Hesperidin downregulates kinases lrrk2 and gsk3ß in a 6-OHDA induced Parkinson's disease model.

The depletion of dopamine in the striatum region and Lewy bodies are the hallmark characteristics of Parkinson's disease. The pathology also includes the upregulation of various Parkinson's disease (PARK) genes and kinases. Two such kinases, LRRK2 and GSK-3ß have been directly implicated in the formation of tau and alpha-synuclein proteins, causing PD. Hesperidin (HES) is a flavanone glycoside that has multiple therapeutic benefits including neuroprotective effects. In this study, we examined the neuroprotective effects of HES against 6-hydroxydopamine (6-OHDA) induced-neurotoxicity in the in-vitro and in-vivo model. Hesperidin significantly protected the SH-SY5Y cells' stress against 6-OHDA induced toxicity by downregulating biomarkers of oxidative stress. Furthermore, HES downregulated the kinases lrrk2 and gsk3ß along with casp3, casp9, and polg in the zebrafish model. The treatment with HES also improved the locomotor pattern of zebrafish that was affected by 6-OHDA. This study suggests that hesperidin could be a drug of choice in targeting kinases against a 6-OHDA model of PD.

Exogenous human beta amyloid peptide interferes osteogenesis through Sox9a in embryonic zebrafish.

The two major hallmarks of Alzheimer's disease (AD) are beta-amyloid plaques and neurofibrillary tangles. Amyloid peptide aggregations in the brain cause loss of synaptic connections and subsequent neurotoxicity leading to neurodegeneration and memory deficits. However, the physiological effects of beta-amyloid on early embryonic development still remain unclear. Administration of human beta-amyloid peptide (1-42) through cerebrospinal ventricular injection was carried out at 24 hpf (hours post fertilization) and it was uptaken into the cellular layers of the early ventricular development without any plaque aggregation. Whole-mount Immunostaining of zebrafish embryos injected with the beta-amyloid at 60 hpf revealed the delay in Sox9a expression. Decreased level of cartilage to bone transformation rate in 15 dpf (days post fertilization) zebrafish was observed by differential staining. These results suggest the possible existence of a genetic relationship between extrinsic amyloid peptide and Sox9a expression. Thus, our results demonstrated that the human beta-amyloid influences bone development through Sox9a expression during osteogenesis in zebrafish.

Safety and toxicity issues associated with lead-based traditional herbo-metallic preparations.

ETHNOPHARMACOLOGICAL RELEVANCE: Herbal and herbo-mineral preparations are being traditionally used in Indian medicines. The herbo-mineral preparations have several benefits that have been instrumental in their widespread use in treatment of different disorders by traditional medicinal practitioners. These include better stability, lower dosage, ease of storability and sustained availability. Naga bhasma (lead sulphide ash), a traditional Indian herbo-mineral medication prepared using lead and several herbal ingredients, has been used as an oral medicine in India for many years for the treatment of diabetes, spleen enlargement, diarrhoea and various skin diseases. The elaborate preparation protocol involved in the traditional medicines is believed to modify the toxic nature of the precursor (metal) and adds therapeutic value. But modern scientists claim that these preparations are toxic to health as they contain large amount of metal. Many factors such as preparation based factors, chemical nature based factors, vehicle used, therapy associated factors, pharmacological factors, etc, determine whether the traditional medicines are toxic or not. This review focuses on the safety and critical issues associated with Naga bhasma-a lead based ayurvedic medicine. MATERIALS AND METHODS: The detailed review of literature about Naga bhasma apart from other lead based formulations are carried out by utilizing the resources including, classical Indian text books, databases such as Pub med, Scopus, Science direct and few other web sources. RESULTS: Though metallic lead is known to be toxic to the biological system, no compelling evidence has been put forth to suggest any toxic manifestations of Naga bhasma. The elemental characterization of preparations containing Naga bhasma has shown extremely high levels of lead content and various parameters must be taken into consideration in deciding the safety and critical issues present in traditional medicines. As there are no molecular targets available for most of the traditional medicine, it is difficult to assure the safety in using this traditional preparation. Highly intensive research encompassing physico-chemical, engineering as well as biological aspects need to be carried out to understand the applicability of such preparations in a modern context. CONCLUSION: As there are no molecular targets available for most of the traditional medicine, it is difficult to assure the safety in using this traditional preparation. Highly intensive research encompassing physico-chemical, engineering as well as biological aspects need to be carried out to understand the applicability of such preparations in a modern context.