Tianma-Gouteng pair ameliorates the cognitive deficits on two transgenic mouse models of Alzheimer's disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) is a progressive neurodegenerative disease. Tianma-Gouteng Pair (TGP), commonly prescribed as a pair-herbs, can be found in many Chinese medicine formulae to treat brain diseases. However, the neuroprotective effects and molecular mechanisms of TGP remained unexplored. AIM OF THE STUDY: This study investigated the difference between the TgCRND8 and 5 × FAD transgenic mice, the anti-AD effects of TGP, and underlying molecular mechanisms of TGP against AD through the two mouse models. METHODS: Briefly, three-month-old TgCRND8 and 5 × FAD mice were orally administered with TGP for 4 and 6 months, respectively. Behavioral tests were carried out to determine the neuropsychological functions. Moreover, immunofluorescence and western blotting assays were undertaken to reveal the molecular mechanisms of TGP. RESULTS: Although TgCRND8 and 5 × FAD mice had different beta-amyloid (Aß) burdens, neuroinflammation status, and cognition impairments, TGP exerted neuroprotective effects against AD in the two models. In detail, behavioral tests revealed that TGP treatment markedly ameliorated the anxiety-like behavior, attenuated the recognition memory deficits, and increased the spatial learning ability as well as the reference memory of TgCRND8 and 5 × FAD mice. Moreover, TGP treatment could regulate the beta-amyloid precursor protein (APP) processing by inhibiting the Aß production enzymes such as ß- and γ-secretases and activating Aß degrading enzyme to reduce Aß accumulation. In addition, TGP reduced the Aß42 level, the ratio of Aß42/Αß40, Aß accumulation, and tau hyperphosphorylation in both the 5 × FAD and TgCRND8 mouse models. Furthermore, TGP ameliorated neuroinflammation by decreasing the densities of activated microglia and astrocytes, and inhibiting the production of inflammatory cytokines. TGP upregulated the SIRT1 and AMPK, and downregulated sterol response element binding protein 2 (SREBP2) in the brain of TgCRND8 mice and deactivation of the EPhA4 and c-Abl in the brain tissues of 5 × FAD mice. CONCLUSION: Our experiments for the first time revealed the neuroprotective effects and molecular mechanism of TGP on 5 × FAD and TgCRND8 transgenic mouse models of different AD stages. TGP decreased the level of Aß aggregates, improved the tauopathy, and reduced the neuroinflammation by regulation of the SIRT1/AMPK/SREBP2 axis and deactivation of EPhA4/c-Abl signaling pathway in the brains of TgCRND8 and 5 × FAD mice, respectively. All these findings unequivocally confirmed that the TGP would be promising in developing into an anti-AD therapeutic pharmaceutical.

Patchouli alcohol ameliorates the learning and memory impairments in an animal model of Alzheimer's disease via modulating SIRT1.

BACKGROUND: Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases. Patchouli alcohol (PA), a major active ingredient isolated from Pogostemonis Herba, exhibits extensive bioactivity in the central nervous system (CNS) and exerts neuroprotective effects. PURPOSE: This study aimed to investigate the anti-AD effects of PA in an animal model of AD and to elucidate the underlying molecular mechanisms. METHODS: The gas chromatography (GC) was used to determine the ability of PA to pass the blood-brain barrier (BBB) in rats after oral administration. The sporadic AD rat model was established by intracerebroventricularly (ICV) injection with streptozotocin (STZ). PA (25 and 50 mg/kg) was given to rat orally once daily for 42 consecutive days. Morris water maze (MWM) test was performed to determine the learning and memory functions of the STZ-induced AD rats. EX527, a silent information regulator 1 (SIRT1) selective inhibitor, was used to investigate the involvement of SIRT1 in the anti-AD effects of PA in rats. RESULTS: PA could penetrate the BBB. MWM test results showed that PA could significantly ameliorate the learning and memory deficits induced by STZ in rats. Meanwhile, PA enhanced the expression of SIRT1, and markedly alleviated the tau pathology by inhibiting the hyperacetylation (at the site of Lys174) and hyperphosphorylation (at the sites of Thr181, Thr205, Ser396 and Ser404) of tau protein. PA also efficiently suppressed the activation of microglia and astrocytes, and the beta-amyloid (Aß) expression and the deacetylation of nuclear factor-kappa B (NF-κB) at Lys 310 (K310) in the STZ-treated AD rats. EX527, a SIRT1 selective inhibitor, could partially abolish the cognitive deficits improving effect of PA and inhibit the down-regulation of acetylated tau and acetylated NF-κB p65, suggesting that PA exhibited neuroprotective effects against AD via upregulating SIRT1. CONCLUSION: This study reported for the first time that PA could penetrate the BBB to exert its protective effects on the brain after a single-dose oral administration. The current experimental findings also amply demonstrated that PA could improve the cognitive and memory impairments in the STZ-induced AD rat model. The underlying mechanisms involve the alleviations of neuroinflammation, tau pathology and Aß deposition via modulating of SIRT1 and NF-κB pathways. All these findings strongly suggest that PA is a promising naturally occurring compound worthy of further development into an anti-AD pharmaceutical.

Effective Treatment of Small Uncomplicated Skin Abscesses with Fire Needle: A Case Series.

BACKGROUND: Uncomplicated skin abscesses are collections of pus within the skin structure and are usually caused by bacterial infections. Clinically, they are quite common and inevitably affect people of any age. The current management strategies comprise prompt initiation of antibiotics and incision and drainage. However, pain and the long healing process of skin lesions can cause distress to a lot of patients. Fire needling is a characteristic treatment in traditional Chinese medicine (TCM) and has proven effective in treating skin abscesses. Moreover, fire needle therapy has a more desirable cosmetic outcome in contrast to surgical debridement. The purpose of the study is to demonstrate the rapid, effective, minimally invasive, and better cosmetic outcomes of fire needles in the treatment of uncomplicated skin abscesses. METHODS: A total of 10 patients, aged between 1 and 45 years, with skin abscesses, were recruited. All patients who fulfilled the inclusion criteria with lesions less than 4 cm in diameter were topically treated with mupirocin ointment twice a day after fire needle therapy. If the lesion was still purulent after 2 days, it was treated again with fire needle therapy. The efficacy was assessed by a 4-grade scale at 2 days, 1 week, 2 weeks, 4 weeks and 12 weeks post-fire needling. RESULTS: Lesions with a diameter of less than 2 cm achieved significant remission (SR) or partial remission (PR), after 2 days post-treatment and reached complete remission (CR) or significant remission (SR) after 1 week following treatment. Meanwhile, lesions with a diameter of 2-4 cm achieved PR after 2 days and were assessed as CR or SR 1 week after post-fire needle therapy. None of the patients had a recurrence within 12 weeks after treatment. CONCLUSION: Fire needle therapy is a promising treatment method for uncomplicated skin abscesses smaller than 4 cm, which warrants further in-depth and more large-scale studies.

Herbal Compatibility of Ginseng and Rhubarb Exerts Synergistic Neuroprotection in Cerebral Ischemia/Reperfusion Injury of Rats.

OBJECTIVE: Ischemic stroke is a complex multifactorial disease caused by interactions among polygenetic, environmental, and lifestyle factors with limited effective treatments. Multi-herbal formulae have long been used for stroke through herbal compatibility in traditional Chinese medicine (TCM); however, there is still a lack of evidence due to their unimaginable complexity. Herbal pairs represent the simplest and basic features of multi-herbal formulae, which are of great significance in clarifying herbal compatibility. Here, we aim to investigate the neuroprotective effects of the herbal compatibility of Ginseng and Rhubarb on a cerebral ischemia/reperfusion (I/R) injury model of rats. METHODS: Male adult SD rats were randomly divided into a sham group, a normal saline (NS) group, a Ginseng group, a Rhubarb group, and a Ginseng + Rhubarb (GR) group, a Carbenoxolone [CBX, gap junction (GJ) specific inhibitor] group, and a GR + CBX group. Each group was further assigned into four subgroups according to ischemic time (6 h, 1 day, 3 days, and 7 days). The cerebral I/R injury model was established according to the modified Zea Longa method. The Neurological Deficiency Score (NDS) was assessed by the Zea-Longa scale; the cerebral infarction area was detected by TTC (2,3,5-triphenyltetrazolium chloride) staining; and the expression of connexin-43 (Cx43) and aquaporin-4 (AQP4) were detected based on an immunofluorescence technique and quantitative real-time-PCR. RESULTS: Compared to the I/R group, both the independent and combined use of Ginseng and Rhubarb can significantly improve NDS (P < 0.05), decrease the percentage of the cerebral infarction area around the infarction penumbra (P < 0.05) and down-regulate the expression of Cx43 and AQP4 after I/R injury (P < 0.05). The GR had more significant effects than that of Ginseng and Rhubarb (P < 0.05). Compared with the GR group, the GR + CBX group significantly improved in NDS (P < 0.05), and decreased the percentage of the cerebral infarction area (P < 0.05) and expression of Cx43 and AQP4 protein (P < 0.05). CONCLUSION: The herbal compatibility of Ginseng and Rhubarb synergistically exerts neuroprotective function during acute cerebral I/R injury, mainly through reducing the expression of Cx43 and AQP4.

Wogonin attenuates liver fibrosis via regulating hepatic stellate cell activation and apoptosis.

Liver fibrosis is the representative features of liver chronic inflammation and the characteristic of early cirrhosis. To date, effective therapy for liver fibrosis is lacking. Recently, Traditional Chinese Medicine (TCM) has attracted increasing attention due to its wide pharmacological effects and more uses in clinical. Wogonin, as one major active constituent of Scutellaria radix, has been reported it plays an important role in anti-inflammatory, anti-cancer, anti-viral, anti-angiogenesis, anti-oxidant and neuro-protective effects. However, the anti-fibrotic effect of wogonin is never covered in liver. In this study, we evaluated the protect effect of wogonin in liver fibrosis. Wogonin significantly attenuated liver fibrosis both in CCl4-induced mice and TGF-ß1 activated HSCs. Meanwhile, wogonin can enhances apoptosis of TGF-ß1 activated HSC-T6 cell from rat and LX-2 cell from human detected by flow cytometry. Additionally, wogonin can largely enhances cle-caspase3, cle-caspase9 expression and the ratio of Bax/Bcl-2 in T6 cells. Pro-apoptosis effect of wogonin in vivo was further verified in situ. In conclusion, wogonin can attenuate liver fibrosis via regulating the activation and apoptosis of hepatic stellate cells, and may be an effective drug to treat and prevent liver fibrosis.

Borneol for Regulating the Permeability of the Blood-Brain Barrier in Experimental Ischemic Stroke: Preclinical Evidence and Possible Mechanism.

Borneol, a natural product in the Asteraceae family, is widely used as an upper ushering drug for various brain diseases in many Chinese herbal formulae. The blood-brain barrier (BBB) plays an essential role in maintaining a stable homeostatic environment, while BBB destruction and the increasing BBB permeability are common pathological processes in many serious central nervous system (CNS) diseases, which is especially an essential pathological basis of cerebral ischemic injury. Here, we aimed to conduct a systematic review to assess preclinical evidence of borneol for experimental ischemic stroke as well as investigate in the possible neuroprotective mechanisms, which mainly focused on regulating the permeability of BBB. Seven databases were searched from their inception to July 2018. The studies of borneol for ischemic stroke in animal models were included. RevMan 5.3 was applied for data analysis. Fifteen studies investigated the effects of borneol in experimental ischemic stroke involving 308 animals were ultimately identified. The present study showed that the administration of borneol exerted a significant decrease of BBB permeability during cerebral ischemic injury according to brain Evans blue content and brain water content compared with controls (P < 0.01). In addition, borneol could improve neurological function scores (NFS) and cerebral infarction area. Thus, borneol may be a promising neuroprotective agent for cerebral ischemic injury, largely through alleviating the BBB disruption, reducing oxidative reactions, inhibiting the occurrence of inflammation, inhibiting apoptosis, and improving the activity of lactate dehydrogenase (LDH) as well as P-glycoprotein (P-GP) and NO signaling pathway.

Buyang Huanwu Decoction Targets SIRT1/VEGF Pathway to Promote Angiogenesis After Cerebral Ischemia/Reperfusion Injury.

Background: Ischemia stroke is known as the major cause of morbidity and mortality. Buyang Huanwu Decoction (BHD), a classical traditional Chinese medicine (TCM) formula, has been used to prevent and treat stoke for hundreds of years. The purpose of present study is to investigate the effects of BHD on angiogenesis in rats after cerebral ischemia/reperfusion (I/R) injury targeting Silent information regulator 1 (SIRT1) / Vascular endothelial growth factor (VEGF) pathway. Methods: The cerebral I/R injury model was induced by middle cerebral artery occlusion (MCAO). Adult Sprag-Dawley (SD) rats were randomly divided into five groups: sham group, normal saline (NS) group, BHD group, BHD+EX527 (SIRT1 specific inhibitor) group, and NS+EX527 group. Each group was divided into the subgroups according to 1, 3, 7, or 14 days time-point after cerebral ischemia/reperfusion, respectively. Neurological function score (NFS) was evaluated by the Rogers scale; microvascular density (MVD) in brain tissue around infarction area was observed by immunofluorescence; and the expression of SIRT1 and VEGF was assessed by Western Blot and Quantitative Real-time-PCR. Results: BHD can significantly improve NFS (P < 0.05), increase the MVD in the boundary ischemic area (P < 0.01) and elevate the expression of protein and mRNA of SIRT1 and VEGF following I/R injury (P < 0.01). In contrast, treatment with EX527 reversed the BHD-induced improvements in NFS (P < 0.01) and decreased the MVD (P < 0.01) and the expression of SIRT1 and VEGF (P < 0.05). Conclusion: BHD exerts neuroprotection targeting angiogenesis through the up-regulation of SIRT1/VEGF pathway against cerebral ischemic injury in rats.

Herbal Medicine Formulas for Parkinson's Disease: A Systematic Review and Meta-Analysis of Randomized Double-Blind Placebo-Controlled Clinical Trials.

Background: Parkinson's disease (PD) is a debitlitating, chronic, progressive neurodegenerative disorder without modifying therapy. Here, we aimed to evaluate the available evidence of herbal medicine (HM) formulas for patients with PD according to randomized double-blind placebo-controlled clinical trials. Methods: HM formulas for PD were searched in eight main databases from their inception to February 2018. The methodological quality was assessed using Cochrane Collaboration risk of bias tool. Meta-analysis was performed using RevMan 5.3 software. Results: Fourteen trials with Seventeen comparisons comprising 1,311 patients were identified. Compared with placebo groups, HM paratherapy (n = 16 comparisons) showed significant better effects in the assessments of total Unified Parkinson's Disease Rating Scale (UPDRS) (WMD: -5.43, 95% CI:-8.01 to -2.86; P < 0.0001), UPDRS I (WMD: -0.30, 95% CI: -0.54 to -0.06; P = 0.02), UPDRS II (WMD: -2.21, 95% CI: -3.19 to -1.22; P < 0.0001), UPDRS III (WMD: -3.26, 95% CI:-4.36 to -2.16; P < 0.00001), Parkinson's Disease Quality of Life Questionnaire (p < 0.01) and Parkinson's Disease Questionnaire-39 (WMD: -7.65, 95% CI: -11.46 to -3.83; p < 0.0001), Non-motor Symptoms Questionnaire (p < 0.01) and Non-Motor Symptoms Scale (WMD: -9.19, 95% CI: -13.11 to -5.28; P < 0.00001), Parkinson's Disease Sleep Scale (WMD: 10.69, 95% CI: 8.86 to 12.53; P < 0.00001), and Hamilton depression rating scale (WMD: -5.87, 95% CI: -7.06 to -4.68; P < 0.00001). The efficiency of HM monotherapy (n = 1 comparison) was not superior to the placebo according to UPDRS II, UPDRS III and total UPDRS score in PD patients who never received levodopa treatment, all P > 0.05. HM formulas paratherapy were generally safe and well tolerated for PD patients (RR: 0.41, 95% CI: 0.21 to 0.80; P = 0.009). Conclusion: The findings of present study supported the complementary use of HM paratherapy for PD patients, whereas the question on the efficacy of HM monotherapy in alleviating PD symptoms is still open.

Chuanxiong Formulae for Migraine: A Systematic Review and Meta-Analysis of High-Quality Randomized Controlled Trials.

Objective: Migraine is a complex, prevalent and disabling neurological disorder characterized by recurrent episodes of headache without ideal treatment. We aim to assess the current available evidence of herbal Chuanxiong (Ligusticum chuanxiong Hort. root) formulae for the treatment of migraine according to the high-quality randomized controlled trials (RCTs). Methods: English and Chinese electronic databases were searched from their inceptions until March 2017. The methodological quality of included study was assessed by the Cochrane Collaboration risk of bias tool. RCTs with Cochrane risk of bias (RoB) score ≥4 were included in the analyses. Meta-analysis was conducted using RevMan 5.3 software. Publication bias was assessed by funnel plot analysis and Egger's test. Results: Nineteen RCTs with 1832 participants were identified. The studies investigated the Chuanxiong formulae vs. placebo (n = 5), Chuanxiong formulae vs. conventional pharmacotherapy (CP) (n = 13 with 15 comparisons), and Chuanxiong formulae plus CP vs. CP (n = 1). Meta-analysis indicated that Chuanxiong formulae could reduce frequency, duration, days and pain severity of migraine and improve the total clinical efficacy rate (P < 0.05). Adverse event monitoring was reported in 16 out of 19 studies and occurrence rate of adverse event was low. Conclusion: The findings of present study indicated that Chuanxiong formulae exerted the symptom reliefs of for migraine.

Chinese Herbal Medicine for Vascular Dementia: A Systematic Review and Meta-Analysis of High-Quality Randomized Controlled Trials.

BACKGROUND: Vascular dementia (VaD) is the second common form of dementia and Chinese herbal medicine (CHM) has been used for aging-related disorders for thousands of years. However, there is still a lack of scientific evidence using CHM for VaD. OBJECTIVE: To conduct a systematic review to assess the current evidence available for the effectiveness and safety of CHM for VaD. METHODS: Six databases were searched for high-quality randomized-controlled clinical trials that met the requirements of at least 4 of the 7 domains of the Cochrane risk of bias tool from their inception to February 2017. RevMan 5.3 was applied for data analysis. RESULTS: Forty studies with 42 comparisons and 3,572 individuals were included. The studies investigated the CHM versus placebo (n = 4), CHM versus western conventional treatment (WCT) (n = 36), and CHM plus WCT versus WCT (n = 2). Meta-analysis showed that CHM for VaD could improve Mini-Mental State Examination (MMSE), the Activities of Daily Living, Hasegawa's dementia scale, and clinical effective rate but had statistically similar effect based on Blessed Behavior Scale (BBS) outcome when compared with WCTs. When compared with placebo, CHMs were more beneficial in improving MMSE but showed no significant difference in BBS scores. CHM as adjuvant therapy exerted an additive anti-VaD benefit on MMSE scores. The participants of CHM group had fewer adverse events than that of the placebo group or WCT group. CONCLUSION: The findings of the present study support, at least to an extent, that CHM can be recommended for routine use for treatment of VaD.

Ethyl Acetate Extract Components of Bushen-Yizhi Formula Provides Neuroprotection against Scopolamine-induced Cognitive Impairment.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder and there is no effective cure for this devastating disease to date. Bushen Yizhi Formula (BSYZ-F), a Chinese herbal compound, has proved to be effective for AD. In this study, we further investigate the effective part of BSYZ-F, ethyl acetate extract components of BSYZ-F (BSYZ-E), protects scopolamine (SCOP)-induced cognitive impairment, which shows a similar effect to BSYZ-F. We also find that BSYZ-E could protect against SCOP-induced cholinergic system dysfunction. In neuron function level, BSYZ-E remarkably elevates protein levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). BSYZ-E also significantly mitigates SCOP-induced apoptosis, oxidative stress and nitrosative stress. Conclusively, BSYZ-E, the effective part of BSYZ-F, can provide neuroprotection against SCOP-induced cognitive impairment through a multifunctional strategy. These findings suggest that BSYZ-E might be developed as a therapeutic drug for AD by targeting multiple pathways of the pathogenesis.

Chinese herbal medicine for Alzheimer's disease: Clinical evidence and possible mechanism of neurogenesis.

Currently, there is lack of cure or disease-modifying treatment for Alzheimer's disease (AD). Chinese herbal medicine (CHM) is purported to ameliorate AD progression, perhaps by promoting hippocampal neurogenesis. Here, we conducted an updated systematic review to investigate the efficacy and safety of CHM for AD based on high-quality randomized controlled trials (RCTs) and reviewed its possible mechanisms of neurogenesis according to animal-based researches. Twenty eligible studies with 1767 subjects were identified in eight database searches from inception to February 2017. The studies investigated the CHM versus placebo (n=3), CHM versus donepezil (n=9 with 10 comparisons), CHM plus donepezil versus donepezil (n=3), CHM versus a basic treatment (n=3), and CHM plus basic treatment versus basic treatment (n=2). Adverse events were reported in 11 studies, analyzed but not observed in 3 studies, and not analyzed in 6 studies. The main findings of present study are that CHM as adjuvant therapy exerted an additive anti-AD benefit, whereas the efficacy of CHM as a monotherapy was inconclusive. Additionally, CHMs were generally safe and well tolerated in AD patients. Active molecules in frequent constituents of CHMs can alter multiple critical signaling pathways regulating neurogenesis. Thus, the present evidence supports, to a limited extent, the conclusion that CHM can be recommended for routine use in AD patients and its possible mechanism enhances adult hippocampal neurogenesis through activating the multi-signal pathways.