A Comprehensive Review on Chemical Profiling of Nelumbo Nucifera: Potential for Drug Development.

[Alchemica]

A Comprehensive Review on Chemical Profiling of Nelumbo Nucifera: Potential for Drug Development.

Full text: http://sci-hub.bz/10.1002/ptr.5732
 

Nelumbo nucifera, also known as sacred lotus, has primarily been used as food throughout the Asian continent, and its medicinal values have been described in Ayurvedic and Traditional Chinese Medicine. The purpose of this study is to systematically characterize the chemical profiling and pharmacological activities of N. nucifera. Herein, we critically reviewed and analysed the phytochemical and pharmacological reports of N. nucifera. Our search for the keyword 'Nelumbo nucifera pharmacology' in all databases reported in Web of Science yielded 373 results excluding reviews and abstracts in document types. Two hundred and forty-three spectrum natural compounds from different parts of N. nucifera belonging to diverse chemical groups, including alkaloids, flavonoids, glycosides, terpenoids, steroids, fatty acids, proteins, minerals, and vitamins have been reported. In addition, distinct pharmacological activities, mainly against cancer, microbial infection, diabetes, inflammation, atherosclerosis, and obesity, have been associated with crude extracts, fractions, and isolated compounds. This review highlights potential use of neferine, liensinine, isoliensinine, and nuciferine in clinical trials. In depth, mechanism of the potential chemical entities from N. nucifera via structure activity relationship needs to be explored to guarantee the stability and safety for the clinical use.

[Alchemica]

While I've had a few people explore the leaf and nuciferine rich extracts, I personally find the embryo the most healing component. 

 

Soma as Nelumbo?

 

 

 

Keen to know anyone who's played with high dose Nelumbo? Particularly embryo. I've seen a few reports on here with stamen are interesting, I found embryo a nicer medicine. I'm keen to have it in my diet more often.

 

A Botanical Perspective on the Identity of Soma (Nelumbo Nucifera Gaertn.) Based on Scriptural and Iconographic Records

 

"If and when Nelumbo proves to possess psychoactive constituents that live up to the reputation of Soma, our current perspectives on the origin and development of eastern religions will require a thorough re-examination."

 

I've explored nearly all parts of the lotus, bar the petals (but have used stamen). They embryo is my preferred part. The root is nice as a grounded healing polyphenol source, the seed mild, the leaf and nuciferine leaf extracts personally not desirable, while the embryo possesses nice qualities. In high doses, I find it possesses an almost dream like hypnotic state of anxiolytic softness, uplift, vividness and peaceful spirited attunement. In the right set and setting and a cultural background involving spiritual awareness, it could be a candidate for something along the lines of Soma.

 

As a plant which can be used as both food and medicine, lotus plumule has high nutritional values and pharmacological effects, such as treating cardiovascular diseases, nervous disorders, insomnia and high fevers, etc Various chemical constituents including alkaloids, flavonoids and volatile oil have been isolated from lotus plumule Among these compounds, alkaloids are the main composition in lotus plumule. Liensinine, dauricine isoliensinine, neferine and nuciferine show good bioactivity and healthcare function [1]

 

 

A few times now I've used embryo at higher doses to de-stress, get some mood improvement, find some spiritual attunement and get a nice sleep. Contrary to many extracts, often from leaf, that are nuciferine rich and not overly spiritual (they possess atypical antipsychotic-like profiles), I can see a spiritual aspect to these parts richer in bisbenzylisoquinolines like neferine with 5-HT1A serotonergic dimensions. Neferine is a direct 5-HT1A receptor agonist and may inhibit 5-HT reuptake or activation of 5-HT metabolism. It alters 5-HT1A receptor binding in stress induced depressive conditions so it may be possible that habitual ritual intake induces changes, too that may heighten day-to-day spirituality? 

 

Neferine is not just serotonergic and active at 5-HT1ARs. These Lotus alkaloids display a weak cannabimimetic- type behavioural effect. In vivo studies demonstrated sedative, and analgesic effect of N. nucifera embryo extract, and sedative and antidepressant effect of neferine Neferine displayed affinities for δ-and µ- opioid receptors with Ki values of 0.7 ± 0.1 and 1.8 ± 0.2 μM, respectively, and was determined to be a weak δ agonist

 

While there have been mixed findings and difficulty in replication, 5-HT1A receptor binding has been implicated in spirituality/self-transcendence (incl. the degree to which an individual feels part of nature and the universe at large, and to extraordinary experiences such as extra sensory perception and sense of a transcendent being or presence). Prosocial behaviour and oxytocin release can be stimulated through 5-HT1A receptors, oxytocin bolsters feelings of spiritual connectedness. It is proposed postsynaptic 5-HT1AR signalling is involved in stress moderation.

 

The other alkaloids liensinine and isoliensinine from Nelumbo nucifera have antidepressant-like effects, closely related to serotonergic mechanisms, also involving 5-HT1ARs. Coupled with alkaloids, the high levels of interesting polyphenols makes it nice.. I've had much more notable responses to Lotus embryo (that's $2 for a bag from the Asian supermarket) than I've ever had from Nymphaea.

The most noticeable subjective effects are that Nelumbo embryo exerts antidepressant, anxiolytic and sedative effects, quietens a chattering mind, increases the vividness of experience, while deepening sleep at the same time. 

 

Lian Zi Xin. (Lotus). (plumule).

 

Embryo of lotus seeds are used in traditional Chinese drug called ‘Lian Zi Xin’, which primarily helps to overcome nervous disorders, insomnia, high fevers (with restlessness) and cardiovascular diseases (e.g. hypertension, arrhythmia).

 

It is a herbal medicine frequently used in treatment of depression in many Asian countries.

 

The green embryo of Nelumbo nucifera seeds mainly contain three structure-related bisbenzylisoquinoline alkaloids including liensinine, neferine, and isoliensinine. These three bisbenzylisoquinoline alkaloids are reported to possess a wide range of biological activities including anticarcinogenesis, anti-arrhythmia, anti-hypertension, anxiolytic/sedation, and anti-depression.

Studies have documented that liensinine, neferine, and isoliensinine can cross the blood–brain barrier and have recently received much attention for their neuroprotective effects.

Liensinine, neferine and isoliensinine have anti-neuroinammatory effect and open a new avenue to understand the potential of this health food in the treatment of neurodegenerative diseases

 

 Experimental evidence suggests Lotus embryo provides drastically greater anti-depressant effects than Hypericum perforatum (commonly referred to as St. John's Wort, perhaps the most widely used natural anti-depressant today). The antidepressant effect was comparable with that of maprotiline and imipramine.

 

 Neferine itself attenuated learning deficits induced by scopolamine

 

"Neferine itself at 10-100mg/kg was able to acutely (within 30 minutes) reduce immobility time in a forced swim test indicative of anti-depressive effects; when compared to Imipramine HCl as active control, it slightly (but nonsignificantly) outperformed at equimolar doses."

 

Neferine, Liensinine, isoliensinine, lotusine, methyl-corypalline, demethyl-coclaurine have been detected in the embryo.

Neferine shows antidepressant-like effects in mice similar to typical antidepressants and that these effects are mediated by the 5-HT1A receptor.  It reverses a decrease in 5-HT1A receptor binding in rats with depression-like symptoms induced by chronic mild stress.

 

Neferine shows anxiolytic activity similar to diazepam

 

"The therapeutic properties of neferine is widely diverse, while it shows toxicity to cancer it also shows cyto-protective effects against cardio-vascular diseases, pulmonary disease, and is also effective against Alzheimer's disease and elicits anti-oxidative effect in many cellular systems." [2]

 

While TCM dose are quite low, a suggested dose on the pack is 10g. That's where I'd start for explorations. I can't particularly notice that dose. I'm not keen on going extremely high dose, Neferine displays hypotensive effects and inhibits platelet aggregation. It has actions on the heart - neferine displays anti-arrhythmic action due to its inhibitory effect on K+, Na+ and Ca2+ currents of the myocardium and inhibitory actions on hERG channels so you need to use caution. That said, it seems to be relatively safe for long-term treatment

 

While neferine did not affect muscle coordination, it dose-dependently inhibited locomotor activity in mice. It induced hypothermia in mice and apparently potentiated thiopental-induced sleeping time. With the seeds, which contain neferine but at lower doses, in an animal model night-time activity reduced by 53%, but total sleep time was increased by 60%. The sleep-promoting effect was associated with up-regulation of GABAA/GABAB and serotonin receptors. There are suggestions that the

Lotus alkaloids exert sedative–hypnotic and anxiolytic effects via binding to the GABAA receptor and activating the monoaminergic system but research on neferine itself seems to be less suggestive on a GABAergic MoA.

 

Other uses of the embryo:

 

Neferine decrease fasting blood glucose, insulin levels, triglycerides and tumor necrosis factor-α and also possess anti-obesity effects. Neferine also enhances the insulin sensitivity in insulin resistance. Thus, neferine is a potent anti-diabetic agent that is equivalent in its potency to rosiglitazone, an insulin sensitizer used in treatment of diabetes mellitus type 2

 

Lotus embryo also contains polysaccharides with strong TLR antagonistic anti-inflammatory effects for inflammatory diseases.

 

Significant anti-cancerous properties of neferine have been reported in a number of studies on different in vitro and in vivo models of cancer There is a direct antitumor effect of neferine, suggesting that consumption of neferine may have cancer-preventive and cancer-therapeutic benefit. Neferine is an apoptosis inducer in lung cancer cells.

 

Neferine has shown anti-amnesic effect with significant improvement in cognitively impaired animal models which had been induced with scopolamine. As I've mentioned, there is strong anti-Alzheimer and neuroprotective effects of Liensinine and neferine, including potent inhibitory activiton β-site amyloid precursor protein cleaving enzyme-1 (BACE-1), Acetylcholine esterase (AChE) and Butyrylcholinesterase (BChE). The anti-amnesic activity of neferine may be occurring through anti-oxidant and anti- inflammatory activities and also due to inhibition of BACE1 and ChEs. Efficacy of neferine is also reported against neuro-degenerative disorders. have been demonstrated to have anti-AD activities by inhibiting acetylcholinesterase (AChE),

 

Contraindications:

This is not well studied. It use as a food and lack of serious indications is a good start but caution is required. While the embryo alkaloids have not been specifically studied, lotus leaf alkaloids has a strong inhibitory effect on CYP2D6 isoenzyme activity in vitro. This seems to be due to the more classic aporphine alkaloids over the bisbenzylisoquinolines. That said, neferine is predominantly metabolised in the liver and undergoes initial bioconversion by CYP2D6 into liensinine, isoliensinine, dimethylliensinine, and dimethyl- isoliensinine. There is also known involvement of CYP3A in neferine metabolism

Lotus might lower blood sugar levels in some people. Watch for signs of low blood sugar (hypoglycemia) and monitor your blood sugar carefully if you have diabetes and use lotus as a medicine.

 

"A close examination of the mythic and artistic records of India and Southeast Asia indicates that the famous inebriant of the ancient Aryans was the eastern lotus, Nelumbo nucifera. Vedic epithets, metaphors, and myths that describe the physical and behavioral characteristics of soma-as a sun, serpent, golden eagle, arrow, lightning bolt, cloud, phallic pillar, womb, chariot, and immortal navel-relate individually or as a whole to the eastern lotus. Since most Hindu and Buddhist gods and goddesses trace their origins from the Vedas (or at least share a pedigree of Vedic origin), and have always shared close symbolic associations with Nelumbo, there is reason to believe the divine status of this symbolic plant derives from India's prehistoric past.

 

Various plants that are known to produce psychoactive properties, such as marijuana (Cannabis sativa L.), Ephedra, opium poppy (Papaver somniferum L.), Syrian rue (Peganum harmala L.), ginseng (Panax), and the fly-agaric fungus, Amanita muscaria (Fr.) S.P. Gray (Doniger 1968; Falk 1989; Flattery and Schwartz 1989; Mahdihassan 1981; Nyberg 1995; Spess 2000), continue to provoke heated debates and discussions among linguists and students of the ancient Orient.

 

Many plant species that have been proposed thus far as possible soma candidates have proven unable to elicit psychoactive responses in human beings, such as rhubarb (Rheum), grapes (Vitis), pomegranates (Punica), moonseeds (Cocculus), ironweeds (Vernonia), hops (Humulus), ginseng, and various milkweeds (Doniger 1968; Flattery and Schwartz 1989; Nyberg 1995)."

The use of 5-HT1A modulators interests me. I find them more social and emotional allies.

 

There is a substantial role of serotonin activity in the expression of social behaviour including affiliative behaviours and 5-HT1ARs seem to be strong modulators of this. There are distinct roles for autoreceptors and postsynaptic receptors in mediating emotion-related behaviour. 5-HT1A receptors modulate the fear memory associated with the social defeat experience. There are decreased levels of 5-HT1A following social defeat in the PFC

 

Mice lacking the 5-HT1A receptor display decreased exploratory activity and increased fear of aversive environments suggesting reductions in density of the receptor might result in heightened anxiety. Some 5-HT1A agonists increase social behaviour and have potent effects on aggressive behaviours, being 'serenic'.

 

Acute and chronic administration of 5-HT1A receptor agonists seems to have antidepressive/anxiolytic effects. There is robust anti-aggressive effects of 5-HT1A receptor agonists in dose ranges that concomitantly inhibit 5-HT neurotransmission. There is a critical role of raphe somatodendritic 5-HT1A autoreceptors, and hence phasic 5-HT neuron activity, in the initiation/execution of aggressive actions. Agonists of 5-HT1A subtype receptors are among the most potent drugs to suppress the initiation and execution of offensive aggressive behavioural displays

 

5-HT1A receptor is the most abundant serotonin subtypes expressed in the brain. It is widely distributed in regions such as prefrontal cortex, limbic system, and hypothalamus that receive serotonergic input from the raphe nuclei. Presynaptically, the 5-HT1A receptor is the major somatodendritic autoreceptor on the soma and dendrites of serotonergic neurons, where it acts as a “brake” to inhibit the activity of the entire 5-HT system while postsynaptic 5-HT1A heteroreceptors are expressed in target areas receiving serotonergic innervation. Activation of 5-HT1A heteroreceptors on these distinct neurons mediates hyperpolarising response to released serotonin and usually reduces neuronal excitability and firing

 

Activation of 5-HT1A heteroreceptors plays a prominent role in the antidepressant and neurogenic actions of SSRIs and 5-HT1ARs are implicated in the prosocial effects of empathogens.

 

Stimulation of 5-HT1A receptors in prefrontal cortex enhances forebrain catecholamine release, an effect possibly involved in the antidepressant action of the receptor agonists. 5-HT1A agonists consistently increase dopamine release in the prefrontal cortex, which is an effect that might be predicted to improve negative symptoms. 5-HT1A receptor agonists may reduce the activity of serotonergic projections that inhibit dopaminergic nigrostriatal neurones, therefore increasing dorsal striatal dopamine levels. 5-HT1A autoreceptors act to modulate dopamine levels in the nucleus accumbens. Postsynaptic 5-HT1A receptors interact with NMDA-receptor subunits important for cognition and depression

Edited March 27, 2018 by Alchemica