Poria cocos Modulates Th1/Th2 Response and Attenuates Airway Inflammation in an Ovalbumin-Sensitized Mouse Allergic Asthma Model.

Poria cocos, called fuling, is a famous tonic in traditional Chinese medicine that reportedly possesses various pharmacological properties, including anti-inflammation and immunomodulation. However, few studies have investigated the effects of P. cocos on allergic diseases, such as allergic asthma. Allergic asthma is caused primarily by Th2 immune response and characterized by airway inflammation. This study first demonstrated the anti-allergic and anti-asthmatic effects of P. cocos extract (Lipucan®). P. cocos extract distinctly exhibited reduced inflammatory cell infiltration in the peribronchial and peribronchiolar regions compared to the asthma group in the histological analysis of pulmonary tissue sections. Prolonged P. cocos extract administration significantly reduced eosinophil infiltration, PGE2 levels, total IgE, and OVA-specific IgE. Moreover, P. cocos extract markedly suppressed Th2 cytokines, IL-4, IL-5, and IL-10. On the other hand, P. cocos extract significantly elevated IL-2 secretion by Th1 immune response. In addition, P. cocos extract elevated the IFN-γ level at a lower dose. We also observed that P. cocos extract increased the activity of NK cells. Our results suggest that P. cocos extract remodels the intrinsic Th1/Th2 response to prevent or alleviate allergy-induced asthma or symptoms.

The Lanostane Triterpenoids in Poria cocos Play Beneficial Roles in Immunoregulatory Activity.

Poria cocos (Schwein) F.A. Wolf (syn. Wolfiporia cocos) dried sclerotium, called fuling, is an edible, saprophytic fungus commonly used as a tonic and anti-aging traditional Chinese medicine. It is traditionally used in combination with other traditional Chinese medicines to enhance immunity. This study showed that P. cocos extract (Lipucan®) containing lanostane triterpenoids has no immunotoxicity and enhances non-specific (innate) immunity though activating natural killer cells and promotes interferon γ (IFN-γ) secretion by Type 1 T-helper (Th1) cells immune response. In addition, P. cocos extract significantly decreased interleukin (IL-4 and IL-5) secretion by Type 2 T-helper (Th2) cells immune response, which are related to the allergy response. The purified lanostane triterpenoids were first identified as active ingredients of P. cocos with enhanced non-specific immunity by promoting interferon γ (IFN-γ) secretion in a preliminary study. Our findings support that the P. cocos extract plays beneficial roles in immunoregulatory activity.

Inhibition of Amyloid Beta Aggregation and Deposition of Cistanche tubulosa Aqueous Extract.

Cistanche tubulosa aqueous extract (CTE) is already used as a botanical prescription drug for treating dementia in China. Our previous studies reported that phenylethanoid glycosides of CTE have anti-Alzheimer's disease (AD) activity by inhibiting amyloid ß peptide (Aß) aggregation and deposition. However, recent studies considered that the phenylethanoid glycosides may be metabolized by intestinal bacteria, because all analysis results showed that the bioavailability of phenylethanoid glycosides is extremely low. In this study we demonstrate how iron chelation plays a crucial role in the Aß aggregation and deposition inhibition mechanism of phenylethanoid glycosides of CTE. In addition, we further proved phenylethanoid glycosides (1⁻3) could reach brain. Active CTE component and action mechanism confirmation will be a great help for product quality control and bioavailability studies in the future. At the same time, we provide a new analysis method useful in determining phenylethanoid glycosides (1⁻3) in plants, foods, blood, and tissues for chemical fingerprint and pharmacokinetic research.

Echinacoside ameliorates the memory impairment and cholinergic deficit induced by amyloid beta peptides via the inhibition of amyloid deposition and toxicology.

Echinacoside is a phenylethanoid glycoside and possesses neuroprotective activity in vitro and in vivo. This study investigates the role of the amyloid cascade and central neuronal function on the protective effects of echinacoside in amyloid ß peptide 1-42 (Aß 1-42)-treated SH-SY5Y cells and an Aß 1-42-infused rat. Echinacoside inhibited Aß 1-42 oligomerization in vitro and restored the cell viability that was reduced by Aß 1-42 in SH-SY5Y cells. Intracisternal infusion with Aß 1-42 by an osmotic pump caused cognitive deficits, an increase in amyloid deposition and acetylcholinesterase activities, and a decrease in the brain's levels of acetylcholine and dopamine. Echinacoside reduced the cognitive deficits and amyloid deposition, and it reversed the cortical cholinergic dysfunction that was caused by Aß 1-42 in rats. Echinacoside further reversed the memory impairment in the Morris water maze task caused by scopolamine in mice. Therefore, we suggest that echinacoside ameliorated cognitive dysfunction that was caused by Aß 1-42 by blocking amyloid deposition via inhibiting amyloid oligomerization and reversing the cortical cholinergic neuronal function via decreasing amyloid neurotoxicity.

Acteoside and Isoacteoside Protect Amyloid ß Peptide Induced Cytotoxicity, Cognitive Deficit and Neurochemical Disturbances In Vitro and In Vivo.

Acteoside and isoacteoside, two phenylethanoid glycosides, coexist in some plants. This study investigates the memory-improving and cytoprotective effects of acteoside and isoacteoside in amyloid ß peptide 1-42 (Aß 1-42)-infused rats and Aß 1-42-treated SH-SY5Y cells. It further elucidates the role of amyloid cascade and central neuronal function in these effects. Acteoside and isoacteoside ameliorated cognitive deficits, decreased amyloid deposition, and reversed central cholinergic dysfunction that were caused by Aß 1-42 in rats. Acteoside and isoacteoside further decreased extracellular Aß 1-40 production and restored the cell viability that was decreased by Aß 1-42 in SH-SY5Y cells. Acteoside and isoacteoside also promoted Aß 1-40 degradation and inhibited Aß 1-42 oligomerization in vitro. However, the memory-improving and cytoprotective effects of isoacteoside exceeded those of acteoside. Isoacteoside promoted exploratory behavior and restored cortical and hippocampal dopamine levels, but acteoside did not. We suggest that acteoside and isoacteoside ameliorated the cognitive dysfunction that was caused by Aß 1-42 by blocking amyloid deposition via preventing amyloid oligomerization, and reversing central neuronal function via counteracting amyloid cytotoxicity.

Reversal by aqueous extracts of Cistanche tubulosa from behavioral deficits in Alzheimer's disease-like rat model: relevance for amyloid deposition and central neurotransmitter function.

BACKGROUND: Cistanche tubulosa (Schenk) R. Wight (CT) is commonly used to treat forgetfulness by traditional Chinese physicians. This study presents the ameliorating effects of CT extract which was quantified with three phenylpropanoid glycosides in Alzheimer's disease (AD)-like rat model. METHODS: Amyloid ß peptide 1-42 (Aß 1-42) intracisternally infused to rats by osmotic pump (Alzet 2002) was used as an AD-like rat model. The major pathological makers were measured including Aß 1-42 immunohistochemical stain, behavioral tests (inhibitory avoidance task and Morris water maze) and central neurotransmitter functions. RESULTS: Aß 1-42 caused the cognitive deficits, the increase in the amyloid deposition and acetylcholinesterase activities, and the decrease in the levels of brain's acetylcholine and dopamine. Daily administration of CT extract throughout Aß 1-42 infusion periods ameliorated the cognitive deficits, decreased amyloid deposition and reversed cholinergic and hippocampal dopaminergic dysfunction caused by Aß 1-42. Donepezil also ameliorated the cognitive dysfunction, but only blocked the amyloid deposition and cholinergic dysfunction caused by Aß 1-42. CONCLUSIONS: We suggest that CT extract, containing enough echinacoside and acteoside, ameliorated the cognitive dysfunction caused by Aß 1-42 via blocking amyloid deposition, reversing cholinergic and hippocampal dopaminergic neuronal function.

Ganoderma tsugae Extract Inhibits Growth of HER2-Overexpressing Cancer Cells via Modulation of HER2/PI3K/Akt Signaling Pathway.

Ganoderma, also known as Lingzhi or Reishi, has been used for medicinal purposes in Asian countries for centuries. It is a medicinal fungus with a variety of biological properties including immunomodulatory and antitumor activities. In this study, we investigated the molecular mechanisms by which Ganoderma tsugae (GT), one of the most common species of Ganoderma, inhibits the proliferation of HER2-overexpressing cancer cells. Here, we show that a quality assured extract of GT (GTE) inhibited the growth of HER2-overexpressing cancer cells in vitro and in vivo and enhanced the growth-inhibitory effect of antitumor drugs (e.g., taxol and cisplatin) in these cells. We also demonstrate that GTE induced cell cycle arrest by interfering with the HER2/PI3K/Akt signaling pathway. Furthermore, GTE curtailed the expression of the HER2 protein by modulating the transcriptional activity of the HER2 gene and the stability/degradation of the HER2 protein. In conclusion, this study suggests that GTE may be a useful adjuvant therapeutic agent in the treatment of cancer cells that highly express HER2.

An open-label, nonplacebo-controlled study on Cistanche tubulosa glycoside capsules (Memoregain(®)) for treating moderate Alzheimer's Disease.

AIM: Efficacy and safety of Cistanche tubulosa glycoside capsules (CTG capsule, Memoregain(®)) for treating Alzheimer's disease (AD) were studied. METHODS: A total of 18 patients with AD administered with Memoregain(®) for 48 weeks were assessed for drug efficacy by Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Mini-Mental State Examination (MMSE), Activities of Daily Living (ADLs), Blessed Behavioral Scale, and Clinical Global Impression (CGI) scales. RESULTS: The MMSE score was 14.78 ± 2.51 at baseline and 14.06 ± 4.26 at study completion. While changes in ADAS-cog score before and after 48 weeks of treatment were statistically insignificant, the score improved, deteriorated, and remained unchanged in 10, 7, and 1 patients, respectively. The ADL and CGI scores showed no significant difference from baseline. All adverse reactions were mild. CONCLUSION: After Memoregain(®) treatment, patients with AD showed no obvious aggravation of cognitive function, independent living ability, and overall conditions but were stable throughout the study. Comparison with other long-term medications with acetylcholinesterase inhibitors suggests that Memoregain(®) has a potential to be a possible treatment option for mild to moderate AD. Large trials with bigger population are required to confirm.

Ganoderma tsugae Induces S Phase Arrest and Apoptosis in Doxorubicin-Resistant Lung Adenocarcinoma H23/0.3 Cells via Modulation of the PI3K/Akt Signaling Pathway.

Ganoderma tsugae (GT) is a traditional Chinese medicine that exhibits significant antitumor activities against many types of cancer. This study investigated the molecular mechanism by which GT suppresses the growth of doxorubicin-resistant lung adenocarcinoma H23/0.3 cells. Our results reveal that GT inhibits the viability of H23/0.3 cells in vitro and in vivo and sensitizes the growth suppression effect of doxorubicin on H23/0.3 cells. The data also show that GT induces S phase arrest by interfering with the protein expression of cyclin A, cyclin E, CDK2, and CDC25A. Furthermore, GT induces cellular apoptosis via induction of a mitochondria/caspase pathway. In addition, we also demonstrate that the suppression of cell proliferation by GT is through down-regulation of the PI3K/Akt signaling pathway. In conclusion, this study suggests that GT may be a useful adjuvant therapeutic agent in the treatment of lung cancer.

The hypocholesterolemic effects of Cistanche tubulosa extract, a Chinese traditional crude medicine, in mice.

The roots of Cistanche (C.) tubulosa (Orobanchaceae), a parasitic plant that grows in the Taklamakan desert, are traditionally used as medicines and foods in China. We prepared aqueous ethanol extract (CTE) from the roots of C. tubulosa and its hypocholesterolemic effect was evaluated. Using gene chip and RT-PCR analysis of the livers of mice given CTE (400 mg/kg) for 14 days, we found mRNA expression of molecules related to cholesterol transport [apolipoprotein B and very low density lipoprotein (VLDL) receptor] and metabolism [cytochrome P450 side chain cleave (SCC) and steroid 5alpha-reductase 2] were up-regulated. The administration of CTE (400 mg/kg) for 14 days significantly suppressed serum cholesterol elevation in high cholesterol diet-fed mice. The mRNA expressions of VLDL receptor and cytochrome P450 SCC were significantly enhanced. In addition, acteoside, a major constituent of CTE, was found to enhance the mRNA expressions of apolipoprotein B, VLDL receptor, and cytochrome P450 SCC in HepG2 hepatocytes. These results suggest that CTE affects the mRNA expressions of molecules related to cholesterol transport and metabolism and exhibits hypocholesterolemic activity in diet-induced hypercholesterolemia mice. Acteoside was involved in the hypocholesterolemic activity of CTE.

Shifting from haloperidol to risperidone for behavioral disturbances in dementia: safety, response predictors, and mood effects.

For agitated dementia showing insufficient response to conventional antipsychotics, the feasibility of transition to atypical agents remains unknown. Sixty-two Chinese inpatients with dementia and disruptive behaviors were recruited into an 8-week screening trial of haloperidol. Thirty-five (56%) of them responded insufficiently. They then entered a prospective, 16-week, open-labeled study. Haloperidol was abruptly shifted to risperidone 0.5 mg/day at weeks 1 to 4 and then 1 mg/day at weeks 5 to 12. At weeks 13 to 16, the regimen was shifted back to haloperidol at previous doses, mostly 1 mg/day. Safety, efficacy, cognition, and moods were evaluated at least every 4 weeks. Generalized estimating equation methods were used for determining the effects of the prognostic variables on the outcome values. Risperidone, particularly at 0.5 mg/day, was generally tolerable. The Brief Psychiatric Rating Scale (BPRS) score decreased progressively under risperidone treatment; at week 12, 16 (46%) patients showed response (>or=25% reduction in the BPRS). Patients with vascular dementia were more likely to respond than those with Alzheimer's disease ( p = 0.02). Haloperidol reinstitution resulted in no further improvement, except trend increments in motor symptoms. Risperidone also tended to benefit the performance on the Behavioral Pathology in Alzheimer's Disease Rating Scale. Six (17%) patients improved on moods and self-care with risperidone. These preliminary results suggest that crossover from haloperidol to risperidone is generally safe and effective and may produce favorable moods in agitated dementia patients. Vascular dementia is a predictor of treatment response. In contrast to the dose (1 mg/day) recommended for most white individuals, 0.5 mg/day could be tried at first in Chinese patients. Because of the design's limitations, further controlled studies are warranted.