Neuroprotective potential of traditionally used medicinal plants of Manipur against rotenone-induced neurotoxicity in SH-SY5Y neuroblastoma cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Alternanthera sessilis (L.) R. Br. ex DC., Eryngium foetidum L., and Stephania japonica (Thunb.) Miers plants are traditionally used to treat various central nervous system disorders like paralysis, epilepsy, seizure, convulsion, chronic pain, headache, sleep disturbances, sprain, and mental disorders. However, their possible neuroprotective effects have not been evaluated experimentally so far. AIM OF THE STUDY: The study aims to examine the neuroprotective potential of the three plants against cytotoxicity induced by rotenone in SH-SY5Y neuroblastoma cells and assess its plausible mechanisms of neuroprotection. MATERIALS AND METHODS: The antioxidant properties of the plant extracts were determined chemically by DPPH and ABTS assay methods. The cytotoxicity of rotenone and the cytoprotective activities of the extracts were evaluated using MTT assays. Microtubule-associated protein 2 (MAP2) expression studies in cells were performed to assess neuronal survival after rotenone and extract treatments. Mitochondrial membrane potential and intracellular levels of reactive oxygen species were evaluated using Rhodamine 123 and DCF-DA dye, respectively. Catalase, glutathione peroxidase, and superoxide dismutase activities were also measured. Apoptotic nuclei were examined using DAPI staining. Liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (LC-QTOF-MS) analysis of the plant extracts was also performed. RESULTS: The methanol extracts of A. sessilis, S. japonica, and E. foetidum showed excellent free radical scavenging activities. MAP2 expression studies show that A. sessilis and S. japonica have higher neuroprotective effects against rotenone-induced neurotoxicity in SH-SY5Y cells than E. foetidum. Pre-treating cells with the plant extracts reverses the rotenone-induced increase in intracellular ROS. The plant extracts could also restore the reduced mitochondrial membrane potential induced by rotenone treatment and reinstate rotenone-induced increases in catalase, glutathione peroxidase, and superoxide dismutase activities. All the extracts inhibited rotenone-induced changes in nuclear morphology and DNA condensation, an early event of cellular apoptosis. LC-QTOF-MS analysis of the plant extracts shows the presence of neuroprotective compounds. CONCLUSIONS: The plant extracts showed neuroprotective activities against rotenone-treated SH-SY5Y cells through antioxidant and anti-apoptotic mechanisms. These findings support the ethnopharmacological uses of these plants in treating neurological disorders. They probably are a good source of neuroprotective compounds that could be further explored to develop treatment strategies for neurodegenerative diseases like Parkinson's disease.

Ethno-entomotherapeutic and metabolite profiling of Coridius chinensis (Dallas), a traditional edible insect species of North-East India.

Edible insects possess several health enhancing properties and play an important role in human nutrition. Coridius chinensis is an edible insect that is considered food and claimed as traditional medicine. In the present study, nutritional contents, chemical composition, antioxidant, and anti-inflammatory properties of C. chinensis were analyzed. It was found that the insect sample contains 50.46% moisture, 44.65% protein, 4.45% carbohydrate, 39.42% crude fats, 3.53% ash and 576.11 (Kcal/100 g) energy. Our study highlighted the presence of a significant amount of phenol and flavonoids. The C. chinensis hydro-alcoholic extract showed high antioxidant property and anti-inflammatory activity. GCMS analysis identified 61 volatile compounds. LC-MS analysis of hydroalcoholic extract of C. chinensis revealed the presence of compounds such as etodolac glucuronide, morphine 3-glucuronide, ecgonine, ecgonine methyl ester, sufentanil, and palmitoyl ethanololamide. These findings suggest that C. chinensis species can be employed as a valuable food source with excellent therapeutic properties.

Bio-economic potential of ethno-entomophagy and its therapeutics in India.

Insects are the largest group of arthropods with the highest faunal diversity of over a million species. Apart from many other roles in the environment, the aspect of several insects being used for human consumption (entomophagy) and as traditional medicine (entomotherapy) by different communities of the world holds special significance for countering global food crisis. The enormous insect resources contribute a reasonable share in improving the livelihoods of many entomophagy practicing communities. Considering this significance, the present review emphasizes the bio-economic potential of insect resources. An overview of entomophagy practices in India; benefits towards the environment, humans and animals; insect species used in entomophagy along with therapeutic importance, nutritional, physical, chemical, and microbiological hazards; farming and mass production technologies; legal status and socio-economic implications in Indian scenario have been presented. Traditionally tested and accepted therapeutic use of edible insects have been reported to cure various disease conditions and calls for scientific exploration and validation to rediscover promising medical products of modern medicine. Edible insects as an alternative food need to be popularized in India with a new policy or regulation to harvest and sell insect-derived food products with proper safe consumption demonstrations. Considering the facts that insects reproduce in large numbers at a faster rate, require less land, water and other resources for farming, and economically and ecologically sustainable harvesting can be done in a short time, insect farming can offer revenue and rural job opportunities in developing countries, especially in India. Therefore, the traditional use of insects as food and medicine has tremendous potential to enhance the economy and living standards.

Drug addiction and treatment: An epigenetic perspective.

Drug addiction is a complex disease affected by numerous genetic and environmental factors. Brain regions in reward pathway, neuronal adaptations, genetic and epigenetic interactions causing transcriptional enhancement or repression of multiple genes induce different addiction phenotypes for varying duration. Addictive drug use causes epigenetic alterations and similarly epigenetic changes induced by environment can promote addiction. Epigenetic mechanisms include DNA methylation and post-translational modifications like methylation, acetylation, phosphorylation, ubiquitylation, sumoylation, dopaminylation and crotonylation of histones, and ADP-ribosylation. Non-coding RNAs also induce epigenetic changes. This review discusses these above areas and stresses the need for exploring epidrugs as a treatment alternative and adjunct, considering the limited success of current addiction treatment strategies. Epigenome editing complexes have lately been effective in eukaryotic systems. Targeted DNA cleavage techniques such as CRISPR-Cas9 system, CRISPR-dCas9 complexes, transcription activator-like effector nucleases (TALENs) and zinc-finger nucleases (ZFNs) have been exploited as targeted DNA recognition or anchoring platforms, fused with epigenetic writer or eraser proteins and delivered by transfection or transduction methods. Efficacy of epidrugs is seen in various neuropsychiatric conditions and initial results in addiction treatment involving model organisms are remarkable. Epidrugs present a promising alternative treatment for addiction.

Acute and sub-acute toxicity evaluation of dihydro-p-coumaric acid isolated from leaves of Tithonia diversifolia Hemsl. A. Gray in BALB/c mice.

In present study, the acute and sub-acute toxicities of Dihydro-p-coumaric acid isolated from the leaves of Tithonia diversifolia (Hemsl.) A. Gray was studied for safety issues in mammals. For acute toxicity tests, isolated compound was administered orally in both male and female BALB/c mice at the doses of 200, 800, and 1,600 mg/kg body weight for 7 days. In sub-acute toxicity study 50 and 500 mg/kg bw of the compound was orally administered for 14 days. Toxicity induced behavioural changes, haematological parameters, biochemical markers and histopathological sections were studied after Dihydro-p-coumaric acid administration. The vital organs like heart, kidney, uterus and testis revealed no adverse effects at doses of upto 1,600 mg/kg bw and 500 mg/kg bw. Slight hepatotoxicity was however demonstrated by ALT and AST assay but histopathological section did not concur as much. The study demonstrated insignificant difference in the percentage of feed intake, water intake, weight gain, haematological parameters and histopathological changes, with no toxicity signs and mortality. Dihydro-p-coumaric acid can be regarded as safe in both acute and sub-acute toxicity assay in both sexes. This indicates Dihydro-p-coumaric acid as a viable alternative to synthetic pesticides.

Breaking the Silence of Tumor Response: Future Prospects of Targeted Radionuclide Therapy.

Therapy-induced tumor resistance has always been a paramount hurdle in the clinical triumph of cancer therapy. Resistance acquired by tumor through interventions of chemotherapeutic drugs, ionizing radiation, and immunotherapy in the patients is a severe drawback and major cause of recurrence of tumor and failure of therapeutic responses. To counter acquired resistance in tumor cells, several strategies are practiced such as chemotherapy regimens, immunotherapy and immunoconjugates, but the outcome is very disappointing for the patients as well as clinicians. Radionuclide therapy using alpha or beta-emitting radionuclide as payload becoming a popular practice for cancer therapy. With the improvement in dosimetric studies, development of high-affinity target molecules and design of several novel chelating agents which provide thermodynamically stable complexes in vivo, the scope of radionuclide therapy has increased by leaps and bounds. Additionally, radionuclide therapy along with the combination of chemotherapy is gaining importance in pre-clinics, which is quite encouraging. Thus, it opens an avenue for newer cancer therapy modalities where chemotherapy, radiation therapy, and immunotherapy are unable to break the silence of tumor response. This article describes, in brief, the causes of tumor resistance and discusses the potential of radionuclide therapy to enhance tumor response.

Association of Dopamine Transporter Gene with Heroin Dependence in an Indian Subpopulation from Manipur.

Dopamine transporter (DAT) or solute carrier family 6 member 3 (SLC6A3) is a transmembrane protein regulating dopaminergic neurotransmission. It has been implicated in playing important roles in the dopaminergic reward pathways, and thus, DAT1 is a strong candidate gene for association studies with heroin dependence. A case-control study involving 279 individuals (147 controls and 132 heroin-dependent cases) was conducted. Ten polymorphisms of the DAT1 (SLC6A3) gene were analysed for its association with heroin dependence. Following the Hardy-Weinberg equilibrium (HWE) test, genetic association analyses were performed for the study groups. The post hoc statistical power of the study was 0.655 (65.5%). Single-nucleotide polymorphism (SNP) rs246997 was found to be significantly associated with heroin dependence at allelic, genotypic, and haplotypic levels. A significant difference in the distribution of 11R allele and 10R/11R genotype of rs28363170 between heroin-dependent cases and controls was also observed. Nominal significance at degrees of freedom (df) = 5 was also observed for rs28363170. Five bimarker-based haplotype combinations were also found to be associated with heroin dependence. For the first time, 13R allele (7R/13R genotype) and 14R allele (7R/14R genotype) were identified for rs3836790 in the population. The study also reports that the 11R allele and 10R/11R genotype of rs28363170 is associated with protection against heroin dependence. 7R and 6R alleles were also found to be the common alleles of rs3836790 in the study population. The study provides evidence for the association of polymorphisms of DAT1 (SLC6A3) with heroin dependence.

Efficiency of RAPD, ISSR, iPBS, SCoT and phytochemical markers in the genetic relationship study of five native and economical important bamboos of North-East India.

10 primers each of random amplified polymorphic DNA (RAPD), inter-simple sequence repeats (ISSR), inter primer binding site (iPBS) and start codon targeted (SCoT) were used to analyze genetic polymorphism and relationship between 50 genotypes of 5 economical important native bamboos (Bambusa cacharensis, B. mizorameana, Dendrocalamus manipureanus, D. hamiltonii and D. sikkimensis) of North-East India. The 40 different primers generated 111, 115, 116 and 138 polymorphic bands for RAPD, ISSR, iPBS and SCoT markers respectively. The comparative analysis of 4 marker systems based on polymorphic information content (PIC), effective multiplex ratio (EMR) and marker index (MI) values showed SCoT to be more informative with higher discriminating power than the other three markers. The correlation value (r) as determined by the Mantel test ranged from 0.60 (SCoT and RAPD) to 0.83 (iPBS and ISSR) indicating a high positive correlation between the markers. The close correspondence between the genetic matrices of RAPD, ISSR, iPBS and SCoT markers revealed the effectiveness of each marker system in determining the genetic relationship between bamboos. UPGMA (Unweighted Pair Group Arithmetic Mean Method) dendrograms generated from DNA marker analysis demonstrated species-specific clustering of different bamboo genotypes. Except for RAPD, the dendrograms of ISSR, iPBS and SCoT markers also showed a close association of bamboo genotypes based on geographical origin. Principal coordinate analysis (PCoA) revealed the distribution of different bamboo genotypes in accordance with the cluster analysis. The cluster grouping based on phytochemical study not only discriminated the different bamboo species but also illustrated a location-specific grouping of the genotypes. The bamboo clustering pattern derived from phytochemical analysis matched closely with the dendrograms generated by the DNA markers. The present investigation established the possibility of using a combined molecular and phytochemical marker approach to determine the genetic relationship between 5 native bamboos of North-East India with high precision.

A single nucleotide polymorphism in OPRM1(rs483481) and risk for heroin use disorder.

Opioid receptor mu1 (OPRM1) is the target of many opioid drugs, and it is known to have affinity toward both endogenous and exogenous opioids, opiate and opioid analgesic drugs. The present study was undertaken to explore association of single nucleotide polymorphisms (SNPs) in the OPRM1 gene with heroin use disorder. Ten OPRM1 polymorphisms were analyzed in 132 cases and 147 healthy controls. The SNP rs483481 showed significant allelic, genotypic and haplotypic association (Allelic: p-value = 0.003, OR = 1.75, CI = 1.21-2.55) (Genotypic: p-value = 0.003, OR = 1.72, CI = 1.08-2.75) with heroin use disorder. Allelic and genotypic association remained significant even after multiple testing corrections with 1000 permutations. A significant positive correlation between 'Number of times drug abstained' and 'rs483481-AA genotype' (p-value = 0.002; Pearson correlation = 0.265) was also observed. One-way ANOVA analysis demonstrated significant association of rs483481 with 'number of times drug abstained' (F = 4.86, p-value =0.009). 'A' allele and 'AA' genotype of marker rs483481 seem to confer protective effect while 'G' allele and 'GG' genotype potentiates risk for heroin use disorder. OPRM1 is found to be associated with heroin use disorder in the studied Manipuri cohort. The study suggests that individuals with G allele and GG genotypes at rs483481 could be more vulnerable to heroin dependence, and it could be taken into consideration in prevention and intervention programs.