticles, which enhance drug stability, bioavailability, and efficacy. These systems can deliver anti-diabetic drugs and natural compounds more effectively, thereby minimizing side effects and improving patient compliance. As the field continues to evolve, the successful clinical implementation of nanodrugs could revolutionize the management of diabetes and improve the quality of life for millions of diabetic patients worldwide.

Objective: Cinnamic acid (CA) is a bioactive compound isolated from cinnamon. It has been demonstrated to ameliorate inflammation and metabolic diseases, which are associated with endothelial dysfunction. This study was aimed to study the potential protective effects of CA against diabetes-associated endothelial dysfunction and its underlying mechanisms. Methods: High-fat diet (HFD) with 60 kcal% fat was used to induce obesity/diabetes in C57BL/6 mice for 12 weeks. These diet-induced obese (DIO) mice were orally administered with CA at 20 or 40 mg/kg/day, pioglitazone (PIO) at 20 mg/kg/day or same volume of vehicle during the last 4 weeks. Isolated mouse aortic segments and primary culture rat aortic endothelial cells (RAECs) were induced with high glucose (HG) to mimic hyperglycemia and co-treated with different concentrations of CA. Results: In DIO mice, four-week administration of CA, particularly at 40 mg/kg/day, diminished the body weights, blood pressure, fasting blood glucose and plasma lipid levels, and ameliorated endothelium-dependent relaxations (EDRs) and oxidative stress in aortas. The beneficial effects of CA were comparable to the positive control group, PIO. Western blotting results indicated that CA treatment upregulated the expression of peroxisome proliferator-activated receptor delta (PPARδ), and activated nuclear factor erythroid 2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1) and AMP-activated protein kinase (AMPK)/ protein kinase B (Akt)/ endothelial nitric oxide synthase (eNOS) signaling pathways in mouse aortas in vivo and ex vivo. HG stimulation impaired EDRs in mouse aortas and inhibited nitric oxide (NO) production but elevated reactive oxygen species (ROS) levels in RAECs. CA reversed these impairments. Importantly, PPARδ antagonist GSK0660 abolished the vasoprotective effects of CA. Molecular docking analysis suggested a high likelihood of mutual binding between CA and PPARδ. Conclusion: CA protects against endothelial dysfunction and oxidative stress in diabetes and obesity by targeting PPARδ through Nrf2/HO-1 and Akt/eNOS signaling pathways.

Ginsenoside Rk1, one kind of ginsenoside, is a minor ginsenoside found in Panax ginseng and used as traditional Chinese medicine for centuries. It exhibits anti-tumor and anti-aggregation effects. However, little research has been done on its effect on endothelial function. This study investigated whether ginsenoside Rk1 improved endothelial dysfunction in diabetes and the underlying mechanisms in vivo and in vitro. Male C57BL/6 mice were fed with a 12 week high-fat diet (60% kcal % fat), whereas treatment groups were orally administered with ginsenoside Rk1 (10 and 20 mg per kg per day) in the last 4 weeks. Aortas isolated from C57BL/6 mice were induced by high glucose (HG; 30 mM) and co-treated with or without ginsenoside Rk1 (1 and 10 μM) for 48 h ex vivo. Moreover, primary rat aortic endothelial cells (RAECs) were cultured and stimulated by HG (44 mM) to mimic hyperglycemia, with or without the co-treatment of ginsenoside Rk1 (10 μM) for 48 h. Endothelium-dependent relaxations of mouse aortas were damaged with elevated oxidative stress and downregulation of three isoforms of peroxisome proliferator-activated receptors (PPARs), PPAR-α, PPAR-β/δ, and PPAR-γ, as well as endothelial nitric oxide synthase (eNOS) phosphorylation due to HG or high-fat diet stimulation, which also existed in RAECs. However, after the treatment with ginsenoside Rk1, these impairments were all ameliorated significantly. Moreover, the vaso-protective and anti-oxidative effects of ginsenoside Rk1 were abolished by PPAR antagonists (GSK0660, GW9662 or GW6471). In conclusion, this study reveals that ginsenoside Rk1 ameliorates endothelial dysfunction and suppresses oxidative stress in diabetic vasculature through activating the PPAR/eNOS pathway.

Hyperglycemia induces chronic stresses, such as oxidative stress and endoplasmic reticulum (ER) stress, which can result in [ ]-cell dysfunction and development of Type 2 Diabetes Mellitus (T2DM). Ginsenoside Rk1 is a minor ginsenoside isolated from Ginseng. It has been shown to exert anti-cancer, anti-inflammatory, anti-oxidant, and neuroprotective effects; however, its effects on pancreatic cells in T2DM have never been studied. This study aims to examine the novel effects of Ginsenoside Rk1 on ER stress-induced apoptosis in a pancreatic [ ]-cell line MIN6 and HFD-induced diabetic pancreas, and their underlying mechanisms. We demonstrated that Ginsenoside Rk1 alleviated ER stress-induced apoptosis in MIN6 cells, which was accomplished by directly targeting and activating insulin-like growth factor 1 receptor (IGF-1R), thus activating the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/Bcl-2-associated agonist of cell death (Bad)-B-cell lymphoma-2 (Bcl-2) pathway. This pathway was also confirmed in an HFD-induced diabetic pancreas. Meanwhile, the use of the IGF-1R inhibitor PQ401 abolished this anti-apoptotic effect, confirming the role of IGF-1R in mediating anti-apoptosis effects exerted by Ginsenoside Rk1. Besides, Ginsenoside Rk1 reduced pancreas weights and increased pancreatic insulin contents, suggesting that it could protect the pancreas from HFD-induced diabetes. Taken together, our study provided novel protective effects of Ginsenoside Rk1 on ER stress-induced [ ]-cell apoptosis and HFD-induced diabetic pancreases, as well as its direct target with IGF-1R, indicating that Ginsenoside Rk1 could be a potential drug for the treatment of T2DM.

Gastrodia elata Bl., one of the well-known edible plants in China, belongs to the family of Orchidaceae. In recent years, the consumption rate of this plant as food supplements or health products is gradually rising in China. However, the traditional industrialization processing procedures (TP) for this plant was found to be too complicated and not friendly to the environment with time and energy consuming. Hence, we investigated whether the processing procedures could be simplified without affecting its overall chemical profile and anti-oxidation activity. In this experiment, a new processing procedure (NP) was designed for processing this plant, and the chemical compositions of the extract for Gastrodia elata produced by two different processing procedures were identified by UPLC-Q-TOF/MS. It was found that phenols and parisins were the most abundant chemical components for this extract. Among all the identified components, the contents of gastrodin and its citric acid derivatives were obviously higher than that of other components. Therefore, the contents of six gastrodin derivatives and ethanol soluble extract rate for Gastrodia elata produced by two different processing procedures, traditional and newly designed processing procedures, were further comparatively investigated for the validation of the applicability. The DPPH radical scavenging activities of the extract from Gastrodia elata produced by two different processing procedures were also investigated. The results demonstrated that the contents of gastrodin and p-hydroxybenzyl alcohol in all samples were slightly decreased in NP samples compared with that of TP samples (except batches of S3 and S6 samples), but no significant difference was observed between these two groups (p = 0.8273 for gastrodin and p= 0.2320 for p-hydroxybenzyl alcohol). Additionally, the total contents of parisins were also in a decreased trend in NP samples but with no significant difference when comparing with that in TP samples (p = 0.1721). The results for ethanol soluble extract rate also had the same situation (p = 0.1094). Taken together, it was suggested that the chemical profiles and contents of gastrodin derivatives and ethanol soluble extract rate for NP samples was not significant different to that of TP samples. The DPPH radical scavenging activity of the extract of Gastrodia elata produced with NP method was not significant different from that of TP samples. As a result, the industrial processing procedures for the preservation of this material plant could be simplified to a more time and energy saving procedure without changing the quality of the products, which is also consistent with the concept of green and sustainable industrial production.

Jatrorrhizine (JAT) is one of the major bioactive protoberberine alkaloids found in rhizoma coptidis, which has hypoglycemic and hypolipidemic potential. This study aimed to evaluate the vasoprotective effects of JAT in diabetes and obesity and the underlying mechanism involved. Mouse aortas, carotid arteries and human umbilical cord vein endothelial cells (HUVECs) were treated with risk factors (high glucose or tunicamycin) with and without JAT ex vivo and in vitro. Furthermore, aortas were obtained from mice with chronic treatment: (1) control; (2) diet-induced obese (DIO) mice fed a high-fat diet (45% kcal% fat) for 15 weeks; and (3) DIO mice orally administered JAT at 50 mg/kg/day for the last 5 weeks. High glucose or endoplasmic reticulum (ER) stress inducer tunicamycin impaired acetylcholine-induced endothelium-dependent relaxations (EDRs) in mouse aortas, induced oxidative stress in carotid arteries and HUVECs, downregulated phosphorylations of Akt at Ser473 and eNOS at Ser1177 and enhanced ER stress in mouse aortas and HUVECs, and these impairments were reversed by cotreatment with JAT. JAT increased NO release in high-glucose-treated mouse aortas and HUVECs. In addition, chronic JAT treatment restored endothelial function with EDRs comparable to the control, increased Akt/eNOS phosphorylation, and attenuated ER stress and oxidative stress in aortas from DIO mice. Blood pressure, glucose sensitivity, fatty liver and its morphological change, as well as plasma levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and plasma lipid profile, were also normalized by JAT treatment. Collectively, our data may be the first to reveal the vasoprotective effect of JAT that ameliorates endothelial dysfunction in diabetes and obesity through enhancement of the Akt/eNOS pathway and NO bioavailability, as well as suppression of ER stress and oxidative stress.