Sacred lotus

Last Updated: November 18, 2022

Nelumbo nucifera (a flower commonly called Indian Lotus or Sacred Lotus) is sometimes used in Asiatic dishes. It is high in phenolics and may be anti-depressant and anti-diabetic; no human studies.


Sacred lotus is most often used for

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Sources and Components



Nelumbo Nucifera (of the family Nymphaeaceae) is a large aquatic Asiatic medicine known as 'Sacred Lotus' that has been used for culinary and ornamental purposes as well as medical.[1] The seed embryos are sometimes referred to as Lian Zi Xin, and are a good source of Neferine relative to other plant parts.[2]



Nelumbo Nucifera tends to contain:

  • Bisbenzylisoquinoline Alkaloids (Nelumboferine, Nelumborine A, Nelumborine B)[3][4] and the 'main' bioactive of Nelumbo Nucifera, Neferine[3][5] as well as the structurally related Linesinine and Isolinesinine compounds[3][5]
  • Aporphine alkaloids such as nuciferine and nornuciferine (not to be confused with neferine) and N-methylasimilobine,[6] as well as 2-Hydroxy-1-methoxyaporphin[7]
  • Alkyl 4-hydroxybenzoates (methyl-, ethyl-, propryl- and butyl-)[8]
  • Anisic Acid[3]
  • The polphenolic catechin[9] and a content of EGCG, sometimes seen as the most potent of the four green tea catechins;[10] these can be found in the seed pod as Procyanidin C1[11][12] and the roots contain Procyanidins of the B class[13]
  • Quercetin[14] and its 3-O-β-D-glucuronide glycoside[15] at 25-30% in flowers but 67.25-90.66% of leaf and seed total flavanoids
  • Isorhamnetin at 0.35-8.86% (outlier at 11.69%) total flavanoids[16]
  • Myrictein and its 3-O-galactoside, 3-O-glucuronide, and 3-O-glucoside at 2.5-15.87% of total flavanoids (highest in flower stalk )[16]
  • Kaempferol and its glycoside at 5.44-19.26% (except in flowers where it reaches 63% total flavanoids)[16]
  • Diosmetin[17] at 0.21-6.36% total flavanoids (outlier at 11.31% in leaf stalks)[16]
  • Syringetin at 0.97-2.64% total flavanoids, absent in leaves[16]
  • Triterpenoids such as Betulinic Acid[18]
  • 2α,24-diacetoxy-3β-hydroxyolean-12-en-28-oic acid[19]
  • Hyptatic acid-A (2α,3β,24-trihydroxyolean-12-en-28-oic acid)[19]
  • Higenamine[20]
  • Hyperoside, a minor component of Hypericum Perforatum[21][15] as well as Astragalin, from Astragalus Membranaceus[21]
  • L-trptophan[22]
  • The triterpenoic ester urs-12-en-3beta-O-9E,12E-octadecadienoate[23]

In regards to the non-caloric bioactives, there is a large amount of flavanoids that are common to several plants with only Neferine appearing to be unique to Nelumbo Nucifera. Interestingly, some other compounds that are thought to be unique to their plants show up in Sacred Lotus (Astragalin and Hyperoside)

With some bioactive polysaccharides:

  • LPPS, a fragment of polysaccharides divided into F1 and F2; all anti-inflammatory[24]

Hot water extracts of Nelumbo Nucifera have been reported to possess up to 14.8% total phenolic acids and 56.1% total flavonoids by weight,[25] a concentration much higher than many other herbs. When looking at the plant itself, the total flavanoids of Nelumbo Nucifera appear to be quite high at 730.95m/100 g (seeds), 771.79mg/100g and 650.67mg/100g (mature and young leaves) and 342.97mg/100g and 359.45mg/100g (flower petal and stamen).[16] This large polyphenolic content underlies most anti-oxidant properties of Nelumbo Nucifera, and may extend to radioprotection (in this study, Procyanidins[26]).






The sum of liensinine, isoliensinine, neferine (bisbenzylisoquinoline alkaloids) appear to have an oral bioavailability of 62.5% when given to rats at 20mg/kg.[27]



When measruing three bisbenzylisoquinoline alkaloids in serum following oral administration it was found that the total alkaloid content (sum of liensinine, isoliensinine, neferine) after a 20mg/kg bolus gave the pharmacokinetic parameters of 0.083 hours (Tmax) reaching a Cmax of 0.457ug/mL with a half-life of 7.5 hours and an AUC0-∞ of 12.202ug/h/mL.[27]

Appears to be rapidly absorbed, but the max concentration it reaches does not seem to differ that greatly from the serum levels measured over the next 12 hours in rats; appears to have a slow half-life as well, and preliminary evidence suggests the alkaloids remain at a fairly steady concentration for up to 12 hours after single dose administration


Enzymatic Interactions

Nuciferine may inhibit with Aromatase (CYP1A2), with an oral intake of 20mg/kg due to altering the elimination of phenacetin.[28] In vitro, Nuciferine was found to inhibit aromatase with and IC50 of 2.12mM, with 5mmol inhibiting 90% of the activity of recombinant CYP1A2 in vitro.[28]





One study that used 1g/kg Nelumbo Nucifera alongside the amnesiac toxin scopolamine over 14 days was found to almost wholly preserve acetylcholinesterase expression in the brain; Nelumbo Nucifera was at 97.7+/-0.9% of control and the active control drug ARICEPT at 97.0+/-0.5%, while scopolamine control declined to 90.3+/-1.1%.[29] Learning deficit in rats was also attenuated in a similar degree in both groups, although not abolished.[29] Another study using this model of amnesia and same dose of Nelumbo Nucifera, the number of Ki67-immunoreactive neurons (histological examination of in vivo neuron count) was decreased by 35.4% with scopolamine alone but increased 168.8% relative to the scopolamine group with Nelumbo;[30] this underperformed relative to 5mg/kg Galantamine (283.5%), and similar trends (benefitting, but underperforming relative to Galantamine) were noted with BDNF and DCX staining.[30]

It is possible Neferine mediates these effects, as it itself attenuated learning deficits from scopolamine at 1-10mg/kg oral administration in a dose-dependent manner.[31] This was more potent than 10mg/kg THA in a passive avoidance test (active control), which may be mediated through mixed acetylcholinesterase inhibition and anti-inflammatory properties (inhibiting LPS-induced SEAP expression with an IC50 of 8.2uM).[31] Other constituents, such as nuciferoside, possess slightly weaker anticholinesterase properties.[32]

Neuroprotection of the hippocampus and preservation of learning under the presecene of toxins is apparent with high dose Nelumbo Nucifera, but does not seem to be more effective than the reference drugs used

Acetylcholinesterase may also be inhibited directly with an IC50 of 1.5+/-0.2μg/mL by the apomorphine alkaloid N-methylasimilobine, which is reversible and noncompetitive that can reduce the Vmax of the enzyme 45% without affecting Km.[6] The sum of all alkoids was a bit weaker with an IC50 of 6.1+/-0.5μg/mL, and the structurally related alkaloids of nuciferine and nornuciferine showed no inhibitory effect,[6] but Neferine itself appears to inhibit Acetycholinesterase with an IC50 of 14.19+/-1.46μM (BChE inhibited with IC50 of 37.18+/-0.59μM).[31]

Neferine may also inhibit the BACE1 enzyme with an IC50 of 15.48+/-0.20μM.[31]

May inhibit acetylcholinesterase and other enzymes of interest to Alzheimer's therapy



Some compounds in Nelumbo appear to regulate the 5-HT3A serotonin receptors, with two compounds (methyl and ethyl-4-hydroxybenzoate) appearing to enhance a serotonin-mediated current with EC50 values of 13+/-0.5 and 16.7+/-4.2uM respectively in transfected oocytes while one (Butyl-4-hydroxybenzoate) attenuated the current, being two-fold more effective than picrotoxin at an IC50 of 18.5+/-3.1uM.[8]

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;[33] when compared to Imipramine HCl as active control, it slightly (but nonsignificantly) outperformed at equimolar doses. These anti-depressant effects were greatly attenuated with the 5-HT1A antagonist WAY 100635, with inhibition of 5-HT1B, 5-HT2, 5-HT3 and 5-HT4 not affecting Neferine.[33]

Some bioactives appear to potently interact with a serotonin receptor and may influence serotonergic function, but due to a lack of in vivo evidence the pracical relevance of this information is unknown



One study using isolated Neferine at 100mg/kg noted a reduction in locomotion in rats, which was independent of serotonin receptors (this study noted that anti-depressive effects were mediated via them);[33] these anti-locomotive effects are noted with the methanolic and CHCl3 extracts[34] and Neferine from these extracts at 50-100mg/kg had more anti-locomotive effects than 5mg/kg Diazepam, reduced rectal temperature, and augmented Thiopental-induced sleep with 100mg/kg being equally effective as 1mg/kg Diazepam.[34]

In a rotor-rod test, Neferine did not appear to adversely affect motor coordination at 25-100mg/kg while Diazepam at 1mg/kg did.[34] This sedative effect (as assessed by reduced locomotion) appears to extend to the structurally related compounds of nelumboferine, liensinine, isoliensinine, and O-methylneferine; with liensinine and isoliensinine being more potent than the neferine structures.[4]


Cardiovascular Health



One rat study feeding 100-800mg/kg Nelumbo Nucifera after physical injury to the endothelium (balloon injury) was able to inhibit ERK1/2 and JNK1/2, which suppressed MMP2 and MMP9 release.[35]

The isolated alkaloid Neferine may be involved in a DDAH–ADMA pathway of releasing Nitric Oxide, a pathway where Asymmetric dimethylarginine (ADMA) competitively inhibits the NOS enzyme and activation of the dimethylarginine dimethylaminohydrolase (DDAH) enzyme can convert ADMA to L-Citrulline and dimethylamine; higher activities of DDAH preserve Nitric Oxide function.[36][37] In an in vitro study with HUVEC (endothelial cells), Neferine in concentrations of 0.1, 1, and 10umol/L was able to preserve DDAH activity in a concentration dependent manner without outright inducing the DDAH enzyme under normal conditions.[38]


Interactions with Glucose Metabolism



Nelumbo Nucifera may be able to prevent carbohydrate absorption via amylase inhibitory potetial in vitro.[39]



An ethanolic extract of Lotus Leaf at 25-150mcg/mL was able to stimulate pancreatic β-cells under the influence of glucose to release glucose, with maximal efficacy at 50-100mcg/mL.[9] The mechanism appears to be related to calcium influx and phoshorylation of ERK1/2 (and secondary to that, PKC) without influencing Akt; these were thought to be due to the catechin component of Nelumbo Nucifera.[9] Nuciferine is an alkaloid that also appears to stimulate insulin secretion in the presence of glucose, and on a molar level appears to be more potent than glibenclamide at 10-20uM (although not competitive with glibenclamide).[40]

Interestingly and possible potent insulin-secreting effects at the level of the pancreas for some bioactive in Nelumbo Nucifera



100mg/kg of Nelumbo Nucifera ethanolic extract to high-fat fed diabetic mice was able to significantly reduce a postprandial AUC of glucose and more than doubled insulin secretion in response to the test meal, and after 2 weeks of consumption improved insulin sensivity; this was thought to be due to the catechin component.[9]


Fat Mass and Obesity



Nelumbo Nucifera appears to inhibit pancreatic lipase with an IC50 value of 0.46mg/mL, wholly due to the phenolic constituents of Nelumbo Nucifera;[39] these were thought to be behind a reduction in the AUC of triglycerides seen in fat-fed mice after 1.5g/kg Nelumbo Nucifera, although these rats did appear to have less circulating triglycerides 3 hours post intervention relative to baseline (suggesting some peripheral mechanism that is not merely a delay in absorption).[39]



At least one rat study has noted that a water extract with Nelumbo Nucifera was associated with a reduction of food intake (20-29% relative to high fat fed control).[41]



One study has noted that Nelumbo exerted anti-adipogenetic effects by preventing triglyceride accumulation into preadipocytes at 0.5-1% solution, with the higher concentration reducing triglyceride accumulation to 46+/-5.9% of control cells.[42] This was related to less mRNA expression and protein content of ADD1/SREBP-1c, and was additive with L-Carnitine.[42]

When incubated in adipocytes, Nelumbo Nucifera causes a dose-dependent release of Glycerol from the cells reaching 8-fold higher than control at 500mcg/mL; wholly abolished with incubation of propanolol, and as such is mediated via the B1/B2 adrenergic receptors.[39] This may be related to the Higenamine content,[39] although the flavanoids may also be suspect by being able to induce lipoysis in vitro.[21] An increase of lipolysis has been noted elsewhere to the magnitude of 356+/-76% of control at 0.5% solution, with no significant increase at 1%; this release of glycerol (biomarker of lipolysis) is independent of an increase in beta-oxidation.[42]

Additionally, an increase in UCP3 mRNA levels were noted in C2C12 myotubes and thought to possibly contribute to energy expenditure.[39]



In a model of young rats put on an obesogenic diet and given a hot water (tea) extract of Nelumbo Nucifera with or without 3% Taurine, but although a reduction in food intake was noted the authors suspected that this did not explain the observed weight loss.[41] While there was no significant synergism between Nelumbo Nucifera and taurine in regards to fat mass, both groups give the hot water extract had similar adipocyte size to normal fed control and the ending weight was not significantly different as normal fed control (despite being fed obesogenic diets).[41]


Inflammation and Immunology



The rhizomes and seeds of Nelumbo have been tested independently (both at 100mg/kg or 300mg/kg; compared to 2mg/kg dexamethasone) noted that both the rhizomes and seeds increased total lymphocyte count and the hydroalcoholic extract of the seeds, at 300mg/kg, increased macrophage phagocytosis.[43]



In studies using whole Nelumbo Nucifera extract, low dose Nelumbo (5, 25, 50mg/kg) were given to mice for four weeks after topical exposure to a proinflammatory irritant and appeared to markedly reduce the Atopic dermatitis-like lesions the test drug gave over 28 days, with near complete resolution at 50mg/kg.[44]

One study that isolated betulinic acid from a methanolic extract of Nelumbo Nucifera noted that 50-100mg/kg oral administration of Betulinic acid was equally effective against a serotonin or carrageenin-induced edema test (inflammation resulting in edema) when compared to the active controls of phenylbutazone and dexamethasone.[45] Another test on paw edema using 100-300mg/kg of either the seed or rhizome extract (high flavanoid content) also noted significant anti-inflammatory effects, but this study was not more effective than 2mg/kg dexamethasone (although 300mg/kg of the seeds was not significantly different).[43]


Interactions with Cancer


Hepatocellular Carcinoma

In isolated HepG2 cells, the alkaloid Neferine reduces cell viability in a dose and time dependent manner with an IC50 of 10μM at 48 hours.[46] This was associated with an increase in ROS and calcium influx into cells which disturbed mitochondrial membrane permeability, which then induces apoptosis.[46]



When testing Neferine in osteosarcoma cells, it appears to suppress proliferation of the two cell lines U2OS and Saos-2 with less efficacy against the normal cell line HCO; the IC50 against U2OS being 4.2-5.5μM while against HCO it required 12.1-18.8μM (about 3-fold selectivity).[47] The mechanism appeared to be a concentration dependent upregulation of p21 activity causing G1 cell cycle arrest secondary to activation of p38 MAPK.[47]


Interactions with Organs



Mechanistically, isolated Neferine at 2-10μmol/L is able to induce apoptosis and attenuate cytokine (TGF-β1 and collagen I; up to 11% and 20% respectively) release in hepatic stellate cells in a concentration dependent manner in vitro.[2] The IC50 in inhibiting proliferation of stellate cells was 22.53μmol/l, and although the EC50 for apoptosis was not calculated in this study it appeared to be mediated via caspase-3 release.[2]

May have anti-fibrotic mechanisms, but do not appear remarkably potent nor have they been tested in vivo

In obese diabetic mice given 0.5% of their diet as Lotus root polyphenolics noted that, without affecting food intake, the polyphenolic group noted a reduction in liver weight (15% less than control) and triglyceride content (62%) without affecting hepatic cholesterol content.[13] This study also noted less serum levels of ALP (17%) and GLP (24%) after 3 weeks, and these changes were thought to be due to a reduction in FAS and malic enzymes; two enzymes associated with lipogenesis (CPT unchanged).[13] Hepatoprotection has been tested wth coingested Taurine (3% of water) and appear to be of larger magnitude (possible additive effects), where serum GOP and GPT were reduced more than Nelumbo Nucifera itself.[48]


Safety and Toxicology

Toxicology studies in rats suggest that the safety threshold for acute toxicity is above 5000mg/kg bodyweight, and no adverse effects are noted at doses below 200mg/kg bodyweight.[49]

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37.^Lin KY, Ito A, Asagami T, Tsao PS, Adimoolam S, Kimoto M, Tsuji H, Reaven GM, Cooke JPImpaired nitric oxide synthase pathway in diabetes mellitus: role of asymmetric dimethylarginine and dimethylarginine dimethylaminohydrolaseCirculation.(2002 Aug 20)
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