Alzheimers 5 - Salvia officinalis

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Salvia officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double blind, randomized and placebo-controlled trial

            (Akhondzadeh, Noroozian et al. 2003) Download

BACKGROUND: Alzheimer's disease is characterized by a slow, progressive decline in cognitive function and behaviour. Acetylcholine esterase inhibitors are the only agents approved by the Food and Drug Administration for the treatment of Alzheimer's disease. All other agents prescribed for the treatment of Alzheimer's disease are used on an off-label basis. Current research into new drugs is focused on agents that will prevent, slow down and/or halt the progress of the disease process. Salvia officinalis has been used in herbal medicine for many centuries. It has been suggested, on the basis of traditional medicine, its in vitro cholinergic binding properties and modulation of mood and cognitive performance in humans, that Salvia officinalis might potentially provide a novel natural treatment for Alzheimer's disease. The objective of this study was to assess the efficacy and safety of Salvia officinalis extract using a fixed dose (60 drops/day), in patients with mild to moderate Alzheimer's disease, over a 4-month period. METHODS: This was a 4-month, parallel group, placebo-controlled trial undertaken in three centres in Tehran, Iran. Patients with mild to moderate Alzheimer's disease aged between 65 and 80 years (n = 42, 18 women) with a score of > or = 12 on the cognitive subscale of Alzheimer's Disease Assessment Scale (ADAS-cog) and < or = 2 on the Clinical Dementia Rating (CDR) were randomized to placebo or fixed dose of S. officinalis extract. Over the 16 weeks, the main efficacy measures were the change in the ADAS-cog and CDR-Sum of Boxes scores compared with baseline. In addition, side-effects were systematically recorded throughout the study using a checklist. RESULTS: At 4 months, S. officinalis extract produced a significant better outcome on cognitive functions than placebo (ADAS-cog: F = 4.77, d.f. = 1, P = 0.03) (CDR-SB: F = 10.84, d.f. = 1, P < 0.003). There were no significant differences in the two groups in terms of observed side-effects except agitation that appears to be more frequent in the placebo group (P = 0.09). CONCLUSIONS: The results of this study indicate the efficacy of S. officinalis extract in the management of mild to moderate Alzheimer's disease. Moreover, S. officinalis may well reduce agitation of patients but this needs to be confirmed.


Herbal medicine in the treatment of Alzheimer's disease

            (Akhondzadeh and Abbasi 2006) Download

Alzheimer's disease (AD) is characterized by profound memory loss sufficient to interfere with social and occupational functioning. It is the most common form of dementia, affecting more than 20 million people worldwide. AD is characterized by an insidious loss of memory, associated functional decline, and behavioral disturbances. Patients may live for more than a decade after they are diagnosed with AD, making it the leading cause of disability in the elderly. The incidence of AD ranges from 1 to 4 percent of the population per year, rising from its lowest level at ages 65 to 70 years to rates that may approach 6 percent for those over the age of 85 years. The first neurotransmitter defect discovered in AD involved acetylcholine (ACh). As cholinergic function is required for short-term memory, the cholinergic deficit in AD was also believed to be responsible for much of the short-term memory deficit. Clinical drug trials in patients with AD have focused on drugs that augment levels of ACh in the brain to compensate for the loss of cholinergic function. These drugs have included ACh precursors, muscarinic agonists, nicotinic agonists, and acetylcholinesterase inhibitors. The most highly developed and successful approaches to date have employed acetylcholinestrase inhibition. Although some Food and Drug Administration-approved drugs are available for the treatment of Alzheimer's disease, the outcomes are often unsatisfactory, and there is a place for alternative medicine, in particular, herbal medicine. This paper reviews the clinical effects of a number of commonly used types of herbal medicines for the treatment of AD.

The use of herbal medicine in Alzheimer's disease-a systematic review

            (Dos Santos-Neto, de Vilhena Toledo et al. 2006) Download

The treatments of choice in Alzheimer's disease (AD) are cholinesterase inhibitors and NMDA-receptor antagonists, although doubts remain about the therapeutic effectiveness of these drugs. Herbal medicine products have been used in the treatment of Behavioral and Psychological Symptoms of Dementia (BPSD) but with various responses. The objective of this article was to review evidences from controlled studies in order to determine whether herbs can be useful in the treatment of cognitive disorders in the elderly. Randomized controlled studies assessing AD in individuals older than 65 years were identified through searches of MEDLINE, LILACS, Cochrane Library, dissertation Abstract (USA), ADEAR (Alzheimer's Disease Clinical Trials Database), National Research Register, Current Controlled trials, Centerwatch Trials Database and PsychINFO Journal Articles. The search combined the terms Alzheimer disease, dementia, cognition disorders, Herbal, Phytotherapy. The crossover results were evaluated by the Jadad's measurement scale. The systematic review identified two herbs and herbal formulations with therapeutic effects for the treatment of AD: Melissa officinalis, Salvia officinalis and Yi-Gan San and BDW (Ba Wei Di Huang Wan). Ginkgo biloba was identified in a meta-analysis study. All five herbs are useful for cognitive impairment of AD. M. officinalis and Yi-Gan San are also useful in agitation, for they have sedative effects. These herbs and formulations have demonstrated good therapeutic effectiveness but these results need to be compared with those of traditional drugs. Further large multicenter studies should be conducted in order to test the cost-effectiveness of these herbs for AD and the impact in the control of cognitive deterioration.

Traditional used Plants against Cognitive Decline and Alzheimer Disease

            (Eckert 2010) Download

Alzheimer's disease (AD) is a neurodegenerative disorder characterized clinically by progressive memory deficits, impaired cognitive function, and altered and inappropriate behavior. Aging represents the most important risk factor for AD and the global trend in the phenomenon of population aging has dramatic consequences for public health, healthcare financing, and delivery systems in the word and, especially in developing countries. Mounting evidence obtained in in vitro and in vivo studies, suggests that various traditionally used plants in Asia, India, and Europe significantly affect key metabolic alterations culminating in AD-typical neurodegeneration. The present article aims to bring the reader up-to-date on the most recent studies and advances describing the direct and indirect activities of traditional used plants and its constituents possibly relieving features of AD. A variety of traditional used plants and its extracts exerted activities on AD related drug targets including AChE activity, antioxidative activity, modulation of Abeta-producing secretase activities, Abeta-degradation, heavy metal chelating, induction of neurotrophic factors, and cell death mechanisms. Although pre-clinical investigations identified promising drug candidates for AD, clinical evidences are still pending.

Salvianic borneol ester reduces beta-amyloid oligomers and prevents cytotoxicity

            (Han, Liu et al. 2011) Download

CONTEXT: The destabilization of beta-amyloid (Abeta) peptide aggregates and the protection of functional cells are the attractive therapeutic strategies for Alzheimer's disease (AD). Some active ingredients of Salvia miltiorrhiza f. alba C.Y.Wu & H.W.Li (Lamiaceae) (SM) have attracted increasing attention for the treatment of neurodegenerative diseases. OBJECTIVE: Salvianic borneol ester (SBE) is a new compound based on SM formulas. The present study was designed to examine the anti-amyloid effects and neuroprotection of SBE in vitro. MATERIALS AND METHODS: The destabilizing effects of SBE and its related compounds (salvianic acid A and borneol) on preformed Abeta oligomers were measured by using fluorescence spectroscopy with thioflavin T (ThT) and the destabilizing effects of SBE were further confirmed visually by transmission electron microscopy (TEM). The neuroprotective effects of SBE against hydrogen peroxide (H(2)O(2))-induced toxicity in human neuroblastoma cells (SH-SY5Y) and motor neuron hybridoma cells (VSC 4.1) were shown by MTT assay and morphological observation. RESULTS: SBE showed the most significant destabilizing effect, though the mixture of salvianic acid A and borneol also destabilized Abeta1-40 oligomers. The destabilizing activity of salvianic acid A or borneol alone was not significant. SBE destabilized Abeta1-40 oligomers in dose- and time-dependent manners and the destabilizing effect could also be seen in the photographs of TEM. Furthermore, SBE could protect SH-SY5Y cells and VSC 4.1 cells against H(2)O(2)-induced toxicity in a dose-dependent manner. DISCUSSION AND CONCLUSION: SBE had the bifunctional activities of anti-amyloid and neuroprotection. It may have therapeutic potential for AD and be an alternative lead compound for developing new drugs against AD.

The role of phytochemicals in the treatment and prevention of dementia

            (Howes and Perry 2011) Download

Dementia pathologies such as Alzheimer's disease (AD) are reaching epidemic proportions, yet they are not successfully managed by effective symptomatic treatments. Only five drugs have been developed to alleviate cognitive symptoms, and more effective and safe treatments are needed for both the cognitive symptoms and behavioural and psychological symptoms of dementia (BPSD). As two of these licensed drugs (cholinesterase inhibitors [ChEIs]) are naturally derived (galantamine and rivastigmine), the potential for plants to yield new therapeutic agents has stimulated extensive research to discover new ChEIs together with plant extracts, phytochemicals and their derivatives with other mechanistic effects relevant to dementia treatment. This review presents the potential and actual therapeutic strategies for dementia in relation to the known mechanisms of dementia pathology. Phytochemicals that have shown mechanistic effects relevant to the pathological targets in dementia are discussed, with an emphasis on those showing positive clinical trial evidence. Those phytochemicals discussed include the alkaloid physostigmine, a ChEI from the calabar bean (Physostigma venenosum), which has been used as a template for the development of synthetic derivatives that inhibit acetylcholinesterase, including the drug rivastigmine. Also discussed are other ChEI alkaloids including huperzine A, from Huperzia serrata, and galantamine, originally from the snowdrop (Galanthus woronowii); both alkaloids improve cognitive functions in AD patients. Other phytochemicals discussed include cannabinoids (e.g. cannabidiol) from Cannabis sativa, which are emerging as potential therapeutic agents for BPSD, and resveratrol (occurs in various plants) and curcumin (from turmeric [Curcuma longa]), which have been investigated for their pharmacological activities relevant to dementia and their potential effects on delaying dementia progression. The review also discusses plant extracts, and their known constituents, that have shown relevant mechanistic effects for dementia and promising clinical data, but require more evidence for their clinical efficacy and safety. Such plants include Ginkgo biloba, which has been extensively studied in numerous clinical trials, with most outcomes showing positive effects on cognitive functions in dementia patients; however, more reliable and consistent clinical data are needed to confirm efficacy. Other plants and their extracts that have produced promising clinical data in dementia patients, with respect to cognition, include saffron (Crocus sativus), ginseng (Panax species), sage (Salvia species) and lemon balm (Melissa officinalis), although more extensive and reliable clinical data are required. Other plants that are used in traditional practices of medicine have been suggested to improve cognitive functions (e.g. Polygala tenuifolia) or have been associated with alleviation of BPSD (e.g. the traditional prescription yokukansan); such remedies are often prescribed as complex mixtures of different plants, which complicates interpretation of pharmacological and clinical data and introduces additional challenges for quality control. Evidence for the role of natural products in disease prevention, the primary but considerably challenging aim with respect to dementia, is limited, but the available epidemiological and clinical evidence is discussed, with most studies focused on ChEIs, nicotine (from Nicotiana species), curcumin, wine polyphenols such as resveratrol and G. biloba. Challenges for the development of phytochemicals as drugs and for quality control of standardized plant extracts are also considered.

The spice sage and its active ingredient rosmarinic acid protect PC12 cells from amyloid-beta peptide-induced neurotoxicity

            (Iuvone, De Filippis et al. 2006) Download

Traditional use and clinical reports suggest that the culinary herb sage (Salvia officinalis) may be effective for patients with mild to moderate Alzheimer's disease (AD). In this study, we evaluated the effect of a standardized extract from the leaves of S. officinalis (SOE) and its active ingredient rosmarinic acid on Alzheimer amyloid-beta peptide (Abeta)-induced toxicity in cultured rat pheochromocytoma (PC12) cells. Incubation of PC12 cells with Abeta (fragment 1-42) for 24 h caused cell death, and this effect was reduced by SOE and its active ingredient, rosmarinic acid. Rosmarinic acid reduced a number of events induced by Abeta. These include reactive oxygen species formation, lipid peroxidation, DNA fragmentation, caspase-3 activation, and tau protein hyperphosphorylation. Moreover, rosmarinic acid inhibited phosphorylated p38 mitogen-activated protein kinase but not glycogen synthase kinase 3beta activation. These data show the neuroprotective effect of sage against Abeta-induced toxicity, which could validate the traditional use of this spice in the treatment of AD. Rosmarinic acid could contribute, at least in part, for sage-induced neuroprotective effect.

Cognitive dysfunctions induced by a cholinergic blockade and Abeta 25-35 peptide are attenuated by salvianolic acid B

            (Kim, Park et al. 2011) Download

Alzheimer's disease (AD) is a neurodegenerative disorder associated with progressive cognitive and memory loss and neuronal cell death. Current therapeutic strategies for AD are very limited; thus, traditional herbal medicines or their active constituents receive much attention. The aim of this study was to investigate the cognitive enhancing effects of salvianolic acid B (SalB) isolated from Salvia miltiorrhiza and its ameliorating effects on various drug-induced amnesic models using the passive avoidance, Y-maze, and Morris water maze tasks. Drug-induced amnesia was induced by administering scopolamine, diazepam, muscimol, or amyloid-beta (Abeta)(25-35) peptide. SalB (10 mg/kg, p.o.) was found to significantly reverse the cognitive impairments induced by scopolamine (1 mg/kg, i.p.) or Abeta(25-35) (10 nmol/5 mul, i.c.v.) injection. This ameliorating effect of SalB was antagonized by the GABA(A) receptor agonists, muscimol or diazepam, respectively. In addition, SalB alone was capable of improving cognitive performances. Furthermore, SalB (100 muM) was found to inhibit GABA-induced outward Cl(-) currents in single hippocampal CA1 neuron. These results suggest that the observed ameliorations of cholinergic dysfunction- or Abeta(25-35)-induced memory impairment by SalB were mediated, in part, via the GABAergic neurotransmitter system after a single administration.

Effect of plant extracts on Alzheimer's disease: An insight into therapeutic avenues

            (Obulesu and Rao 2011) Download

Alzheimer's disease (AD) is a devastative neurodegenerative disorder which needs adequate studies on effective treatment options. The extracts of plants and their effect on the amelioration of AD symptoms have been extensively studied. This paper summarizes the mechanisms like acetylcholinesterase (AChE) inhibition, modification of monoamines, antiamyloid aggregation effect, and antioxidant activity which are actively entailed in the process of amelioration of AD symptoms. These effects are induced by extracts of a few plants of different origin like Yizhi Jiannao, Moringa oleifera (Drumstick tree), Ginkgo Biloba (Ginkgo/Maidenhair tree), Cassia obtisufolia (Sicklepod), Desmodium gangeticum (Sal Leaved Desmodium), Melissa officinalis (Lemon Balm), and Salvia officinalis (Garden sage, common sage).


Medicinal plants and Alzheimer's disease: Integrating ethnobotanical and contemporary scientific evidence

            (Perry, Pickering et al. 1998) Download

The use of complementary medicines such as plant extracts in dementia therapy, varies according to the different cultural traditions. In orthodox Western medicine, contrasting with that in China and the Far East for example, pharmacological properties of traditional cognitive or memory enhancing plants have not been widely investigated in the context of current models of Alzheimer's disease. An exception is Ginkgo biloba in which the ginkgolides have antioxidant, neuroprotective, and cholinergic activities relevant to Alzheimer's disease mechanisms. The therapeutic efficacy of Ginkgo biloba extracts in Alzheimer's disease in placebo-controlled clinical trials is reportedly similar to currently prescribed drugs such as tacrine or donepezil and, importantly, undesirable side effects of Ginkgo biloba are minimal. Old European reference books (eg, medical herbals) document a variety of other plants such as Salvia officinalis (sage) and Melissa officinalis (balm) with memory improving properties, and cholinergic activities have recently been identified in extracts of these plants. Precedents for modern discovery of clinically relevant pharmacological activities in plants with long-established medicinal use include, for example, the interaction of alkaloid opioids in Papaver somniferum (Opium poppy) with endogenous opiate receptors in the brain. With recent major advances in understanding the neurobiology of Alzheimer's disease, and as yet limited efficacy of so-called rationally designed therapies, it may be timely to re-explore historical archives for new directions in drug development. This article considers not only the value of an integrative traditional and modern scientific approach to developing new treatments for dementia, but also in the understanding of disease mechanisms. Long before the current biologically based hypothesis of cholinergic derangement in Alzheimer's disease emerged, plants now known to contain cholinergic antagonists were recorded for their amnesic and dementia-inducing properties.

Medicinal plants and Alzheimer's disease: from ethnobotany to phytotherapy

            (Perry, Pickering et al. 1999) Download

The use of complementary medicines, such as plant extracts, in dementia therapy varies according to the different cultural traditions. In orthodox Western medicine, contrasting with that in China and the Far East for example, pharmacological properties of traditional cognitive- or memory-enhancing plants have not been widely investigated in the context of current models of Alzheimer's disease. An exception is Gingko biloba in which the gingkolides have antioxidant, neuroprotective and cholinergic activities relevant to Alzheimer's disease mechanisms. The therapeutic efficacy of Ginkgo extracts in Alzheimer's disease in placebo controlled clinical trials is reportedly similar to currently prescribed drugs such as tacrine or donepezil and, importantly, undesirable side effects of Gingko are minimal. Old European reference books, such as those on medicinal herbs, document a variety of other plants such as Salvia officinalis (sage) and Melissa officinalis (balm) with memory-improving properties, and cholinergic activities have recently been identified in extracts of these plants. Precedents for modern discovery of clinically relevant pharmacological activity in plants with long-established medicinal use include, for example, the interaction of alkaloid opioids in Papaver somniferum (opium poppy) with endogenous opiate receptors in the brain. With recent major advances in understanding the neurobiology of Alzheimer's disease, and as yet limited efficacy of so-called rationally designed therapies, it may be timely to re-explore historical archives for new directions in drug development. This article considers not only the value of an integrative traditional and modern scientific approach to developing new treatments for dementia, but also in the understanding of disease mechanisms. Long before the current biologically-based hypothesis of cholinergic derangement in Alzheimer' s disease emerged, plants now known to contain cholinergic antagonists were recorded for their amnesia- and dementia-inducing properties.

Traditional Chinese medicines and Alzheimer's disease

            (Wu, Chen et al. 2011) Download

Traditional Chinese medicines have been widely investigated for the treatment of Alzheimer's disease (AD) because none of the current therapies-either the cholinesterase inhibitors or antagonist of N-methyl-d-aspartate receptors-has profound effects on halting the progression of AD. In recent years, scientists have isolated many active compounds from herbs, which can alleviate dementia and neurodegenerative syndrome with fewer side effects than conventional drugs and, thus, are regarded as promising drug candidates for AD therapy. In this review, we summarize the latest research progress on six herbs for AD therapy-Huperzia serrata, Amaryllidaceae family, Ginkgo biloba, Uncaria rhynchophylla, Polygala tenuifolia, and Salvia officinalis-and focus on the analysis of their active components and possible mechanisms of pharmacological actions on AD.


In Salvia miltiorrhiza, phenolic acids possess protective properties against amyloid beta-induced cytotoxicity, and tanshinones act as acetylcholinesterase inhibitors

            (Zhou, Li et al. 2011) Download

Radix Salvia miltiorrhiza (RSM), a traditional Chinese medicinal herb, has been alleged to possess therapeutic effects against senile dementia, also known as Alzheimer's disease (AD). However, the effects of the major components in RSM on cytotoxicity induced by amyloid-beta peptide (Abeta) and on acetylcholinesterase activity have not been studied in depth to date. In this report, the effects of RSM aqueous/ethanol extracts, total polyphenols, total tanshinones and 3 phenolic compounds against toxicity mediated by Abeta(25-35) were tested with PC-12 cells. The results showed that Abeta(25-35)-induced cytotoxicity was revised by RSM aqueous/ethanol extracts and total polyphenols and that danshensu and salvianolic acid B could protect PC-12 cells by blocking Abeta(25-35)-induced Ca(2+)-intake, lactate dehydrogenase release, cell viability decrease and apoptosis. In addition, the activities of RSM extracts and relevant constituents in their inhibition of acetylcholinesterase were investigated using rat brain homogenates as an enzyme resource. Galanthamine hydrobromide, an accepted acetylcholinesterase inhibitor, was employed as a positive control agent. Our preliminary studies demonstrated that RSM ethanol extract, total tanshinones, tanshinone I and dihydrotanshinone I had remarkable inhibition effects on acetylcholinesterase in vitro. These findings suggest that both tanshinones and polyphenols in RSM are the active constituents responsible for the beneficial effects of this herb in AD treatment.


References

Akhondzadeh, S. and S. H. Abbasi (2006). "Herbal medicine in the treatment of Alzheimer's disease." Am J Alzheimers Dis Other Demen 21(2): 113-8.

Akhondzadeh, S., M. Noroozian, et al. (2003). "Salvia officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double blind, randomized and placebo-controlled trial." J Clin Pharm Ther 28(1): 53-9.

Dos Santos-Neto, L. L., M. A. de Vilhena Toledo, et al. (2006). "The use of herbal medicine in Alzheimer's disease-a systematic review." Evid Based Complement Alternat Med 3(4): 441-5.

Eckert, G. P. (2010). "Traditional used Plants against Cognitive Decline and Alzheimer Disease." Front Pharmacol 1: 138.

Han, M., Y. Liu, et al. (2011). "Salvianic borneol ester reduces beta-amyloid oligomers and prevents cytotoxicity." Pharm Biol 49(10): 1008-13.

Howes, M. J. and E. Perry (2011). "The role of phytochemicals in the treatment and prevention of dementia." Drugs Aging 28(6): 439-68.

Iuvone, T., D. De Filippis, et al. (2006). "The spice sage and its active ingredient rosmarinic acid protect PC12 cells from amyloid-beta peptide-induced neurotoxicity." J Pharmacol Exp Ther 317(3): 1143-9.

Kim, D. H., S. J. Park, et al. (2011). "Cognitive dysfunctions induced by a cholinergic blockade and Abeta 25-35 peptide are attenuated by salvianolic acid B." Neuropharmacology 61(8): 1432-40.

Obulesu, M. and D. M. Rao (2011). "Effect of plant extracts on Alzheimer's disease: An insight into therapeutic avenues." J Neurosci Rural Pract 2(1): 56-61.

Perry, E. K., A. T. Pickering, et al. (1998). "Medicinal plants and Alzheimer's disease: Integrating ethnobotanical and contemporary scientific evidence." J Altern Complement Med 4(4): 419-28.

Perry, E. K., A. T. Pickering, et al. (1999). "Medicinal plants and Alzheimer's disease: from ethnobotany to phytotherapy." J Pharm Pharmacol 51(5): 527-34.

Wu, T. Y., C. P. Chen, et al. (2011). "Traditional Chinese medicines and Alzheimer's disease." Taiwan J Obstet Gynecol 50(2): 131-5.

Zhou, Y., W. Li, et al. (2011). "In Salvia miltiorrhiza, phenolic acids possess protective properties against amyloid beta-induced cytotoxicity, and tanshinones act as acetylcholinesterase inhibitors." Environ Toxicol Pharmacol 31(3): 443-52.