Volatile Constituent Analysis of Wintergreen Essential Oil and Comparison with Synthetic Methyl Salicylate for Authentication

A comparative analysis of Gaultheria fragrantissima (Ericaceae) essential oils based on geographical location, distillation time, and varying distillation conditions was carried out, and their compositions were evaluated by gas chromatography–mass spectrometry (GC–MS), chiral GC–MS, and gas chromatography–flame ionization detection (GC–FID). In addition, each of seven commercial wintergreen essential oil samples from Nepal and China were analyzed. The highest extraction yield was 1.48% and the maximum number of compounds identified in natural wintergreen oil was twenty-two. Based on distillation time, the maximum numbers of identified compounds are present in 120 min. Linalool, phenol, vetispirane, and ethyl salicylate were present in commercial wintergreen oils both from Nepal and China. The presence of compounds such as elsholtzia ketone and β-dehydroelsholtzia ketone in the China samples represented a significant difference in wintergreen oil between the two geographical sources. Dimethyl 2-hydroxyterephthalate is a well-known synthetic marker for wintergreen oil when synthesis is carried out using salicylic acid, but the synthetic marker was absent while using acetylsalicylic acid as a precursor during synthesis. Adulteration analysis of wintergreen oil showed an increase in the concentration of dimethyl 2-hydroxyterephthalate, whereas the concentrations of minor components decreased and methyl salicylate remained unchanged. To the best of our knowledge, this is the first report of the enantioselective analysis of wintergreen essential oil. Furthermore, three samples showed notable antibacterial activity against Staphylococcus epidermidis, with an MIC value of 156.3 μg/mL. Similarly, one sample showed effectiveness against Aspergillus niger (MIC = 78.1 μg/mL)

Drug Act 1978 of Nepal: A Critical Analysis

Background: With the enactment of the Drug Act in 1978, through the establishment of different bodies under the act, drug-related activities have been regulated and controlled in Nepal so as to provide safe and efficacious drugs of standard quality to the general public.  However, with the overgrowing use of drugs, cosmetics, biotechnological products, nutraceuticals, and veterinary products in the present market and the present act failing to include these aspects, this paper tries to critically analyze the Drug Act 1978 of Nepal which will comprise strengths, weaknesses, opportunities, and threats faced in current scenario regarding the act. The regulation of drugs in Nepal was started with the enactment of the Drugs Act in 1978 AD, which is being carried out by the Department of Drug Administration as provisioned in the section 5 of the act. To facilitate the proper implementation of the act, various rules, regulations and guidelines are framed. The objective of this study was to explore the areas to improve in the Drugs Act and help foster the use of safe, efficacious and quality drugs. Method: The Drugs Act 1978 was critically analyzed focusing on the strengths, weaknesses, opportunities, and threats of the act as of current scenario. Result: After critically analyzing the drugs act 1978 we found out that there is lack in regulations of use of cosmetics, newer biotechnology products, nutraceuticals, veterinary product, innovative pharmaceutical products as well as the online pharmacy services. Conclusion: A major amendment and periodic revision is required with the consequence of meeting timely needs and promoting the idea of safety and efficacy in drug related activities

Essential Oil Composition Analysis of <i>Cymbopogon</i> Species from Eastern Nepal by GC-MS and Chiral GC-MS, and Antimicrobial Activity of Some Major Compounds

Cymbopogon species essential oil (EO) carries significant importance in pharmaceuticals, aromatherapy, food, etc. The chemical compositions of Cymbopogon spp. Viz. Cymbopogon winterianus (citronella) Cymbopogon citratus (lemongrass), and Cymbopogon martini (palmarosa) were analyzed by gas chromatography–mass spectrometry (GC-MS), enantiomeric distribution by chiral GC-MS, and antimicrobial activities of some selected pure major compound and root and leaves EOs of citronella. The EO of leaves of Cymbopogon spp. showed comparatively higher yield than roots or other parts. Contrary to citral (neral and geranial) being a predominant compound of Cymbopogon spp., α-elemol (53.1%), α-elemol (29.5%), geraniol (37.1%), and citral (90.4%) were detected as major compounds of the root, root hair with stalk, leaf, and root stalk with shoot of citronella EO, respectively. Palmarosa leaves’ EO contains neral (36.1%) and geranial (53.1) as the major compounds. In the roots of palmarosa EO, the prime components were α-elemol (31.5%), geranial (25.0%), and neral (16.6%). Similarly, lemongrass leaves’ EO contains geraniol (76.6%) and geranyl acetate (15.2%) as major compounds, while the root EO contains a higher amount of geraniol (87.9%) and lower amount of geranyl acetate (4.4%). This study reports for the first time chiral terpenoids from Cymbopogon spp. EOs. Chiral GC-MS gave specific enantiomeric distributions of nine, six, and five chiral terpenoids in the root, root stalk with a shoot, and leaves of citronella EOs, respectively. Likewise, four and three chiral terpenoids in the root and leaves of lemongrass oil followed by two chiral terpenoids in the leaves and root of palmarosa EOs each. Additionally, the root and leaves’ EOs of citronella exhibit noticeable activity on bacteria such as Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus pyogenes and fungus such as Candida albicans, Microsporum canis, and Trichophyton mentagrophytes. So, geranial-, neral-, geraniol-, and citronellal-rich EOs can be used as an alternative antimicrobial agent

Neuroprotective effects of antidepressants via upregulation of neurotrophic factors in the MPTP model of Parkinson's disease

Neurotrophic factors are essential for neuronal survival, plasticity, and development and have been implicated in the action mechanism of antidepressants. In this study, we assessed the neurotrophic factor-inducing and neuroprotective properties of antidepressants. In the first part of the study, we found that fluoxetine, imipramine, and milnacipran (i.p., 20 mg/kg/day for 1 week or 3 weeks) upregulated brain-derived neurotrophic factor in the striatum and substantia nigra both at 1 week and 3 weeks. In contrast, an increase in the glial-derived neurotrophic factor was more obvious at 3 weeks after the antidepressants treatment. Specifically, it was found that fluoxetine and imipramine are more potent in raising the levels of neurotrophic factors than milnacipran. Furthermore, antidepressants elevated the phosphorylation of extracellular signal-regulated-protein kinase (ERK1/2) and the serine/threonine kinase Akt. In the second part of the study, we compared the neuroprotective effects of fluoxetine, imipramine, and milnacipran in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease. Pretreament with fluoxetine, imipramine or milnacipran for 3 weeks reduced MPTP-induced dopaminergic neurodegeneration and microglial activation in the nigrostriatal pathway. Neurochemical analysis by HPLC exhibited that antidepressants attenuated the depletion of striatal dopamine. In consistent, beam test showed that behavioral impairment was ameliorated by antidepressants. Neuroprotective effects were more prominent in the fluoxetine or imipramine treatment group than in milnacipran treatment group. Finally, we found that neuroprotection of the antidepressants against 1-methyl-4-phenylpyridinium neurotoxicity in SH-SY5Y cells was attenuated by ERK or Akt inhibitor. These results indicate that neuroprotection by antidepressants might be associated with the induction of neurotrophic factors, and antidepressant could be a potential therapeutic intervention for treatment of Parkinson's disease

Enhanced dopaminergic neurotoxicity mediated by MPTP in IL-32β transgenic mice

Parkinson's disease (PD) is a neurodegenerative disorder characterized by prominent loss of the nigral dopaminergic neurons and motor symptoms, such as resting tremor and bradykinesia. Evidence suggests that neuroinflammation may play a critical role in PD pathogenesis. Interleukin (IL)-32 is a newly-identified proinflammatory cytokine, which regulates innate and adaptive immune responses by activating p38 MAPK and NF-κB signaling pathways. The cytokine has been implicated in cancers and autoimmune, inflammatory, and infectious diseases. In this study, we attempted to identify the effects of IL-32β on dopaminergic neurotoxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), using IL-32β transgenic mice. Male wild type and IL-32β transgenic mice received intraperitoneal injections of vehicle or MPTP (15\ua0mg/kg\ua0×\ua04). Immunohistochemistry showed that overexpression of IL-32β significantly increased MPTP-mediated loss of dopaminergic neurons in the substantia nigra and deletion of tyrosine hydroxylase-positive fibers in the striatum. Dopamine depletion in the striatum and deficit in locomotor activity were enhanced in IL-32β transgenic mice. These results were accompanied by higher neuroinflammatory responses in the brains of transgenic mice. Finally, we found that IL-32β exaggerated MPTP-mediated activation of p38 MAPK and JNK pathways, which have been shown to be involved in MPTP neurotoxicity. These results suggest that IL-32β exacerbates MPTP neurotoxicity through enhanced neuroinflammatory responses