Parkinson’s disease (PD) is the second most common neurodegenerative disease. It is caused by the death of dopaminergic neurons in the substantia nigra pars compacta. Oxidative stress and mitochondrial dysfunction contribute to the loss of dopaminergic neurons in PD. Sulfuretin is a potent antioxidant that is reported to be beneficial in the treatment of neurodegenerative diseases. In this study, we examined the protective effect of sulfuretin against 1-methyl-4-phenyl pyridinium (MPP⁺)-induced cell model of PD in SH-SY5Y cells and the underlying molecular mechanisms. Sulfuretin significantly decreased MPP⁺-induced apoptotic cell death, accompanied by a reduction in caspase 3 activity and polyADP-ribose polymerase (PARP) cleavage. Furthermore, it attenuated MPP⁺-induced production of intracellular reactive oxygen species (ROS) and disruption of mitochondrial membrane potential (MMP). Consistently, sulfuretin decreased p53 expression and the Bax/Bcl-2 ratio. Moreover, sulfuretin significantly increased the phosphorylation of Akt, GSK3β, and ERK. Pharmacological inhibitors of PI3K/Akt and ERK abolished the cytoprotective effects of sulfuretin against MPP⁺. An inhibitor of GSK3β mimicked sulfuretin-induced protection against MPP⁺. Taken together, these results suggest that sulfuretin significantly attenuates MPP⁺-induced neurotoxicity through Akt/GSK3β and ERK signaling pathways in SH-SY5Y cells. Our findings suggest that sulfuretin might be one of the potential candidates for the treatment of PD.

Royal jelly (RJ) has been used traditionally for dietary, cosmetic and health purposes for a long time in different parts of the world. Scientific studies have also shown its numerous health-promoting properties including hypoglycemic and anti-hypercholesterolemic action. In this study, we investigated the anti-adipogenic activity of RJ in 3 T3-L1 cells and isolated the major responsible root component for the activity. An active anti-adipogenic compound was isolated through bioassay-guided isolation process by successive treatment of RJ and its active fractions on 3 T3-L1 cell line. (E)-10-Hydroxy-2-decenoic Acid (10-HDA) was identified using NMR spectroscopy and ultra-performance liquid chromatography (UPLC). As 10-HDA showed significant anti-adipogenic activity with Oil Red O staining and TG content assay on 3 T3-L1 adipocytes, further study was carried out in molecular level for the expression of adipogenic transcription factors such as PPARγ, FABP4, C/EBPα, SREBP-1c, and Leptin. The effect of 10-HDA on preliminary molecules such as pAkt, pERK, C/EBPβ, and pCREB were studied in the early stage of adipogenesis. The effect of 10-HDA on reactive oxygen species (ROS) production in fully differentiating adipocytes was measured by nitro blue tetrazolium (NBT) assay. Results showed that triacylglycerol accumulation and ROS production was markedly suppressed by 10-HDA. Preliminary molecules such as pAkt, pERK, pCERB, and C/EBPβ were found to be down-regulated by 10-HDA, which led to down-regulation of key adipogenic transcription factors such as PPARγ, FABP4, CEBPα, SREBP-1c, and Leptin on 3 T3-L1 adipocytes. Our results suggest that anti-adipogenesis of 10-HDA on 3 T3-L1 adipocyte takes place via two mechanisms: inhibition of cAMP/PKA pathway and inhibition of p-Akt and MAPK dependent insulin signaling pathway. So it is considered that 10-HDA, a major component of RJ, can be a potential therapeutic medicine for obesity.

Background: Ponciri Fructus, a crude drug consisting of the dried immature fruits of Poncirus trifoliata (L.) Raf., is a popular folk medicine used for the treatment of allergy and gastrointestinal disorders in Korea and China. In this study, the anti-adipogenic activity of extracts and isolated compounds were evaluated using 3T3-L1 preadipocytes. Methods: Dried immature fruits were extracted and fractionated into n-hexane, ethyl acetate (EtOAc), n-butanol and water-soluble fractions. The ethanol extract and fractions were tested for anti-adipogenic activity in the 3T3-L1 cell line. The active fractions (n-hexane and EtOAc fractions) were further subjected to chromatographic techniques to isolate and identify active compounds. Furthermore, the isolated compounds were evaluated for their anti-adipogenic activity. Results: Altogether, seven compounds, including two flavonoids, one phytosteroid and four coumarin derivatives, were isolated. Ethanol extract, n-hexane fraction, EtOAc fraction and three isolated compounds (phellopterin, oxypeucedanin and poncirin) showed significant anti-adipogenic activity as observed by reduced lipid deposition in differentiated 3T3-L1 cells. Further, oxypeucedanin downregulated the key adipogenic markers, such as peroxisome proliferator-activated receptors proteins γ (PPAR-γ), sterol response element binding proteins-1 (SREBP-1), CCAAT/enhancer binding proteins-α (C/EBP-α), adipocyte-specific lipid binding proteins (FABP-4), adipocyte fatty acid binding proteins (aP2), lipoprotein lipase (LPL) and leptin. Conclusion: This study indicated that the ethanol extract, hexane fraction and ethyl acetate fraction of P. trifoliata fruits possess strong anti-adipogenic activity, containing the active compounds such as phellopterin, oxypeucedanin and poncirin. Further research is recommended to explore their efficacy and safety in animal and clinical models.

Angiopteris helferiana C.Presl is a gigantic fleshy-type fern, belonging to Marattiaceae family. In previous study, we reported the potent anti-adipogenic and anti-inflammatory activities of ethylacetate (EtOAc) and n-butanol (BuOH) fractions of methanol extract of rhizomes of A. helferiana. In continuation, in this study, we report the isolation, characterization, and bioactivity analysis of principle bioactive compounds in these fractions. (−)-epi-Osmundalactone (1) and angiopteroside (2) were isolated from EtOAc and BuOH fractions, respectively. The structures of these compounds were established on the basis of NMR spectroscopic data. The quantification study using UPLC revealed the contents of compounds 1 and 2 in the dried rhizome to be 1.54% and 3.2%, respectively. These compounds were evaluated for their anti-adipogenic and anti-inflammatory activities using 3T3-L1 and RAW 264.7 cells, respectively. Compound 1 (2.5 µg/mL) and 2 (20 µg/mL) inhibited the lipid production by 35% and 25%, respectively. Regarding the anti-inflammatory activity, compound 1 (5 µg/mL) inhibited the nitrite production by nearly 82%. In conclusion, the presence of potent anti-adipogenic and anti-inflammatory compounds in A. helferiana indicate its potential role in the use of herb-based treatment for obesity and other related diseases.

The Cheilanthes albomarginata Clarke (CA), a fern belonging to Pteridaceae family, is found mainly in India, Nepal, Pakistan and Bhutan at an altitude of 1300–2700 m. It grows mostly in the rock crevices on slopes. Juice from the rhizome of CA has been used to treat peptic ulcer. In this study, the biological activities (antioxidant, anti-inflammatory, anti-adipogenic and anti-obesity) of the extracts of CA were investigated. The total phenolic content of each extract was quantified. This is the first report regarding the study of biological activities on CA. In the current study, the crude methanol and fractionated extract of the aerial part of CA were investigated for the antioxidant tests which were namely DPPH assay, hydrogen peroxide scavenging assay and nitrite scavenging assay. Their phenolic contents were measured by the Folin-Ciocalteu’s method. In vitro anti-inflammatory and anti-adipogenic assays were evaluated against the RAW 264.7 macrophage cells and 3 T3-L1 cells respectively. The crude methanol extract and phenolic fraction (combination of ethyl acetate and butanol fraction) were studied for the in vivo anti-obesity test using male Sprague Dawley rats. The ethyl acetate fraction showed the strongest DPPH radical scavenging (82.54 ± 0.48%), hydrogen peroxide scavenging (3.41 ± 0.21 mg/ml) and nitrite scavenging activity (61.39%). The highest phenolic content was found in the ethyl acetate fraction followed by the butanol fraction. The ethyl acetate fraction showed the highest in vitro anti-inflammatory and anti-adipogenic activities. From the in vivo study on rats, the crude methanol extract and phenolic fraction showed plasma triglyceride lowering activity as well as reduction of weight of adipose tissue in high fat diet induced obese rats. The current study suggests that the ethyl acetate and butanol extracts of CA are potential source for antioxidant, anti-inflammatory and anti-adipogenic remedies. In addition to that the results of in vivo studies evidenced the possibility of CA as a source of anti-obesity drug remedies.

Myrrh essential oil (MEO) is widely used as remedies for the different human ailment in different parts of the world. The misuse of this natural product in higher doses may lead to fever, inflammation, and liver and kidney problems. In this study, we performed the acute and subacute toxicity analysis of MEO in mice model after subcutaneous injection and evaluated the safe dose to prevent the possible risk and side effects. Initially (first phase study) higher dose of MEO (20, 40, and 80 μL) was injected, and later in the second phase study lower dose of MEO (1, 5, and 10 μL) was injected for three days in each group of mice. Blood samples were taken for the investigation of hematological parameters and activity of various enzymes. The liver, kidney, spleen, lungs, and heart were excised for histological study. The body weight and skin abnormalities were also evaluated. In the first phase study, the mice showed granuloma formation at the site of injection. The liver showed dilated sinusoids and enlarged central vein. In the spleen the distinction between red and white pulp was lost. The kidney showed the degeneration of glomerulus. The enzyme activity and body weight were also decreased by the higher dose. The WBC count also increased nearly by twofold. Pruritus and self-trauma were also evident. Later in the second phase study, the skin abnormalities (granuloma) and damage in the structure of tissue (in liver, spleen, and kidney) were absent along with no change in enzyme levels, blood parameters, and body weight compared to the control. The MEO was toxic to liver, spleen, and kidney in the higher doses. The safe volume of MEO useful for various studies in mice was evaluated. The safe use of MEO should be assured, it should not be misused, being considered as a natural remedy, and there should be awareness of its toxicity and side effects.