Part 2 Herbal Drugs And Natural Bioactive Products As Potential Therapeutics: A Review On Pro-cognitives And Brain Boosters Perspectives
Mar 09, 2022
Part 2 How do Cistanche and other herbs improve memory?
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5. Other advantageous compounds
Ascorbic acid (23) is found mainly in citrus fruits (e.g. lemon). Studies in aged mice have shown that 23 increased step-down latency and decreased transfer latency, which indicated its ability to improve learning and memory. Moreover, memory impairment induced by diazepam and scopolamine was significantly reduced in young mice treated with 23. Bacosides (24) (bacoside A (42) and bacoside B) are derived from the well-reputed Bacopa monnieri. However, a recent study identified bacoside A (42) as the mixture of four different saponins, termed bacoside A3 (3), bacon aside II (4), bacopasaponin C (6), and an isomer of bacopasaponin C (5) (Fig. 2). Similarly, bacoside B represents the mixture of saponins, which exact constitution is not identified to date. To the best of our knowledge, bacoside B consists of four following saponins: bacon aside N1 (7), bacon aside N2 (8), bacon aside IV (9), and bacon aside V (10) (Fig. 2) (Deepak et al., 2013). In a clinical trial, 24 were administrated to elderly people (65 years or older) without a clinical sign of dementia in a double-blind and placebo-controlled study (Table 4). The results showed significant enhancement in their auditory verbal learning and word recall. There are possibilities that the 24 can help to manage AD too (Kumar et al., 2012).
Curcuminoids (25) represent major chemical components present in turmeric (Curcuma longa). Specifically, it is a mixture consisting of curcumin (11), demethoxycurcumin (71), and bisdemethoxycurcumin (68) (Table 4). Effective on rats showing AD-like neuronal loss caused by a b-peptide infusion. 25 also increased PSD-95 and synaptophysin expression in the rat hippocampus. Epigallocatechin-3-gallate (EGCG, 12) is the major catechin derivative found in green tea (Camellia sinensis). EGCG represents the most effective therapeutic component of green tea. EGCG possesses antioxidant properties and reduces lipid peroxidation in biological systems caused by free radicals (Kumar et al., 2012). A study in rats revealed the ability of EGCG to increase neurogenesis in the hippocampus. Moreover, dietary EGCG study in mice proved enhancement of spatial memory and object recognition.
Ginkgolides (28), a kind of terpene lactones, are derived from the living fossil tree Ginkgo biloba. Extract from Ginkgo biloba enhances the rate of acetylcholine turnover. Further, the stimulation of ligands binding to muscarinic receptors in the hippocampus was observed after the application of the extract. It improves dementia and cognitive deficits. The extract also proves significant antioxidant activity via the reduction of free radicals in animals. In a study, patients with dementia of AD type and multi-infract dementia were administrated with 28 supplements. The results showed improvement in their task-assessing speed for processing ability
Ginsenosides are extracted from the plant Panax ginseng. There are about 30 major members of ginsenosides, including Rb1 (19) and Rg1 (20) (Fig. 2), as the most active compounds. Other active ingredients are Rg2 (20), Rg3 (30), etc. Both major active ginsenosides 20 and 19 can increase the neuroplasticity in efficacy and structure. A study in normal adult mice proved that small molecular drug 20 can improve the proliferation and differentiation of neural progenitor cells in the hippocampus. Moreover, it also improved a global ischemia model in gerbils. Further beneficial effects of 20 include the following results: enhancement of the deteriorated immune system, improvement of motor and behavior response caused by age-related alterations, promoting activity of the hippocampal neuronal function in aged rats, and partial protection against the glutamate-induced excitotoxicity. The structure of 20 consists of panaxatriol and two sugar moieties, while the structure of 19 is composed of panaxatriol with four sugar moieties. Another study revealed the potential of ginsenoside Rh2 (22) to reverse the suppression of long-term potentiation induced by scopolamine in the CA1 hippocampal region (Kumar et al., 2012). Standardized ginseng extract (G115) significantly improved retention, improves learning, greatly increased the locomotor activity of mice.
Login (17) was used in the oral treatment of mice in a passive avoidance test with Cornus Officinalis fruits (100 mg/kg b.w.) as one of its major constituents (1 and 2 mg/kg b.w.). Login (Fig. 2) considerably reversed memory deficits induced by scopolamine. Further, orally treated mice with 17 in the Morris water maze test significantly improved memory deficits induced by scopolamine, which showed the formation of long-term and/or short-term spatial memory. Moreover, considerable inhibition of AChE activity was observed after administration of 17 (2 mg/kg b.w.) (Lee et al., 2009).
Nobiletin (18) is derived from the herb Aurantii Nobilis, a component of TCM. Nobiletin (Fig. 2) administered daily within four months avoided the memory impairment in fear conditioning. Immunohistochemical analysis in transgenic mice shows a hippocampal decrease of the Ab deposit
Pseudocoptisine (34) is a hexacyclic quaternary alkaloid found in tubers of Corydalis turns chaninovii, which showed a dose-dependent inhibitory activity of AChE with IC50 = 12.8 lM. The oral administration of 34 at the dose of 2.0 mg/kg in mice reversed the cognitive impairment in the passive avoidance test and decreased the escape latencies in training trials. According to these results, it is assumed that 34 can be a useful remedy for the treatment of cognitive impairment.
6. Quality and safety of herbal drugs
The phytochemical profile of plants is significantly affected by the environment. In the same species, levels of bioactive constituents can vary according to geographical location, weather condition, soil composition, and other aspects. Even in the same location, the chemical composition in plants varies from year to year due to local weather divergency (temperature, drought, FL flood, etc.). The constituent levels in wild plants are in general more variable. These negative effects in commercial plants can be reduced by the standardization of cultivation techniques. Indeed, plants that originate from characterized and uniform genetic sources and that are grown under controlled conditions contain more stable levels of bioactive compounds.
The concentration of nootropics depends on the mechanism of plant processing. The whole plant, essential oil, roots, leaves, fruits, etc. contain various levels of desired compounds, therefore it is important to use parts of the plant with a higher concentration of drugs. Diverse extraction methods produce a mixture of substances at various levels. Solvents, temperature, time of extraction, etc. significantly affect the composition of the final mixture. In addition, some of the natural products containing bioactive compounds are pre-pared without standardization, therefore the composition of the products may vary between producers and even batches. Detailed standardization in-plant processing is needed for a higher quality of final products.
An application of the same nootropic may result in various biological effects. The major advantage of herbal drugs is the presence of several active or supporting compounds compared to a single component drug. This fact represents a unique challenge for the identification of active constituents and further evaluation of their bioactivity. It is further important to detect and separate any potential hazardous compounds. Inadequate separation techniques may reduce the levels of the active compounds and lead to reduced bioactivity. Further, the application of nootropics plays a crucial role in bioavailability. Natural products are applied in different forms such as tablets, capsules, dried plants, raw herbs, tinctures (alcoholic extracts), tisanes (hot water extracts), and others. This also impacts the biological activity of drugs.
Another interesting point to consider represents assumptions and expectations of customers in extraordinary effects of natural products. The customers usually believe that natural products on the markets are high-quality products only. However, even if the herb has been reported to have remarkable bioactivity, there can be a significant difference in the levels of active constituents. Moreover, it is generally believed that natural products are inherently safe without adverse effects and without any chance of overdosing. Although natural products may also have adverse effects and interactions type herb-herb or herb-drug are possible. Therefore, further studies are needed for a deeper insight into the interactions of nootropics.
7. Conclusions and future directions
From this study, it is clear that plants, in the forms of herb foods and spices, play a vital role in enhancing poor memory (Eufoliye et al., 2012). Various medicinal plants are used worldwide (i.e. in Indian Ayurveda, TCM, Korean medicine, African medicine, American medicine, etc.) and they have shown significant memory and cognition improving activity on animal models. These medicinal plants contain a variety of phytochemicals that are proven to improve cognition, intelligence, attention, and concentration by maintaining the proper level of neurotransmitter Acetylcholine (ACh) inside the brain by providing a controlled activity of the enzyme Acetylcholinesterase (AChE). The different kinds of polyherbal formulations also work well on the central nervous system. Besides preclinical studies, some clinical trials are also being made which have also given positive results. As these medicinal plants show significant results on animal models of amnesia, dementia, and AD-type dementia, it can be said that there is a possibility that these herbs can be used for the treatment of some serious brain disorders in humans (e.g. AD) in near future.
Declaration of Competing Interest
The authors declare that they have no known competing for financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgments
A.D. was supported by Faculty Research and Professional Development Fund” (FRPDF) from Govt. of West Bengal and Presidency University and DBT-BUILDER from Department of Biotechnology, Govt. of India.
Funding
The author ’PO’ would also like to acknowledge the funding received from UHK VT2019-2021.
