Neuroprotective mechanisms of red clover and soy isoflavones in Parkinson's disease models.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by nigrostriatal degeneration and the spreading of aggregated forms of the presynaptic protein α-synuclein (aSyn) throughout the brain. PD patients are currently only treated with symptomatic therapies, and strategies to slow or stop the progressive neurodegeneration underlying the disease's motor and cognitive symptoms are greatly needed. The time between the first neurobiochemical alterations and the initial presentation of symptoms is thought to span several years, and early neuroprotective dietary interventions could delay the disease onset or slow PD progression. In this study, we characterized the neuroprotective effects of isoflavones, a class of dietary polyphenols found in soy products and in the medicinal plant red clover (Trifolium pratense). We found that isoflavone-rich extracts and individual isoflavones rescued the loss of dopaminergic neurons and the shortening of neurites in primary mesencephalic cultures exposed to two PD-related insults, the environmental toxin rotenone and an adenovirus encoding the A53T aSyn mutant. The extracts and individual isoflavones also activated the Nrf2-mediated antioxidant response in astrocytes via a mechanism involving inhibition of the ubiquitin-proteasome system, and they alleviated deficits in mitochondrial respiration. Furthermore, an isoflavone-enriched soy extract reduced motor dysfunction exhibited by rats lesioned with the PD-related neurotoxin 6-OHDA. These findings suggest that plant-derived isoflavones could serve as dietary supplements to delay PD onset in at-risk individuals and mitigate neurodegeneration in the brains of patients.

[Posttraumatic Osteomyelitis: Improvement in Outcome by Negative Pressure Wound Therapy with Instillation Technique]. / Posttraumatische Osteomyelitis: bessere Behandlungsergebnisse durch innovative Vakuumversiege­lungstechnik mit Instillationstherapie.

Posttraumatic Osteomyelitis: Improvement in Outcome by Negative Pressure Wound Therapy with Instillation Technique Abstract. Surgical treatment of post-traumatic (fistula) osteomyelitis can be difficult and is associated with an increased risk of later recurrence. Very often osteomyelitis is accompanied by a soft tissue (defective) wound. After surgical debridement, the use of the vacuum sealing technique can stimulate wound healing and improve local blood circulation. In particular, the introduction of the innovative instillation technique for wound sponges can increase the effectiveness of the treatment of the infection. By regularly rinsing the sponges with an antiseptic polyhexanide solution, the duration of treatment, the number of operations, the in-patient stay and the recurrence rate in this patient group can be statistically significantly reduced.

Lumbee traditional medicine: Neuroprotective activities of medicinal plants used to treat Parkinson's disease-related symptoms.

ETHNOPHARMACOLOGICAL RELEVANCE: Parkinson's disease (PD) is a neurodegenerative disorder characterized by a loss of dopaminergic neurons in the substantia nigra pars compacta and the presence in surviving neurons of Lewy body inclusions enriched with aggregated forms of the presynaptic protein α-synuclein (aSyn). Although current therapies provide temporary symptomatic relief, they do not slow the underlying neurodegeneration in the midbrain. In this study, we analyzed contemporary herbal medicinal practices used by members of the Lumbee tribe to treat PD-related symptoms, in an effort to identify safe and effective herbal medicines to treat PD. AIM OF THE STUDY: The aims of this study were to (i) document medicinal plants used by Lumbee Indians to treat PD and PD-related symptoms, and (ii) characterize a subset of plant candidates in terms of their ability to alleviate neurotoxicity elicited by PD-related insults and their potential mechanisms of neuroprotection. MATERIALS AND METHODS: Interviews of Lumbee healers and local people were carried out in Pembroke, North Carolina, and in surrounding towns. Plant samples were collected and prepared as water extracts for subsequent analysis. Extracts were characterized in terms of their ability to induce activation of the nuclear factor E2-related factor 2 (Nrf2) antioxidant response in cortical astrocytes. An extract prepared from Sambucus caerulea flowers (elderflower extract) was further examined for the ability to induce Nrf2-mediated transcription in induced pluripotent stem cell (iPSC)-derived astrocytes and primary midbrain cultures, to ameliorate mitochondrial dysfunction, and to alleviate rotenone- or aSyn-mediated neurotoxicity. RESULTS: The ethnopharmacological interviews resulted in the documentation of 32 medicinal plants used to treat PD-related symptoms and 40 plants used to treat other disorders. A polyphenol-rich extract prepared from elderflower activated the Nrf2-mediated antioxidant response in cortical astrocytes, iPSC-derived astrocytes, and primary midbrain cultures, apparently via the inhibition of Nrf2 degradation mediated by the ubiquitin proteasome system. Furthermore, the elderflower extract rescued mitochondrial functional deficits in a neuronal cell line and alleviated neurotoxicity elicited by rotenone and aSyn in primary midbrain cultures. CONCLUSIONS: These results highlight potential therapeutic benefits of botanical extracts used in traditional Lumbee medicine, and they provide insight into mechanisms by which an elderflower extract could suppress neurotoxicity elicited by environmental and genetic PD-related insults.

In vitro lipolytic, antioxidant and anti-inflammatory activities of roasted pistachio kernel and skin constituents.

A comprehensive phytochemical analysis was conducted on pistachios to identify the differential contributions of skin and kernel phytochemicals to in vitro bioactivity. Qualitative and quantitative analyses of skin and kernel non-polar extracts (SNP and KNP, respectively) indicated that the major components are fatty acids (696.36 and 879.70 mg g-1), phytosterols (16.08 and 4.28 mg g-1), and γ-tocopherol (304.17 and 397.10 µg g-1). Analysis of the skin and kernel polar extracts (SP and KP, respectively) showed that skin accumulated higher levels of phenolic compounds, especially flavan-3-ols, compared to the kernel. An (epi)catechin hexoside was the major component in SP and KP (9.8 mg g-1 and 3.3 mg g-1, respectively). Flavan-3-ols with different degrees of polymerization were detected in SP, but only the monomers were identified in the KP. Quercetin glycosides were the major flavonols present in both SP and KP. Bioassays with 3T3L1 mouse adipocytes demonstrated that all extracts decreased lipid accumulation, with SNP demonstrating the highest activity (17% inhibition). Bioassay guided fractionation of SNP indicated that the lipolytic activity was highest in the fraction consisting of linoleic acid (20%), linolenic acid (10%), and ß-sitosterol (50%). Radical scavenging assays indicated that all pistachio extracts significantly inhibited ROS, while SP was the most inhibiting to NO production in LPS-stimulated RAW 264.7 macrophages. Gene expression profiles associated with inflammation (IL6, iNOS, and COX2) were characterized in the LPS-stimulated RAW264.7 macrophages after treatment with pistachio extracts. SP and KP were the most potent to inhibit the expression of COX2. The SNP had the strongest effect in decreasing non-mitochondrial oxidative burst associated with inflammatory response in macrophages.

Chemical composition, antioxidant and anti-inflammatory properties of pistachio hull extracts.

Phytochemical and bioactivity analyses of pistachio hulls revealed the presence of anacardic acids (3198mg/100g), fatty acids (1500mg/100g), and phytosterols (192mg/100g) as major components. Carotenoids (4.93mg/100g), chlorophylls (10.27mg/100g), tocopherols (8.83mg/100g), and three triterpene acids (mangiferolic, isomangiferolic and mangiferonic acids) were characterized. A polar (P) extract contained quercetin-3-O-glucoside (6.27mg/g), together with smaller concentrations of quercetin, myricetin and luteolin flavonoids, accounting for 5.53mg/g. Gallotannins and other phenolic compounds esterified with a gallic acid moiety characterized the P extract. P extract potently inhibited the release of nitric oxide (NO) and reactive oxygen species (ROS) in lipopolysaccharide-stimulated RAW 264.7 macrophage cells. The mRNA expression levels of the anti-inflammatory cytokine COX-2 were significantly inhibited by fractions P2-P5, while IL-6 was only inhibited by fraction P3. Moreover, the P extract significantly decreased the non-mitochondrial oxidative burst associated with inflammatory response in macrophages.

Characterization of Phenolic Compounds and Antioxidant and Anti-inflammatory Activities from Mamuyo (Styrax ramirezii Greenm.) Fruit.

Extracts of Styrax ramirezii Greenm., a fruit traditionally valued for health and wellness in Mexico, were analyzed phytochemically and evaluated for antioxidant and anti-inflammatory activity. Six norneolignans were identified by HPLC-TOF-MS, and the two major compounds were isolated for further evaluation. The effects of the isolated norneolignans, egonol and homoegonol, on lipopolysaccharide (LPS)-induced nitric oxide (NO) production, reactive oxygen species (ROS) production, and biomarkers of inflammation were evaluated. Of the tested compounds, egonol potently inhibited the production of NO and also significantly reduced the release of ROS. Consistent with these observations, the mRNA expression levels of inducible nitric oxide synthase (iNOS) (0.668 ± 0.108), cyclooxygenase-2 (COX-2) (0.553 ± 0.007), interleukin-1ß (IL-1ß) (0.093 ± 0.005), and interleukin-6 (IL-6) (0.298 ± 0.076) were reduced by egonol. The activity for both egonol and homoegonol increased in a concentration-dependent manner. These results suggest the potential of S. ramirezii Greenm. fruit to contribute to a healthy diet, rich in antioxidant and anti-inflammatory compounds.

Phenylphenalenones and oxabenzochrysenones from the Australian plant Haemodorum simulans.

Chemical investigation of the Australian plant Haemodorum simulans (Haemodoraceae) resulted in the isolation of two new phenylphenalenones, haemoxiphidone and haemodordioxolane from the bulbs together with the first report of an oxabenzochrysenone glycoside, haemodoroxychrysenose from the aerial parts of the plant. Also isolated were two previously described phenylphenalenones 5,6-dimethoxy-7-phenyl-1H,3H-naphtho[1,8-cd]pyran-1,3-dione and haemodorone and two oxabenzochrysenones 5-hydroxyl-2-methoxy-1H-naphtho[2,1,8-mna]xanthen-1-one and 5-methoxy-1H-naphtho[2,1,8-mna]xanthen-1-one. The X-ray structure of the phenylphenalenone 5,6-dimethoxy-7-phenyl-1H,3H-naphtho[1,8-cd]pyran-1,3-dione was secured for the first time. All compounds were deduced by detailed spectroscopic analyses. HPLC-NMR chemical profiling of an enriched fraction containing a mixture of haemodordioxolane and 5,6-dimethoxy-7-phenyl-1H,3H-naphtho[1,8-cd]pyran-1,3-dione facilitated the partial identification of these secondary metabolites. The structure previously assigned as xiphidone in our initial studies of this plant was re-assigned as the new isomer haemoxiphidone.

Application of HPLC-NMR in the identification of plocamenone and isoplocamenone from the marine red alga Plocamium angustum.

A combination of on-line HPLC-NMR and off-line chemical investigations has resulted in the identification of the previously reported polyhalogenated monoterpene plocamenone, together with the new structural analogue isoplocamenone from the crude extract of the marine alga Plocamium angustum. On-flow and stop-flow HPLC-NMR analyses (including the acquisition of WET 2D NMR spectra) rapidly assisted in the identification of the major component plocamenone and in the partial identification of its unstable double bond isomer isoplocamenone. Conventional off-line isolation and structural characterization techniques were employed to unequivocally confirm both structures, leading to a structural revision for plocamenone, as well as to obtain sufficient quantities for biological testing.

On-line (HPLC-NMR) and off-line phytochemical profiling of the Australian plant, Lasiopetalum macrophyllum.

On-line (HPLC-NMR) and off-line (HPLC, NMR and MS) methodologies were used to profile the constituents present in the crude extract of Lasiopetalum macrophyllum. On-flow and stop-flow HPLC-NMR supported the presence of trans-tiliroside and permitted partial identification of cis-tiliroside and 4'-methoxy-trans-tiliroside. Off-line isolation led to the unequivocal identification of four flavanoid glycosides including a new structural derivative, 4'-methoxycis-tiliroside. This is the first report of flavonoid glycosides occurring in this plant genus. In addition, a number of structure revisions have been proposed for previously reported flavonoid glycosides that were incorrectly assigned.

On-line (HPLC-NMR) and off-line phytochemical profiling of the Australian plant, Lasiopetalum macrophyllum.

On-line (HPLC-NMR) and off-line (HPLC, NMR and MS) methodologies were used to profile the constituents present in the crude extract of Lasiopetalum macrophyllum. On-flow and stop-flow HPLC-NMR supported the presence of trans-tiliroside and permitted partial identification of cis-tiliroside and 4'-methoxy-trans-tiliroside. Off-line isolation led to the unequivocal identification of four flavanoid glycosides including a new structural derivative, 4'-methoxy-cis-tiliroside. This is the first report of flavonoid glycosides occurring in this plant genus. In addition, a number of structure revisions have been proposed for previously reported flavonoid glycosides that were incorrectly assigned.

Negative pressure wound treatment with polyvinyl alcohol foam and polyhexanide antiseptic solution instillation in posttraumatic osteomyelitis.

In a retrospective, case-control cohort study an assessment was made of the clinical outcome of patients with osteomyelitis treated with a new modality of negative pressure wound therapy, so called negative pressure instillation therapy. In this approach, after surgical debridement, a site of osteomyelitis is treated with negative pressure of at least 300 mmHg applied through polyvinyl alcohol dressing. The polyvinyl alcohol foam is irrigated through the tubes three times a day with a polyhexanide antiseptic solution. In 30 patients (14 males; mean age 52 [range, 26-81]) admitted between 1999 and 2003 with osteomyelitis of the pelvis or lower extremity, we assessed time to wound closure, number of surgical procedures and rate of recurrence of infection as well as need for rehospitalizations. For comparison, a control group of 94 patients (males, 58; mean age 47 [range, 9-85]), matched for site and severity of osteomyelitis, was identified in hospital records between 1982 and 2002. These patients underwent standard surgical debridement, implantation of gentamicin polymethylmethacrylate beads and long-term intravenous antibiotics. In the Instillation group the rate of recurrence of infection was 3/30 (10%), whereas 55/93 (58.5%) of the controls had a recurrence (p<0.0001). Moreover, in those treated with instillation the total duration of hospital stay was shorter and number of surgical procedures smaller as compared with the controls (all p<0.0001). We conclude that in posttraumatic osteomyelitis negative pressure instillation therapy reduces the need for repeated surgical interventions in comparison with the present standard approach.