Biomarkers in diabetic neuropathy.

CONTEXT: The prevalence of diabetic neuropathy is drastically increasing in the world. To halt the progression of diabetic neuropathy, there is an unmet need to have potential biomarkers for the diagnosis and new drug discovery. OBJECTIVE: To study various biomarkers involved in the pathogenesis of diabetic neuropathy. METHODS: The literature was searched with the help of various scientific databases and resources like PubMed, ProQuest, Scopus, and Google scholar from the year 1976 to 2020. RESULTS: Biomarkers of diabetic neuropathy are categorised as inflammatory biomarkers such as MCP-1, VEGF, TRPV1, NF-κB; oxidative biomarkers such as adiponectin, NFE2L2; enzyme biomarkers like NADPH, ceruloplasmin, HO-1, DPP-4, PARP α; miscellaneous biomarkers such as SIRT1, caveolin 1, MALAT1, and microRNA. All biomarkers have a significant role in the pathogenesis of diabetic neuropathy. CONCLUSION: These biomarkers have a potential role in the progression of diabetic neuropathy and can be considered as potential targets for new drug discovery.

Paeonol attenuates retinopathy in streptozotocin-induced diabetes in rats by regulating the oxidative stress and polyol pathway.

The current research work was planned to study the effects of paeonol in the management of diabetic retinopathy. Diabetes was induced in male Sprague Dawley rats using Streptozotocin (55 mg/kg, i.p.). After 4 weeks, the diabetic animals were treated with paeonol at a dose of 50, 100, and 200 mg/kg body weight daily for the next 4 weeks. At the end of treatment, retinal physiology was studied by recording an electroretinogram (ERG); biochemical parameters and oxidative stress were estimated. The histopathology of the retina was also carried out at the end of the study. The ERG of paeonol-treated animals showed a significant improvement in a-wave amplitude, b-wave amplitude, a-wave latency, and b-wave latency (p < 0.001) at 15 cd s/m2 when compared with the diabetic control animals. The paeonol treatment (200 mg/kg) in diabetic animals showed a significant decrease in the plasma glucose level (p < 0.001) when compared to the animals in diabetic control group. Paeonol also significantly decreased the lactate dehydrogenase, aldose reductase, and sorbitol dehydrogenase levels when compared with the diabetic control animals. The oxidative stress in the eye was significantly reduced after the paeonol treatment in the diabetic rats. The histopathology showed a significant reduction (p < 0.05) in the retinal thickness after the paeonol treatment. The results of the study indicate that paeonol can be considered an effective management option for diabetic retinopathy.

Neuroprotective effect of paeonol in streptozotocin-induced diabetes in rats.

BACKGROUND: Diabetic neuropathy is one of the most common microvascular complication of diabetes. It is associated with neuronal dysfunction and pain. Paeonol is an important natural product reported for its antioxidant, anti-inflammatory and antidiabetic activities. AIM: The present research was planned to study effect of paeonol in diabetic peripheral neuropathy in rats. METHODS: Diabetes was induced in Sprague Dawley rats by using Streptozotocin (55 mg/kg, i.p.). After six weeks, diabetic animals were treated daily with paeonol at a dose of 50, 100 and 200 mg/kg for four weeks. At the end of the treatment, plasma glucose, mechanical allodynia, mechanical hyperalgesia, thermal hyperalgesia and nerve conduction velocities were recorded. Oxidative stress parameters were studied in sciatic nerve. Histopathology study of sciatic nerve, NF-κB and MCP-1 expression were also studied at the end of study. KEY FINDINGS: Paeonol treatment significantly lowered the plasma glucose levels, mechanical allodynia, mechanical hyperalgesia and thermal hyperalgesia as compared to diabetic control group. Paeonol treatment also enhanced the motor and sensory nerve conduction velocity. Paeonol treated diabetic animals showed significant changes in oxidative stress parameters. Histopathology study indicated that paeonol treatment prevented the neuronal damage, lowered demyelination and leukocyte infiltration. NF-κB and MCP-1 expression was significantly decreased in sciatic nerve of diabetic animals treated with paeonol. SIGNIFICANCE: Results of the present study indicate that paeonol may be considered as effective option for management of diabetic neuropathy.

In Silico and In Vivo Toxicological Evaluation of Paeonol.

Paeonol is a phenolic compound reported for its various pharmacological activities such as antioxidant, anti-inflammatory and antidiabetic activity. There are no systematic scientific reports on the in vivo toxicity of paeonol. So, the present work was designed to study in silico and in vivo toxicity of paeonol. In silico toxicity predictions were carried out using pkCSM, ProTox-II, pre-ADMET server and OSIRIS property explorer. Acute oral toxicity study of paeonol was carried out in female Sprague Dawley rats at a single dose of 300 mg/kg, 2000 mg/kg and 5000 mg/kg. Animals were observed for toxicity signs and mortality for 14 days. Repeated dose oral toxicity study of paeonol was carried out in female and male Sprague Dawley rats at a dose of 50, 100 and 200 mg/kg body weight for 28 days. At the end of the study, hematological, biochemical and urine parameters were assessed. Histopathology of vital organs was also carried out. In silico toxicity study predicted that paeonol is non-toxic. The maximally tolerated dose of paeonol was found to be 5000 mg/kg in acute toxicity study in female rats. Paeonol was found to be safe at a dose of 50, 100 and 200 mg/kg in repeated dose toxicity study in male and female rats.

Chemistry, pharmacokinetics, pharmacology and recent novel drug delivery systems of paeonol.

Paeonol is a bioactive phenol present in Dioscorea japonica, Paeonia suffruticosa and Paeonia lactiflora. It is reported for various pharmacological activities. AIM: To review chemistry, pharmacokinetics, pharmacological activities as well as various formulations of paeonol. MATERIALS AND METHODS: A literature search was done using different search terms for paeonol by using different scientific databases like PubMed, Scopus and ProQuest. Scientific papers published during the period 1969 to 2019 were comprehensively reviewed. KEY FINDINGS: Researchers have synthesized methoxy, ethoxy, piperazine, chromonylthiazolidine, phenol-phenylsulfonyl, alkyl ether, aminothiazole, tryptamine hybrids and paeononlsilatie derivatives to enhance the stability of paeonol. These derivatives were synthesized and evaluated for in vitro series of biological activities like anti-inflammatory, tyrosinase inhibitory, neuroprotective, anticancer and antiviral activity. Regardless of valuable therapeutic potential, the clinical use of paeonol is restricted due to poor water solubility, low oral bioavailability, low stability and high volatility at room temperature. To enhance the bioavailability of paeonol various formulations are prepared and evaluated for its activity. Paeonol formulations can be categorized as conventional-tablets, topical gel and hydrogel; polymeric delivery system-microparticles, microsponges, dendrimers, nanocapsules, polymeric nanoparticles, nanospheres; lipid-based delivery systems-microemulsion, self-micro-emulsifying drug delivery, liposome, transethosomes, ethosomes, niosomes, proniosomes, lipid-based nanoparticles and nanoemulsion of paeonol. SIGNIFICANCE: Paeonol has a potential to be developed as a techno-commercial product with respect to its multi-faceted pharmacological properties. Even though in vitro and in vivo studies have been reported the important activities of paeonol, its commercial utilization requires extensive safety and efficacy data.

Potential Biomarkers in Diabetic Retinopathy.

BACKGROUND: Diabetic retinopathy is one of the important complications of diabetes. In major cases, diabetic retinopathy is unnoticed until the irreversible damage to eye occurs and leads to blurred vision and, eventually, blindness. OBJECTIVE: The pathogenesis and diagnosis of diabetic retinopathy are very complex and not fully understood. Currently, well-established laser techniques and medications are available, but these treatment options have their own shortcomings on biological systems. Biomarkers can help to overcome this problem due to easy, fast and economical options for diagnosis of diabetic retinopathy. METHODS: The search terms used were "Diabetic retinopathy", "Biomarkers in diabetic retinopathy", "Novel biomarkers in diabetic retinopathy" and "Potential biomarkers of diabetic retinopathy" by using different scientific resources and databases like EBSCO, ProQuest, PubMed and Scopus. Eligibility criteria included biomarkers involved in diabetic retinopathy in the detectable range. Exclusion criteria included the repetition and duplication of the biomarker in diabetic retinopathy. RESULTS: Current review and literature study revealed that biomarkers of diabetic retinopathy can be categorized as inflammatory: tumor necrosis factor-α, monocyte chemoattractant protein-1, transforming growth factor- ß; antioxidant: nicotinamide adenine dinucleotide phosphate oxidase; nucleic acid: poly ADP ribose polymerase- α, Apelin, Oncofetal; enzyme: ceruloplasmin, protein kinase C; and miscellaneous: erythropoietin. These biomarkers have a great potential in the progression of diabetic retinopathy hence can be used in the diagnosis and management of this debilitating disease. CONCLUSION: Above mentioned biomarkers play a key role in the pathogenesis of diabetic retinopathy; hence they can also be considered as potential targets for new drug development.

Marine natural products for multi-targeted cancer treatment: A future insight.

Cancer is world's second largest alarming disease, which involves abnormal cell growth and have potential to spread to other parts of the body. Most of the available anticancer drugs are designed to act on specific targets by altering the activity of involved transporters and genes. As cancer cells exhibit complex cellular machinery, the regeneration of cancer tissues and chemo resistance towards the therapy has been the main obstacle in cancer treatment. This fact encourages the researchers to explore the multitargeted use of existing medicines to overcome the shortcomings of chemotherapy for alternative and safer treatment strategies. Recent developments in genomics-proteomics and an understanding of the molecular pharmacology of cancer have also challenged researchers to come up with target-based drugs. The literature supports the evidence of natural compounds exhibiting antioxidant, antimitotic, anti-inflammatory, antibiotic as well as anticancer activity. In this review, we have selected marine sponges as a prolific source of bioactive compounds which can be explored for their possible use in cancer and have tried to link their role in cancer pathway. To prove this, we revisited the literature for the selection of cancer genes for the multitargeted use of existing drugs and natural products. We used Cytoscape network analysis and Search tool for retrieval of interacting genes/ proteins (STRING) to study the possible interactions to show the links between the antioxidants, antibiotics, anti-inflammatory and antimitotic agents and their targets for their possible use in cancer. We included total 78 pathways, their genes and natural compounds from the above four pharmacological classes used in cancer treatment for multitargeted approach. Based on the Cytoscape network analysis results, we shortlist 22 genes based on their average shortest path length connecting one node to all other nodes in a network. These selected genes are CDKN2A, FH, VHL, STK11, SUFU, RB1, MEN1, HRPT2, EXT1, 2, CDK4, p14, p16, TSC1, 2, AXIN2, SDBH C, D, NF1, 2, BHD, PTCH, GPC3, CYLD and WT1. The selected genes were analysed using STRING for their protein-protein interactions. Based on the above findings, we propose the selected genes to be considered as major targets and are suggested to be studied for discovering marine natural products as drug lead in cancer treatment.