Dementia Herbal Treatment Hopes

Effective symptomatic therapies and preventative methods have yet to be developed for a growing “epidemic” of diseases like Alzheimer’s. Cholinesterase inhibitors, such as galantamine, which comes from the snowdrop, are among a few modern prescription medications.

Sage, Ginkgo biloba, and complicated mixes of other traditional treatments have all been studied in clinical investigations for cognitive function. Some plant species can help with symptoms (for example, lemon balm and lavender can help with agitation in dementia patients, while St John’s wort can help with depression in the general population).

Medicinal plants for Behavioral and Psychological Symptoms (BPSD) tend to be more promising in general, given the lack of safe and effective pharmaceuticals. Traditional treatment prioritizes such drugs for symptoms like anxiety, aggressiveness, sadness, and sleep difficulties, regardless of whether or not dementia is present.

Two of the four primary medications now approved to treat dementia-related cognitive impairments are derived from plants (galantamine and rivastigmine). As a result, natural products could be a source of various single active ingredients that could be developed as dementia medications. Indeed, as recently highlighted, several attempts have been made to change the chemical structures of naturally generated AChE inhibitors in order to improve efficacy and limit side effects.

Dementia

In modern medicine, dementia in the elderly is an epidemic of unparalleled proportions and a problem.
The most prevalent type of dementia is Alzheimer’s disease (AD), followed by vascular (VaD) and Lewy body dementia (LBD—dementia with Lewy bodies and Parkinson’s disease (PD) dementia (PDD), with mixed pathologies being more likely than not.

Cholinesterase inhibitors (four medications intended to block acetylcholinesterase (AChE)) and, for some, butyrylcholinesterase (BuChE) and memantine are the only approved drugs for dementia (a glutamate NMDA receptor antagonist). Antipsychotics, antidepressants, tranquilizers, and hypnotics are some of the other medicines that are frequently prescribed inadvertently.

A variety of cognitive deficits (especially memory—specifically the ability to form new memories, attention, and executive function) are common symptoms. Behavioral and psychological symptoms of dementia are equally essential, as they are the primary cause of institutionalization in the absence of stabilizing cognitive therapy (BPSD).

Psychosis, agitation, anxiety, sleep disturbances, and sadness are among them. In the case of psychosis, neuroleptics (drugs created for schizophrenia, not dementia) have limited efficacy and come with a slew of side effects, including stroke and lower mortality in dementia patients.

Depression is linked to a lower quality of life, more disability, faster cognitive decline, a higher rate of nursing home placement, higher mortality, more depression, and caregiver burden, but there is little evidence that antidepressants are an effective treatment for depression and dementia patients.

Herbal Treatment Methodology

Although scientific research into medicinal plants or herbs for dementia began about 15-16 years ago, a more empirical form of inquiry dates back hundreds or thousands of years as cultures explored which plants were useful for what conditions (ethno– or archao–pharmacology) and passed information on species, preparation, and dose through the ages, a more empirical form of inquiry dates back hundreds or thousands of years as cultures explored which plants were useful for what conditions (ethno– or archao–pharmacology) and passed information.

This extensive history of use, which can be traced back to traditional Chinese medicine and European herbal medicine, provides an excellent resource on the safety and efficacy of a wide range of species. Because they’ve survived as medicines, it’s safe to presume that when correctly used (plant part, preparation, and dose), they’ll be safe and tolerable.

Herbal medicine has the potential for the kind of “built in” polypharmacology that is increasingly evident for orthodox pharmaceuticals due to the complexity of chemical composition (in terms of both various classes and multiple analogues within each class) and range of bioactivities. Ephedrine (Ephedra sinica Stapf), hyoscine (Hyoscyamus niger L.), morphine (Papaver somniferum L.), physostigma venenosum Balf., and galantamine from Galanthus and Narcissus species are just a few examples of medications derived from plants that have central nervous system (CNS) effects.

Numerous oncology treatments, possible infectious disease drugs (e.g., antibacterials and antivirals), analgesics, and immunological and inflammatory illnesses have all set precedents for the continued discovery of plants or phytochemicals in various areas of medicine.

The biosynthesis of phytochemicals to deter predators or attract pollinators or disseminators by targeting the nervous system has also been exploited to develop insecticides such as the pyrethrins derived from Chrysanthemum species; this action has also been exploited to develop insecticides such as the pyrethrins derived from Chrysanthemum species.

Dementia can be treated using a variety of herbs and plants. Adams et al. (2007), for example, gathered data on over 150 plant species in a variety of preparations and mixes for the treatment of age-related cognitive impairments (mainly from European herbals from the 16th and 17th century, alongside traditional Chinese and Indian medicinal works).
The evidence supporting potential species like sage (Salvia species), lemon balm (Melissa officinalis L.), Huperzia serrata (Thunb.) Trevis., and combinations of other traditional Chinese medicinal herbs, in addition to ginkgo (Ginkgo biloba L.), has recently been evaluated.

Neuroprotective effects of phenolic compounds, such as resveratrol from grapes and red wine, curcumin from turmeric (Curcuma longa L.), and epigallocatechin from green tea (Camellia sinensis Kuntze) (relevant to oxidative mechanisms), as well as research data on novel plant extracts and their bioactivities with antiamnesic effects on different neurotransmitter systems, have all been shown to be effective for dementia management in controlled clinical studies.

European Plants

Galantamine
This selective reversible and competitive inhibitor of AChE was first extracted from snowdrops (Galanthus) and is presently manufactured for the treatment of Alzheimer’s disease. These, along with other galantamine-containing plants like Narcissus species, haven’t been employed for age-related cognition or memory in the past.

Though new sources of natural AChE inhibitors are still being discovered, some lycopodane-type alkaloids from the Icelandic club moss Lycopodium annotinum ssp. alpestre and a monoterpene diglycoside (cyclogeraniol diglycoside) from Nelumbo nucifera, a plant used traditionally in Asia for nervous conditions, have recently been identified.

Galantamine is useful in Alzheimer’s disease in terms of cognition, behavioral symptoms, and everyday activities, but not in mild cognitive impairment. While it is widely considered that the major biological outcome of treatment is an increase in acetylcholine (ACh), other unintended consequences of cholinesterase inhibitor (ChEI) drugs include considerably increased sensitivity of another enzyme, aryl acylamidase, when compared to AChE.

Sage
Salvia officinalis L. or S. lavandulifolia Vahl. have a range of relevant neurobiological activities: in vitro—antiAChE and antiBuChE activities, antiinflammatory and estrogenic activities, antioxidant effects, antiamylodogenic activity, and in vivo—antiAChE and memory enhancement, according to European herbal encyclopedias.

Sage improves memory (including accuracy of instant recall) in both young and elderly normal volunteers, and there is one open label experiment and one randomized controlled trial (RCT) in Alzheimer’s disease that show good cognitive and behavioral effects.

Lemon balm (Melissa officinalis) is a herb that has been used for centuries.
Sage, on the other hand, is a European herbal remedy that is said to improve memory and have relaxing and antidepressant qualities. nicotinic and muscarinic receptor binding, 5HT1A, 5HT2A, and GABAA binding activity of the essential oil; physiological effects of the essential oil on GABAA mediated transmission and reducing spontaneous synaptic transmission implying novel channel actions are among the neurobiological activities of Melissa officinalis extracts that distinguish them from Sage.

Lemon Balm enhances memory and measures of calmness in normal young adults, as well as boosting cognitive function under experimental stress and reducing anxiety in normal young people. M. officinalis decreased cognitive impairment in Alzheimer’s patients in one randomized controlled trial.

Periwinkle
The lesser periwinkle (Vinca minor L.) is said to enhance brain blood flow, and there is evidence for this as well as the neuroprotective benefits of vinpocetine, a synthetic derivative of the vincamine alkaloid. Vinpocetine has shown promise in clinical trials for cognitive enhancement in dementia patients, as well as improved memory and learning in VaD patients.

Traditional Chinese Medicine Plants

Ginkgo
Ginkgo biloba has significantly more mechanistic and clinical data related to dementia than any other plant species. This could be due to ginkgo’s extensive usage for a variety of ailments other than memory (e.g., tinnitus, premenstrual tension, intermittent claudication), the availability of standardized extracts, and the lack of major adverse effects. There are, however, interactions between ginkgo and other medicines, just as there are with any other drug.

Kaschel (2009) recently reviewed the mechanistic effects relevant to dementia (summarized in Table 2), which include endothelial protection, inhibiting low-density lipoprotein oxidation, reducing mitochondrial DNA damage, reducing stroke damage, reducing amyloid aggregation and deposition (also promoting clearance and protection against toxicity), as well as genomic effects—increasing transthyretin expression.

The Kaschel study looked at psychological data from 29 pooled RCTs and found that there were substantial favourable benefits on selective attention and executive function in patients with dementia when compared to placebo. Napryeyenko et al. (2009) found similar favourable results in AD and VaD, with less negative effects than placebo, in non-AD dementias (in a secondary RCT analysis). It’s still unclear whether ginkgo is more appropriate as a cognitive enhancer in normal individuals, as early results suggested.

Ginseng
While there is a wealth of pertinent molecular data for this antiaging “panacea,” clinical data on dementia is promising but not yet conclusive. Although there is some indication of enhanced cognition in Alzheimer’s patients, the overall evidence for efficacy in this disease is minimal. Lee et al. (2009) found that the results of two RCTs of Panax ginseng in persons with Alzheimer’s disease revealed a significant effect in favoгr of Ginseng.

Huperzine is a compound found in the moss Huperzia serrata, which has been used in Traditional Chinese Medicine to cure and prevent dementia. It contains huperzine A, a neuroprotective anti-AChE alkaloid known for its ability to reduce oxidative stress, regulate apoptotic protein production, protect mitochondria, and modulate amyloid precursor protein (APP) metabolism.

In 1996, China produced “Shuangyiping,” a pill version of huperzine A for the symptomatic treatment of Alzheimer’s disease; huperzine A is also sold in the United States as a dietary supplement as powdered H. serrata for memory impairment. The only clinical data available comes from Chinese studies. Wang et al. (2009) found enhanced cognition (MiniMental State Examination: MMSE) with few side effects in a metaanalysis of RCTs, which, if confirmed, would support the superiority of natural products with standard dementia usage.

Traditional Chinese and Japanese Herbal Medicines

Chinese Herbal Medicines

In an eight-week RCT with mild to severe dementia patients, the traditional Chinese medicine (TCM) mixture Ba Wei Di Huang Wan (which includes Alisma orientale (Sam.) Juz. rhizome and Rehmannia glutinosa Steud. root) reduces scopolamine-induced memory impairment and has muscarinic receptor actions.

In a doubleblind placebocontrolled trial, another TCM tonic, luweidihuangtang (which has some of the same components as ba wei di huang wan), improved cognitive performance in normal human participants, indicating that more clinical research in dementia patients are needed. Other TCMs have been studied for possible dementia efficacy, with a Cochrane database evaluation of one decoction (zhiling; 15 components) stating that further evidence is needed for benefit in VaD.

More controlled trials, like those for other promising natural agents like Ginkgo biloba, are needed.

Japanese Herbal Medicines

Yokukansan (Chinese: Yi Gan San) is a traditional Japanese medication that was established in the 16th century as a cure for restlessness and agitation in infants. It consists of seven components. It cures learning deficits in an AD transgenic mouse and lowers glutamate toxicity in a variety of mechanistic studies. Despite this, and in line with historic use, this combination does not improve cognition but does help with BPSD.

Another Japanese treatment, kamiutanto (KUT), has showed promise in dementia patients’ cognition.

References

Elaine Perry and Melanie‐Jayne R. Howes. Medicinal Plants and Dementia Therapy: Herbal Hopes for Brain Aging? CNS Neurosci Ther. 2011 Dec; 17(6): 683–698.

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