Effect of herbal formulation on glimepiride pharmacokinetics and pharmacodynamics in nicotinamide-streptozotocin-induced diabetic rats.

BACKGROUND: Traditional medicinal herbs are widely consumed in developing countries to treat diabetes as they are perceived to be safer, less expensive, and have fewer side effects as compared to the conventional medicines. Diabecon (DB), Himalaya Herbal Healthcare, India is herbal over-the-counter formulation which contains several herbs that are reported in the traditional texts for the treatment of diabetes. The majority of these herbs have been investigated and found to interfere with the cytochrome pathway. The most common oral antihyperglycemic drug used today in clinical practice is Glimepiride (GP).The CYP2C9 enzyme is mainly responsible for the metabolism of GP. Herein we hypothesize that the co-administration of GP with DB may result in possible Herb-Drug Interactions (HDIs) as DB has the potential to significantly inhibit the CYP2C9 enzyme. OBJECTIVE: In the current study, the pharmacokinetic and pharmacodynamic interactions of GP (0.82 mg/kg) with DB (110.95 mg/kg) was investigated in diabetes induced (Nicotinamide-STZ) rats by co-administering both drugs orally for 21 days. MATERIALS AND METHODS: For the study of the HDI, Bioanalytical RP-HPLC/PDA method for quantifying GP in plasma of rats was developed and validated as per US-FDA guidelines. In vivo pharmacokinetic and pharmacodynamic parameters were studied on day 1 and day 21 post administration. RESULTS: The RP-HPLC/PDA method was successfully employed for quantification of GP in the PK studies. The co-administration of GP and DB in diabetic rats resulted in beneficial pharmacodynamic interactions, but there were no notable changes in the pharmacokinetic parameters of GP. CONCLUSION: This current investigation in an animal model suggests that co-administration of GP and DB may have significant therapeutic benefits in the treatment of diabetes; however, additional research, randomized clinical trials or case studies in humans, is needed.

A novel approach to develop an animal model for oral submucous fibrosis.

Epidemiological data have proved the association of consumption of areca nut with the causation of oral submucous fibrosis (OSF). OSF is a chronic inflammatory disease with the potential for malignant transformation from 7 to 13%. The establishment of animal models makes it easier for researchers to focus on the therapeutic options to combat this disease further. We developed and compared two areca nut extract (ANE) administration methods in Swiss albino mice to establish OSF. This study compared an invasive intrabuccal injection technique with a non-invasive intraoral droplet administration. The duration of induction was around 12 weeks. Histopathology (H&E, Masson's trichrome staining) and gene expression analysis (COL-I, COL-II, and α-SMA) were performed using RT-PCR to confirm the OSF in animals. Our study showed that ANE administration through the intraoral droplet method exhibited significantly higher fibrosis than the intrabuccal injections, as evidenced by the H&E and Masson's trichrome staining. Furthermore, intraoral administration of ANE significantly upregulated the mRNA expression of COL-I, COL-II, and α-SMA, as revealed by the RT-PCR analysis. The non-invasive droplet method could simulate the absorption of areca nut seen in humans through daily dosing. This study establishes the intraoral droplet method as an efficient and non-invasive method to administer the ANE to develop OSF. These findings will aid in the efficient development of OSF animal models for interventional studies, including screening novel drugs in the reversal of the OSF.

Emendation of autophagic dysfuction in neurological disorders: a potential therapeutic target.

BACKGROUND: Neurological disorders have been continuously contributing to the global disease burden and affect millions of people worldwide. Researchers strive hard to extract out the ultimate cure and serve for the betterment of the society, and yet the treatments available provide only symptomatic relief. Aging and abnormal mutations seem to be the major culprits responsible for neurotoxicity and neuronal death. One of the major causes of these neurological disorders that has been paid utmost attention recently, is Autophagic Dysfunction. AIM: The aim of the study was to understand the autophagic process, its impairment in neurological disorders and targeting the impairments as a therapeutic option for the said disorders. METHODS: For the purpose of review, we carried out an extensive literature study to excerpt the series of steps involved in autophagy and to understand the mechanism of autophagic impairment occurring in a range of neurodegenerative and neuropsychiatric disorders like Parkinson, Alzheimer, Depression, Schizophrenia, Autism etc. The review also involved the exploration of certain molecules that can help in triggering the compromised autophagic members. RESULTS: We found that, a number of genes, proteins, receptors and transcription factors interplay to bring about autophagy and plethora of neurological disorders are associated with the diminished expression of one or more autophagic member leading to inhibition of autophagy. CONCLUSION: Autophagy is a significant process for the removal of misfolded, abnormal, damaged protein aggregates and nonfunctional cell organelles in order to suppress neurodegeneration. Therefore, triggering autophagy could serve as an important therapeutic target to treat neurological disorders.