Transcranial near-infrared light in treatment of neurodegenerative diseases.

Light is a natural agent consisting of a range of visible and invisible electromagnetic spectrum travels in waves. Near-infrared (NIR) light refers to wavelengths from 800 to 2,500 nm. It is an invisible spectrum to naked eyes and can penetrate through soft and hard tissues into deep structures of the human body at specific wavelengths. NIR light may carry different energy levels depending on the intensity of emitted light and therapeutic spectrum (wavelength). Stimulation with NIR light can activate intracellular cascades of biochemical reactions with local short- and long-term positive effects. These properties of NIR light are employed in photobiomodulation (PBM) therapy, have been linked to treating several brain pathologies, and are attracting more scientific attention in biomedicine. Transcranial brain stimulations with NIR light PBM in recent animal and human studies revealed a positive impact of treatment on the progression and improvement of neurodegenerative processes, management of brain energy metabolism, and regulation of chronic brain inflammation associated with various conditions, including traumatic brain injury. This scientific overview incorporates the most recent cellular and functional findings in PBM with NIR light in treating neurodegenerative diseases, presents the discussion of the proposed mechanisms of action, and describes the benefits of this treatment in neuroprotection, cell preservation/detoxification, anti-inflammatory properties, and regulation of brain energy metabolism. This review will also discuss the novel aspects and pathophysiological role of the glymphatic and brain lymphatics system in treating neurodegenerative diseases with NIR light stimulations. Scientific evidence presented in this overview will support a combined effort in the scientific community to increase attention to the understudied NIR light area of research as a natural agent in the treatment of neurodegenerative diseases to promote more research and raise awareness of PBM in the treatment of brain disorders.

Danshen-Honghua Ameliorates Stress-Induced Menopausal Depression in Rats.

Objective: Previously, we have shown that Danshen-Honghua (DSHH) for cognitive deficits after ischemia induced impairments of the hippocampus. Here, we investigate the effects of DSHH on stress-induced depression in menopausal rats. Methods: A rat model with menopausal depression was established with bilateral ovariectomies in female SD rats followed by chronic mild stress treatment for 21 days. 40 rats were randomly divided into the sham surgery group (sham surgery and no stress treatment), surgery group (surgery with no stress treatment), surgery/stress group (surgery and stress treatment), fluoxetine group (2.4 mg·kg-1, with surgery and stress treatment), and DSHH group (35 g·kg-1, with surgery and stress treatment). The rats in the last two groups were treated with stresses together with intragastric drug administration for three weeks after the surgery. Then open-field locomotor scores and sucrose intake were tested for behavior changes. Also, the levels of norepinephrine (NE), dopamine (DA), serotonin (5-HT), and cortisone were determined by high-performance liquid chromatography (HPLC). Serum estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were determined by radioimmunoassay. Results: The results of open-field locomotor scores, sucrose intake in both the fluoxetine group and DSHH group, were significantly higher than those of the surgery/stress group (P < 0.01). Serum LH, FSH, and cortisone levels in both the DSHH group and fluoxetine group were significantly lower than those in the surgery/stress group (P < 0.01). Serum E2 levels in these groups were slightly increased in these medicine groups (P < 0.01). The monoamine levels in the DSHH group were much higher than those in the surgery/stress group (P < 0.01). Conclusion: DSHH can ameliorate stress-induced depressed syndromes in the surgery/stressed rats via regulating LH and FSH levels as well as monoamine levels.

Catalpol protects synaptic proteins from beta-amyloid induced neuron injury and improves cognitive functions in aged rats.

Synapse loss is one of the common factors contributing to cognitive disorders, such as Alzheimer's disease (AD), which is manifested by the impairment of basic cognitive functions including memory processing, perception, problem solving, and language. The current therapies for patients with cognitive disorders are mainly palliative; thus, regimens preventing and/or delaying dementia progression are urgently needed. In this study, we evaluated the effects of catalpol, isolated from traditional Chinese medicine Rehmannia glutinosa, on synaptic plasticity in aged rat models. We found that catalpol markedly improved the cognitive function of aged male Sprague-Dawley rats and simultaneously increased the expression of synaptic proteins (dynamin 1, PSD-95, and synaptophysin) in the cerebral cortex and hippocampus, respectively. In beta-amyloid (Aß) injured primary rat's cortical neuron, catalpol did not increase the viability of neuron but extended the length of microtubule-associated protein 2 (MAP-2) positive neurites and reversed the suppressive effects on expression of synaptic proteins induced by Aß. Additionally, the effects of catalpol on stimulating the growth of MAP-2 positive neurites and the expression of synaptic proteins were diminished by a PKC inhibitor, bisindolylmaleimide I, suggesting that PKC may be implicated in catalpol's function of preventing the neurodegeneration induced by Aß. Altogether, our study indicates that catalpol could be a potential disease-modifying drug for cognitive disorders such as AD.

Cambogin is preferentially cytotoxic to cells expressing PDGFR.

Platelet-derived growth factor receptors (PDGFRs) have been implicated in a wide array of human malignancies, including medulloblastoma (MB), the most common brain tumor of childhood. Although significant progress in MB biology and therapeutics has been achieved during the past decades, MB remains a horrible challenge to the physicians and researchers. Therefore, novel inhibitors targeting PDGFR signaling pathway may offer great promise for the treatment of MB. In the present study, we investigated the cytotoxicity and mechanisms of cambogin in Daoy MB cells. Our results show that cambogin triggers significant S phase cell cycle arrest and apoptosis via down regulation of cyclin A and E, and activation of caspases. More importantly, further mechanistic studies demonstrated that cambogin inhibits PDGFR signaling in Daoy and genetically defined mouse embryo fibroblast (MEF) cell lines. These results suggest that cambogin is preferentially cytotoxic to cells expressing PDGFR. Our findings may provide a novel approach by targeting PDGFR signaling against MB.

Dulxanthone A induces cell cycle arrest and apoptosis via up-regulation of p53 through mitochondrial pathway in HepG2 cells.

Natural products derived from plants provide a rich source for development of new anticancer drugs. Dulxanthone A was found to be an active cytotoxic component in Garcinia cowa by bioactivity-directed isolation. Studies to elucidate the cytotoxic mechanisms of dulxanthone A showed that dulxanthone A consistently induced S phase arrest and apoptosis in the most sensitive cell line HepG2. Furthermore, p53 was dramatically up-regulated, leading to altered expression of downstream proteins upon dulxanthone A treatment. Cell cycle related proteins, such as cyclin A, cyclin B, cyclin E, cdc-2, p21 and p27 were down-regulated. Some apoptosis correlated proteins were also altered following the drug treatment. Bcl-2 family members PUMA was up-regulated while Bcl-2 and Bax were down-regulated. However, the expression ratio of Bax/Bcl-2 was increased. This resulted in the release of cytochrome C from the mitochondria to the cytosol. Concurrently, Apaf-1 was stimulated with p53 by dulxanthone A. In result, cytochrome C, Apaf-1 and procaspase-9 form an apoptosome, which in turn triggered the activation of caspase-9, caspase-3 and downstream caspase substrates. Lamin A/C and PARP were down-regulated or cleaved, respectively. Moreover, cell cycle arrest and apoptosis in HepG2 cells induced by dulxanthone A were markedly inhibited by siRNA knockdown of p53. In summary, dulxanthone A is an active cytotoxic component of G. cowa. It induces cell cycle arrest at lower concentrations and triggers apoptosis at higher concentrations via up-regulation of p53 through the intrinsic mitochondrial pathway in HepG2 cells. Dulxanthone A is therefore likely a promising preventive and/or therapeutic agent against Hepatoma.

Cimicifuga foetida extract inhibits proliferation of hepatocellular cells via induction of cell cycle arrest and apoptosis.

The purpose of this study is to determine whether the ethyl acetate fraction (EAF) from the aerial part of Cimicifuga foetida Linnaeus possesses the anti-tumor action on hepatoma, and therefore, provide evidence for the traditional use of the plant as a detoxification agent. EAF was extracted and its cytotoxicity was evaluated on a panel of Hepatocytes by MTT assay. The IC(50) values of EAF on HepG2, R-HepG2 and primary cultured normal mouse hepatocytes were 21, 43 and 80 microg/mL, respectively. Morphology observation, Annexin V-FITC/PI staining, cell cycle analysis and western blot were used to further elucidate the cytotoxic mechanism of EAF. EAF induced G(0)/G(1)cell cycle arrest at lower concentration (25 microg/mL), and triggered G(2)/M arrest and apoptosis at higher concentrations (50 and 100 microg/mL, respectively). An increase in the ratio of Bax/Bcl-2, activation of downstream effector Caspase 3, and cleavage of poly-ADP-ribose polymerase (PARP) were implicated in EAF-induced apoptosis. In addition, EAF inhibited the growth of the implanted mouse H(22) tumor in a dose-dependent manner with the growth inhibitory rate of 63.32% at 200 mg/kg. In conclusion, EAF may potentially find use as a new therapy for the treatment of hepatoma.

Antitumor activity and mechanisms of action of total glycosides from aerial part of Cimicifuga dahurica targeted against hepatoma.

BACKGROUND: Medicinal plant is a main source of cancer drug development. Some of the cycloartane triterpenoids isolated from the aerial part of Cimicifuga dahurica showed cytotoxicity in several cancer cell lines. It is of great interest to examine the antiproliferative activity and mechanisms of total triterpenoid glycosides of C. dahurica and therefore might eventually be useful in the prevention or treatment of Hepatoma. METHODS: The total glycosides from the aerial part (TGA) was extracted and its cytotoxicity was evaluated in HepG2 cells and primary cultured normal mouse hepatocytes by an MTT assay. Morphology observation, Annexin V-FITC/PI staining, cell cycle analysis and western blot were used to further elucidate the cytotoxic mechanism of TGA. Implanted mouse H22 hepatoma model was used to demonstrate the tumor growth inhibitory activity of TGA in vivo. RESULTS: The IC50 values of TGA in HepG2 and primary cultured normal mouse hepatocytes were 21 and 105 mug/ml, respectively. TGA induced G0/G1 cell cycle arrest at lower concentration (25 mug/ml), and triggered G2/M arrest and apoptosis at higher concentrations (50 and 100 mug/ml respectively). An increase in the ratio of Bax/Bcl-2 was implicated in TGA-induced apoptosis. In addition, TGA inhibited the growth of the implanted mouse H22 tumor in a dose-dependent manner. CONCLUSION: TGA may potentially find use as a new therapy for the treatment of hepatoma.

[Cytotoxicity and mechanism of 23-O-acetylcimigenol-3-O-beta-D-xylopyranoside on HepG2 cells].

OBJECTIVE: To elucidate the cytotoxicity and mechanism of 23-O-acetylcimigenol-3-O-beta-D-xylopyranoside isolated from C. dahurica on HepG2 cells and to find the leading compound for new drug development. METHOD: MTT, AO/EB staining observation, flow cytometry and western blot methods were used to study the cytotoxicity, morphological changes, cell cycle distribution and protein expression profile of 23-O-acetylcimigenol-3-O-beta-D-xylopyranoside on HepG2 cells. RESULT: 23-O-acetylcimigenol-3-O-beta-D-xylopyranoside could inhibit the proliferation of HepG2 cells with IC50 at 16 micromol x L(-1), and could also induce apoptosis and G2-M cell cycle arrest. Further study demonstrated that the compound could cleavage PARP, regulate protein expression of bcl-2 family and decrease the expression of cdc 2 and cyclin B. CONCLUSION: 23-O-acetylcimigenol-3-O-beta-D-xylopyranoside exerts its cytotoxicity on HepG2 cells via apoptosis and G2-M arrest. In addition, caspases family activation, regulation of protein expression of bcl-2 family and down regulation of cdc 2 and cyclin B were involved in apoptosis and G2-M arrest induced by it.