Herbs and Phytochemicals in the Fight Against Diabetic Retinopathy: An Emerging Frontier

The Growing Threat of Diabetic Retinopathy
Diabetic retinopathy (DR) is one of the most severe complications arising from diabetes mellitus (DM), posing a significant risk of visual impairment and blindness. As the global prevalence of diabetes escalates, so does the incidence of DR, necessitating the urgent development of effective treatments. DR, characterized by complex pathological changes, presents a formidable challenge for existing therapies. However, a recent Herbs And Phytochemicals study review by researchers from West China Hospital, Sichuan University, Chengdu-China highlights the potential of natural products (NPs) in managing and potentially treating this debilitating condition.


Phytochemicals That Can Be Used To Treat Diabetic Retinopathy
 
The Pathophysiology of Diabetic Retinopathy
Understanding the pathophysiological changes in Diabetic retinopathy is essential for developing effective treatments. Chronic hyperglycemia, a hallmark of diabetes, triggers a cascade of physiological and biochemical alterations in the retina, leading to microvascular injury and retinal dysfunction. Key pathological features of DR include:
 
-Microaneurysms and Hemorrhages: Persistent high blood glucose levels induce the formation of microaneurysms and hemorrhages in the retinal blood vessels.

-Increased Vascular Permeability: The retinal basement membrane thickens, increasing the permeability of the blood-retina barrier (BRB) and causing leakage from retinal vessels.
 
-Retinal Hypoxia and Neovascularization: Capillary occlusion and subsequent retinal hypoxia stimulate the production of vascular endothelial growth factor (VEGF), leading to neovascularization, a hallmark of proliferative diabetic retinopathy (PDR).
 
-Diabetic Macular Edema (DME): Disruption of the BRB results in fluid accumulation in the macula, causing increased macular thickness and edema.
 
-Inflammation and Oxidative Stress: Central Players in Diabetic retinopathy
Inflammation and oxidative stress are pivotal in the progression of DR. Inflammatory factors such as tumor necrosis factor-alpha (TNF-α) and interleukins are consistently elevated in Diabetic retinopathy patients and animal models, contributing to retinal damage. Moreover, chronic hyperglycemia leads to the excessive production of reactive oxygen species (ROS), overwhelming the retina's antioxidant defenses and exacerbating oxidative stress.
 
Current Treatments and Their Limitations
The current therapeutic landscape for DR includes:
 
-Medications: Drugs to control blood glucose, hypertension, and lipid levels.
Anti-VEGF Injections: These are used to inhibit retinal neovascularization and reduce macular edema but require frequent administration and can have side effects.
 
-Laser Photocoagulat ion: This procedure helps reduce the risk of vision loss in DME patients but can cause central visual loss and other complications.
 
-Vitrectomy: A surgical intervention for advanced PDR complicated by vitreous hemorrhage or retinal detachment.
 
Despite these treatments, many patients do not achieve satisfactory visual recovery, highlighting the need for novel therapeutic strategies.
 
Natural Products or Phytochemicals: A Promising Avenue for Diabetic retinopathy Management
Emerging research suggests that natural products (NPs) could offer effective treatments for DR, thanks to their anti-inflammatory, antioxidant, anti-neovascular, and anti-apoptotic properties. Here's a closer look at some key NPs and their potential roles in DR treatment:
 
-Astragaloside-IV
Astragaloside-IV (AS-IV), a bioactive agent from Astragalus membranaceus, exhibits potent antioxidant capacity. Research indicates that AS-IV can reduce inflammation, inhibit apoptosis, and enhance retinal cell survival by modulating the PI3K/AKT and Sirt1/Nrf2 pathways. Studies in diabetic rat models have shown that AS-IV administration can increase retinal thickness and alleviate histopathological changes associated with Diabetic retinopathy.
 
-Resveratrol
Resveratrol, a polyphenolic compound, has demonstrated significant ROS-scavenging efficacy. In diabetic rat models, resveratrol reduces inflammation, oxidative stress, and apoptosis in retinal cells. It modulates multiple genes and proteins related to apoptotic pathways and has shown promising results in reducing hyperglycemia and improving energy metabolism.
 
-Astaxanthin
Astaxanthin (ASX), known for its anticancer and antioxidant functions, has shown potential in increasing retinal thickness and reducing pericyte apoptosis in diabetic models. ASX enhances the expression of antioxidant enzymes and mitigates Diabetic retinopathy-related damage by decreasing the production of advanced glycation end products (AGEs).
 
-Quercetin
Quercetin, a flavonoid found in various vegetables and fruits, exerts anti-inflammatory, antioxidant, and neuroprotective effects. In diabetic rats, quercetin supplementation has been shown to protect retinal neurons against oxidative stress and apoptosis, highlighting its potential in Diabetic retinopathy management.
 
-Berberine
Berberine (BBR), an alkaloid from Rhizoma Coptidis, has shown extensive medical value, including anticancer and antibacterial effects. In diabetic mouse models, BBR has been found to improve retinopathy, reduce neovascularization, and decrease neuronal injury, complementing insulin therapy.
 
Challenges and Future Directions
Despite the promising potential of NPs in Diabetic retinopathy treatment, several challenges remain. The clinical application of NPs is hindered by suboptimal specificity, poor bioavailability, and potential toxicity. Prospective clinical studies are imperative to validate the therapeutic potential of NPs in delaying or preventing Diabetic retinopathy.
 
Improving Bioavailability and Targeting
One major challenge in the clinical use of NPs is their bioavailability. Innovative drug delivery systems, such as nano-synthetic drugs, are being explored to improve the safety and efficacy of NP delivery. For example, quercetin's high oral dose requirement and limited bioavailability have led researchers to develop Fe-Quer nanozymes (NZs), which show increased delivery efficacy and robust ROS scavenging capabilities.
 
Safety and Drug-Drug Interactions
The safety of NPs remains a primary concern. While NPs are generally considered to have lower toxicity, rigorous clinical trial validation is needed to ensure their safety. Additionally, drug-drug interactions (DDIs) are a significant concern when NPs are used in combination with conventional medicines. Research indicates that NPs can have bidirectional influences on pharmacological agents, potentially enhancing or diminishing their efficacy.
 
Conclusion: A Promising Frontier in Diabetic retinopathy Treatment
DR is a severe complication of diabetes, and its complex pathogenesis makes it challenging to treat effectively with current therapies. Natural products offer a promising avenue for DR management, with their anti-inflammatory, antioxidant, anti-neovascular, and anti-apoptotic properties. However, further research is needed to improve their bioavailability, ensure safety, and validate their efficacy in clinical settings. As the field advances, NPs could become a cornerstone in the prevention and treatment of DR, offering hope for millions of patients worldwide.
 
The findings of the study review were published in the peer reviewed journal: Biomedicines. https://www.mdpi.com/2227-9059/12/6/1138
 
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